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
| ISRCTN | ISRCTN70618692 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN70618692 |
| Secondary identifying numbers | DND-ASM-07 |
- Submission date
- 21/11/2008
- Registration date
- 27/11/2008
- 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 Neena Valecha
Scientific
Scientific
National Institute of Malaria Research
New Delhi
110029
India
Study information
| Study design | Multicentre single-arm open-label clinical trial |
|---|---|
| Primary study design | Interventional |
| Secondary study design | Randomised controlled trial |
| Study setting(s) | Hospital |
| Study type | Treatment |
| Participant information sheet | Not available in web format, please use the contact details to request a patient information sheet |
| 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 |
| Study objectives | 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(s) | Institutional Ethics Committee of the National Institute of Malaria Research (ICMR), 23/10/2007 |
| Health condition(s) or problem(s) studied | 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 |
| Pharmaceutical study type(s) | |
| Phase | Phase III |
| Drug / device / biological / vaccine name(s) | 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 study start date | 01/12/2007 |
| Completion date | 31/12/2008 |
Eligibility
| Participant type(s) | Patient |
|---|---|
| Age group | Adult |
| Lower age limit | 18 Years |
| Sex | Both |
| Target number of participants | 84 patients |
| Key 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 |
| Key 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 |
| Date of first enrolment | 01/12/2007 |
| Date of final enrolment | 31/12/2008 |
Locations
Countries of recruitment
- India
Study participating centre
National Institute of Malaria Research
New Delhi
110029
India
110029
India
Sponsor information
Drugs for Neglected Diseases initiative (DNDi) (Switzerland)
Research organisation
Research organisation
15 Chemin Louis Dunant
Geneva
CH-1202
Switzerland
| Website | http://www.dndi.org/ |
|---|---|
"ROR" |
https://ror.org/022mz6y25 |
Funders
Funder type
Government
Ministerie van Buitenlandse Zaken
Government organisation / National government
Government organisation / National government
- Alternative name(s)
- Dutch Ministry of Foreign Affairs, Ministry of Foreign Affairs, Ministry of Foreign Affairs of the Kingdom of the Netherlands
- Location
- Netherlands
Spanish Agency for International Cooperation (Agencia Espanola de Cooperacion Internacional) (Spain)
No information available
Results and Publications
| Intention to publish date | |
|---|---|
| Individual participant data (IPD) Intention to share | No |
| IPD sharing plan summary | Not provided at time of registration |
| Publication and dissemination plan | 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 | 23/05/2014 | Yes | No | |
| Results article | results | 28/12/2015 | Yes | No |
Editorial Notes
28/03/2017: Publication reference added.
