CompletedNCT00682630Updated Feb 3, 2023Results posted

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

A Phase 1 interventional study of pyronaridine artesunate clinical trial reference tablets and pyronaridine artesunate to-be-marketed tablets in Malaria, sponsored by Medicines for Malaria Venture. Completed at 1 site in Switzerland. Open to participants aged 18 Years to 45 Years, including healthy volunteers. Per ClinicalTrials.gov, last updated 2023-02-03.

Sponsored by Medicines for Malaria Venture · Phase 1, Interventional, and Treatment

Phase: Phase 1
Study type: Interventional
Enrollment: 42
Allocation: Randomized
Ages: 18 Years to 45 Years
Sex: All

Study 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.

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 studied

Malaria

Browse trials for

Malaria 1,299

Keywords

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

In context

Malaria

1,299 studies on the registry are indexed under Malaria; 86 are open to participants now.

This study's enrollment of 42 is below the median of 220 across 1,027 interventional studies indexed under Malaria.

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Lead sponsor

Medicines for Malaria Venture is the lead sponsor of 66 studies on the registry; 3 are open to participants now.

Counted across the registry records on this site, refreshed daily.

Who can participate

Ages eligible: 18 Years to 45 Years
Sexes eligible: All
Accepts healthy volunteers: Yes

Inclusion criteria

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

Exclusion criteria

Exclusion Criteria:

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

Study design

Phase: Phase 1
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Crossover assignment
Masking: None (open label)
Enrollment: 42 participants (actual)

Study arms

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

Drugpyronaridine artesunate clinical trial reference tablets
Single total oral dose of 720:240 mg (4 tablets of 180:60 mg)
Also known as: Pyramax, PA
Drugpyronaridine artesunate to-be-marketed tablets
Single total oral dose of 720:240 mg (4 tablets of 180:60 mg)
Also known as: Pyramax, PA

What researchers measure

Primary outcomes

Pyronaridine Pharmacokinetics: Tmax, Half-life
Tmax: time to maximum concentration Half-life: computed as ln (2)/kel
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
Pyronaridine (PP), Artesunate (AS), Dihydroartemisinin (DHA) Pharmacokinetics: Cmax
Cmax: maximum peak observed concentration
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
Artesunate (AS) and Dihydroartemisinin (DHA) Pharmacokinetics: Tmax, Half-life
Tmax: time to maximum concentration Half-life: computed as ln (2)/kel
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
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
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
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
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

Results

Posted Feb 3, 2023

Participant flow

First Intervention (Day 0)

Participant flow — First Intervention (Day 0)
Milestone	Clinical Trial Reference Tablets First, Then To-Be-Marketed Tablets	To-Be-Marketed Tablets First, Then Clinical Trial Reference Tablets
Started	21	21
Completed	20	21
Not completed	1	0

Washout (43 Days)

Participant flow — Washout (43 Days)
Milestone	Clinical Trial Reference Tablets First, Then To-Be-Marketed Tablets	To-Be-Marketed Tablets First, Then Clinical Trial Reference Tablets
Started	20	21
Completed	18	19
Not completed	2	2

Second Intervention (Day 43)

Participant flow — Second Intervention (Day 43)
Milestone	Clinical Trial Reference Tablets First, Then To-Be-Marketed Tablets	To-Be-Marketed Tablets First, Then Clinical Trial Reference Tablets
Started	18	19
Completed	18	19
Not completed	0	0

Follow-up (42 Days)

Participant flow — Follow-up (42 Days)
Milestone	Clinical Trial Reference Tablets First, Then To-Be-Marketed Tablets	To-Be-Marketed Tablets First, Then Clinical Trial Reference Tablets
Started	18	19
Completed	18	19
Not completed	0	0

Outcome measures

PrimaryPyronaridine Pharmacokinetics: Tmax, Half-life

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

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
Reported as:: Mean · days

Pyronaridine Pharmacokinetics: Tmax, Half-life
days	Clinical Trial Reference Tablets	To-Be-Marketed Tablets
Tmax	0.184 ± 0.145	0.166 ± 0.131
Half-life	14.2 ± 5.28	14.1 ± 4.00

PrimaryPyronaridine (PP), Artesunate (AS), Dihydroartemisinin (DHA) Pharmacokinetics: Cmax

Cmax: maximum peak observed concentration

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
Reported as:: Mean · ng/ml

Pyronaridine (PP), Artesunate (AS), Dihydroartemisinin (DHA) Pharmacokinetics: Cmax
ng/ml	Clinical Trial Reference Tablets	To-Be-Marketed Tablets
PP Cmax	512 ± 183	533 ± 190
AS Cmax	183 ± 175	154 ± 101
DHA Cmax	987 ± 476	959 ± 356

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

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

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
Reported as:: Mean · hours

Artesunate (AS) and Dihydroartemisinin (DHA) Pharmacokinetics: Tmax, Half-life
hours	Clinical Trial Reference Tablets	To-Be-Marketed Tablets
AS Tmax	0.488 ± 0.226	0.548 ± 0.279
DHA Tmax	1.14 ± 0.555	1.39 ± 0.823
AS half-life	0.549 ± 0.447	0.538 ± 0.717
DHA half-life	1.53 ± 0.452	1.84 ± 0.571

