Clinical trial NCT06028321: Study of Comparative Bioavailability and Pharmacokinetics of ACM-001.1) and Pindolol in Healthy Volunteers (HV)
Official title: 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)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Cachexia
Lead sponsor: Actimed Therapeutics Ltd
Sponsor class: INDUSTRY
Collaborators: name: Quotient Sciences
First posted: 2023-09-08
Enrollment: 51
Sex: ALL
Minimum age (years): 20
Maximum age (years): 45
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Intervention model description: 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.

Group 2: open label, non-randomized and in parallel with Group 1. Part 2: single-blind (subject blinded), randomized, parallel-group.
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility criteria: 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.

Primary outcomes:
measure: Part 1 Composite of PK parameters following single doses
timeFrame: Up to 5 days
measure: Part 1 PK parameters following single doses
timeFrame: Up to 5 days
measure: Part 1 PK parameters following single doses
timeFrame: Up to 5 days
measure: PK parameters following single doses
timeFrame: Up to 5 days
measure: PK parameters following single doses
timeFrame: Up to 5 days
measure: PK parameters following single doses
timeFrame: Up to 5 days
measure: Stoichiometric dose relationship measured using PK parameters following single doses
timeFrame: Up to 5 days
measure: Stoichiometric dose relationship measured using PK parameters following single doses
timeFrame: Up to 5 days
measure: Part 2 Composite of PK parameters following multiple doses in plasma
timeFrame: Up to 6 days
measure: Part 2 Composite of PK parameters following multiple doses in plasma
timeFrame: Up to 6 days
measure: Part 2 Composite of PK parameters following multiple doses in plasma
timeFrame: Up to 6 days
measure: Pharmacodynamics of ACM-001.1: Cardiovascular vital parameter- heart rate
timeFrame: Up to 6 days
measure: Cardiovascular vital parameter- blood pressure
timeFrame: Up to 6 days
measure: Serum biomarker- DHEA/Cortisol
timeFrame: Day 1 at pre-dose. Day 4 at pre-dose, 1.5 hours
measure: Serum biomarker- Myostatin
timeFrame: Day 1 at pre-dose. Day 4 at pre-dose, 1.5 hours.
measure: Serum biomarker- Folistatin
timeFrame: Day 1 at pre-dose. Day 4 at pre-dose, 1.5 hours.
measure: Serum biomarker-IGF1
timeFrame: Day 1 at pre-dose. Day 4 at pre-dose, 1.5 hours.
measure: Serum biomarker - (Type 3 procollagen peptide) PIIINP
timeFrame: Day 1 at pre-dose. Day 4 at pre-dose, 1.5 hours.
measure: Serum biomarker - monokine-induced by gamma interferon (MIG/CXL9) Leptin
timeFrame: Day 1 at pre-dose. Day 4 at pre-dose, 1.5 hours.
measure: Serum biomarker - epithelial neutrophil activating peptide 78 (ENA78)
timeFrame: Day 1 at pre-dose. Day 4 at pre-dose, 1.5 hours.
measure: Serum biomarker - Ghrelin
timeFrame: Day 1 at pre-dose. Day 4 at pre-dose, 1.5 hours.
measure: Serum biomarker - Growth Hormone Receptor Hormone
timeFrame: Day 1 at pre-dose. Day 4 at pre-dose, 1.5 hours.
measure: Serum biomarker - Somatostatin
timeFrame: Day 1 at pre-dose (baseline). Day 4 at pre-dose, 1.5 hours.
Secondary outcomes:
measure: Part 1 Composite PK parameters in urine following single doses
timeFrame: Up to 5 days
measure: Part 2 Composite PK parameters in urine following multiple doses and pindolol
timeFrame: Up to 7 days
measure: Part 1 and Part 2 Analysis of S-pindolol and R-pindolol concentrations in plasma for any in vivo conversion
timeFrame: Up to 4 days
measure: Part 1 Number of participants with adverse events following single doses as a measure of safety and tolerability
timeFrame: From screening: day -28 to follow up call on day 8 (part 1), up to 36 days.
measure: Part 2 Number of participants with adverse events following single doses as a measure of safety and tolerability
timeFrame: From screening: day -28 to follow up call on day 11 (part 2), up to 39 days.
measure: Part 2 only - Pulmonary function test
timeFrame: Up to 32 days
Other outcomes:
Locations:
city: Ruddington
country: United Kingdom
facility: Quotient Sciences Ltd
Study officials:
References: