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

Single-center, Open-label, Randomized, Multiple-dose, Parallel-group Study to Investigate Safety and Effects on Heart Rate, Blood Pressure, and Pharmacokinetic Interactions of ACT-334441 Combined With Calcium-channel Blocker (Diltiazem) or Beta-blocker (Atenolol) Treatment in Healthy Subjects

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

Study Overview

• Status: Terminated
• Conditions: Healthy Subjects
• Intervention / Treatment: Drug: ACT-334441 2 mg; Drug: Atenolol; Drug: Diltiazem ER; Drug: ACT-334441 4 mg; Drug: Placebo

Detailed Description

The study will consist of two parts: a pilot part (Part A) that will be completed prior to the start of the main part (Part B). The Subjects who will participate in Part A are excluded from Part B.

• Study Type: Interventional
• Enrollment (Actual): 10
• Phase: Phase 1

Contacts and Locations

Study Locations

• France
  • Rennes, France, CS 34246
    • Biotrial

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 25 years to 55 years (Adult)
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• 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

Exclusion Criteria:

• 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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Part A ACT-334441 + atenolol; 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; capsule containing ACT-334441 at a strength of 2 mg; Drug: Atenolol; film-coated tablet containing atenolol at a strength of 50 mg; Other Names: Tenormine
Experimental: Part A ACT-334441 + diltiazem; 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; capsule containing ACT-334441 at a strength of 2 mg; Drug: Diltiazem ER; film-coated tablet containing diltiazem at a strength of of 120 mg; Other Names: Bi-tildiem
Experimental: Part B ACT-334441 + atenolol; 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: Atenolol; film-coated tablet containing atenolol at a strength of 50 mg; Other Names: Tenormine; Drug: ACT-334441 4 mg; capsule containing ACT-334441 at a strength of 4 mg; Drug: Placebo; ACT-33441-matching placebo
Experimental: Part B ACT-334441 + diltiazem; 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: Diltiazem ER; film-coated tablet containing diltiazem at a strength of of 120 mg; Other Names: Bi-tildiem; Drug: ACT-334441 4 mg; capsule containing ACT-334441 at a strength of 4 mg; Drug: Placebo; ACT-33441-matching placebo

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
Areas under the plasma concentration-time curves (AUC) for ACT-334441, diltiazem and atenolol (Part B)	AUCs will be calculated will be calculated according to the linear trapezoidal rule for the following periods: from zero to time t of the last measured concentration above the limit of quantification, from zero to 24h after study drug administration, from zero to infinity)	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)	The measured individual concentrations of ACT-334441, diltiazem and atenolol will be used to obtain their respective Cmax	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)	The measured individual concentrations of ACT-334441, diltiazem and atenolol will be used to obtain their respective tmax	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)	Time required for the plasma concentration of a drug to decrease by 50% in the final stage of its elimination	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)	Ctrough will be used to determine the attainment of steady state conditions	From Day 1 to Day 15 for diltiazem and atenolol; from Day 8 to Day 15 for ACT-33444
Number of subjects with adverse events as a measure of safety	An AE is defined as any unfavorable and unintended sign, including an abnormal laboratory finding, symptom or disease, that occurs during the course of the study, whether or not considered related to the study drug	From baseline to end of study [Day 20-23 (Part A), Day 556-59 (Part B)]

Other Outcome Measures

Outcome Measure	Time Frame
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)

Collaborators and Investigators

• Sponsor: Viatris Innovation GmbH
• Investigators: Study Director: Clinical Trials, Viatris Innovation GmbH

Study record dates

Study Major Dates

• Study Start (Actual): April 28, 2015
• Primary Completion (Actual): May 1, 2016
• Study Completion (Actual): May 1, 2016

Study Registration Dates

• First Submitted: June 17, 2015
• First Submitted That Met QC Criteria: June 19, 2015
• First Posted (Estimated): June 24, 2015

Study Record Updates

• Last Update Posted (Estimated): September 22, 2025
• Last Update Submitted That Met QC Criteria: September 16, 2025
• Last Verified: July 1, 2018

More Information

Terms related to this study

• Keywords: safety; pharmacokinetics; heart rate
• Additional Relevant MeSH Terms: Organic Chemicals; Amines; Alcohols; Phenoxypropanolamines; Propanolamines; Amino Alcohols; Propanols; Atenolol
• Other Study ID Numbers: AC-064-102