Study of Comparative Bioavailability and Pharmacokinetics of ACM-001.1) and Pindolol in Healthy Volunteers (HV)

NCT ID: NCT06028321

Last Updated: 2023-10-10

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 51 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2021-11-26
• Study Completion Date: 2022-06-02

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.

Conditions

Cachexia

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: TREATMENT
• Blinding Strategy: TRIPLE

Study Groups

Part 2 Group G

Subjects received one of the four regimens over a four day treatment period. Regimen G = 15 mg ACM-001.1 and placebo BID for four days.

Group Type: EXPERIMENTAL

Part 2 Group G (ACM-001.1)

Intervention Type: DRUG

Drug: ACM-001.1 immediate release tablets for oral use and matching placebo. Subjects were dosed over a four day treatment period twice daily. Subjects receiving ACM-001.1 in regimens E, F and G also received placebo tablets to match the tablet number received by subjects receiving pindolol in Regimen D.

Part 2 Group G ( Placebo)

Intervention Type: OTHER

Placebo for oral use. Subjects were dosed over a four day treatment period twice daily. Subjects receiving ACM-001.1 in regimens E, F and G also received placebo tablets to match the tablet number received by subjects receiving pindolol in Regimen D.

Part 1 Group1 (AB)

Part 1 Group1 Subjects were randomised to two treatment regimens (A and B) and received treatment sequence AB in a 2-period cross over.

Regimen A = 15 mg ACM-001.1 and matching placebo. Regimen B = 30 mg pindolol.

Group Type: EXPERIMENTAL

Part 1 Group 1 Regime A (ACM-001.1)

Intervention Type: DRUG

Drug: ACM-001.1 immediate release tablets for oral use and matching placebo, and pindolol tablets for oral use.

Subjects randomised to Regimen A received placebo tablets to match the tablet number received by subjects in Regimen B.

Part 1 Group 1 Regimen B (Pindolol)

Intervention Type: DRUG

Drug: pindolol tablets for oral use. Subjects randomised to Regimen A received placebo tablets to match the tablet number received by subjects in Regimen B.

Part 1 Group 1 Regimen A (Placebo)

Intervention Type: OTHER

Placebo for oral use. Subjects randomised to Regimen A received placebo tablets to match the tablet number received by subjects in Regimen B.

Part 1 Group 1 (BA)

Subjects were randomised to two treatment regimens (A and B) and received treatment sequence BA in a 2-period cross over.

Regimen B = 30 mg pindolol. Regimen A = 15 mg ACM-001.1 and matching placebo.

Group Type: EXPERIMENTAL

Part 1 Group 1 Regime A (ACM-001.1)

Intervention Type: DRUG

Drug: ACM-001.1 immediate release tablets for oral use and matching placebo, and pindolol tablets for oral use.

Subjects randomised to Regimen A received placebo tablets to match the tablet number received by subjects in Regimen B.

Part 1 Group 1 Regimen B (Pindolol)

Intervention Type: DRUG

Drug: pindolol tablets for oral use. Subjects randomised to Regimen A received placebo tablets to match the tablet number received by subjects in Regimen B.

Part 1 Group 1 Regimen A (Placebo)

Intervention Type: OTHER

Placebo for oral use. Subjects randomised to Regimen A received placebo tablets to match the tablet number received by subjects in Regimen B.

Part 1 Group 2 (C)

Subjects were non-randomised; received regimen C in parallel with Group 1 in a single period.

Regimen C = 15 mg pindolol.

Group Type: EXPERIMENTAL

Part 1 Group 2 Regimen C (Pindolol)

Intervention Type: DRUG

Drug: Pindolol tablets for oral use.

Part 2 Group D

Subjects received one of the four regimens over a four day treatment period. Regimen D = 20 mg pindolol BID (bis in die) for four days.

Group Type: EXPERIMENTAL

Part 2 Group D (Pindolol)

Intervention Type: DRUG

Drug: Pindolol tablets for oral use. Subjects were dosed over a four day treatment period twice daily. Subjects receiving ACM-001.1 in regimens E, F and G also received placebo tablets to match the tablet number received by subjects receiving pindolol in Regimen D.

Part 2 Group E

Subjects received one of the four regimens over a four day treatment period. Regimen E = 5 mg ACM-001.1 and placebo BID for four days.

Group Type: EXPERIMENTAL

Part 2 Group E (ACM-001.1)

Intervention Type: DRUG

Drug: ACM-001.1 immediate release tablets for oral use and matching placebo. Subjects were dosed over a four day treatment period twice daily. Subjects receiving ACM-001.1 in regimens E, F and G also received placebo tablets to match the tablet number received by subjects receiving pindolol in Regimen D.

