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.
- Conditions
- Healthy Subjects
- Interventions
- Drug: Combined oral contraceptives (COC)Drug: Matching PlaceboOther: Charcoal, activated
- Registration Number
- NCT04255277
- Lead Sponsor
- Idorsia Pharmaceuticals Ltd.
- 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).
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 97
- 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.
- 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) .
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Period 1: First administration of combined oral contraceptives Combined oral contraceptives (COC) 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. Period 2: Second administration of Combined Oral Contraceptive Combined oral contraceptives (COC) 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. Period 2: Second administration of Combined Oral Contraceptive Cenerimod 0.5 mg 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. Period 2: Second administration of Combined Oral Contraceptive Cenerimod 4 mg 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. Period 2: Cenerimod 0.5 mg Combined oral contraceptives (COC) Participants randomized to cenerimod 0.5 mg will receive a single oral dose in the morning from Day 7 to Day 56. Period 2: Cenerimod 4 mg Combined oral contraceptives (COC) Participants randomized to cenerimod 4 mg will receive a single oral dose in the morning from Day 7 to Day 56. Period 2: Moxifloxacin Moxifloxacin 400mg Participants randomized to moxifloxacin will receive a single oral 400 mg dose in the morning of Day 42. Period 2: Placebo Matching Placebo Participants randomized to placebo will receive a single oral dose of placebo in the morning from Day 7 to Day 56. Period 3: Cenerimod 0.5 mg and charcoal Cenerimod 0.5 mg 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. Period 3: Cenerimod 0.5 mg and charcoal Charcoal, activated 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. Period 3: Cenerimod 4 mg and charcoal Cenerimod 4 mg 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. Period 3: Cenerimod 4 mg and charcoal Charcoal, activated 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.
- Primary Outcome Measures
Name Time Method Placebo-corrected, change-from-baseline QTcF (ΔΔQTcF) Day 6, 7, 14, 21, 35, and 56. ECG variables will be assessed from ECGs extracted in replicates at predefined time points from continuous 24 hour Holter ECG recordings.
Maximum plasma concentration (Cmax): levonorgestrel Day 1 to Day 3; Day 42 to Day 44 Blood samples for determination of pharmacokinetic parameters will be collected at multiple predefined time points.
Time to reach Cmax (tmax): levonorgestrel Day 1 to Day 3; Day 42 to Day 44 Blood samples for determination of pharmacokinetic parameters will be collected at multiple predefined time points.
Maximum plasma concentration (Cmax): ethinylestradiol Day 1 to Day 3; Day 42 to Day 44 Blood samples for determination of pharmacokinetic parameters will be collected at multiple predefined time points.
Terminal elimination half-life (t1/2): ethinylestradiol Day 56 to Day 68 Blood samples for determination of pharmacokinetic parameters will be collected at multiple predefined time points.
Terminal elimination half-life (t1/2): cenerimod Day 56 to Day 68 Blood samples for determination of pharmacokinetic parameters will be collected at multiple predefined time points.
Area under the plasma concentration-time curve (AUC) from Day 56 to infinity (AUC56-inf) for cenerimod Day 56 to Day 68 Blood samples for determination of pharmacokinetic parameters will be collected at multiple predefined time points.
The area under the plasma concentration-time curve (AUC) from zero to t (AUC0-t): levonorgestrel Day 1 to Day 3; Day 42 to Day 44 Blood samples for determination of PK parameters will be collected at predefined
The area under the plasma concentration-time curve (AUC) from zero to infinity (AUC0-inf): ethinylestradiol Day 1 to Day 3; Day 42 to Day 44 Blood samples for determination of pharmacokinetic parameters will be collected at multiple predefined time points.
The area under the plasma concentration-time curve (AUC) from zero to t (AUC0-t): ethinylestradiol Day 1 to Day 3; Day 42 to Day 44 Blood samples for determination of pharmacokinetic parameters will be collected at multiple predefined time points.
Terminal elimination half-life (t1/2): levonorgestrel Day 56 to Day 68 Blood samples for determination of pharmacokinetic parameters will be collected at multiple predefined time points.
Time to reach Cmax (tmax): ethinylestradiol Day 1 to Day 3; Day 42 to Day 44 Blood samples for determination of pharmacokinetic parameters will be collected at multiple predefined time points.
The area under the plasma concentration-time curve (AUC) from zero to infinity (AUC0-inf): levonorgestrel Day 1 to Day 3; Day 42 to Day 44 Blood samples for determination of pharmacokinetic parameters will be collected at multiple predefined time points.
- Secondary Outcome Measures
Name Time Method Change from baseline in total lymphocyte count to each time point Day 5, Day 7, Day 14, Day 21, Day 35, Day 56, Day 57, Day 58, Day 1, Day 64, and Day 67 Blood samples (fasting) collected at predefined time points as part of the normal hematology analysis.
Time to reach Cmax (tmax): cenerimod Day 7, Day 14, Day 21, Day 35, and Day 56 Blood samples for determination of pharmacokinetic parameters will be collected at multiple predefined time points.
Maximum plasma concentration (Cmax): cenerimod Day 7, Day 14, Day 21, Day 35, and Day 56 Blood samples for determination of pharmacokinetic parameters will be collected at multiple predefined time points.
Trial Locations
- Locations (1)
Site 1
🇫🇷Rennes, France
Site 1🇫🇷Rennes, France