MalariaPhase 1NCT00682630
Bioequivalence Trial of Pyronaridine Artesunate To-be-marketed Tablet to the Clinical Trial Reference Tablet
A Phase 1 study testing pyronaridine artesunate clinical trial reference tablets and pyronaridine artesunate to-be-marketed tablets in people with Malaria, run by Medicines for Malaria Venture at 1 site in Switzerland.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 45 yearsHealthy volunteers can take part
- Conditions the study is for
- Malaria
- What is being tested?
- pyronaridine artesunate clinical trial reference tablets and pyronaridine artesunate to-be-marketed tablets
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 42 participants
- Where
- 1 siteSwitzerland
- Study dates
- Sep 2007to Sep 2008
- 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 18 to 45 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- 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
Who cannot join
- 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)
Show all 14Show fewer
- 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
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Phase I, Randomized, Single Dose, Bioequivalence Trial of Pyronaridine Artesunate To-be-marketed Tablet to the Clinical Trial Reference Tablet
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.
Read the detailed description
This is a phase I, randomized, single dose, two-way cross-over study of two tablet formulations of the combination of pyronaridine and artesunate (180:60 mg). The study will include 42 healthy participants, comprising male and female adults.
Participants will be randomized to receive either reference tablet formulation or to-be-marketed formulation first and then will be crossed over to receive the opposite Intervention. The study will consist of two single dose treatments of 720:240 mg tablets, separated by a washout period of 43 days.
Participants will go to the clinic the evening before dosing (dosing days were Day 0 for period 1 and Day 43 for period 2) under fasting condition and remain in the hospital for 24 hours after receiving dosing.
Participants will stay in the hospital for 24 hours after their arrival at the clinic. They will return to the clinic at Day 2, 3, 5, 7, 14, 21, 28, 35 and 42 on an ambulatory basis. At Day 43, the dosing for the second sequence will start and a similar schedule of visits will be followed. Each participant will be followed-up for an additional 42 days after the start of the second study period, until the final visit (Day 85). The total duration of participation is 85 days plus a maximum of 2 weeks screening period.
- Conditions
- Malaria
- Being tested
- pyronaridine artesunate clinical trial reference tablets, pyronaridine artesunate to-be-marketed tablets
- Keywords
- Malaria, anti-malarial, pyronaridine, pyronaridine artesunate (Pyramax), 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 clinical trial reference tabletsDrug
Also called Pyramax, PA
Single total oral dose of 720:240 mg (4 tablets of 180:60 mg)
pyronaridine artesunate to-be-marketed tabletsDrug
Also called Pyramax, PA
Single total oral dose of 720:240 mg (4 tablets of 180:60 mg)
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: 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. Receives: Drug: pyronaridine artesunate clinical trial reference tablets; Drug: pyronaridine artesunate to-be-marketed tablets |
What is being measured
The primary outcome is the main question the study is designed to answer.
Pyronaridine Pharmacokinetics: Tmax, Half-life
Tmax: time to maximum concentration Half-life: computed as ln (2)/kel
Measured: 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
Measured: 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
Measured: 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
Measured: 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
Measured: 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
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 May 2008 (estimated)
- Study startSep 2007
- Primary completionJul 2008
- Study completionSep 2008
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
- 42 participants (actual)
Sponsor and investigators
- Lead sponsor
- Medicines for Malaria Venture
- Sponsor type
- University, hospital or other
- Collaborators
- Shin Poong Pharmaceuticals
- Responsible party
- Sponsor
- Investigators
- Isabelle Borghini Fuhrer, PhD, Study director, Medicines for Malaria Venture
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00682630
- Sponsor's protocol ID
- SP-C-009-07
- Status last verified
- Feb 2023
- First submitted
- 19 May 2008
- Last updated
- 3 Feb 2023
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 3 Feb 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase I, Randomized, Single Dose, Bioequivalence Trial of Pyronaridine Artesunate To-be-marketed Tablet to the Clinical Trial Reference Tablet
- ClinicalTrials.gov ID
- NCT00682630
- Acronym / sponsor ID
- SP-C-009-07
- Conditions
- Malaria
- Keywords
- Malaria, anti-malarial, pyronaridine, pyronaridine artesunate (Pyramax), artemisinin based combination therapy (ACT)
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 42 participants (actual)
- Lead sponsor
- Medicines for Malaria VentureUniversity, hospital or other
- Collaborators
- Shin Poong Pharmaceuticals
- Study start
- Sep 2007
- Primary completion
- Jul 2008 (actual)
- Study completion
- Sep 2008 (actual)
- First posted
- 22 May 2008 (estimated)
- Results
- Posted 3 Feb 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 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.