Part 2 Group E (Placebo)

Intervention Type: OTHER

Placebo for oral use. Subjects were dosed over a four day treatment period twice daily.

Subjects receiving ACM-001.1 in regimens E, F and G also received placebo tablets to match the tablet number received by subjects receiving pindolol in Regimen D.

Part 2 Group F

Subjects received one of the four regimens over a four day treatment period. Regimen F = 10 mg ACM-001.1 and placebo BID for four days.

Group Type: EXPERIMENTAL

Part 2 Group F (ACM-001.1 )

Intervention Type: DRUG

Drug: ACM-001.1 immediate release tablets for oral use and matching placebo. Subjects were dosed over a four day treatment period twice daily. Subjects receiving ACM-001.1 in regimens E, F and G also received placebo tablets to match the tablet number received by subjects receiving pindolol in Regimen D.

Part 2 Group F (Placebo)

Intervention Type: OTHER

Placebo for oral use. Subjects were dosed over a four day treatment period twice daily. Subjects receiving ACM-001.1 in regimens E, F and G also received placebo tablets to match the tablet number received by subjects receiving pindolol in Regimen D.

Interventions

Part 1 Group 1 Regime A (ACM-001.1)

Drug: ACM-001.1 immediate release tablets for oral use and matching placebo, and pindolol tablets for oral use.

Subjects randomised to Regimen A received placebo tablets to match the tablet number received by subjects in Regimen B.

Intervention Type: DRUG

Part 1 Group 2 Regimen C (Pindolol)

Drug: Pindolol tablets for oral use.

Intervention Type: DRUG

Part 2 Group D (Pindolol)

Drug: Pindolol tablets for oral use. Subjects were dosed over a four day treatment period twice daily. Subjects receiving ACM-001.1 in regimens E, F and G also received placebo tablets to match the tablet number received by subjects receiving pindolol in Regimen D.

Intervention Type: DRUG

Part 2 Group E (ACM-001.1)

Drug: ACM-001.1 immediate release tablets for oral use and matching placebo. Subjects were dosed over a four day treatment period twice daily. Subjects receiving ACM-001.1 in regimens E, F and G also received placebo tablets to match the tablet number received by subjects receiving pindolol in Regimen D.

Intervention Type: DRUG

Part 2 Group F (ACM-001.1 )

Drug: ACM-001.1 immediate release tablets for oral use and matching placebo. Subjects were dosed over a four day treatment period twice daily. Subjects receiving ACM-001.1 in regimens E, F and G also received placebo tablets to match the tablet number received by subjects receiving pindolol in Regimen D.

Intervention Type: DRUG

Part 2 Group G (ACM-001.1)

Drug: ACM-001.1 immediate release tablets for oral use and matching placebo. Subjects were dosed over a four day treatment period twice daily. Subjects receiving ACM-001.1 in regimens E, F and G also received placebo tablets to match the tablet number received by subjects receiving pindolol in Regimen D.

Intervention Type: DRUG

Part 1 Group 1 Regimen B (Pindolol)

Drug: pindolol tablets for oral use. Subjects randomised to Regimen A received placebo tablets to match the tablet number received by subjects in Regimen B.

Intervention Type: DRUG

Part 1 Group 1 Regimen A (Placebo)

Placebo for oral use. Subjects randomised to Regimen A received placebo tablets to match the tablet number received by subjects in Regimen B.

Intervention Type: OTHER

Part 2 Group E (Placebo)

Placebo for oral use. Subjects were dosed over a four day treatment period twice daily.

Subjects receiving ACM-001.1 in regimens E, F and G also received placebo tablets to match the tablet number received by subjects receiving pindolol in Regimen D.

Intervention Type: OTHER

Part 2 Group F (Placebo)

Placebo for oral use. Subjects were dosed over a four day treatment period twice daily. Subjects receiving ACM-001.1 in regimens E, F and G also received placebo tablets to match the tablet number received by subjects receiving pindolol in Regimen D.

Intervention Type: OTHER

Part 2 Group G ( Placebo)

Placebo for oral use. Subjects were dosed over a four day treatment period twice daily. Subjects receiving ACM-001.1 in regimens E, F and G also received placebo tablets to match the tablet number received by subjects receiving pindolol in Regimen D.

Intervention Type: OTHER

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.

• Minimum Eligible Age: 20 Years
• Maximum Eligible Age: 45 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Quotient Sciences

INDUSTRY

Sponsor Role: collaborator

Actimed Therapeutics Ltd

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

Quotient Sciences Ltd

Ruddington, , United Kingdom

Countries

United Kingdom

Other Identifiers

QSC205141

Identifier Type: OTHER

Identifier Source: secondary_id

ACM-2021-1-CT

Identifier Type: -

Identifier Source: org_study_id