Open-label randomised clinical trial of pharmacokinetics, efficacy, and tolerability of the fixed-dose artesunate/amodiaquine combination therapy versus both drugs administered separately for treatment of uncomplicated falciparum malaria in Kenya

ISRCTN	ISRCTN16409445
DOI	https://doi.org/10.1186/ISRCTN16409445
Protocol serial number	1199
Sponsor	Drugs for Neglected Diseases initiative (DNDi) (Switzerland)
Funders	Drugs for Neglected Diseases initiative (DNDi) (Switzerland), Ministerie van Buitenlandse Zaken, Medecins Sans Frontieres (MSF) (International)

Submission date: 05/07/2007
Registration date: 21/08/2007
Last edited: 28/03/2017

Recruitment status: No longer recruiting
Overall study status: Completed
Condition category: Infections and Infestations

Prospectively registered

Protocol

Statistical analysis plan

Results

Individual participant data

Plain English summary of protocol

Not provided at time of registration

Contact information

Dr Bernhards Ogutu
Scientific

Walter Reed Project
Centre for Clinical Research
KEMRI
PO Box 54
Kisumu
-
Kenya

Study information

Primary study design	Interventional
Study design	Open-label randomised single-centre clinical trial
Secondary study design	Randomised controlled trial
Study type	Participant information sheet
Scientific title	Open-label randomised clinical trial of pharmacokinetics, efficacy, and tolerability of the fixed-dose artesunate/amodiaquine combination therapy versus both drugs administered separately for treatment of uncomplicated falciparum malaria in Kenya
Study objectives	1. To investigate pharmacokinetic parameters of the fixed-dose artesunate/amodiaquine (AS/AQ) combination in adults with comparison to separate administration of the two drugs using a population pharmacokinetic design 2. To measure the clinical and parasitological efficacy of the fixed-dose AS/AQ combination therapy 3. To measure the parasite reduction ratio at 48 hours of treatment, parasite and fever clearance rates, proportions of patients with gametocyte persistence during follow up 4. To evaluate the incidence of adverse events 5. To formulate recommendations and to enable the Kenyan Ministry of Health to make informed decisions about the possible need for updating of the current national antimalarial treatment guidelines
Ethics approval(s)	Ethics committee of the Kenya Medical Research Institute, 22/05/2007
Health condition(s) or problem(s) studied	Uncomplicated falciparum malaria
Intervention	Patients will be equally randomised into the following treatment groups: Group A: fixed-dose AS/AQ combination tablets (100 mg/270 mg), two tablets once daily for three consecutive days. Group B: AS tablets (50 mg): four tablets once a day for three consecutive days, and AQ tablets (153 mg): four tablets once a day for three consecutive days. Patients will be followed-up for 28 days, and the total follow-up for the study will be 9 months.
Intervention type	Drug
Phase	Not Applicable
Drug / device / biological / vaccine name(s)	Artesunate, amodiaquine
Primary outcome measure(s)	The primary objective of this study is to investigate the pharmacokinetic properties of fixed-dose combination AS/AQ. Blood sampling will be performed at predefined time points in both groups of patients. The evaluation of pharmacokinetics variables will take place over the three-day treatment and the entire follow-up off-treatment.
Key secondary outcome measure(s)	1. Treatment outcomes: the classification of treatment outcomes will be based on an assessment of the parasitological and clinical outcome of antimalarial treatment according to the latest (2005) guidelines of World Health Organisation (WHO). Accordingly, all patients will be classified as having an Early Treatment Failure, a Late Clinical Failure, a Late Parasitological Failure, or an Adequate Clinical and Parasitological Response 2. Safety variables: the occurrence of any adverse event will be documented. All patients will be routinely asked about old symptoms and new symptoms emerging since previous visit during follow-up
Completion date	30/03/2008

Eligibility

Participant type(s)	Patient
Age group	Adult
Lower age limit	18 Years
Sex	All
Target sample size at registration	50
Key inclusion criteria	1. Adults from 18 to 60 years of age; either gender 2. Presenting with acute uncomplicated falciparum malaria: 2.1. Oral temperature greater than 37.5°C, or 2.2. History of fever in the last 24 hours 3. Positive P. falciparum parasitaemia (greater than 1000 asexual parasites/µL) 4. Written informed consent
Key exclusion criteria	1. Any other concomitant febrile illness, e.g. upper respiratory tract infection or Ear, Nose and Throat (ENT) infection 2. Features of severe malaria 3. Mixed Plasmodium infection
Date of first enrolment	09/07/2007
Date of final enrolment	30/03/2008

Locations

Countries of recruitment

Kenya

Study participating centre

Walter Reed Project

Kisumu
-
Kenya

Results and Publications

Individual participant data (IPD) Intention to share	No
IPD sharing plan summary	Not provided at time of registration
IPD sharing plan

Study outputs

Output type	Details	Date created	Date added	Peer reviewed?	Patient-facing?
Results article	results	01/06/2010		Yes	No
Participant information sheet	Participant information sheet	11/11/2025	11/11/2025	No	Yes

Editorial Notes

28/03/2017: Publication reference added.