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 0835 or +27 21 938 0967
Email: pactradmin@mrc.ac.za Website: pactr.samrc.ac.za
Trial no.: PACTR202111661886287 Date of Registration: 17/11/2021
Trial Status: Registered in accordance with WHO and ICMJE standards
TRIAL DESCRIPTION
Public title Primaquine bioequivalence study
Official scientific title Single dose oral bioequivalence study of Primaquine 15 mg tablet (test product) and Primaquine 15 mg tablet (reference product) in healthy adult human subjects under fasting conditions
Brief summary describing the background and objectives of the trial Primaquine (PQ) was originally developed as 0.25–0.5 mg base/kg body weight for 14-day course of treatment for the radical cure of P. vivax and P. ovale through clearance of hypnozoites following administration of blood-stage schizonticidal drugs such as chloroquine or artemisinin-based combination therapies (ACTs) (Vale, Moreira et al. 2009). There is now a growing interest in single low dose PQ for blocking the transmission of P. falciparum, following WHO’s recommendation in 2012 (World Health Organization 2016). Children are disproportionally affected by malaria of which vivax malaria affects young children less than 15 years of age peaking between 2 and 6 years that carries the highest risk of morbidity and mortality. Children under the age of 5 years accounted 67% of deaths from malaria in African region in 2019 (WHO 2020). However, there are no paediatric PQ formulations that are friendly to children. The availability of paediatric drugs in the right dosage forms with acceptable taste and odour/flavour is critically important for increasing adherence and allowing PQ regimens that do not need tablet fractions or require crushing tablets. PQ is now considered essential for eliminating malaria but to ensure child friendly PQ is made available it either has to be WHO prequalified or registered with a stringent drug regulatory authority. WHO prequalification offers the possibility of a line extension based on demonstrating proportionality with the adult 15 mg tablet. For a generic manufacturer, a bioequivalence study must be performed comparing the generic (test) product with the reference 15 mg of PQ. STUDY OBJECTIVES • To compare and evaluate the oral bioavailability of Primaquine 15 mg tablet of IPCA with that of Primaquine 15 mg tablet of Sanofi in healthy, adult, human subjects under fasting conditions. • Assess tolerability
Type of trial RCT
Acronym (If the trial has an acronym then please provide) PBE
Disease(s) or condition(s) being studied Bioequivalence study
Sub-Disease(s) or condition(s) being studied
Purpose of the trial Bioequivalence study
Anticipated trial start date 01/02/2024
Actual trial start date 13/07/2024
Anticipated date of last follow up 30/04/2024
Actual Last follow-up date 22/08/2024
Anticipated target sample size (number of participants) 40
Actual target sample size (number of participants) 40
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
Crossover: all participants receive all interventions in different sequence during study Randomised Simple randomization using a randomization table created by a computer software program Allocation was determined by the holder of the sequence who is situated off site Open-label(Masking Not Used)
INTERVENTIONS
Intervention type Intervention name Dose Duration Intervention description Group size Nature of control
Experimental Group Primaquine 15 mg tablet of IPCA One tablet PQ 15 mg Sigle dose PQ 15 mg IPCA tablet is a generic product 50
Control Group PQ 15 mg of Sanofi One tablet of PQ 15 mg Single dose PQ 15 mg of Sanofi is a reference product 50 Dose Comparison
ELIGIBILITY CRITERIA
List inclusion criteria List exclusion criteria Age Category Minimum age Maximum age Gender
1) Age: 18 to 55 years old, inclusive. 2) Gender: Male and/or non-pregnant, non-lactating female. 3) BMI: 18.5 to 30.0 kg/m2, both inclusive; BMI value should be rounded off to one significant digit after decimal point (e.g. 30.04 rounds down to 30.0, while 18.45 rounds up to 18.5). 4) Able to communicate effectively with study personnel. 5) Willing to provide written informed consent to participate in the study. 6) Non-smokers and nontobacco user (i.e. having no past history of smoking and tobacco consuming for at least one year prior to study). 7) All volunteers must be judged by the principal or sub-investigator or physician as normal and healthy during a pre-study safety assessment performed within 28 days of the first dose of study medication 1) History of allergic responses to Primaquine or other related drugs, or any of its formulation ingredients. 2) Have known significant diseases or clinically significant abnormal findings during screening (medical history, physical examination, laboratory evaluations, ECG). 