PrimaryPyronaridine 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

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
Reported as:: Mean · ng*day/ml

Pyronaridine Pharmacokinetics: AUC0-last, AUC0-∞
ng*day/ml	Clinical Trial Reference Tablets	To-Be-Marketed Tablets
AUC0-last	729 ± 216	762 ± 272
AUC0-∞	877 ± 244	904 ± 291

PrimaryArtesunate (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
Reported as:: Mean · ng*hr/ml

Artesunate (AS) and Dihydroartemisinin (DHA): AUC0-last, AUC0-∞
ng*hr/ml	Clinical Trial Reference Tablets	To-Be-Marketed Tablets
AS AUC0-last	139 ± 106	121 ± 79.7
DHA AUC0-last	2150 ± 889	2120 ± 834
AS AUC0-∞	155 ± 107	137 ± 83.9
DHA AUC0-∞9	2166 ± 896	2143 ± 849

Adverse events

Collected over 85 days (43 days Period 1, 42 days Period 2). Non-serious events are listed at a 0% frequency threshold.

Adverse event summary by group
Group	Deaths	Serious	Other
To-Be-Marketed Tablets	0/39 (0%)	0/39 (0%)	26/39 (66.7%)
Clinical Trial Reference Tablets	0/40 (0%)	0/40 (0%)	28/40 (70%)

Most frequent other events

Showing 10 of 15

Most frequent other events
Event	To-Be-Marketed Tablets	Clinical Trial Reference Tablets
VomitingGastrointestinal disorders	15/39	12/40
NauseaGastrointestinal disorders	14/39	15/40
Abdominal discomfortGastrointestinal disorders	9/39	9/40
DiarrhoeaGastrointestinal disorders	9/39	6/40
HeadacheNervous system disorders	3/39	8/40
DizzinessNervous system disorders	1/39	4/40
DyspepsiaGastrointestinal disorders	3/39	1/40
Viral upper respiratory tract infectionInfections and infestations	1/39	2/40
Alanine aminotransferase increasedInvestigations	1/39	2/40
Abdominal pain upperGastrointestinal disorders	1/39	0/40

Baseline characteristics

Safety population: all subjects who received at least one dose of study drug

Age, Continuous
Age, Continuous(years)	Clinical Trial Reference Tablets First, Then To-Be-Marketed Tablets	To-Be-Marketed Tablets First, Then Clinical Trial Reference Tablets	Total
Mean	34 ± 7.8	33.5 ± 4.9	33.8 ± 7.1

Sex: Female, Male
Sex: Female, Male(Participants)	Clinical Trial Reference Tablets First, Then To-Be-Marketed Tablets	To-Be-Marketed Tablets First, Then Clinical Trial Reference Tablets	Total
Female	7	11	18
Male	14	10	24

Ethnicity (NIH/OMB)
Ethnicity (NIH/OMB)(Participants)	Clinical Trial Reference Tablets First, Then To-Be-Marketed Tablets	To-Be-Marketed Tablets First, Then Clinical Trial Reference Tablets	Total
Hispanic or Latino	8	7	15
Not Hispanic or Latino	13	14	27
Unknown or Not Reported	0	0	0

Race (NIH/OMB)
Race (NIH/OMB)(Participants)	Clinical Trial Reference Tablets First, Then To-Be-Marketed Tablets	To-Be-Marketed Tablets First, Then Clinical Trial Reference Tablets	Total
American Indian or Alaska Native	0	0	0
Asian	0	0	0
Native Hawaiian or Other Pacific Islander	0	0	0
Black or African American	0	0	0
White	13	14	27
More than one race	0	0	0
Unknown or Not Reported	8	7	15

BMI
BMI(kg/m^2)	Clinical Trial Reference Tablets First, Then To-Be-Marketed Tablets	To-Be-Marketed Tablets First, Then Clinical Trial Reference Tablets	Total
Mean	23.5 ± 1.4	23.3 ± 3.0	23.4 ± 2.0

Study locations

1 site

Cross Research S.A., Phase I Unit
Arzo, 6864, Switzerland

Updates

Tracking since Sep 25, 2026

No changes since tracking began. The registry record was last updated on Feb 3, 2023, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗

Registry details

Key details

Study ID: NCT00682630
Lead sponsor: Medicines for Malaria Venture
Collaborators: Shin Poong Pharmaceuticals
Responsible party: Sponsor
First posted: May 22, 2008
Start date: Sep 2007
Primary completion: Jul 2008
Completion: Sep 2008
Results posted: Feb 3, 2023
Last update: Feb 3, 2023

Study contacts

Isabelle Borghini Fuhrer, PhD

study director · Medicines for Malaria Venture

Oversight

Data monitoring committee: Yes

View the source record on ClinicalTrials.gov ↗

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