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
Overview
- Phase
- Phase 1
- Intervention
- AC-076 for s.c. administration
- Conditions
- Healthy Subjects
- Sponsor
- Viatris Innovation GmbH
- Enrollment
- 72
- Locations
- 1
- Primary Endpoint
- Number of participants with adverse events (AEs)
- Status
- Completed
- Last Updated
- 10 months ago
Overview
Brief Summary
The main objective of the study is to investigate the safety and tolerability of single ascending doses of AC-076 administered as subcutaneous injection
Investigators
Eligibility Criteria
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
Arms & Interventions
AC-076 sc administration - single ascending dose
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)
Intervention: AC-076 for s.c. administration
Placebo
For each AC-076 dose level tested, 2 healthy male subjects will receive matching placebo in the same condition
Intervention: Placebo
Outcomes
Primary Outcomes
Number of participants with adverse events (AEs)
Time Frame: From study treatment administration up to day 3
Treatment-emergent AEs and treatment-emergent serious AEs
Changes from baseline in electrocardiogram (ECG) variables
Time Frame: From study treatment administration up to day 3
ECG variables are to be recorded at rest using a standard 12-lead ECG
Changes from baseline in supine blood pressure
Time Frame: From study treatment administration up to day 3
Supine blood pressure (mmHg)
Changes from baseline in pulse rate
Time Frame: From study treatment administration up to day 3
Pulse rate (bpm)
Secondary Outcomes
- Maximum plasma concentration (Cmax) of AC-076(From baseline up to day 3)
- time to reach Cmax (tmax)(From baseline up to day 3)
- Measurement of inhibition of platelet aggregation (IPA) using anticoagulant assays(From baseline up to day 3)
- Area under the plasma concentration-time curves from time 0 to inf [AUC(0-inf)](From baseline up to day 3)
- Area under the plasma concentration-time curves during a dosing interval [AUC(0-t)] of(From baseline up to day 3)
- terminal half-life (t1/2)(From baseline up to day 3)