Study of Selexipag and Its Metabolite ACT-333679 on Cardi... | NCT02206204

Status Module

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
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

Name	Type	Description	Arm Group Labels	Other Names
selexipag	Drug		Group A
placebo for selexipag

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
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

Measure	Description	Time Frame
Baseline adjusted placebo corrected change in heart rate 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.	24 days

Eligibility Module

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.

ID	Term
C523468	selexipag
D000077266	Moxifloxacin

ID	Term
D024841	Fluoroquinolones
D042462	4-Quinolones
D015363	Quinolones
D011804	Quinolines
D006574	Heterocyclic Compounds, 2-Ring
D000072471	Heterocyclic Compounds, Fused-Ring
D006571	Heterocyclic Compounds