Neurocysticercosis: Combined Treatment With Praziquantel (PZQ) and Albendazole (ABZ)

Epilepsy Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00441285
• Other study ID #: R01NS054805
• Secondary ID: R01NS054805
• Status: Completed
• Phase: Phase 2/Phase 3
• First received: February 27, 2007
• Last updated: May 15, 2015
• Start date: January 2010
• Est. completion date: September 2013

Study information

• Verified date: May 2015
• Source: Universidad Peruana Cayetano Heredia
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Federal Government
• Study type: Interventional

Clinical Trial Summary

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

Description:

Neurocysticercosis 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 Neurocysticercosis. The disease occurs when a parasite called Taenia solium, or the pig tapeworm, infects the brain, forming cysts. Neurocysticercosis is generally treated with 1 of 2 drugs, praziquantel or albendazole. 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 praziquantel and albendazole is safe and more effective to cure Neurocysticercosis than either drug administered alone. This trial will consist of two sub-studies and a parent study.

In the first substudy which was performed and completed as the initial part and guide to the design of the parent study, a series of 32 patients with viable cystic intraparenchymal Neurocysticercosis were treated with either albendazole ( 15 mg / kg /d ) + praziquantel ( 50 mg / kg/ d ) or albendazole+Placebo in a double blind randomized study. Half of patients in each group had their seizure disorder treated with phenytoin and the other half with carbamazepine (not assigned by the study). The study was designed and powered for pharmacokinetic evaluation and exploratory safety so comparative cysticidal efficacy has not yet been analyzed. There were no safety concerns. Pharmacokinetics of ABZ and PZQ were obtained and described.

In the parent study, a total of 240 participants ( including the 32 participants from the first substudy ) will be randomly chosen to receive albendazole + praziquantel, albendazole + placebo or albendazole at an increased dose + placebo for 10 days. These 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 21 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 156
• Est. completion date: September 2013
• Est. primary completion date: December 2012
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 16 Years to 65 Years

Eligibility

For parent study:

Inclusion Criteria:

• Male or female individuals between 16 to 65 years of age, with a diagnosis of Neurocysticercosis and 20 or less viable cysts.

• Patients with a diagnosis of epilepsy secondary to Neurocysticercosis 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.

• If female of child bearing potential, negative urine pregnancy testing and willingness to use an adequate method of contraception while on study medications and for at least 3 months following Albendazole therapy.

• Normal laboratory values for hematocrit, platelets, white blood cells and glucose and normal or decreased values for Alanine transaminase, Aspartate transaminase and creatinine.

• Negative PPD measurement and if positive ( > 9mm induration in the absence of other findings or immunosuppression ) , negative smears for TB.

• Negative fecal exam for Taenia eggs or Strongyloides larvae.

Exclusion Criteria:

• Primary generalized seizures ( e.g., not caused by Neurocysticercosis )

• A history of generalized epileptic status .

• A type of Neurocysticercosis which can expose the patient to increased risk during the study.

• Patients with persistent or progressive symptomatic intracranial hypertension or intracranial hypertension.

• Previous therapy with Albendazole or Praziquantel in the previous year.

• 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 antiparasitic treatment

• History of hypersensitivity to Albendazole or Praziquantel

• Concurrent treatment with Cimetidine or Theophylline

• Chronic alcohol or drug abuse

• Unwilling or unable to provide a Computed tomography initially or an Magnetic resonance imaging at 6 months ( as patients with ferromagnetic implants ) , Computed tomography at the end of therapy.

• Unwillingness of subject or legal representative to give written informed consent.

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Cysticercosis
• Epilepsy
• Neurocysticercosis

Intervention

Drug:
• Praziquantel
- Praziquantel 50 mg / kg / d (up to 3600 mg / d ) for 10 days.
• Albendazole
Albendazole 15 mg / kg / d ( up to 800 mg /d ) in Arm I for 10 days. Albendazole at an increased dose, 22.5 mg / kg / d (up to 1200 mg / d ), in Arm II for 10 days.
• ABZ Placebo
- Placebo (of Albendazole ) 7.5 mg / kg / d in Arm I and II for 10 days.
• PZQ Placebo
- Placebo (of Praziquantel) 50 mg / kg / d in Arm II and III for 10 days.

