Mitochondrial Diseases are rare progressive, multi-system, often early fatal disorders affecting both children and adults. KH176 is a novel chemical entity currently under development for the treatment of inherited mitochondrial diseases, including MELAS (Mitochondrial Encephalomyopathy, Lactic acidosis, and Stroke-like episodes), Leigh's Disease and Leber's Hereditary Optic Neuropathy (LHON). KH176 is a potent intracellular redox modulating agent targeting the reactive oxygen species which are important in the pathogenesis of disorders of mitochondrial oxidative phosphorylation. After demonstrating a favourable safety profile in the pre-clinical testing, the safety, tolerability and pharmacokinetic and pharmacodynamic characteristics of the compound will now be evaluated in healthy male subjects in this trial
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
DOUBLE
Enrollment
32
Drug Research Unit Ghent
Ghent, Belgium
SAD: Change From Baseline in ECG Results by Timepoint: Corrected QT Interval According to Fridericia's Formula (QTcF)
The baseline ECG recording consists of a triplicate recording (3 recordings of a least 3 complexes within a 5 minute window) prior to dosing on Day 1. For the evaluation of the corrected QT intervals the average of the 3 recordings will be taken as baseline. Other ECG recordings will be singlet (one recording of at least 3 complexes) prior to dosing. QTcF is calculated as the quotient between the QT interval in milliseconds and the cube root of the RR interval in seconds, according to Fridericia's formula.
Time frame: Baseline, 1, 2, 4, 6, 8, 12, 24 hours, 7 day follow up
Pharmacodynamics of KH176
Change from baseline in biochemistry related to Oxidative Phosphorylation (OXPHOS) (glutathione, lactate); MAD group
Time frame: Day 1, day 7
Relationship to Study Drug and Severity of Treatment-emergent Adverse Events
Time frame: 4 months
Change From Baseline in Hematology Laboratory Test Results by Timepoint: Red Blood Cell Count. SAD Group
Blood samples were collected from participants at the indicated timepoints for evaluation of hematology parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.
Time frame: Baseline (pre-dose Day 1), 24h post dose, FU (7 days after last dosing)
Change From Baseline in Hematology Laboratory Test Results by Timepoint: Erythrocyte Sedimentation Rate (SAD Group)
Time frame: Baseline (pre-dose Day1), 24h post dose, FU (7 days after last dosing)
Change From Baseline in Hematology Laboratory Test Results by Timepoint: Erythrocyte Sedimentation Rate MAD Group
Time frame: Baseline (pre-dose Day 1), Day 3, Day 8, FU (7 days after last dosing)
Change From Baseline in Hematology Laboratory Test Results by Timepoint: Hematocrit SAD Group
Hematocrit is a measure of the ratio of red blood cells (RBCs) in the blood by volume. Blood samples were collected from participants at the indicated timepoints for evaluation of hematology parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.
Time frame: Baseline (pre-dose Day 1), 24 h postdose, FU (7 days after last dosing)
Change From Baseline in Hematology Laboratory Test Results by Timepoint: Mean Corpuscular Haemoglobin. SAD
Blood samples were collected from participants at the indicated timepoints for evaluation of hematology parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.
Time frame: Baseline (pre-dose Day 1), 24 h post dose, FU (7 days after last dosing)
Change From Baseline in Hematology Laboratory Test Results by Timepoint: Mean Corpuscular Hemoglobin Concentration - SAD
Erythrocyte mean corpuscular hemoglobin concentration (MCHC) is a measure of the average concentration of hemoglobin per red blood cell. Blood samples were collected from participants at the indicated timepoints for evaluation of hematology parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.
Time frame: Baseline (pre-dose Day 1), 24 h post dose, FU (7 days after last dosing)
Change From Baseline in Hematology Laboratory Test Results by Timepoint: Mean Corpuscular Volume - SAD
Blood samples were collected from participants at the indicated timepoints for evaluation of hematology parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.
Time frame: Baseline (pre-dose Day 1), 24 h post dose, FU (7 days after last dosing)
MAD: Change From Baseline in ECG Results by Time Point: QTcF
The baseline ECG recording consists of a triplicate recording (3 recordings of a least 3 complexes within a 5 minute window) prior to dosing on Day 1. For the evaluation of the corrected QT intervals the average of the 3 recordings will be taken as baseline. Other ECG recordings will be singlet (one recording of at least 3 complexes) prior to dosing, or around the expected Cmax on Day 1 or 7 for the multiple-dose part. QTcF is calculated as the quotient between the QT interval in milliseconds and the cube root of the RR interval in seconds, according to Fridericia's formula.
Time frame: Baseline, Day1, Day 2, Day 3, Day 4, Day 5, Day 6, Day 7
Change From Baseline in Hematology Laboratory Test Results by Timepoint: White Blood Cell Count. SAD Group
Blood samples were collected from participants at the indicated timepoints for evaluation of hematology parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.
