Clinical trial NCT04255277: To Study the Effect of Cenerimod on the Electrical Activity of the Heart, in Men and Women. To Study the Effect of Cenerimod on the Use of Oral Contraceptives in Women. To Study the Effect That Charcoal Has on the Elimination of Cenerimod From the Body, in Women and Men.
Official title: A Single-center, Double-blind for Cenerimod, Open-label for Moxifloxacin, Placebo-controlled, Parallel-group, Randomized Study in Healthy Male and Female Subjects to Investigate I: the Effect of Cenerimod on the QTc Interval II: the Effect of Cenerimod on the Pharmacokinetics of Combined Oral Contraceptives III: the Effect of Charcoal on the Pharmacokinetics of Cenerimod.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy Subjects
Lead sponsor: Idorsia Pharmaceuticals Ltd.
Sponsor class: INDUSTRY
First posted: 2020-02-05
Enrollment: 97
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Period 1: Pharmacokinetic study, Period 2: Thorough-QT and Drug-drug-interaction study. Period 3: Accelerated elimination study.
Primary purpose: OTHER

Brief summary: This is a single-center, randomized, double-blind for cenerimod, open-label for moxifloxacin, placebo- and moxifloxacin-controlled, parallel-group study to investigate the effect of cenerimod on the duration of the QT interval in healthy male and female participants.

Participants will be randomly assigned to one of the 4 treatments: placebo, cenerimod 0.5 mg, cenerimod 4 mg or moxifloxacin.

Detailed description: Participants randomized in one of the cenerimod or placebo groups will receive combined oral contraceptives on Day 1 (i.e., prior to cenerimod or placebo administration, Period 1) and on Day 42 (i.e., 36 days after the stat of cenerimod or placebo, Period 2).

Half of the participants randomized in one of the cenerimod or placebo groups will be enrolled in an accelerated elimination procedure part (Period 3).

Eligibility criteria: Inclusion Criteria:

* Signed informed consent in a language understandable to the participant prior to any study-mandated procedure.
* Body mass index of 18.0 to 29.9 kg/m\^2 (inclusive) at the screening.
* No clinically relevant findings on the physical examination at screening.
* Systolic blood pressure 90 to 145 mmHg, diastolic blood pressure 45 to 90 mmHg, and pulse rate 50 to 100 bpm (inclusive), measured on the same arm, after 5 min in the supine position at screening and on Day -1.
* 12-lead ECG without clinically relevant abnormalities, measured after 5 min in the supine position at screening and on admission.
* No clinically relevant findings in clinical laboratory tests (hematology, clinical chemistry, and urinalysis) at screening and on admission.
* Negative results from urine drug screen and breath alcohol tests at screening and on admission.
* Women of non-childbearing potential (i.e., postmenopausal \[defined as 12 consecutive months with no menses without an alternative medical cause, confirmed by a follicle-stimulating hormone test\], with previous bilateral salpingectomy, bilateral salpingo-oophorectomy or hysterectomy, or with premature ovarian failure \[confirmed by a specialist\]).
* Women of childbearing potential must have a negative serum pregnancy test at Screening and a negative urine pregnancy test on Day -1. They must consistently and correctly use (from screening, during the entire study, and up to end-of-study) a highly effective method of contraception with a failure rate of less than 1% per year (i.e., intrauterine device, bilateral tubal occlusion) or be sexually inactive, or have a vasectomized partner. Hormonal contraceptive must not be used within 3 months prior to screening until end of study visit.

Exclusion Criteria:

