Praziquantel-Pharmacokinetic Study
Condition: Schistosomiasis
MeSH terms: Schistosomiasis
Study type: Interventional
Phase: Phase 1

Summary: 
      The purpose of the study is to understand whether the drug praziquantel (PZQ) is metabolized
      or broken down differently when women are pregnant versus not pregnant. PZQ is used to treat
      schistosomiasis (worm infection). Researchers will study how PZQ is broken down among 15
      women who are 12-16 weeks pregnant, 15 women who are 30-36 weeks pregnant, and 15 women
      nonpregnant women who are producing breast milk. All women will be 18 or older and otherwise
      healthy. The usual practice is to wait until after mothers have finished pregnancy and breast
      feeding before giving PZQ. Participants will receive 2 doses of PZQ separated by 3 hours.
      Study procedures will include a 24 hour hospital stay following administration of PZQ, blood,
      stool and urine samples, ultrasound if pregnant, and physical exams of mother and baby.
      Patient participation for mother/infant pair is about 9 months.
    

Detailed description: 
      Schistosomiasis infects over 200 million individuals and remains a significant cause of
      morbidity and mortality in developing countries, despite the availability of effective
      pharmacologic therapy with praziquantel (PZQ). Researchers propose to conduct a phase I study
      of the pharmacokinetics (PK) and safety of PZQ for the treatment of Schistosomiasis (S.)
      japonicum among pregnant and lactating women living in the province of Leyte, The
      Philippines. In practice, treatment of schistosomiasis is withheld for both pregnant and
      lactating post partum women in the Philippines as well as other countries endemic for
      schistosomiasis. Without treatment, these women accrue known morbidities identified among
      non-pregnant subjects including hepatic fibrosis, under-nutrition, and anemia. The overall
      aims of this study are to see if there are differences in PZQ PK and safety during pregnancy
      compared to post partum, to describe the kinetics of breast milk transfer of PZQ and to
      estimate the dose of PZQ received by a nursing infant whose mother is treated with PZQ. This
      protocol will enroll 15 pregnant women in early pregnancy (12-16 weeks gestation), 15
      pregnant women in late pregnancy (30-36 weeks gestation) and 15 lactating nonpregnant women
      between 5 and 7 months postpartum. The study population will consist of S. japonicum infected
      women in study villages or at the Municipal Health Centers. Women must be: age 18 or older,
      otherwise healthy without disease of any major organ system, without history of seizures,
      chronic medical problem or any neurologic disorders, without history of severe allergic
      reaction to PZQ and willing to provide informed consent to participate. The pregnant women
      must: have a singleton pregnancy, be carrying a fetus without evidence of anomaly by
      ultrasound. Pregnant subjects will be treated with PZQ in early pregnancy (12-16 weeks
      gestation) or late pregnancy (30-36 weeks gestation), lactating nonpregnant (5-7 months
      postpartum inclusive ). A total dose of 60 mg/kg of study medication will be provided in 2
      split doses over 3 hours as this has been shown to substantially reduce drug side effects.
      All subjects will be hospitalized overnight for intensive blood sampling and for monitoring
      for adverse events. Serial breast milk samples will be collected from lactating women. Plasma
      and breast milk will be assayed for PZQ concentration. PK parameters in pregnant and
      postpartum women will be compared and kinetics of praziquantel breast milk transfer and
      estimation of infant PZQ dose from breast milk will be determined. Safety assessments will be
      performed on pregnant women and their infants through 1 month postpartum, and on postpartum
      women through 2 weeks post dosing. This study is linked to Division of Microbiology and
      Infectious Disease (DMID) protocol 06-0039.
    

Intervention name(s): Praziquantel
Intervention type(s): Drug
Intervention description(s): Praziquantel (PZQ), 60 mg/kg, administered orally in split dose (30 mg/kg each dose) separated by three hours.
Intervention MeSH terms: Praziquantel
Allocation: Non-Randomized
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: Praziquantal, Schistosomiasis, pregnant women, Philippines