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)

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.

Study Overview

• Status: Completed
• Conditions: Tuberculosis
• Intervention / Treatment: Drug: bedaquiline

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.

• Study Type: Interventional
• Enrollment (Actual): 24
• Phase: Early Phase 1

Contacts and Locations

Study Locations

• South Africa
  • Western Cape
    • Bellville, Western Cape, South Africa, 7530
      • TASK Clinical Research Centre

Participation Criteria

Eligibility Criteria

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

Description

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)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: OTHER
• Allocation: RANDOMIZED
• Interventional Model: CROSSOVER
• Masking: NONE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
OTHER: 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	Drug: bedaquiline; Other Names: Sirturo
OTHER: 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	Drug: bedaquiline; Other Names: Sirturo

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Bioequivalence of bedaquiline 4 x 100mg given to healthy adult males and females orally in tablet form compared to crushed form	The bioequivalence evaluation will be based on primary PK parameters affecting the extent of absorption, i.e. the bioavailability.	Two single treatment sequences, separated by a 14-day wash-out period

Collaborators and Investigators

• Sponsor: International Maternal Pediatric Adolescent AIDS Clinical Trials Group
• Collaborators: Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD); National Institute of Mental Health (NIMH); US National Institute of Allergy and Infectious Diseases
• Investigators: Study Chair: Jeannine du Bois, MD, TASK Clinical Research Centre; Study Chair: Anthony Garcia-Pratts, MD, Desmond Tutu TB Centre, Stellenbosch University

Study record dates

Study Major Dates

• Study Start (ACTUAL): November 10, 2016
• Primary Completion (ACTUAL): December 9, 2016
• Study Completion (ACTUAL): January 11, 2017

Study Registration Dates

• First Submitted: January 24, 2017
• First Submitted That Met QC Criteria: January 25, 2017
• First Posted (ESTIMATE): January 26, 2017

Study Record Updates

• Last Update Posted (ACTUAL): July 28, 2017
• Last Update Submitted That Met QC Criteria: July 26, 2017
• Last Verified: July 1, 2017

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Infections; Bacterial Infections; Bacterial Infections and Mycoses; Gram-Positive Bacterial Infections; Actinomycetales Infections; Mycobacterium Infections; Tuberculosis; Anti-Infective Agents; Anti-Bacterial Agents; Antitubercular Agents; Bedaquiline
• Other Study ID Numbers: TASK-002

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

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.: No