MalariaPhase 1NCT01868438
Relative Bioavailability of Pyronaridine-artesunate in Tablet and Granule Formulations in Healthy Volunteers
A Phase 1 study testing Pyronaridine-artesunate granules and Pyronaridine-artesunate tablets in people with Malaria, run by Medicines for Malaria Venture at 1 site in South Korea.
Trial 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. Read more about this study
- Who is it for?
- Ages 20 to 45 yearsHealthy volunteers can take part
- Conditions the study is for
- Malaria
- What is being tested?
- Pyronaridine-artesunate granules and Pyronaridine-artesunate tablets
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 60 participants
- Where
- 1 siteSouth Korea
- Study dates
- May 2013to Jan 2014
- Phase
- Phase 1
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 20 to 45 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- 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 :
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- 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.
Who cannot join
- 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)
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- 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
Trial locations and contacts
1 site in 1 country.
South Korea1 site
Dept. of Clinical Pharmacology and Therapeutics, Asan Medical Center, Univ. of Ulsan
Seoul
About this study
Official title: Phase 1, Open-label, Cross-over Study to Investigate the Relative Bioavailability of Pyramax (Pyronaridine-artesunate) in Tablet and Granule Formulations, in Healthy Volunteers
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.
Read the 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.
- Conditions
- Malaria
- Being tested
- Pyronaridine-artesunate granules, Pyronaridine-artesunate tablets
- Keywords
- Pyronaridine artesunate tablet, Pyronaridine artesunate granules, Pyramax tablet, Pyramax granules, Bioavailability, artemisinin based combination therapy (ACT)
- Medical subject headings
- Malaria
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Pyronaridine-artesunate granulesDrug
Also called Pyramax granules, PA granules
Pyronaridine-artesunate tabletsDrug
Also called Pyramax tablets, PA tablets
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: 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. Receives: Drug: Pyronaridine-artesunate granules; Drug: Pyronaridine-artesunate tablets |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: 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
Pharmacokinetic blood sampling for first or second intervention dose
Measured: 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
Measured: End of study (Day 103)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 Jun 2013 (estimated)
- Study startMay 2013
- Primary completionOct 2013
- Study completionJan 2014
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for MalariaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Enrolment
- 60 participants (actual)
Sponsor and investigators
- Lead sponsor
- Medicines for Malaria Venture
- Sponsor type
- University, hospital or other
- Collaborators
- Shin Poong Pharmaceutical Co. Ltd.
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01868438
- Sponsor's protocol ID
- SP-C-017-12
- Status last verified
- Dec 2023
- First submitted
- 30 May 2013
- Last updated
- 18 Dec 2023
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 18 Dec 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase 1, Open-label, Cross-over Study to Investigate the Relative Bioavailability of Pyramax (Pyronaridine-artesunate) in Tablet and Granule Formulations, in Healthy Volunteers
- ClinicalTrials.gov ID
- NCT01868438
- Acronym / sponsor ID
- SP-C-017-12
- Conditions
- Malaria
- Keywords
- Pyronaridine artesunate tablet, Pyronaridine artesunate granules, Pyramax tablet, Pyramax granules, Bioavailability, artemisinin based combination therapy (ACT)
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 60 participants (actual)
- Lead sponsor
- Medicines for Malaria VentureUniversity, hospital or other
- Collaborators
- Shin Poong Pharmaceutical Co. Ltd.
- Study start
- May 2013
- Primary completion
- Oct 2013 (actual)
- Study completion
- Jan 2014 (actual)
- First posted
- 4 Jun 2013 (estimated)
- Results
- Posted 18 Dec 2023
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Pyronaridine-artesunate granules (Period 1) | Active comparator | Drug: Pyronaridine-artesunate granules, Drug: Pyronaridine-artesunate tabletsPeriod 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. |
| Pyronaridine-artesunate tablets (Period1) | Active comparator | Drug: Pyronaridine-artesunate granules, Drug: Pyronaridine-artesunate tabletsPeriod 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. |
Who may qualify
- Ages
- 20 to 45 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (9 listed)
- 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)]
Key exclusion criteria (16 listed)
- 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)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Pyronaridine-artesunate granulesAlso: Pyramax granules, PA granules | Drug | Pyronaridine-artesunate granules (Period 1), Pyronaridine-artesunate tablets (Period1) |
| Pyronaridine-artesunate tabletsAlso: Pyramax tablets, PA tablets | Drug | Pyronaridine-artesunate granules (Period 1), Pyronaridine-artesunate tablets (Period1) |
Primary outcome
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
2 secondary outcomes
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)
Safety Evaluation - Summary of Adverse Events
Time frame: End of study (Day 103)
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 18 Dec 2023.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Pyronaridine-artesunate granules and Pyronaridine-artesunate tablets in people with Malaria, run by Medicines for Malaria Venture at 1 site in South Korea.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 9 inclusion and 16 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 18 Dec 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in South Korea. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 18 Dec 2023). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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)). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 18 Dec 2023.