Study in Women on the Effect of JNJ-64530440 on Oral Contraceptive and Midazolam, and the Effect of a High-fat Meal on JNJ-64530440

NCT03890341 | Withdrawn Phase 1 FDA Drug

• 1 other identifier: JNJ-0440-1302
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to evaluate the effect of JNJ-64530440 single- and multiple-dose administration on the single-dose pharmacokinetics of drospirenone and ethinylestradiol (oral contraceptive) in healthy female participants.

Conditions

Healthy

Outcome Measures

Primary Outcomes (6)

• Maximum Observed Plasma Analyte Concentration (Cmax) of Drospirenone

  Cmax is defined as maximum observed plasma analyte concentration.

  Days 1, 13, and 19: Predose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 18, 24, 48, 72, 96, 120 hours postdose

• Area Under the Plasma Analyte Concentration-Time Curve from Time Zero to Last Quantifiable Concentration Time (AUC [0-Last]) of Drospirenone

  AUC(0-Last) is area under the plasma analyte concentration-time curve from time zero to time of the last measurable (non-below quantification limit) concentration, calculated by linear-linear trapezoidal summation.

  Days 1, 13, and 19: Predose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 18, 24, 48, 72, 96, 120 hours postdose

• Area Under the Plasma Concentration-Time Curve from Time Zero to Infinite Time (AUC [0-infinity]) of Drospirenone

  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.

  Days 1, 13, and 19: Predose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 18, 24, 48, 72, 96, 120 hours postdose

• Maximum Observed Plasma Analyte Concentration (Cmax) of Ethinylestradiol

  Cmax is defined as maximum observed plasma analyte concentration.

  Days 1, 13, and 19: Predose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 18, 24, 48, 72, 96, 120 hours postdose

• Area Under the Plasma Analyte Concentration-Time Curve from Time Zero to Last Quantifiable Concentration Time (AUC [0-Last]) of Ethinylestradiol

  AUC(0-Last) is area under the plasma analyte concentration-time curve from time zero to time of the last measurable (non-below quantification limit) concentration, calculated by linear-linear trapezoidal summation.

  Days 1, 13, and 19: Predose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 18, 24, 48, 72, 96, 120 hours postdose

• Area Under the Plasma Concentration-Time Curve from Time Zero to Infinite Time (AUC [0-infinity]) of Ethinylestradiol

  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.

  Days 1, 13, and 19: Predose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 18, 24, 48, 72, 96, 120 hours postdose

Secondary Outcomes (6)

• Maximum Observed Plasma Analyte Concentration (Cmax) of Midazolam

  Days 1, 13, and 19: Predose, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 10, and 12 hours postdose

• Area Under the Plasma Analyte Concentration-Time Curve from Time Zero to Last Quantifiable Concentration Time (AUC [0-Last]) of Midazolam

  Days 1, 13, and 19: Predose, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 10, and 12 hours postdose

• Area Under the Plasma Concentration-Time Curve from Time Zero to Infinite Time (AUC [0-infinity]) of Midazolam

  Days 1, 13, and 19: Predose, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 10, and 12 hours postdose

• Cmax of JNJ-64530440 Under Fed Conditions (High-Fat Meal)

  Days 13 and 19: Predose, 0.5, 1, 2, 4, 6, 8, 10, 12, 18 and 24 hours)

• Maximum Observed Plasma Concentration (Cmax) of JNJ-64530440

  Days 13 and19: Predose, 0.5, 1, 2, 4, 6, 8, 10, 12, 18 and 24 hours

Study Arms (1)

Drospirenone/Ethinylestradiol + Midazolam + JNJ-64530440

EXPERIMENTAL

Participants will receive single oral dose of drospirenone/ethinylestradiol 3 milligram (mg)/0.02 mg (oral contraceptive \[OC\]) and midazolam 2 mg with under fed conditions (high fat meal) on Day 1 followed by JNJ-64530440 2,000 mg on Days 6 under fasted conditions ; JNJ-64530440 2,000 mg plus single oral dose of OC and midazolam 2 mg under fed conditions on Day 13; JNJ-64530440 2,000 mg once daily under fed conditions (standard meal) from Days 14 to 18; single oral dose of JNJ-64530440 2,000 mg plus single oral dose of OC and midazolam 2 mg on Day 19 under fed conditions (high fat meal); and JNJ-64530440 2,000 mg once daily under fed conditions (standard meal) on Days 20 to 22.

