Working...
ClinicalTrials.gov
ClinicalTrials.gov Menu

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT00441285
Recruitment Status : Completed
First Posted : February 28, 2007
Results First Posted : August 7, 2013
Last Update Posted : June 11, 2015
Sponsor:
Collaborator:
National Institute of Neurological Disorders and Stroke (NINDS)
Information provided by (Responsible Party):
Universidad Peruana Cayetano Heredia

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Conditions Neurocysticercosis
Epilepsy
Interventions Drug: Praziquantel
Drug: Albendazole
Drug: ABZ Placebo
Drug: PZQ Placebo
Enrollment 156
Recruitment Details This protocol (2 groups, n=180) was modified by the DSMB to add a pharmacokinetics / safety substudy (two groups, n=32). After the substudy results were available, we were approved to proceed with a modified study design (3 groups, n=240). This second study was terminated after enroling patient 124 because of early efficacy (total n= 132+24, 156)
Pre-assignment Details  
Arm/Group Title PK Substudy ABZ+PZQ PK Substudy ABZ+Placebo Phase III Trial - ABZ+PZQ Phase III Trial - Increased ABZ Phase III Trial - Standard ABZ
Hide Arm/Group Description
  • Albendazole was given at 15 mg / kg / d , divided two daily doses, morning and evening. It is supplied in 200 mg tablets, so the dose was rounded up to the next 100 mg level, up to a maximum 800 mg / d , for 10 days.
  • Praziquantel was given at 50 mg / kg / d , divided in two daily doses, morning and evening.It is supplied in 600 mg tablets divided in four, so the dose was rounded up to the next 100 mg level, up to a maximum 3.6 g / d , for 9 1/2 days.
  • Albendazole was given at 15 mg / kg / d , divided two daily doses, morning and evening. It is supplied in 200 mg tablets, so the dose was rounded up to the next 100 mg level, up to a maximum 800 mg / d , for 10 days.
  • Praziquantel placebo was given in two daily doses, morning and evening,for 9 1/2 days.
  • Albendazole was given at 15 mg / kg / d , divided two daily doses, morning and evening. It is supplied in 200 mg tablets, so the dose was rounded up to the next 100 mg level, up to a maximum 800 mg / d , for 10 days.
  • Placebo of ABZ was added to mask the dose of ABZ (see Increased ABZ arm)
  • Praziquantel was given at 50 mg / kg / d , divided in two daily doses, morning and evening.It is supplied in 600 mg tablets divided in four, so the dose was rounded up to the next 100 mg level, up to a maximum 3.6 g / d , for 9 1/2 days.
  • Albendazole was given at 22.5 mg / kg / d , divided in two daily doses, morning and evening. It is supplied in 200 mg tablets, so the dose was rounded up to the next 100 mg level, up to a maximum of 1200 mg / d, for 10 days.
  • Praziquantel was given at 50 mg / kg / d , divided in two daily doses, morning and evening. It is supplied in 600 mg tablets divided in four, so the dose was rounded up to the next 100 mg level, up to a maximum 3.6 g / d , for 9 1/2 days.
  • Albendazole was given at 15 mg / kg / d , divided two daily doses, morning and evening. It is supplied in 200 mg tablets, so the dose was rounded up to the next 100 mg level, up to a maximum 800 mg / d , for 10 days.
  • Placebo of ABZ was added to mask the dose of ABZ (see Increased ABZ arm)
  • Placebo of Praziquantel was given at 50 mg / kg / d , divided in two daily doses, morning and evening.It is supplied in 600 mg tablets divided in four, so the dose was rounded up to the next 100 mg level, up to a maximum 3.6 g / d , for 9 1/2 days.
Period Title: Overall Study
Started 16 16 41 40 43
Completed 16 16 41 40 43
Not Completed 0 0 0 0 0
Arm/Group Title Albendazole + Praziquantel Albendazole + Placebo Phase III Trial ABZ+PZQ Phase III Trial Increased ABZ Phase III Trial Standard ABZ Total
Hide Arm/Group Description
  • Albendazole was given at 15 mg / kg / d , divided two daily doses, morning and evening. It is supplied in 200 mg tablets, so the dose was rounded up to the next 100 mg level, up to a maximum 800 mg / d , for 10 days.
