Clinical Study to Investigate Safety and Effects on Heart Rate, Blood Pressure, and Pharmacokinetic Interactions of ACT-334441

NCT02479204 | Terminated Phase 1

• 1 other identifier: AC-064-102
• Study Type: interventional
• Target: 10
• Locations: 1 country
• Sites: 1

Brief Summary

The aim of the study is to investigate the safety of the concomitant administration of ACT-334441 with cardiovascular drugs.

Conditions

Healthy Subjects

Keywords

safety; heart rate; pharmacokinetics

Outcome Measures

Primary Outcomes (3)

• PR intervals measured by 12-lead ECG (Part A + Part B)

  Absolute PR intervals and corresponding changes from baseline at the different days of measurement

  Days 1 and 6 (Part A); Days 1, 6, 8, 9, 15, and 16 (Part B)

• Heart rate (HR) measured by 12-lead ECG (PArt A + Part B)

  Absolute heart rates at the different days of measurement

  Days 1 and 6 (Part A); Days 1, 6, 8, 9, 15, and 16 (Part B)

• Hourly mean heart rate (HR) measured by 24-hour Holter ECG

  Absolute and change from baseline in hourly mean HR on each day of measurement

  Days 1 and 6 (Part A); Days 1, 6, 8, 9, 15, and 16 (Part B

Secondary Outcomes (6)

• Areas under the plasma concentration-time curves (AUC) for ACT-334441, diltiazem and atenolol (Part B)

  Blood samples from Day 1 to Day 20 for the PK profile of diltiazem and atenolol, and from Day 8 to Day 21 for the PK profile of ACT-334441.

• Maximum plasma concentration (Cmax) for ACT-334441, diltiazem and atenolol (Part B)

  From Day 1 to Day 20 for diltiazem and atenolol; from Day 8 to Day 21 for ACT-33444.

• Time to reach the maximum plasma concentration (tmax) for ACT-334441, diltiazem and atenolol (Part B)

  From Day 1 to Day 20 for diltiazem and atenolol; from Day 8 to Day 21 for ACT-33444

• Terminal half-life [t(1/2)] of ACT-334441, diltiazem and atenolol (Part B)

  From Day 1 to Day 20 for diltiazem and atenolol; from Day 8 to Day 21 for ACT-33444

• Trough plasma levels (Ctrough) of of ACT-334441, diltiazem and atenolol (Part B)

  From Day 1 to Day 15 for diltiazem and atenolol; from Day 8 to Day 15 for ACT-33444

Other Outcomes (1)

• Lymphocyte count as a measure of immunomodulation (Part A + Part B)

  Day 1, Day 6, Day 12 and Day 20 (Part A); Day 1 and Day 8 toDay 16 (Part B)

Study Arms (4)

Part A ACT-334441 + atenolol

EXPERIMENTAL

4 subjects will receive 50 mg of atenolol once daily for 6 days, and a concomitant single administration of ACT-334441 2 mg on Day 6

Drug: ACT-334441 2 mg; Drug: Atenolol

Part A ACT-334441 + diltiazem

EXPERIMENTAL

4 subjects will receive 240 mg of diltiazem once daily for 6 days, and a concomitant single administration of ACT-334441 2 mg on Day 6

Drug: ACT-334441 2 mg; Drug: Diltiazem ER

Part B ACT-334441 + atenolol

EXPERIMENTAL

12 subjects will receive 50 mg of atenolol (once daily) from day 1 to day 15, placebo once on day 6, and ACT-334441 4 mg (once daily) from day 8 to day 15

Drug: ACT-334441 4 mg; Drug: Placebo; Drug: Atenolol

Part B ACT-334441 + diltiazem

EXPERIMENTAL

12 subjects will receive 240 mg of diltiazem (once daily) from day 1 to day 15, placebo once on day 6, and ACT-334441 4 mg (once daily) from day 8 to day 15

Drug: ACT-334441 4 mg; Drug: Placebo; Drug: Diltiazem ER

Interventions

ACT-334441 2 mg DRUG

capsule containing ACT-334441 at a strength of 2 mg

Part A ACT-334441 + atenolol; Part A ACT-334441 + diltiazem

ACT-334441 4 mg DRUG

capsule containing ACT-334441 at a strength of 4 mg

Part B ACT-334441 + atenolol; Part B ACT-334441 + diltiazem

Placebo DRUG

ACT-33441-matching placebo

Part B ACT-334441 + atenolol; Part B ACT-334441 + diltiazem

Atenolol DRUG

film-coated tablet containing atenolol at a strength of 50 mg

Also known as: Tenormine

Part A ACT-334441 + atenolol; Part B ACT-334441 + atenolol

Diltiazem ER DRUG

film-coated tablet containing diltiazem at a strength of of 120 mg

Also known as: Bi-tildiem

Part A ACT-334441 + diltiazem; Part B ACT-334441 + diltiazem

Eligibility Criteria

• Age: 25 Years - 55 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Signed informed consent
• Body mass index (BMI) between 18.0 and 30.0 kg/m2 (inclusive) at screening.
• Women of childbearing potential must have a negative pregnancy test and they must use reliable methods of contraception
• Healthy on the basis of physical examination,cardiovascular assessments and laboratory tests

You may not qualify if:

• Pregnant or lactating women
• Any contraindication to the study drugs
• History or presence of any disease or condition or treatment, which may put the subject at risk of participation in the study or may interfere with the absorption, distribution, metabolism or excretion of the study drugs
• Any clinically significant abnormalities in laboratory tests, vital signs, ECG variables and pulmonary variables
• Any circumstances or conditions, which, in the opinion of the investigator, may affect the subject's full participation in the study or compliance with the protocol

Sponsors & Collaborators

• Viatris Innovation GmbH: lead

Study Sites (1)

BIOTRIAL

Rennes, CS 34246, France

Location

MeSH Terms

Interventions

Atenolol

Intervention Hierarchy (Ancestors)

Phenoxypropanolamines; Propanolamines; Amino Alcohols; Alcohols; Organic Chemicals; Propanols; Amines

Study Officials

• Clinical Trials

  Viatris Innovation GmbH

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: OTHER
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 17, 2015
• First Posted: June 24, 2015
• Study Start: April 28, 2015
• Primary Completion: May 1, 2016
• Study Completion: May 1, 2016
• Last Updated: September 22, 2025

Record last verified: 2018-07

Locations

FR (1)