RBx11160 Phase II Dose Ranging Study RBx/MMV05-06
The trial will identify the best dose of the synthetic peroxide RBx11160 to treat uncomplicated malaria. Patients will be treated over 7 days with daily doses of 50, 100 or 200 mg RBx11160.
The study is designed to assess the antimalarial activity and safety of 3 dose levels of RBx 11160 administered once daily for 7 consecutive days. The primary endpoint will be the time to 90% parasite clearance. In future regulatory studies, RBx 11160 is likely to be administered in combination with another antimalarial agent since the development plan follows the current recommendation of WHO for the treatment of uncomplicated malaria. However, it is critical to gather data on RBx 11160 when used as monotherapy in adult patients suffering from acute uncomplicated P. falciparum malaria. In malaria-endemic regions, an adult population is defined on the basis of immune status rather than the legal age of consent. Thus, patients as young as 13 years of age can be enrolled provided consent has been obtained from a legal guardian in accordance with local practices and regulations. This study will be conducted in compliance with International Conference on Harmonization (ICH) Good Clinical Practice (GCP).
Plasmodium Falciparum Malaria
Drug: Treatment with 3 dose groups of RBx11160 over 7 days
|Study Design:||Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Primary Purpose: Treatment
|Official Title:||A Phase II, Double-Blind, Parallel-Group, Randomized, Dose-Ranging Study Assessing the Antimalarial Activity and Safety of RBx 11160 Administered for 7 Days in Patients With Acute Uncomplicated Plasmodium Falciparum Malaria|
- Median time to 90% parasite clearance (PC90).
- Median time to 50% parasite clearance
- Median parasite clearance time
- Fever clearance time
- Proportion of patients with Polymerase Chain Reaction (PCR)-corrected Adequate Clinical and Parasitological Response (ACPR) on Day 28. Proportion of patients with PCR-uncorrected ACPR on Day 28.
- Proportion of patients with PCR-uncorrected ACPR on Day 14.
- Relationship between RBx 11160 plasma concentrations at approximately 3 hours and 8 hours after study medication administration on Days 0 and 6 and PC90, PC50 and PCT.
- Number of gametocytes at Days 0, 3, 6, 14, 21, and 28.
- Safety endpoints:
- Incidence of adverse events or clinically significant changes in laboratory parameters, physical examination, ECG, or vital signs.
|Study Start Date:||June 2006|
|Study Completion Date:||January 2007|
This is a Phase II, double-blind, multicenter, randomized, parallel-group, dose-ranging study of the antimalarial activity and safety of 3 (50, 100, and 200 mg) RBx 11160 dose levels administered as a single dose orally for 7 consecutive days in patients with acute uncomplicated P. falciparum malaria (mono-infection).
At least 255 patients will be randomized at 4 study sites in South East Asia, India and Africa. Each investigational site will enroll between 60 and 90 patients to yield approximately 65 "per protocol" patients in each treatment arm . Patients will be randomized to 1 of 3 dose groups. Patients will be administered RBx 11160 with matching placebo tablets as required to maintain the study blind.
The study is divided into 3 main periods including the Pre-Treatment Period (Screening/Day 0), the Treatment Period (Days 0 through 6; Day 0 is the first day of study medication dosing), and the Post-Treatment Period (Day 14 +/- 1 day; Day 21 +/- 1 day; and Day 28 +/- 2 days).
Patient participation will be for at least 28 (± 2) days following the first dose of study medication. Patients will be hospitalized for at least 4 days (Days 0, 1, 2, and 3), but may remain in the hospital or live in the vicinity of the study site for the study duration. If a patient is discharged from the hospital on Day 3, he/she will return to the study site or an authorized study staff member will visit the patient on Days 4 and 5 to administer study medication and perform indicated assessments. The patient will return to the study site for study visits on Days 6 (last dose of study medication administration), 14, 21, and 28.
If adverse events reported during the study are unresolved by Day 28, patients will be followed for an additional 30 days or until resolution of the event or determination that no further medical management is deemed necessary. Similarly, the investigator will instruct the patient to return to the study site if any untoward event occurs within 30 days of completing study medication.
|Field Station Malaria Reseach Centre (Indian Council of Medical Research)|
|Rourkela, Orissa, India, 769 002|
|Public Health Care Center|
|Kivunge, Zanzibar, Tanzania|
|District Hospital Bagamayo|
|Dar es Salaam, Tanzania|
|Faculty of Tropical Medicine, 420/6 Rajavithee Road|
|Bangkok, Thailand, 10400|
|Principal Investigator:||Sornchai Looareesuwan, MD||Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand|
|Principal Investigator:||Salim M Abdulla, MD||District Hospital Bagamoyo, Dar es Salaam, Tanzania|
|Principal Investigator:||Anders Björkman, MD||Kivunge Public Health Care Center, Zanzibar, Tanzania|
|Principal Investigator:||Neena Valecha, MD||Malaria Research Center, Rourkela, India|