  • Praziquantel was given at 50 mg / kg / d , divided in two daily doses, morning and evening.It is supplied in 600 mg tablets divided in four, so the dose was rounded up to the next 100 mg level, up to a maximum 3.6 g / d , for 9 1/2 days.
  • Albendazole was given at 15 mg / kg / d , divided two daily doses, morning and evening. It is supplied in 200 mg tablets, so the dose was rounded up to the next 100 mg level, up to a maximum 800 mg / d , for 10 days.
  • Praziquantel placebo was given in two daily doses, morning and evening,for 9 1/2 days.
  • Albendazole was given at 15 mg / kg / d , divided two daily doses, morning and evening. It is supplied in 200 mg tablets, so the dose was rounded up to the next 100 mg level, up to a maximum 800 mg / d , for 10 days.
  • A placebo of ABZ was added to complete to the doses in the Increased ABZ arm
  • Praziquantel was given at 50 mg / kg / d , divided in two daily doses, morning and evening.It is supplied in 600 mg tablets divided in four, so the dose was rounded up to the next 100 mg level, up to a maximum 3.6 g / d , for 10 days.
  • Albendazole was given at 22.5 mg / kg / d , divided in two daily doses, morning and evening. It is supplied in 200 mg tablets, so the dose was rounded up to the next 100 mg level, up to a maximum of 1200 mg / d , for 10 days.
  • Praziquantel placebo was given in two daily doses, morning and evening,for 10 days.
  • Albendazole was given at 15 mg / kg / d , divided two daily doses, morning and evening. It is supplied in 200 mg tablets, so the dose was rounded up to the next 100 mg level, up to a maximum 800 mg / d , for 10 days.
  • A placebo of ABZ was added to complete the doses to the dosage in the Increased ABZ arm
  • Praziquantel placebo was given in two daily doses, morning and evening,for 10 days.
Total of all reporting groups
Overall Number of Baseline Participants 16 16 41 40 43 156
Hide Baseline Analysis Population Description
The population involves 32 patients in the Phase II substudy and 124 patients in the Phase III main study
Age, Categorical  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 16 participants 16 participants 41 participants 40 participants 43 participants 156 participants
<=18 years
2
  12.5%
2
  12.5%
0
   0.0%
2
   5.0%
2
   4.7%
8
   5.1%
Between 18 and 65 years
14
  87.5%
14
  87.5%
39
  95.1%
38
  95.0%
41
  95.3%
146
  93.6%
>=65 years
0
   0.0%
0
   0.0%
2
   4.9%
0
   0.0%
0
   0.0%
2
   1.3%
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 16 participants 16 participants 41 participants 40 participants 43 participants 156 participants
29.3  (9.7) 27.5  (11) 34  (14) 34  (12) 35  (13) 28  (10.2)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 16 participants 16 participants 41 participants 40 participants 43 participants 156 participants
Female
5
  31.3%
6
  37.5%
15
  36.6%
19
  47.5%
14
  32.6%
59
  37.8%
Male
11
  68.8%
10
  62.5%
26
  63.4%
21
  52.5%
29
  67.4%
97
  62.2%
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
Peru Number Analyzed 16 participants 16 participants 41 participants 40 participants 43 participants 156 participants
16 16 41 40 43 156
1.Primary Outcome
Title PK Substudy - Area Under the Curve of Albendazole in Treatment in Day 1
Hide 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
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Albendazole + Praziquantel Albendazole + Placebo
Hide Arm/Group Description:
  • Albendazole was given at 15 mg / kg / d , divided two daily doses, morning and evening. It is supplied in 200 mg tablets, so the dose was rounded up to the next 100 mg level, up to a maximum 800 mg / d , for 10 days.
  • Praziquantel was given at 50 mg / kg / d , divided in two daily doses, morning and evening.It is supplied in 600 mg tablets divided in four, so the dose was rounded up to the next 100 mg level, up to a maximum 3.6 g / d , for 9 1/2 days.
