A Study to Investigate the Safety, Tolerability and Pharmacokinetics of OZ439 in Healthy Male and Female Subjects
January 7, 2015 updated by: Medicines for Malaria Venture
A Phase I Study To Investigate The Safety, Tolerability And Pharmacokinetic Profile Of OZ439 In Healthy Male and Female Subjects
OZ439 is a synthetic trioxolane that has potential value as a peroxide antimalarial agent.
This was a Phase I, single-centre, multi-component, double-blind, randomised, placebo-controlled study in healthy male and female subjects. The study was conducted in 3 parts:
- Part A investigated the safety, tolerability and pharmacokinetics (PK) of single oral escalating doses of OZ439. Up to 6 dose levels will be investigated to estimate dose proportionality.
- Part B, the effect of food on a single oral dose of OZ439 was investigated in a 2-way crossover design.
- Part C investigated the safety, tolerability and PK profile of multiple oral doses of OZ439.
The starting oral dose was 50 mg and the maximum single dose to be administered did not exceed 1600 mg per subject. The maximum duration of dosing proposed was 3 days.
Study Overview
Status
Completed
Conditions
Intervention / Treatment
- Drug: Placebo
- Drug: OZ439 50mg API capsules
- Drug: OZ439 100mg API capsules
- Drug: OZ439 200mg API capsules
- Drug: OZ439 400mg API capsules
- Drug: OZ439 400mg aqueous dispersion
- Drug: OZ439 800mg API capsules
- Drug: OZ439 800mg aqueous dispersion
- Drug: OZ439 1200mg API capsules
- Drug: OZ439 1600mg aqueous dispersion
- Drug: OZ439 200mg aqueous dispersion
Study Type
Interventional
Enrollment (Actual)
63
Phase
- Phase 1
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Locations
-
-
Florida
-
Miramar, Florida, United States, 33025
- Comprehensive Phase One Miramar; 3400 Enterprise Way
-
-
Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
18 years to 55 years (Adult)
Accepts Healthy Volunteers
Yes
Genders Eligible for Study
All
Description
Inclusion Criteria:
- Healthy male//female subjects between 18- 55 years of age (inclusive).
- Body mass Index (BMI) between 18 - 30 kg/m2, inclusive; and a total body weight >60 kg (132 lbs).
- Healthy as determined by pre-study medical history, PE, 12 Lead ECG.
Females of childbearing potential must use 1 of birth control methods throughout study and for 30 days after last dose of study drug:
- Surgically sterile (bilateral tubal ligation, hysterectomy, bilateral oophorectomy) 6 months minimum prior to first dose of study drug.
- Intrauterine device (IUD) in place for at least 3 months prior to first dose of study drug.
- Barrier methods (condom or diaphragm) with spermicide starting at least 14 days prior to first dose of study drug through 30 days after last dose of study drug.
- Surgical sterilization of the partner(s) (vasectomy with zero sperm count for 6 months minimum prior to the first dose of study drug).
- Hormonal contraceptives starting at least 3 months prior to first dose of study drug. In addition, subjects must agree to use a barrier method (condom or diaphragm) with spermicide at least 14 days prior to first dose of study drug through 30 days after the last dose of study drug.
- Post-menopausal women with amenorrhea for at least 1 year will be eligible confirmed by FSH.
- Male subjects must agree to use double barrier method of contraception, from time of first dose of study drug through 90 days after last dose of study drug and must also agree to not donate sperm for 90 days after last dose of study drug. Clinical laboratory tests within the reference ranges.
- Able/willing to give written informed consent.
- Willing/to adhere to lifestyle guideline restrictions outlined in protocol.
- Willing and able to be confined to Clinical Research Unit as required by the protocol.
Exclusion Criteria:
- Evidence/history of clinically significant oncologic, pulmonary, hepatic, cardiovascular, hematologic, metabolic, neurological, immunologic, nephrologic, endocrine, psychiatric disease, current infection.
- Evidence/history of clinically significant gastrointestinal (some exclusions exist) disease, current infection.
- Any condition that affecting drug absorption, e.g., gastrectomy.
- History of post-antibiotic colitis.
- Breast feeding.
- QTc greater than 450 msec for males and 470 msec for females as corrected by the Bazett formula.
- History of drug or alcohol abuse within the past 2 years prior to Screening.
- Tobacco users
- Received investigational drug/ participated in another research study within 30 days of first dose of study drug in any part of study.
- Use of prescription drugs within 14 days prior to the first dose of study drug in Period 1, or need for any antibiotic during study.
- Received any non prescription meds, vitamins, herbal/dietary supplements within 7 days of administration of first dose of study drug in Period 1 (exceptions exist)
- Consumed alcohol within 72 hours of Day -1 in any part of study, or have a positive alcohol screen at screening or each admission to Clinical Research Unit (CRU).
- Consumed grapefruit juice or juices containing grapefruit or ate grapefruit within 7 days prior to first dose of study drug in any part of study.
- Positive serum pregnancy test at the Screening Visit or on Day -1 prior to inclusion in any part of the study.
- Positive test for HIV-1, HBsAg,HCV.
- Positive urine drug screen at Screening or admission to CRU.
- History of intolerance/ hypersensitivity to artemisinins.
- Likelihood of requiring treatment during study period with drugs not permitted by protocol.
- Subjects who have donated blood or experienced significant blood loss within 60 days of screening for study.
- Subjects whose hemoglobin is <12.5 g/dL for males/ <11.5 g/dL for females.
- Any concern by investigator regarding safe participation of the subject in study or for any other reason investigator considers subject inappropriate for participation in study.
