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Trial registered on ANZCTR


Registration number
ACTRN12616000856415
Ethics application status
Approved
Date submitted
27/06/2016
Date registered
30/06/2016
Date last updated
13/09/2016
Type of registration
Prospectively registered

Titles & IDs
Public title
A Single Infusion Study of DUR-928 in Healthy Volunteers
Scientific title
A Randomized, Double-Blind, Placebo-Controlled, Single Ascending Dose Intravenous Infusion Study to Assess the Safety, Tolerability and Pharmacokinetics of DUR-928 in Healthy Volunteers
Secondary ID [1] 289546 0
Nil Known
Universal Trial Number (UTN)
Trial acronym
C928-006
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Acute Kidney Injury 299267 0
Condition category
Condition code
Renal and Urogenital 299270 299270 0 0
Other renal and urogenital disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
DUR-928 (powder for constitution): 30 mg/mL DUR-928 solution after constitution with sterile vehicle solution.
Placebo: sterile vehicle solution. The sterile vehicle solution contains hydroxypropyl betadex in phosphate buffered water.
Each subject will receive a single dose of either active DUR-928 or placebo. The constituted DUR-928 solution, or placebo vehicle, is appropriately diluted with glucose 5% intravenous solution to prepare the infusion solution. The dose will be administered via intravenous (IV) infusion. The doses of the intervention are described below per cohort:
Cohort 1: 50 mg/100 mL DUR-928 or placebo (vehicle solution) administered over 2 hours via IV infusion
Cohort 2: TBD* mg/100 mL of DUR 928 or placebo (vehicle solution) administered over 2 hours via IV infusion
*Note: Dose level for Cohort 2 will be determined after review of safety, tolerability, and pharmacokinetic data of Cohort 1 and will not exceed 300 mg.
Study participants will take part in only one cohort. All study participants will be confined to the study unit for the treatment period. Study staff will administer all doses.
Intervention code [1] 295142 0
Treatment: Drugs
Comparator / control treatment
Placebo: sterile vehicle solution. The sterile vehicle solution contains hydroxypropyl betadex in phosphate buffered water.
Each subject will receive a single dose of either active DUR-928 or placebo according to the intervention they are randomised to. The dose will be administered via intravenous (IV) infusion.
Control group
Placebo

Outcomes
Primary outcome [1] 298749 0
To evaluate the safety and tolerability of single, ascending intravenous (IV) doses of DUR-928 in healthy volunteers.
Timepoint [1] 298749 0
Routine vital sign measurements (blood pressure [BP], heart rate [HR] and respiratory rate [RR]) will be measured at screening, Day -1, pre-dose, 15, 30, 45 minutes and 1, 1.25, 1.5, 1.75, 2, 3, 4, 8, 12, 24, 36 and 48 hours post-dose, and at trial completion (Day 7). Temperature measurements will be measured at screening, Day-1, pre-dose, 48 hours post-dose initiation and at trial completion (Day 7).
Continuous telemetry monitoring will be initiated pre-dose and continue throughout intravenous infusion of study drug (at least 2 hours post-dose).
Physical examination will be performed at screening, Day -1, and at trial completion (Day 7). The physical exam done on Day -1 will be abbreviated.
Safety Laboratory tests (Chemistry, Hematology, Gamma-glutamyl transpeptidase (GGT), and Urinalysis) will be drawn at screening, Day 1, 24 and 48 hours post-dose, and at trial completion (Day 7).
All adverse events will be collected from Day -1 and continues through to trial completion (Day 7).
Twelve-lead ECGs will be obtained from subjects at screening, Day -1, pre-dose, and at approximately 1, 2 and 48 hours post-dose initiation. Additional ECGs may be obtained if clinically indicated.
Primary outcome [2] 298750 0
To characterize the pharmacokinetics of DUR-928 in plasma following administration of single, ascending intravenous doses in healthy volunteers.
Timepoint [2] 298750 0
The following PK parameters will be assessed - Cmax, Tmax, Clast, Tlast, Terminal elimination rate constant, AUC0-last, AUC0-t, AUCinf, %AUCexp, T1/2, Vz/F, CL/F.
Blood samples will be collected for analysis of plasma concentrations of DUR-928 and 25 hydroxycholesterol (25-HC) up to 48 hours after initiation of study drug administration. The samples will be collected at pre-dose and at 0.5, 1, 1.5, 2, 3, 4, 8, 12, 24, 36 and 48 hours post study drug initiation.
Secondary outcome [1] 325132 0
To determine any dose limiting adverse drug effects following single ascending intravenous doses of DUR-928 in healthy volunteers.
Timepoint [1] 325132 0
There are no known systemic, dose-related or serious adverse reactions to DUR-928 when given as an oral solution to healthy volunteers in doses up to 1000 mg or when given as an intramuscular injection to healthy volunteers in doses up to 300mg. Hypersensitivity reactions have not been observed to date
Possible adverse reactions to the intravenous infusion of DUR-928 may include pain or discomfort at the infusion site. Any other adverse events will be recorded on a standard case report form and will be followed until resolution.
Timepoint: Adverse events are collected for the duration of the study; from Day -1 to the study completion visit (Day 7).