  • Albendazole was given at 15 mg / kg / d , divided two daily doses, morning and evening. It is supplied in 200 mg tablets, so the dose was rounded up to the next 100 mg level, up to a maximum 800 mg / d , for 10 days.
  • Praziquantel placebo was given in two daily doses, morning and evening,for 9 1/2 days.
Overall Number of Participants Analyzed 16 16
Mean (95% Confidence Interval)
Unit of Measure: ng*h/mL
1412.2
(1115.5 to 1709)
1111
(931.1 to 1290.8)
2.Primary Outcome
Title PK Substudy - Area Under the Curve of Albendazole in Treatment Days 10 and 11
Hide 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
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Albendazole + Praziquantel Albendazole + Placebo
Hide Arm/Group Description:
  • Albendazole was given at 15 mg / kg / d , divided two daily doses, morning and evening. It is supplied in 200 mg tablets, so the dose was rounded up to the next 100 mg level, up to a maximum 800 mg / d , for 10 days.
  • Praziquantel was given at 50 mg / kg / d , divided in two daily doses, morning and evening.It is supplied in 600 mg tablets divided in four, so the dose was rounded up to the next 100 mg level, up to a maximum 3.6 g / d , for 9 1/2 days.
  • Albendazole was given at 15 mg / kg / d , divided two daily doses, morning and evening. It is supplied in 200 mg tablets, so the dose was rounded up to the next 100 mg level, up to a maximum 800 mg / d , for 10 days.
  • Praziquantel placebo was given in two daily doses, morning and evening,for 9 1/2 days.
Overall Number of Participants Analyzed 16 16
Mean (95% Confidence Interval)
Unit of Measure: ng*h/ml
4925.3
(3548.6 to 6302)
2969.6
(2543.8 to 3395.4)
3.Primary Outcome
Title PK Substudy - Maximum Concentration of Albendazole
Hide Description Highest serum level of Albendazole measured from all level assessments in the curve.
Time Frame Treatment day 1 and Treatment days 10-11
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Albendazole + Praziquantel Albendazole + Placebo
Hide Arm/Group Description:
  • Albendazole was given at 15 mg / kg / d , divided two daily doses, morning and evening. It is supplied in 200 mg tablets, so the dose was rounded up to the next 100 mg level, up to a maximum 800 mg / d , for 10 days.
  • Praziquantel was given at 50 mg / kg / d , divided in two daily doses, morning and evening.It is supplied in 600 mg tablets divided in four, so the dose was rounded up to the next 100 mg level, up to a maximum 3.6 g / d , for 9 1/2 days.
  • Albendazole was given at 15 mg / kg / d , divided two daily doses, morning and evening. It is supplied in 200 mg tablets, so the dose was rounded up to the next 100 mg level, up to a maximum 800 mg / d , for 10 days.
  • Praziquantel placebo was given in two daily doses, morning and evening,for 9 1/2 days.
Overall Number of Participants Analyzed 16 16
Mean (Standard Deviation)
Unit of Measure: ng/mL
1293.9  (3471.6) 2232.8  (6500.7)
4.Primary Outcome
Title Phase III Trial - Proportion of Patients Without Remaining Live Cysts
Hide Description Proportion of patients whose 6 month MR does not show viable parasites anymore
Time Frame Day 180
Hide Outcome Measure Data
Hide Analysis Population Description
Some patients did not reach the analysis time point.
Arm/Group Title Phase III Trial - ABZ+PZQ Phase III Trial - Increased ABZ Phase III Trial - Standard ABZ
Hide Arm/Group Description:
Main Trial, Arm receiving standard ABZ doses plus active PZQ
Main Trial, Arm receiving increased ABZ doses, no PZQ
Main Trial, Arm receiving standard ABZ doses, no PZQ
Overall Number of Participants Analyzed 39 38 42
Measure Type: Number
Unit of Measure: participants
25 19 15
5.Secondary Outcome
Title PK Substudy - Area Under the Curve of Praziquantel by Antiepileptic Drug in Treatment Day 1
Hide 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
Hide Outcome Measure Data
Hide Analysis Population Description
Carbamazepine and Phenytoin were not assigned by the study.
