Praziquantel-Pharmacokinetic Study

Learn more about:
Related Clinical Trial
Correlating Protection Against Malaria With Serum Profiles Against Plasmodium Falciparum Antigen Repertoires Prevalence of Chronic Kidney Disease (CKD) and Risk Factors in Sub-Saharan Africa S. Japonicum and Pregnancy Outcomes Artemisinin-based Combination Therapy-Intermittent Preventive Treatment (ACT-IPT) Trial Among Schoolchildren in Kassena-Nankana, Ghana Study of Safety and Immune Response of the Sm14 Vaccine in Adults of Endemic Regions L-praziquantel Orodispersible Tablets (L-PZQ ODT) in Schistosoma Infected Children The Effect of Praziquantel Treatment on Schistosoma Mansoni Morbidity and re-Infection Along Lake Victoria, Uganda Praziquantel in Children Under Age 4 Schistosoma Haematobium Infections and Praziquantel Antioxidant Supplements in the Reversal of Schistosomal Peri-portal Fibrosis Single-sex Controlled Human Schistosomiasis Infection: Safety and Dose Finding A Phase Ib Study of the Safety, Reactogenicity, and Immunogenicity of Sm-TSP-2/Alhydrogel)(R) With or Without AP 10-701 for Intestinal Schistosomiasis in Healthy Exposed Adults Single-sex Female Controlled Human Schistosomiasis Mansoni Infection An Open Label Dose Finding Safety and Efficacy in Children and Infants Infected With Schistosomiasis (S.Mansoni) Schistosomiasis Effect on Response to Vaccines, Anaemia and Nutritional Status of Children of Northern Senegal Praziquantel-Pharmacokinetic Study Schistosomiasis in Women of Reproductive Age in Burkina Faso: Implications for Control Iron Supplementation in Schistosomiasis and Soil Transmitted Helminths Control Programmes in Zambia Schistosomiasis in Formal and Non-Formal Schools in Uganda: Implications for Control Programmes Using Community-Based Volunteers to Reach Non-Enrolled School Aged Children Through Community-Directed Treatment of Schistosomiasis in School-Aged Children in Rural Northern Ghana Sm-TSP-2 Schistosomiasis Vaccine in Healthy Ugandan Adults Clinical Trial of Bilhvax,a Vaccine Candidate Against Schistosomiasis A Phase I Study of the Safety, Reactogenicity, and Immunogenicity of Sm-TSP-2/Alhydrogel® With or Without GLA-AF for Intestinal Schistosomiasis in Healthy Adults Treatment of Female Genital Schistosomiasis (FGS) With Praziquantel: A Proof-of-Concept Study Schistosomiasis in Senegal Repeated Doses of Praziquantel in Schistosomiasis Treatment (RePST) Childhood Schistosomiasis: a Novel Strategy Extending the Benefits/Reach of Antihelminthic Treatment Anti-Schistosomiasis Vaccine: Sm14 Phase 2b-Sn in School Children Study to Evaluate the Safety of the Vaccine Prepared sm14 Against Schistosomiasis Arachidonic Acid Treatment Against Schistosomiasis Infection in Children Detection of Schistosomiasis CAA in Travellers After High-risk Water Contact Evaluation of Strategies for Improved Uptake of Preventive Treatment for Intestinal Schistosomiasis Health Benefits of Repeated Treatment in Pediatric Schistosomiasis Seropositivity and Adverse Birth Events in Migrants From Bilharzia-endemic Areas Women and Children as the Focus for Control of Schistosomiasis Infections in the Irrigations Area of Burkina Faso

Brief Title

Praziquantel-Pharmacokinetic Study

Official Title

Praziquantel Pharmacokinetics in Pregnancy and During Lactation

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.
    

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.
    

Study Phase

Phase 1

Study Type

Interventional


Primary Outcome

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).


Condition

Schistosomiasis

Intervention

Praziquantel

Study Arms / Comparison Groups

 Praziquantel
Description:  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.

Publications

* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.

Recruitment Information


Recruitment Status

Drug

Estimated Enrollment

47

Start Date

January 2012

Completion Date

August 2013

Primary Completion Date

August 2013

Eligibility 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.
      

Gender

Female

Ages

18 Years - 99 Years

Accepts Healthy Volunteers

No

Contacts

, , 

Location Countries

Philippines

Location Countries

Philippines

Administrative Informations


NCT ID

NCT01288872

Organization ID

08-0049

Secondary IDs

5U01AI066050-07

Responsible Party

Sponsor

Study Sponsor

National Institute of Allergy and Infectious Diseases (NIAID)


Study Sponsor

, , 


Verification Date

September 2013