Locations

Country	Name	City	State
Peru	Hospital Nacional Cayetano Heredia	Lima
Peru	Hospital Nacional Edgardo Rebagliati	Lima
Peru	Hospital Nacional Guillermo Almenara	Lima
Peru	Instituto Nacional de Ciencias Neurologicas	Lima
Peru	Universidad Peruana Cayetano Heredia	Lima

Sponsors (2)

Lead Sponsor	Collaborator
Universidad Peruana Cayetano Heredia	National Institute of Neurological Disorders and Stroke (NINDS)

Country where clinical trial is conducted

Peru, 

References & Publications (2)

Garcia HH, Gonzales I, Lescano AG, Bustos JA, Zimic M, Escalante D, Saavedra H, Gavidia M, Rodriguez L, Najar E, Umeres H, Pretell EJ; Cysticercosis Working Group in Peru. Efficacy of combined antiparasitic therapy with praziquantel and albendazole for ne — View Citation

Garcia HH, Lescano AG, Lanchote VL, Pretell EJ, Gonzales I, Bustos JA, Takayanagui OM, Bonato PS, Horton J, Saavedra H, Gonzalez AE, Gilman RH; Cysticercosis Working Group in Peru. Pharmacokinetics of combined treatment with praziquantel and albendazole i — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	PK Substudy - Area Under the Curve of Albendazole in Treatment in Day 1	- To evaluate kinetic disposition of Albendazole we calculated the Area under the curve of the active metabolite of Albendazole (Albendazole Sulphoxide) with Praziquantel or Placebo (of Praziquantel).	0, 0.5, 1, 1.5, 2, 3, 4, 8, 10 and 12 hours post dose on Treatment day 1	No
Primary	PK Substudy - Area Under the Curve of Albendazole in Treatment Days 10 and 11	- To evaluate kinetic disposition of Albendazole we calculated the Area under the curve of the active metabolite of Albendazole (Albendazole Sulphoxide) with Praziquantel or Placebo (of Praziquantel).	0.5, 1, 1.5, 2, 3, 4, 8, 10, 12, 24 and 36 hours post dose on Treatment days 10-11	No
Primary	PK Substudy - Maximum Concentration of Albendazole	Highest serum level of Albendazole measured from all level assessments in the curve.	Treatment day 1 and Treatment days 10-11	Yes
Primary	Phase III Trial - Proportion of Patients Without Remaining Live Cysts	Proportion of patients whose 6 month MR does not show viable parasites anymore	Day 180	No
Secondary	PK Substudy - Area Under the Curve of Praziquantel by Antiepileptic Drug in Treatment Day 1	- To evaluate the kinetic disposition of Praziquantel by antiepileptic drug after the last praziquantel dose, we calculated the Area Under the Curve of Praziquantel with Carbamazepine or Phenytoin	0, 0.5, 1, 1.5, 2, 3, 4, 8, 10 and 12 hours post dose in treatment day 1	No
Secondary	PK Substudy - Area Under the Curve of Praziquantel by Antiepileptic Drug in Treatment Days 10 and 11	- To evaluate the kinetic disposition of Praziquantel by antiepileptic drug after the last praziquantel dose, we calculated the Area Under the Curve of Praziquantel with Carbamazepine or Phenytoin	0.5, 1, 1.5, 2, 3, 4, 8, 10, 12, 24 and 36 hours post dose on treatment days 10-11	No
Secondary	PK Substudy - Safety of Combined Albendazole Plus Praziquantel Therapy	- Describe if some Serious Adverse Event was associated to combined Albendazole plus Praziquantel therapy.	90 days post tx	Yes
Secondary	Phase III Trial - Proportion of Cysts Which Resolved	Proportion of Viable Brain Parasites which Are not Alive Anymore at 6 Months MRI	Day 180	No
Secondary	Phase III Trial - Seizure Frequency	Seizure frequency by treatment group	Day 1 - 540	No