Additional identifiers
EudraCT number
ClinicalTrials.gov number
Protocol/serial number
DND-ASM-07
Study information
Scientific title
Assessment of efficacy, safety and population-pharmacokinetics of the fixed-dose combination of artesunate-mefloquine in the treatment of acute uncomplicated Plasmodium falciparum malaria in India
Acronym
Study hypothesis
1. To evaluate the clinical and parasitological efficacy of artesunate-mefloquine fixed-dose combination in adult patients with uncomplicated falciparum malaria, by determining the proportion of patients achieving a negative parasitaemia without recrudescence by 63 days (cure rate)
2. To measure the parasite reduction ratio at 48 hours of treatment, parasite clearance time, fever clearance time, gametocyte carriage
3. To evaluate cure rate at 28 days
4. To evaluate the population-pharmacokinetics of artesunate-mefloquine in adult patients in India
5. To evaluate the incidence of adverse events
6. To collect information to enable the Ministry of Health to make informed decisions about the possible need for updating of the current national anti-malarial treatment guidelines
Ethics approval
Institutional Ethics Committee of the National Institute of Malaria Research (ICMR), 23/10/2007
Study design
Multicentre single-arm open-label clinical trial
Primary study design
Interventional
Secondary study design
Randomised controlled trial
Trial setting
Hospitals
Trial type
Treatment
Patient information sheet
Not available in web format, please use the contact details to request a patient information sheet
Condition
Malaria
Intervention
All patients recruited into the study will be given full, supervised treatment with oral artesunate-mefloquine 100 mg and 220 mg tablets (two tablets daily for three days). Total duration of treatment and follow-up is 3 days of treatment and 60 days of follow-up.
Intervention type
Drug
Phase
Phase III
Drug names
Artesunate, mefloquine
Primary outcome measure
Cure rate as determined by polymerase chain reaction (PCR)-corrected adequate clinical and parasitological response (ACPR) on day 63. Treatment success or failures will be classified according to WHO Guidelines 2005.
Secondary outcome measures
1. Pharmacokinetic parameters: population pharmacokinetic parameters for artesunate (AS), dihidroartemisinin (DHA), and mefloquine (MQ)
2. Parasite reduction ratio (PRR) at 48 hours: baseline parasite count/parasite count at 48 hours
3. Parasite clearance time (PCT): time in hours from the initiation of therapy until the first of two successive (within an interval of 8 to 24 hours) parasite negative smears are obtained
4. Fever clearance time (FCT): time in hours from the initiation of therapy until disappearance of fever for at least 24 hours
5. Gametocyte carriage: percentage of patients without gametocytes at day 28
6. Proportion of patients with early treatment failure, late treatment failure, and late parasitological failure
7. Proportion of patients with mixed infections in the follow-up assessments
8. Proportion of patients with development of symptoms of severe malaria
Overall trial start date
01/12/2007
Overall trial end date
31/12/2008
Reason abandoned (if study stopped)
Eligibility
Participant inclusion criteria
1. Male or female patients greater than or equal to 18 years of age
2. Presence of acute uncomplicated P. falciparum mono-infection confirmed by:
2.1. Fever, as defined by axillary temperature greater than or equal to 37.5°C or history of fever in the previous 24 hours, and
2.2. Positive microscopy of P. falciparum with parasite density between 1,000 and 100,000 asexual parasite count/µl of blood
3. Written informed consent provided by patient; if the patient is unable to write, witnessed consent is permitted according to local ethical considerations
4. Screening laboratory values within the following limits:
4.1. Haemoglobin (Hb) greater than or equal to 7 g/dl
4.2. Total bilirubin less than or equal to 2.5 times upper limit of normal (ULN)
4.3. Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) less than or equal to 2.5 times ULN
4.4. Serum creatinine less than or equal to 1.5 times ULN
5. Negative urine pregnancy test before the first dose of fixed-dose combination (FDC) if the subject is a female of childbearing potential
Participant type
Patient
Age group
Adult
Gender
Both
Target number of participants
84 patients
Participant exclusion criteria
1. Patients with signs and symptoms of severe/complicated malaria requiring parenteral treatment according to the World Health Organization Criteria 2000 (Annex 1)
2. Mixed Plasmodium infection
3. Known history or evidence of clinically significant disorders such as cardiovascular (including arrhythmia), respiratory (including active tuberculosis), hepatic, renal, gastrointestinal, immunological (including active human immunodeficiency virus [HIV]/acquired immune deficiency syndrome [AIDS]), neurological (including auditory), endocrine, infectious, malignancy, psychiatric (active depression, recent history of depression, generalised anxiety, psychosis, schizophrenia or other major psychiatric disorders), history of convulsions or other abnormality (including recent head trauma)
4. Presence of febrile conditions caused by diseases other than malaria
5. Known history of hypersensitivity, allergic or serious adverse reactions to mefloquine, quinine, quinidine, artesunate or other artemisinins
6. History of use of any other anti-malarial agent within 2 weeks prior to start of the study
7. Except for women of non-childbearing potential sexually active individuals participating in the study must agree to use a medically acceptable form of contraception during the study and for at least 15 days after day 63
8. Received an investigational drug within the past 4 weeks
9. Inability to swallow oral medication
Recruitment start date
01/12/2007
Recruitment end date
31/12/2008
Locations
Countries of recruitment
India
Trial participating centre
National Institute of Malaria Research
New Delhi
110029
India
Sponsor information
Organisation
Drugs for Neglected Diseases initiative (DNDi) (Switzerland)
Sponsor details
15 Chemin Louis Dunant
Geneva
CH-1202
Switzerland
Sponsor type
Research organisation
Website
Funders
Funder type
Government
Funder name
Ministerie van Buitenlandse Zaken
Alternative name(s)
Dutch Ministry of Foreign Affairs, Ministry of Foreign Affairs, Ministry of Foreign Affairs of the Kingdom of the Netherlands
Funding Body Type
government organisation
Funding Body Subtype
Federal/National Government
Location
Netherlands
Funder name
Spanish Agency for International Cooperation (Agencia Espanola de Cooperacion Internacional) (Spain)
Alternative name(s)
Funding Body Type
Funding Body Subtype
Location
Results and Publications
Publication and dissemination plan
Not provided at time of registration
Intention to publish date
Participant level data
Not provided at time of registration
Basic results (scientific)
Publication list
2014 results in: http://www.ncbi.nlm.nih.gov/pubmed/24886117
2015 results in: http://www.ncbi.nlm.nih.gov/pubmed/26711749