Time frame: Baseline (pre-dose Day 1), 24h post dose, FU (7 days after last dosing)
Change From Baseline in Hematology Laboratory Test Results by Timepoint: Lymphocytes. SAD Group
Blood samples were collected from participants at the indicated timepoints for evaluation of hematology parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.
Time frame: Baseline (pre-dose Day 1), 24h post dose, FU (7 days post dose)
Change From Baseline in Hematology Laboratory Test Results by Timepoint: Neutrophils. SAD Group
Blood samples were collected from participants at the indicated timepoints for evaluation of hematology parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.
Time frame: Baseline (pre-dose Day 1), 24h post dose, FU (7 days after last dosing)
Change From Baseline in Hematology Laboratory Test Results by Timepoint: Hematocrit MAD Group
Hematocrit is a measure of the ratio of red blood cells (RBCs) in the blood by volume. Blood samples were collected from participants at the indicated timepoints for evaluation of hematology parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value
Time frame: Baseline (pre-dose Day 1), Day 3, Day 8, FU (7 days post dose)
Change From Baseline in Hematology Laboratory Test Results by Timepoint: Eosinophils. SAD Group
Blood samples were collected from participants at the indicated timepoints for evaluation of hematology parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.
Time frame: Baseline (pre-dose Day 1), 24h post dose, FU (7 days after last dosing)
Change From Baseline in Hematology Laboratory Test Results by Timepoint: Thrombocytes. SAD Group
Blood samples were collected from participants at the indicated timepoints for evaluation of hematology parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.
Time frame: Baseline (pre-dose Day 1), 24h, FU (7 days post-dose)
Change From Baseline in Hematology Laboratory Test Results by Timepoint: Basophils. SAD Group
Blood samples were collected from participants at the indicated timepoints for evaluation of hematology parameters. The baseline value at visit and the change from baseline value ateach timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.
Time frame: Baseline (pre-dose Day 1), 24h post dose, FU (7 days post-dose)
Change From Baseline in Hematology Laboratory Test Results by Timepoint: Monocytes. SAD Group
Blood samples were collected from participants at the indicated timepoints for evaluation of hematology parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.
Time frame: Baseline (pre-dose Day 1), 24h post dose, FU (7 days post-dose)
Change From Baseline in Hematology Laboratory Test Results by Timepoint: Mean Corpuscular Volume. MAD Group
Blood samples were collected from participants at the indicated timepoints for evaluation of hematology parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.
Time frame: Baseline (pre-dose Day 1), Day 3, Day 8, FU (7 days post dose)
Change From Baseline in Hematology Laboratory Test Results by Timepoint: Hemoglobin. MAD Group
Blood samples were collected from participants at the indicated timepoints for evaluation of hematology parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.
Time frame: Baseline (pre-dose Day 1), Day 3, Day 8, FU (7 days post dose)
Change From Baseline in Hematology Laboratory Test Results by Timepoint: White Blood Cell Count. MAD
Blood samples were collected from participants at the indicated time points for evaluation of hematology parameters. The baseline value at visit and the change from baseline value at each time point are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.
Time frame: Baseline (pre-dose Day 1), Day 3, Day 8, FU (7 days post dose)
Change From Baseline in Hematology Laboratory Test Results by Timepoint: Neutrophils. MAD Group
Blood samples were collected from participants at the indicated timepoints for evaluation of hematology parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.
Time frame: Baseline (pre-dose Day 1), Day 3, Day 8, FU (7 days post dose)
Change From Baseline in Hematology Laboratory Test Results by Timepoint: Mean Corpuscular Haemoglobin Concentration. MAD Group
Blood samples were collected from participants at the indicated timepoints for evaluation of hematology parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.
Time frame: Baseline (pre-dose Day 1), Day 3, Day 8, FU (7 days post dose)
Change From Baseline in Hematology Laboratory Test Results by Timepoint: Lymphocytes. MAD Group
Blood samples were collected from participants at the indicated timepoints for evaluation of hematology parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.
Time frame: Baseline (pre-dose Day 1), Day 3, Day 8, FU (7 days post dose)
Change From Baseline in Hematology Laboratory Test Results by Timepoint: Mean Corpuscular Hemoglobin. MAD Group
Blood samples were collected from participants at the indicated timepoints for evaluation of hematology parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.
Time frame: Baseline (pre-dose Day 1), Day 3, Day 8, FU (7 days post dose)
Change From Baseline in Hematology Laboratory Test Results by Timepoint: Red Blood Cell Count. MAD Group
Blood samples were collected from participants at the indicated timepoints for evaluation of hematology parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.
Time frame: Baseline (pre-dose Day 1), Day 3, Day 8, FU (7 days post dose)
Change From Baseline in Hematology Laboratory Test Results by Timepoint: Eosinophils. MAD Group
Blood samples were collected from participants at the indicated timepoints for evaluation of hematology parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.
