A Study in Healthy Adult Participants to Assess the Effects of Ciclosporin Administration on Rilematovir

Study Overview
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Brief Summary
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The purpose of this study is to evaluate the pharmacokinetic (PK) of a single-dose of rilematovir co-administered with a single-dose of ciclosporin compared to a single-dose administration of rilematovir alone.

Official Title
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A Phase 1, Open-label Study in Healthy Adult Participants to Assess the Effects of Ciclosporin Administration on the Single-dose Pharmacokinetics of Rilematovir

Conditions
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Healthy

Intervention / Treatment
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* Drug: Rilematovir
* Drug: Ciclosporin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Body weight not less than 50 kilograms (kg) and body mass index (BMI; weight kg/height^2 [meter {m^2}]) within the range 18.0 to 30.0 kilograms per meter square (kg/m^2) (inclusive) Female participants, except those that are of non-childbearing potential, must have a negative highly sensitive serum (beta-human chorionic gonadotropin [beta-hCG]) at screening and a negative urine pregnancy test on Day -1 of Treatment Period 1 A female participant using hormonal contraceptives as a means of birth control (a stable treatment for at least 30 days prior to screening) must agree to continue use of the same hormonal contraceptives throughout the study and for 90 days after the end of last study treatment Blood pressure (after the participant is supine for at least 5 minutes) between 90 and 140 millimeter of mercury (mmHg) systolic, inclusive, and no higher than 90 mmHg diastolic A 12-lead electrocardiogram (ECG) consistent with normal cardiac conduction and function, including: normal sinus rhythm (heart rate between 45 and 90 beats per minute, extremes included); QTc interval less than or equal to (<=) 450 milliseconds (ms) for men, <= 470 for women; QRS interval of less than (<) 110 ms; PR interval <= 200 ms; electrocardiogram morphology consistent with healthy cardiac conduction and function Exclusion Criteria: Participants with abnormal values for alanine aminotransferase (ALT) and aspartate aminotransferase (AST) Grade 1 or greater (greater than [>] 1.25* upper limit of normal [ULN]) Participants with any history of clinically significant skin disease such as, but not limited to, dermatitis, eczema, drug rash, psoriasis, food allergy, and urticaria Known allergies, hypersensitivity, or intolerance to rilematovir or its excipients. Known allergies, hypersensitivity, or intolerance to ciclosporin or its excipients Participant has received an experimental drug, vaccine or used an experimental medical device within 1 month or within a period less than 10 times the drug's half-life, whichever is longer, before the first dose of the study intervention is scheduled Participant has a history of human immunodeficiency virus (HIV) antibody positive, or tests positive for HIV at screening

