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

NCT01853475 | Completed Phase 1 Results

• 2 other identifiers: MMV_OZ439_13_0022013-000983-28
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 1

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

Conditions

Malaria

Keywords

pharmacokinetics; safety; tolerability; bioavailability

Outcome Measures

Primary Outcomes (2)

• OZ439 Cmax

  OZ439 maximum concentration observed

  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 AUC0-inf

  Area under the OZ439 plasma concentration time curve from time zero to time infinity using observed values.

  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

Secondary Outcomes (2)

• Piperaquine Cmax

  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 AUC0-inf

  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

Study Arms (3)

Treatment A

EXPERIMENTAL

PQP tablets 1440mg and OZ439+TPGS 800mg co-administered as a single oral dose fasted.

Drug: PQP tablets 1440mg; Drug: OZ439+TPGS 800mg

Treatment B

EXPERIMENTAL

PQP tablets 960mg and OZ439+TPGS 800mg co-administered as a single oral dose fasted.

Drug: PQP tablets 960mg; Drug: OZ439+TPGS 800mg

Treatment C - Reference

ACTIVE COMPARATOR

PQP Tablets 1440 mg and OZ439 PIB 800mg + full fat cow's milk

Drug: PQP tablets 1440mg; Drug: OZ439 PIB 800mg

Interventions

PQP tablets 960mg DRUG

Piperaquine phosphate tablets 960mg

Treatment B

PQP tablets 1440mg DRUG

Piperaquine phosphate tablets 1440mg

Treatment A; Treatment C - Reference

OZ439+TPGS 800mg DRUG

OZ439+TPGS prototype formulation 800mg

Treatment A; Treatment B

OZ439 PIB 800mg DRUG

OZ439 Powder in Bottle Aqueous Solution 800mg

Treatment C - Reference

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Healthy male/female of any race aged 18-55 years at screening
• Body Mass Index 18-30kg/m2; body weight \>50kg but no more than 100kg at screening
• Females with negative pregnancy test at screening and admission, non-lactating and of non-child bearing potential confirmed
• Agree to use acceptable methods of contraception
• Should not donate egg and sperm from the time of administration of treatment or study medication until 3 months following dose of study medication
• 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

You may not qualify if:

• Male subjects with a female partner(s) who is (are) pregnant or lactating from the time of the administration of study medication
• Has a clinically significant disease or any condition or disease that might affect drug absorption, distribution or excretion, e.g. gastrectomy, diarrhoea.
• History of allergic reactions to artemisinin-based compounds, 4-aminoquinolines such as piperaquine or any other clinically relevant allergy to drugs or food.
• Any clinically relevant history of cow's milk intolerance/allergy.
• 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.
• 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
• History of post-antibiotic colitis
• 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
• 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

Sponsors & Collaborators

• Medicines for Malaria Venture: lead
• Richmond Pharmacology Limited: collaborator

Study Sites (1)

Richmond Pharmacology Limited

Croyden, London, CR7 7YE, United Kingdom

Location

MeSH Terms

Conditions

Malaria

Condition Hierarchy (Ancestors)

Protozoan Infections; Parasitic Diseases; Infections; Mosquito-Borne Diseases; Vector Borne Diseases

Results Point of Contact

• Title: Dr Thomas Rueckle
• Organization: Medicines for Malaria Ventire (MMV)

ruecklet@mmv.org

+41 22 799 4567

Study Officials

• Ulrike Lorch, MD FRCA FFPM

  Richmond Pharmacology Limited

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 10, 2013
• First Posted: May 15, 2013
• Study Start: April 1, 2013
• Primary Completion: July 1, 2013
• Study Completion: July 1, 2013
• Last Updated: April 30, 2015
• Results First Posted: April 8, 2015

Record last verified: 2015-04

Locations

GB (1)