Time frame: Baseline (pre-dose Day 1), Day 3, Day 8, FU (7 days post dose)
Change From Baseline in Hematology Laboratory Test Results by Timepoint: Monocytes. MAD Group
Blood samples were collected from participants at the indicated timepoints for evaluation of hematology parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.
Time frame: Baseline (pre-dose Day 1), Day 3, Day 8, FU (7 days post dose)
Change From Baseline in Hematology Laboratory Test Results by Timepoint: Thrombocytes. MAD Group
Blood samples were collected from participants at the indicated timepoints for evaluation of hematology parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.
Time frame: Baseline (pre-dose Day 1), Day 3, Day 8, FU (7 days post dose)
Change From Baseline in Hematology Laboratory Test Results by Timepoint: Basophils. MAD Group
Blood samples were collected from participants at the indicated timepoints for evaluation of hematology parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.
Time frame: Baseline (pre-dose Day 1), Day 3, Day 8, FU (7 days post dose)
Change From Baseline in Chemistry Laboratory Test Results by Timepoint: Aspartate Aminotransferase. SAD Group
Blood samples were collected from participants at the indicated timepoints for evaluation of clinical chemistry parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.
Time frame: Baseline (pre-dose Day 1), 24h post dose, FU (7 days post dose)
Change From Baseline in Chemistry Laboratory Test Results by Timepoint: Total Protein. SAD Group
Blood samples were collected from participants at the indicated timepoints for evaluation of clinical chemistry parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.
Time frame: Baseline (pre-dose Day 1), 24h post dose, FU (7 days post dose)
Change From Baseline in Chemistry Laboratory Test Results by Timepoint: Gamma-GT. SAD Group
Blood samples were collected from participants at the indicated timepoints for evaluation of hematology parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value
Time frame: Baseline (pre-dose Day 1), 24h post dose, FU (7 days post dose)
Change From Baseline in Chemistry Laboratory Test Results by Timepoint: Alkaline Phosphatase. SAD Group
Blood samples were collected from participants at the indicated timepoints for evaluation of clinical chemistry parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.
Time frame: Baseline (pre-dose Day 1), 24h post dose, FU (7 days post dose)
Change From Baseline in Chemistry Laboratory Test Results by Timepoint: Creatinine. SAD Group
Blood samples were collected from participants at the indicated timepoints for evaluation of clinical chemistry parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.
Time frame: Baseline (pre-dose Day 1), 24h post dose, FU (7 days post dose)
Change From Baseline in Chemistry Laboratory Test Results by Timepoint: Chloride. SAD Group
Blood samples were collected from participants at the indicated timepoints for evaluation of clinical chemistry parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.
Time frame: Baseline (pre-dose Day 1), 24h post dose, FU (7 days post dose)
Change From Baseline in Chemistry Laboratory Test Results by Timepoint: Total Bilirubin. SAD Group
Blood samples were collected from participants at the indicated timepoints for evaluation of hematology parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.
Time frame: Baseline (pre-dose Day 1), 24h post dose, FU (7 days post dose)
Change From Baseline in Chemistry Laboratory Test Results by Timepoint: Alanine Aminotransferase. SAD Group
Blood samples were collected from participants at the indicated timepoints for evaluation of clinical chemistry parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.
Time frame: Baseline (pre-dose Day 1), 24h post dose, FU (7 days post dose)
Change From Baseline in Chemistry Laboratory Test Results by Timepoint: Creatinine Kinase. SAD Group
Blood samples were collected from participants at the indicated timepoints for evaluation of clinical chemistry parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.
Time frame: Baseline (pre-dose Day 1), 24h post dose, FU (7 days post dose)
Change From Baseline in Chemistry Laboratory Test Results by Timepoint: Urea. SAD Group
Blood samples were collected from participants at the indicated timepoints for evaluation of clinical chemistry parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.
Time frame: Baseline (pre-dose Day 1), 24h post dose, FU (7 days post dose)
Change From Baseline in Chemistry Laboratory Test Results by Timepoint: Sodium. SAD Group
Blood samples were collected from participants at the indicated timepoints for evaluation of clinical chemistry parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.
Time frame: Baseline (pre-dose Day 1), 24h post dose, FU (7 days post dose)
Change From Baseline in Chemistry Laboratory Test Results by Timepoint: Potassium. SAD Group
Blood samples were collected from participants at the indicated timepoints for evaluation of clinical chemistry parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.
Time frame: Baseline (pre-dose Day 1), 24h post dose, FU (7 days post dose)
Change From Baseline in Chemistry Laboratory Test Results by Timepoint: Phosphate. SAD Group
Blood samples were collected from participants at the indicated timepoints for evaluation of clinical chemistry parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.
