Back to resultsBioavailability Study of Oral OZ439 Prototype Granule Formulations Administered With Piperaquine Phosphate (PQP) Tablets
Primary Purpose
Malaria
Status
Completed
Phase
Phase 1
Locations
United Kingdom
Study Type
Interventional
Intervention
OZ439 + TPGS
OZ439 Prototype 1
OZ439 Prototype 3
PQP
Sponsored by
About this trial
This is an interventional treatment trial for Malaria focused on measuring Malaria, Bioavailability, Formulation
Eligibility Criteria
Inclusion Criteria:
- Healthy males, or healthy females of non-childbearing potential ie surgically sterilised or post-menopausal
- Body mass index of 18.0 to 30.0 kg/m2 inclusive. Total body weight >50 kg at screening.
- Must agree to use an adequate method of contraception.
- Normal laboratory tests as judged by the Investigator.
- Must have QTcF ≤450 ms, QTcB ≤450 ms for male subjects, QTcF ≤470 ms, QTcB ≤470 ms for female subjects and PR interval ≤200 ms for screening and pre-dose ECG measurements.
Exclusion Criteria:
- Male subjects who have currently pregnant partners or who have partners planning to be pregnant.
- Evidence or history of clinically significant disease, or current infection.3.
- Clinically relevant abnormalities in the ECG.
- Family history of sudden death or of congenital prolongation of the QTc interval or known congenital prolongation of the QTc interval or any clinical condition known to prolong the QTc interval.
- History of symptomatic cardiac arrhythmias or with clinically relevant bradycardia, heart rate ≤39 bpm.
- Electrolyte disturbances, particularly hypokalaemia, hypocalcaemia or hypomagnesaemia.
- History of any drug or alcohol abuse in the past 2 years prior to screening.
- Receipt of an investigational drug or participation in another clinical research study within 90 days prior to drug administration.
- Use of any prescription or non-prescription medications, vitamins, herbal supplements or dietary supplements, including protein supplements, within 14 days prior to the first dose of study drug.
- Positive hepatitis B surface antigen, hepatitis C virus antibody or human immunodeficiency virus results.
- Clinically significant abnormal biochemistry, haematology or urinalysis.
- Positive urine drug screen result.
- History of intolerance or hypersensitivity to PQP or any 4-aminoquinoline, or ascertained or presumptive hypersensitivity to the active principle and/or formulation ingredients; history of anaphylaxis to drugs or allergic reactions in general, that the investigator considers may affect the outcome of the study.
- Presence or history of allergy requiring treatment; hayfever is allowed unless it is active.
- Donation or loss of >400 mL of blood within 90 days prior to drug administration.
Sites / Locations
- Quotient Clinical
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm 4
Arm 5
Arm 6
Arm Type
Active Comparator
Experimental
Experimental
Active Comparator
Experimental
Experimental
Arm Label
Regimen A: OZ439 + TPGS and PQP
Regimen B: OZ439 Prototype 1 and PQP - 110mL
Regimen C: OZ439 Prototype 3 and PQP - 110mL
Regimen D: OZ439 + TPGS and PQP
Regimen E: OZ439 Prototype 1 or 3 and PQP - XmL
Regimen F: OZ439 Prototype 1 or 3 and PQP - XmL
Arm Description
800 mg OZ439 + TPGS granules (oral suspension 240 mL volume and 100 mL rinse volume) and 960 mg (3 × 320 mg) PQP tablets
800 mg OZ439 Prototype 1 granules (oral suspension 60 mL volume and 50 mL rinse volume) and 960 mg (3 × 320 mg) PQP tablets
800 mg OZ439 Prototype 3 granules (oral suspension 60 mL volume and 50 mL rinse volume) and 960 mg (3 × 320 mg) PQP tablets
800 mg OZ439 + TPGS granules (oral suspension 240 mL volume and 100 mL rinse volume) and 960 mg (3 × 320 mg) PQP tablets
800 mg OZ439 Prototype 1 or 3 granules (oral suspension and rinse volume to be determined) and 960 mg (3 × 320 mg) PQP tablets
800 mg OZ439 Prototype 1 or 3 granules (oral suspension and rinse volume to be determined) and 960 mg (3 × 320 mg) PQP tablets
Outcomes
Primary Outcome Measures
OZ439 Cmax
OZ439 Maximum observed concentration
OZ439 AUC(0-168 h)
