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.

Healthy Subjects Clinical Trial

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.

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04255277
• Other study ID #: ID-064-105
• Secondary ID: 2019-003156-36
• Status: Completed
• Phase: Phase 1
• Start date: January 31, 2020
• Est. completion date: October 18, 2021

Study information

• Verified date: November 2022
• Source: Idorsia Pharmaceuticals Ltd.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Completed
• Enrollment: 97
• Est. completion date: October 18, 2021
• Est. primary completion date: September 14, 2021
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

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) .

Related Conditions & MeSH terms

• Healthy Subjects

Intervention

Drug:
• Combined oral contraceptives (COC)
A commercially available COC consisting of 0.1mg levonorgestrel and 0.02 mg ethinylestradiol will be used and administered open-label.
• Moxifloxacin 400mg
A commercially available formulation of moxifloxacin 400 mg will be used and administered open-label. All tablets will be from the same batch.
• Cenerimod 0.5 mg
This will be administered orally as a film-coated tablet in the morning.
• Cenerimod 4 mg
This will be administered orally as a film-coated tablet in the morning.

Other:
• Charcoal, activated
Granules for oral suspension will be used and administered open-label.

Drug:
• Matching Placebo
Cenerimod matching placebo tablets will be administered once daily orally in the morning.

Locations

Country	Name	City	State
France	Site 1	Rennes

Sponsors (1)

Lead Sponsor	Collaborator
Idorsia Pharmaceuticals Ltd.

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Placebo-corrected, change-from-baseline QTcF (??QTcF)	ECG variables will be assessed from ECGs extracted in replicates at predefined time points from continuous 24 hour Holter ECG recordings.	Day 6, 7, 14, 21, 35, and 56.
Primary	Maximum plasma concentration (Cmax): levonorgestrel	Blood samples for determination of pharmacokinetic parameters will be collected at multiple predefined time points.	Day 1 to Day 3; Day 42 to Day 44
Primary	Maximum plasma concentration (Cmax): ethinylestradiol	Blood samples for determination of pharmacokinetic parameters will be collected at multiple predefined time points.	Day 1 to Day 3; Day 42 to Day 44
Primary	Time to reach Cmax (tmax): levonorgestrel	Blood samples for determination of pharmacokinetic parameters will be collected at multiple predefined time points.	Day 1 to Day 3; Day 42 to Day 44
Primary	Time to reach Cmax (tmax): ethinylestradiol	Blood samples for determination of pharmacokinetic parameters will be collected at multiple predefined time points.	Day 1 to Day 3; Day 42 to Day 44
Primary	The area under the plasma concentration-time curve (AUC) from zero to infinity (AUC0-inf): levonorgestrel	Blood samples for determination of pharmacokinetic parameters will be collected at multiple predefined time points.	Day 1 to Day 3; Day 42 to Day 44
Primary	The area under the plasma concentration-time curve (AUC) from zero to t (AUC0-t): levonorgestrel	Blood samples for determination of PK parameters will be collected at predefined	Day 1 to Day 3; Day 42 to Day 44
Primary	The area under the plasma concentration-time curve (AUC) from zero to infinity (AUC0-inf): ethinylestradiol	Blood samples for determination of pharmacokinetic parameters will be collected at multiple predefined time points.	Day 1 to Day 3; Day 42 to Day 44
Primary	The area under the plasma concentration-time curve (AUC) from zero to t (AUC0-t): ethinylestradiol	Blood samples for determination of pharmacokinetic parameters will be collected at multiple predefined time points.	Day 1 to Day 3; Day 42 to Day 44
Primary	Terminal elimination half-life (t1/2): levonorgestrel	Blood samples for determination of pharmacokinetic parameters will be collected at multiple predefined time points.	Day 56 to Day 68
Primary	Terminal elimination half-life (t1/2): ethinylestradiol	Blood samples for determination of pharmacokinetic parameters will be collected at multiple predefined time points.	Day 56 to Day 68
Primary	Terminal elimination half-life (t1/2): cenerimod	Blood samples for determination of pharmacokinetic parameters will be collected at multiple predefined time points.	Day 56 to Day 68
Primary	Area under the plasma concentration-time curve (AUC) from Day 56 to infinity (AUC56-inf) for cenerimod	Blood samples for determination of pharmacokinetic parameters will be collected at multiple predefined time points.	Day 56 to Day 68
Secondary	Change from baseline in total lymphocyte count to each time point	Blood samples (fasting) collected at predefined time points as part of the normal hematology analysis.	Day 5, Day 7, Day 14, Day 21, Day 35, Day 56, Day 57, Day 58, Day 1, Day 64, and Day 67
Secondary	Maximum plasma concentration (Cmax): cenerimod	Blood samples for determination of pharmacokinetic parameters will be collected at multiple predefined time points.	Day 7, Day 14, Day 21, Day 35, and Day 56
Secondary	Time to reach Cmax (tmax): cenerimod	Blood samples for determination of pharmacokinetic parameters will be collected at multiple predefined time points.	Day 7, Day 14, Day 21, Day 35, and Day 56