Time frame: Baseline (pre-dose Day 1), 24h post dose, FU (7 days post dose)
Change From Baseline in Chemistry Laboratory Test Results by Timepoint: Calcium (Corrected for Albumin). SAD Group
Blood samples were collected from participants at the indicated timepoints for evaluation of clinical chemistry parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.
Time frame: Baseline (pre-dose Day 1), 24h post dose, FU (7 days post dose)
Change From Baseline in Chemistry Laboratory Test Results by Timepoint: Uric Acid. SAD Group
Blood samples were collected from participants at the indicated timepoints for evaluation of clinical chemistry parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.
Time frame: Baseline (pre-dose Day 1), 24h post dose, FU (7 days post dose)
Change From Baseline in Chemistry Laboratory Test Results by Timepoint: Triiodothyronine (T3). SAD Group
Blood samples were collected from participants at the indicated timepoints for evaluation of clinical chemistry parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.
Time frame: Baseline (pre-dose Day 1), 24h post dose, FU (7 days post dose)
Change From Baseline in Chemistry Laboratory Test Results by Timepoint: Lipase. SAD Group
Blood samples were collected from participants at the indicated timepoints for evaluation of clinical chemistry parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.
Time frame: Baseline (pre-dose Day 1), 24h post dose, FU (7 days post dose)
Change From Baseline in Chemistry Laboratory Test Results by Timepoint: (Fasting) Glucose. SAD Group
Blood samples were collected from participants at the indicated timepoints for evaluation of clinical chemistry parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.
Time frame: Baseline (pre-dose Day 1), 24h post dose, FU (7 days post dose)
Change From Baseline in Chemistry Laboratory Test Results by Timepoint: Human Serum Albumin. SAD Group
Blood samples were collected from participants at the indicated timepoints for evaluation of clinical chemistry parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.
Time frame: Baseline (pre-dose Day 1), 24h post dose, FU (7 days post dose)
Change From Baseline in Chemistry Laboratory Test Results by Timepoint: Cholesterol. SAD Group
Blood samples were collected from participants at the indicated timepoints for evaluation of clinical chemistry parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.
Time frame: Baseline (pre-dose Day 1), 24h post dose, FU (7 days post dose)
Change From Baseline in Chemistry Laboratory Test Results by Timepoint: High Density Lipoproteins. SAD Group
Blood samples were collected from participants at the indicated timepoints for evaluation of clinical chemistry parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.
Time frame: Baseline (pre-dose Day 1), 24h post dose, FU (7 days post dose)
Change From Baseline in Chemistry Laboratory Test Results by Timepoint: Triglycerides. SAD Group
Blood samples were collected from participants at the indicated timepoints for evaluation of clinical chemistry parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.
Time frame: Baseline (pre-dose Day 1), 24h post dose, FU (7 days post dose)
Change From Baseline in Chemistry Laboratory Test Results by Timepoint: Low Density Lipoproteins. SAD Group
Blood samples were collected from participants at the indicated timepoints for evaluation of clinical chemistry parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.
Time frame: Baseline (pre-dose Day 1), 24h post dose, FU (7 days post dose)
Change From Baseline in Chemistry Laboratory Test Results by Timepoint: Bicarbonate. SAD Group
Blood samples were collected from participants at the indicated timepoints for evaluation of clinical chemistry parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.
Time frame: Baseline (pre-dose Day 1), 24h post dose, FU (7 days post dose)
Change From Baseline in Chemistry Laboratory Test Results by Timepoint: Thyroid-stimulating Hormone. SAD Group
Blood samples were collected from participants at the indicated timepoints for evaluation of clinical chemistry parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.
Time frame: Baseline (pre-dose Day 1), 24h post dose, FU (7 days post dose)
Change From Baseline in Chemistry Laboratory Test Results by Timepoint: Thyroxine (T4). SAD Group
Blood samples were collected from participants at the indicated timepoints for evaluation of clinical chemistry parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.
Time frame: Baseline (pre-dose Day 1), 24h post dose, FU (7 days post dose)
Change From Baseline in Chemistry Laboratory Test Results by Timepoint: Lactate. SAD Group
Blood samples were collected from participants at the indicated timepoints for evaluation of clinical chemistry parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.
Time frame: Baseline (pre-dose Day 1), 24h post dose, FU (7 days post dose)
Change From Baseline in Chemistry Laboratory Test Results by Time Point: Total Protein. MAD Group
Blood samples were collected from participants at the indicated timepoints for evaluation of hematology parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.
Time frame: Baseline (pre-dose Day1), Day 3, Day 8, FU (one week after last dosing)
Change From Baseline in Chemistry Laboratory Test Results by Time Point: Alkaline Phosphatase. MAD Group
Blood samples were collected from participants at the indicated timepoints for evaluation of chemistry parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.
Time frame: Baseline, Day 3, Day 8, FU (one week after last dosing)
Change From Baseline in Chemistry Laboratory Test Results by Time Point: Aspartate Aminotransferase. MAD Group
Blood samples were collected from participants at the indicated timepoints for evaluation of chemistry parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.
