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

Janssen (J&J Innovative Medicine)

Status and phase: Completed; Phase 1

Conditions: Healthy

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

Study type: Interventional

Funder types: Industry

Identifiers

NCT03882255

2018-003550-24 (EudraCT Number)

AC-058-117 (Other Identifier)

CR108589

Details and patient eligibility

About

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.

Enrollment: 52 patients

Sex: All

Ages: 18 to 55 years old

Volunteers: Accepts Healthy Volunteers

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

Trial design

Primary purpose: Other

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

---

52 participants in 2 patient groups

Treatment Period 1: Ponesimod (2 mg)

Experimental group

Description:

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.

Treatment:

Drug: Ponesimod dose range (2 - 20 mg)

Treatment Period 2:Ponesimod, Propranolol, Placebo Propranolol

Experimental group

Description:

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.

Treatment:

Drug: Ponesimod dose range (2 - 20 mg)

Drug: Placebo Propranolol

Drug: Propranolol 80 mg