- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT01868438
Relative Bioavailability of Pyronaridine-artesunate in Tablet and Granule Formulations in Healthy Volunteers
Phase 1, Open-label, Cross-over Study to Investigate the Relative Bioavailability of Pyramax (Pyronaridine-artesunate) in Tablet and Granule Formulations, in Healthy Volunteers
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
This is a Phase I, single centre, open-label, randomised, two-way cross-over study in healthy volunteers to compare the bioavailability of two formulations of pyronaridine-artesunate, in tablet and in granule formulation. The study population will include 60 healthy volunteers, comprising male and female adults aged 20 to 45 years inclusive.
The volunteers will be randomised equally on Day -1 to one of two sequences: Sequence 1 (tablets in Period 1, granules in Period 2), or Sequence 2 (granules in Period 1, tablets in Period 2). The periods will be separated by a 60-day wash-out period. Each of the two pyronaridine-artesunate formulations will be administered as a single dose of either 180:60 mg pyronaridine-artesunate tablets (3 tablets) or 60:20 mg pyronaridine-artesunate granules (9 sachets). The total dose of each formulation administered is 540:180 mg pyronaridine-artesunate.
The study duration from the first study drug administration (Day 1) through to the last follow-up will be approximately 103 days. Screening is to be performed within 28 days before Day 1. Adverse events will be monitored throughout the study (and to resolution if necessary) to assess the general safety and tolerability of the treatments.
Study Type
Enrollment (Actual)
Phase
- Phase 1
Contacts and Locations
Study Locations
-
-
-
Seoul, Korea, Republic of
- Dept. of Clinical Pharmacology and Therapeutics, Asan Medical Center, Univ. of Ulsan
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Description
Inclusion Criteria:
- 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.
Exclusion Criteria:
- 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
- Participation AND having had drug administration in any other clinical study within the 60 days before start of study drug administration
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Crossover Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Active Comparator: Pyronaridine-artesunate granules (Period 1)
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. |
Other Names:
Other Names:
|
Active Comparator: Pyronaridine-artesunate tablets (Period1)
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. |
Other Names:
Other Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Area Under the Concentration-time Curve From Hour 0 to the Last Sampling Point (AUC 0-t) for Pyronaridine and Dihydroartemisinin (DHA)
Time Frame: 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)
|
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 Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Tmax and Terminal Half Life for Pyronaridine, Artesunate and DHA
Time Frame: 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)
|
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)
|
Safety Evaluation - Summary of Adverse Events
Time Frame: End of study (Day 103)
|
End of study (Day 103)
|
Collaborators and Investigators
Sponsor
Collaborators
Study record dates
Study Major Dates
Study Start
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimated)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
- Infections
- Vector Borne Diseases
- Parasitic Diseases
- Protozoan Infections
- Malaria
- Anti-Infective Agents
- Antiviral Agents
- Antineoplastic Agents
- Antiprotozoal Agents
- Antiparasitic Agents
- Antimalarials
- Anthelmintics
- Schistosomicides
- Antiplatyhelmintic Agents
- Artesunate
- Pyronaridine
- Pyronaridine tetraphosphate, artesunate drug combination
Other Study ID Numbers
- SP-C-017-12
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
Clinical Trials on Malaria
-
University of California, San FranciscoCenters for Disease Control and Prevention; University of Massachusetts, Amherst and other collaboratorsRecruitingPlasmodium Falciparum Malaria | Plasmodium Vivax MalariaLao People's Democratic Republic
-
Menzies School of Health ResearchInternational Centre for Diarrhoeal Disease Research, Bangladesh; Addis Ababa... and other collaboratorsCompletedMalaria | Vivax Malaria | Falciparum MalariaEthiopia, Bangladesh, Indonesia
-
University of OxfordWellcome Trust; Ministry of public Health AfghanistanCompletedVivax Malaria | Uncomplicated Falciparum MalariaAfghanistan
-
Medicines for Malaria VentureAsociacion Civil Selva AmazonicaCompletedPlasmodium Falciparum Malaria | Plasmodium Vivax MalariaPeru
-
Gadjah Mada UniversityMenzies School of Health Research; Eijkman Institute for Molecular Biology; Timika...Completed
-
Menzies School of Health ResearchNational Health and Medical Research Council, Australia; Wellcome Trust; National...CompletedVivax Malaria | Falciparum MalariaIndonesia
-
London School of Hygiene and Tropical MedicineWorld Health Organization; United Nations High Commissioner for Refugees; HealthNet... and other collaboratorsCompletedMalaria | Vivax Malaria | Falciparum MalariaPakistan
-
Menzies School of Health ResearchNational Health and Medical Research Council, Australia; Wellcome Trust; National...CompletedVivax Malaria | Falciparum MalariaIndonesia
-
University of IbadanShin Poong Pharm Co Ltd 161 yoksam-ro, Gangnam-Gu Seoul 135-925, Korea; Institute...CompletedPlasmodium Falciparum Malaria | Uncomplicated Malaria | Malaria FeverNigeria
-
Research Institute for Tropical Medicine, PhilippinesWorld Health OrganizationCompletedTES of Artemether-lumefantrine for Pf and Chloroquine for Pv in the Philippines From 2013-2014 (TES)Malaria | Vivax Malaria | Falciparum Malaria | Malaria Recrudescence
Clinical Trials on Pyronaridine-artesunate tablets
-
Merck Healthcare KGaA, Darmstadt, Germany, an affiliate...RecruitingAcute MalariaBurkina Faso, Gabon, Mozambique, Uganda
-
Shin Poong Pharmaceutical Co. Ltd.Recruiting
-
University of OxfordCompleted
-
Medicines for Malaria VentureShin Poong PharmaceuticalsCompletedFalciparum MalariaCambodia, India, Thailand, Burkina Faso, Côte D'Ivoire, Tanzania, Vietnam
-
Medicines for Malaria VentureShin Poong PharmaceuticalsCompleted
-
Centre de Recherche Médicale de LambarénéInstitute of Tropical Medicine, University of TuebingenNot yet recruitingSevere Malarial TreatmentGabon
-
Medicines for Malaria VentureShin Poong Pharmaceutical Co. Ltd.CompletedPlasmodium Falciparum MalariaCambodia, Gambia, Indonesia, Senegal, Thailand, Uganda
-
Shin Poong Pharmaceutical Co. Ltd.CompletedCOVID-19Korea, Republic of
-
University of OxfordNCHADS - Ministry of Health of CambodiaCompletedEfficacy and Safety of Pyronaridine-artesunate for the Treatment in Uncomplicated Falciparum MalariaMalaria, FalciparumCambodia
-
Shin Poong Pharmaceutical Co. Ltd.CompletedPilot Clinical Trial to Explore Efficacy and Safety of Pyramax in Mild to Moderate COVID-19 PatientsCOVID-19Korea, Republic of