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Trial registered on ANZCTR


Registration number
ACTRN12609000846224
Ethics application status
Approved
Date submitted
28/09/2009
Date registered
30/09/2009
Date last updated
30/09/2009
Type of registration
Prospectively registered

Titles & IDs
Public title
Multiple-dose pharmacokinetics and ex vivo pharmacodynamics of the fixed-dosed artemisinin based combination therapies (ACTs) of the antimalarial drugs Artequick (artemisinin-piperaquine) and Coarsucam (artesunate-amodiaquine) in healthy male Vietnamese volunteers
Scientific title
Multiple-dose pharmacokinetics and ex vivo pharmacodynamics of the fixed-dosed combinations of Artequick (artemisinin-piperaquine) and Coarsucam (artesunate-amodiaquine) in healthy male Vietnamese volunteers
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Characterization of the pharmacokinetics (absorption, metabolism, distribution and elimination) of the components of the antimalarial drugs Artequick and Coarsucam in healthy Vietnamese volunteers will provide important data for dose optimization and measurement of interindividual variability in plasma drug concentrations. 251930 0
Condition category
Condition code
Infection 252115 252115 0 0
Other infectious diseases

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Two groups of 22 healthy male Vietnamese volunteers will be recruited to receive 3-day courses of either Artequick or Coarsucam. Group 1 healthy volunteers (n=22) will be administered a daily dose of two tablets of Artequick (each tablet contains 62.5 mg artemisinin and 375 mg piperaquine) for 3 days. Group 2 healthy volunteers (n=22) will be administered a daily dose of two tablets of Coarsucam (each tablet contains 100 mg artesunate and 270 mg amodiaquine) for 3 days.
Intervention code [1] 241352 0
Treatment: Drugs
Comparator / control treatment
The tolerability and safety of Artequick and Coarsucam in healthy subjects will be compared. Also the ex vivo pharmacodynamics of plasma artemisinin-piperaquine and artesunate-amodiaquine concentrations collected from the volunteers will be compared against the chloroquine-sensitive D6 and chloroquine-resistant K1 strains of Plasmodium falciparum, in vitro.
Control group
Active

Outcomes
Primary outcome [1] 252995 0
The pharmacokinetics of the components of Artequick (artemisinin-piperaquine) and Coarsucam (artesunate-amodiaquine) will be derived from plasma concentration versus time curves generated from the analysis of plasma samples collected from healthy volunteers.
Timepoint [1] 252995 0
For pharmacokinetic analysis plasma samples will be measured at day 0 (pre-dose), 1, 3, and 6 hours after the first and second day of Artequick or Coarsucam administration. Plasma sample will also be measured before the third dose (day 2) and then at 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10 and 12 hours after the last dose. Additional plasma samples will be measured at days 3, 4, 7, 14, 21, 28, 35 and 42 after commencement of Artequick administration and at days 3, 4, 5, 7, 10, 14, 21 and 28 after starting Coarsucam administration.

Plasma concentrations of artemisinin, piperaquine, artesunate and its active metabolite, dihydroartemisinin and amodiaquine and its active metabolite desethylamodiaquine will be measured by liquid chromatography-tandem mass spectrometry. Non-compartmental analysis will be used to determine the pharmacokinetics of the drugs.
Primary outcome [2] 252996 0
The tolerability and safety of the two ACTs will be compared. Possible adverse events can be gastrointestinal disturbances such as vomiting, nausea and abdominal discomfort. Other adverse events can be abnormal biochemical and haematological indices.
Timepoint [2] 252996 0
Adverse events will be monitored before drug administration and at 24 hours after each dose.