Drug: Drospirenone/Ethinylestradiol; Drug: Midazolam; Drug: JNJ-64530440

Interventions

Drospirenone/Ethinylestradiol DRUG

A single oral dose of drospirenone/ethinylestradiol 3 mg/0.02 mg (OC) tablets will be administered on Days 1, 13 and 19.

Also known as: Betadex clathrate

Drospirenone/Ethinylestradiol + Midazolam + JNJ-64530440

Midazolam DRUG

Midazolam 2 mg will be administered orally on Days 1, 13 and 19.

Drospirenone/Ethinylestradiol + Midazolam + JNJ-64530440

JNJ-64530440 DRUG

A single oral dose of JNJ-64530440 2,000 mg will be administered on Day 6 and once daily on Days 13 to 22.

Drospirenone/Ethinylestradiol + Midazolam + JNJ-64530440

Eligibility Criteria

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

You may qualify if:

• Must have a body mass index between 18.0 and 30.0 kilogram per meter square (kg/m\^2), extremes included, and a body weight not less than 50.0 kilogram (kg)
• Healthy on the basis of physical examination, medical history, and vital signs performed at screening. If there are abnormalities, the participant may be included only if the Investigator judges the abnormalities to be not clinically significant or to be appropriate and reasonable for the population under study. This determination must be recorded in the participant's source documents and initialed by the Investigator
• Must have a negative highly sensitive urine pregnancy test at Day -1 (all participants)
• Must have a negative highly sensitive serum beta-human chorionic gonadotropin pregnancy test at screening (all participants except for postmenopausal participants)
• Must agree not to donate eggs (ova, oocytes) for the purposes of assisted reproduction during the study and for a period of 90 days after the last study drug administration

You may not qualify if:

• Any evidence of heart block or bundle branch block
• History of liver or renal dysfunction (estimated creatinine clearance less than \[\<\] 90 milliliter per minute (mL/min) at screening, calculated by the Modification of Diet in Renal Disease (MDRD) formula), significant cardiac, vascular, pulmonary, gastrointestinal (such as significant diarrhea, gastric stasis, or constipation that in the Investigator's opinion could influence drug absorption or bioavailability), endocrine, neurologic, hematologic, rheumatologic, psychiatric, neoplastic, or metabolic disturbances
• Past history of clinically significant cardiac arrhythmias (example \[eg\], premature ventricular contractions, premature atrial contractions, extrasystoli, tachycardia at rest), history of risk factors for Torsade de Pointes syndrome (eg, hypokalemia, family history of long QT Syndrome)
• Current human immunodeficiency virus type 1 (HIV-1) or HIV-2 infection (confirmed by antibodies) at screening
• Current hepatitis A virus infection (confirmed by hepatitis A antibody immunoglobulin M \[IgM\]), or Hepatitis B Virus (HBV) infection (confirmed by Hepatitis B surface antigen \[HBsAg\]), or Hepatitis C Virus (HCV) infection (confirmed by HCV antibody), or hepatitis E virus infection (confirmed by hepatitis E antibody IgM) at screening

Sponsors & Collaborators

• Janssen Research & Development, LLC: lead

Study Sites (1)

PRA Health Sciences

Salt Lake City, Utah, 84124, United States

Location

MeSH Terms

Interventions

drospirenone; Ethinyl Estradiol; Midazolam

Intervention Hierarchy (Ancestors)

Norpregnatrienes; Norpregnanes; Norsteroids; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Estrogenic Steroids, Alkylated; Estradiol Congeners; Gonadal Steroid Hormones; Gonadal Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Benzodiazepines; Benzazepines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Study Officials

• Janssen Research & Development, LLC Clinical Trial

  Janssen Research & Development, LLC

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 25, 2019
• First Posted: March 26, 2019
• Study Start: June 1, 2021
• Primary Completion: August 1, 2021
• Study Completion: November 1, 2021
• Last Updated: March 26, 2021

Record last verified: 2021-03

Data Sharing

• IPD Sharing: Will share

Locations

US (1)