Pharmacokinetic of Mefloquine-Artesunate in Plasmodium Falciparum Malaria Infection in Pregnancy

NCT00701961 | Completed Phase 2 DMC

• 1 other identifier: ITMP0208
• Study Type: interventional
• Target: 48
• Locations: 1 country
• Sites: 1

Brief Summary

Malaria in pregnancy is a major public health problem in Sub-Saharan Africa. Over the past decades, P. falciparum has shown increasing resistance to chloroquine and Sulphadoxine-Pyrimethamine, which has prompted a change in treatment approach; artemisinin containing combination therapies (ACTs) are now the standard treatment of P. falciparum malaria in areas with established resistance to traditional therapies. However, a standard approach for using ACT in pregnancy does not exist in Africa, where some countries keep on using quinine, while others allow the use of ACTs. Thus, there is need of establishing the safety and efficacy of ACTs in malaria-infected pregnant women. Since the pharmacokinetic of antimalarials may be altered during pregnancy and since available pharmacokinetic data are still somewhat limited, we propose to carry out a study confirming or disproving existing pharmacokinetic data (collected in South-East Asia), before starting any larger African efficacy and safety trials. The fixed-dose combination mefloquine-artesunate (MQ-AS), developed by the Drugs for Neglected Diseases Initiative, will be used in the study, which will compare the pharmacokinetics of MQ-AS for treatment of P.falciparum in 24 pregnant women in the second and third trimesters, to the pharmacokinetics of this regimen in 24 matched non-pregnant P.falciparum infected women. The study will be carried out in Burkina Faso.

Conditions

Plasmodium Falciparum Malaria

Keywords

Mefloquine-artesunate; Malaria; Pregnancy; Pharmacokinetics; Sub-Saharan Africa; P falciparum malaria infection in pregnancy

Outcome Measures

Primary Outcomes (1)

• To estimate the pharmacokinetic of MQ-AS for treatment of P. falciparum or mixed infection in pregnant compared to non-pregnant women.

  6 months

Secondary Outcomes (1)

• The proportion of women in each treatment group with parasitological cure at 63 days, corrected by PCR for re-infection.

  6 months

Study Arms (2)

1

EXPERIMENTAL

Pregnat women receiving MQ-AS fixed dose combination comprised of 100 mg of artesunate and 220mg of mefloquine per tablet, dosed once daily such that mefloquine dose is approximately 8mg/kg/day for 3 days.

Drug: Mefloquine-artesunate

2

ACTIVE COMPARATOR

Non-pregnant women receiving MQ-AS fixed dose combination comprised of 100 mg of artesunate and 220mg of mefloquine per tablet, dosed once daily such that mefloquine dose is approximately 8mg/kg/day for 3 days.

Drug: Mefloquine-artesunate

Interventions

Mefloquine-artesunate DRUG

Mefloquine-artesunate fixed dose combination comprised of 100 mg of artesunate and 220mg of mefloquine per tablet, developed by DNDi and manufactured by farmanguinhos (Brazil).

Also known as: MQ-AS

1; 2

Eligibility Criteria

• Age: 18 Years - 49 Years
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Plasmodium falciparum monoinfection (any density)
• At least 18 years old;
• Haemoglobin at leats 7 g/dL;
• Residence within the health facility catchment's area;
• Willing to adhere to the study requirements
• Willing to deliver in health facility
• Ability to provide written informed consent
• EITHER pregnant women in the 2nd or 3rd trimester (cases)or non-pregnant women between the ages of 18 and 49 years (controls).

You may not qualify if:

• Pregnancy 1st trimester
• History of known pregnancy complications or bad obstetric history such as repeated stillbirths or eclampsia;
• Known major illnesses likely to influence pregnancy outcome including diabetes mellitus, severe renal or heart disease, or active tuberculosis;
• Current cotrimoxazole prophylaxis or ARV treatment;
• Any significant presenting illness that requires hospitalization, including severe malaria;
• Intent to move out of the study catchment area before delivery or deliver at relative's home out of the catchment area.
• Prior enrollment in the study or concurrent enrollment in another study.
• Unable to take oral medication
• Clear evidence of treatment with antimicrobials with antimalarial activity (erythromycin or other macrolides, co-trimoxazole or other sulfonamides, any tetracycline including doxycycline, quinolones and clindamycin) or exposure to antimalarial drugs within the week prior enrollment.
• History of allergy or hypersensivity to interventional drugs
• Patients taking drugs with possible interaction with study drugs (i.e. digoxin or warfarin)
• History or family history of epilepsy or psychiatric disorder
• Presence of signs and symptoms of severe malaria

Sponsors & Collaborators

• Institute of Tropical Medicine, Belgium: lead
• Centre Muraz: collaborator
• Liverpool School of Tropical Medicine: collaborator

Study Sites (1)

Centre Muraz

Nanoro, Burkina Faso

Location

Related Publications (2)

• Birgersson S, Valea I, Tinto H, Traore-Coulibaly M, Toe LC, Hoglund RM, Van Geertruyden JP, Ward SA, D'Alessandro U, Abelo A, Tarning J. Population pharmacokinetics of artesunate and dihydroartemisinin in pregnant and non-pregnant women with uncomplicated Plasmodium falciparum malaria in Burkina Faso: an open label trial. Wellcome Open Res. 2019 Mar 7;4:45. doi: 10.12688/wellcomeopenres.14849.2. eCollection 2019.

  PMID: 32025570 DERIVED

• Valea I, Tinto H, Traore-Coulibaly M, Toe LC, Lindegardh N, Tarning J, Van Geertruyden JP, D'Alessandro U, Davies GR, Ward SA. Pharmacokinetics of co-formulated mefloquine and artesunate in pregnant and non-pregnant women with uncomplicated Plasmodium falciparum infection in Burkina Faso. J Antimicrob Chemother. 2014 Sep;69(9):2499-507. doi: 10.1093/jac/dku154. Epub 2014 Jun 2.

  PMID: 24891429 DERIVED

MeSH Terms

Conditions

Malaria, Falciparum; Malaria

Condition Hierarchy (Ancestors)

Protozoan Infections; Parasitic Diseases; Infections; Mosquito-Borne Diseases; Vector Borne Diseases

Study Officials

• Tinto Halidou, PhD

  Centre Muraz

  PRINCIPAL INVESTIGATOR

• Umberto D'Alessandro, MD

  ITM Belgium

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER

Study Record Dates

• First Submitted: June 18, 2008
• First Posted: June 19, 2008
• Study Start: October 1, 2008
• Primary Completion: July 1, 2009
• Study Completion: July 1, 2009
• Last Updated: September 14, 2010

Record last verified: 2010-09

Locations

BU (1)