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

Healthy Subjects Clinical Trial

Official title:

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT02479204
• Other study ID #: AC-064-102
• Status: Terminated
• Phase: Phase 1
• Start date: April 28, 2015
• Est. completion date: May 1, 2016

Study information

• Verified date: July 2018
• Source: Idorsia Pharmaceuticals Ltd.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 10
• Est. completion date: May 1, 2016
• Est. primary completion date: May 1, 2016
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 25 Years to 55 Years

Eligibility

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

Related Conditions & MeSH terms

• Healthy Subjects

Intervention

Drug:
• ACT-334441 2 mg
capsule containing ACT-334441 at a strength of 2 mg
• ACT-334441 4 mg
capsule containing ACT-334441 at a strength of 4 mg
• Placebo
ACT-33441-matching placebo
• Atenolol
film-coated tablet containing atenolol at a strength of 50 mg
• Diltiazem ER
film-coated tablet containing diltiazem at a strength of of 120 mg

Locations

Country	Name	City	State
France	BIOTRIAL	Rennes

Sponsors (1)

Lead Sponsor	Collaborator
Idorsia Pharmaceuticals Ltd.

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	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)
Primary	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)
Primary	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)
Primary	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	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.
Secondary	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.
Secondary	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
Secondary	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
Secondary	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
Secondary	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)]