Clinical trial NCT03800550: A Study to Assess the Drug-Drug Interaction Between Bedaquiline and Clarithromycin in Healthy Adult Participants
Official title: A Phase 1, Open-label, Randomized, Crossover Study to Assess the Drug-Drug Interaction Between Bedaquiline and Clarithromycin in Healthy Adult Volunteers
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy
Lead sponsor: Janssen Research & Development, LLC
Sponsor class: INDUSTRY
First posted: 2019-01-11
Enrollment: 16
Sex: ALL
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: OTHER

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.


Eligibility criteria: Inclusion Criteria:

* 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

Exclusion Criteria:

* 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

Primary outcomes:
measure: Maximum Observed Analyte Concentration (Cmax) of Bedaquiline and its Metabolite (M2)
timeFrame: Pre-dose, 1, 2, 3, 4, 5, 6, 8, 12, 24, 48, 72, 120, 168, and 240 hours Post-dose
measure: Minimum Observed Analyte Concentration (Cmin) of Bedaquiline and its Metabolite (M2)
timeFrame: Pre-dose, 1, 2, 3, 4, 5, 6, 8, 12, 24, 48, 72, 120, 168, and 240 hours Post-dose
measure: 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)
timeFrame: Pre-dose, 1, 2, 3, 4, 5, 6, 8, 12, 24, 48, and 72 hours Post-dose
measure: 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)
timeFrame: Pre-dose, 1, 2, 3, 4, 5, 6, 8, 12, 24, 48, 72, 120, 168, and 240 hours Post-dose
Secondary outcomes:
measure: Cmax of Clarithromycin and its Metabolite 14-OH-Clarithromycin
timeFrame: Pre-dose, 1, 2, 3, 4, 5, 6, 8, and 12 hours Post-dose
measure: Time to Reach Maximum Observed Analyte Concentration (Tmax) of Clarithromycin and its Metabolite 14-OH-Clarithromycin
timeFrame: Pre-dose, 1, 2, 3, 4, 5, 6, 8, and 12 hours Post-dose
measure: Cmin of Clarithromycin and its Metabolite 14-OH-Clarithromycin
timeFrame: Pre-dose, 1, 2, 3, 4, 5, 6, 8, and 12 hours Post-dose
measure: 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
timeFrame: Pre-dose, 1, 2, 3, 4, 5, 6, 8, and 12 hours Post-dose
measure: Number of Participants with Adverse Events as a Measure of Safety and Tolerability
timeFrame: Up to 90 days
Other outcomes:
Locations:
city: Antwerpen
country: Belgium
facility: SGS Life Science Services
Study officials:
affiliation: Janssen Research & Development, LLC
name: Janssen Research & Development, LLC Clinical Trial
role: STUDY_DIRECTOR
References: