Safety, Tolerability & Pharmacokinetics (PK) of Co-administered Single Doses of OZ439 and Mefloquine (MQ) in Healthy Volunteers

NCT01615822 | Terminated Phase 1 Results DMC

• 1 other identifier: MMV_OZ439_12_001
• Study Type: interventional
• Target: 25
• Locations: 1 country
• Sites: 1

Brief Summary

OZ439 is a novel, synthetic trioxolane medicine which is related to artemisinin, but has the advantage of a longer elimination half-life so is being developed to be administered together with a potential partner drug e.g. mefloquine as a single dose cure for uncomplicated malaria. The study findings will be used to inform the dose and design of future studies. The aim of the study is to establish the safety, tolerability and pharmacokinetics of co-administered OZ439 and MQ at a range of doses up to the maximum tolerated dose, in healthy volunteers.

Conditions

Malaria

Keywords

Malaria; PK; OZ439; Mefloquine; Healthy Volunteers

Outcome Measures

Primary Outcomes (1)

• OZ439 AUC0-t

  Area under the plasma concentration versus time curve (AUC) of OZ439

  Up to 42 days post-dose

Secondary Outcomes (3)

• OZ439 Cmax

  Up to 42 days post-dose

• MQ AUC0-t

  Up to 42 days post-dose

• MQ Cmax

  Up to 42 days post-dose

Study Arms (5)

OZ439 100mg single dose

EXPERIMENTAL

OZ439 100mg single dose oral suspension

Drug: OZ439 100mg

OZ439 100mg plus MQ 250mg single doses

EXPERIMENTAL

Single dose OZ439 100mg oral suspension in combination with single dose MQ 250mg tablet

Drug: OZ439 100mg; Drug: MQ 250 mg, single dose

OZ439 400mg single dose

EXPERIMENTAL

OZ439 400mg single dose oral suspension

Drug: OZ439 400mg

OZ439 400mg plus MQ 750mg single doses

EXPERIMENTAL

Single dose OZ439 400mg oral suspension in combination with single dose MQ 750mg tablets

Drug: OZ439 400mg; Drug: MQ 750mg, single dose

Placebo

PLACEBO COMPARATOR

Placebo

Drug: Placebo

Interventions

OZ439 100mg DRUG

OZ439 100mg oral suspension, single dose

OZ439 100mg plus MQ 250mg single doses; OZ439 100mg single dose

OZ439 400mg DRUG

OZ439 400mg oral suspension, single dose

OZ439 400mg plus MQ 750mg single doses; OZ439 400mg single dose

MQ 250 mg, single dose DRUG

Mefloquine 250 mg tablet, single dose

OZ439 100mg plus MQ 250mg single doses

MQ 750mg, single dose DRUG

Mefloquine 750mg oral tablet, single dose

OZ439 400mg plus MQ 750mg single doses

Placebo DRUG

Placebo

Eligibility Criteria

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

You may qualify if:

• Healthy male and non-childbearing potential female volunteers of between 18 and 55 years of age
• Female volunteers must have a negative serum pregnancy test at screening
• Females must be of non-childbearing potential
• Male volunteers and their partner(s) must agree to use a double barrier method of contraception for at least 14 days prior to first dose of study drug through 90 days after the last dose.
• Body mass Index between 18 and 30kg/m2, inclusive; and a total body weight \>50 kg
• Laboratory tests at screening within normal ranges or not clinically significant as judged by the Investigator.

You may not qualify if:

• Received an investigational drug or participated in another research study within 30 days of the first dose of study drug or at any time through the study
• Evidence of current or history of clinically significant oncologic, pulmonary, hepatic, cardiovascular, gastrointestinal, haematologic, metabolic, neurological, immunologic, nephrologic, endocrine, psychiatric disease, or clinically significant current infection.
• Any condition that could possibly affect drug absorption, such as gastrectomy, diarrhea and lactose intolerance
• Use of any medications, vitamins, herbal supplements, dietary supplements or vaccinations within 14 days of the first dose of study drug or at any time through the study, unless prior approval is granted. This includes any drugs that are substrates, inhibitors or inducers of CYP3A4. Intermittent use of acetaminophen at doses of up to 2g/day is permitted
• History of drug or alcohol abuse within 2 years of Screening
• History of alcohol consumption within 24 hours of any study visit
• Tobacco users
• Consumption of fruit juices within 7 days prior to dosing
• Participation in unaccustomed strenuous exercise within 7 days prior to
• Positive urine drug screen
• Positive test for HIV-1, HBsAg or HCV
• Known hypersensitivity to MQ or artemisinins
• QTcF greater than 450msec

Sponsors & Collaborators

• Medicines for Malaria Venture: lead
• University of Cape Town: collaborator

Study Sites (1)

Division of Clinical Pharmacology, University of Cape Town

Cape Town, 7925, South Africa

Location

MeSH Terms

Conditions

Malaria

Interventions

artefenomel

Condition Hierarchy (Ancestors)

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

Results Point of Contact

• Title: Fiona Macintyre, PhD
• Organization: Medicines for Malaria Venture

macintyref@mmv.org

+41 22 555 0319

Study Officials

• Karen I Barnes

  University of Cape Town

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 7, 2012
• First Posted: June 11, 2012
• Study Start: August 1, 2012
• Primary Completion: April 1, 2013
• Study Completion: April 1, 2013
• Last Updated: April 16, 2015
• Results First Posted: March 26, 2015

Record last verified: 2015-03

Locations

ZA (1)