Pan African Clinical Trials Registry
South African Medical Research Council, South African Cochrane Centre
PO Box 19070, Tygerberg, 7505, South Africa
Telephone: +27 21 938 0506 / +27 21 938 0834 Fax: +27 21 938 0836
Email: pactradmin@mrc.ac.za Website: pactr.samrc.ac.za
Trial no.: PACTR202306775627089 Date of Approval: 15/06/2023
Trial Status: Registered in accordance with WHO and ICMJE standards
TRIAL DESCRIPTION
Public title TASK 011-RPT-Crush:Relative bioavailability of three generic rifapentine and isoniazid compounds when manipulated in adults with latent tuberculosis: a bridge to paediatric dosing needs (“RPT CRUSH”)
Official scientific title TASK 011-RPT-Crush:Relative bioavailability of three generic rifapentine and isoniazid compounds when manipulated in adults with latent tuberculosis: a bridge to paediatric dosing needs (“RPT CRUSH”)
Brief summary describing the background and objectives of the trial Tuberculosis (TB) remains a leading cause of morbidity and mortality globally. The COVID-19 pandemic has dramatically reduced achievements made in TB case detection, prevention and treatment, resulting in an increase in TB-related mortality for the first time in two decades in 2020 (1). Children < 15 years of age accounted for approximately 11% of the global TB case load in 2020 (approximately one million children estimated to develop TB each year), and contribute to a disproportionate 16% of TB related deaths (2). Paediatric TB is preventable and children with TB disease have good treatment outcomes when diagnosed and treated appropriately. Children with TB exposure are at high risk of progression to disease and to severe forms of disease, with the highest risk occurring in children < 2 years of age, children living with HIV and those with malnutrition. Young children are typically exposed to TB in the household and also in the broader community as they become older and more mobile. TB preventive therapy (TPT) significantly reduces the risk of progression of TB infection to active disease in children, adolescents and adults. TPT is effective, safe, well-tolerated and cost-effective, with a long-standing recommendation for TPT in those at high risk of TB by the World Health Organization (WHO). The 3HP regimen (12 weekly doses of rifapentine (RPT) and isoniazid (INH) is a simplified, effective, and approved regimen for TPT. As the development of child-friendly formulations of RPT drugs is lengthy and access is currently limited in the field, there is a clear and immediate need to see whether available and affordable genetic formulations of RPT/INH can be manipulated to enable their use in children. The primary objective of this study is to estimate the relative bioavailability of (RPT) and (INH) following dosing with 1) RPT/INH FDC (MacLeods), 2) RPT/INH FDC (Lupin) or 3) RPT single compound (Lupin) given with INH single compound (Winthrop/Macleods), in water.
Type of trial RCT
Acronym (If the trial has an acronym then please provide) TASK011RPTCrush
Disease(s) or condition(s) being studied Infections and Infestations
Sub-Disease(s) or condition(s) being studied Tuberculosis
Purpose of the trial Treatment: Drugs
Anticipated trial start date 01/01/2023
Actual trial start date 17/10/2023
Anticipated date of last follow up 31/12/2023
Actual Last follow-up date 23/05/2024
Anticipated target sample size (number of participants) 24
Actual target sample size (number of participants) 24
Recruitment status Completed
Publication URL
Secondary Ids Issuing authority/Trial register
STUDY DESIGN
Intervention assignment Allocation to intervention If randomised, describe how the allocation sequence was generated Describe how the allocation sequence/code was concealed from the person allocating the participants to the intervention arms Masking If masking / blinding was used
Parallel: different groups receive different interventions at same time during study Randomised Simple randomization using a randomization table created by a computer software program Sealed opaque envelopes Open-label(Masking Not Used)
INTERVENTIONS
Intervention type Intervention name Dose Duration Intervention description Group size Nature of control
Experimental Group Study Group 1 Rifapentine 300mg/Isoniazid 300 mg fixed dose combination (FDC) tablet (MacLeods, India), Rifapentine 300mg/Isoniazid 300 mg FDC tablet (Lupin, India)with water, as per standard dosing recommendations, administered with a standard breakfast, at the initial four dosing occasions. 12 weeks RPT/INH on the second day of each admission period (days 1, 8, 15 and 22), and weekly over the last 8 weeks of the study. 8
Experimental Group Study Group 2 Rifapentine 300 mg/Isoniazid 300 mg FDC tablets (generic formulation manufactured by Lupin Pharmaceuticals, India) Isoniazid 300 mg (Winthrop Pharmaceuticals, South Africa or MacLeods Pharmaceuticals, India) Rifapentine 300 mg tablets (generic formulation manufactured by Lupin Pharmaceuticals, India), orally with water. 12 weeks RPT/INH on the second day of each admission period (days 1, 8, 15 and 22), and weekly over the last 8 weeks of the study. 8