Time frame: Baseline, Day 3, Day 8, FU (one week after last dosing)
Change From Baseline in Chemistry Laboratory Test Results by Time Point: Creatine Kinase. MAD Group
Blood samples were collected from participants at the indicated timepoints for evaluation of chemistry parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.
Time frame: Baseline, Day 3, Day 8, FU (one week after last dosing)
Change From Baseline in Chemistry Laboratory Test Results by Time Point: Gamma GT. MAD Group
Blood samples were collected from participants at the indicated timepoints for evaluation of chemistry parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.
Time frame: Baseline, Day 3, Day 8, FU (one week after last dosing)
Change From Baseline in Chemistry Laboratory Test Results by Time Point: Total Bilirubin. MAD Group
Blood samples were collected from participants at the indicated timepoints for evaluation of chemistry parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.
Time frame: Baseline, Day 3, Day 8, FU (one week after last dosing)
Change From Baseline in Chemistry Laboratory Test Results by Time Point: Urea. MAD Group
Blood samples were collected from participants at the indicated timepoints for evaluation of chemistry parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.
Time frame: Baseline, Day 3, Day 8, FU (one week after last dosing)
Change From Baseline in Chemistry Laboratory Test Results by Time Point: Creatinine. MAD Group
Blood samples were collected from participants at the indicated timepoints for evaluation of chemistry parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.
Time frame: Baseline, Day 3, Day 8, FU (one week after last dosing)
Change From Baseline in Chemistry Laboratory Test Results by Time Point: Sodium. MAD Group
Blood samples were collected from participants at the indicated timepoints for evaluation of chemistry parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.
Time frame: Baseline, Day 3, Day 8, FU (one week after last dosing)
Change From Baseline in Chemistry Laboratory Test Results by Time Point: Potassium. MAD Group
Blood samples were collected from participants at the indicated timepoints for evaluation of chemistry parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.
Time frame: Baseline, Day 3, Day 8, FU (one week after last dosing)
Change From Baseline in Chemistry Laboratory Test Results by Time Point: Chloride. MAD Group
Blood samples were collected from participants at the indicated timepoints for evaluation of chemistry parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.
Time frame: Baseline, Day 3, Day 8, FU (one week after last dosing)
Change From Baseline in Chemistry Laboratory Test Results by Time Point: Calcium (Corrected for Albumin). MAD Group
Blood samples were collected from participants at the indicated timepoints for evaluation of chemistry parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.
Time frame: Baseline, Day 3, Day 8, FU (one week after last dosing)
Change From Baseline in Chemistry Laboratory Test Results by Time Point: Uric Acid. MAD Group
Blood samples were collected from participants at the indicated timepoints for evaluation of chemistry parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.
Time frame: Baseline, Day 3, Day 8, FU (one week after last dosing)
Change From Baseline in Chemistry Laboratory Test Results by Time Point: Lipase. MAD Group
Blood samples were collected from participants at the indicated timepoints for evaluation of chemistry parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.
Time frame: Baseline, Day 3, Day 8, FU (one week after last dosing)
Change From Baseline in Chemistry Laboratory Test Results by Time Point: Alanine Aminotransferase. MAD Group
Blood samples were collected from participants at the indicated timepoints for evaluation of chemistry parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.
Time frame: Baseline, Day 3, Day 8, FU (one week after last dosing)
Change From Baseline in Chemistry Laboratory Test Results by Time Point: Phosphate. MAD Group
Blood samples were collected from participants at the indicated timepoints for evaluation of chemistry parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.
Time frame: Baseline, Day 3, Day 8, FU (one week after last dosing)
Change From Baseline in Chemistry Laboratory Test Results by Time Point: Human Serum Albumin. MAD Group
Blood samples were collected from participants at the indicated timepoints for evaluation of chemistry parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.
Time frame: Baseline, Day 3, Day 8, FU (one week after last dosing)
Change From Baseline in Chemistry Laboratory Test Results by Time Point: Fasting Glucose. MAD Group
Blood samples were collected from participants at the indicated timepoints for evaluation of chemistry parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.
Time frame: Baseline, Day 3, Day 8, FU (one week after last dosing)
Change From Baseline in Chemistry Laboratory Test Results by Time Point: Cholesterol. MAD Group
Blood samples were collected from participants at the indicated timepoints for evaluation of chemistry parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.
Time frame: Baseline, Day 3, Day 8, FU (one week after last dosing)
Change From Baseline in Chemistry Laboratory Test Results by Time Point: Triglycerides. MAD Group
Blood samples were collected from participants at the indicated timepoints for evaluation of chemistry parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.
