Back to resultsSafety, Tolerability & Pharmacokinetics (PK) of Co-administered Single Doses of OZ439 and Mefloquine (MQ) in Healthy Volunteers
Primary Purpose
Malaria
Status
Terminated
Phase
Phase 1
Locations
South Africa
Study Type
Interventional
Intervention
OZ439 100mg
OZ439 400mg
MQ 250 mg, single dose
MQ 750mg, single dose
Placebo
Sponsored by
About this trial
This is an interventional treatment trial for Malaria focused on measuring Malaria, PK, OZ439, Mefloquine, Healthy Volunteers
Eligibility Criteria
Inclusion Criteria:
- 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.
Exclusion Criteria:
- 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
Sites / Locations
- Division of Clinical Pharmacology, University of Cape Town
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm 4
Arm 5
Arm Type
Experimental
Experimental
Experimental
Experimental
Placebo Comparator
Arm Label
OZ439 100mg single dose
OZ439 100mg plus MQ 250mg single doses
OZ439 400mg single dose
OZ439 400mg plus MQ 750mg single doses
Placebo
Arm Description
OZ439 100mg single dose oral suspension
Single dose OZ439 100mg oral suspension in combination with single dose MQ 250mg tablet
OZ439 400mg single dose oral suspension
Single dose OZ439 400mg oral suspension in combination with single dose MQ 750mg tablets
Placebo
Outcomes
Primary Outcome Measures
OZ439 AUC0-t
Area under the plasma concentration versus time curve (AUC) of OZ439
Secondary Outcome Measures
OZ439 Cmax
Peak Plasma Concentration (Cmax) of OZ439
MQ AUC0-t
Area under the plasma concentration versus time curve (AUC) of MQ
MQ Cmax
Peak Plasma Concentration (Cmax) of MQ
Full Information
NCT ID
NCT01615822
First Posted
June 7, 2012
Last Updated
March 27, 2015
Sponsor
Medicines for Malaria Venture
Collaborators
University of Cape Town
1. Study Identification
Unique Protocol Identification Number
NCT01615822
Brief Title
Safety, Tolerability & Pharmacokinetics (PK) of Co-administered Single Doses of OZ439 and Mefloquine (MQ) in Healthy Volunteers
Official Title
A Phase I Healthy Volunteer Study Investigating the Safety, Tolerability & Pharmacokinetics of Co-administered Single Doses of OZ439 and Mefloquine
Study Type
Interventional
2. Study Status
Record Verification Date
March 2015
Overall Recruitment Status
Terminated
Why Stopped
Decision taken to halt progression of mefloquine as a potential partner for OZ439 as a single dose cure due to low probability of success
Study Start Date
August 2012 (undefined)
Primary Completion Date
April 2013 (Actual)
Study Completion Date
April 2013 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Medicines for Malaria Venture
Collaborators
University of Cape Town
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Malaria
Keywords
Malaria, PK, OZ439, Mefloquine, Healthy Volunteers
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
25 (Actual)
8. Arms, Groups, and Interventions
Arm Title
OZ439 100mg single dose
Arm Type
Experimental
Arm Description
OZ439 100mg single dose oral suspension
Arm Title
OZ439 100mg plus MQ 250mg single doses
Arm Type
Experimental
Arm Description
Single dose OZ439 100mg oral suspension in combination with single dose MQ 250mg tablet
Arm Title
OZ439 400mg single dose
Arm Type
Experimental
Arm Description
OZ439 400mg single dose oral suspension
Arm Title
OZ439 400mg plus MQ 750mg single doses
Arm Type
Experimental
Arm Description
Single dose OZ439 400mg oral suspension in combination with single dose MQ 750mg tablets
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
Placebo
Intervention Type
Drug
Intervention Name(s)
OZ439 100mg
Intervention Description
OZ439 100mg oral suspension, single dose
Intervention Type
Drug
Intervention Name(s)
OZ439 400mg
Intervention Description
OZ439 400mg oral suspension, single dose
Intervention Type
Drug
Intervention Name(s)
MQ 250 mg, single dose
Intervention Description
Mefloquine 250 mg tablet, single dose
Intervention Type
Drug
Intervention Name(s)
MQ 750mg, single dose
Intervention Description
Mefloquine 750mg oral tablet, single dose
Intervention Type
Drug
Intervention Name(s)
Placebo
Primary Outcome Measure Information:
Title
OZ439 AUC0-t
Description
Area under the plasma concentration versus time curve (AUC) of OZ439
Time Frame
Up to 42 days post-dose
Secondary Outcome Measure Information:
Title
OZ439 Cmax
Description
Peak Plasma Concentration (Cmax) of OZ439
Time Frame
Up to 42 days post-dose
Title
MQ AUC0-t
Description
Area under the plasma concentration versus time curve (AUC) of MQ
Time Frame
Up to 42 days post-dose
Title
MQ Cmax
Description
Peak Plasma Concentration (Cmax) of MQ
Time Frame
Up to 42 days 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 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.
Exclusion Criteria:
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Karen I Barnes
Organizational Affiliation
University of Cape Town
Official's Role
Principal Investigator
Facility Information:
Facility Name
Division of Clinical Pharmacology, University of Cape Town
City
Cape Town
ZIP/Postal Code
7925
Country
South Africa
12. IPD Sharing Statement
Learn more about this trial
Safety, Tolerability & Pharmacokinetics (PK) of Co-administered Single Doses of OZ439 and Mefloquine (MQ) in Healthy Volunteers
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