Back to resultsTASK-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)
Primary Purpose
Tuberculosis
Status
Completed
Phase
Early Phase 1
Locations
South Africa
Study Type
Interventional
Intervention
bedaquiline
Sponsored by
About this trial
This is an interventional other trial for Tuberculosis
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)
- aspartate aminotransferase (AST) grade 3 (≥3.0 x ULN)
- alanine aminotransferase (ALT) grade 3 (≥3.0 x ULN)
Sites / Locations
- TASK Clinical Research Centre
Arms of the Study
Arm 1
Arm 2
Arm Type
Other
Other
Arm Label
Sequence 1
Sequence 2
Arm Description
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
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
Outcomes
Primary Outcome Measures
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.
Secondary Outcome Measures
Full Information
NCT ID
NCT03032367
First Posted
January 24, 2017
Last Updated
July 26, 2017
Sponsor
International Maternal Pediatric Adolescent AIDS Clinical Trials Group
Collaborators
US National Institute of Allergy and Infectious Diseases, Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), National Institute of Mental Health (NIMH)
1. Study Identification
Unique Protocol Identification Number
NCT03032367
Brief Title
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)
Official Title
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)
Study Type
Interventional
2. Study Status
Record Verification Date
July 2017
Overall Recruitment Status
Completed
Study Start Date
November 10, 2016 (Actual)
Primary Completion Date
December 9, 2016 (Actual)
Study Completion Date
January 11, 2017 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
International Maternal Pediatric Adolescent AIDS Clinical Trials Group
Collaborators
US National Institute of Allergy and Infectious Diseases, Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), National Institute of Mental Health (NIMH)
4. Oversight
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
Data Monitoring Committee
No
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Tuberculosis
7. Study Design
Primary Purpose
Other
Study Phase
Early Phase 1
Interventional Study Model
Crossover Assignment
Model Description
Participants are randomized to receive study drug (bedaquiline (BDQ)) in either tablet form or crushed form in one of two sequences:
Sequence 1: BDQ 4 x 100mg administered in a whole tablet form, followed by BDQ 4 x 100mg administered in crushed form as a once only dose
Sequence 2: BDQ 4 x 100mg administered in crushed form, followed by BDQ 4 x 100mg administered in tablet form as a once only dose
Masking
None (Open Label)
Allocation
Randomized
Enrollment
24 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Sequence 1
Arm Type
Other
Arm Description
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
Arm Title
Sequence 2
Arm Type
Other
Arm Description
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
Intervention Type
Drug
Intervention Name(s)
bedaquiline
Other Intervention Name(s)
Sirturo
Primary Outcome Measure Information:
Title
Bioequivalence of bedaquiline 4 x 100mg given to healthy adult males and females orally in tablet form compared to crushed form
Description
The bioequivalence evaluation will be based on primary PK parameters affecting the extent of absorption, i.e. the bioavailability.
Time Frame
Two single treatment sequences, separated by a 14-day wash-out period
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
55 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
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)
aspartate aminotransferase (AST) grade 3 (≥3.0 x ULN)
alanine aminotransferase (ALT) grade 3 (≥3.0 x ULN)
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Jeannine du Bois, MD
Organizational Affiliation
TASK Clinical Research Centre
Official's Role
Study Chair
First Name & Middle Initial & Last Name & Degree
Anthony Garcia-Pratts, MD
Organizational Affiliation
Desmond Tutu TB Centre, Stellenbosch University
Official's Role
Study Chair
Facility Information:
Facility Name
TASK Clinical Research Centre
City
Bellville
State/Province
Western Cape
ZIP/Postal Code
7530
Country
South Africa
12. IPD Sharing Statement
Plan to Share IPD
No
Learn more about this trial
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)
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