OZ439 Area under the plasma concentration (AUC) versus time curve
Piperaquine Cmax
Piperaquine Maximum observed concentration
Piperaquine AUC(0-168 h)
PQP Area under the plasma concentration versus time curve
Secondary Outcome Measures
Full Information
NCT ID
NCT02387580
First Posted
March 5, 2015
Last Updated
January 13, 2016
Sponsor
Medicines for Malaria Venture
Collaborators
Quotient Clinical
1. Study Identification
Unique Protocol Identification Number
NCT02387580
Brief Title
Bioavailability Study of Oral OZ439 Prototype Granule Formulations Administered With Piperaquine Phosphate (PQP) Tablets
Official Title
A Phase I Bioavailability Study of Selected Oral Prototype Granule Formulations of OZ439 in Healthy Subjects, to Evaluate the Pharmacokinetics of OZ439 When Co-Administered With Piperaquine Phosphate Tablets in the Fasted State
Study Type
Interventional
2. Study Status
Record Verification Date
January 2016
Overall Recruitment Status
Completed
Study Start Date
April 2015 (undefined)
Primary Completion Date
June 2015 (Actual)
Study Completion Date
June 2015 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Medicines for Malaria Venture
Collaborators
Quotient Clinical
4. Oversight
Data Monitoring Committee
No
5. Study Description
Brief Summary
This is a single-centre, 2-part, randomised, single-dose parallel group study in healthy male subjects and female subjects of non-childbearing potential.
Detailed Description
Parts 1 and 2 will be randomised with 8 subjects receiving each regimen:
Part 1:
Regimen A: Reference: 800 mg OZ439 + α-Tocopherol polyethylene glycol 1000 succinate (TPGS) granules (oral suspension 240 mL volume and 100 mL rinse volume) and 960 mg (3 × 320 mg) PQP tablets
Regimen B: Prototype 1: 800 mg OZ439 granules (oral suspension 60 mL volume and 50 mL rinse volume) and 960 mg (3 × 320 mg) PQP tablets
Regimen C: Prototype 3: 800 mg OZ439 granules (oral suspension 60 mL volume and 50 mL rinse volume) and 960 mg (3 × 320 mg) PQP tablets
There will be an interim decision after Part 1 to determine the formulation prototypes and the oral suspension volume to be administered in Part 2.
Part 2
Regimen D: Reference: 800 mg OZ439 + TPGS granules (oral suspension 240 mL volume and 100 mL rinse volume) and 960 mg (3 × 320 mg) PQP tablets
Regimen E: Prototype 1 or 3: 800 mg OZ439 granules (oral suspension and rinse volume to be determined) and 960 mg (3 × 320 mg) PQP tablets
Regimen F: Prototype 1 or 3: 800 mg OZ439 granules (oral suspension and rinse volume to be determined) and 960 mg (3 × 320 mg) PQP tablets
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Malaria
Keywords
Malaria, Bioavailability, Formulation
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
48 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Regimen A: OZ439 + TPGS and PQP
Arm Type
Active Comparator
Arm Description
800 mg OZ439 + TPGS granules (oral suspension 240 mL volume and 100 mL rinse volume) and 960 mg (3 × 320 mg) PQP tablets
Arm Title
Regimen B: OZ439 Prototype 1 and PQP - 110mL
Arm Type
Experimental
Arm Description
800 mg OZ439 Prototype 1 granules (oral suspension 60 mL volume and 50 mL rinse volume) and 960 mg (3 × 320 mg) PQP tablets
Arm Title
Regimen C: OZ439 Prototype 3 and PQP - 110mL
Arm Type
Experimental
Arm Description
800 mg OZ439 Prototype 3 granules (oral suspension 60 mL volume and 50 mL rinse volume) and 960 mg (3 × 320 mg) PQP tablets
Arm Title
Regimen D: OZ439 + TPGS and PQP
Arm Type
Active Comparator
Arm Description
800 mg OZ439 + TPGS granules (oral suspension 240 mL volume and 100 mL rinse volume) and 960 mg (3 × 320 mg) PQP tablets
Arm Title
Regimen E: OZ439 Prototype 1 or 3 and PQP - XmL
Arm Type
Experimental
Arm Description
800 mg OZ439 Prototype 1 or 3 granules (oral suspension and rinse volume to be determined) and 960 mg (3 × 320 mg) PQP tablets
Arm Title
Regimen F: OZ439 Prototype 1 or 3 and PQP - XmL
Arm Type
Experimental
Arm Description
800 mg OZ439 Prototype 1 or 3 granules (oral suspension and rinse volume to be determined) and 960 mg (3 × 320 mg) PQP tablets
Intervention Type
Drug
Intervention Name(s)
OZ439 + TPGS
