Study of the Electrocardiographic Effects of Ponesimod in Healthy Male and Female Subjects

NCT02136888 | Completed Phase 1

• 1 other identifier: AC-058-110
• Study Type: interventional
• Target: 116
• Locations: 1 country
• Sites: 1

Brief Summary

The aim of this study is to demonstrate that therapeutic and supratherapeutic plasma exposures to ponesimod do not have an effect on cardiac repolarization exceeding the threshold of regulatory concern as measured by the QTc (interval from beginning of the Q wave until end of the T wave corrected for heart rate) interval duration after administration of multiple oral doses of 40 mg and 100 mg to healthy male and female subjects.

Conditions

Healthy

Keywords

Ponesimod; Safety

Outcome Measures

Primary Outcomes (2)

• Baseline-adjusted, placebo-corrected effect on QTc interval (time interval from beginning of the Q wave until end of the T wave (ΔΔQTc interval)) on Day 12 (after 5 days of 40 mg ponesimod)

  Replicate electrocardiograms (ECGs) (at least 3 and up to 10) for the determination of ΔΔQTc interval will be extracted from the continuous digital 12-lead ECG recording within 20 minutes prior to dosing and then at 1, 2, 2.5, 3, 4, 5, 6, 8, 9, 10, 11, and 12 hours (total of 13 time points) post-dose on Days -1, 1, and 12.

  12 Days

• Baseline-adjusted, placebo-corrected effect on QTc interval (time interval from beginning of the Q wave until end of the T wave (ΔΔQTc interval)) on Day 23 (after 5 days of 100 mg ponesimod)

  Replicate electrocardiograms (ECGs) (at least 3 and up to 10) for the determination of ΔΔQTc interval will be extracted from the continuous digital 12-lead ECG recording within 20 minutes prior to dosing and then at 1, 2, 2.5, 3, 4, 5, 6, 8, 9, 10, 11, and 12 hours (total of 13 time points) post-dose on Days -1, 1, and 23.

  23 Days

Secondary Outcomes (39)

• Baseline-adjusted, placebo-corrected effect on QT beat-to-beat interval (QTbtb interval) on Day 12 (after 5 days of 40 mg ponesimod)

  12 Days

• Baseline-adjusted, placebo-corrected effect on QT beat-to-beat interval (QTbtb interval) on Day 23 (after 5 days of 100 mg ponesimod)

  23 Days

• Baseline-adjusted, placebo-corrected effect on heart rate on Day 12 (after 5 days of 40 mg ponesimod)

  12 Days

• Baseline-adjusted, placebo-corrected effect on heart rate on Day 23 (after 5 days of 100 mg ponesimod)

  23 Days

• Baseline-adjusted, placebo-corrected effect on the R-to-R interval (interval from the peak of one QRS complex to the peak of the next (RR interval)) on Day 12 (after 5 days of 40 mg ponesimod)

  12 Days

Study Arms (2)

Group A

EXPERIMENTAL

Ponesimod will be administered orally, once daily for 22 days starting on Day 2, and will comprise the following multiple-dose up-titration: 3 days of 10 mg (Days 2 to 4), 3 days of 20 mg (Days 5 to 7), 5 days of 40 mg (Days 8 to 12), 3 days of 60 mg (Days 13 to 15), 3 days of 80 mg (Days 16 to 18), and 5 days of 100 mg (19 to 23). Placebo matched for ponesimod will be given on Day -1. Placebo tablets matched for moxifloxacin will be administered on Days 1 and 24.

Drug: Ponesimod Placebo; Drug: Moxifloxacin Placebo; Drug: Ponesimod 10 mg; Drug: Ponesimod 20 mg; Drug: Ponesimod 40 mg; Drug: Ponesimod 60 mg; Drug: Ponesimod 80 mg; Drug: Ponesimod 100 mg

Group B

EXPERIMENTAL

Placebo matched for ponesimod will be administered orally, once daily on Day -1 and on Day 2 through Day 23. In half of Group B subjects, 400 mg moxifloxacin will be administered orally on Day 1 and a matching placebo tablet on Day 24. In the other half of Group B subjects, a matching placebo tablet will be administered on Day 1 and 400 mg moxifloxacin on Day 24.

