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Trial registered on ANZCTR


Registration number
ACTRN12615000267550
Ethics application status
Approved
Date submitted
5/03/2015
Date registered
20/03/2015
Date last updated
5/08/2016
Type of registration
Prospectively registered

Titles & IDs
Public title
A Multiple Daily Oral Dose Study of DUR-928 in Healthy Volunteers
Scientific title
A Randomized, Double-Blind, Placebo-Controlled, Multiple Dose Study to Assess the Safety and Pharmacokinetics of DUR-928 in Healthy Volunteers Following Daily Oral Dosing
Secondary ID [1] 286321 0
Nil known
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Treatment of Fatty Liver Disease 294418 0
Condition category
Condition code
Metabolic and Endocrine 294728 294728 0 0
Other metabolic disorders
Oral and Gastrointestinal 294810 294810 0 0
Other diseases of the mouth, teeth, oesophagus, digestive system including liver and colon

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
DUR-928 powder for reconstitution.
In Cohort 1 and Cohort 2, each subject will receive 5 daily doses of either active DUR-928 or placebo (calcium carbonate) according to the Cohort they are participating in and the intervention they are randomised to. In Cohort 3 each subject will receive a single dose of DUR-298 in an open-label (fasted/fed) crossover design. There will be a 3-7 day washout between fasted and fed periods.
The doses of the intervention are described below per cohort:
Cohort 1: DUR-928 or placebo (100 mg)
Cohort 2: DUR-928 or placebo (300 mg)
Cohort 3: DUR-928 (300mg), in fasted and fed state
Intervention code [1] 291364 0
Treatment: Drugs
Comparator / control treatment
Placebo (Calcium carbonate powder for reconstitution)
In Cohort 1 and Cohort 2, each subject will receive 5 daily doses of either active DUR-928 or placebo (calcium carbonate) according to the Cohort they are participating in and the intervention they are randomised to. There is no placebo in Cohort 3; all subjects receive active DUR-928.
Control group
Placebo

Outcomes
Primary outcome [1] 294493 0
To evaluate the safety of multiple doses of DUR-928 in healthy volunteers at steady state.
Timepoint [1] 294493 0
Safety Timepoints: Safety assessments including vital sign measurement, safety laboratory tests, 12-lead ECGs and Adverse Event collection are carried out at various timepoints during the 5 day dosing period, in the 48 hours post Dose 5 (last study drug administration), and during the follow up visit (7 days post Dose 5).
Pharmacokinetic Timepoints: PK samples are collected at the following timepoints: Dose 1(Pre-dose, and at 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, 8, 12, and 16 hours post Dose 1), Dose 2 – 4 (Pre-dose), Dose 5 (Pre-dose, and at 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, 8, 12, 16, 24, 36 and 48 hours post Dose 5).
Primary outcome [2] 294557 0
To evaluate the pharmacokinetics of multiple doses of DUR-928 in healthy volunteers at steady state.
Timepoint [2] 294557 0
Pharmacokinetic timepoints are: Dose 1(Pre-dose, and at 0.5 , 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, 8, 12, and 16 hours post Dose 1), Dose 2-4 (Pre-dose), and Dose 5 (Pre-dose, and at 0.5 , 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, 8, 12, 16, 24, 36 and 48 hours post Dose 5).
Secondary outcome [1] 313452 0
To determine any dose limiting adverse drug effects at steady state following multiple oral dosing of DUR 928 in healthy volunteers.
Timepoint [1] 313452 0
Timepoint: Adverse events are collected for the duration of the study; from Day 1 (Dose 1) to Day 12 (follow-up visit).

Based on currently available animal toxicology and the first in human trial experience, adverse drug effects are not expected. Therefore, subjects will be monitored for any and all adverse events.
Secondary outcome [2] 313453 0
Evaluate dose proportionality of DUR-928 at steady state.
Timepoint [2] 313453 0
Timepoint: Dose proportionality information will be obtained by comparing plasma levels at all Pharmacokinetic timepoints, across the two dose levels (100 and 300 mg) evaluated.
Pharmacokinetic timepoints are: Dose 1(Pre-dose, and at 0.5 , 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, 8, 12, and 16 hours post Dose 1), Dose 2-4 (Pre-dose), and Dose 5 (Pre-dose, and at 0.5 , 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, 8, 12, 16, 24, 36 and 48 hours post Dose 5).
Secondary outcome [3] 315277 0
To evaluate the effect of a standard meal on the pharmacokinetics of DUR-928.
Timepoint [3] 315277 0
Timepoint: Standard PK parameters will be determined for DUR-928 from treatment Period 1 (fasted) and Period 2 (fed) in Cohort 3 and the food effect will be determined from the exposure data (Cmax and AUC).