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Crossover Assignment
- Masking: Quadruple
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
|---|---|
|
Experimental: Part A - 50 mg Single Dose
OZ439 Single doses of 50mg (capsules)
|
Other Names:
|
|
Experimental: Part A - 100mg Single Dose
OZ439 Single doses of 100mg (capsules)
|
OZ439 100mg (2x50mg API capsules)
Other Names:
|
|
Experimental: Part A - 200mg Single Dose
OZ439 Single doses of 200mg (capsules)
|
Other Names:
|
|
Experimental: Part A - 400mg Single Dose
OZ439 Single doses of 400mg (capsules)
|
OZ439 400mg (2x200mg API capsules)
Other Names:
|
|
Experimental: Part A - 400mg Single Dose + Food
OZ439 Single doses of 400mg (capsules) administered with food.
|
OZ439 400mg (2x200mg API capsules)
Other Names:
|
|
Experimental: Part A - 400mg AD Single Dose
OZ439 Single doses of 400mg (aqueous dispersion)
|
|
|
Experimental: Part A - 800mg Single Dose
OZ439 Single doses of 800mg (capsules)
|
OZ439 800mg (4x200 API capsules)
Other Names:
|
|
Experimental: Part A - 800mg AD Single Dose
OZ439 Single doses of 800mg (aqueous dispersion)
|
Other Names:
|
|
Experimental: Part A - 1200mg Single Dose
OZ439 Single doses of 1200mg (capsules)
|
OZ439 1200mg (6x200mg API capsules)
Other Names:
|
|
Experimental: Part A - 1600mg AD Single Dose
OZ439 Single doses of 800mg (aqueous dispersion)
|
Other Names:
|
|
Placebo Comparator: Part A - Placebo
Placebo control for Single rising Part A
|
|
|
Experimental: Part B - 800mg AD Single Dose Fed
Single dose of OZ439 800mg aqueous dispersion administered under fed conditions
|
Other Names:
|
|
Experimental: Part B - 800mg AD Single Dose Fast
Single dose of OZ439 800mg aqueous dispersion administered under fast conditions
|
Other Names:
|
|
Experimental: Part C - 200mg AD Multiple Dose
200mg aqueous solution OZ439 or placebo once daily for 3 days fasted
|
Other Names:
|
|
Experimental: Part C - 400mg AD Multiple Dose
400mg aqueous solution OZ439 or placebo once daily for 3 days fasted
|
|
|
Experimental: Part C - 800mg AD Multiple Dose
800mg aqueous solution OZ439 or placebo once daily for 3 days fasted
|
Other Names:
|
|
Placebo Comparator: Part C - Placebo
Placebo control for Multiple rising Part C
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
|---|---|---|
|
Adverse Events
Time Frame: From screening and at 10 (+/-2) days after last dose of study medication
|
Safety/Tolerability evaluation took into account the recorded AE profile, clinical laboratory safety tests, vital signs, 12 lead and continuous (Parts A and C) ECG monitoring, audiometry/Brainstem Auditory Evoked Potentials (BAEP) parameters (Parts A and C) including any additional tests required to evaluate any safety concerns.
|
From screening and at 10 (+/-2) days after last dose of study medication
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
|---|---|---|
|
OZ439 AUC0-t
Time Frame: Samples collected from Pre-dose up to 96h post dose
|
Area under the plasma concentration-time curve from zero to time t of the last measured concentration above the limit of quantification (AUC0-t).
|
Samples collected from Pre-dose up to 96h post dose
|
|
OZ439 AUC0-∝
Time Frame: Samples collected from Pre-dose up to 96h post dose
|
Area under the plasma concentration-time curve from zero to infinity (AUC0-∝).
|
Samples collected from Pre-dose up to 96h post dose
|
|
OZ439 Cmax
Time Frame: Samples collected from Pre-dose up to 96h post dose
|
Maximum observed plasma drug concentration (Cmax).
|
Samples collected from Pre-dose up to 96h post dose
|
|
OZ439 Tmax
Time Frame: Samples collected from Pre-dose up to 96h post dose
|
Time to maximum observed plasma drug concentration of OZ439
|
Samples collected from Pre-dose up to 96h post dose
|
|
OZ439 t1/2
Time Frame: Samples collected from Pre-dose up to 96h post dose
|
Apparent terminal half-life (t1/2)
|
Samples collected from Pre-dose up to 96h post dose
|
|
OZ439 Rac
Time Frame: Samples collected from Pre-dose up to 96h post dose
|
Accumulation index is the ratio of drug exposure observed during a dosing interval at steady-state divided by drug exposure after a single first dose, as described by the following equations: Accumulation index (Rac) = AUC0-(Day 3)/ AUC0-(Day 1) |
Samples collected from Pre-dose up to 96h post dose
|
Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Sponsor
Investigators
- Study Director: Joerg Moehrle, PhD, Medicines for Malaria Venture
- Principal Investigator: Maria Gutierrez, MD, Comprehensive Phase One Miramar, 3400 Enterprise Way, Miramar, FL 33025
Publications and helpful links
The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.
Helpful Links
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start
April 1, 2009
Primary Completion (Actual)
October 1, 2009
Study Completion (Actual)
December 1, 2009
Study Registration Dates
First Submitted
June 24, 2009
First Submitted That Met QC Criteria
June 24, 2009
First Posted (Estimate)
June 25, 2009
Study Record Updates
Last Update Posted (Estimate)
January 8, 2015
Last Update Submitted That Met QC Criteria
January 7, 2015
Last Verified
January 1, 2015
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
Other Study ID Numbers
- MMV_OZ439_09_001
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.