Other Intervention Name(s)
800 mg OZ439 + TPGS Reference Treatment
Intervention Type
Drug
Intervention Name(s)
OZ439 Prototype 1
Other Intervention Name(s)
OZ439 Granules Prototype 1 Granules Formulation
Intervention Type
Drug
Intervention Name(s)
OZ439 Prototype 3
Other Intervention Name(s)
OZ439 Granules Prototype 3 Granules Formulation
Intervention Type
Drug
Intervention Name(s)
PQP
Other Intervention Name(s)
PQP 960 mg tablets
Primary Outcome Measure Information:
Title
OZ439 Cmax
Description
OZ439 Maximum observed concentration
Time Frame
Pre-dose, 0, 0.5, 1, 2, 3, 4, 5, 6, 8, 12, 16, 24, 48, 72, 96 and 168 hours post-dose
Title
OZ439 AUC(0-168 h)
Description
OZ439 Area under the plasma concentration (AUC) versus time curve
Time Frame
pre-dose, 0, 0.5, 1, 2, 3, 4, 5, 6, 8, 12, 16, 24, 48, 72, 96 and 168 hours post-dose
Title
Piperaquine Cmax
Description
Piperaquine Maximum observed concentration
Time Frame
Pre-dose, 0, 0.5, 1, 2, 3, 4, 5, 6, 8, 12, 16, 24, 48, 72, 96 and 168 hours and Day36 post-dose
Title
Piperaquine AUC(0-168 h)
Description
PQP Area under the plasma concentration versus time curve
Time Frame
Pre-dose, 0, 0.5, 1, 2, 3, 4, 5, 6, 8, 12, 16, 24, 48, 72, 96 and 168 hours and Day36 post-dose
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
55 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
Inclusion Criteria:
Healthy males, or healthy females of non-childbearing potential ie surgically sterilised or post-menopausal
Body mass index of 18.0 to 30.0 kg/m2 inclusive. Total body weight >50 kg at screening.
Must agree to use an adequate method of contraception.
Normal laboratory tests as judged by the Investigator.
Must have QTcF ≤450 ms, QTcB ≤450 ms for male subjects, QTcF ≤470 ms, QTcB ≤470 ms for female subjects and PR interval ≤200 ms for screening and pre-dose ECG measurements.
Exclusion Criteria:
Male subjects who have currently pregnant partners or who have partners planning to be pregnant.
Evidence or history of clinically significant disease, or current infection.3.
Clinically relevant abnormalities in the ECG.
Family history of sudden death or of congenital prolongation of the QTc interval or known congenital prolongation of the QTc interval or any clinical condition known to prolong the QTc interval.
History of symptomatic cardiac arrhythmias or with clinically relevant bradycardia, heart rate ≤39 bpm.
Electrolyte disturbances, particularly hypokalaemia, hypocalcaemia or hypomagnesaemia.
History of any drug or alcohol abuse in the past 2 years prior to screening.
Receipt of an investigational drug or participation in another clinical research study within 90 days prior to drug administration.
Use of any prescription or non-prescription medications, vitamins, herbal supplements or dietary supplements, including protein supplements, within 14 days prior to the first dose of study drug.
Positive hepatitis B surface antigen, hepatitis C virus antibody or human immunodeficiency virus results.
Clinically significant abnormal biochemistry, haematology or urinalysis.
Positive urine drug screen result.
History of intolerance or hypersensitivity to PQP or any 4-aminoquinoline, or ascertained or presumptive hypersensitivity to the active principle and/or formulation ingredients; history of anaphylaxis to drugs or allergic reactions in general, that the investigator considers may affect the outcome of the study.
Presence or history of allergy requiring treatment; hayfever is allowed unless it is active.
Donation or loss of >400 mL of blood within 90 days prior to drug administration.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Fiona Macintyre, PhD
Organizational Affiliation
Medicines for Malaria Ventire
Official's Role
Study Director
Facility Information:
Facility Name
Quotient Clinical
City
Nottingham
State/Province
Nottinghamshire
ZIP/Postal Code
NG11 6JS
Country
United Kingdom
12. IPD Sharing Statement
Learn more about this trial
Bioavailability Study of Oral OZ439 Prototype Granule Formulations Administered With Piperaquine Phosphate (PQP) Tablets
We'll reach out to this number within 24 hrs