Study of Pharmacokinetics and Pharmacodynamics of Artesunate in Pregnant Women in the Democratic Republic of Congo

NCT00538382 | Completed Phase 1 DMC

• 1 other identifier: GN02- PK/PD of artesunate
• Study Type: interventional
• Target: 51
• Locations: 1 country
• Sites: 1

Brief Summary

The objective of this study is to assess the pharmacokinetics (PK) and pharmacodynamics (PD) of a standard dose of orally administered artesunate, in order to determine if the current adult dose (200 mg) is appropriate in parasitemic pregnant women when compared to the same women at three months postpartum and to parasitemic non-pregnant women. Preliminary evidence on safety, tolerability and efficacy will be gathered.

Conditions

Malaria

Keywords

Malaria; Pregnancy; Artesunate; Pharmacokinetics; Pharmacodynamics; Democratic Republic of Congo

Outcome Measures

Primary Outcomes (1)

• Levels of the unbound active major metabolite, dihydroartemisinin (DHA), will be similar for parasitemic pregnant women during their 2nd and 3rd trimesters vs. the same women 3 months postpartum

  48 hours

Secondary Outcomes (5)

• The levels of unbound DHA will be similar for parasitemic pregnant women (during the second and third trimesters) vs. parasitemic non-pregnant women.

  48 hours after drug administration

• The pharmacokinetics of ARTS and total DHA will be similar for parasitemic pregnant women (during the second and third trimesters) vs. the same women three months postpartum and parasitemic non-pregnant women.

  48 hours after drug administration

• The pharmacodynamics of therapy will be similar for parasitemic pregnant women (during the 2nd and 3rd trimesters) vs. parasitemic non-pregnant women. Pharmacodynamics will be determined by measuring the parasite clearance time (PCT), PC50, and PC90.

  48 hours after drug administration

• The pharmacodynamics and pharmacokinetic outcomes (as elaborated above) will be similar between the 2nd and 3rd trimester in parasitemic pregnant women.

  48 hours after drug administration

• Description of safety and tolerability of Artesunate in the target population (pregnant women in the 2nd and 3rd trimester).

  0ne year postpartum

Study Arms (3)

Case

EXPERIMENTAL

Cases are defined as parasitemic pregnant women during the second trimester (22-26 weeks gestation) and the third trimester (32-36 weeks gestation).

Drug: Artesunate

Non-pregnant Control

ACTIVE COMPARATOR

Non-pregnant controls are defined as parasitemic non-pregnant women recruited from the same community as the cases.

Drug: Artesunate

Internal Control

ACTIVE COMPARATOR

Internal controls are defined as the same women(cases)at three months postpartum.

Drug: Artesunate

Interventions

Artesunate DRUG

A 200 mg dose of orally administered artesunate at the beginning of a 48-hour clinical sampling period.

Also known as: Arsumax®

Case; Internal Control; Non-pregnant Control

Eligibility Criteria

• Age: 18 Years - 40 Years
• Sex: female
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• nd trimester (22-26 weeks) or 3rd trimester (32-36 weeks) of pregnancy, based on an ultrasound conducted at \<22 weeks gestation (composite of BPD, HC, AC, FL)
• Singleton pregnancy documented by ultrasound
• Parasitemic (\> 500 parasites/μl)
• Afebrile and asymptomatic
• Hematocrit ≥ 30%
• Negative HIV test result
• At least 18 years of age and less than 40 years of age
• Able to spend three days in the clinic following their laboratory screening visit and again at three months postpartum
• Willing to provide informed consent
• Negative urine pregnancy test
• Parasitemic (\> 500 parasites/μl)
• Afebrile and asymptomatic
• Hematocrit ≥ 30%
• Negative Determine® HIV test result
• At least 18 years of age and less than 40 years of age

You may not qualify if:

• Parasitemia \> 300,000 parasites/μl or symptomatic malaria
• Medical contraindications to participation or medical disorders (known high blood pressure, diabetes, sickle cell disease or tuberculosis)
• Have taken artesunate or any medicine containing artesunate during the current pregnancy
• Have taken any antimalarial in the past two weeks
• Have taken any medication in the past two weeks other than antipyretics (e.g., acetyl- salicylic acid, acetaminophen), folic acid or iron
• Have a fetus with any ultrasonographically visible structural fetal abnormalities identified on entry by ultrasound
• Past or present pregnancy complications that would preclude participation in the study (gestational diabetes/diabetes, incompetent cervix, pre-eclampsia/ eclampsia, and high blood pressure)
• Between 32-36 weeks gestation and have already participated in the study at 22-26 weeks gestation
• Parasitemia \> 300,000 parasites/μl or have symptomatic malaria
• Medical contraindications to participation or medical disorders (known high blood pressure, diabetes, sickle cell disease or tuberculosis)
• Have taken any antimalarial in the past two weeks
• Have taken any medication in the past two weeks other than antipyretics (e.g., acetyl- salicylic acid, acetaminophen), folic acid or iron
• Parasitemia \> 300,000 parasites/μl or have symptomatic malaria
• Have taken antimalarial medication in the past two weeks.
• Have taken any medication in the past two weeks other than antipyretics (e.g., acetyl- salicylic acid, acetaminophen), folic acid or iron

Sponsors & Collaborators

• NICHD Global Network for Women's and Children's Health: lead
• Global Network for Women's and Children's Health Research: collaborator
• Bill and Melinda Gates Foundation: collaborator
• Fogarty International Center of the National Institute of Health: collaborator
• National Center for Complementary and Integrative Health (NCCIH): collaborator
• National Institute of Dental and Craniofacial Research (NIDCR): collaborator
• National Cancer Institute (NCI): collaborator
• RTI International: collaborator
• University of North Carolina: collaborator
• Kinshasa School of Public Health: collaborator

Study Sites (1)

Kingasani Maternity Clinic

Kinshasa, Democratic Republic of the Congo

Location

Related Publications (1)

• Onyamboko MA, Meshnick SR, Fleckenstein L, Koch MA, Atibu J, Lokomba V, Douoguih M, Hemingway-Foday J, Wesche D, Ryder RW, Bose C, Wright LL, Tshefu AK, Capparelli EV. Pharmacokinetics and pharmacodynamics of artesunate and dihydroartemisinin following oral treatment in pregnant women with asymptomatic Plasmodium falciparum infections in Kinshasa DRC. Malar J. 2011 Feb 28;10:49. doi: 10.1186/1475-2875-10-49.

  PMID: 21352601 DERIVED

Related Links

• Website of the Global Network for Women's and Children's Health Research
• RTI International

MeSH Terms

Conditions

Malaria

Interventions

Artesunate

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Artemisinins; Reactive Oxygen Species; Free Radicals; Inorganic Chemicals; Organic Chemicals; Sesquiterpenes; Terpenes; Hydrocarbons

Study Officials

• Carl Bose, M.D.

  University of North Carolina

  PRINCIPAL INVESTIGATOR

• Antoinette Tshefu, M.D., M.P.H.

  Kinshasa School of Public Health

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Intervention Model: SINGLE GROUP
• Sponsor Type: NETWORK
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 28, 2007
• First Posted: October 2, 2007
• Study Start: May 1, 2007
• Primary Completion: November 1, 2008
• Study Completion: December 1, 2008
• Last Updated: July 31, 2014

Record last verified: 2014-07

Locations

DE (1)