A Study to Evaluate the Effect of Cyclosporine, a P-Glycoprotein, Breast Cancer Resistance Protein, and Organic-Anion-Transporting Polypeptide Inhibitor, on Pimodivir in Healthy Adults

A Randomized, Open-label, Single-dose, 2-period, 2-sequence, Crossover, Phase 1 Study to Evaluate the Effect of Cyclosporine, a P-glycoprotein, Breast Cancer Resistance Protein, and Organic-anion-transporting Polypeptide Inhibitor, on the Pharmacokinetics of Pimodivir in Healthy Adult Subjects

The purpose of this study is to evaluate the effect of a single oral dose of cyclosporine on the pharmacokinetics of a single oral dose of pimodivir when coadministered to healthy adult participants under fasted conditions.

Study Overview

• Status: Completed
• Conditions: Healthy
• Intervention / Treatment: Drug: Pimodivir; Drug: Cyclosporine

• Study Type: Interventional
• Enrollment (Actual): 18
• Phase: Phase 1

Contacts and Locations

Study Locations

• Belgium
  • Merksem, Belgium, 2170
    • Clinical Pharmacology Unit

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Willing and able to adhere to the prohibitions and restrictions specified in this protocol
• A woman of childbearing potential must have a negative highly sensitive serum (beta-human chorionic gonadotropin [beta-hCG]) at screening and on Day -1 of each treatment period
• A woman must agree not to donate eggs (ova, oocytes) for the purposes of assisted reproduction during the study and for a period of at least 30 days after the last study drug intake
• A male participant must wear a condom when engaging in any activity that allows for passage of ejaculate to another person (male participants should also be advised of the benefit for a female partner to use a highly effective method of contraception as condom may break or leak)
• A male participant must agree not to donate sperm for the purpose of reproduction during the study and for a minimum of 90 days after last study drug intake

Exclusion Criteria:

• History of or current clinically significant medical illness including (but not limited to) cardiac arrhythmias or other cardiac disease, hematologic disease, coagulation disorders (including any abnormal bleeding or blood dyscrasias), lipid abnormalities, significant pulmonary disease, including bronchospastic respiratory disease, diabetes mellitus, hepatic or renal insufficiency (creatinine clearance below 90 milliliter per minute at screening), gastrointestinal disease (such as significant diarrhea, gastric stasis, or constipation that in the investigator's opinion could influence drug absorption or bioavailability), thyroid disease, neurologic or psychiatric disease, infection, or any other illness that the investigator considers should exclude the participant or that could interfere with the interpretation of the study results
• History of clinically significant skin disease such as, but not limited to, dermatitis, eczema, drug rash, psoriasis, food allergy, or urticaria
• Known allergies, hypersensitivity, or intolerance to pimodivir and/or cyclosporine or their excipients
• History of clinically significant drug allergy such as, but not limited to, sulfonamides and penicillins, or drug allergy diagnosed in previous studies with experimental drugs

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Group 1: Sequence AB; Participants will receive Treatment A (pimodivir 600 milligram [mg] orally as two tablets of 300 mg each) on Day 1 in Period 1 followed by Treatment B (pimodivir 600 mg as two tablets of 300 mg each plus cyclosporine 400 mg orally as four capsules of 100 mg each) on Day 1 in Period 2. Study drug intake in subsequent treatment periods will be separated by a washout period of at least 14 days.	Drug: Pimodivir; Participants will be administered pimodivir 600 mg orally as two tablets of 300 mg each.; Other Names: JNJ-63623872; Drug: Cyclosporine; Participants will be administered cyclosporine 400 mg orally as 4 capsules of 100 mg each.; Other Names: NEORAL
Experimental: Group 2: Sequence BA; Participants will receive Treatment B on Day 1 in Period 1 followed by Treatment A on Day 1 in Period 2. Study drug intake in subsequent treatment periods will be separated by a washout period of at least 14 days.	Drug: Pimodivir; Participants will be administered pimodivir 600 mg orally as two tablets of 300 mg each.; Other Names: JNJ-63623872; Drug: Cyclosporine; Participants will be administered cyclosporine 400 mg orally as 4 capsules of 100 mg each.; Other Names: NEORAL

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Maximum Observed Plasma Concentration (Cmax)	Cmax is defined as maximum observed plasma concentration.	Predose, 0.5, 1, 1.5, 2, 3, 4, 5, 6 , 8, 12, 16, 24, 48, 72, 96, 120, 144, 168 hours postdose on Day 8
Area Under the Plasma Concentration-Time Curve From Time Zero to Last Quantifiable Concentration Time (AUC [0-Last])	AUC(0-Last) is area under the plasma concentration-time curve from time zero to time of the last measurable (non-below quantification limit) concentration, calculated by linear-linear trapezoidal summation.	Predose, 0.5, 1, 1.5, 2, 3, 4, 5, 6 , 8, 12, 16, 24, 48, 72, 96, 120, 144, 168 hours postdose on Day 8
Area Under the Plasma Concentration-Time Curve From Time Zero to Infinite Time (AUC [0-infinity])	AUC (0-infinity) is the area under the plasma concentration-time curve from time zero to infinite time, calculated as the sum of AUC(last) and C(last)/lambda(z); where C(last) is the last observed measurable (non-below quantification limit) concentration.	Predose, 0.5, 1, 1.5, 2, 3, 4, 5, 6 , 8, 12, 16, 24, 48, 72, 96, 120, 144, 168 hours postdose on Day 8

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants with Adverse Events (AEs) as a Measure of Safety and Tolerability	An AE is any untoward medical occurrence in a clinical study participant administered a medicinal (investigational or non investigational) product. An AE does not necessarily have a causal relationship with the treatment.	Approximately 65 days

Collaborators and Investigators

• Sponsor: Janssen-Cilag International NV

Study record dates

Study Major Dates

• Study Start (Actual): December 6, 2018
• Primary Completion (Actual): March 6, 2019
• Study Completion (Actual): March 12, 2019

Study Registration Dates

• First Submitted: December 6, 2018
• First Submitted That Met QC Criteria: December 6, 2018
• First Posted (Actual): December 7, 2018

Study Record Updates

• Last Update Posted (Actual): April 29, 2019
• Last Update Submitted That Met QC Criteria: April 26, 2019
• Last Verified: April 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Enzyme Inhibitors; Antirheumatic Agents; Immunosuppressive Agents; Immunologic Factors; Dermatologic Agents; Antifungal Agents; Calcineurin Inhibitors; Cyclosporine; Cyclosporins
• Other Study ID Numbers: CR108557; 2018-002819-10 (EudraCT Number); 63623872FLZ1015 (Other Identifier: Janssen-Cilag International NV)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Yes
• IPD Plan Description: 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 Access (YODA) Project site at yoda.yale.edu

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No