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| ID | Type | Description | Link |
|---|---|---|---|
| 2018-003550-24 | EudraCT Number | ||
| AC-058-117 | Other Identifier | Janssen Pharmaceutica N.V., Belgium |
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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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| 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. |
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| 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. |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| 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. |
| Measure | Description | Time Frame |
|---|---|---|
| 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 |
| Measure | Description | Time Frame |
|---|---|---|
| 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. | Baseline, Days 4, 16, and 19 |
| Minimum of the Mean Arterial Blood Pressure |
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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:
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:
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
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| Name | Affiliation | Role |
|---|---|---|
| Janssen Pharmaceutica N.V., Belgium Clinical Trial | Janssen Pharmaceutica N.V., Belgium | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| SGS Clinical Pharmacology Unit (located in ZNA Stuivenberg) | Antwerp | 2060 | Belgium |
The data sharing policy of the Janssen Pharmaceutical Companies of Johnson & Johnson is available at www.janssen.com/clinical-trials/transparency.
As noted on this site, requests for access to the study data can be submitted through Yale open Data Access (YODA) Project site at yoda.yale.edu
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| ID | Term |
|---|---|
| D011433 | Propranolol |
| ID | Term |
|---|---|
| D050198 | Phenoxypropanolamines |
| D011412 | Propanolamines |
| D000605 | Amino Alcohols |
| D000438 | Alcohols |
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| Placebo Propranolol | Drug | Participants will be administered placebo propranolol oral capsule from Day 1 to Day 19 in Treatment A of Treatment period 2. |
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| 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. |
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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.
| Days 4, 5, 16, and 19 |
| Change from Baseline in Average Heart Rate | Change from baseline in average heart rate on Days 4, 5, 16 and 19 will be assessed in Treatment Period 2. | Baseline, Days 4, 5, 16, and 19 |
| Change from Baseline in Average PR Interval | Change from baseline in PR interval on Days 4, 5, 16 and 19 will be assessed in Treatment Period 2. PR intervals will be derived from 12-lead safety electrocardiogram (ECG). | Baseline, Days 4, 5, 16, and 19 |
| Maximum Observed Plasma Analyte Concentration (Cmax) of Ponesimod | Cmax is defined as maximum observed plasma analyte concentration. | Days 5, 9 (Predose; 1, 2, 3, 4, 5, 6, 8, 10, 12 and 24 hours postdose) |
| Maximum Observed Plasma Analyte Concentration (Tmax) of Ponesimod | Tmax is defined as maximum observed plasma analyte concentration. | Days 5, 19 (Predose; 1, 2, 3, 4, 5, 6, 8, 10, 12 and 24 hours postdose) |
| Area Under the Plasma Analyte Concentration-Time Curve (AUC [0-24]) of Ponesimod | (AUC [0-24]) is defined as area under the plasma analyte concentration-time curve (AUC) from time 0 to 24 hours postdose, calculated by linear-linear trapezoidal summation. | Day 5 (Predose; 1, 2, 3, 4, 5, 6, 8, 10, 12 and 24 Hours postdose) |
| Trough Plasma Analyte Concentration (Ctrough) of Ponesimod | (Ctrough) is defined as observed analyte concentration just prior to the beginning of a dosing interval. | Day 19 (Predose; 1, 2, 3, 4, 5, 6, 8, 10, 12 and 24 hours postdose) |
| Area Under the Curve From Time Zero to End of Dosing Interval (AUCtau) | The AUCtau is the measure of the plasma analyte concentration from time zero to end of dosing interval. AUC during a dosing interval (τ) at steady state, calculated by linear-linear trapezoidal summation. | Day 19 (Predose; 1, 2, 3, 4, 5, 6, 8, 10, 12 and 24 hours postdose) |
| Maximum Observed Plasma Analyte Concentration (Cmax) of Propranolol and 4 hydroxypropranolol | Cmax is defined as maximum observed plasma analyte concentration. | Days 4, 5, and 19 (Predose; 1, 2, 3, 4, 5, 6, 8, 10, 12 and 24 hours postdose) |
| Maximum Observed Plasma Analyte Concentration (Tmax) of Propranolol and 4 hydroxypropranolol | Tmax is defined as maximum observed plasma analyte concentration. | Days 4, 5, and 19 (Predose; 1, 2, 3, 4, 5, 6, 8, 10, 12 and 24 hours postdose) |
| Trough Plasma Analyte Concentration (Ctrough) of Propranolol and 4 hydroxypropranolol | (Ctrough) is defined as observed analyte concentration just prior to the beginning of a dosing interval. | Days 4, 5, and 19 (Predose; 1, 2, 3, 4, 5, 6, 8, 10, 12 and 24 hours postdose) |
| Area Under the Curve from Time Zero to End of Dosing Interval (AUCtau) of Propranolol and 4 hydroxypropranolol | The AUCtau is the measure of the plasma analyte concentration from time zero to end of dosing interval. AUC during a dosing interval (τ) at steady state, calculated by linear-linear trapezoidal summation. | Days 4, 5, and 19 (Predose; 1, 2, 3, 4, 5, 6, 8, 10, 12 and 24 hours postdose) |
| Total apparent Oral Clearance of Propranolol | Total apparent clearance is defined as total apparent oral clearance at steady state, calculated as dose/AUC (tau). | Days 4, 5, and 19 (Predose; 1, 2, 3, 4, 5, 6, 8, 10, 12 and 24 hours postdose) |
| Number of Participants with Adverse Events as a Measure of Safety and Tolerability | An adverse event is any adverse change, that is, any unfavorable and unintended sign, including an abnormal laboratory finding, symptom, or disease, that occurs in a participant during the course of the study, whether or not considered related to the study treatment. | Approximately 2.5 months |
| D009930 |
| Organic Chemicals |
| D020005 | Propanols |
| D000588 | Amines |
| D009281 | Naphthalenes |
| D011084 | Polycyclic Aromatic Hydrocarbons |
| D006841 | Hydrocarbons, Aromatic |
| D006844 | Hydrocarbons, Cyclic |
| D006838 | Hydrocarbons |
| D011083 | Polycyclic Compounds |