Praziquantel-Pharmacokinetic Study

• Status: Completed
• Trial end date: 2013-08-01
• Target enrollment: 0
• Participant gender: Female

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.

• Phase: Phase 1
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: National Institute of Allergy and Infectious Diseases (NIAID)
• Treatments: Praziquantel

Criteria

Inclusion Criteria:

Screening:

• Woman must be age 18 or over.

• Present to a study midwife or health center.

• Live in a study village.

Inclusion criteria for the study are as follows:

• Infected with Schistosomiasis (S.) japonicum.

• Age 18 or older.

• Participant is otherwise healthy as determined by history, physical exam, ultrasound (if pregnant) and laboratory assessment, with the exception of laboratory values cited in Exclusion Criteria.

• 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.

Exclusion Criteria:

• 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:

1. 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.

2. Grade 3 or higher laboratory abnormality of blood urea nitrogen (BUN), creatinine, bilirubin, white blood cell count, or platelet count will warrant exclusion. Grade 2 or higher abnormality of alanine aminotransferase (ALT) or aspartate aminotransferase (AST) will warrant exclusion. For hemoglobin, women with severe anemia defined as hemoglobin less than 7.0 g/dL will be excluded.

3. 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.

4. 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.

5. 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.

• Woman has been enrolled into this study or its companion study ("S. japonicum and pregnancy outcomes: A Randomized, Double Blind, Placebo Controlled Trial (RCT). DMID Protocol Number: 06-0039") for a previous pregnancy.

• Inability to comprehend study procedures and provide informed consent due to limited cognitive abilities or other reason, or refuses to provide informed consent.

• Subjects receiving during the previous month any of the following drugs which may interact with praziquantel (PZQ) bioavailability, metabolism and/or elimination: carbamazepine, chloroquine, cimetidine, dexamethasone, erythromycin, fosphenytoin, itraconazole, ketoconazole, phenobarbital, phenytoin, rifampin, or any protease inhibitor or non-nucleoside reverse transcriptase inhibitor.

• Subjects ingesting grapefruit juice during the previous week.