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

This study has been completed.
Sponsor:
Collaborators:
Global Network for Women's and Children's Health Research
Bill and Melinda Gates Foundation
RTI International
University of North Carolina
Kinshasa School of Public Health
Information provided by (Responsible Party):
NICHD Global Network for Women's and Children's Health
ClinicalTrials.gov Identifier:
NCT00538382
First received: September 28, 2007
Last updated: July 29, 2014
Last verified: July 2014
  Purpose

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.


Condition Intervention Phase
Malaria
Drug: Artesunate
Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Pharmacokinetics/Dynamics Study
Intervention Model: Single Group Assignment
Masking: Open Label
Official Title: Phase I Study of Pharmacokinetics and Pharmacodynamics of Artesunate in Pregnant Women in the Democratic Republic of Congo

Resource links provided by NLM:


Further study details as provided by NICHD Global Network for Women's and Children's Health:

Primary Outcome Measures:
  • 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 [ Time Frame: 48 hours ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • The levels of unbound DHA will be similar for parasitemic pregnant women (during the second and third trimesters) vs. parasitemic non-pregnant women. [ Time Frame: 48 hours after drug administration ] [ Designated as safety issue: No ]
  • 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. [ Time Frame: 48 hours after drug administration ] [ Designated as safety issue: No ]
  • 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. [ Time Frame: 48 hours after drug administration ] [ Designated as safety issue: No ]
  • The pharmacodynamics and pharmacokinetic outcomes (as elaborated above) will be similar between the 2nd and 3rd trimester in parasitemic pregnant women. [ Time Frame: 48 hours after drug administration ] [ Designated as safety issue: No ]
  • Description of safety and tolerability of Artesunate in the target population (pregnant women in the 2nd and 3rd trimester). [ Time Frame: 0ne year postpartum ] [ Designated as safety issue: No ]

Enrollment: 51
Study Start Date: May 2007
Study Completion Date: December 2008
Primary Completion Date: November 2008 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Case
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
A 200 mg dose of orally administered artesunate at the beginning of a 48-hour clinical sampling period.
Other Name: Arsumax®
Active Comparator: Non-pregnant Control
Non-pregnant controls are defined as parasitemic non-pregnant women recruited from the same community as the cases.
Drug: Artesunate
A 200 mg dose of orally administered artesunate at the beginning of a 48-hour clinical sampling period.
Other Name: Arsumax®
Active Comparator: Internal Control
Internal controls are defined as the same women(cases)at three months postpartum.
Drug: Artesunate
A 200 mg dose of orally administered artesunate at the beginning of a 48-hour clinical sampling period.
Other Name: Arsumax®

  Show Detailed Description

  Eligibility

Ages Eligible for Study:   18 Years to 40 Years
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria for Cases:

  • 2nd 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

Inclusion Criteria for Non-pregnant Controls:

  • 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
  • Able to spend three days in the clinic following screening
  • Willing to provide informed consent

Inclusion Criteria for Internal controls:

  • Negative urine pregnancy test

Exclusion Criteria for Cases:

  • 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

Exclusion Criteria for Non-pregnant Controls:

  • 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

Exclusion Criteria for Internal Controls:

  • 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
  • Pregnant
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00538382

Locations
Congo, The Democratic Republic of the
Kingasani Maternity Clinic
Kinshasa, Congo, The Democratic Republic of the
Sponsors and Collaborators
NICHD Global Network for Women's and Children's Health
Global Network for Women's and Children's Health Research
Bill and Melinda Gates Foundation
RTI International
University of North Carolina
Kinshasa School of Public Health
Investigators
Principal Investigator: Carl Bose, M.D. University of North Carolina
Principal Investigator: Antoinette Tshefu, M.D., M.P.H. Kinshasa School of Public Health
  More Information

Additional Information:
No publications provided by NICHD Global Network for Women's and Children's Health

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: NICHD Global Network for Women's and Children's Health
ClinicalTrials.gov Identifier: NCT00538382     History of Changes
Other Study ID Numbers: GN02- PK/PD of artesunate
Study First Received: September 28, 2007
Last Updated: July 29, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by NICHD Global Network for Women's and Children's Health:
Malaria
Pregnancy
Artesunate
Pharmacokinetics
Pharmacodynamics
Democratic Republic of Congo

Additional relevant MeSH terms:
Malaria
Protozoan Infections
Parasitic Diseases
Artesunate
Amebicides
Antiprotozoal Agents
Antiparasitic Agents
Anti-Infective Agents
Therapeutic Uses
Pharmacologic Actions
Antimalarials

ClinicalTrials.gov processed this record on August 20, 2014