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Pyronaridine/Artesunate -Ritonavir Drug Drug Interaction Study

This study has been completed.
Sponsor:
Collaborator:
Shin Poong Pharmaceuticals
Information provided by:
Medicines for Malaria Venture
ClinicalTrials.gov Identifier:
NCT01156389
First received: July 1, 2010
Last updated: March 18, 2011
Last verified: March 2011
  Purpose

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.


Condition Intervention Phase
Malaria
Drug: Ritonavir and pyronaridine/artesunate
Drug: pyronaridine/artesunate
Phase 1

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Pharmacokinetics Study
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

Resource links provided by NLM:


Further study details as provided by Medicines for Malaria Venture:

Primary Outcome Measures:
  • Pharmacokinetics [ Time Frame: Until Day 50 for Arm A and until Day 43 for Arm B ] [ Designated as safety issue: No ]

    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.



Secondary Outcome Measures:
  • Safety and clinical evaluations [ Time Frame: Throughout the study ] [ Designated as safety issue: Yes ]
    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.


Estimated Enrollment: 34
Study Start Date: July 2010
Study Completion Date: September 2010
Primary Completion Date: August 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.
Drug: pyronaridine/artesunate
Pyronaridine/artesunate 180 mg/60 mg (3 to 4 tablets once per day according to weight for 3 days).

Detailed Description:

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:

Arm A:

  • 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)

Arm B:

  • 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.
  Eligibility

Ages Eligible for Study:   18 Years to 55 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  1. Male or female subjects between the ages of 18 and 55 years with a body weight between 50 and 90 kg and a body mass index calculated using Quetelet's Index - weight (kg)/height2 (m2) between 18.5-30.0
  2. Signed and dated a written informed consent form (ICF) before undergoing any study related activities, including discontinuation of any prohibited medications
  3. Medically normal subjects with no significant abnormal findings at the screening physical examination as evaluated by the investigator
  4. Strictly normal values of ALT, AST and bilirubin and normal or abnormal and clinically insignificant results (if agreed by the Investigator and the Sponsor on a case by case evaluation) of the other blood and urine laboratory parameters at screening
  5. Female subjects of non-childbearing potential (i.e., physiologically incapable of becoming pregnant, including any female who was post-menopausal (i.e., one year without menses) or who has undergone sterilization (via hysterectomy or bilateral tubal ligation)
  6. Female subjects of childbearing potential with a negative urine pregnancy test at screening and a negative plasma pregnancy test prior to inclusion and who agreed to one of the following methods:

    • Double barrier method of contraception for 2 weeks before first study drug administration and throughout the entire study follow up period
    • Partner(s) who had undergone vasectomy and has been negative for sperm for at least 6 months
  7. The ability to understand the requirements of the study and willingness to comply with all study procedures

Exclusion Criteria:

  1. Known history or evidence of clinically significant disorders such as cardiovascular (including arrhythmia, acute QTc interval greater or equal to 450 mseconds), respiratory (including active tuberculosis), hepatic, renal, gastrointestinal, immunological (including active HIV-AIDS), neurological (including auditory), endocrine, infectious, malignancy, psychiatric or other clinical abnormality
  2. Known history of hypersensitivity, allergic or adverse reactions to pyronaridine or artesunate or other artemisinins or ritonavir
  3. Known active Hepatitis A IgM (HAV-IgM), Hepatitis B surface antigen (HBsAg) or Hepatitis C antibody (HCV Ab)
  4. Seropositive HIV antibody
  5. Previous participation in any clinical study with Pyramax
  6. Presence or recent history (last two years) of tobacco abuse (≥10 cigarettes/day)
  7. Known or suspected alcohol abuse or illicit drug use in the last 10 years before the study start or positive findings on urine drug screen
  8. Intake of grapefruit and grapefruit juice alcoholic beverages or caffeine-containing food or beverages, such as coffee, tea, chocolate, or cola, 48 hours before study drug administration
  9. Use of over-the-counter (OTC) medications, including vitamins, analgesics, or antacids, 1 week before the study start
  10. Use of prescription medications 14 days before the study start or required chronic use of any prescription medication
  11. Use of enzyme-altering agents (e.g., barbiturates, phenothiazines, cimetidine, etc.) within 30 days or 5 half lives, whichever the longer, before the study start
  12. Plasma donation 1 month before the study start
  13. Blood donation of 450 mL or more in the last 3 months before the study start
  14. Participation in any clinical study in last 2 months
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01156389

Locations
Switzerland
Covance Clinical Research Unit AG
Allschwil, Basel, Switzerland, 4123
Sponsors and Collaborators
Medicines for Malaria Venture
Shin Poong Pharmaceuticals
Investigators
Study Director: Isabelle Borghini Fuhrer, PhD Medicines for Malaria Venture
  More Information

No publications provided

Responsible Party: Carlo Lanza, Medicines for Malaria Venture
ClinicalTrials.gov Identifier: NCT01156389     History of Changes
Other Study ID Numbers: SP-C-010-10
Study First Received: July 1, 2010
Last Updated: March 18, 2011
Health Authority: Switzerland: Swissmedic

Keywords provided by Medicines for Malaria Venture:
malaria
artemisinin-based combination therapy

Additional relevant MeSH terms:
Malaria
Parasitic Diseases
Protozoan Infections
Artemisinins
Artesunate
Pyronaridine
Ritonavir
Amebicides
Anti-HIV Agents
Anti-Infective Agents
Anti-Retroviral Agents
Antimalarials
Antiparasitic Agents
Antiprotozoal Agents
Antiviral Agents
Enzyme Inhibitors
HIV Protease Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Protease Inhibitors
Therapeutic Uses

ClinicalTrials.gov processed this record on November 20, 2014