Working…
COVID-19 is an emerging, rapidly evolving situation.
Get the latest public health information from CDC: https://www.coronavirus.gov.

Get the latest research information from NIH: https://www.nih.gov/coronavirus.
ClinicalTrials.gov
ClinicalTrials.gov Menu

Healthy Volunteer Study of the Pharmacokinetics of Oral Piperaquine With OZ439 + TPGS Formulation in the Fasted State

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT01853475
Recruitment Status : Completed
First Posted : May 15, 2013
Results First Posted : April 8, 2015
Last Update Posted : April 30, 2015
Sponsor:
Collaborator:
Richmond Pharmacology Limited
Information provided by (Responsible Party):
Medicines for Malaria Venture

Tracking Information
First Submitted Date  ICMJE May 10, 2013
First Posted Date  ICMJE May 15, 2013
Results First Submitted Date  ICMJE March 27, 2015
Results First Posted Date  ICMJE April 8, 2015
Last Update Posted Date April 30, 2015
Study Start Date  ICMJE April 2013
Actual Primary Completion Date July 2013   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: April 8, 2015)
  • OZ439 Cmax [ Time Frame: Day 1 pre-dose and post-dose at 0.5, 1, 2, 3, 4, 5, 6, 8, 12, 16 and 24 hours(Day 2), and, 48 (Day 3), 72 (Day 4), 96 (Day 5),168 (Day 8), Day 11, Day 15, Day 29 and Day 43 ]
    OZ439 maximum concentration observed
  • OZ439 AUC0-inf [ Time Frame: Day 1 pre-dose and post-dose at 0.5, 1, 2, 3, 4, 5, 6, 8, 12, 16 and 24 hours(Day 2), and, 48 (Day 3), 72 (Day 4), 96 (Day 5),168 (Day 8), Day 11, Day 15, Day 29 and Day 43 ]
    Area under the OZ439 plasma concentration time curve from time zero to time infinity using observed values.
Original Primary Outcome Measures  ICMJE
 (submitted: May 10, 2013)
  • maximum concentration [ Time Frame: 1, 2, 3, 4, 5, 6, 12, 16, 24, 48, 72, 96 and 168 hours post-dose and on Days 11, 15, 29 and 43 ]
  • Area under the plasma concentration time curve from time zero to the time of the time of last measurable concentration post-dose [ Time Frame: 1, 2, 3, 4, 5, 6, 12, 16, 24, 48, 72, 96 and 168 hours post-dose and on Days 11, 15, 29 and 43 ]
  • Area under the plasma concentration time curve from time zero to infinity [ Time Frame: 1, 2, 3, 4, 5, 6, 12, 16, 24, 48, 72, 96 and 168 hours post-dose and on Days 11, 15, 29 and 43 ]
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: April 8, 2015)
  • Piperaquine Cmax [ Time Frame: Day 1 pre-dose and post-dose at 0.5, 1, 2, 3, 4, 5, 6, 8, 12, 16 and 24 hours(Day 2), and, 48 (Day 3), 72 (Day 4), 96 (Day 5),168 (Day 8), Day 11, Day 15, Day 29 and Day 43 ]
    Piperaquine maximum concentration observed
  • Piperaquine AUC0-inf [ Time Frame: Day 1 pre-dose and post-dose at 0.5, 1, 2, 3, 4, 5, 6, 8, 12, 16 and 24 hours(Day 2), and, 48 (Day 3), 72 (Day 4), 96 (Day 5),168 (Day 8), Day 11, Day 15, Day 29 and Day 43 ]
    Area under the Piperaquine plasma concentration time curve from time zero to time infinity using observed values.
Original Secondary Outcome Measures  ICMJE
 (submitted: May 10, 2013)
  • Time to reach maximum plasma concentration [ Time Frame: 1, 2, 3, 4, 5, 6, 12, 16, 24, 48, 72, 96 and 168 hours post-dose and on Days 11, 15, 29 and 43 ]
  • the terminal elimination half-life [ Time Frame: Up to Day 43 post-dose ]
  • Terminal elimination rate constant [ Time Frame: 1, 2, 3, 4, 5, 6, 12, 16, 24, 48, 72, 96 and 168 hours post-dose and on Days 11, 15, 29 and 43 ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Healthy Volunteer Study of the Pharmacokinetics of Oral Piperaquine With OZ439 + TPGS Formulation in the Fasted State
Official Title  ICMJE Open Label, Parallel Group Study to Investigate the Pharmacokinetics (PK) Following Oral Co-administration of Piperaquine Phosphate (PQP) Tablets With a Prototype OZ439 + TPGS Formulation in the Fasted State in Healthy Volunteers
Brief Summary

