A Study of Ponesimod in Healthy Adult Participants Receiving Propranolol at Steady State

NCT ID: NCT03882255

Last Updated: 2025-04-27

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 52 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2019-03-20
• Study Completion Date: 2019-08-26

Brief Summary

The primary purpose of this study is to evaluate the effect of the up-titration regimen of ponesimod on heart rate (HR) and other electrocardiogram (ECG) parameters when administrated to healthy adult participants receiving propranolol at steady state.

Conditions

Healthy

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: OTHER
• Blinding Strategy: DOUBLE

Study Groups

Treatment Period 1: Ponesimod (2 mg)

Participants will receive a single dose ponesimod 2 milligram (mg) oral tablet under fed conditions on Day 1. Participants not fulfilling discontinuation criteria can continue to Treatment Period 2 after a washout period of at least 7 days and a maximum of 14 days.

Group Type: EXPERIMENTAL

Ponesimod dose range (2 - 20 mg)

Intervention Type: DRUG

Participants will receive ponesimod oral tablet at a dose of 2 mg in Treatment period 1 and as an up-titrating regimen (dose range: 2mg-20mg) in Treatments period 2.

Treatment Period 2:Ponesimod, Propranolol, Placebo Propranolol

Participants who do not fulfill any of discontinuation criteria will be randomized to 1 of 2 Treatments (Treatment A or B) on Day 1. Treatment A: up-titration regimen of ponesimod (2mg-20mg) once daily from Day 5 to Day 19 plus placebo propranolol once daily from Day 1 to Day 19; Treatment B: up-titration regimen of ponesimod (2mg-20mg) once daily from Day 5 to Day 19 plus 80 mg propranolol once daily from Day 1 to Day 19.

Group Type: EXPERIMENTAL

Ponesimod dose range (2 - 20 mg)

Intervention Type: DRUG

Participants will receive ponesimod oral tablet at a dose of 2 mg in Treatment period 1 and as an up-titrating regimen (dose range: 2mg-20mg) in Treatments period 2.

Placebo Propranolol

Intervention Type: DRUG

Participants will be administered placebo propranolol oral capsule from Day 1 to Day 19 in Treatment A of Treatment period 2.

Propranolol 80 mg

Intervention Type: DRUG

Participants will receive propranolol 80 mg long acting oral capsule from Day 1 to Day 19 in Treatment B of Treatment period 2.

Interventions

Ponesimod dose range (2 - 20 mg)

Participants will receive ponesimod oral tablet at a dose of 2 mg in Treatment period 1 and as an up-titrating regimen (dose range: 2mg-20mg) in Treatments period 2.

Intervention Type: DRUG

Placebo Propranolol

Participants will be administered placebo propranolol oral capsule from Day 1 to Day 19 in Treatment A of Treatment period 2.

Intervention Type: DRUG

Propranolol 80 mg

Participants will receive propranolol 80 mg long acting oral capsule from Day 1 to Day 19 in Treatment B of Treatment period 2.

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• Systolic blood pressure (SBP) 90 to 140 millimeters of mercury (mmHg) and diastolic blood pressure (DBP) 50 to 90 mmHg measured on the right arm in supine position after at least 5 minutes rest in the supine position at screening, on Day 1 of the Treatment Period 1, and on Day -2 of Treatment Period 2
• Body mass index (BMI) between 18.0 and 30.0 kilogram per meter square (kg/m^2 ) (inclusive) at screening and body weight not less than 50.0 kg
• 12-lead safety electrocardiogram (ECG) without clinically relevant abnormalities at screening, on Day 1 of the Treatment Period 1, and on Day-2 of Treatment Period 2, including:

1. QT interval corrected for heart rate using the Fridericia correction (QTcF) of less than or equal to (=<) 450 millisecond (ms) for male participants and =< 470 ms for female participants

2. Heart rate (HR) 55 to 100 Beats per minute (bpm) (inclusive)

3. QRS interval less than (<) 120 ms

4. PR interval =< 200 ms

5. ECG morphology consistent with healthy cardiac conduction and function

• Female participant must have a negative highly sensitive serum (beta human chorionic gonadotropin [beta- hCG]) pregnancy test at screening and a negative urine pregnancy test on Day 1 of Treatment Period 1 and Day 2 of Treatment Period 2
• Negative results from urine drug screen at screening, on Day -1 of Treatment Period 1, and on Day -2 of Treatment Period 2

Exclusion Criteria

• Any cardiac condition or illness (including ECG abnormalities) with a potential to increase the cardiac risk of the participant based on medical history, physical examination, 12-lead safety ECG, or 24-hour Holter ECG at screening, including:

1. 24-hour Holter ECG with clinically relevant abnormalities

2. History or evidence of Atrioventricular (AV) block second degree or higher

3. Any cardiac condition or illness (including ECG abnormalities based on standard 12-lead safety ECG or d- 24-hour Holter ECG) with a potential to increase the cardiac risk of the participant

• Family history of sick-sinus syndrome
• Hepatitis A antibody immunoglobulin M (IgM) positive, positive hepatitis B surface antigen (HBsAg) or hepatitis C antibody (anti-hepatitis C virus [anti-HCV]) tests, or other clinically active liver disease at screening
• Known hypersensitivity to any excipients of the ponesimod drug formulation (lactose, microcrystalline cellulose, povidone, sodium lauryl sulfate, croscarmellose sodium, colloidal anhydrous silica, magnesium stearate, opadry II brown), or lactose
• History of significant propranolol side effects or known hypersensitivity to propranolol or to any of its excipients

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 55 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Janssen Pharmaceutica N.V., Belgium

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Janssen Pharmaceutica N.V., Belgium Clinical Trial

Role: STUDY_DIRECTOR

Janssen Pharmaceutica N.V., Belgium

Locations

SGS Clinical Pharmacology Unit (located in ZNA Stuivenberg)

Antwerp, , Belgium

Countries

Belgium

Other Identifiers

2018-003550-24

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

AC-058-117

Identifier Type: OTHER

Identifier Source: secondary_id

CR108589

Identifier Type: -

Identifier Source: org_study_id