Relative Bioavailability of Pyronaridine-artesunate in Tablet and Granule Formulations in Healthy Volunteers

NCT01868438 | Completed Phase 1 Results

• 1 other identifier: SP-C-017-12
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 1

Brief Summary

The primary objective of this study is to compare the bioavailability of two formulations (tablets and granules for dispersion) of the antimalarial drug pyronaridine-artesunate \[3:1\] (Pyramax, PA) in healthy adults. The secondary objective is to compare the safety of the two PA formulations and liver function test changes following the first and second administrations.

Conditions

Malaria

Keywords

Pyronaridine artesunate tablet; Pyronaridine artesunate granules; Pyramax tablet; Pyramax granules; Bioavailability; artemisinin based combination therapy (ACT)

Outcome Measures

Primary Outcomes (1)

• Area Under the Concentration-time Curve From Hour 0 to the Last Sampling Point (AUC 0-t) for Pyronaridine and Dihydroartemisinin (DHA)

  Pharmacokinetic blood sampling for first or second intervention dose

  First intervention: Day 1 pre-dose to Day 43 visit (D1, 2, 3, 4, 6, 8, 15, 22, 29, 36, 43) ; second intervention: Day 61 pre-dose to Day 103 visit (D61, 62, 63, 64, 66, 68, 75, 82, 89, 96, 103)

Secondary Outcomes (2)

• Tmax and Terminal Half Life for Pyronaridine, Artesunate and DHA

  First intervention: Day 1 pre-dose to Day 43 visit (D1, 2, 3, 4, 6, 8, 15, 22, 29, 36, 43) ; second intervention: Day 61 pre-dose to Day 103 visit (D61, 62, 63, 64, 66, 68, 75, 82, 89, 96, 103)

• Safety Evaluation - Summary of Adverse Events

  End of study (Day 103)

Study Arms (2)

Pyronaridine-artesunate granules (Period 1)

ACTIVE COMPARATOR

Period 1: single administration of pyronaridine-artesunate granules: total dose 540mg pyronaridine + 180mg artesunate. Period 2: cross-over to single administration of pyronaridine-artesunate tablets: total dose 540mg pyronaridine + 180mg artesunate.

Drug: Pyronaridine-artesunate granules; Drug: Pyronaridine-artesunate tablets

Pyronaridine-artesunate tablets (Period1)

ACTIVE COMPARATOR

Period 1: single administration of pyronaridine-artesunate tablets: total dose 540mg pyronaridine + 180mg artesunate. Period 2: cross-over to single administration of pyronaridine-artesunate granules: total dose 540mg pyronaridine + 180mg artesunate.

Drug: Pyronaridine-artesunate granules; Drug: Pyronaridine-artesunate tablets

Interventions

Pyronaridine-artesunate granules DRUG

Also known as: Pyramax granules, PA granules

Pyronaridine-artesunate granules (Period 1); Pyronaridine-artesunate tablets (Period1)

Pyronaridine-artesunate tablets DRUG

Also known as: Pyramax tablets, PA tablets

Pyronaridine-artesunate granules (Period 1); Pyronaridine-artesunate tablets (Period1)

Eligibility Criteria

• Age: 20 Years - 45 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Healthy male and/or female subjects between the ages of 20 and 45 years, inclusive. (Healthy is defined as no clinically relevant abnormalities identified by a detailed medical history, full physical examination, including blood pressure and pulse rate measurement, 12-lead ECG and clinical laboratory tests)
• Weight between 50 kg and 80 kg and Body Mass Index (BMI) calculated using Quetelet's Index - weight(kg)/height (m2) between 18.5 to 27 kg/m2;
• An informed consent document signed and dated by the subject (prior to screening and any study activities, including discontinuation of any prohibited medications)
• Strictly normal values of alanine aminotransferase(ALT), aspartate aminotransferase (AST), and bilirubin, and normal or abnormal but clinically insignificant results of the other blood and urine laboratory parameters at screening.
• Female subjects of non-childbearing potential \[i.e., physiologically incapable of becoming pregnant, including any female who was post-menopausal (i.e., one year without menses) or who has undergone sterilization (via hysterectomy or bilateral tubal ligation)\]
• Female subjects of childbearing potential with a negative urine pregnancy test at screening, and a negative pregnancy blood test on admission, and who :
• agree to double barrier method of contraception for 4 weeks before first study drug administration and throughout the entire study follow up period, or
• whose partner has undergone vasectomy and has been negative for sperm for at least 6 months
• Subjects who are willing and able to comply with scheduled visits, treatment plan, laboratory tests, and other study procedures.

You may not qualify if:

• Known history or evidence of clinically significant disorders such as cardiovascular (including arrhythmia, acute corrected QT interval (QTc) greater or equal to 450 milliseconds), 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)
• Seropositive HIV antibody, seropositive syphilis \[Syphilis reagin test (+)\]
• Previous exposure to pyronaridine-artesunate (Pyramax)
• Present or recent history (last two years) of tobacco abuse (≥10 cigarettes/day)
• Known or suspected alcohol abuse or illicit drug use up to 5 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, 48 hours before study drug administration
• Intake of grapefruit, Seville oranges or products containing these from 72 hours before the start of study drug administration
• Gilbert's disease
• Use of over-the-counter (OTC) medications, including vitamins, analgesics, antipyretics or antacids within 7 days before study drug administration
• Use of prescription medications within 14 days before the start of study drug administration or required chronic use of any prescription medication
• Use of enzyme-altering agents (e.g. barbiturates, phenothiazines, cimetidine, etc.) within 30 days before the start of study drug administration
• Plasma donation within 60 days before the start of study drug administration
• Blood donation of 500 mL or more within 60 days before the start of study drug administration

Sponsors & Collaborators

• Medicines for Malaria Venture: lead
• Shin Poong Pharmaceutical Co. Ltd.: collaborator

Study Sites (1)

Dept. of Clinical Pharmacology and Therapeutics, Asan Medical Center, Univ. of Ulsan

Seoul, South Korea

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: Stephan Duparc
• Organization: Medicines for Malaria Venture

duparcs@mmv.org

+41 22 799 4070

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 30, 2013
• First Posted: June 4, 2013
• Study Start: May 1, 2013
• Primary Completion: October 1, 2013
• Study Completion: January 1, 2014
• Last Updated: December 18, 2023
• Results First Posted: December 18, 2023

Record last verified: 2023-12

Locations

KR (1)