Blood samples for biochemical and haematological analysis will be collected before drug administration and at day 7 after commencement of the 3-day course.
Secondary outcome [1] 257761 0
Ex vivo antimalarial activivity will be carried out on plasma artemisinin-piperaquine and artesunate-amodiaquine concentrations collected from the volunteers against two Plasmodium falciparum isolates (D6 and K1).
Timepoint [1] 257761 0
Blood samples for ex vivo antimalarial activity will be collected collected at 0 (pre-dose), 1, 3, and 6 hours after the first and second day of Artequick or Coarsucam administration. Blood samples will also be collected immediately before the third day of drug administration and then at 1, 3, 6, 12, 24, 48, 120, 288, 456 and 624 hours after the last dose.
Secondary outcome [2] 257762 0
The inhibitory concentration (IC90 for spiked drug samples) and inhibitory dilution (ID90 for patient plasma samples) will be determined using the in vitro tritiated-hypoxanthine assay.
Timepoint [2] 257762 0
ID90 values will be determined on plasma samples at 0 (pre-dose), 1, 3, and 6 hours after the first and second day of Artequick or Coarsucam administration. Plasma samples will also be collected immediately before the third day of drug administration and then at 1, 3, 6, 12, 24, 48, 120, 288, 456 and 624 hours after the last dose.

Eligibility
Key inclusion criteria
Inclusion criteria
(i) Males: 17-40 years
(ii) Normal clinical parameters: medical history, physical examination
(iii) Normal haematological and biochemical indices, and electrocardiogram
(iv) The volunteer is willing not to drink alcohol and caffeine containing beverages one day before and after drug administration
(v) Able to understand and willing to provide written informed consent
Minimum age
17 Years
Maximum age
40 Years
Sex
Males
Can healthy volunteers participate?
Yes
Key exclusion criteria
Exclusion criteria
(i) A history of serious past medical diseases
(ii) A history of drug or alcohol abuse
(iii) Use of regular medications including prescribed and natural therapies

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Two different groups of 22 healthy male Vietnamese volunteers will be recruited to receive 3-day courses of either Artequick or Coarsucam.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 2
Type of endpoint/s
Pharmacokinetics / pharmacodynamics
Statistical methods / analysis

Recruitment
Recruitment status
Not yet recruiting
Date of first participant enrolment
Anticipated
10/10/2009
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
44
Accrual to date
Final
Recruitment outside Australia
Country [1] 2159 0
Viet Nam
State/province [1] 2159 0
Hanoi

Funding & Sponsors
Funding source category [1] 243807 0
Government body
Name [1] 243807 0
Australian Department of Defence
Country [1] 243807 0
Australia
Primary sponsor type
Government body
Name
Australian Department of Defence
Address
Australian Army Malaria Institute
Weary Dunlop Drive
Gallipoli Barracks
Enoggera
Brisbane QLD 4051
Country
Australia
Secondary sponsor category [1] 237159 0
Government body
Name [1] 237159 0
Vietnam People's Army
Address [1] 237159 0
Military Institute of Hygiene and Epidemiology, 21-Trung Liet, Dong Da, Hanoi, Vietnam
Country [1] 237159 0
Viet Nam

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 243939 0
Australian Defence Human Research Ethics Committee
Ethics committee address [1] 243939 0
Ethics committee country [1] 243939 0
Australia
Date submitted for ethics approval [1] 243939 0
Approval date [1] 243939 0
25/09/2009
Ethics approval number [1] 243939 0
ADHREC 562/09

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 30337 0
Address 30337 0
Country 30337 0
Phone 30337 0
Fax 30337 0
Email 30337 0
Contact person for public queries
Name 13584 0
Dr Mike Edstein
Address 13584 0
Australian Army Malaria Institute
Weary Dunlop Drive
Gallipoli Barracks
Enoggera
Brisbane, QLD 4051
Country 13584 0
Australia
Phone 13584 0
61-7-33324930
Fax 13584 0
61-7-33324800
Email 13584 0
Mike.Edstein@defence.gov.au
Contact person for scientific queries
Name 4512 0
Dr Mike Edstein
Address 4512 0
Australian Army Malaria Institute
Weary Dunlop Drive
Gallipoli Barracks
Enoggera
Brisbane, QLD 4051
Country 4512 0
Australia
Phone 4512 0
61-7-33324930
Fax 4512 0
61-7-33324800
Email 4512 0
Mike.Edstein@defence.gov.au

No information has been provided regarding IPD availability


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

Documents added manually
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Documents added automatically
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