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

Primary Purpose

Neurocysticercosis, Epilepsy

Status
Completed
Phase
Phase 2
Locations
Peru
Study Type
Interventional
Intervention
Praziquantel
Albendazole
ABZ Placebo
PZQ Placebo
Sponsored by
Universidad Peruana Cayetano Heredia
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Neurocysticercosis focused on measuring neurocysticercosis, NCC, praziquantel, PZQ, albendazole, ABZ, parasite, pig tapeworm, Taenia solium, epilepsy, late-onset epilepsy, acquired epilepsy

Eligibility Criteria

16 Years - 65 Years (Child, Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

  • Hospital Nacional Edgardo Rebagliati
  • Hospital Nacional Cayetano Heredia
  • Hospital Nacional Guillermo Almenara
  • Instituto Nacional de Ciencias Neurologicas
  • Universidad Peruana Cayetano Heredia

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Active Comparator

Active Comparator

Active Comparator

Arm Label

I. ABZ + ABZ Placebo + PZQ

II.- ABZ + ABZ Placebo + PZQ Placebo

III .- Albendazole + PZQ Placebo

Arm Description

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)

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

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.

Outcomes

Primary Outcome Measures

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).
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).
PK Substudy - Maximum Concentration of Albendazole
Highest serum level of Albendazole measured from all level assessments in the curve.
Phase III Trial - Proportion of Patients Without Remaining Live Cysts
Proportion of patients whose 6 month MR does not show viable parasites anymore

Secondary Outcome Measures

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
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
PK Substudy - Safety of Combined Albendazole Plus Praziquantel Therapy
- Describe if some Serious Adverse Event was associated to combined Albendazole plus Praziquantel therapy.
Phase III Trial - Proportion of Cysts Which Resolved
Proportion of Viable Brain Parasites which Are not Alive Anymore at 6 Months MRI
Phase III Trial - Seizure Frequency
Seizure frequency by treatment group

Full Information

First Posted
February 27, 2007
Last Updated
May 15, 2015
Sponsor
Universidad Peruana Cayetano Heredia
Collaborators
National Institute of Neurological Disorders and Stroke (NINDS)
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1. Study Identification

Unique Protocol Identification Number
NCT00441285
Brief Title
Neurocysticercosis: Combined Treatment With Praziquantel (PZQ) and Albendazole (ABZ)
Official Title
Antiparasitic Therapy for Neurocysticercosis: Phase II/III Study on Safety and Efficacy of Combined Treatment With Praziquantel and Albendazole
Study Type
Interventional

2. Study Status

Record Verification Date
May 2015
Overall Recruitment Status
Completed
Study Start Date
January 2010 (undefined)
Primary Completion Date
December 2012 (Actual)
Study Completion Date
September 2013 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Universidad Peruana Cayetano Heredia
Collaborators
National Institute of Neurological Disorders and Stroke (NINDS)

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

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.
Detailed 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Neurocysticercosis, Epilepsy
Keywords
neurocysticercosis, NCC, praziquantel, PZQ, albendazole, ABZ, parasite, pig tapeworm, Taenia solium, epilepsy, late-onset epilepsy, acquired epilepsy

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2, Phase 3
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
156 (Actual)

