Antiparasitic Therapy for Neurocysticercosis: Phase II/III Study on Safety and Efficacy of Combined Treatment With Praziquantel and Albendazole
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 156
- 试验地点
- 5
- 主要终点
- PK Substudy - Area Under the Curve of Albendazole in Treatment in Day 1
研究概览
简要总结
The purpose of this study is to determine if combination drug therapy of praziquantel and albendazole is safe and effective to cure neurocysticercosis.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 16 Years 至 65 Years（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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.
排除标准
- •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.
研究组 & 干预措施
I. ABZ + ABZ Placebo + PZQ
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)
干预措施: Praziquantel (Drug)
I. ABZ + ABZ Placebo + PZQ
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)
干预措施: Albendazole (Drug)
I. ABZ + ABZ Placebo + PZQ
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)
干预措施: ABZ Placebo (Drug)
II.- ABZ + ABZ Placebo + PZQ Placebo
Albendazole 15 mg / kg / d ( until 800 mg / d ) + Placebo of Albendazole ( 7.5 mg / Kg / d ) + Placebo of Praziquantel ( 50 mg / kg / d )
干预措施: Albendazole (Drug)
II.- ABZ + ABZ Placebo + PZQ Placebo
Albendazole 15 mg / kg / d ( until 800 mg / d ) + Placebo of Albendazole ( 7.5 mg / Kg / d ) + Placebo of Praziquantel ( 50 mg / kg / d )
干预措施: ABZ Placebo (Drug)
II.- ABZ + ABZ Placebo + PZQ Placebo
Albendazole 15 mg / kg / d ( until 800 mg / d ) + Placebo of Albendazole ( 7.5 mg / Kg / d ) + Placebo of Praziquantel ( 50 mg / kg / d )
干预措施: PZQ Placebo (Drug)
III .- Albendazole + PZQ Placebo
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.
干预措施: Albendazole (Drug)
III .- Albendazole + PZQ Placebo
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.
干预措施: PZQ Placebo (Drug)
结局指标
主要结局
PK Substudy - Area Under the Curve of Albendazole in Treatment in Day 1
时间窗: 0, 0.5, 1, 1.5, 2, 3, 4, 8, 10 and 12 hours post dose on Treatment 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 - Maximum Concentration of Albendazole
时间窗: Treatment day 1 and Treatment days 10-11
Highest serum level of Albendazole measured from all level assessments in the curve.
PK Substudy - Area Under the Curve of Albendazole in Treatment Days 10 and 11
时间窗: 0.5, 1, 1.5, 2, 3, 4, 8, 10, 12, 24 and 36 hours post dose on Treatment days 10-11
- 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).
Phase III Trial - Proportion of Patients Without Remaining Live Cysts
时间窗: Day 180
Proportion of patients whose 6 month MR does not show viable parasites anymore
次要结局
- Phase III Trial - Seizure Frequency(Day 1 - 540)
- PK Substudy - Safety of Combined Albendazole Plus Praziquantel Therapy(90 days post tx)
- Phase III Trial - Proportion of Cysts Which Resolved(Day 180)
- 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)