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

Medicines for Malaria Venture (MMV)

Status and phase: Completed; Phase 1

Conditions: Malaria

Treatments: Drug: OZ439 Prototype 3; Drug: OZ439 Prototype 1; Drug: OZ439 + TPGS; Drug: PQP

Study type: Interventional

Funder types: Other

Identifiers

NCT02387580

MMV_OZ439_15_001

Details and patient eligibility

About

This is a single-centre, 2-part, randomised, single-dose parallel group study in healthy male subjects and female subjects of non-childbearing potential.

Full 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

Enrollment: 48 patients

Sex: All

Ages: 18 to 55 years old

Volunteers: Accepts Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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48 participants in 6 patient groups

Regimen A: OZ439 + TPGS and PQP

Active Comparator group

Description:

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

Treatment:

Drug: PQP

Drug: OZ439 + TPGS

Regimen B: OZ439 Prototype 1 and PQP - 110mL

Experimental group

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

Treatment:

Drug: PQP

Drug: OZ439 Prototype 1

Regimen C: OZ439 Prototype 3 and PQP - 110mL

Experimental group

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

Treatment:

Drug: PQP

Drug: OZ439 Prototype 3

Regimen D: OZ439 + TPGS and PQP

Active Comparator group

Description:

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

Treatment:

Drug: PQP

Drug: OZ439 + TPGS

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

Experimental group

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

Treatment:

Drug: PQP

Drug: OZ439 Prototype 1

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

Experimental group

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

Treatment:

Drug: PQP

Drug: OZ439 Prototype 3