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

NCT03882255 | Completed Phase 1

• 3 other identifiers: CR1085892018-003550-24AC-058-117
• Study Type: interventional
• Target: 52
• Locations: 1 country
• Sites: 1

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

Outcome Measures

Primary Outcomes (4)

• Maximum Decrease from Baseline in Mean Hourly Heart Rate (HR) (Emax HR) on Day 5

  Emax HR is defined as the maximum decrease from baseline in mean hourly HR.

  Baseline and Day 5

• Maximum Decrease from Baseline in Mean Hourly Heart Rate (HR) (Emax HR) on Day 19

  Emax HR is defined as the maximum decrease from baseline in mean hourly HR.

  Baseline and Day 19

• Minimum of the Mean Hourly HR for each day (HR nadir) on Day 5

  HR nadir will be defined as the minimum of the mean hourly HR for each day and will be summarized by descriptive statistics.

  Day 5

• Minimum of the Mean Hourly HR for each day (HR nadir) on Day 19

  HR nadir will be defined as the minimum of the mean hourly HR for each day and will be summarized by descriptive statistics.

  Day 19

Secondary Outcomes (15)

• Maximum Decrease from Baseline in Mean Hourly Heart Rate (HR) (Emax HR) on Days 4,16, and 19

  Baseline, Days 4, 16, and 19

• Minimum of the Mean Arterial Blood Pressure

  Days 4, 5, 16, and 19

• Change from Baseline in Average Heart Rate

  Baseline, Days 4, 5, 16, and 19

• Change from Baseline in Average PR Interval

  Baseline, Days 4, 5, 16, and 19

• Maximum Observed Plasma Analyte Concentration (Cmax) of Ponesimod

  Days 5, 9 (Predose; 1, 2, 3, 4, 5, 6, 8, 10, 12 and 24 hours postdose)

Study Arms (2)

Treatment Period 1: Ponesimod (2 mg)

EXPERIMENTAL

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.

Drug: Ponesimod dose range (2 - 20 mg)

Treatment Period 2:Ponesimod, Propranolol, Placebo Propranolol

EXPERIMENTAL

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.

Drug: Ponesimod dose range (2 - 20 mg); Drug: Placebo Propranolol; Drug: Propranolol 80 mg

Interventions

Ponesimod dose range (2 - 20 mg) 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 1: Ponesimod (2 mg); Treatment Period 2:Ponesimod, Propranolol, Placebo Propranolol

Placebo Propranolol DRUG

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

Treatment Period 2:Ponesimod, Propranolol, Placebo Propranolol

Propranolol 80 mg DRUG

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

Treatment Period 2:Ponesimod, Propranolol, Placebo Propranolol

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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
• 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:
• 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
• Heart rate (HR) 55 to 100 Beats per minute (bpm) (inclusive)
• QRS interval less than (\<) 120 ms
• PR interval =\< 200 ms
• 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

You may not qualify if:

• 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:
• hour Holter ECG with clinically relevant abnormalities
• History or evidence of Atrioventricular (AV) block second degree or higher
• 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

Sponsors & Collaborators

• Janssen Pharmaceutica N.V., Belgium: lead

Study Sites (1)

SGS Clinical Pharmacology Unit (located in ZNA Stuivenberg)

Antwerp, 2060, Belgium

Location

MeSH Terms

Interventions

Propranolol

Intervention Hierarchy (Ancestors)

Phenoxypropanolamines; Propanolamines; Amino Alcohols; Alcohols; Organic Chemicals; Propanols; Amines; Naphthalenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Polycyclic Compounds

Study Officials

• Janssen Pharmaceutica N.V., Belgium Clinical Trial

  Janssen Pharmaceutica N.V., Belgium

  STUDY DIRECTOR

Study Design

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

Study Record Dates

• First Submitted: March 18, 2019
• First Posted: March 20, 2019
• Study Start: March 20, 2019
• Primary Completion: August 26, 2019
• Study Completion: August 26, 2019
• Last Updated: April 27, 2025

Record last verified: 2025-04

Data Sharing

• IPD Sharing: Will share

Locations

BE (1)