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.: PACTR201302000483287 Date of Registration: 14/01/2013
Trial Status: Registered in accordance with WHO and ICMJE standards
TRIAL DESCRIPTION
Public title ARTEM-TB STUDY
Official scientific title EVALUATING PHARMACOKINETIC INTERACTIONS BETWEEN ARTEMISININ-BASED THERAPIES AND RIFAMPICIN-BASED TUBERCULOSIS TREATMENT IN AFRICAN PATIENTS
Brief summary describing the background and objectives of the trial Recent work conducted at IDI by this group has demonstrated that the most widely used first-line antimalarial drug (artemether-lumefantrine) interacts unfavourably with rifampicin. There are no evidence-based treatment options for malaria treatment in rifampicin-treated patients with tuberculosis (TB). This project aims to investigate drug interactions between antimalarial and anti-TB drugs with the overall goal of developing co-treatment strategies for malaria and TB co-infection. Primary objectives: ¿ Group 1: To investigate the single dose pharmacokinetics (PK) of dihydroartemisinin (DHA) and piperaquine following oral administration of dihydroartemisinin-piperaquine to patients receiving rifampicin and to the same patients after stopping rifampicin intake. ¿ Group 2: To investigate the single dose PK of artesunate, DHA and desethylamodiaquine (DEAQ) following oral administration of artesunate-amodiaquine to patients receiving rifampicin and to the same patients after stopping rifampicin intake. ¿ Group 3: To investigate the single dose PK of artesunate and DHA following intravenous administration of artesunate to patients receiving rifampicin and to the same patients after stopping rifampicin intake.
Type of trial CCT
Acronym (If the trial has an acronym then please provide)
Disease(s) or condition(s) being studied Infections and Infestations
Sub-Disease(s) or condition(s) being studied Malaria,Tuberculosis
Purpose of the trial Treatment: Drugs
Anticipated trial start date 31/01/2013
Actual trial start date 26/09/2013
Anticipated date of last follow up 30/06/2014
Actual Last follow-up date 24/11/2014
Anticipated target sample size (number of participants) 36
Actual target sample size (number of participants) 36
Recruitment status Completed
Publication URL
Secondary Ids Issuing authority/Trial register
HS1294 Uganda National Council for Science and Technology
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 Open-label(Masking Not Used)
Parallel: different groups receive different interventions at same time during study Non-randomised Open-label(Masking Not Used)
INTERVENTIONS
Intervention type Intervention name Dose Duration Intervention description Group size Nature of control
Experimental Group Tablets dihydroartemisinin-piperaquine (40mg/320mg) Three tablets (Single dose) One (1) day in each study phase Participants receive a single dose of dihydroartemisinin-piperaquine tablets in Phase 1 (while on rifampicin-based TB treatment) and in Phase 2 (greater than 3 weeks after stopping rifampicin intake) 12
Experimental Group Tablets artesunate-amodiaquine (100mg/270mg) Two tablets (single dose) One (1) day in each study phase Participants receive a single dose of artesunate-amodiaquine tablets in Phase 1 (while on rifampicin-based TB treatment) and in Phase 2 (greater than 3 weeks after stopping rifampicin intake) 12
Experimental Group Intravenous artesunate 2.4mg/kg (single dose) One (1) day in each study phase Participants receive a single dose of intravenous artesunate in Phase 1 (while on rifampicin-based TB treatment) and in Phase 2 (greater than 3 weeks after stopping rifampicin intake) 12
ELIGIBILITY CRITERIA
List inclusion criteria List exclusion criteria Age Category Minimum age Maximum age Gender
¿ Evidence of a personally signed and dated informed consent document indicating that the subject (or a legal representative) has been informed of all pertinent aspects of the study. ¿ Subjects who are willing and able to comply with scheduled visits, treatment plan, laboratory tests, and other study procedures. ¿ Aged between 18 to 65 years, inclusive. ¿ Receiving TB-therapy containing rifampicin for at least 2 weeks ¿ Hypersensitivity to any of the study drugs or excipients ¿ HIV infection ¿ Malaria infection at screening ¿ Serum hemoglobin < 8g/dL ¿ Elevations in serum levels of alanine transaminase, aspartate transaminase or creatinine above 3 times the upper limit of normal ¿ History of cardiac disease ¿ Diarrhea lasting greater than one week ¿ Use of herbal medications ¿ Use of potent inhibitors of CYP3A4 including grapefruit juice within 1 week of first dose of study drug and for the duration of the study ¿ Pregnant or lactating females 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 08/11/2012 Joint Clinical Research Centre IRB
Ethics Committee Address
Street address City Postal code Country
Plot 101 Lubowa, Off Entebbe Road Kampala 0256 Uganda
OUTCOMES
Type of outcome Outcome Timepoint(s) at which outcome measured
Primary Outcome Tablets dihydroartemisinin-piperaquine group: Plasma concentrations of piperaquine during rifampicin treatment and after stopping rifampicin intake Phase 1 (Day 1,7,14 and 21) and Phase 2 (Day 1,7,14 and 21).
