Bioequivalence Trial of Pyronaridine Artesunate To-be-marketed Tablet to the Clinical Trial Reference Tablet

NCT00682630 | Completed Phase 1 Results DMC

• 1 other identifier: SP-C-009-07
• Study Type: interventional
• Target: 42
• Locations: 1 country
• Sites: 1

Brief Summary

The primary objective of this study is to determine the bioequivalence of the combination of pyronaridine and artesunate (180:60mg) to-be-marketed tablet to the clinical trial reference tablet administered as a single total dose of 720:240 mg in healthy adults. The secondary objective is to assess the safety of the two formulations.

Conditions

Malaria

Keywords

Malaria; anti-malarial; pyronaridine; pyronaridine artesunate (Pyramax); artemisinin based combination therapy (ACT)

Outcome Measures

Primary Outcomes (5)

• Pyronaridine Pharmacokinetics: Tmax, Half-life

  Tmax: time to maximum concentration Half-life: computed as ln (2)/kel

  Sampling performed at predose at 0 h and at, 0.5, 1, 1.5, 2.5, 4, 6, 8, 12, 24, 48, 72 h and on Day 5, 7, 14, 21, 28, 35, 42 for each period

• Pyronaridine (PP), Artesunate (AS), Dihydroartemisinin (DHA) Pharmacokinetics: Cmax

  Cmax: maximum peak observed concentration

  PP sampling performed at predose at at 0 h and at, 0.5, 1, 1.5, 2.5, 4, 6, 8, 12, 24, 48, 72 h and on Day 5, 7, 14, 21, 28, 35, 42 for each period AS, DHA sampling performed at predose at 0 h and at 0.25, 0.5, 1, 1.5, 2.5, 4, 6, 8, 12 h for each period

• Artesunate (AS) and Dihydroartemisinin (DHA) Pharmacokinetics: Tmax, Half-life

  Tmax: time to maximum concentration Half-life: computed as ln (2)/kel

  Sampling performed at predose at 0 h and at 0.25, 0.5, 1, 1.5, 2.5, 4, 6, 8, 12 h for each period

• Pyronaridine Pharmacokinetics: AUC0-last, AUC0-∞

  AUC0-last: Area under the concentration-time curve from time 0 (0 h) through the last quantifiable concentration time (LQCT), where LQCT is the time at which the last sample with a quantifiable concentration was drawn AUC0-∞: Area under the concentration-time curve from time 0 (0 h) to infinity, computed using the linear trapezoidal rule as AUClast + CLQCT / Kel

  Sampling performed at predose at 0 h and at, 0.5, 1, 1.5, 2.5, 4, 6, 8, 12, 24, 48, 72 h and on Day 5, 7, 14, 21, 28, 35, 42 for each period

• Artesunate (AS) and Dihydroartemisinin (DHA): AUC0-last, AUC0-∞

  AUC0-last: Area under the concentration-time curve from time 0 (0 h) through the last quantifiable concentration time (LQCT), where LQCT is the time at which the last sample with a quantifiable concentration was drawn AUC0-∞: Area under the concentration-time curve from time 0 (0 h) to infinity, computed using the linear trapezoidal rule as AUClast + CLQCT / Kel

  Sampling performed at predose at 0 h and at 0.25, 0.5, 1, 1.5, 2.5, 4, 6, 8, 12 h for each period

Study Arms (2)

Clinical Trial Reference Tablets first, then To-Be-Marketed Tablets

EXPERIMENTAL

Participants first received clinical trial reference 720:240 mg tablets on Day 0. After a washout period of 43 days, they then received to-be-marketed 720:240 mg tablets on Day 43, with a follow-up period of 42 days.

Drug: pyronaridine artesunate clinical trial reference tablets; Drug: pyronaridine artesunate to-be-marketed tablets

To-Be-Marketed Tablets first, then Clinical Trial Reference Tablets

EXPERIMENTAL

Participants first received to-be-marketed 720:240 mg tablets on Day 0. After a washout period of 43 days, they then received clinical trial reference 720:240 mg tablets on Day 43, with a follow-up period of 42 days.

Drug: pyronaridine artesunate clinical trial reference tablets; Drug: pyronaridine artesunate to-be-marketed tablets

Interventions

pyronaridine artesunate clinical trial reference tablets DRUG

Single total oral dose of 720:240 mg (4 tablets of 180:60 mg)

Also known as: Pyramax, PA

Clinical Trial Reference Tablets first, then To-Be-Marketed Tablets; To-Be-Marketed Tablets first, then Clinical Trial Reference Tablets

pyronaridine artesunate to-be-marketed tablets DRUG

Single total oral dose of 720:240 mg (4 tablets of 180:60 mg)

Also known as: Pyramax, PA

Clinical Trial Reference Tablets first, then To-Be-Marketed Tablets; To-Be-Marketed Tablets first, then Clinical Trial Reference Tablets

Eligibility Criteria

• Age: 18 Years - 45 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 45 years with a body weight between 55 and 75 kg and a body mass index using Quetelet's Index - weight (kg)/height2 (m2) between 18-28
• Signed and dated written informed consent form 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 clinical investigator
• Normal (or abnormal and clinically insignificant) laboratory values 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)
• Female subjects of childbearing potential with a negative urine pregnancy test at screening and who agreed to one of the accepted forms of contraception
• 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 abnormality (including head trauma)
• Known history of hypersensitivity, allergic or adverse reactions to pyronaridine or artesunate or other artemisinins
• Known active Hepatitis A IgM (HAV-IgM), Hepatitis B surface antigen (HBsAg) or Hepatitis C antibody (HCV Ab)
• Known seropositive HIV antibody
• Previous participation in any clinical trial with pyronaridine artesunate
• Presence or recent history (last two years) of tobacco abuse (≥10 cigarettes/day)
• Known or suspected alcohol abuse or illicit drug use 10 years before the study start or positive findings on urine drug screen
• Intake of alcoholic beverages or caffeine-containing food or beverages, such as coffee, tea, chocolate, or cola, 24 h before study drug administration
• Use of over-the-counter (OTC) medications, including vitamins, analgesics, or antacids, 72 h 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.) 30 days before the study start
• Plasma donation 3 months before the study start
• Blood donation of 500 mL or more 3 months before the study start
• Participation in an investigational drug study 3 months before randomization

Sponsors & Collaborators

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

Study Sites (1)

Cross Research S.A., Phase I Unit

Arzo, 6864, Switzerland

Location

MeSH Terms

Conditions

Malaria

Interventions

pyronaridine tetraphosphate, artesunate drug combination

Condition Hierarchy (Ancestors)

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

Results Point of Contact

• Title: Jansik 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: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 19, 2008
• First Posted: May 22, 2008
• Study Start: September 1, 2007
• Primary Completion: July 1, 2008
• Study Completion: September 1, 2008
• Last Updated: February 3, 2023
• Results First Posted: February 3, 2023

Record last verified: 2023-02

Locations

CH (1)