A Study Conducted in Healthy Male Subjects to Investigate the Safety and Tolerability of AC-76, Its Fate in the Body, and Its Effect on the Body

Study Overview
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Brief Summary
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The main objective of the study is to investigate the safety and tolerability of single ascending doses of AC-076 administered as subcutaneous injection

Official Title
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Single-center, Double-blind, Placebo-controlled, Randomized, Single-ascending Dose Study to Investigate the Tolerability, Safety, Pharmacokinetics, and Pharmacodynamics of AC-076 in Healthy Male Subjects

Conditions
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Healthy Subjects

Intervention / Treatment
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* Drug: AC-076 for s.c. administration
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Signed informed consent Body mass index (BMI) of 18.0 to 31.0 kg/m2 (inclusive) at screening Systolic blood pressure (SBP) 100-145 mmHg, diastolic blood pressure (DBP) 50-90 mmHg, and pulse rate 45-90 beats per minute (inclusive) at screening Healthy on the basis of physical examination, electrocardiogram and laboratory tests Maximum (at peak) platelet aggregation ≥ 40% Values of closure time tested with the Platelet Function Analyzer (PFA) equipment, for both cartridges of collagen/epinephrine and collagen/ADP below the upper limit of normal range at screening Exclusion Criteria: Known hypersensitivity to AC-076 or drugs of the same class, or any of their excipients Family or personal history of prolonged bleeding or bleeding disorders, intracranial vascular diseases, stroke, reasonable suspicion of vascular malformations, or peptic ulcers Platelet count < 120 × 109 L-1 at screening Known platelet disorders Orthostatic hypotension at screening (i.e., decrease from supine to standing BP of > 20 mmHg in SBP or > 10 mmHg in DBP after being in standing position for 3 min) Previous treatment with acetylsalicylate, non-steroidal anti-inflammatory drugs or any medication with blood thinning activity within 3 weeks prior to study drug administration; or with any other prescribed medications (including vaccines) or over the counter medications within 2 weeks prior to study drug administration Any circumstances or conditions, which, in the opinion of the investigator, may affect full participation in the study or compliance with the protocol

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 45 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Other
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: AC-076 sc administration - single ascending dose<br>On Day 1, 48 subjects will receive AC-076 at different single dose levels in a sequential manner and in a maximum of 6 dose levels, starting from 1 mg. Subjects will be followed by an observation period of 48 h. Each dose level will be investigated in a new group of 8 healthy male subjects (6 on active drug and 2 on placebo) | Drug: AC-076 for s.c. administration<br>* Lyophilized AC-076A to be reconstituted with 1 mL of water for injection<br>|
| Placebo Comparator: Placebo<br>For each AC-076 dose level tested, 2 healthy male subjects will receive matching placebo in the same condition | Drug: Placebo<br>* Sterile 0.9% w/v sodium chloride solution<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of participants with adverse events (AEs) | Treatment-emergent AEs and treatment-emergent serious AEs | From study treatment administration up to day 3 | 
| Changes from baseline in electrocardiogram (ECG) variables | ECG variables are to be recorded at rest using a standard 12-lead ECG | From study treatment administration up to day 3 | 
| Changes from baseline in supine blood pressure | Supine blood pressure (mmHg) | From study treatment administration up to day 3 | 
| Changes from baseline in pulse rate | Pulse rate (bpm) | From study treatment administration up to day 3 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Measurement of inhibition of platelet aggregation (IPA) using anticoagulant assays | Maximum (MPA) and final (FPA) platelet aggregation using light transmission aggregometry (LTA) assay. % inhibition of platelet aggregation (IPA), MPA and FPA. P2Y12 reaction units (PRU) using the VerifyNow P2Y12 assay. IPA PRU | From baseline up to day 3 | 
| Maximum plasma concentration (Cmax) of AC-076 | Cmax of AC-076 will be derived by non-compartmental analysis of the plasma concentration-time profile | From baseline up to day 3 | 
| time to reach Cmax (tmax) | tmax of AC-076 will be derived by non-compartmental analysis of the plasma concentration-time profile | From baseline up to day 3 | 
| terminal half-life (t1/2) | t1/2 of AC-076 will be derived by non-compartmental analysis of the plasma concentration-time profile | From baseline up to day 3 | 
| Area under the plasma concentration-time curves during a dosing interval [AUC(0-t)] of | AUC(0-t) of AC-076 will be derived by non-compartmental analysis of the plasma concentration-time profile | From baseline up to day 3 | 
| Area under the plasma concentration-time curves from time 0 to inf [AUC(0-inf)] | AUC(0-inf) of AC-076 will be derived by non-compartmental analysis of the plasma concentration-time profile | From baseline up to day 3 |