Bioavailability Study of Oral OZ439 Prototype Granule Formulations Administered With Piperaquine Phosphate (PQP) Tablets

NCT ID: NCT02387580

Last Updated: 2016-02-08

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 48 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2015-04-30
• Study Completion Date: 2015-06-30

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

Conditions

Malaria

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Regimen A: OZ439 + TPGS and PQP

800 mg OZ439 + TPGS granules (oral suspension 240 mL volume and 100 mL rinse volume) and 960 mg (3 × 320 mg) PQP tablets

Group Type: ACTIVE_COMPARATOR

OZ439 + TPGS

Intervention Type: DRUG

PQP

Intervention Type: DRUG

Regimen B: OZ439 Prototype 1 and PQP - 110mL

800 mg OZ439 Prototype 1 granules (oral suspension 60 mL volume and 50 mL rinse volume) and 960 mg (3 × 320 mg) PQP tablets

Group Type: EXPERIMENTAL

OZ439 Prototype 1

Intervention Type: DRUG

PQP

Intervention Type: DRUG

Regimen C: OZ439 Prototype 3 and PQP - 110mL

800 mg OZ439 Prototype 3 granules (oral suspension 60 mL volume and 50 mL rinse volume) and 960 mg (3 × 320 mg) PQP tablets

Group Type: EXPERIMENTAL

OZ439 Prototype 3

Intervention Type: DRUG

PQP

Intervention Type: DRUG

Regimen D: OZ439 + TPGS and PQP

800 mg OZ439 + TPGS granules (oral suspension 240 mL volume and 100 mL rinse volume) and 960 mg (3 × 320 mg) PQP tablets

Group Type: ACTIVE_COMPARATOR

OZ439 + TPGS

Intervention Type: DRUG

PQP

Intervention Type: DRUG

Regimen E: OZ439 Prototype 1 or 3 and PQP - XmL

800 mg OZ439 Prototype 1 or 3 granules (oral suspension and rinse volume to be determined) and 960 mg (3 × 320 mg) PQP tablets

Group Type: EXPERIMENTAL

OZ439 Prototype 1

Intervention Type: DRUG

PQP

Intervention Type: DRUG

Regimen F: OZ439 Prototype 1 or 3 and PQP - XmL

800 mg OZ439 Prototype 1 or 3 granules (oral suspension and rinse volume to be determined) and 960 mg (3 × 320 mg) PQP tablets

Group Type: EXPERIMENTAL

OZ439 Prototype 3

Intervention Type: DRUG

PQP

Intervention Type: DRUG

Interventions

OZ439 + TPGS

Intervention Type: DRUG

OZ439 Prototype 1

Intervention Type: DRUG

OZ439 Prototype 3

Intervention Type: DRUG

PQP

Intervention Type: DRUG

Other Intervention Names

800 mg OZ439 + TPGS Reference Treatment; OZ439 Granules Prototype 1 Granules Formulation; OZ439 Granules Prototype 3 Granules Formulation; PQP 960 mg tablets

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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 55 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Quotient Clinical

OTHER

Sponsor Role: collaborator

Medicines for Malaria Venture

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Fiona Macintyre, PhD

Role: STUDY_DIRECTOR

Medicines for Malaria Ventire

Locations

Quotient Clinical

Nottingham, Nottinghamshire, United Kingdom

Countries

United Kingdom

Other Identifiers

MMV_OZ439_15_001

Identifier Type: -

Identifier Source: org_study_id