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

NCT03768609 | Completed Phase 1

• 3 other identifiers: CR1085572018-002819-1063623872FLZ1015
• Study Type: interventional
• Target: 18
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Healthy

Outcome Measures

Primary Outcomes (3)

• 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 Outcomes (1)

• Number of Participants with Adverse Events (AEs) as a Measure of Safety and Tolerability

  Approximately 65 days

Study Arms (2)

Group 1: Sequence AB

EXPERIMENTAL

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; Drug: Cyclosporine

Group 2: Sequence BA

EXPERIMENTAL

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; Drug: Cyclosporine

Interventions

Pimodivir DRUG

Participants will be administered pimodivir 600 mg orally as two tablets of 300 mg each.

Also known as: JNJ-63623872

Group 1: Sequence AB; Group 2: Sequence BA

Cyclosporine DRUG

Participants will be administered cyclosporine 400 mg orally as 4 capsules of 100 mg each.

Also known as: NEORAL

Group 1: Sequence AB; Group 2: Sequence BA

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Janssen-Cilag International NV: lead

Study Sites (1)

Clinical Pharmacology Unit

Merksem, 2170, Belgium

Location

MeSH Terms

Interventions

pimodivir; Cyclosporine

Intervention Hierarchy (Ancestors)

Cyclosporins; Peptides, Cyclic; Macrocyclic Compounds; Polycyclic Compounds; Peptides; Amino Acids, Peptides, and Proteins

Study Officials

• Janssen-Cilag International NV Clinical Trial

  Janssen-Cilag International NV

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: OTHER
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 6, 2018
• First Posted: December 7, 2018
• Study Start: December 6, 2018
• Primary Completion: March 6, 2019
• Study Completion: March 12, 2019
• Last Updated: April 29, 2019

Record last verified: 2019-04

Data Sharing

• IPD Sharing: Will share

Locations

BE (1)