Two Part Study to Assess Comparative Bioavailability, Pharmacokinetics of a Single Dose of ACM-001.1, Two Single Doses of Pindolol (Part1) Followed by Evaluation of Steady State Pharmacokinetics, Pharmacodynamics of ACM-001.1 in HV (Part2)

ACM-2021-1-CT

The aim of this early phase two-part study was to compare the bioavailability (BA) pharmacokinetics (PK) and pharmacodynamics (PD) of racemic pindolol with the benzoate salt of the S-enantiomer of pindolol (ACM-001.1) and provide safety information. A total of 51 healthy male and female subjects were enrolled, and 48 healthy subjects completed the study. Part 1 consisted of two Groups to compare BA and PK, Group 1 received two treatment sequences of a single dose of ACM-001.1 versus racemic pindolol; Group 2 ran in parallel with Group 1 and assessed the PK of a single dose of racemic pindolol in a single period. Part 2 consisted of four groups, to evaluate the steady state PK and PD of ACM-001.1 with multiple ascending doses over 4 days.

2021-11-26

2022-06-02

2022-06-02

Completed

Early phase I

51

Inclusion Criteria: * Healthy males or non-pregnant, non-lactating healthy females * Aged 20 to 45 years inclusive at the time of signing informed consent * Body Mass Index (BMI) of 18.0 to 30.0 kg/m2 as measured at screening * Weight of 50 to 100 kg at screening Exclusion Criteria: * Subjects who had received any investigational medicinal product in a clinical research study within the 90 days prior to Day 1, * Subjects for whom pindolol was contraindicated: hypersensitivity to the active substance or to any of its listed excipients. * Evidence of current Severe Acute Respiratory Coronavirus 2 infection. * History of any drug or alcohol abuse in the past 2 years. * Females of childbearing potential who were pregnant or lactating. * History of clinically significant cardiovascular disease, Raynaud's disease or phenomenon, renal, hepatic, dermatological, chronic respiratory or gastrointestinal disease, neurological or psychiatric disorder. * Subjects who were found to have mean heart rate less than 50 bpm at rest or mean systolic blood pressure (BP) less than 100 mmHg or mean diastolic heart rate less than 50 mmHg. * Subjects who were taking, or had taken, any prescribed or over-the-counter drug or herbal remedies (other than paracetamol, hormonal replacement therapy/hormonal contraception). Pindolol should not be taken in conjunction with agents which inhibit calcium transport.

{'studyType': 'INTERVENTIONAL', 'phases': ['PHASE1'], 'designInfo': {'allocation': 'RANDOMIZED', 'interventionModel': 'CROSSOVER', 'interventionModelDescription': 'Part 1: part - blinded, part randomized, partial cross- over study. Group 1: double - blinded and randomized to two treatment sequences in a two period cross- over.\n\nGroup 2: open label, non-randomized and in parallel with Group 1. Part 2: single-blind (subject blinded), randomized, parallel-group.', 'primaryPurpose': 'TREATMENT', 'maskingInfo': {'masking': 'TRIPLE', 'maskingDescription': 'Part 2 was single - blind study (subject blinded). Masking was not triple for all parts of the study or all arms.', 'whoMasked': ['PARTICIPANT', 'INVESTIGATOR', 'OUTCOMES_ASSESSOR']}}, 'enrollmentInfo': {'count': 51, 'type': 'ACTUAL'}}

2023-10-10