A Study of Bedaquiline 100 Milligram (mg) Tablets Administered as Different Test Formulations Compared to the Commercial Tablet Formulation (F001) in Healthy Adult Participants

Phase 1, Open-label, Randomized Crossover Study in Healthy Adult Subjects to Assess the Relative Oral Bioavailability and Food Effect of Bedaquiline 100-mg Tablets Administered as Different Test Formulations Compared to the Commercial Tablet Formulation (F001)

The purpose of this study is to assess the rate and extent of absorption of bedaquiline following administration of a single oral dose of 100 milligram (mg) equivalent (1*100 mg) given as different test tablet formulations compared to the administration of a single oral dose of 100 mg equivalent (1*100 mg) formulated as SIRTURO commercial tablet (formulation F001), under fasted conditions in healthy adult participants. Also, to assess the effect of a standardized breakfast on the rate and extent of absorption of bedaquiline compared to fasted conditions following administration of a single oral dose of 100 mg equivalent (1*100 mg) for each of the different test tablet formulations.

Study Overview

• Status: Completed
• Conditions: Healthy
• Intervention / Treatment: Drug: Bedaquiline (Test formulation); Drug: Bedaquiline (Reference formulation)

• Study Type: Interventional
• Enrollment (Actual): 36
• Phase: Phase 1

Contacts and Locations

Study Locations

• Belgium
  • Antwerpen, Belgium, 2060
    • SGS Life Science Services

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• A female participant must have a negative highly sensitive serum beta-human chorionic gonadotropin (beta-hCG) pregnancy test at screening and a negative urine pregnancy test on Day -1 in each treatment period
• Contraceptive use by women should be consistent with local regulations regarding the use of contraceptive methods for participant participating in clinical studies
• Participant must have a blood pressure (BP); supine after at least 5 minutes rest) between 90 and 140 millimeter of mercury (mmHg) systolic, extremes included, and no higher than 90 mmHg diastolic at screening
• Participant must be healthy on the basis of physical examination, medical history, vital signs, and electrocardiogram (ECG) performed at screening (results must be available on Day -1). If there are abnormalities participant may be included only if the investigator judges the abnormalities or deviations from normal to be not clinically significant. This determination must be recorded in the participant's source documents and initialed by the investigator
• Participant must have a body mass index (BMI); weight per height square between 18.0 and 30.0 kilogram per meter square (kg/m^2) (extremes included) at screening. The minimum body weight must be 50.0 kg at screening

Exclusion Criteria:

• Participant with any history of clinically significant skin disease such as, but not limited to, dermatitis, eczema, drug rash, psoriasis, food allergy, or urticaria
• Participant has known allergies, hypersensitivity, or intolerance to bedaquiline or its excipients
• Participant has received an investigational drug or used an invasive investigational medical device within 30 days or within a period less than 10 times the drug's elimination half-life (whichever is longer), or participant has received a biological product within 3 months or within a period less than 5 elimination half-lives (whichever is longer) before the planned first intake of study drug
• Participant has a history of human immunodeficiency virus (HIV)-1 or HIV-2 infection, or tests positive for HIV-1 or -2 at screening
• Participant has previously been dosed with bedaquiline, either in single or multiple dose studies, or participant with a previous history of pulmonal infection with Mycobacterium species

