RBx11160 Phase II Dose Ranging Study RBx/MMV05-06

• Status: Completed
• Trial end date: 2007-01-01
• Target enrollment: 0
• Participant gender: All

Summary

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).

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Medicines for Malaria Venture
• Collaborators: Ranbaxy Laboratories Limited; Swiss Tropical & Public Health Institute

Criteria

Inclusion Criteria:

• Male or female patients aged 13 to 65 years, inclusive.

• Body weight > 30 kg with no clinical evidence of severe malnutrition.

• Presence of acute symptomatic uncomplicated malaria with a diagnosis confirmed by a positive blood smear with asexual forms of P. falciparum parasites only. Initial parasite densities appropriate for inclusion will be between 1000 and 100,000 asexual parasites/microL blood.

• Presence of fever (axillary temperature > 37.5 °C or oral or rectal temperature > 38 °C).

• Female patients must be non-lactating and willing to use contraceptive methods during the study period.

• Written informed consent, in accordance with local practice, provided by patient and/or parent/guardian/spouse. If a patient is unable to provide informed consent in writing, a thumbprint to indicate consent in the presence of at least 1 witness is acceptable. If applicable, for adolescents providing written informed consent, assent should be obtained from the patient's legally accepted representative/guardian.

• Willingness and ability to comply with the study protocol for the duration of the study.

• Patient resides within a reasonable distance of the investigational site, so that attendance of all study visits and follow-up by medical staff are logistically feasible.

Exclusion Criteria:

• Patients presenting with a mixed infection (i.e., malaria due to more than 1 causative parasite).

• Patients with severe malaria.

• Any antimalarial treatment during 2 weeks prior to Screening, as assessed by medical history.

• History of hypersensitivity or allergic reactions to artemisinins.

• Patients who have been treated with RBx 11160 in any study.

• Participation in any investigational drug study during the 30 days prior to Screening.

• Electrocardiogram (ECG) abnormalities with clinical significance or relevance that require urgent management. These abnormalities include QTc interval > 450 msec at Screening and cardiac conduction disorders, with the exception of right bundle branch block.

• A female patient who is lactating or pregnant at Screening.

• Gastrointestinal dysfunction that could alter absorption or motility (e.g., diarrhea defined as > 3 episodes of watery stools in the previous 24 hours or patients who have had 3 episodes of vomiting within 24 hours prior to Screening).

• Patients with known significant renal or hepatic impairment indicated by the following laboratory evaluations at Screening:

Serum creatinine > 1.5 x upper limit of normal (ULN). Aspartate transaminase > 2.5 x ULN. Alanine transaminase > 2.5 x ULN. Alkaline phosphatase > 2.5 x ULN. Total bilirubin > 1.5 x ULN.

• Patients who have had a splenectomy.

• Immunocompromised patients, patients receiving immunosuppressive agents, or patients with known human immunodeficiency virus (HIV) infection. (Screening for these conditions is not required for entry in the study.)

• Evidence of clinically significant cardiovascular, pulmonary, metabolic, gastrointestinal, neurological, psychiatric (e.g., depression, anxiety, psychosis, or schizophrenia) or endocrine diseases, malignancy, or other abnormalities (other than the indication being studied).

• Patients who have epilepsy or a history of convulsions.