Arm/Group Title Albendazole + Praziquantel
Hide Arm/Group Description:
  • Albendazole was given at 15 mg/kg/day, divided two daily doses, morning and evening. It is supplied in 200 mg tablets, so the dose was rounded up to the next 100 mg level, up to a maximum 800 mg/day, for 10 days.
  • Praziquantel was given at 50 mg/kg/day, divided in two daily doses, morning and evening.It is supplied in 600 mg tablets divided in four, so the dose was rounded up to the next 100 mg level, up to a maximum 3.6 g/day,for 9 1/2 days.
Overall Number of Participants Analyzed 16
Mean (Standard Deviation)
Unit of Measure: ng*h / mL
Carbamazepine (n=8) 548.3  (320.9)
Phenytoin (n=8) 923.7  (424.7)
6.Secondary Outcome
Title PK Substudy - Area Under the Curve of Praziquantel by Antiepileptic Drug in Treatment Days 10 and 11
Hide 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
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Carbamazepine Phenytoin
Hide Arm/Group Description:
Area Under the Curve of Praziquantel in Patients Receiving Carbamazepine
Area Under the Curve of Praziquantel in Patients Receiving Phenytoin
Overall Number of Participants Analyzed 8 8
Mean (95% Confidence Interval)
Unit of Measure: ng*h/ml
240.2
(151.7 to 328.7)
550.1
(83.3 to 1183.4)
7.Secondary Outcome
Title PK Substudy - Safety of Combined Albendazole Plus Praziquantel Therapy
Hide Description - Describe if some Serious Adverse Event was associated to combined Albendazole plus Praziquantel therapy.
Time Frame 90 days post tx
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Albendazole + Praziquantel Albendazole + Placebo
Hide Arm/Group Description:
  • Albendazole was given at 15 mg / kg / d , divided two daily doses, morning and evening. It is supplied in 200 mg tablets, so the dose was rounded up to the next 100 mg level, up to a maximum 800 mg / d , for 10 days.
  • Praziquantel was given at 50 mg / kg / d , divided in two daily doses, morning and evening.It is supplied in 600 mg tablets divided in four, so the dose was rounded up to the next 100 mg level, up to a maximum 3.6 g / d , for 9 1/2 days.
  • Albendazole was given at 15 mg / kg / d , divided two daily doses, morning and evening. It is supplied in 200 mg tablets, so the dose was rounded up to the next 100 mg level, up to a maximum 800 mg / d , for 10 days.
  • Praziquantel placebo was given in two daily doses, morning and evening,for 9 1/2 days.
Overall Number of Participants Analyzed 16 16
Measure Type: Number
Unit of Measure: Events
0 0
8.Secondary Outcome
Title Phase III Trial - Proportion of Cysts Which Resolved
Hide Description Proportion of Viable Brain Parasites which Are not Alive Anymore at 6 Months MRI
Time Frame Day 180
Hide Outcome Measure Data
Hide Analysis Population Description
Final population numbers for this analysis not yet defined
Arm/Group Title Phase III Trial - ABZ+PZQ Phase III Trial - Increased ABZ Phase III Trial - Standard ABZ
Hide Arm/Group Description:
Main Trial, Arm receiving standard ABZ doses plus active PZQ
Main Trial, Arm receiving increased ABZ doses, no PZQ
Main Trial, Arm receiving standard ABZ doses, no PZQ
Overall Number of Participants Analyzed 0 0 0
No data displayed because Outcome Measure has zero total analyzed.
9.Secondary Outcome
Title Phase III Trial - Seizure Frequency
Hide Description Seizure frequency by treatment group
Time Frame Day 1 - 540
Hide Outcome Measure Data
Hide Analysis Population Description
Final population numbers for this analysis not yet defined
Arm/Group Title Phase III Trial - ABZ+PZQ Phase III Trial - Increased ABZ Phase III Trial - Standard ABZ
Hide Arm/Group Description:
Main Trial, Arm receiving standard ABZ doses plus active PZQ
Main Trial, Arm receiving increased ABZ doses, no PZQ
Main Trial, Arm receiving standard ABZ doses, no PZQ
Overall Number of Participants Analyzed 0 0 0
No data displayed because Outcome Measure has zero total analyzed.
Time Frame Number of Serious Adverse Events along the entire follow up (Days 1 - 540)
Adverse Event Reporting Description Adverse events by treatment arm in Phase III arms are not yet available because of the blinded nature of the trial
 
Arm/Group Title Albendazole + Praziquantel Albendazole + Placebo
Hide Arm/Group Description
  • Albendazole was given at 15 mg / kg / d , divided two daily doses, morning and evening. It is supplied in 200 mg tablets, so the dose was rounded up to the next 100 mg level, up to a maximum 800 mg / d , for 10 days.
  • Praziquantel was given at 50 mg / kg / d , divided in two daily doses, morning and evening.It is supplied in 600 mg tablets divided in four, so the dose was rounded up to the next 100 mg level, up to a maximum 3.6 g / d , for 9 1/2 days.
  • Albendazole was given at 15 mg / kg / d , divided two daily doses, morning and evening. It is supplied in 200 mg tablets, so the dose was rounded up to the next 100 mg level, up to a maximum 800 mg / d , for 10 days.
  • Praziquantel placebo was given in two daily doses, morning and evening,for 9 1/2 days.
All-Cause Mortality
Albendazole + Praziquantel Albendazole + Placebo
Affected / at Risk (%) Affected / at Risk (%)
Total   --/--      --/--    
Show Serious Adverse Events Hide Serious Adverse Events
Albendazole + Praziquantel Albendazole + Placebo
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   2/16 (12.50%)      2/16 (12.50%)    
Nervous system disorders     
Prolonged hospitalization  [1]  2/16 (12.50%)  2 2/16 (12.50%)  2
Indicates events were collected by systematic assessment
[1]
The Prolonged hospitalization was associated with the disease itself, not because of antiparasitic treatment
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Albendazole + Praziquantel Albendazole + Placebo
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   15/16 (93.75%)      12/16 (75.00%)    
Blood and lymphatic system disorders     
Decreased neutrophilos   1/16 (6.25%)  1 0/16 (0.00%)  0
Decreased Red blood cells   1/16 (6.25%)  1 0/16 (0.00%)  0
Decreased White blood cells   2/16 (12.50%)  2 1/16 (6.25%)  1
Gastrointestinal disorders     
Abdominal distension   1/16 (6.25%)  1 0/16 (0.00%)  0
Abdominal pain   2/16 (12.50%)  2 2/16 (12.50%)  2
Decreased indirect bilirubin   1/16 (6.25%)  1 0/16 (0.00%)  0
Diarrhea   0/16 (0.00%)  0 1/16 (6.25%)  1
Increased ALT   8/16 (50.00%)  9 10/16 (62.50%)  17
Increased AST   3/16 (18.75%)  3 7/16 (43.75%)  9
Nausea   1/16 (6.25%)  1 2/16 (12.50%)  2
Nervous system disorders     
Headache   4/16 (25.00%)  6 5/16 (31.25%)  9
Dizziness   0/16 (0.00%)  0 2/16 (12.50%)  2
Hypoesthesia   0/16 (0.00%)  0 3/16 (18.75%)  4
Paresis   0/16 (0.00%)  0 1/16 (6.25%)  1
Paresthesia   1/16 (6.25%)  2 1/16 (6.25%)  1
Skin and subcutaneous tissue disorders     
Acne   2/16 (12.50%)  2 0/16 (0.00%)  0
Indicates events were collected by systematic assessment
Certain Agreements
All Principal Investigators ARE employed by the organization sponsoring the study.
Results Point of Contact
Name/Title: Hector H. Garcia, MD, PhD
Organization: Universidad Peruana Cayetano Heredia
Phone: +511 3287360
Responsible Party: Universidad Peruana Cayetano Heredia
ClinicalTrials.gov Identifier: NCT00441285     History of Changes
Other Study ID Numbers: R01NS054805 ( U.S. NIH Grant/Contract )
R01NS054805 ( U.S. NIH Grant/Contract )
First Submitted: February 27, 2007
First Posted: February 28, 2007
Results First Submitted: January 28, 2010
Results First Posted: August 7, 2013
Last Update Posted: June 11, 2015