Pyronaridine Artesunate-Ritonavir Drug-drug Interaction Study

NCT01156389 | Completed Phase 1 Results

• 1 other identifier: SP-C-010-10
• Study Type: interventional
• Target: 34
• Locations: 1 country
• Sites: 1

Brief Summary

The primary objective of the study is to determine any drug interaction between the antimalarial Pyramax (pyronaridine artesunate) and the protease inhibitor ritonavir in healthy subjects. The secondary objective of the study is to assess further the safety of Pyramax in this setting.

Conditions

Malaria

Keywords

malaria; artemisinin-based combination therapy (ACT); antimalarial; pyronaridine artesunate (Pyramax)

Outcome Measures

Primary Outcomes (3)

• Pharmacokinetics Analysis: Half-life, Tmax

  Half-life and Tmax for pyronaridine, artesunate, DHA: Tmax - time of the maximum observed concentration Half life - apparent plasma terminal elimination half-life, computed as ln (2)/Kel Blood samples for pyronaridine analysis were taken at Day 8 predose, Day 9 predose, Day 10 predose and 0.5, 1, 1.5, 2, 3, 4, 6, 8 and 12 hours postdose, and Days 11,12, 13, 15, 22, 29, 36 and 43. Blood samples for artesunate / DHA analysis were taken at Day 10 predose, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8 and 12 hours postdose.

  Until Day 50 for Arm A and until Day 43 for Arm B

• Pharmacokinetics Analysis: Cmax

  Cmax for pyronaridine, artesunate, DHA: Cmax - maximum peak observed concentration Blood samples for pyronaridine analysis were taken at Day 8 predose, Day 9 predose, Day 10 predose and 0.5, 1, 1.5, 2, 3, 4, 6, 8 and 12 hours postdose, and Days 11,12, 13, 15, 22, 29, 36 and 43. Blood samples for artesunate / DHA analysis were taken at Day 10 predose, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8 and 12 hours postdose.

  Until Day 50 for Arm A and until Day 43 for Arm B

• Pharmacokinetics Analysis: AUC0-tau, AUC0-∞

  AUC0-tau, AUC0-∞ for pyronaridine, artesunate, DHA: AUC0-tau - area under the concentration-time curve from Hour 0 to the scheduled time of the next dose AUC0-∞ - area under the concentration-time curve from Hour 0 through the last quantifiable concentration time Blood samples for pyronaridine analysis were taken at Day 8 predose, Day 9 predose, Day 10 predose and 0.5, 1, 1.5, 2, 3, 4, 6, 8 and 12 hours postdose, and Days 11,12, 13, 15, 22, 29, 36 and 43. Blood samples for artesunate / DHA analysis were taken at Day 10 predose, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8 and 12 hours postdose.

  Until Day 50 for Arm A and until Day 43 for Arm B

Secondary Outcomes (1)

• Summary of Treatment Emergent Adverse Events

  Throughout the study

Study Arms (2)

Arm A Ritonavir plus Pyramax

ACTIVE COMPARATOR

7 days of ritonavir followed by 3 days of ritonavir plus Pyramax followed by 7 days of ritonavir followed by a 33 day follow-up period (40 days since last Pyramax dosing) and a study completion evaluation.

Drug: Ritonavir and Pyramax

Arm B Pyramax

ACTIVE COMPARATOR

3 day treatment course of Pyramax, followed by a follow up period of 40 days since last Pyramax dosing and a study completion evaluation.

Drug: Pyramax

Interventions

Ritonavir and Pyramax DRUG

100 mg ritonavir (one soft gelatin capsule twice per day over 17 days, the evening capsule on day 1 will be omitted) and Pyramax (pyronaridine/artesunate) 180:60 mg (3 to 4 tablets once per day according to weight for 3 days).

Arm A Ritonavir plus Pyramax

Pyramax DRUG

Pyramax (pyronaridine/artesunate) 180:60 mg (3 to 4 tablets once per day according to weight for 3 days).

Also known as: pyronaridine artesunate, PA

Arm B Pyramax

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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)/height (m2) between 18.5-30.0
• Signed and dated a written informed consent form (ICF) before undergoing any study related activities, including discontinuation of any prohibited medications
• Medically normal subjects with no significant abnormal findings at the screening physical examination as evaluated by the investigator
• 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
• 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)
• 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
• The ability to understand the requirements of the study and willingness to comply with all study procedures

You may not qualify if:

• 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
• Known history of hypersensitivity, allergic or adverse reactions to pyronaridine or artesunate or other artemisinins or ritonavir
• Known active Hepatitis A IgM (HAV-IgM), Hepatitis B surface antigen (HBsAg) or Hepatitis C antibody (HCV Ab)
• Seropositive HIV antibody
• Previous participation in any clinical study with Pyramax
• Presence or recent history (last two years) of tobacco abuse (≥10 cigarettes/day)
• 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
• 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
• Use of over-the-counter (OTC) medications, including vitamins, analgesics, or antacids, 1 week before the study start
• Use of prescription medications 14 days before the study start or required chronic use of any prescription medication
• 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
• Plasma donation 1 month before the study start
• Blood donation of 450 mL or more in the last 3 months before the study start
• Participation in any clinical study in last 2 months

Sponsors & Collaborators

• Medicines for Malaria Venture: lead
• Shin Poong Pharmaceuticals: collaborator

Study Sites (1)

Covance Clinical Research Unit AG

Allschwil, Basel, 4123, Switzerland

Location

MeSH Terms

Conditions

Malaria

Interventions

Ritonavir; pyronaridine tetraphosphate, artesunate drug combination

Condition Hierarchy (Ancestors)

Protozoan Infections; Parasitic Diseases; Infections; Mosquito-Borne Diseases; Vector Borne Diseases

Intervention Hierarchy (Ancestors)

Thiazoles; Sulfur Compounds; Organic Chemicals; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Results Point of Contact

• Title: Jangsik Shin
• Organization: Shin Poong Pharmaceutical Co., Ltd.

jsshin@shinpoong.co.kr

+82-2-2189-3468

Study Officials

• Isabelle Borghini Fuhrer, PhD

  Medicines for Malaria Venture

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 1, 2010
• First Posted: July 2, 2010
• Study Start: July 1, 2010
• Primary Completion: August 1, 2010
• Study Completion: September 1, 2010
• Last Updated: February 3, 2023
• Results First Posted: February 3, 2023

Record last verified: 2023-02

Locations

CH (1)