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

6

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Treatment Sequence BAE; Participants will receive a single dose of bedaquiline in 3 subsequent sessions as bedaquiline oral test tablet 1 under fasted condition (Treatment B) in period 1, followed by bedaquiline oral reference tablet under fasted condition (Treatment A) in period 2, thereafter will receive bedaquiline oral test tablet 1 under fed condition (Treatment E) in period 3. Each treatment period will be separated with a washout period of at least 28 days.	Drug: Bedaquiline (Test formulation); Participants will receive bedaquiline orally.; Other Names: JNJ-16175328; Drug: Bedaquiline (Reference formulation); Participants will receive bedaquiline orally.; Other Names: SIRTURO, TMC207
Experimental: Treatment Sequence CAF; Participants will receive a single dose of bedaquiline in 3 subsequent sessions as bedaquiline oral test tablet 2 under fasted condition (Treatment C) in period 1, followed by bedaquiline oral reference tablet under fasted condition (Treatment A) in period 2, thereafter will receive bedaquiline oral test tablet II under fed condition (Treatment F) in period 3. Each treatment period will be separated with a washout period of at least 28 days.	Drug: Bedaquiline (Test formulation); Participants will receive bedaquiline orally.; Other Names: JNJ-16175328; Drug: Bedaquiline (Reference formulation); Participants will receive bedaquiline orally.; Other Names: SIRTURO, TMC207
Experimental: Treatment Sequence DAG; Participants will receive a single dose of bedaquiline in 3 subsequent sessions as bedaquiline oral test tablet 3 under fasted condition (Treatment D) in period 1, followed by bedaquiline oral reference tablet under fasted condition (Treatment A) in period 2, thereafter will receive bedaquiline oral test tablet 3 under fed condition (Treatment G) in period 3. Each treatment period will be separated with a washout period of at least 28 days.	Drug: Bedaquiline (Test formulation); Participants will receive bedaquiline orally.; Other Names: JNJ-16175328; Drug: Bedaquiline (Reference formulation); Participants will receive bedaquiline orally.; Other Names: SIRTURO, TMC207
Experimental: Treatment Sequence ABE; Participants will receive a single dose of bedaquiline in 3 subsequent sessions as bedaquiline oral reference tablet under fasted condition (Treatment A) in period 1, followed by bedaquiline oral test tablet 1 under fasted condition (Treatment B) in period 2, thereafter will receive bedaquiline oral test tablet 1 under fed condition (Treatment E) in period 3. Each treatment period will be separated with a washout period of at least 28 days.	Drug: Bedaquiline (Test formulation); Participants will receive bedaquiline orally.; Other Names: JNJ-16175328; Drug: Bedaquiline (Reference formulation); Participants will receive bedaquiline orally.; Other Names: SIRTURO, TMC207
Experimental: Treatment Sequence ACF; Participants will receive a single dose of bedaquiline in 3 subsequent sessions as bedaquiline oral reference tablet under fasted condition (Treatment A) in period 1, followed by bedaquiline oral test tablet 2 under fasted condition (Treatment C) in period 2, thereafter will receive bedaquiline oral test tablet 2 under fed condition (Treatment F) in period 3. Each treatment period will be separated with a washout period of at least 28 days.	Drug: Bedaquiline (Test formulation); Participants will receive bedaquiline orally.; Other Names: JNJ-16175328; Drug: Bedaquiline (Reference formulation); Participants will receive bedaquiline orally.; Other Names: SIRTURO, TMC207
Experimental: Treatment Sequence ADG; Participants will receive a single dose of bedaquiline in 3 subsequent sessions as bedaquiline oral reference tablet under fasted condition (Treatment A) in period 1, followed by bedaquiline oral test tablet 3 under fasted condition (Treatment D) in period 2, thereafter will receive bedaquiline oral test tablet 3 under fed condition (Treatment G) in period 3. Each treatment period will be separated with a washout period of at least 28 days.	Drug: Bedaquiline (Test formulation); Participants will receive bedaquiline orally.; Other Names: JNJ-16175328; Drug: Bedaquiline (Reference formulation); Participants will receive bedaquiline orally.; Other Names: SIRTURO, TMC207

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Maximum Observed Analyte Concentration (Cmax) of Bedaquiline	Cmax is the maximum observed analyte concentration.	Predose, 1, 2, 3, 4, 5, 6, 8, 12, 24, 48, 72, 120, 168, 216, 264, 336, 504, and 672 hours postdose
Area Under the Analyte Concentration-time Curve from Time 0 to 72 Hours (AUC [0-72 hours]) of Bedaquiline	AUC (0-72 hours) is area under the analyte concentration-time curve from time 0 to 72 hours, calculated by linear-linear trapezoidal summation.	Predose, 1, 2, 3, 4, 5, 6, 8, 12, 24, 48, and 72 hours postdose
Area Under the Concentration-time Curve from Time Zero to the Last Measurable Concentration (AUC [0-last]) of Bedaquiline	AUC (0-last) is area under the analyte concentration-time curve from time zero to the time of the last measurable (non-below quantification limit) concentration, calculated by linear-linear trapezoidal summation.	Predose, 1, 2, 3, 4, 5, 6, 8, 12, 24, 48, 72, 120, 168, 216, 264, 336, 504, and 672 hours postdose
Area Under the Concentration-time Curve from Time Zero to Infinity (AUC [0-infinity]) of Bedaquiline	AUC (0-infinity) is the area under the analyte concentration-time curve from time zero to infinity time, calculated as the sum of AUC (0-last) and C(last)/lambda(z); wherein AUC (0-last) is area under the plasma concentration-time curve from time zero to last measurable concentration, C(last) is the last observed measurable concentration, and lambda(z) is apparent terminal elimination rate constant.	Predose, 1, 2, 3, 4, 5, 6, 8, 12, 24, 48, 72, 120, 168, 216, 264, 336, 504, and 672 hours postdose

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 does not necessarily have a causal relationship with the treatment. Therefore, it can be any unfavorable and unintended sign (including an abnormal finding), symptom, or disease temporally associated with the use of a medicinal product, whether or not related to that medicinal product.	Up to 112 Days

Collaborators and Investigators

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

Study record dates

Study Major Dates

• Study Start (Actual): September 16, 2019
• Primary Completion (Actual): January 7, 2020
• Study Completion (Actual): January 7, 2020

Study Registration Dates

• First Submitted: September 11, 2019
• First Submitted That Met QC Criteria: September 11, 2019
• First Posted (Actual): September 12, 2019

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: January 31, 2025
• Last Verified: January 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Anti-Bacterial Agents; Anti-Infective Agents; Antitubercular Agents; Bedaquiline; Diarylquinolines
• Other Study ID Numbers: CR108659; 2018-004306-26 (EudraCT Number); TMC207TBC1004 (Other Identifier: Janssen Research & Development, LLC)

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 Data 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
• product manufactured in and exported from the U.S.: Yes