A Study to Assess the Drug-Drug Interaction Between Bedaquiline and Clarithromycin in Healthy Adult Participants

NCT03800550 | Completed Phase 1

• 3 other identifiers: CR1085702018-004302-25TMC207NTM1001
• Study Type: interventional
• Target: 16
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to assess the effect of steady-state clarithromycin once every 12 hour on the pharmacokinetic parameters of bedaquiline and its active metabolite M2 after a single dose of bedaquiline.

Conditions

Healthy

Outcome Measures

Primary Outcomes (4)

• Maximum Observed Analyte Concentration (Cmax) of Bedaquiline and its Metabolite (M2)

  Cmax is the maximum observed analyte concentration.

  Pre-dose, 1, 2, 3, 4, 5, 6, 8, 12, 24, 48, 72, 120, 168, and 240 hours Post-dose

• Minimum Observed Analyte Concentration (Cmin) of Bedaquiline and its Metabolite (M2)

  Cmin is the minimum observed analyte concentration.

  Pre-dose, 1, 2, 3, 4, 5, 6, 8, 12, 24, 48, 72, 120, 168, and 240 hours Post-dose

• Area Under the Analyte Concentration versus Time Curve (AUC) From Time of Administration up to 72 Hours Post Dosing (AUC72h) of Bedaquiline and its Metabolite (M2)

  AUC72h is the area under the analyte concentration versus time curve (AUC) from time of administration up to 72 hours post dosing, calculated by linear-linear trapezoidal summation.

  Pre-dose, 1, 2, 3, 4, 5, 6, 8, 12, 24, 48, and 72 hours Post-dose

• Area Under the Analyte Concentration versus Time Curve (AUC) From Time of Administration up to 240 Hours Post Dosing (AUC240h) of Bedaquiline and its Metabolite (M2)

  AUC240h is the area under the analyte concentration-time curve from time 0 to 240 hours, calculated by linear-linear trapezoidal summation.

  Pre-dose, 1, 2, 3, 4, 5, 6, 8, 12, 24, 48, 72, 120, 168, and 240 hours Post-dose

Secondary Outcomes (5)

• Cmax of Clarithromycin and its Metabolite 14-OH-Clarithromycin

  Pre-dose, 1, 2, 3, 4, 5, 6, 8, and 12 hours Post-dose

• Time to Reach Maximum Observed Analyte Concentration (Tmax) of Clarithromycin and its Metabolite 14-OH-Clarithromycin

  Pre-dose, 1, 2, 3, 4, 5, 6, 8, and 12 hours Post-dose

• Cmin of Clarithromycin and its Metabolite 14-OH-Clarithromycin

  Pre-dose, 1, 2, 3, 4, 5, 6, 8, and 12 hours Post-dose

• Area Under the Analyte Concentration versus Time Curve (AUC) From Time of Administration up to 12 Hours Post Dosing (AUC12h) of Clarithromycin and its Metabolite 14-OH-Clarithromycin

  Pre-dose, 1, 2, 3, 4, 5, 6, 8, and 12 hours Post-dose

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

  Up to 90 days

Study Arms (2)

Treatment Sequence 1: Bedaquiline and Clarithromycin

EXPERIMENTAL

Participants will receive bedaquiline on Day 1 in Period 1, followed by clarithromycin on Days 1-14 and bedaquiline on Day 5 in Period 2. There will be washout period of at least 28 days starting on Day 1.

Drug: Bedaquiline; Drug: Clarithromycin

Treatment Sequence 2: Clarithromycin and Bedaquiline

EXPERIMENTAL

Participants will receive clarithromycin on Days 1-14 and bedaquiline on Day 5 in Period 1, followed by bedaquiline on Day 1 in Period 2. There will be a washout period of at least 28 days starting after bedaquiline administration on Day 5.

Drug: Bedaquiline; Drug: Clarithromycin

Interventions

Bedaquiline DRUG

Bedaquiline tablet will be administered, orally.

Treatment Sequence 1: Bedaquiline and Clarithromycin; Treatment Sequence 2: Clarithromycin and Bedaquiline

Clarithromycin DRUG

Clarithromycin tablet will be administered, orally.

Treatment Sequence 1: Bedaquiline and Clarithromycin; Treatment Sequence 2: Clarithromycin and Bedaquiline

Eligibility Criteria

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

You may qualify if:

• A female participant must have a negative highly sensitive serum (beta-human chorionic gonadotropin \[beta-hCG\]) pregnancy test at screening and on Day -1 in each treatment period
• Contraceptive use by women should be consistent with local regulations regarding the use of contraceptive methods for participants participating in clinical studies
• A female participant must agree not to donate eggs (ova, oocytes) for the purposes of assisted reproduction during the study and for at least 90 days after receiving the last dose of bedaquiline
• During the study and for a minimum of at least 90 days after receiving the last dose of bedaquiline: a) 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. b) A male participant must agree not to donate sperm for the purpose of reproduction
• Body mass index (BMI between 18.0 and 30.0 kilogram (kg) per meter square (inclusive), and body weight not less than 50 kg at screening

You may not qualify if:

• Participant has history 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 (for example, estimated creatinine clearance below 60 milliliter per minute \[mL/min\] 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
• Participant with a past history of heart arrhythmias (extrasystoles or tachycardia at rest), or history of risk factors for Torsade de Pointes syndrome (for example, hypokalemia, or family history of long QT syndrome). Family history of sudden unexplained death (including sudden infant death syndrome in a first-degree relative (that is, sibling, offspring, or biological parent). Ongoing bradyarrhythmias or ongoing hypothyroidism (confirmed by elevated thyroid-stimulating hormone \[TSH\] level)
• 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 taken any disallowed therapies before the planned first intake of study drug
• Participant has a history of drug or alcohol abuse according to Diagnostic and Statistical Manual of Mental Disorders (5th edition) criteria within 5 years before screening or positive test result(s) for alcohol and/or drugs of abuse (including barbiturates, opiates, cocaine, amphetamines, methadone, benzodiazepines, methamphetamine, tetrahydrocannabinol, phencyclidine, and tricyclic antidepressants) at screening and on Day 1 of each treatment period

Sponsors & Collaborators

• Janssen Research & Development, LLC: lead

Study Sites (1)

SGS Life Science Services

Antwerp, 2060, Belgium

Location

MeSH Terms

Interventions

bedaquiline; Clarithromycin

Intervention Hierarchy (Ancestors)

Erythromycin; Macrolides; Polyketides; Lactones; Organic Chemicals

Study Officials

• Janssen Research & Development, LLC Clinical Trial

  Janssen Research & Development, LLC

  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: January 9, 2019
• First Posted: January 11, 2019
• Study Start: February 13, 2019
• Primary Completion: June 4, 2019
• Study Completion: June 4, 2019
• Last Updated: February 3, 2025

Record last verified: 2025-01

Data Sharing

• IPD Sharing: Will share

Locations

BE (1)