Time frame: Baseline, Day 3, Day 8, FU (one week after last dosing)
Change From Baseline in Chemistry Laboratory Test Results by Time Point: Low Density Lipoproteins. MAD Group
Blood samples were collected from participants at the indicated timepoints for evaluation of chemistry parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.
Time frame: Baseline, Day 3, Day 8, FU (one week after last dosing)
Change From Baseline in Chemistry Laboratory Test Results by Time Point: High Density Lipoproteins. MAD Group
Blood samples were collected from participants at the indicated timepoints for evaluation of chemistry parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.
Time frame: Baseline, Day 3, Day 8, FU (one week after last dosing)
Change From Baseline in Chemistry Laboratory Test Results by Time Point: Thyroid-stimulating Hormone. MAD Group
Blood samples were collected from participants at the indicated timepoints for evaluation of chemistry parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.
Time frame: Baseline, Day 3, Day 8, FU (one week after last dosing)
Change From Baseline in Chemistry Laboratory Test Results by Time Point: Trilodothyronine (T3). MAD Group
Blood samples were collected from participants at the indicated timepoints for evaluation of chemistry parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.
Time frame: Baseline, Day 3, Day 8, FU (one week after last dosing)
Change From Baseline in Chemistry Laboratory Test Results by Time Point: Thyroxine (T4). MAD Group
Blood samples were collected from participants at the indicated timepoints for evaluation of chemistry parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.
Time frame: Baseline, Day 3, Day 8, FU (one week after last dosing)
Change From Baseline in Chemistry Laboratory Test Results by Time Point: Bicarbonate. MAD Group
Blood samples were collected from participants at the indicated timepoints for evaluation of chemistry parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.
Time frame: Baseline, Day 3, Day 8, FU (one week after last dosing)
Change From Baseline in Chemistry Laboratory Test Results by Time Point: Lactate. MAD Group
Blood samples were collected from participants at the indicated timepoints for evaluation of chemistry parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.
Time frame: Baseline, Day 3, Day 8, FU (one week after last dosing)
Phospholipidosis
Change from Day 1 to Day 7 in di-docosahexaenoyl (22:6)-bis(monoacylglycerol) phosphate (di-22:6-BMP) and normalized di-22:6-BMP (urine) - MAD
Time frame: Day 1, Day 7
MAD: Change From Baseline in ECG Results by Time Point: Corrected QT Interval According to Barret's Formaula (QTcB)
The baseline ECG recording consists of a triplicate recording (3 recordings of a least 3 complexes within a 5 minute window) prior to dosing on Day 1. For the evaluation the average of the 3 recordings will be taken as baseline. Other ECG recordings will be singlet (one recording of at least 3 complexes) prior to dosing, or around the expected Cmax on Day 1 or 7 for the multiple- dose part.
Time frame: Baseline (pre-dose Day 1), Day1, Day 2, Day 3, Day 4, Day 5, Day 6, Day 7, Follow-up
MAD: Change From Baseline in ECG Results by Time Point: P Wave-Q Wave Interval (PQ Interval)
The baseline ECG recording consists of a triplicate recording (3 recordings of a least 3 complexes within a 5 minute window) prior to dosing on Day 1. For the evaluation of the PQ interval the average of the 3 recordings will be taken as baseline.
Time frame: Baseline (pre-dose Day 1), Day1, Day 2, Day 3, Day 4, Day 5, Day 6, Day 7, Follow-up
MAD: Change From Baseline in ECG Results by Time Point: the Interval That Denotes Depolarization of the Ventricles, Between the Beginning of the Q Wave and the End of the S Wave (QRS Interval)
The baseline ECG recording consists of a triplicate recording (3 recordings of a least 3 complexes within a 5 minute window) prior to dosing on Day 1. For the evaluation the average of the 3 recordings will be taken as baseline. Other ECG recordings will be singlet (one recording of at least 3 complexes) prior to dosing, or around the expected Cmax on Day 1 or 7 for the multiple- dose part.
Time frame: Baseline (pre-dose Day 1), Day1, Day 2, Day 3, Day 4, Day 5, Day 6, Day 7, Follow-up
MAD: Change From Baseline in ECG Results by Time Point: QT Interval
The baseline ECG recording consists of a triplicate recording (3 recordings of a least 3 complexes within a 5 minute window) prior to dosing on Day 1. For the evaluation the average of the 3 recordings will be taken as baseline. Other ECG recordings will be singlet (one recording of at least 3 complexes) prior to dosing, or around the expected Cmax on Day 1 or 7 for the multiple- dose part.
Time frame: Baseline (pre-dose Day 1), Day1, Day 2, Day 3, Day 4, Day 5, Day 6, Day 7, Follow-up
SAD: Change From Baseline in ECG Results by Time Point: PQ Interval
The baseline ECG recording consists of a triplicate recording (3 recordings of a least 3 complexes within a 5 minute window) prior to dosing on Day 1. For the evaluation the average of the 3 recordings will be taken as baseline.