Eligibility
Key inclusion criteria
-Be in good health as determined by medical history, physical examination, 12 lead ECG and clinical laboratory evaluations at screening;
-Male subjects must agree to use a medically acceptable method of contraception/birth control throughout the study duration and for 90 days after the study is completed;
-Female subjects must be of non-childbearing potential (i.e., surgically sterilized via hysterectomy, oophorectomy, or bilateral tubal ligation, physiologically incapable of becoming pregnant, including any female who is post-menopausal; post menopausal is defined as documented amenorrhea for at least 1 year with an FSH >/= 40 mIU/ml if menses has occurred within 2 years);
-Willing and be able to be admitted to the clinical study unit for 7 nights and 8 days;
-Able to abstain from alcohol and tobacco use during the trial.
Minimum age
19 Years
Maximum age
55 Years
Gender
Both males and females
Can healthy volunteers participate?
Yes
Key exclusion criteria
-Significant blood loss or donated blood in the 30 days prior to study participation
-Participation in an investigational drug study within 30 days prior to dosing.
-History of drug or alcohol abuse.
-Use of any medications, including OTC and herbal or nutritional supplements during the week prior to drug dosing
-Positive tests for HIV, hepatitis B/C, drugs of abuse or alcohol breath-test.
-Clinically significant abnormalities

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)
In Cohort 1 and Cohort 2, ten subjects per cohort will be randomized with a 4:1 randomization whereby 8 subjects receive DUR-928 and 2 subjects receive placebo. The dose will be provided to blinded study staff in a blinded fashion.
A central randomization schedule will be generated by the INC Research Head of Biometrics – who will have no further involvement in the study. The central Randomization schedule will be provided only to the site pharmacy staff (unblinded) who will be exclusively responsible for preparing the doses. Subjects will be assigned a randomization number in sequential order, as their eligibility is confirmed, by blinded site staff (who have no access to the Randomization schedule).

In Cohort 3, all eight subjects will receive a single dose of DUR-298 in an open-label (fasted/fed) crossover design. There is no requirement to conceal treatment allocation.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Simple randomisation using a randomisation table/schedule generated by computer software.
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
Intervention assignment
Parallel
Other design features
In Cohort 1 and Cohort 2, ten subjects per cohort with a 4:1 randomization ratio will be treated with 8 subjects receiving DUR-928 and 2 subjects receiving placebo for a total of 2 cohorts (20 subjects total will be enrolled). The second cohort of 10 subjects continues only after the safety assessment of the first cohort.
Following review of all data from Cohort 1 and Cohort 2, eight new subjects will be enrolled into Cohort 3. All eight subjects in Cohort 3 will receive a single dose of DUR-298 in an open-label (fasted/fed) crossover design.
Phase
Phase 1
Type of endpoint(s)
Safety
Statistical methods / analysis
Safety – Safety will be evaluated by assessment of clinical laboratory tests, physical examinations including vital signs, and ECGs, and by the documentation of all spontaneously reported adverse events.
Pharmacokinetics – Plasma concentration data of DUR-928 and its metabolite at each dose level will be used to calculate relevant pharmacokinetic parameters.
Pharmacokinetic parameters will summarized by dose level and fasted vs fed state, using descriptive statistics.
Due to the exploratory nature of this study, no power or sample size calculations have been performed.

Recruitment
Recruitment status
Completed
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 postcode(s) [1] 9346 0
3004 - Melbourne

Funding & Sponsors
Funding source category [1] 290893 0
Commercial sector/Industry
Name [1] 290893 0
DURECT Corporation
Address [1] 290893 0
10260 Bubb Road
Cupertino, CA 95014, USA
Country [1] 290893 0
United States of America
Primary sponsor type
Commercial sector/Industry
Name
INC Research
Address
159 Port Rd, Hindmarsh South Australia, 5007
Country
Australia
Secondary sponsor category [1] 289573 0
None
Name [1] 289573 0
Address [1] 289573 0
Country [1] 289573 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 292495 0
Alfred Hospital Ethics Committee
Ethics committee address [1] 292495 0
Ethics committee country [1] 292495 0
Australia
Date submitted for ethics approval [1] 292495 0
04/02/2015
Approval date [1] 292495 0
27/02/2015
Ethics approval number [1] 292495 0
44/15

Summary
Brief summary
This research project is being conducted to look at how safe and well tolerated a new drug called DUR-928 is when given to healthy volunteers, once daily for 5 days at 2 different dose levels. The pharmacokinetics of DUR-928 will also be studied; this is done by measuring the amount of DUR-928 in the blood at different times throughout the 5 day dosing period, allowing us to evaluate how DUR-928 is handled by the body (for example how quickly it gets into the blood stream). This study will also look at the effect the food may have of the pharmacokinetics of DUR-928.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 55594 0
Dr Jason Lickliter
Address 55594 0
Nucleus Network
5th Floor, Burnet Tower, AMREP Precinct
89 Commercial Road
Melbourne, Victoria, Australia, 3004

Country 55594 0
Australia
Phone 55594 0
+ 61 3 9076 8906
Fax 55594 0
+ 61 3 9076 8911
Email 55594 0
j.lickliter@nucleusnetwork.com.au
Contact person for public queries
Name 55595 0
Ms Jemma Lawson
Address 55595 0
INC Research
159 Port Road,
Hindmarsh, SA 5007, Australia
Country 55595 0
Australia
Phone 55595 0
+61 8 7202 1510
Fax 55595 0
+61 8 7202 1599
Email 55595 0
jemma.lawson@incresearch.com
Contact person for scientific queries
Name 55596 0
Ms Jemma Lawson
Address 55596 0
INC Research
159 Port Road,
Hindmarsh, SA 5007, Australia
Country 55596 0
Australia
Phone 55596 0
+61 8 7202 1510
Fax 55596 0
+61 8 7202 1599
Email 55596 0
jemma.lawson@incresearch.com

No information has been provided regarding IPD availability
Summary results
Have study results been published in a peer-reviewed journal?
Other publications
Have study results been made publicly available in another format?
Results – basic reporting
Results – plain English summary