8. Arms, Groups, and Interventions

Arm Title
I. ABZ + ABZ Placebo + PZQ
Arm Type
Active Comparator
Arm Description
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)
Arm Title
II.- ABZ + ABZ Placebo + PZQ Placebo
Arm Type
Active Comparator
Arm Description
Albendazole 15 mg / kg / d ( until 800 mg / d ) + Placebo of Albendazole ( 7.5 mg / Kg / d ) + Placebo of Praziquantel ( 50 mg / kg / d )
Arm Title
III .- Albendazole + PZQ Placebo
Arm Type
Active Comparator
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
Praziquantel
Other Intervention Name(s)
PZQ
Intervention Description
- Praziquantel 50 mg / kg / d (up to 3600 mg / d ) for 10 days.
Intervention Type
Drug
Intervention Name(s)
Albendazole
Other Intervention Name(s)
ABZ
Intervention Description
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.
Intervention Type
Drug
Intervention Name(s)
ABZ Placebo
Other Intervention Name(s)
Placebo of Albendazole
Intervention Description
- Placebo (of Albendazole ) 7.5 mg / kg / d in Arm I and II for 10 days.
Intervention Type
Drug
Intervention Name(s)
PZQ Placebo
Other Intervention Name(s)
Placebo of PZQ
Intervention Description
- Placebo (of Praziquantel) 50 mg / kg / d in Arm II and III for 10 days.
Primary Outcome Measure Information:
Title
PK Substudy - Area Under the Curve of Albendazole in Treatment in Day 1
Description
- 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).
Time Frame
0, 0.5, 1, 1.5, 2, 3, 4, 8, 10 and 12 hours post dose on Treatment day 1
Title
PK Substudy - Area Under the Curve of Albendazole in Treatment Days 10 and 11
Description
- 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).
Time Frame
0.5, 1, 1.5, 2, 3, 4, 8, 10, 12, 24 and 36 hours post dose on Treatment days 10-11
Title
PK Substudy - Maximum Concentration of Albendazole
Description
Highest serum level of Albendazole measured from all level assessments in the curve.
Time Frame
Treatment day 1 and Treatment days 10-11
Title
Phase III Trial - Proportion of Patients Without Remaining Live Cysts
Description
Proportion of patients whose 6 month MR does not show viable parasites anymore
Time Frame
Day 180
Secondary Outcome Measure Information:
Title
PK Substudy - Area Under the Curve of Praziquantel by Antiepileptic Drug in Treatment Day 1
Description
- 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
Time Frame
0, 0.5, 1, 1.5, 2, 3, 4, 8, 10 and 12 hours post dose in treatment day 1
Title
PK Substudy - Area Under the Curve of Praziquantel by Antiepileptic Drug in Treatment Days 10 and 11
Description
- 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
Time Frame
0.5, 1, 1.5, 2, 3, 4, 8, 10, 12, 24 and 36 hours post dose on treatment days 10-11
Title
PK Substudy - Safety of Combined Albendazole Plus Praziquantel Therapy
Description
- Describe if some Serious Adverse Event was associated to combined Albendazole plus Praziquantel therapy.
Time Frame
90 days post tx
Title
Phase III Trial - Proportion of Cysts Which Resolved
Description
Proportion of Viable Brain Parasites which Are not Alive Anymore at 6 Months MRI
Time Frame
Day 180
Title
Phase III Trial - Seizure Frequency
Description
Seizure frequency by treatment group
Time Frame
Day 1 - 540

10. Eligibility

Sex
All
Minimum Age & Unit of Time
16 Years
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Hector H. Garcia, MD
Organizational Affiliation
Universidad Peruana Cayetano Heredia
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
E. Javier Pretell, MD
Organizational Affiliation
Hospital Alberto
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Javier A. Bustos, MD
Organizational Affiliation
Universidad Peruana Cayetano Heredia
Official's Role
Principal Investigator
Facility Information:
Facility Name
Hospital Nacional Edgardo Rebagliati
City
Lima
ZIP/Postal Code
Lima 11
Country
Peru
Facility Name
Hospital Nacional Cayetano Heredia
City
Lima
ZIP/Postal Code
Lima 31
Country
Peru
Facility Name
Hospital Nacional Guillermo Almenara
City
Lima
ZIP/Postal Code
Lima 5
Country
Peru
Facility Name
Instituto Nacional de Ciencias Neurologicas
City
Lima
Country
Peru
Facility Name
Universidad Peruana Cayetano Heredia
City
Lima
Country
Peru

12. IPD Sharing Statement

Citations:
PubMed Identifier
21332573
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 in neurocysticercosis. Br J Clin Pharmacol. 2011 Jul;72(1):77-84. doi: 10.1111/j.1365-2125.2011.03945.x.
Results Reference
result
PubMed Identifier
24999157
Citation
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.
Results Reference
result
PubMed Identifier
26984901
Citation
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.
Results Reference
derived

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

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