Pharmacokinetics of Mefloquine-Artesunate in Pregnant Women With Uncomplicated Plasmodium Falciparum Infection
Information source: Centers for Disease Control and Prevention
ClinicalTrials.gov processed this data on August 23, 2015
Link to the current ClinicalTrials.gov record.
Condition(s) targeted: Malaria; Pregnancy
Intervention: Mefloquine Artesunate (Drug)
Phase: Phase 2/Phase 3
Status: Withdrawn
Sponsored by: Centers for Disease Control and Prevention Official(s) and/or principal investigator(s):
Meghna Desai, MPH PhD, Principal Investigator, Affiliation: Centers for Disease Control and Prevention
Summary
Artemisinin-based combination therapies (ACTs) are now the treatment of choice for malaria
in non-pregnant individuals living in areas with established chloroquine resistance; they
have been shown to be both safe and highly efficacious. There is rapidly increasing
experience with artemisinin derivatives in the 2nd and 3rd trimesters of pregnancy, with
over 1,000 well documented cases with no reported serious adverse effects to mother or fetus
(WHO Malaria Treatment Guidelines, 2006). Many countries in Latin America have abandoned the
previous 1st line regimen of Quinine-Clindamycin for treatment of malaria in pregnancy, a
complex and poorly tolerated regimen with low adherence, in favor of ACTs, despite limited
safety and pharmacokinetic data on the use of these compounds in pregnant women. Lack of
pharmacokinetic data may lead to underdosing of pregnant women, with subsequent reduced
efficacy and increased potential for development of resistance.
One ACT regimen, Artesunate-Mefloquine, has been developed as a fixed-dose combination
(Farmanguinhos Artesunato + Mefloquina), as part of an international collaborative research
effort led by Drugs for Neglected Diseases Initiative (DNDi), and manufactured by
Farmanguinhos, laboratory of the Brazilian Ministry of Health. Initial clinical trials
suggest that it is very well tolerated and efficacious in both pregnant and non-pregnant
individuals. The convenient dosing afforded by a fixed drug combination make this a very
promising candidate for treatment of pregnant women with malaria. Preliminary
pharmacokinetic data from mefloquine monotherapy and prophylaxis suggest that the peak
concentration of mefloquine is lowered in pregnant women. Prior to wide-spread adoption of
the Artesunate-Mefloquine combination, further studies on safety, efficacy, and dose
optimization are imperative. We propose to compare the pharmacokinetics of the fixed
combination of mefloquine-artesunate (MA) for treatment of P. falciparum in 28 pregnant women
in the second and third trimesters to the pharmacokinetics of this regimen in 28 matched
non-pregnant P. falciparum infected women. This will allow us to determine whether the
standard adult dose is sufficient for pregnant women.
Clinical Details
Official title: Pharmacokinetics of Mefloquine-Artesunate in Pregnant Women With Uncomplicated Plasmodium Falciparum Infection
Study design: Allocation: Non-Randomized, Endpoint Classification: Pharmacokinetics/Dynamics Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment
Primary outcome: Area under the curve of Mefloquine - artesunate in pregnant versus matched non-pregnant women with P. falciparum malaria
Secondary outcome: PCR correct cure rate on Day 63
Eligibility
Minimum age: 18 Years.
Maximum age: N/A.
Gender(s): Female.
Criteria:
Inclusion Criteria:
1. Cases: Pregnant women, age ≥18 years, in 2nd or 3rd trimester (gestational age ≥12
weeks determined by LMP and confirmed by fundal height measurement) Controls:
Non-pregnant women ≥18 years old (negative urine pregnancy test)
2. Presence of P. falciparum ≤ 50,000 parasites/microliter
3. Fever (≥37. 5C) or history of fever in preceding 48 hours
4. Willing to sign or thumb print informed consent
5. Willing to be hospitalized for 3 days and to return for scheduled follow up visits
for treatment and observation until delivery
6. Willing to deliver in health facility
Exclusion Criteria:
1. Pregnancy < 12 weeks
2. Presence of malaria species other than P. falciparum on the slide (P. vivax, P.
malariae, or P. ovale, or mixed infection (P. falciparum in combination with any
other malaria species)
3. History of allergy or hypersensitivity to interventional drugs
4. Exposure to antimalarial drugs and other drugs with antimalarial activity within the
past 2 months, as determined by history from the woman.
5. Patients taking drugs with possible interaction with study drugs (ie, digoxin or
warfarin)
6. History or family history of epilepsy or psychiatric disorder
7. Presence of signs and symptoms of severe malaria
8. Inability to tolerate oral medication (repeated vomiting, impairment of
consciousness). Vomiting of any of the treatment doses will lead to exclusion from
the pharmacokinetic sampling, but not the follow-up for drug efficacy.
9. History of chronic disease including diabetes, renal failure, hepatic failure, heart
disease requiring anti-arrhythmic drugs or warfarin, AIDS (HIV itself will not be an
exclusion, but anyone with AIDS or HIV requiring HAART will be excluded),
hemoglobinopathy,
10. Participant's inability to return for follow up visits
11. Age <18 years
12. Hb<8g/dl
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Starting date: March 2010
Last updated: April 12, 2012
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