Condition category
Infections and Infestations
Date applied
21/11/2008
Date assigned
27/11/2008
Last edited
16/01/2015
Prospective/Retrospective
Retrospectively registered
Overall trial status
Completed
Recruitment status
No longer recruiting

Plain English Summary

Not provided at time of registration

Trial website

Contact information

Type

Scientific

Primary contact

Dr Neena Valecha

ORCID ID

Contact details

National Institute of Malaria Research
New Delhi
110029
India

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) approval given on the 23rd October 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 below 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 measures

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

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

http://www.dndi.org/

Funders

Funder type

Government

Funder name

The Netherlands Ministry of Foreign Affairs (DGIS) (The Netherlands)

Alternative name(s)

Funding Body Type

Funding Body Subtype

Location

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

Results - basic reporting

Publication summary

2014 results in: http://www.ncbi.nlm.nih.gov/pubmed/24886117

Publication citations

Additional files

Editorial Notes