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.

Idorsia Pharmaceuticals

Status and phase: Completed; Phase 1

Conditions: Healthy Subjects

Treatments: Drug: Moxifloxacin 400mg; Drug: Combined oral contraceptives (COC); Drug: Matching Placebo; Other: Charcoal, activated; Drug: Cenerimod 0.5 mg; Drug: Cenerimod 4 mg

Study type: Interventional

Funder types: Industry

Identifiers

NCT04255277

ID-064-105

2019-003156-36 (EudraCT Number)

Details and patient eligibility

About

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.

Full 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).

Enrollment: 97 patients

Sex: All

Ages: 18 to 65 years old

Volunteers: Accepts Healthy Volunteers

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) .

Trial design

Primary purpose: Other

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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97 participants in 9 patient groups, including a placebo group

Period 1: First administration of combined oral contraceptives

Other group

Description:

Participants randomized to placebo or cenerimod will receive a single oral dose of levonorgestrel (100 μg) and ethinylestradiol (20 μg) in the morning on Day 1.

Treatment:

Drug: Combined oral contraceptives (COC)

Period 2: Second administration of Combined Oral Contraceptive

Other group

Description:

Participants randomized to placebo or cenerimod will receive a single oral dose of levonorgestrel (100 μg) and ethinylestradiol (20 μg) in the morning on Day 42.

Treatment:

Drug: Cenerimod 4 mg

Drug: Cenerimod 0.5 mg

Drug: Combined oral contraceptives (COC)

Period 2: Cenerimod 0.5 mg

Experimental group

Description:

Participants randomized to cenerimod 0.5 mg will receive a single oral dose in the morning from Day 7 to Day 56.

Treatment:

Drug: Combined oral contraceptives (COC)

Period 2: Cenerimod 4 mg

Experimental group

Description:

Participants randomized to cenerimod 4 mg will receive a single oral dose in the morning from Day 7 to Day 56.

Treatment:

Drug: Combined oral contraceptives (COC)

Period 2: Moxifloxacin

Other group

Description:

Participants randomized to moxifloxacin will receive a single oral 400 mg dose in the morning of Day 42.

Treatment:

Drug: Moxifloxacin 400mg

Period 2: Placebo

Placebo Comparator group

Description:

Participants randomized to placebo will receive a single oral dose of placebo in the morning from Day 7 to Day 56.

Treatment:

Drug: Matching Placebo

Period 3: Cenerimod 0.5 mg and charcoal

Experimental group

Description:

Participants randomized to cenerimod 0.5 mg in Period 2 will receive 50 g of activated charcoal every 12 hours from Day 57 to Day 67.

Treatment:

Drug: Cenerimod 0.5 mg

Other: Charcoal, activated

Period 3: Cenerimod 4 mg and charcoal

Experimental group

Description:

Participants randomized to cenerimod 4 mg in Period 2 will receive 50 g of activated charcoal every 12 hours from Day 57 to Day 67.

Treatment:

Drug: Cenerimod 4 mg

Other: Charcoal, activated

Period 3: Cenerimod elimination period

No Intervention group

Description:

Participants randomized to cenerimod 0.5 mg or 4 mg in Period 2 will receive no treatment (i.e., activated charcoal from Day 57 to Day 67) but will have blood samples taken.