Experimental Group Study Group 3 Rifapentine 300 mg/Isoniazid 300 mg FDC tablets (generic formulation manufactured by MacLeods Pharmaceuticals, India) Isoniazid 300 mg (Winthrop Pharmaceuticals, South Africa or MacLeods Pharmaceuticals, India) Rifapentine 300 mg tablets (generic formulation manufactured by Lupin Pharmaceuticals, India), orally with water, as per standard dosing recommendations, 12 weeks RPT/INH on the second day of each admission period (days 1, 8, 15 and 22), and weekly over the last 8 weeks of the study. 8
Control Group NA N/A N/A N/A 0 Uncontrolled
ELIGIBILITY CRITERIA
List inclusion criteria List exclusion criteria Age Category Minimum age Maximum age Gender
1. Written informed consent 2. Able/willing to comply with the protocol requirements 3. Aged between 18 and 65 years 4. Documented recent TB exposure 5. Evidence of TB infection (positive IGRA or TST <3 months prior to enrolment) 6. Body weight ≥40kg and ≤ 90 kg 7. If of child-bearing potential, agree to use effective birth-control measures throughout the study. 1. Diseases or conditions in which use of RPT/INH contraindicated; 2. Known hypersensitivity or intolerance to RPT or INH; 3. Recent TB exposure to drug-resistant TB 4. Confirmed or suspected active TB 5. HIV infection; 6. Active chronic hepatitis B (HBsAg positive) 7. Females who are pregnant, breastfeeding, or planning to conceive a child within the study period 8. Laboratory abnormalities at screening; including anemia, leukopenia, thrombopenia, renal failure or hepatitis. 9. Use of any prohibited medication 10. Current participation in any other intervention trial of a therapeutic agent 11. Screening drug test positive for amphetamines/methamphetamines, opioids, methaqualone, benzodiazepines 12. Self-reported alcohol use exceeding 28 units per week for men, or 21 units for women 13. Clinically significant diseases/abnormalities that might compromise safety of the participant/interpretability of data. Adult: 19 Year-44 Year,Middle Aged: 45 Year(s)-64 Year(s) 18 Year(s) 65 Year(s) Both
ETHICS APPROVAL
Has the study received appropriate ethics committee approval Date the study will be submitted for approval Date of approval Name of the ethics committee
Yes 13/12/2022 The Stellenbosch University Health Research Ethics Committee
Ethics Committee Address
Street address City Postal code Country
Stellenbosch University Stellenbosch 7602 South Africa
OUTCOMES
Type of outcome Outcome Timepoint(s) at which outcome measured
Primary Outcome 1. To estimate the relative bioavailability of Rifapentine (RPT) and Isoniazid (INH) following dosing with 1) RPT/INH FDC (MacLeods), 2) RPT/INH FDC (Lupin) or 3) RPT single compound (Lupin) given with INH single compound (Winthrop/MacLeods), administered suspended in water compared to dosing as whole tablets Day 1,8, 15 and 22
Secondary Outcome 1. To investigate potential differences in absorption rate and variability of RPT and INH following dosing as whole tablets versus suspended in water Day 1,8, 15 and 22
Secondary Outcome 2. To describe other derived pharmacokinetic (PK) parameters including Cmax, Tmax and area under the concentration-time curve (AUC)0-168hr for RPT and 25-Desacetyl-Rifapentine metabolite Day 1,8, 15 and 22
Secondary Outcome 3. To describe other derived pharmacokinetic parameters including Cmax, Tmax and AUC0-24hr INH Day 1,8, 15 and 22
Secondary Outcome 4. To describe the short-term safety of suspended RPT/INH Days 15 and 29
Secondary Outcome 5. To describe the palatability and acceptability of suspended RPT/INH Day 1,8, 15 and 22
Secondary Outcome 6. To estimate the relative bioavailability of RPT and INH following dosing with RPT/INH FDC (MacLeods) or RPT/INH FDC (Lupin) compared to RPT single compound (Lupin) given with INH single compound (Winthrop/MacLeods), respectively, administered as whole tablets Day 1,8, 15 and 22
RECRUITMENT CENTRES
Name of recruitment centre Street address City Postal code Country
TASK Brooklyn 1 Stanberry Road Yesterplaat 7405 South Africa
FUNDING SOURCES
Name of source Street address City Postal code Country
Unitaid Global Health Campus, Chemin du Pommier 40, 5th floor,1218 Grand-Saconnex Geneva Switzerland
SPONSORS
Sponsor level Name Street address City Postal code Country Nature of sponsor
Primary Sponsor Stellenbosch University Francie van Zijl Drive, Tygerberg Cape Town 8001 South Africa University
COLLABORATORS
Name Street address City Postal code Country
Prof Elin Svensson Department of Pharmacy, Faculty of Pharmacy, Uppsala University Box 591 Uppsala 75124 Sweden
CONTACT PEOPLE
Role Name Email Phone Street address
Principal Investigator Caryn Upton dr.caryn@task.org.za +27215102209 1 Stanberry Road
City Postal code Country Position/Affiliation
Cape Town 7405 South Africa Investigator
Role Name Email Phone Street address
Scientific Enquiries Saskia Janssen dr.saskia@task.org.za +27211003606 1 Smal Street
