Pyronaridine/Artesunate -Ritonavir Drug Drug Interaction Study
Pyronaridine/ artesunate (Pyramax) is an antimalarial therapy which has been demonstrated to be a safe and effective treatment in patients with Plasmodium falciparum and vivax malaria.
This drug interaction study is intended to investigate if there is any interaction between Pyramax and the protease inhibitor ritonavir in healthy subjects using ritonavir as a probe substrate.
|Malaria||Drug: Ritonavir and pyronaridine/artesunate Drug: pyronaridine/artesunate||Phase 1|
|Study Design:||Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||Open-label, Randomised, Drug Interaction Study of Pyramax (Pyronaridine Artesunate) and the Protease Inhibitor Ritonavir in Healthy Volunteers|
- Pharmacokinetics [ Time Frame: Until Day 50 for Arm A and until Day 43 for Arm B ]
Pharmacokinetic parameters for pyronaridine, artesunate, DHA and ritonavir will be analysed.
Cmax, C trough, Tmax, AUC0-tau AUC0-t, AUC0-infinity and half-life will be calculated.
- Safety and clinical evaluations [ Time Frame: Throughout the study ]The incidence of adverse events and serious adverse events or clinically significant abnormal laboratory parameters will be assessed. Changes in vital signs, clinical signs and symptoms and physical examination will be described. The incidence and nature of clinically significant ECG abnormalities will be assessed.
|Study Start Date:||July 2010|
|Study Completion Date:||September 2010|
|Primary Completion Date:||August 2010 (Final data collection date for primary outcome measure)|
Active Comparator: Ritonavir plus Pyramax arm
Subjects in arm A will take 7 days of ritonavir followed by 3 days of ritonavir plus Pyramax followed by 7 days of ritonavir followed by 33 days follow-up period (40 days since last Pyramax dosing) and a study completion evaluation.
Drug: Ritonavir and pyronaridine/artesunate
100 mg ritonavir (one soft gelatin capsule twice per day over 17 days, the evening capsule on day 1 will be omitted) and pyronaridine/artesunate 180 mg/60 mg (3 to 4 tablets once per day according to weight for 3 days).
Active Comparator: Pyramax arm
Subjects in arm B will take a three day treatment course of Pyramax, followed by a follow up period of 40 days since last Pyramax dosing and a study completion evaluation.
Pyronaridine/artesunate 180 mg/60 mg (3 to 4 tablets once per day according to weight for 3 days).
This is an open label phase I, randomized, study to determine any drug interaction between Pyramax (pyronaridine/artesunate) and the protease inhibitor ritonavir in healthy volunteers. A total of 34 healthy volunteers (17 per treatment arm) will be enrolled in the study to have at least 30 (15 per treatment arm) completed, and they will be randomly assigned in a 1:1 ratio to receive either ritonavir (100 mg bid) for 17 days from Day 1-17 plus pyronaridine/artesunate (180:60 mg) once daily for 3 days from Day 8-10 in arm A or pyronaridine/artesunate (180:60 mg) alone once daily for 3 days from Day 1-3 in arm B.
Subjects will come to the clinic the evening before first dosing of Pyramax / ritonavir. If enrolled, and according to the treatment arm subjects will stay in the clinic and attend subsequent visits as follows:
- Inpatient day -1 (evening) to day 17
- Ambulatory clinic visit once daily (morning) on day 22, 29, 36, 43 and 50 (end of study visit)
- Inpatient day -1 (evening) to day 4 (morning),
- Ambulatory clinic visit once daily (morning) on Day 5, 6, 8, 15, 22, 29, 36, and 43.(end of study visit) The subjects will be evaluated for pharmacokinetic parameters and safety/tolerability.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01156389
|Covance Clinical Research Unit AG|
|Allschwil, Basel, Switzerland, 4123|
|Study Director:||Isabelle Borghini Fuhrer, PhD||Medicines for Malaria Venture|