The primary objective of the study is to assess the safety and tolerability of single and multiple subcutaneous doses of OLP-1002 in healthy subjects.
The exploratory objectives of the study are to evaluate the pharmacodynamic effect of OLP-1002 following single subcutaneous doses in healthy volunteers using a capsaicin pain model, and to monitor the effects of a single subcutaneous doses of OLP-1002 on cardiac QT interval. Where possible, single and/or multiple subcutaneous dose pharmacokinetics of OLP-1002 in healthy subjects will be determined.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
TRIPLE
Enrollment
116
Subcutaneous Injection: 30 ng, 120 ng, 400 ng, 1.2 µg, 3 µg, 6 µg, 12 µg, 20 µg, 40 μg, 80 μg, 160 μg
Subcutaneous Injection: 5 x 2 μg, 5 x 5 μg, 5 x 10 μg, 5 x 20 μg, 5 x 40 μg, 5 x 80 μg
Subcutaneous Injection: Placebo
Leeds CRU
Leeds, United Kingdom
Number of Participants With Adverse Events Stratified by Overall and Severity
Participants were observed for any signs or symptoms of adverse events and asked about their condition by open questioning, such as "How have you been feeling since you were last asked?", at least once each day while resident at the study site and at each study visit.
Time frame: Part A: From screening through study completion, up to 32 days. Part B: From screening through study completion, up to 60 days.
Number of Participants Who Experienced Clinically Important Changes in Supine Diastolic and Systolic Blood Pressure
Number of participants who experienced clinically important changes from baseline (the last value recorded prior to first dose) to scheduled timepoints in supine diastolic and systolic blood pressure. Participants were supine for at least 5 minutes before blood pressure measurements. Blood pressure was measured in triplicate and the time of measurement are below: Single ascending dose: Predose, 1, 2, 4, 8, 24 (± 1 hours), and 48 hours posdose Multiple ascending dose: Day 1 (Predose, 1, 2, 4, and 8 hours postdose), Day 2, Day 4 (postdose), Day 5, Day 7 (postdose), Day 9, Day 10 (postdose), Day 12, Day 13 (predose, 1, 2, 4, and 8 hours postdose), and Day 15 No treatment or dose related trends and no clinically significant changes were observed in mean or individual participant supine blood pressure. Supine diastolic blood pressure reference range: 90 to 140 mmHg. Supine systolic blood pressure reference range: 50 to 90 mmHg.
Time frame: Part A: From screening through study completion, up to 32 days. Part B: From screening through study completion, up to 60 days.
Number of Participants Who Experienced Clinically Important Changes in Supine Pulse Rate
Number of participants who experienced clinically important changes from baseline (the last value recorded prior to first dose) to scheduled timepoints in supine pulse rate. Participants were supine for at least 5 minutes before pulse rate measurements. Pulse rate was measured in triplicate and the time of measurement are below: Single ascending dose: Predose, 1, 2, 4, 8, 24 (± 1 hours), and 48 hours posdose Multiple ascending dose: Day 1 (Predose, 1, 2, 4, and 8 hours postdose), Day 2, Day 4 (postdose), Day 5, Day 7 (postdose), Day 9, Day 10 (postdose), Day 12, Day 13 (predose, 1, 2, 4, and 8 hours postdose), and Day 15 No treatment or dose related trends and no clinically significant changes were observed in mean or individual participant supine pulse rate. Reference range: 40 to 100 beats per minute.
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Subcutaneous Injection: Placebo x 5
Time frame: Part A: From screening through study completion, up to 32 days. Part B: From screening through study completion, up to 60 days.
