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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT01383096




Registration number
NCT01383096
Ethics application status
Date submitted
23/06/2011
Date registered
28/06/2011
Date last updated
29/01/2015

Titles & IDs
Public title
Study To Investigate The Relative Bioavailability of OZ439 Formulations In Healthy Volunteers
Scientific title
A Phase I Study To Investigate The Relative Bioavailability of OZ439 Formulations In Healthy Volunteers
Secondary ID [1] 0 0
MMV_OZ439_11_001
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Healthy Volunteers 0 0
Condition category
Condition code

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - OZ439 mesylate 800mg Powder in Bottle for Oral Suspension
Treatment: Drugs - OZ439 mesylate 400mg Prototype Solution Formula 1
Treatment: Drugs - OZ439 mesylate 800mg Prototype Solution Formula 1
Treatment: Drugs - OZ439 mesylate 800mg Prototype Solution Formula 2

Active Comparator: Cohort 1 - Treatment A: OZ439 800mg PIB, fed - OZ439 800 mg (as free base) as powder in a bottle (PIB)for reconstitution in a suspension prior to administration. Administered 30 minutes after a standard fatty breakfast.

Experimental: Cohort 1 - Treatment D: OZ439 800 mg Prototype F1 fasted - OZ439 800 mg (as free base) as a prototype solution formulation 1. Administered fasted.

Experimental: Cohort 2 - Treatement H: OZ439 800 mg Prototype F2 fasted - OZ439 800 mg (as free base) as a prototype solution formulation 2. Administered fasted.

Experimental: Cohort 3 - Treatement K: OZ439 400mg Prototype F1 fasted - Best Prototype Solution - OZ439 400 mg as prototype solution formulation 1. Administered fasted.

Experimental: Cohort 1 - Treatement B: OZ439 800mg PIB fasted - OZ439 800 mg (as free base) as powder in a bottle (PIB) for reconstitution in a suspension prior to oral administration. Administered fasted.

Experimental: Cohort 1 - Treatment C:OZ439 800mg PIB with milk - OZ439 800 mg (as free base) as powder in a bottle (PIB) for reconstitution in a suspension prior to oral administration. Administered following 200 mL milk.

Experimental: Cohort 3 - Treatment J: OZ439 800mg Prototype F1 fasted - Best Prototype Solution - OZ439 800 mg (as free base) as prototype solution formulation 1. Administered fasted.

Experimental: Cohort 1 - Treatement E: OZ439 800mg Prototype F1 with milk - OZ439 800 mg (as free base) as a prototype solution formulation 1. Administered with milk.

Experimental: Cohort 2 - Treatement F: OZ439 800 mg PIB fasted - OZ439 800 mg (as free base) as powder in a bottle (PIB) for reconstitution in a suspension prior to oral administration. Administered fasted.

Experimental: Cohort 2 - Treatement G: OZ439 800mg PIB with milk - OZ439 800 mg (as free base) as powder in a bottle (PIB) for reconstitution in a suspension prior to oral administration. Administered following 200 mL milk.

Experimental: Cohort 2 - Treatement I: OZ349 800mg Prototype F2 with milk - OZ439 800 mg (as free base) as a prototype solution formulation 2. Administered with milk.


Treatment: Drugs: OZ439 mesylate 800mg Powder in Bottle for Oral Suspension
OZ439 800 mg (as free base) as powder in a bottle for reconstitution in a suspension prior to oral administration

Treatment: Drugs: OZ439 mesylate 400mg Prototype Solution Formula 1
OZ439 400 mg (as free base) as a prototype solution formulation 1

Treatment: Drugs: OZ439 mesylate 800mg Prototype Solution Formula 1
OZ439 800 mg (as free base) as a prototype solution formulation 1

Treatment: Drugs: OZ439 mesylate 800mg Prototype Solution Formula 2
OZ439 800 mg (as free base) as a prototype solution formulation 2

Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
OZ439 Cmax - The maximum observed plasma drug concentrations (Cmax)
Timepoint [1] 0 0
1, 2, 3, 4, 6, 8, 12, 24, 48, 72, 96 and 168 hours post dosing
Primary outcome [2] 0 0
OZ439 AUC0-8 - Area under the plasma concentration-time curve from zero to infinity (AUC0-8)
Timepoint [2] 0 0
1, 2, 3, 4, 6, 8, 12, 24, 48, 72, 96 and 168 hours post dosing
Primary outcome [3] 0 0
OZ439 t1/2 - Apparent terminal half life (t1/2)
Timepoint [3] 0 0
1, 2, 3, 4, 6, 8, 12, 24, 48, 72, 96 and 168 hours post dosing

Eligibility
Key inclusion criteria
- Healthy male and female volunteers between 18 and 55 years (inclusive).
Post-menopausal women with amenorrhoea for at least 2 years are eligible confirmed by
FSH level >/ = 25microlU/ml

- Body mass Index between 18 and 30 kg/m2, inclusive; and body weight > 50 kg.