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Treatment Sequence ABC<br>Participants will receive a single oral dose of rilematovir (Treatment A) in Treatment Period 1, followed by a single oral dose of ciclosporin (Treatment B) in Treatment Period 2 and then single oral dose of ciclosporin plus single oral dose of rilematovir (Treatment C) in Treatment Period 3 on Day 1 of each Treatment Period under fasted conditions. Each treatment period will be separated by a washout period of at least 5 days and maximum 21 days between subsequent intakes of study intervention. | Drug: Rilematovir<br>* Rilematovir will be administered orally as per assigned treatment sequence.<br>* Other names: JNJ-53718678;Drug: Ciclosporin<br>* Ciclosporin will be administered orally as per assigned treatment sequence.<br>|
| Experimental: Treatment Sequence BCA<br>Participants will receive Treatment B in Treatment Period 1, followed by Treatment C in Treatment Period 2 and then Treatment A in Treatment Period 3 on Day 1 of each Treatment Period under fasted conditions. Each treatment period will be separated by a washout period of at least 5 days and maximum 21 days between subsequent intakes of study intervention. | Drug: Rilematovir<br>* Rilematovir will be administered orally as per assigned treatment sequence.<br>* Other names: JNJ-53718678;Drug: Ciclosporin<br>* Ciclosporin will be administered orally as per assigned treatment sequence.<br>|
| Experimental: Treatment Sequence CAB<br>Participants will receive Treatment C in Treatment Period 1, followed by Treatment A in Treatment Period 2 and then Treatment B in Treatment Period 3 on Day 1 of each Treatment Period under fasted conditions. Each treatment period will be separated by a washout period of at least 5 days and maximum 21 days between subsequent intakes of study intervention. | Drug: Rilematovir<br>* Rilematovir will be administered orally as per assigned treatment sequence.<br>* Other names: JNJ-53718678;Drug: Ciclosporin<br>* Ciclosporin will be administered orally as per assigned treatment sequence.<br>|
| Experimental: Treatment Sequence ACB<br>Participants will receive Treatment A in Treatment Period 1, followed by Treatment C in Treatment Period 2 and then Treatment B in Treatment Period 3 on Day 1 of each Treatment Period under fasted conditions. Each treatment period will be separated by a washout period of at least 5 days and maximum 21 days between subsequent intakes of study intervention. | Drug: Rilematovir<br>* Rilematovir will be administered orally as per assigned treatment sequence.<br>* Other names: JNJ-53718678;Drug: Ciclosporin<br>* Ciclosporin will be administered orally as per assigned treatment sequence.<br>|
| Experimental: Treatment Sequence BAC<br>Participants will receive Treatment B in Treatment Period 1, followed by Treatment A in Treatment Period 2 and then Treatment C in Treatment Period 3 on Day 1 of each Treatment Period under fasted conditions. Each treatment period will be separated by a washout period of at least 5 days and maximum 21 days between subsequent intakes of study intervention. | Drug: Rilematovir<br>* Rilematovir will be administered orally as per assigned treatment sequence.<br>* Other names: JNJ-53718678;Drug: Ciclosporin<br>* Ciclosporin will be administered orally as per assigned treatment sequence.<br>|
| Experimental: Treatment Sequence CBA<br>Participants will receive Treatment C in Treatment Period 1, followed by Treatment B in Treatment Period 2 and then Treatment A in Treatment Period 3 on Day 1 of each Treatment Period under fasted conditions. Each treatment period will be separated by a washout period of at least 5 days and maximum 21 days between subsequent intakes of study intervention. | Drug: Rilematovir<br>* Rilematovir will be administered orally as per assigned treatment sequence.<br>* Other names: JNJ-53718678;Drug: Ciclosporin<br>* Ciclosporin will be administered orally as per assigned treatment sequence.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Treatment A and Treatment C: Maximum Observed Plasma Analyte Concentration (Cmax) of Rilematovir | Cmax is defined as maximum observed plasma analyte concentration of rilematovir. | Pre-dose up to 24 hours | 
| Treatment A and Treatment C: The Actual Sampling Time to Reach the Maximum Observed Plasma Analyte Concentration (Tmax) of Rilematovir | Tmax is defined as the actual sampling time to reach the maximum observed plasma analyte concentration of rilematovir. | Pre-dose up to 24 hours | 
| Treatment A and Treatment C: Apparent Terminal Elimination Half-life (T1/2) of Rilematovir | T1/2 is defined as the apparent terminal elimination half-life associated with the terminal slope of the semilogarithmic drug concentration-time curve. | Pre-dose up to 96 hours | 
| Treatment A and Treatment C: Area Under the Plasma Analyte Concentration Versus Time Curve From Time Zero to the Time of the Last Measurable Concentration (AUC[0-last]) of Rilematovir | AUC(0-last) is defined as area under the plasma analyte concentration versus time curve from time zero to the time of the last measurable concentration of rilematovir. | Pre-dose up to 96 hours | 
| Treatment A and Treatment C: Area Under the Plasma Analyte Concentration Versus Time Curve From Time Zero to Infinite Time (AUC[0-infinity]) of Rilematovir | AUC(0-infinity) is defined as area under the plasma analyte concentration versus time curve from time zero to infinite time of rilematovir. | Pre-dose up to 96 hours | 
| Treatment A and Treatment C: Total Apparent Oral Clearance (CL/F) of Rilematovir | CL/F is defined as total apparent oral clearance of rilematovir. | Pre-dose up to 96 hours | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Treatment B and Treatment C: Maximum Observed Whole Blood Analyte Concentration (Cmax) of Ciclosporin | Cmax is defined as maximum observed whole blood analyte concentration of ciclosporin. | Pre-dose up to 24 hours | 
| Treatment B and Treatment C: The Actual Sampling Time to Reach the Maximum Observed Whole Blood Analyte Concentration (Tmax) of Ciclosporin | Tmax is defined as the actual sampling time to reach the maximum observed whole blood analyte concentration of ciclosporin. | Pre-dose up to 24 hours | 
| Treatment B and Treatment C: Apparent Terminal Elimination Half-life (T1/2) of Ciclosporin | T1/2 is defined as apparent terminal elimination half-life associated with the terminal slope of the semilogarithmic drug concentration-time curve. | Pre-dose up to 96 hours | 
| Treatment B and Treatment C: Area Under the Whole Blood Analyte Concentration Versus Time Curve From Time Zero to the Time of the Last Measurable Concentration (AUC[0-last]) of Ciclosporin | AUC(0-last) is defined as area under the whole blood analyte concentration versus time curve from time zero to the time of the last measurable concentration of ciclosporin. | Pre-dose up to 96 hours | 
| Treatment B and Treatment C: Area Under the Whole Blood Analyte Concentration Versus Time Curve From Time Zero to Infinite Time (AUC[0-infinity]) of Ciclosporin | AUC(0-infinity) is defined as area under the whole blood analyte concentration versus time curve from time Zero to infinite time of ciclosporin. | Pre-dose up to 96 hours | 
| Treatment B and Treatment C: Total Apparent Oral Clearance (CL/F) of Ciclosporin | CL/F is defined as total apparent oral clearance of ciclosporin. | Pre-dose up to 96 hours | 
| Percentage of Participants with Adverse Events (AEs) | An AE is any untoward medical occurrence in a clinical study participant administered a pharmaceutical (investigational or non-investigational) product. An AE does not necessarily have a causal relationship with the intervention. | Up to Week 12 | 
| Percentage of Participants with Abnormalities in Electrocardiogram (ECG) | Percentage of participants with abnormalities in ECG will be reported. | Up to Week 12 | 
| Percentage of Participants with Abnormalities in Physical Examination | Percentage of participants with abnormalities in physical examination (including height, body weight and examination of all body systems and dermatologic examinations) will be reported. | Up to Week 12 | 
| Percentage of Participants with Abnormalities in Vital Signs | Percentage of participants with abnormalities in vital signs (including temperature [tympanic], pulse/heart rate, blood pressure [systolic and diastolic]) will be reported. | Up to Week 12 | 
| Percentage of Participants with Abnormalities in Clinical Laboratory Tests | Percentage of participants with abnormalities in clinical laboratory tests (including serum chemistry, hematology and routine urinalysis) will be reported. | Up to Week 12 |