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.: PACTR202106791732070 Date of Approval: 01/06/2021
Trial Status: Retrospective registration - This trial was registered after enrolment of the first participant
TRIAL DESCRIPTION
Public title Pharmacokinetics and pharmacogenomics of Tamoxifen in healthy volunteers: The effects of African specific CYP2D6*17 genotype on the plasma levels of Tamoxifen and its metabolites
Official scientific title Pharmacokinetics and pharmacogenomics of Tamoxifen in healthy volunteers: The effects of African specific CYP2D6*17 genotype on the plasma levels of Tamoxifen and its metabolites
Brief summary describing the background and objectives of the trial About a third of patients who receive tamoxifen therapy do not benefit from tamoxifen therapy due to various factors including reduced capacity to generate the active metabolite, endoxifen. The major enzyme involved in the metabolism of tamoxifen to endoxifen is CYP2D6. This enzyme exhibits extensive genetic variation which results in high inter-individual and inter-population differences in metabolism. It has been shown that people with no or reduced CYP2D6 activity will have poor response to tamoxifen. There is therefore a need to know whether genetic variation of CYP2D6*17 unique to African populations could explain why people of African descent have been reported to respond poorly to tamoxifen compared to their Caucasian counterparts. It will also be important to explore whether increasing the dose of tamoxifen for patients with CYP2D6*17/17 can result in therapeutic levels of the active metabolite endoxifen. the main objective of the study is to determine the effect of the African specific CYP2D6*17 genetic variant in tamoxifen pharmacokinetics and formation of its metabolites in healthy volunteers.
Type of trial CCT
Acronym (If the trial has an acronym then please provide) PHAT
Disease(s) or condition(s) being studied Cancer
Sub-Disease(s) or condition(s) being studied
Purpose of the trial Treatment: Drugs
Anticipated trial start date 07/01/2019
Actual trial start date 22/04/2019
Anticipated date of last follow up 30/09/2021
Actual Last follow-up date
Anticipated target sample size (number of participants) 42
Actual target sample size (number of participants)
Recruitment status Recruiting
Publication URL
Secondary Ids Issuing authority/Trial register
A2386 Medical Research Council of Zimbabwe
CT1702018 Medicines Control Authority of Zimbabwe
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 Non-randomised 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
Control Group Tamoxifen 20mg, single dose p.o 1 day Tamoxifen 20mg tablet single dose normal CYP2D6 activity *1/*1 diplotype 14 Active-Treatment of Control Group
Experimental Group Tamoxifen 20 mg as a single dose 1 day Tamoxifen 20mg given as a single dose to participants with genotype CYP2D6*1/*17 enzyme 14
Experimental Group Tamoxifen 20 mg as a single dose 1 day Tamoxifen 20mg given as a single dose to participants with genotype CYP2D6*17/*17 enzyme 14
ELIGIBILITY CRITERIA
List inclusion criteria List exclusion criteria Age Category Minimum age Maximum age Gender
Male and female subjects aged 18 to 30 years (inclusive). Good health as determined by past medical history, physical examination, vital signs, ECG, and laboratory tests at screening. Be able to communicate and understand the consent process Be of the following CYP2D6 genotypes: CYP2D6*1/*1, CYP2D6*1/*2, CYP2D6*2/*2, CYP2D6*1/*17 and CYP2D6*17/*17 BMI between 19 to 27 kg/m2 (inclusive) 1. Pregnant women 2. On medication that is known to inhibit CYP2D6 such as antidepressants and antipsychotics 3. Any other CYP2D6 genotypes which are not CYP2D6*1/*1, CYP2D6*1/*2, CYP2D6*2/*2, CYP2D6*1/*17 and CYP2D6*17/*17 4. Breastfeeding women 5. Smokers who report a daily use more than 10 cigarettes 6. Use of prescription drugs or OTC medication 7. Participation in any clinical in Adult: 19 Year-44 Year 18 Year(s) 30 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 05/12/2018 Medical Research Council of Zimbabwe
Ethics Committee Address
Street address City Postal code Country
Josiah Tongogara/ Mazoe Street Harare 0000 Zimbabwe
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 05/02/2019 Medical Research Council of Zimbabwe
Ethics Committee Address
Street address City Postal code Country
Josiah Tongogara and Mazowe Street Harare Harare Zimbabwe
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 05/12/2018 Medical Research Council of Zimbabwe
Ethics Committee Address
Street address City Postal code Country
Mozowe Street / J. Tongogara Harare 0000 Zimbabwe
OUTCOMES
Type of outcome Outcome Timepoint(s) at which outcome measured
Primary Outcome Pharmacokinetics of Tamoxifen and formation of endoxifen in subgroups of different CYP2D6 genotypes of interest to the study. Assessment and comparison between the PK parameters of Tamoxifen for 3 subgroups of the respective value of AUC0-t, AUCinf, Cmax, Tmax and T1/2. 0, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, 16, 24 hours and daily for 21 days
Secondary Outcome PK modeling and simulation based pharmacogenetics guided dosing algorithm in the use of Tamoxifen carriers of the CYP2D17 variants. 0, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, 16, 24 hours and daily for 21 days
RECRUITMENT CENTRES
Name of recruitment centre Street address City Postal code Country
African Institute of Biomedical Science and Technology Chitungwiza Central Hospital Clinical Trial Unit 12096 Batanai Street Zengeza 4 Harare 0000 Zimbabwe
FUNDING SOURCES
Name of source Street address City Postal code Country
Norvatis Forum 1, Novartis Campus Basel CH-4056 Switzerland
SPONSORS
Sponsor level Name Street address City Postal code Country Nature of sponsor
Primary Sponsor AiBST Wilkins Hospital Block C corner Josiah Tongogara and Princess Road Harare 0000 Zimbabwe Other Collaborative Groups
COLLABORATORS
Name Street address City Postal code Country
CONTACT PEOPLE
Role Name Email Phone Street address
Principal Investigator Collen Masimirembwa collenmasimirembwa@yahoo.com +26377422951 Wilkins Hospital Block C Cnr J. Tongogara/ Princess Road
City Postal code Country Position/Affiliation
Harare 0000 Zimbabwe Principle Investigator
Role Name Email Phone Street address
Scientific Enquiries Roslyn Thelingwani roslyn.thelingwani@aibst.com +263773817401 Wilkins Hospital Block C Corner Josiah Tongogara/ Princess Road
City Postal code Country Position/Affiliation
Harare 0000 Zimbabwe Senior Scientist
Role Name Email Phone Street address
Public Enquiries Georginah Nyabadza georginah.nyabadza@aibst.com +263773069254 Wilkins Hospital Block C Corner Princess Road and Josiah Tongongara Road
City Postal code Country Position/Affiliation
Harare 0000 Zimbabwe Clinical Trial Manager
REPORTING
Share IPD Description Additional Document Types Sharing Time Frame Key Access Criteria
Yes Individual participant data that underlie the results reported in this article, after deidentification (text, tables, figures, and appendices) Clinical Study Report Beginning 9 months and ending 36 months following article publication nvestigators whose proposed use of the data has been approved by an independent review committee identified for this purpose
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