Time frame: Pre-dose, Day 1, Day 7
SAD: Change From Baseline in ECG Results by Time Point: QRS Interval
The baseline ECG recording consists of a triplicate recording (3 recordings of a least 3 complexes within a 5 minute window) prior to dosing on Day 1. For the evaluation the average of the 3 recordings will be taken as baseline.
Time frame: Pre-dose, Day 1, Day 7
SAD: Change From Baseline in ECG Results by Time Point: QT Interval
The baseline ECG recording consists of a triplicate recording (3 recordings of a least 3 complexes within a 5 minute window) prior to dosing on Day 1. For the evaluation the average of the 3 recordings will be taken as baseline.
Time frame: Pre-dose, Day 1, Day 7
SAD: Change From Baseline in ECG Results by Time Point: QTcB Interval
The baseline ECG recording consists of a triplicate recording (3 recordings of a least 3 complexes within a 5 minute window) prior to dosing on Day 1. For the evaluation the average of the 3 recordings will be taken as baseline.
Time frame: Pre-dose, Day1, Day 7
Terminal Elimination Half-life (T1/2) of KH176 Over 24 Hours: SAD
Plasma concentrations of KH176 were analysed after single dose administration of doses 10mg, 30mg, 100mg (with and without food), 300mg, 800mg, 2000mg b.i.d.
Time frame: Pre-dose (5 min before dosing) and 0.5, 1, 1.5, 2, 3, 6, 8, 12, and 24 hours post-dose
Terminal Elimination Half-life (T1/2) of KH183: SAD
Plasma concentrations of KH183 were analysed after single dose administration of doses 10mg, 30mg, 100mg (with and without food) , 300mg, 800mg, 2000mg b.i.d.
Time frame: Pre-dose (5 min before dosing) and 0.5, 1, 1.5, 2, 3, 6, 8, 12, and 24 hours post-dose
Maximum Concentration (Cmax) of KH176: SAD Group
Plasma concentrations of KH176 were analysed after single dose administration of doses 10mg, 30mg, 100mg (with and without food), 300mg, 800mg, 2000mg b.i.d.
Time frame: Pre-dose (5 min before dosing) and 0.5, 1, 1.5, 2, 3, 6, 8, 12, and 24 hours post-dose
Maximum Concentration (Cmax) of KH183 Over 24 Hours: SAD
Plasma concentrations of KH183 were analysed after single dose administration of doses 10mg, 30mg, 100mg (with and without food) , 300mg, 800mg, 2000mg b.i.d.
Time frame: Pre-dose (5 min before dosing) and 0.5, 1, 1.5, 2, 3, 6, 8, 12, and 24 hours post-dose
Maximum Concentration (Cmax) of KH183 (Active Metabolite of KH176): MAD Group
Plasma concentrations of KH183 were analysed after multiple-dose administration of doses of 100, 200 and 400 mg b.i.d.: Cmax was obtained directly from the concentration-time data.
Time frame: Predose at Day 1, 2, 4, 7, and post-dose at Day 1 and Day 7 at 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 hours
Maximum Concentration (Cmax) of KH176: MAD
Plasma concentrations of KH176 were analysed after multiple-dose administration of doses of 100, 200 and 400 mg b.i.d.
Time frame: pre-dose at Day 1, 2, 4, 7, and post-dose at Day 1 and Day 7 at 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 hours
Time to Maximum Concentration (Tmax) of KH176 Over 24 Hours: SAD
Plasma concentrations of KH176 were analysed after single dose administration of doses 10mg, 30mg, 100mg (with and without food), 300mg, 800mg, 2000mg b.i.d.
Time frame: Pre-dose (5 min before dosing) and 0.5, 1, 1.5, 2, 3, 6, 8, 12, and 24 hours post-dose
Time to Reach Peak Plasma Concentration (Tmax) of KH183: SAD
Plasma concentrations of KH183 were analysed after single dose administration of doses 10mg, 30mg, 100mg (with and without food), 300mg, 800mg, 2000mg b.i.d.
Time frame: Pre-dose (5 min before dosing) and 0.5, 1, 1.5, 2, 3, 6, 8, 12, and 24 hours post-dose
Time to Maximum Concentration (Tmax) of KH176 at Day 1, Day 7: MAD Group
Plasma concentrations of KH176 were analysed after multiple-dose administration of doses of 100, 200 and 400 mg b.i.d.
Time frame: pre-dose at Day 1, 2, 4, 7, and post-dose at Day 1 and Day 7 at 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 hours
Time to Maximum Concentration (Tmax) of KH183 (Active Metabolite of KH176): MAD Group
Plasma concentrations of KH183 were analysed after multiple-dose administration of doses of 100, 200 and 400 mg b.i.d.. tmax was obtained directly from the concentration-time data.