Detailed description
This is a phase I, randomized, single dose, two-way cross-over study of two tablet formulations of the combination of pyronaridine and artesunate (180:60 mg). The study will include 42 healthy participants, comprising male and female adults.
Participants will be randomized to receive either reference tablet formulation or to-be-marketed formulation first and then will be crossed over to receive the opposite Intervention. The study will consist of two single dose treatments of 720:240 mg tablets, separated by a washout period of 43 days.
Participants will go to the clinic the evening before dosing (dosing days were Day 0 for period 1 and Day 43 for period 2) under fasting condition and remain in the hospital for 24 hours after receiving dosing.
Participants will stay in the hospital for 24 hours after their arrival at the clinic. They will return to the clinic at Day 2, 3, 5, 7, 14, 21, 28, 35 and 42 on an ambulatory basis. At Day 43, the dosing for the second sequence will start and a similar schedule of visits will be followed. Each participant will be followed-up for an additional 42 days after the start of the second study period, until the final visit (Day 85). The total duration of participation is 85 days plus a maximum of 2 weeks screening period.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Clinical Trial Reference Tablets first, then To-Be-Marketed Tablets | Experimental | Drug: pyronaridine artesunate clinical trial reference tablets, Drug: pyronaridine artesunate to-be-marketed tabletsParticipants 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. |
| To-Be-Marketed Tablets first, then Clinical Trial Reference Tablets | Experimental | Drug: pyronaridine artesunate clinical trial reference tablets, Drug: pyronaridine artesunate to-be-marketed tabletsParticipants 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. |
Who may qualify
- Ages
- 18 to 45 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (7 listed)
- 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)
Key exclusion criteria (14 listed)
- 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
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 clinical trial reference tabletsAlso: Pyramax, PASingle total oral dose of 720:240 mg (4 tablets of 180:60 mg) | Drug | 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 tabletsAlso: Pyramax, PASingle total oral dose of 720:240 mg (4 tablets of 180:60 mg) | Drug | Clinical Trial Reference Tablets first, then To-Be-Marketed Tablets, To-Be-Marketed Tablets first, then Clinical Trial Reference Tablets |
Primary outcome
Pyronaridine Pharmacokinetics: Tmax, Half-life
Time frame: 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
Tmax: time to maximum concentration Half-life: computed as ln (2)/kel
Pyronaridine (PP), Artesunate (AS), Dihydroartemisinin (DHA) Pharmacokinetics: Cmax
Time frame: 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
Cmax: maximum peak observed concentration
Artesunate (AS) and Dihydroartemisinin (DHA) Pharmacokinetics: Tmax, Half-life
Time frame: 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
Tmax: time to maximum concentration Half-life: computed as ln (2)/kel
Pyronaridine Pharmacokinetics: AUC0-last, AUC0-∞
Time frame: 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
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
Artesunate (AS) and Dihydroartemisinin (DHA): AUC0-last, AUC0-∞
Time frame: 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
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
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 3 Feb 2023.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Related trials for Malaria
Active, not recruitingObservational study
Trajectories and Mechanisms of Recovery From Malaria: An Observational Study
Malaria
Not yet recruiting
Positron Emission Tomography and Organ-Specific Changes in Participants Co-Enrolled in NIH Studies of Plasmodium Vivax Controlled Human Malaria Infection
Healthy Volunteer, Malaria
Recruiting
The Effects of Iron Treatment on Vaccine Immunogenicity in Kenyan Infants With Iron Deficiency
Iron Deficiencies
RecruitingObservational study
Host and Parasite Factors That Influence Susceptibility to Malaria Infection and Disease During Pregnancy and Early Childhood in Ouelessebougou and Bamako, Mali
Malaria
RecruitingPhase 1
Safety, Tolerability and Efficacy of PfSPZ-LARC2 Vaccine Against CHMI in Malaria-Naïve Adults
Malaria Falciparum
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.
Isabelle Borghini Fuhrer, PhD study director
Medicines for Malaria Venture
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 clinical trial reference tablets and pyronaridine artesunate to-be-marketed tablets in people with Malaria, run by Medicines for Malaria Venture at 1 site in Switzerland.
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 7 inclusion and 14 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 3 Feb 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 Switzerland. 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 3 Feb 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?
Pyronaridine Pharmacokinetics: Tmax, Half-life (time frame: 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). The study lists 5 primary outcomes in all. 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 3 Feb 2023.