3) Any disease or condition like diabetes, psychosis or others, which might compromise the haemopoietic, gastrointestinal, renal, hepatic, cardiovascular, respiratory, central nervous system or any other body system. 4) History or presence of bronchial asthma. 5) Use of any hormone replacement therapy within 3 months prior to the first dose of study medication. 6) A depot injection or implant of any drug within 3 months prior to the first dose of study medication. 7) Use of CYP enzyme inhibitors or inducers within 30 days prior to the first dose of study medication (see http://medicine.iupui.edu/clinpharm/ddis/main-table). 8) History or evidence of drug dependence or of alcoholism or of moderate alcohol use (> 14 units/week: 1 unit = 1 shot of spirits, ½ pint of beer, 1.5 = 125 mL of wine Alcohol units - NHS (www.nhs.uk). 9) History of difficulty with donating blood or difficulty in accessibility of veins. 10) A positive hepatitis screen (includes subtypes B & C). 11) A positive test result for HIV antibody and / or syphilis (RPR). 12) Volunteers who have received a known investigational drug within seven elimination half-lives of the administered drug prior to first dose of study medication or who have participated in a clinical drug study or bioequivalence study within 90 days prior to the first dose of study medication, whichever is greater. 13) Volunteers who have donated blood or loss of blood > 300 mL within 90 days (excluding volume drawn at screening for this study) prior to first dose of study medication, whichever is greater. 14) History of difficulty in swallowing or of any gastrointestinal disease, which could affect drug absorption. 15) Intolerance to venepuncture Adult: 18 Year(s)-44 Year(s),Middle Aged: 45 Year(s)-64 Year(s) 18 Year(s) 55 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 05/09/2022 AHRI ALERT Research Ethics Review Committee
Ethics Committee Address
Street address City Postal code Country
Zenebework, Jimma Road, ALERT Compound Addis Ababa 1005 Ethiopia
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 19/04/2022 Oxford Tropical Research Ethics Committee
Ethics Committee Address
Street address City Postal code Country
Research Services, University Offices Oxford OX1 2JD United Kingdom
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 05/06/2022 AHRI ALERT Ethics Review Committee
Ethics Committee Address
Street address City Postal code Country
Kolfe-Keranyo SC, Jimma Road, ALERT Compound Addis Ababa 1005 Ethiopia
OUTCOMES
Type of outcome Outcome Timepoint(s) at which outcome measured
Primary Outcome • Cmax • AUCt • AUCi, and • Tmax, Kel, AUC_%Extrap_obs, tHalf over 24 hours
Secondary Outcome Tolerability, assessed by the detection of clinical and laboratory adverse events over 24 hours post intervention
RECRUITMENT CENTRES
Name of recruitment centre Street address City Postal code Country
Armauer Hansen Research Institute Zenebework, JImma Road, ALERT Compound Addis Ababa 1005 Ethiopia
FUNDING SOURCES
Name of source Street address City Postal code Country
European and Developing Countries Clinical Trials Partnership 2509 AA The Hague The Hague 93015 Netherlands
SPONSORS
Sponsor level Name Street address City Postal code Country Nature of sponsor
Primary Sponsor The University of Oxford University of Oxford, University Offices, Wellington Square Oxford OX1 2JD United Kingdom University
COLLABORATORS
Name Street address City Postal code Country
CONTACT PEOPLE
Role Name Email Phone Street address
Principal Investigator Mekonnen Teferi Mekonnen mekonnen.teferi@ahri.gov.et +251911103233 Zenebework, Jimma Road, ALERT Copmound
City Postal code Country Position/Affiliation
Addis Ababa 1005 Ethiopia Researcher
Role Name Email Phone Street address
Scientific Enquiries Bob Taylor bob@tropmedres.ac +6622036333 MORU, Bangkok
City Postal code Country Position/Affiliation
Bangkok Thailand Scientist
Role Name Email Phone Street address
Public Enquiries Fikir Tadesse fiker.taddesse@gmail.com +25111820354 Zenebework, Jimma Road, ALERT Compound
City Postal code Country Position/Affiliation
Addis Ababa 1005 Ethiopia Researcher
REPORTING
Share IPD Description Additional Document Types Sharing Time Frame Key Access Criteria
Yes The data generated in this study belongs to the study group as a whole. The final database will be shared amongst the site PI and key members of the research team. The deidentified database may be shared with researchers not directly involved in this study but only after the main paper has been published and in accordance with AHRI Pharmacology unit and Mahidol Oxford Tropical Medicine Research unit guidelines on data sharing. The database will only be shared if future publications are not compromised. Clinical Study Report,Statistical Analysis Plan,Study Protocol Immediately after publication and if foreseeable publications are unlikely Researchers who wishes to access the data
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