Time frame: Predose at Day 1, 2, 4, 7, and post-dose at Day 1 and Day 7 at 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 hours
Accumulation Factor (Racc) of KH176 Over 7 Days: MAD Group
Plasma concentrations of KH176 were analysed after multiple-dose administration of doses of 100, 200 and 400 mg b.i.d.. Racc was calculated as follows: AUCtau day 7/ AUCtau day 1.
Time frame: Pre-dose at Day 1, 2, 4, 7, and post-dose at Day 1 and Day 7 at 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 hours
Accumulation Factor (Racc) of KH183 (Active Metabolite of KH176): MAD Group
Plasma concentrations of KH183 were analysed after multiple-dose administration of doses of 100, 200 and 400 mg b.i.d.: Accumulation factor was calculated as follows: AUCtau day 7/ AUCtau day 1.
Time frame: Predose at Day 1, 2, 4, 7, and post-dose at Day 1 and Day 7 at 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 hours
Area Under the Plasma Concentration Versus Time Curve (AUClast) of KH183: SAD Group
Plasma concentrations of KH183 were analysed after single dose administration of doses 10mg, 30mg, 100mg (with and without food) , 300mg, 800mg, 2000mg b.i.d.
Time frame: Pre-dose (5 min before dosing) and 0.5, 1, 1.5, 2, 3, 6, 8, 12, and 24 hours post-dose
Area Under the Plasma Concentration Versus Time Curve (AUClast) of KH176: SAD Group
Plasma concentrations of KH176 were analysed after single dose administration of doses 10mg, 30mg, 100mg (with and without food), 300mg, 800mg, 2000mg b.i.d.
Time frame: pre-dose (5 min before dosing) and 0.5, 1, 1.5, 2, 3, 6, 8, 12, and 24 hours post-dose
Area Under the Plasma Concentration-time Curve (AUCtau) of KH176: MAD Group:
Plasma concentrations of KH176 were analysed after multiple-dose administration of doses of 100, 200 and 400 mg b.i.d.
Time frame: Pre-dose at Day 1, 2, 4, 7, and post-dose at Day 1 and Day 7 at 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 hours
Area Under the Plasma Concentration-time Curve During a Dose Interval (AUCtau) of KH183 (Active Metabolite of KH176): MAD Group
Plasma concentrations of KH183 were analysed after multiple-dose administration of doses of 100, 200 and 400 mg b.i.d.
Time frame: Predose at Day 1, 2, 4, 7, and post-dose at Day 1 and Day 7 at 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 hours
Area Under the Plasma Concentration-time Curve From Time Zero Until Infinity (AUCl0-inf) of KH183: SAD
Plasma concentrations of KH183 were analysed after single dose administration of doses 10mg, 30mg, 100mg (with and without food) , 300mg, 800mg, 2000mg b.i.d.
Time frame: Pre-dose (5 min before dosing) and 0.5, 1, 1.5, 2, 3, 6, 8, 12, and 24 hours post-dose
Area Under the Plasma Concentration-time Curve From Time Zero Until Infinity (AUCl0-inf) of KH176: SAD
Plasma concentrations of KH176 were analysed after single dose administration of doses 10mg, 30mg, 100mg (with and without food) , 300mg, 800mg, 2000mg b.i.d.
Time frame: Pre-dose (5 min before dosing) and 0.5, 1, 1.5, 2, 3, 6, 8, 12, and 24 hours post-dose
KH176: Percentage of Administered Dose Excreted in Urine: SAD
Urine concentrations of KH176 were analysed after single dose administration of doses 10mg, 30mg, 100mg (with and without food), 300mg, 800mg, 2000mg b.i.d.
Time frame: 24 hours post-dose
KH183: Percentage of Administered Dose Excreted in Urine: SAD
Urine concentrations of KH176 were analysed after single dose administration of doses 10mg, 30mg, 100mg (with and without food), 300mg, 800mg, 2000mg b.i.d.
Time frame: 24 hours post-dose
KH176 + KH183: Percentage of Administered Dose Excreted in Urine: SAD
Urine concentrations of KH176 were analysed after single dose administration of doses 10mg, 30mg, 100mg (with and without food), 300mg, 800mg, 2000mg b.i.d.
Time frame: 24 hours post-dose
KH176: Percentage of Administered Dose Excreted in Urine: MAD
Urine concentrations of KH176 were analysed after multiple-dose administration of doses of 100, 200 and 400 mg b.i.d.
Time frame: Day 7 post dose
KH183: Percentage of Administered Dose Excreted in Urine: MAD
Urine concentrations of KH183 were analysed after multiple-dose administration of doses of 100, 200 and 400 mg b.i.d.
Time frame: Post dose Day 7
KH173 + KH183: Percentage of Administered Dose Excreted in Urine: MAD
Urine concentrations of KH176 and KH183 were analysed after multiple-dose administration of doses of 100, 200 and 400 mg b.i.d.
Time frame: Day 7 Post dose
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