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

NCT02206204 | Completed Phase 1

• 1 other identifier: AC-065-106
• Study Type: interventional
• Target: 159
• Locations: 1 country
• Sites: 1

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

Keywords

Selexipag; ACT-333679

Outcome Measures

Primary Outcomes (1)

• Baseline adjusted placebo corrected change in corrected QTc interval (time interval from beginning of the Q wave until end of the T wave) (ΔΔQTcI) at various time points

  Electrocardiograms (ECGs) will be extracted in replicate at predefined timepoints from replicated 12-lead Holter ECGs. Cardiodynamic endpoints will be assessed at steady-state for 800 μg selexipag on Day 11 and at steady-state for 1600 μg selexipag on Day 23. Based on prospective criteria, QTcI will be the primary method for heart rate (HR) correction.

  24 days

Secondary Outcomes (18)

• Baseline adjusted placebo corrected change in heart rate at various time points

  24 days

• Baseline adjusted placebo corrected change in RR interval (interval from the peak of one QRS complex to the peak of the next) at various time points

  24 days

• Baseline adjusted placebo corrected change in PR interval (time interval from the beginning of the P wave to the beginning of the QRS complex) at various time points

  24 days

• Baseline adjusted placebo corrected change in QRS interval (time interval from the beginning of the Q wave to the end of the S wave) at various time points

  24 days

• Number of time points at which T-wave morphology changes were observed

  24 days

Study Arms (3)

Group A

EXPERIMENTAL

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).

Drug: selexipag; Drug: moxifloxacin-matching placebo

Group B1

EXPERIMENTAL

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.

Drug: placebo for selexipag; Drug: moxifloxacin; Drug: moxifloxacin-matching placebo

Group B2

EXPERIMENTAL

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.

Drug: placebo for selexipag; Drug: moxifloxacin; Drug: moxifloxacin-matching placebo

Interventions

selexipag DRUG

Group A

placebo for selexipag DRUG

Group B1; Group B2

moxifloxacin DRUG

Group B1; Group B2

moxifloxacin-matching placebo DRUG

Group A; Group B1; Group B2

Eligibility Criteria

• Age: 18 Years - 45 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Actelion: lead

Study Sites (1)

Covance Clinical Research Unit

Evansville, Indiana, 47710, United States

Location

MeSH Terms

Interventions

selexipag; Moxifloxacin

Intervention Hierarchy (Ancestors)

Fluoroquinolones; 4-Quinolones; Quinolones; Quinolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Study Officials

• Matthias Hoch, PhD

  Actelion

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 30, 2014
• First Posted: August 1, 2014
• Study Start: June 1, 2012
• Primary Completion: November 1, 2012
• Study Completion: November 1, 2012
• Last Updated: August 1, 2014

Record last verified: 2014-07

Locations

US (1)