Official Title: “Antiparasitic Therapy for Neurocysticercosis: Phase II/III Study on Safety and Efficacy of Combined Treatment With Praziquantel and Albendazole”

The purpose of this study is to determine if combination drug therapy of praziquantel and albendazole is safe and effective to cure neurocysticercosis.

Study Type: Interventional

Study Design: Treatment, Randomized, Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Placebo Control, Parallel Assignment, Safety/Efficacy Study

Study Primary Completion Date: July 2008

Neurocysticercosis (NCC) is the single major cause of acquired or late-onset epilepsy in the world, and a common diagnosis in immigrant populations in the United States and other industrialized countries. An estimated 50 million humans are affected by NCC. The disease occurs when a parasite called Taenia solium, or the pig tapeworm, infects the brain, forming cysts. NCC is generally treated with 1 of 2 drugs, praziquantel (PZQ) or albendazole (ABZ).

However, current treatment with either of these drugs alone is not totally effective.

The goal of this trial is to determine if combination drug therapy of PZQ and ABZ is safe and more effective to cure NCC than either drug administered alone. This trial will consist of both a sub-study and a parent study.

In the sub-study—which will be performed as the initial part and guide to the design of the parent study—32 participants will be randomly chosen to receive either ABZ and PZQ or ABZ and placebo (an inactive substance) for 10 days. Both groups will also receive other standard medications to manage the disease. Participants will stay in the hospital for at least 2 weeks after treatment begins. After discharge from the hospital, participants will have follow-up visits. During one of the visits, participants will provide an additional blood sample for safety testing. Participants will be followed for 3 months. The purpose of this sub-study is to evaluate the safety and pharmacokinetics of ABZ and PZQ. Enrollment for the sub-study is now complete. Enrollment for the parent study has not yet begun.

In the parent study, a total of 180 participants (including the 32 participants from the sub-study) will be randomly chosen to receive either ABZ and PZQ or ABZ and placebo for 10 days. Both groups will also receive other standard medications to manage the disease including appropriate anti-epileptic drug therapy. Participants will stay in the hospital for at least 2 weeks after treatment begins, which includes 5 days after the end of anti-parasitic treatment. After discharge from the hospital, follow-up visits will be on days 22 and 30 after treatment begins, then monthly until day 90, and finally every 3 months until completing 18 months. Brain images will be taken at 6 and 12 months after treatment begins.

For participants, duration of the trial is 1 year and a half.

Intervention(s) in this Clinical Trial

• Drug: praziquantel
  • Participants will receive ABZ and PZQ for 10 days. Combination of ABZ+PZQ (Addition of PZQ to the standard treatment for NCC.
• Drug: albendazole
  • Participants will receive ABZ and placebo (an inactive substance) for 10 days.

Arms, Groups and Cohorts in this Clinical Trial

• Experimental: I
  • ABZ+PZQ
• Active Comparator: II
  • ABZ+Placebo

Primary Measures

• Maximum plasma concentration (Cmax) and area under the curve (AUC), for ABZSO4 and PZQ
  • Time Frame: Treatment days 1 to 10
    Safety Issue?: Yes

Secondary Measures

• Difference in plasma levels of ABZ between patients in the ABZ+PCB group compared to those in the ABZ+PZQ group.
  • Time Frame: Treament days 1 to 10
    Safety Issue?: Yes
• effects of phenytoin and carbamazepine in PZQ levels when given in addition to ABZ, dexamethasone, and ranitidine.
  • Time Frame: Treatment days 1 to 10
    Safety Issue?: Yes
• safety of the combination ABZ+PZQ compared to ABZ alone
  • Time Frame: Days 1 to 90
    Safety Issue?: Yes

Inclusion Criteria:

• Male or female individuals between 16 to 65 years of age, with a diagnosis of NCC and 20 or less viable cysts.
• Patients with a diagnosis of epilepsy secondary to NCC and a history of one or more spontaneous seizures within the previous year but not longer than 10 years.
• Willingness to complete a minimum of two weeks of hospitalization.

Exclusion Criteria:

• Primary generalized seizures (e.g., not caused by neurocysticercosis)
• A history of generalized status epilepticus.
• Patients with persistent or progressive symptomatic intracranial hypertension or intracranial hypertension.
• Previous therapy with ABZ or PZQ in the past two years.
• Pulmonary tuberculosis, or symptoms compatible with tuberculosis not otherwise explained.
• Active hepatitis
• Systemic disease that may affect short-term prognosis.
• Patients in unstable condition (consistently abnormal vital signs: body temperature, heart rate, respiratory rate, and blood pressure)
• Pregnancy during anti-parasitic treatment
• History of hypersensitivity to ABZ or PZQ
• Concurrent treatment with cimetidine or teophylline
• Chronic alcohol or drug abuse

Gender Eligibility for this Clinical Trial: Both

Minimum Age for this Clinical Trial: 16 Years

Maximum Age for this Clinical Trial: 65 Years

Are Healthy Volunteers Accepted for this Clinical Trial?: No

Lead Sponsor: Universidad Peruana Cayetano Heredia

Overall Clinical Trial Officials and Contacts

Hector H. Garcia, MD Principal Investigator Universidad Peruana Cayetano Heredia  

Information obtained from ClinicalTrials.gov on August 28, 2008

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00441285

Study ID Number: R01NS054805

ClinicalTrials.gov Identifier: NCT00441285

Health Authority: United States: Federal Government