* Previous exposure to cenerimod.
* Previous exposure to combined oral contraceptive(s), moxifloxacin, or charcoal within 3 months prior to screening.
* Known hypersensitivity to treatments of the same class as cenerimod, or any of the excipients.
* Known hypersensitivity to combined oral contraceptive(s), moxifloxacin, or charcoal or treatments of the same class, or any of their excipients.
* Any contraindication to combined oral contraceptive(s) or moxifloxacin treatment.
* Known hypersensitivity or allergy to natural rubber latex.
* Lymphopenia (\< 1000 cells/μL) at Screening and on Day -1.
* Familial history of sick-sinus syndrome.
* Any cardiac condition or illness (including ECG abnormalities) with a potential to increase the cardiac risk of the subject based on the standard 12-lead ECG at screening.
* History of major medical or surgical disorders which, in the opinion of the investigator, are likely to interfere with the absorption, distribution, metabolism, or excretion of the study treatment (appendectomy and herniotomy allowed, cholecystectomy not allowed).
* Acute, ongoing, recurrent, or chronic systemic disease able to interfere with the evaluation.
* Clinically relevant history of fainting, collapse, syncope, orthostatic hypotension, or vasovagal reactions.
* Any immunosuppressive treatment within 6 weeks or 5 terminal half-lives (t½), whichever is longer, before first study drug administration.
* History or clinical evidence of alcoholism or drug abuse.
* Excessive caffeine consumption, defined as 800 mg or more per day at screening.
* Nicotine consumption within 3 months prior to screening and inability to refrain from nicotine consumption.
* Previous treatment with any prescribed medications (including vaccines) or over-the-counter (OTC) medications (including herbal medicines such as St John's Wort, homeopathic preparations, vitamins, and minerals).
* Viral, fungal, bacterial or protozoal infection and / or serology.
* History of deep vein thrombophlebitis or thromboembolic disorders.
* Legal incapacity or limited legal capacity at screening.
* Pregnant or lactating women.
* History or presence of rhythm disorders (e.g., sinoatrial heart block, sick-sinus syndrome, second- or third-degree atrioventricular block, long QT syndrome, symptomatic bradycardia, atrial flutter, or atrial fibrillation) .

Primary outcomes:
measure: Placebo-corrected, change-from-baseline QTcF (ΔΔQTcF)
timeFrame: Day 6, 7, 14, 21, 35, and 56.
measure: Maximum plasma concentration (Cmax): levonorgestrel
timeFrame: Day 1 to Day 3; Day 42 to Day 44
measure: Maximum plasma concentration (Cmax): ethinylestradiol
timeFrame: Day 1 to Day 3; Day 42 to Day 44
measure: Time to reach Cmax (tmax): levonorgestrel
timeFrame: Day 1 to Day 3; Day 42 to Day 44
measure: Time to reach Cmax (tmax): ethinylestradiol
timeFrame: Day 1 to Day 3; Day 42 to Day 44
measure: The area under the plasma concentration-time curve (AUC) from zero to infinity (AUC0-inf): levonorgestrel
timeFrame: Day 1 to Day 3; Day 42 to Day 44
measure: The area under the plasma concentration-time curve (AUC) from zero to t (AUC0-t): levonorgestrel
timeFrame: Day 1 to Day 3; Day 42 to Day 44
measure: The area under the plasma concentration-time curve (AUC) from zero to infinity (AUC0-inf): ethinylestradiol
timeFrame: Day 1 to Day 3; Day 42 to Day 44
measure: The area under the plasma concentration-time curve (AUC) from zero to t (AUC0-t): ethinylestradiol
timeFrame: Day 1 to Day 3; Day 42 to Day 44
measure: Terminal elimination half-life (t1/2): levonorgestrel
timeFrame: Day 56 to Day 68
measure: Terminal elimination half-life (t1/2): ethinylestradiol
timeFrame: Day 56 to Day 68
measure: Terminal elimination half-life (t1/2): cenerimod
timeFrame: Day 56 to Day 68
measure: Area under the plasma concentration-time curve (AUC) from Day 56 to infinity (AUC56-inf) for cenerimod
timeFrame: Day 56 to Day 68
Secondary outcomes:
measure: Change from baseline in total lymphocyte count to each time point
timeFrame: Day 5, Day 7, Day 14, Day 21, Day 35, Day 56, Day 57, Day 58, Day 1, Day 64, and Day 67
measure: Maximum plasma concentration (Cmax): cenerimod
timeFrame: Day 7, Day 14, Day 21, Day 35, and Day 56
measure: Time to reach Cmax (tmax): cenerimod
timeFrame: Day 7, Day 14, Day 21, Day 35, and Day 56
Other outcomes:
Locations:
city: Rennes
country: France
facility: Site 1
Study officials:
affiliation: Idorsia Pharmaceuticals Ltd.
name: Clinical Trials
role: STUDY_DIRECTOR
References: