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

NCT00441285 | Completed Phase 2 Results DMC

• 1 other identifier: R01NS054805
• Study Type: interventional
• Target: 156
• Locations: 1 country
• Sites: 5

Brief Summary

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

Conditions

Neurocysticercosis; Epilepsy

Keywords

neurocysticercosis; NCC; praziquantel; PZQ; albendazole; ABZ; parasite; pig tapeworm; Taenia solium; epilepsy; late-onset epilepsy; acquired epilepsy

Outcome Measures

Primary Outcomes (4)

• 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

• 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

• 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

• 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

Secondary Outcomes (5)

• PK Substudy - Area Under the Curve of Praziquantel by Antiepileptic Drug in Treatment Day 1

  0, 0.5, 1, 1.5, 2, 3, 4, 8, 10 and 12 hours post dose in treatment day 1

• PK Substudy - Area Under the Curve of Praziquantel by Antiepileptic Drug in Treatment Days 10 and 11

  0.5, 1, 1.5, 2, 3, 4, 8, 10, 12, 24 and 36 hours post dose on treatment days 10-11

• PK Substudy - Safety of Combined Albendazole Plus Praziquantel Therapy

  90 days post tx

• Phase III Trial - Proportion of Cysts Which Resolved

  Day 180

• Phase III Trial - Seizure Frequency

  Day 1 - 540

Study Arms (3)

I. ABZ + ABZ Placebo + PZQ

ACTIVE COMPARATOR

Albendazole 15 mg / kg / d (until 800 mg / d) + Placebo of Albendazole ( 7.5 mg / Kg / d )+ Praziquantel 50 mg / kg / d (until 3600 mg / d)

Drug: Praziquantel; Drug: Albendazole; Drug: ABZ Placebo

II.- ABZ + ABZ Placebo + PZQ Placebo

ACTIVE COMPARATOR

Albendazole 15 mg / kg / d ( until 800 mg / d ) + Placebo of Albendazole ( 7.5 mg / Kg / d ) + Placebo of Praziquantel ( 50 mg / kg / d )

Drug: Albendazole; Drug: ABZ Placebo; Drug: PZQ Placebo

III .- Albendazole + PZQ Placebo

ACTIVE COMPARATOR

Albendazole 22.5 mg / kg / d (until 1200 mg / d) + Placebo of Praziquantel ( 50 mg / kg / d ) This arm was not used in the first substudy ( initial part and guide to the design of the parent study ) however it will be used henceforward.

Drug: Albendazole; Drug: PZQ Placebo

Interventions

Praziquantel DRUG

\- Praziquantel 50 mg / kg / d (up to 3600 mg / d ) for 10 days.

Also known as: PZQ

I. ABZ + ABZ Placebo + PZQ

Albendazole DRUG

* 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.

Also known as: ABZ

I. ABZ + ABZ Placebo + PZQ; II.- ABZ + ABZ Placebo + PZQ Placebo; III .- Albendazole + PZQ Placebo

ABZ Placebo DRUG

\- Placebo (of Albendazole ) 7.5 mg / kg / d in Arm I and II for 10 days.

Also known as: Placebo of Albendazole

I. ABZ + ABZ Placebo + PZQ; II.- ABZ + ABZ Placebo + PZQ Placebo

PZQ Placebo DRUG

\- Placebo (of Praziquantel) 50 mg / kg / d in Arm II and III for 10 days.

Also known as: Placebo of PZQ

II.- ABZ + ABZ Placebo + PZQ Placebo; III .- Albendazole + PZQ Placebo

Eligibility Criteria

• Age: 16 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Universidad Peruana Cayetano Heredia: lead
• National Institute of Neurological Disorders and Stroke (NINDS): collaborator

Study Sites (5)

Hospital Nacional Edgardo Rebagliati

Lima, Lima Province, Lima 11, Peru

Location

Hospital Nacional Cayetano Heredia

Lima, Lima Province, Lima 31, Peru

Location

Hospital Nacional Guillermo Almenara

Lima, Lima Province, Lima 5, Peru

Location

Instituto Nacional de Ciencias Neurologicas

Lima, Peru

Location

Universidad Peruana Cayetano Heredia

Lima, Peru

Location

Related Publications (3)

• 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 in neurocysticercosis. Br J Clin Pharmacol. 2011 Jul;72(1):77-84. doi: 10.1111/j.1365-2125.2011.03945.x.

  PMID: 21332573 RESULT

• 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 neurocysticercosis: a double-blind, randomised controlled trial. Lancet Infect Dis. 2014 Aug;14(8):687-695. doi: 10.1016/S1473-3099(14)70779-0. Epub 2014 Jul 3.

  PMID: 24999157 RESULT

• Garcia HH, Lescano AG, Gonzales I, Bustos JA, Pretell EJ, Horton J, Saavedra H, Gonzalez AE, Gilman RH; Cysticercosis Working Group in Peru. Cysticidal Efficacy of Combined Treatment With Praziquantel and Albendazole for Parenchymal Brain Cysticercosis. Clin Infect Dis. 2016 Jun 1;62(11):1375-9. doi: 10.1093/cid/ciw134. Epub 2016 Mar 16.

  PMID: 26984901 DERIVED

MeSH Terms

Conditions

Neurocysticercosis; Epilepsy; Taeniasis

Interventions

Praziquantel; Albendazole

Condition Hierarchy (Ancestors)

Central Nervous System Helminthiasis; Central Nervous System Parasitic Infections; Central Nervous System Infections; Infections; Parasitic Diseases; Cysticercosis; Cestode Infections; Helminthiasis; Central Nervous System Diseases; Nervous System Diseases; Brain Diseases

Intervention Hierarchy (Ancestors)

Isoquinolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Carbamates; Acids, Acyclic; Carboxylic Acids; Organic Chemicals; Benzimidazoles

Results Point of Contact

• Title: Hector H. Garcia, MD, PhD
• Organization: Universidad Peruana Cayetano Heredia

hgarcia@jhsph.edu

+511 3287360

Study Officials

• Hector H. Garcia, MD

  Universidad Peruana Cayetano Heredia

  PRINCIPAL INVESTIGATOR

• E. Javier Pretell, MD

  Hospital Alberto

  PRINCIPAL INVESTIGATOR

• Javier A. Bustos, MD

  Universidad Peruana Cayetano Heredia

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 27, 2007
• First Posted: February 28, 2007
• Study Start: January 1, 2010
• Primary Completion: December 1, 2012
• Study Completion: September 1, 2013
• Last Updated: June 11, 2015
• Results First Posted: August 7, 2013

Record last verified: 2015-05

Locations

PE (5)