TASK-002: Bioequivalence of Bedaquiline 400mg Administered in Crushed Form Compared to Tablet Form in Healthy Male and Female Adults Under Fed Conditions (BDQ Crush Study)

NCT ID: NCT03032367

Last Updated: 2017-07-28

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: EARLY_PHASE1
• Total Enrollment: 24 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2016-11-10
• Study Completion Date: 2017-01-11

Brief Summary

This is a randomized, open-label, cross-over study comparing the bioequivalence of bedaquiline administered in whole tablet form versus bedaquiline administered in crushed (experimental) form in healthy adult volunteers.

Detailed Description

This is a randomized, open-label, cross-over, bioequivalence study with two single treatment periods, separated by a 14-day wash-out period, conducted among 24 healthy adult males and females, who receive 400mg (4 x 100mg) bedaquiline orally in one of two sequences: either first in whole tablet form and second in crushed (experimental) form, or vice versa under fed conditions. The bioequivalence evaluation will be based on primary pharmacokinetic (pk) parameters affecting the extent of absorption, i.e., the bioavailability. If bioequivalence is not shown, the knowledge about the differences in bioavailability between whole and crushed tablets will be used for assessing the need of dose adjustment in children receiving the crushed form.

Conditions

Tuberculosis

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: OTHER
• Blinding Strategy: NONE

Study Groups

Sequence 1

Bedaquiline 4 x 100mg administered in a whole tablet form, followed by bedaquiline 4 x 100mg administered in crushed form as a once only oral dose

Group Type: OTHER

bedaquiline

Intervention Type: DRUG

Sequence 2

Bedaquiline 4x 100mg administered in crushed form, followed by bedaquiline 4 x 100mg administered in a whole tablet form, as a once only oral dose

Group Type: OTHER

bedaquiline

Intervention Type: DRUG

Interventions

bedaquiline

Intervention Type: DRUG

Other Intervention Names

Sirturo

Eligibility Criteria

Inclusion Criteria

• Written informed consent, including HIV testing
• Male or female between 18 and 55 years of age inclusive
• Body weight (in light clothing and with no shoes) between 40 and 90 kg, inclusive
• In the opinion of the investigator, able to comply with the requirements of the protocol e.g. able to attend all visits for PK analysis
• Be of non-childbearing potential or using effective methods of birth control

Exclusion Criteria

• Known or suspected hypersensitivity or intolerance to bedaquiline or any other constituents of the study drug, i.e. lactose
• A history or clinical evidence of any clinically significant cardiac condition including but not limited to congenital long QT syndrome, Torsades de Pointes, bradyarrhythmias
• Uncontrolled cardiac dysrhythmias
• Severe hepatic impairment (Child Pugh C)
• History, symptoms or signs of heart failure
• History, symptoms or signs of hypothyroidism, whether currently controlled or uncontrolled
• Any other serious uncontrolled medical condition or clinically significant abnormality, which, in the opinion of the investigator, might compromise the safety of the subject or which might interfere with the study.
• Evidence of clinically significant (as judged by the investigator), metabolic, gastrointestinal, cardiovascular, musculoskeletal, ophthalmological, pulmonary, neurological, psychiatric or endocrine diseases, malignancy, or other abnormalities.
• Concomitant use of medicines known to prolong the QTc interval, or use of CYP3A4 inducers/inhibitors including but not limited to, carbamazepine, phenytoin, St. John's wort, ciprofloxacin, erythromycin, clarithromycin, fluconazole, ketoconazole, ritonavir or other anti-retroviral medications, fluoroquinolones and clofazamine.
• HIV positive, already known or as per HIV test done at screening.
• Hepatitis B or C positive
• QTc prolongation as per ECG with a QTcF of >450msec or any other significant finding on the ECG as per the investigator
• Receipt of any study drug within the past 3 months.
• Scheduled to receive any other investigational drug during the course of the study.
• Known or suspected, current or history of within the past 2 years, alcohol or drug abuse, that is, in the opinion of the Investigator, sufficient to compromise the safety or cooperation of the volunteer.
• Evidence or suspicion of active TB or documented recent (within the last year) household contact with an infectious TB case.
• The following toxicities at screening as defined by the DAIDS toxicity table (November 2014)

1. aspartate aminotransferase (AST) grade 3 (≥3.0 x ULN)

2. alanine aminotransferase (ALT) grade 3 (≥3.0 x ULN)

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 55 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

US National Institute of Allergy and Infectious Diseases

UNKNOWN

Sponsor Role: collaborator

Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)

NIH

Sponsor Role: collaborator

National Institute of Mental Health (NIMH)

NIH

Sponsor Role: collaborator

International Maternal Pediatric Adolescent AIDS Clinical Trials Group

NETWORK

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Jeannine du Bois, MD

Role: STUDY_CHAIR

TASK Clinical Research Centre

Anthony Garcia-Pratts, MD

Role: STUDY_CHAIR

Desmond Tutu TB Centre, Stellenbosch University

Locations

TASK Clinical Research Centre

Bellville, Western Cape, South Africa

Countries

South Africa

Other Identifiers

TASK-002

Identifier Type: -

Identifier Source: org_study_id