Number of Participants Who Experienced Clinically Important Changes in Respiratory Rate
Number of participants who experienced clinically important changes from baseline (the last value recorded prior to first dose) to scheduled timepoints in respiratory rate. Participants were supine for at least 5 minutes before respiratory rate measurements. Respiratory rate was measured in triplicate and the time of measurement are below: Single ascending dose: Predose, 1, 2, 4, 8, 24 (± 1 hours), and 48 hours posdose Multiple ascending dose: Day 1 (Predose, 1, 2, 4, and 8 hours postdose), Day 2, Day 4 (postdose), Day 5, Day 7 (postdose), Day 9, Day 10 (postdose), Day 12, Day 13 (predose, 1, 2, 4, and 8 hours postdose), and Day 15 No treatment or dose related trends and no clinically significant changes were observed in mean or individual participant respiratory rate. Reference range: 10 to 24 breaths per minute.
Time frame: Part A: From screening through study completion, up to 32 days. Part B: From screening through study completion, up to 60 days.
12-lead Electrocardiogram Parameters
Resting 12-lead electrocardiogram parameters were recorded after the participant had been supine and at rest for at least 5 minutes. Baseline: the last value recorded prior to first dose; QTcB: QT interval corrected for heart rate using Bazett's formula; QTcF: QT interval corrected for heart rate using Fridericia's method.
Time frame: Part A: From screening through study completion, up to 32 days. Part B: From screening through study completion, up to 60 days.
Number of Participants With Findings of Clinical Importance in Clinical Chemistry, Hematology, and Urinalysis Test Results
Number of participants with findings of clinical importance in clinical chemistry, hematology, and urinalysis test results. Clinical laboratory evaluations included: Clinical chemistry: Alanine aminotransferase; Albumin; Alkaline phosphatase; Aspartate aminotransferase; Calcium; Chloride; Cholesterol; Creatinine; Direct bilirubin; Gamma-glutamyl transferase; Glucose; Inorganic phosphate; Potassium; Sodium; Total bilirubin; Total protein; Urea Hematology: Hematocrit; Hemoglobin; Mean cell hemoglobin; Mean cell hemoglobin concentration; Mean cell volume; Platelet count; Red blood cell count; White blood cell count; White blood cell differential (Basophils; Eosinophils; Lymphocytes; Monocytes; Neutrophils) Urinalysis: Blood; Glucose; Ketones; pH; Protein; Specific gravity; Urobilinogen; Microscopic examination
Time frame: Part A: From screening through study completion, up to 32 days. Part B: From screening through study completion, up to 60 days.
Number of Participants With Full and Symptom-Directed Physical Examination Results
A full physical examination and symptom-directed physical examinations were performed at specified timepoints.
Time frame: Part A: From screening through study completion, up to 32 days. Part B: From screening through study completion, up to 60 days.
Number of Participants With Injection Site Assessment Results
Evaluation of the dosing site for the following: Pain: Grade 0 to 4 Redness (assessed by estimating the size of the red patch at the injection site across its widest point): Grade 0: 0-24 mm; Grade 1: 25-50 mm; Grade 2: 51-100 mm; Grade 3: More than 100 mm; Grade 4: Requires medical intervention greater than analgesia Swelling (assessed by estimating the size of the raised area around the injection site across its widest point): Grade 0: 0-24 mm; Grade 1: 25-50 mm and does not interfere with activity; Grade 2: 51-100 mm or interferes with activity; Grade 3: More than 100 mm and prevents daily activity; Grade 4: Requires medical intervention greater than analgesia Tenderness: Grade 0 to 4 Bruising and ulceration were evaluated as present or absent.
Time frame: Part A: From screening through study completion, up to 32 days. Part B: From screening through study completion, up to 60 days.
Number of Participants With Exposure to OLP-1002 That Exceeded Pre-define Exposure Limits From Non-clinical Studies
Participants were assessed to demonstrate that exposure to OLP-1002 did not exceed pre-defined exposure limits from non-clinical studies. Participants with temporary detected plasma concentrations between the low limit of detection \[0.2 ng/mL\] and lower limit of quantification \[1 ng/mL\] are presented in the results.
Time frame: Part A: Day 1 postdose. Part B: Day 1 postdose and Day 13 postdose.