Piperaquine tablets (coated) + OZ439 granules + TPGS granules will be co-administered in Phase IIb (adults). However, safety and PK data (for OZ439 plus piperaquine) were obtained using piperaquine tablets plus OZ439 as Powder in Bottle with milk. Piperaquine has not yet been administered together with TPGS. Co-administration of piperaquine plus OZ439 as Powder in Bottle (PIB) with milk results in an increase in OZ439 exposure (current estimate ~ 70% due to a small drug drug interaction).

This study investigates the exposure of piperaquine and OZ439 when co-administered as piperaquine phosphate tablets and OZ439 + TPGS prototype (a formulation close to that of Phase IIb, but not identical), in order to select the appropriate doses for Phase IIb. The reference treatment is piperaquine phosphate tablets + OZ439 Powder in Bottle + full fat milk

Detailed Description

Objectives:

  1. To evaluate the piperaquine and OZ439 pharmacokinetics when administered as a combination of piperaquine phosphate tablets with OZ439 / TPGS formulation in the fasted state
  2. To evaluate the piperaquine and OZ439 pharmacokinetics of a reference free combination formulation: piperaquine phosphate tablets with OZ439 powder in bottle (PIB) given with full fat milk
  3. To determine safety and tolerability of OZ439 and piperaquine phosphate when co-administered.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Malaria
Intervention  ICMJE
  • Drug: PQP tablets 960mg
    Piperaquine phosphate tablets 960mg
  • Drug: PQP tablets 1440mg
    Piperaquine phosphate tablets 1440mg
  • Drug: OZ439+TPGS 800mg
    OZ439+TPGS prototype formulation 800mg
  • Drug: OZ439 PIB 800mg
    OZ439 Powder in Bottle Aqueous Solution 800mg
Study Arms  ICMJE
  • Experimental: Treatment A
    PQP tablets 1440mg and OZ439+TPGS 800mg co-administered as a single oral dose fasted.
    Interventions:
    • Drug: PQP tablets 1440mg
    • Drug: OZ439+TPGS 800mg
  • Experimental: Treatment B
    PQP tablets 960mg and OZ439+TPGS 800mg co-administered as a single oral dose fasted.
    Interventions:
    • Drug: PQP tablets 960mg
    • Drug: OZ439+TPGS 800mg
  • Active Comparator: Treatment C - Reference
    PQP Tablets 1440 mg and OZ439 PIB 800mg + full fat cow's milk
    Interventions:
    • Drug: PQP tablets 1440mg
    • Drug: OZ439 PIB 800mg
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: May 10, 2013)
24
Original Estimated Enrollment  ICMJE Same as current
Actual Study Completion Date  ICMJE July 2013
Actual Primary Completion Date July 2013   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  1. Healthy male/female of any race aged 18-55 years at screening
  2. Body Mass Index 18-30kg/m2; body weight >50kg but no more than 100kg at screening
  3. Females with negative pregnancy test at screening and admission, non-lactating and of non-child bearing potential confirmed
  4. Agree to use acceptable methods of contraception
  5. Should not donate egg and sperm from the time of administration of treatment or study medication until 3 months following dose of study medication
  6. Must be capable of understanding and complying with the requirements of the protocol and must have signed the informed consent form prior to undergoing any study-related procedures

Exclusion Criteria:

  1. Male subjects with a female partner(s) who is (are) pregnant or lactating from the time of the administration of study medication
  2. Has a clinically significant disease or any condition or disease that might affect drug absorption, distribution or excretion, e.g. gastrectomy, diarrhoea.
  3. History of allergic reactions to artemisinin-based compounds, 4-aminoquinolines such as piperaquine or any other clinically relevant allergy to drugs or food.
  4. Any clinically relevant history of cow's milk intolerance/allergy.
  5. Any clinically significant abnormal laboratory, vital signs or other safety findings as determined by medical history, physical examination or other evaluations conducted at screening or on admission. Exception is PR, QTcB, QTcF, cardiac rhythm, liver function tests and haemoglobin that must be within the normal reference range at screening and on admission.
  6. History or current evidence of any clinically relevant cardiovascular, pulmonary, hepatic, renal, gastrointestinal (excluding appendectomy and cholecystectomy), haematological, endocrinological, immunological, metabolic, neurological, oncological, psychiatric, urological or other disease, or current infection
  7. History of post-antibiotic colitis
  8. Electrocardiogram abnormalities in the standard 12-lead (at screening) and/or 24-hour 5 lead Holter (at screening) which in the opinion of the Investigator is clinically relevant or will interfere with the analysis
  9. A history of clinically significant electrocardiogram abnormalities, or any of the following abnormalities at screening or admission:

    • PR >200 msec
    • QRS complex >120 msec
    • QTcB or QTcF >450 msec or shortened QTcB or QTcF less than 340 msec for males and females or family history of long QT syndrome or sudden death
    • Any degree of heart block (such as first, second or third degree atrioventricular block, incomplete, full or intermittent bundle branch block)
    • Abnormal T wave morphology / prominent U waves
    • Potassium levels out of the normal range at screening and prior to dosing
  10. Positive results in any of the serology tests for Hepatitis B Surface Antigen, anti Hepatitis core antibody, Hepatitis C antibodies, and Human Immunodeficiency Virus 1 and 2 antibodies
  11. Confirmed positive results from urine drug screen (amphetamines, benzodiazepines, cocaine, cannabinoids, opiates, barbiturates, and methadone) or from the alcohol breath test at screening and admission
  12. History or clinical evidence of alcohol abuse, or any recreational drug abuse within the 2 years prior to screening
  13. Mentally handicapped
  14. Participation in a drug trial within 90 days prior to drug administration
  15. Use of ANY prescription or over the counter medications, within 3 weeks of study drug administration, or vitamins or herbal supplements within 2 week of administration of the drug administration of study drug (or at least 5 half-lives of the compound whichever period is the longer), unless prior approval is granted by both the Investigator and Sponsor. Excluded from this list is intermittent use of paracetamol at up to 2g/day.
  16. Use moderate or strong inhibitors and/or inducers of cytochrome CYP450 within 4 weeks prior to the planned drug administration (or at least 5 half-lives of the compound whichever period is the longer)
  17. Subjects have veins unsuitable for intravenous puncture or cannulation on either arm (e.g. veins that are difficult to locate, access or puncture veins with a tendency to rupture during or after puncture)
  18. Blood liver function tests not in the normal range at screening and on admission
  19. Haemoglobin is less than the lower limit of the reference range at screening and on admission.
  20. Donation of more than 500mL blood within 90 days prior to drug administration
  21. Subjects must be non-smokers for at least 3 months prior to screening Note: "Tobacco use" includes smoking and the use of snuff and chewing tobacco, and other nicotine or nicotine containing products
  22. Any consumption of grapefruit, Seville oranges, wild grapes, black mulberries, pomegranates in the form of fruit juice, marmalade or as a raw fruit within 7 days prior to dosing of study drug and throughout the study. Any circumstances or conditions, which, in the opinion of the investigator may affect full participation in the trial or compliance with the protocol
  23. Legal incapacity or limited legal capacity at screening
  24. Vegetarians, vegans or any dietary restrictions conflicting with the study standardised menus
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 55 Years   (Adult)
Accepts Healthy Volunteers  ICMJE Yes
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United Kingdom
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT01853475
Other Study ID Numbers  ICMJE MMV_OZ439_13_002
2013-000983-28 ( EudraCT Number )
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Medicines for Malaria Venture
Study Sponsor  ICMJE Medicines for Malaria Venture
Collaborators  ICMJE Richmond Pharmacology Limited
Investigators  ICMJE
Principal Investigator: Ulrike Lorch, MD FRCA FFPM Richmond Pharmacology Limited
PRS Account Medicines for Malaria Venture
Verification Date April 2015

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP