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

• ClinicalTrials.gov Identifier: NCT03890341
• Recruitment Status: Not yet recruiting
• First Posted: March 26, 2019
• Last Update Posted: December 6, 2019
• Sponsor: Janssen Research & Development, LLC
• Information provided by (Responsible Party): Janssen Research & Development, LLC

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Healthy	Drug: Drospirenone/Ethinylestradiol; Drug: Midazolam; Drug: JNJ-64530440	Phase 1

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 16 participants
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Basic Science
• Official Title: A Study in Healthy Female Participants to Investigate the Effect of JNJ-64530440 on the Single-dose of Ethinylestradiol and Drospirenone (Oral Contraceptive), and Midazolam, and the Effect of a High-fat Meal on the Single-dose of JNJ-64530440
• Estimated Study Start Date: December 1, 2019
• Estimated Primary Completion Date: April 30, 2020
• Estimated Study Completion Date: April 30, 2020

Arms and Interventions

Arm

Intervention/treatment

Experimental: Drospirenone/Ethinylestradiol + Midazolam + JNJ-64530440; 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; A single oral dose of drospirenone/ethinylestradiol 3 mg/0.02 mg (OC) tablets will be administered on Days 1, 13 and 19.; Other Name: Betadex clathrate; Drug: Midazolam; Midazolam 2 mg will be administered orally on Days 1, 13 and 19.; Drug: JNJ-64530440; A single oral dose of JNJ-64530440 2,000 mg will be administered on Day 6 and once daily on Days 13 to 22.

Outcome Measures

Primary Outcome Measures :

1. Maximum Observed Plasma Analyte Concentration (Cmax) of Drospirenone [ Time Frame: 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 ]
   Cmax is defined as maximum observed plasma analyte concentration.
2. Area Under the Plasma Analyte Concentration-Time Curve from Time Zero to Last Quantifiable Concentration Time (AUC [0-Last]) of Drospirenone [ Time Frame: 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 ]
   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.
3. Area Under the Plasma Concentration-Time Curve from Time Zero to Infinite Time (AUC [0-infinity]) of Drospirenone [ Time Frame: 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 ]
   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.
4. Maximum Observed Plasma Analyte Concentration (Cmax) of Ethinylestradiol [ Time Frame: 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 ]
   Cmax is defined as maximum observed plasma analyte concentration.
5. Area Under the Plasma Analyte Concentration-Time Curve from Time Zero to Last Quantifiable Concentration Time (AUC [0-Last]) of Ethinylestradiol [ Time Frame: 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 ]
   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.
6. Area Under the Plasma Concentration-Time Curve from Time Zero to Infinite Time (AUC [0-infinity]) of Ethinylestradiol [ Time Frame: 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 ]
   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.

Secondary Outcome Measures :

1. Maximum Observed Plasma Analyte Concentration (Cmax) of Midazolam [ Time Frame: 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 ]
   The Cmax is the maximum observed plasma analyte concentration.
2. Area Under the Plasma Analyte Concentration-Time Curve from Time Zero to Last Quantifiable Concentration Time (AUC [0-Last]) of Midazolam [ Time Frame: 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 ]
   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.
3. Area Under the Plasma Concentration-Time Curve from Time Zero to Infinite Time (AUC [0-infinity]) of Midazolam [ Time Frame: 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 ]
   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.
4. Cmax of JNJ-64530440 Under Fed Conditions (High-Fat Meal) [ Time Frame: Days 13 and 19: Predose, 0.5, 1, 2, 4, 6, 8, 10, 12, 18 and 24 hours) ]
   Cmax is defined as the maximum observed plasma concentration. Cmax will be assessed under fed conditions (high-fat meal).
5. Maximum Observed Plasma Concentration (Cmax) of JNJ-64530440 [ Time Frame: Days 13 and19: Predose, 0.5, 1, 2, 4, 6, 8, 10, 12, 18 and 24 hours ]
   The Cmax is the maximum observed plasma analyte concentration.
6. Number of Participants with Adverse Events (AEs) as a Measure of Safety and Tolerability [ Time Frame: Approximately up to 70 days ]
   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.

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 55 Years (Adult)
• Sexes Eligible for Study: Female
• Accepts Healthy Volunteers: Yes

Criteria

Inclusion Criteria:

• 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

Exclusion Criteria:

• 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

Contacts and Locations

Contacts

Contact: Study Contact; 844-434-4210; JNJ.CT@sylogent.com

Locations

United States, Utah

PRA Health Sciences; Not yet recruiting

Salt Lake City, Utah, United States, 84124

Contact 801-269-8200

Sponsors and Collaborators

Janssen Research & Development, LLC

Investigators

• Study Director: Janssen Research & Development, LLC Clinical Trial; Janssen Research & Development, LLC

More Information

Additional Information:

To learn how to participate in this trial please click here. 

• Responsible Party: Janssen Research & Development, LLC
• ClinicalTrials.gov Identifier: NCT03890341 History of Changes
• Other Study ID Numbers: JNJ-0440-1302; JNJ-0440-1302 ( Other Identifier: Janssen Research & Development, LLC )
• First Posted: March 26, 2019
• Last Update Posted: December 6, 2019
• Last Verified: December 2019

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Yes
• 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 Data Access (YODA) Project site at yoda.yale.edu
• URL: https://www.janssen.com/clinical-trials/transparency

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:

Drospirenone; Drospirenone and ethinyl estradiol combination; Ethinyl Estradiol; Midazolam; Contraceptive Agents; Contraceptives, Oral; Adjuvants, Anesthesia; Hypnotics and Sedatives; Central Nervous System Depressants; Physiological Effects of Drugs; Anti-Anxiety Agents; Tranquilizing Agents; Psychotropic Drugs; Anesthetics, Intravenous; Anesthetics, General; Anesthetics; GABA Modulators; GABA Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Reproductive Control Agents; Contraceptive Agents, Female; Estrogens; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Mineralocorticoid Receptor Antagonists; Hormone Antagonists; Diuretics, Potassium Sparing; Diuretics; Natriuretic Agents