Primary Outcome Tablets dihydroartemisinin-piperaquine group: Plasma concentrations of dihydroartemisin during rifampicin treatment and after stopping rifampicin intake Phase 1 (Day 1) and Phase 2 (Day 1).
Primary Outcome Tablets artesunate-amodiaquine group: Plasma concentrations of artesunate and dihydroartemisinin during rifampicin intake and after stopping rifampicin intake Phase 1 (Day 1) and Phase 2 (Day 1).
Primary Outcome Tablets artesunate-amodiaquine group: Plasma concentrations of amodiaquine and desethylamodiaquine during rifampicin intake and after stopping rifampicin intake Phase 1 (Day 1,7,14 and 21) and Phase 2 (Day 1,7,14 and 21).
Primary Outcome Intravenous artesunate group: Plasma concentrations of artesunate and dihydroartemisinin during rifampicin intake and after stopping rifampicin intake Phase 1 (Day 1) and Phase 2 (Day 1).
Secondary Outcome Frequency of adverse events for each study drug during rifampicin intake and after stopping rifampicin intake Phase 1 (Day 7,14 and 21) and Phase 2 (Day 7,14 and 21).
RECRUITMENT CENTRES
Name of recruitment centre Street address City Postal code Country
Mulago Hospital Mulago Hill Road Kampala 0256 Uganda
FUNDING SOURCES
Name of source Street address City Postal code Country
European & Developing Countries Clinical Trials Partnership 334 Laan Van Nieuw Oost Indie The Hague 2509AA Netherlands
SPONSORS
Sponsor level Name Street address City Postal code Country Nature of sponsor
Primary Sponsor Infectious Diseases Institute, Makerer University College of Health Sciences Mulago Hospital Complex Kampala 0256 Uganda University
COLLABORATORS
Name Street address City Postal code Country
Pauline Byakika-Kibwika Infectious Diseases Institute, Mulago Hospital Complex Kampala 0256 Uganda
Andrew Kambugu Infectious Diseases Institute, Mulago Hospital Complex Kampala 0256 Uganda
Lydia Nakiyingi Infectious Diseases Institute, Mulago Hospital Complex Kampala 0256 Uganda
Saye Khoo Department of Molecular and Clinical Pharmacology, University of Liverpool Liverpool United Kingdom
Concepta Merry Trinity College Dublin Dublin 2 Ireland
CONTACT PEOPLE
Role Name Email Phone Street address
Principal Investigator Mohammed Lamorde mlamorde@idi.co.ug +256-414-307291 Infectious Diseases Institute, Mulago Hospital Complex, Mulago Hill Road
City Postal code Country Position/Affiliation
Kampala 0256 Uganda Research Fellow / Infectious Diseases Institute
Role Name Email Phone Street address
Public Enquiries Michael Enyakoit menyakoit@idi.co.ug +256-414-307224 Infectious Diseases Institute, Mulago Hospital Complex, Mulago Hill Road
City Postal code Country Position/Affiliation
Kampala 0256 Uganda Regulatory Officer / Infectious Diseases Institute
Role Name Email Phone Street address
Scientific Enquiries Mohammed Lamorde mlamorde@idi.co.ug +256-414-307291 Infectious Diseases Institute, Mulago Hospital Complex, Mulago Hill Road
City Postal code Country Position/Affiliation
Kampala 0256 Uganda Research Fellow / Infectious Diseases Institute
REPORTING
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