City Postal code Country Position/Affiliation
Bellville 7530 South Africa Co Principal Investigator
Role Name Email Phone Street address
Public Enquiries Caryn Upton dr.caryn@task.org.za +27215102209 1 Stanberry Road
City Postal code Country Position/Affiliation
Ysterplaat 7405 South Africa Investigator
REPORTING
Share IPD Description Additional Document Types Sharing Time Frame Key Access Criteria
Yes A Data Management Plan is currently under development. The data management plan will describe in relevant detail the procedures for collecting, storing, and protecting personal data of participants in the trial. The plan will be designed to align with the data sharing regulations under the local South African Protection of Personal Information Act (POPIA), General Data Protection Regulation (GDPR) relevant for the EU and other applicable data protection laws. Anonymized clinical study data will be deposited in an open access data repository like clintrials.gov, after presentation of clinical study report. Data will be presented in CDISC format. The FAIR principles (findable, accessible, interoperable, re-usable) will be followed all along this process. Privacy and security are the priority throughout the entire data stewardship life cycle, starting with proper study design, data capture, data processing, curation and finally linking and analysis for interpretation. Data will be shared with UNITAID, the World Health Organization (WHO) and all other relevant stakeholders since the aim of the study is to inform and broaden access. The study protocol itself will also be available upon request for the larger research community. We anticipate sharing data immediately with WHO to inform their policy guidance. Individual participant data will be available upon completion of this trial. After deidentification, all individual participant data collected during the trial will be deposited in an open access data repository like clintrials.gov. Study Protocol, Statistical Analysis Plan, Informed Consent form and Clinical Study Report will be available upon request after publication of the study findings. Data will be available indefinitely at an open access data repository. Clinical Study Report Immediately, following publication Not yet available
URL Results Available Results Summary Result Posting Date First Journal Publication Date
No
Result Upload 1: Result Upload 2: Result Upload 3: Result Upload 4: Result Upload 5:
Result URL Hyperlinks Link To Protocol
Result URL Hyperlinks
Changes to trial information
Section Name Field Name Date Reason Old Value Updated Value
Trial Information Actual trial start date 06/11/2024 Study completed. 17 Oct 2023
Section Name Field Name Date Reason Old Value Updated Value
Trial Information Completion date 06/11/2024 Study completed. 23 May 2024
Section Name Field Name Date Reason Old Value Updated Value
Trial Information Final no of participants 06/11/2024 Study completed. 24
Section Name Field Name Date Reason Old Value Updated Value
Trial Information Recruitment status 06/11/2024 Study completed Not yet recruiting Completed
Section Name Field Name Date Reason Old Value Updated Value
Reporting IPD description 17/05/2023 IPD Sharing statement added. Not yet available. A Data Management Plan is currently under development. The data management plan will describe in relevant detail the procedures for collecting, storing, and protecting personal data of participants in the trial. The plan will be designed to align with the data sharing regulations under the local South African Protection of Personal Information Act (POPIA), General Data Protection Regulation (GDPR) relevant for the EU and other applicable data protection laws. Anonymized clinical study data will be deposited in an open access data repository like clintrials.gov, after presentation of clinical study report. Data will be presented in CDISC format. The FAIR principles (findable, accessible, interoperable, re-usable) will be followed all along this process. Privacy and security are the priority throughout the entire data stewardship life cycle, starting with proper study design, data capture, data processing, curation and finally linking and analysis for interpretation. Data will be shared with UNITAID, the World Health Organization (WHO) and all other relevant stakeholders since the aim of the study is to inform and broaden access. The study protocol itself will also be available upon request for the larger research community. We anticipate sharing data immediately with WHO to inform their policy guidance. Individual participant data will be available upon completion of this trial. After deidentification, all individual participant data collected during the trial will be deposited in an open access data repository like clintrials.gov. Study Protocol, Statistical Analysis Plan, Informed Consent form and Clinical Study Report will be available upon request after publication of the study findings. Data will be available indefinitely at an open access data repository.