Drug: Ponesimod Placebo; Drug: Moxifloxacin Placebo; Drug: Moxifloxacin 400 mg

Interventions

Ponesimod Placebo DRUG

Group A; Group B

Moxifloxacin Placebo DRUG

Group A; Group B

Ponesimod 10 mg DRUG

Also known as: ACT-128800

Group A

Ponesimod 20 mg DRUG

Also known as: ACT-128800

Group A

Ponesimod 40 mg DRUG

Also known as: ACT-128800

Group A

Ponesimod 60 mg DRUG

Also known as: ACT-128800

Group A

Ponesimod 80 mg DRUG

Also known as: ACT-128800

Group A

Ponesimod 100 mg DRUG

Also known as: ACT-128800

Group A

Moxifloxacin 400 mg DRUG

Group B

Eligibility Criteria

• Age: 18 Years - 45 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Signed informed consent prior to any study-mandated procedure.
• Body mass index between 18.0 and 30.0 kg/m\^2 (inclusive) at screening.
• Healthy on the basis of medical history and the assessments performed at screening.
• Women of childbearing potential must have a negative serum pregnancy test at screening and a negative urine pregnancy test prior to the first drug administration.
• Systolic blood pressure between 90 and 150 mmHg and diastolic blood pressure between 50 and 90 mmHg.
• lead electrocardiogram (ECG) and 24-hour Holter ECG, without clinically relevant abnormalities at screening.
• Hematology and clinical chemistry test results not deviating from the normal range to a clinically relevant extent at screening.
• Negative results from urine drug screen at screening.
• Ability to communicate well with the investigator and to understand and comply with the requirements of the study.

You may not qualify if:

• Pregnant or lactating women.
• Known hypersensitivity to moxifloxacin or to any excipients of the drug formulations.
• Veins unsuitable for intravenous puncture on either arm.
• Treatment with another investigational drug within 3 months prior to screening.
• Excessive caffeine consumption, defined as ≥ 800 mg per day at screening.
• History or clinical evidence of any disease and/or existence of any surgical or medical condition which might interfere with the absorption, distribution, metabolism or excretion of the study drugs.
• Smoking within 3 months prior to screening.
• Any immunosuppressive treatment within 6 weeks before study drug administration.
• Previous treatment with any prescribed or over-the-counter medications within 2 weeks prior to screening or five half-lives of the drug, whichever is longer.
• Donation of blood, plasma or platelets within 3 months prior to screening or donations made on more than two occasions within the 12 months preceding the first dose administration.
• Lymphopenia (\< 1,000 cells/μL\^9).
• Viral, systemic, fungal, bacterial or protozoal infection within 4 weeks before the first study drug administration.
• History or clinical evidence suggestive of active or latent tuberculosis at screening.
• Positive hepatitis B surface antigen or hepatitis C antibody tests at screening.
• Positive results from human immunodeficiency virus serology at screening.

Sponsors & Collaborators

• Actelion: lead

Study Sites (1)

Covance Clinical Research Unit (CRU)

Evansville, Indiana, 47710, United States

Location

Related Publications (1)

• Hoch M, Darpo B, Brossard P, Zhou M, Stoltz R, Dingemanse J. Effect of ponesimod, a selective S1P1 receptor modulator, on the QT interval in healthy individuals. Basic Clin Pharmacol Toxicol. 2015 May;116(5):429-37. doi: 10.1111/bcpt.12336. Epub 2014 Nov 8.

  PMID: 25287214 DERIVED

MeSH Terms

Interventions

ponesimod; Moxifloxacin

Intervention Hierarchy (Ancestors)

Fluoroquinolones; 4-Quinolones; Quinolones; Quinolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Study Officials

• Patrick Brossard, PhD

  Actelion

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 9, 2014
• First Posted: May 13, 2014
• Study Start: August 1, 2011
• Primary Completion: February 1, 2012
• Study Completion: February 1, 2012
• Last Updated: May 13, 2014

Record last verified: 2014-05

Locations

US (1)