Study of Selexipag and Its Metabolite ACT-333679 on Cardiac Repolarization in Healthy Male and Female Subjects

NCT ID: NCT02206204

Last Updated: 2014-08-01

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 159 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2012-06-30
• Study Completion Date: 2012-11-30

Brief Summary

This is a single-center, double-blind, randomized, placebo- and positive-controlled, double-dummy, parallel-group, multiple-dose, up-titration study with a nested cross-over comparison between moxifloxacin and placebo in healthy male and female subjects. The primary objective is to demonstrate that selexipag and its metabolite ACT-333679 do not have an effect on cardiac repolarization exceeding the threshold of regulatory concern, at two orally administered dose levels (800 and 1600 μg twice daily) in healthy male and female subjects. Moxifloxacin is included as a positive control.

Conditions

Cardiodynamics; Safety; Tolerability; Pharmacokinetics

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Blinding Strategy: TRIPLE

Study Groups

Group A

Subjects in Group A receive selexipag on Days 3 to 23 and moxifloxacin-matching placebo on Days 2 and 24. Selexipag administered orally, twice a day, for 21 days according to the following multiple dose up-titration regimen: 400 μg on Days 3-5, 600 μg on Days 6-8, 800 μg on Days 9-11, 1000 μg on Days 12-14, 1200 μg on Days 15-17, 1400 μg on Days 18-20, and 1600 μg on Days 21-23 (only morning dose on Day 23).

Group Type: EXPERIMENTAL

selexipag

Intervention Type: DRUG

moxifloxacin-matching placebo

Intervention Type: DRUG

Group B1

Subjects in Group B1 receive 400 mg moxifloxacin, orally on Day 2 and moxifloxacin-matching placebo, orally on Day 24. Subjects receive placebo for selexipag, orally on Days 3 to 23.

Group Type: EXPERIMENTAL

placebo for selexipag

Intervention Type: DRUG

moxifloxacin

Intervention Type: DRUG

moxifloxacin-matching placebo

Intervention Type: DRUG

Group B2

Subjects in Group B2 receive moxifloxacin-matching placebo, orally on Day 2 and 400 mg moxifloxacin, orally on Day 24. Subjects receive placebo for selexipag, orally on Days 3 to 23.

Group Type: EXPERIMENTAL

placebo for selexipag

Intervention Type: DRUG

moxifloxacin

Intervention Type: DRUG

moxifloxacin-matching placebo

Intervention Type: DRUG

Interventions

selexipag

Intervention Type: DRUG

placebo for selexipag

Intervention Type: DRUG

moxifloxacin

Intervention Type: DRUG

moxifloxacin-matching placebo

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• Signed, dated written informed consent prior to any study procedure.
• Ability to communicate well with the investigator in local language, and to understand and comply with the requirements of the study.
• Women of childbearing potential must have had a negative serum pregnancy test at screening and a negative serum pregnancy test on Day -1. Women of childbearing potential must have consistently and correctly used a reliable method of contraception with a failure rate of < 1% per year, been sexually inactive, or have vasectomized partner.
• Healthy based on medical history and assessments performed at screening and on Day -1.
• Body mass index ≥ 18.5 and ≤ 32 kg/m^2 at screening. Body weight at least 50 kg.
• Negative results from urine drug screen at screening and on Day -1 and negative urine alcohol test on Day -1.
• Willing to refrain from alcohol consumption from at least 48 hours prior to clinic admission to the end of study.
• Systolic blood pressure 90-145 mmHg, diastolic blood pressure 50-90 mmHg, and pulse rate 45-90 beats per minute, at screening and Day -1.
• Hematology, blood chemistry, and urinalysis results not deviating from the normal range to a clinically relevant extent at screening and Day -1.

Exclusion Criteria

• Known hypersensitivity to selexipag, moxifloxacin, or excipients of the drug formulations used in this study.
• Treatment with selexipag or an investigational drug prior to screening within 30 days or 6 half-lives, whichever was longer.
• History or clinical evidence of any disease and/or the existence of any surgical or medical condition, which might interfere with the absorption, distribution, metabolism, or excretion of selexipag and moxifloxacin.
• Caffeine consumption of equal to or greater than 800 mg per day at screening.
• History of fainting, collapse, syncope, blackouts, orthostatic hypotension, or vasovagal reactions.
• Chronic or relevant acute infections.
• History of relevant allergy / hypersensitivity.
• History of clinical evidence of psychiatric disease, alcoholism, or drug abuse within the 3-year period prior to screening.
• Smoking within the 3 months prior to screening and inability to refrain from smoking during the study.
• Loss of 500 mL or more of blood within 56 days prior to screening.
• Positive results from the hepatitis serology, except for vaccinated subjects at screening.
• Positive results from human immunodeficiency virus serology at screening.
• Previous treatment with any prescribed or over-the-counter medications, with the exception of contraceptives and hormone replacement therapy, within the 2 weeks prior to first study drug administration or 5 half-lives, whichever longer.
• Excessive physical activities within 1 week prior to administration of study drug.
• Any cardiac condition (including ECG abnormalities) or illness with a potential to increase the cardiac risk of the subject or that may affect QTc analysis.
• QTc > 450 ms or > 470 ms for male or female subjects, respectively, at screening and Day -1.
• Clinically relevant abnormalities on ECG, at screening and Day -1.
• Personal or family history of long QT syndrome or hypokalemia.
• Legal incapacity or limited legal capacity.
• Veins unsuitable for intravenous puncture on either arm.
• Any circumstances or conditions, which, in the opinion of the investigator, may affected the subject's participation in the study or compliance with the protocol.
• Pregnant or nursing women.
• Women who plan to become pregnant within 1 month of the end of study.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 45 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Actelion

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Matthias Hoch, PhD

Role: STUDY_DIRECTOR

Actelion

Locations

Covance Clinical Research Unit

Evansville, Indiana, United States

Countries

United States

Other Identifiers

AC-065-106

Identifier Type: -

Identifier Source: org_study_id