Praziquantel-Pharmacokinetic Study

NCT01288872 | Completed Phase 1

• 2 other identifiers: 08-00495U01AI066050-07
• Study Type: interventional
• Target: 47
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Schistosomiasis

Keywords

Praziquantal, Schistosomiasis, pregnant women, Philippines

Outcome Measures

Primary Outcomes (6)

• Comparison of PZQ and 4-hydroxy PZQ PK parameters in pregnant and nonpregnant lactating subjects, central tendency and distribution (Cmax, Tmax, t ½, AUC, CL/F and Vd/F).

  Up to 24 hours after the first dose of PZQ

• Early Pregnancy Cohort only: Assessed for the presence of pre-eclampsia.

  Assessed for the presence of pre-eclampsia at both the 22 and 32 week visits.

• Pregnant women only: newborn congenital anomalies. The number of infants with congenital anomalies

  Newborn examined by the midwife (or pediatrician if in hospital) at delivery and within 2-6 days of delivery to assess the presence of congenital anomalies and well-being. Newborn examined by study pediatrician at 28 days of life.

• Early Pregnancy Cohort only: number of subjects experiencing a spontaneous abortion and number of stillbirths reported after drug administration; and live birth rate among pregnant subjects.

  Women will be observed in hospital for 24 hours after dosing and asked to return for any bleeding at any time.

• Toxicity to maternal bone marrow, kidney, and liver will be assessed by measurement of complete blood count, blood urea nitrogen (BUN) and creatinine, and liver function tests (AST, ALT, and bilirubin).

  Collected just before the dose, 24 hours after the dose and at either 20 weeks after the dose (early gestation subjects) or 10-14 days after the dose (late gestation and lactating postpartum subjects).

• Subjects will be observed in hospital for adverse events/serious adverse events (AE/SAEs).

  Up to 9 months from enrollment

Study Arms (1)

Praziquantel

EXPERIMENTAL

45 women in 3 cohorts (15 early pregnancy: 12-16 weeks gestation; 15 late pregnancy: 30-36 weeks gestation; and 15 lactating nonpregnant women who are 5-7 months (inclusive) postpartum) given praziquantel (PZQ), 60 mg/kg orally in split dose (30 mg/kg each) separated by 3 hours.

Drug: Praziquantel

Interventions

Praziquantel DRUG

Praziquantel (PZQ), 60 mg/kg, administered orally in split dose (30 mg/kg each dose) separated by three hours.

Praziquantel

Eligibility Criteria

• Age: 18 Years - 99 Years
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Screening:
• Woman must be age 18 or over.
• Present to a study midwife or health center.
• Live in a study village.
• Infected with Schistosomiasis (S.) japonicum.
• Age 18 or older.

You may not qualify if:

• Early pregnancy cohort: pregnant, between 12-16 weeks gestation.
• Late pregnancy cohort: pregnant, between 30-36 weeks gestation
• Lactating nonpregnant: 5-7 months postpartum inclusive (up to 7 months and 31 days) with negative pregnancy test.
• Ability to provide informed consent to participate.
• Presence of significant disease/illness that is either acute or chronic. This will be defined by history, physical examination, ultrasound (if pregnant) and laboratory assessment. In particular:
• History of seizures or other neurologic disorder, chronic medical problem determined by history or physical examination, e.g., active hepatitis, renal disease, tuberculosis, heart disease.
• If pregnant, with myoma on ultrasound that are sub-mucosal OR women with myoma that are in any location and greater than 5 cm in size.
• If pregnant, with congenital anomalies of the reproductive tract that would be expected to cause decreased fetal weight or greatly increase the risk of pre-maturity such as duplicate uterus, uterine septum.
• For less clear cases, we will define significant illness as one that significantly alters a woman's ability to perform activities of daily living, causes symptoms at least two days per week, or necessitates regular use of medication. In the case of acute medical conditions, such as urinary tract infection, pneumonia, or febrile illness, enrollment may be postponed until the illness is successfully treated (not currently on any medication for the illness).
• For lactating postpartum subjects: milk supply suspected to be marginal so that 24 hour interruption of nursing likely to lead to inability to restart breast feeding, evidence of breast infection, or history of breast surgery.
• Presence of cysts in the eye suggestive of neurocysticercosis.
• Regular use of a medication for a chronic medical condition.
• History of severe allergic reaction (anaphylaxis, facial swelling, or difficulty breathing) or seizure with praziquantel administration.
• If pregnant, fetus has congenital anomaly determined by ultrasound or is determined to be nonviable e.g., blighted ovum.
• Twin or higher order pregnancy.

Sponsors & Collaborators

• National Institute of Allergy and Infectious Diseases (NIAID): lead

Study Sites (1)

Research Institute for Tropical Medicine - Health Compound

Muntinlupa City, National Capital Region, 1781, Philippines

Location

MeSH Terms

Conditions

Schistosomiasis

Interventions

Praziquantel

Condition Hierarchy (Ancestors)

Trematode Infections; Helminthiasis; Parasitic Diseases; Infections; Vector Borne Diseases

Intervention Hierarchy (Ancestors)

Isoquinolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Study Design

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

Study Record Dates

• First Submitted: January 28, 2011
• First Posted: February 3, 2011
• Study Start: January 1, 2012
• Primary Completion: August 1, 2013
• Study Completion: August 1, 2013
• Last Updated: January 18, 2019

Record last verified: 2013-09

Locations

PH (1)