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

Healthy Clinical Trial

Official title:

A Phase 1, Open-label, Randomized, Crossover Study to Assess the Drug-Drug Interaction Between Bedaquiline and Clarithromycin in Healthy Adult Volunteers

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03800550
• Other study ID #: CR108570
• Secondary ID: 2018-004302-25TM
• Status: Completed
• Phase: Phase 1
• Start date: February 13, 2019
• Est. completion date: June 4, 2019

Study information

• Verified date: August 2019
• Source: Janssen Research & Development, LLC
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 16
• Est. completion date: June 4, 2019
• Est. primary completion date: June 4, 2019
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 55 Years

Eligibility

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

Related Conditions & MeSH terms

• Healthy

Intervention

Drug:
• Bedaquiline
Bedaquiline tablet will be administered, orally.
• Clarithromycin
Clarithromycin tablet will be administered, orally.

Locations

Country	Name	City	State
Belgium	SGS Life Science Services	Antwerpen

Sponsors (1)

Lead Sponsor	Collaborator
Janssen Research & Development, LLC

Country where clinical trial is conducted

Belgium, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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
Primary	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
Primary	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	Cmax of Clarithromycin and its Metabolite 14-OH-Clarithromycin	Cmax is the maximum observed analyte concentration.	Pre-dose, 1, 2, 3, 4, 5, 6, 8, and 12 hours Post-dose
Secondary	Time to Reach Maximum Observed Analyte Concentration (Tmax) of Clarithromycin and its Metabolite 14-OH-Clarithromycin	Tmax is the actual sampling time to reach the maximum observed analyte concentration.	Pre-dose, 1, 2, 3, 4, 5, 6, 8, and 12 hours Post-dose
Secondary	Cmin of Clarithromycin and its Metabolite 14-OH-Clarithromycin	Cmin is the minimum observed analyte concentration.	Pre-dose, 1, 2, 3, 4, 5, 6, 8, and 12 hours Post-dose
Secondary	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	AUC12h is the area under the analyte concentration versus time curve (AUC) from time of administration up to 12 hours post dosing, calculated by linear-linear trapezoidal summation.	Pre-dose, 1, 2, 3, 4, 5, 6, 8, and 12 hours Post-dose
Secondary	Number of Participants with Adverse Events as a Measure of Safety and Tolerability	An adverse event is any untoward medical event that occurs in a participant administered an investigational product, and it does not necessarily indicate only events with clear causal relationship with the relevant investigational product.	Up to 90 days

External Links

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