- Healthy as determined by pre-study medical history, physical examination (including
body temperature), 12 Lead ECG.

- Male volunteers must agree to use a double barrier method of contraception including
abstinence, condom plus diaphragm or condom plus IUD or condom plus stable
oral/transdermal/injectable hormonal contraceptive by female partner for at least 14
days prior to the time of the first dose of study drug through 90 days after the last
dose of study drug and must also agree to not donate sperm for 90 days after the last
dose of study drug. Vasectomy with zero sperm count for 6 months minimum prior to the
first dose of study drug is an acceptable form of contraception

- Clinical laboratory tests at screening within the reference ranges or if outside the
normal range not clinically significant. ALT, AST and total bilirubin must be within
the normal range

- Able and willing to give written informed consent

- Willing and able to adhere to the lifestyle guideline requirements

- Willing and able to be confined to the Clinical Research Unit as required by the
protocol
Minimum age
18 Years
Maximum age
55 Years
Gender
Both males and females
Can healthy volunteers participate?
Yes
Key exclusion criteria
- Evidence of or history of clinically significant oncologic, pulmonary, hepatic,
cardiovascular, hematologic, metabolic, neurological, immunologic, nephrologic,
endocrine, psychiatric disease, or current infection

- Evidence of or history of clinically significant gastrointestinal (excluding
appendectomy and cholecystectomy) disease or current infection.

- Any condition that could possibly affect drug absorption, e.g. gastrectomy, diarrhea

- History of post-antibiotic colitis

- Pregnancy or breastfeeding

- QTc greater than 450 msec for males and females as corrected by the Fredricia's
formula or evidence or history of abnormal cardiac rhythm

- History of drug or alcohol abuse within the past 2 years prior to Screening

- Tobacco users (includes stopping smoking less than 90 days prior to screening.
"Tobacco use" includes smoking and the use of snuff and chewing tobacco, and other
nicotine containing products

- Received an investigational drug or participated in another research study within 30
days of the first dose of study drug in any part of the 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 the study

- Received any non prescription medications, vitamins, herbal supplements or dietary
supplements within 7 days of the first dose of study drug in Period 1, unless prior
approval is granted. Excluded from this list is intermittent use of acetaminophen at
doses of up to 2 g/day

- Consumed alcohol within 72 hours of Day -1 in any part of the study, or have a
positive alcohol screen at screening or each admission

- Consumed fruit juice or ate grapefruit within 7 days prior to the first dose of study
drug in any part of the study

- Positive test for human immunodeficiency virus, hepatitis B surface antigen or
anti-hepatitis C virus

- Positive urine drug screen at Screening or admission

- History of intolerance or hypersensitivity to artemisinins

- Likelihood of requiring treatment during the study period with drugs not permitted by
the study protocol

- Volunteers who have donated blood or experienced significant blood loss within 90 days
of screening

- Hemoglobin < 13.5 g/dL for males and < 12.5 g/dL for females

- Any concern by the investigator regarding the safe participation of the volunteer or
any reason the investigator considers the volunteer inappropriate for participation

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Crossover
Other design features
Phase
Phase 1
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
VIC
Recruitment hospital [1] 0 0
AMREP Centre for Clinical Studies - Melbourne
Recruitment postcode(s) [1] 0 0
VIC 3004 - Melbourne

Funding & Sponsors
Primary sponsor type
Other
Name
Medicines for Malaria Venture
Address
Country
Other collaborator category [1] 0 0
Other
Name [1] 0 0
Nucleus Network Ltd
Address [1] 0 0
Country [1] 0 0
Other collaborator category [2] 0 0
Other
Name [2] 0 0
Syneos Health
Address [2] 0 0
Country [2] 0 0

Ethics approval
Ethics application status

Summary
Brief summary
This study is designed to assess prototype formulations compared to the aqueous dispersion of
Active Pharmaceutical Ingredient used in Phase I and Phase IIa studies to date. It is hoped
that the bioavailability of OZ439 can be enhanced in the fasted state to be close to that
observed when given after food. This will improve the utility of OZ439 in the field as well
as decreasing the cost of treatment (by decreasing the dose of OZ439 required) which is very
important for an antimalarial drug product destined for use in developing counties.
Trial website
https://clinicaltrials.gov/show/NCT01383096
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Peter Peter Hodsman, MD
Address 0 0
AMREP Centre for Clinical Studies, Nucleus Network, 89 Commercial Road, Melbourne, VIC 3004 Australia
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

Summary results
Other publications