This study evaluates the safety and tolerability of HER-096 in healthy volunteer subjects by comparing the effects of active study treatment HER-096 to placebo (0.9% physiological saline). In addition, the pharmacokinetic profile of HER-096 in humans will be investigated. The investigational medicinal products will be administered as a single dose by subcutaneous injection.
This is a Phase I, double-blind, placebo-controlled, clinical study, in which safety, tolerability and pharmacokinetic profile of HER-096 will be investigated after a subcutaneously (s.c.) administered single ascending doses of HER-096 to healthy volunteer subjects (HVS). Altogether 60-64 HVS will be enrolled into the study and the study will be conducted in two parts, part 1 being randomised and part 2 being open-label. In part 1, up to 48 young male HVS will be randomised 6:2 either to receive HER-096 or placebo (0.9% physiological saline) solution. In part 1, up to 6 dosing cohorts have been planned with single ascending doses of HER-096. In part 2, 12-16 older and elderly HVS, both males and females, will be administered with single dose of HER-096 to evaluate the blood-brain-barrier penetration of HER-096. The investigational medicinal products (HER-096 or placebo solution) will be administered as a s.c. injection. The total duration of the study will be up to 36 days for each subject, consisting of screening and treatment period.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
QUADRUPLE
Enrollment
60
Clinical Research Services Turku - CRST Oy
Turku, Finland
Adverse Events (AEs)
Incidence, type and severity of treatment-emergent AEs
Time frame: 8 +/- 1 days
Physical examination
Incidence of clinically significant physical examination findings
Time frame: 8 +/- 1 days
Vital signs
Incidence of clinically significant findings in systolic and diastolic blood pressure, heart rate and body temperature
Time frame: 8 +/- 1 days
12-lead electrocardiogram (ECG)
Incidence of clinically significant findings in heart rate, PR interval, RR, QRS interval and QTcF
Time frame: 24 hours
Pulse oximetry
Incidence of clinically significant changes in blood oxygen saturation
Time frame: 8 hours
Laboratory safety assessments - Haematology
Incidence of clinically significant laboratory variables in haemoglobin, erythrocytes, leucocytes, thrombocytes, mean corpuscular volume (MCV), mean corpuscular haemoglobin concentration (MCHC) and differential leucocyte count
Time frame: 8 +/- 1 days
Laboratory safety assessments - Clinical chemistry
Incidence of clinically significant laboratory variables in alanine aminotransferase (ALT), aspartate aminotransferase (AST), gamma-glutamyl transferase (GGT), bilirubin total, bilirubin conjugated, albumin, creatinine, glucose, sodium, potassium, calcium, C-reactive protein (CRP), creatine kinase (CK), thyroid-stimulating hormone (TSH) and prolactin
Time frame: 8 +/- 1 days
Laboratory safety assessments - Coagulation
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Incidence of clinically significant laboratory variables in plasma activated partial thromboplastin time (P-APTT) and international normalized ratio (INR)
Time frame: 8 +/- 1 days
Laboratory safety assessments - Urinalysis
Incidence of clinically significant laboratory variables in pH, erythrocytes, leukocytes, nitrite, protein, glucose and ketones
Time frame: 8 +/- 1 days
Laboratory safety assessments - CSF (Part 2 only)
Incidence of clinically significant laboratory variables in cell count and protein concentration
Time frame: 12 hours
Columbia-Suicide Severity Rating Scale (C-SSRS)
Incidence of subjects with increased suicidal tendencies measured by C-SSRS questionnaire consisting of maximum of 4 sections. Suicidal ideation: 5 yes/no questions with "yes" indicating suicidal ideation and "no" indicating no suicidal ideation. Intensity of ideation: 5 questions to be rated with respect to the most severe type if ideation (5 being the most severe intensity and 1 being the least intensity). Suicidal behavior: 5 yes/no questions with "yes" indicating suicidal behavior and "no" indicating no suicidal behavior. Actual attempts only: 2 questions to be rated with respect to the most severe outcome of the suicide attempt (highest score indicating the most severe outcome and 0 indicating no harm).
Time frame: 8 +/- 1 days
HER-096 concentration levels
Changes in HER-096 concentration levels in plasma and urine
Time frame: 24 hours
HER-096 concentration in CSF (Part 2 only)
Changes in HER-096 concentration levels in CSF
Time frame: 12 hours