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

Janssen Pharmaceutica N.V., Belgium52 enrolled

Overview

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.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

OTHER

Masking

DOUBLE

Enrollment

Conditions

Healthy

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.

Placebo PropranololDRUG

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

Propranolol 80 mgDRUG

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

Eligibility

Sex: ALLMin age: 18 YearsMax age: 55 YearsHealthy volunteers:

Medical Language ↔ Plain English

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

Locations (1)

SGS Clinical Pharmacology Unit (located in ZNA Stuivenberg)

Antwerp, Belgium

Outcomes

Primary Outcomes

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.

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: Day 19

Secondary Outcomes

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

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

Time frame: Baseline, Days 4, 16, and 19

Minimum of the Mean Arterial Blood Pressure

Minimum of the Mean arterial blood pressure (MAP) will be assessed. The MAP will be derived from the systolic blood pressure (SBP) and diastolic blood pressure (DBP) for each participant at the same time point as follows: MAP = 1/3 SBP + 2/3 DBP.

Time frame: Days 4, 5, 16, and 19

Change from Baseline in Average Heart Rate

Data from ClinicalTrials.gov

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