Eligibility
Key inclusion criteria
Be in good health as determined by medical history, physical examination, 12 lead ECG and clinical laboratory evaluations at screening;
Weight at least 50kg and BMI between 18.0 kg/m2 and 30.0 kg/m2, inclusive;
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;
Willing and be able to be admitted to the clinical study unit for 3 nights and 2 days;
Able to abstain from alcohol and tobacco use during the trial.
Minimum age
18 Years
Maximum age
55 Years
Sex
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)
2 cohorts of 8 subjects will be dosed with a 3:1 randomisation ratio - 6 subjects receiving DUR-928 and 2 subjects receiving placebo. The dose will be provided to blinded subjects by study staff in a blinded fashion.
A central randomization schedule will be generated by the INC Research Head of Biometrics personnel – 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).
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
The people analysing the results/data
Intervention assignment
Other
Other design features
2 cohorts (8 subjects per cohort) will be given a single intravenous infusion of DUR-928 or placebo. For each cohort, subjects will be randomized in 3:1 ratio - 6 subjects will receive active (DUR-928) and 2 subjects will receive placebo. Cohort 2 continues only after the safety assessment of Cohort 1. 16 subjects in total will be enrolled.
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. Safety will be summarised by dose level.
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, 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
25/07/2016
Actual
26/07/2016
Date of last participant enrolment
Anticipated
24/08/2016
Actual
24/08/2016
Date of last data collection
Anticipated
3/09/2016
Actual
3/09/2016
Sample size
Target
16
Accrual to date
Final
16
Recruitment in Australia
Recruitment state(s)
VIC
Recruitment hospital [1] 6025 0
Nucleus Network - Melbourne
Recruitment postcode(s) [1] 13475 0
3004 - Melbourne

Funding & Sponsors
Funding source category [1] 293923 0
Commercial sector/Industry
Name [1] 293923 0
DURECT Corporation
Country [1] 293923 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] 292746 0
None
Name [1] 292746 0
Address [1] 292746 0
Country [1] 292746 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 295341 0
Alfred Health
Ethics committee address [1] 295341 0
Ethics committee country [1] 295341 0
Australia
Date submitted for ethics approval [1] 295341 0
01/06/2016
Approval date [1] 295341 0
29/06/2016
Ethics approval number [1] 295341 0
268/16

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 66942 0
Dr Jason Lickliter
Address 66942 0
Nucleus Network
5th Floor, Burnet Tower, AMREP Precinct
89 Commercial Road
Melbourne, Victoria, Australia, 3004
Country 66942 0
Australia
Phone 66942 0
+ 61 3 9076 8960
Fax 66942 0
Email 66942 0
j.lickliter@nucleusnetwork.com.au
Contact person for public queries
Name 66943 0
Biljana Georgievska
Address 66943 0
Nucleus Network
5th Floor, Burnet Tower, AMREP Precinct
89 Commercial Road
Melbourne, Victoria, Australia, 3004
Country 66943 0
Australia
Phone 66943 0
+ 61 3 9076 9017
Fax 66943 0
Email 66943 0
B.Georgievska@nucleusnetwork.com.au
Contact person for scientific queries
Name 66944 0
Jemma Lawson
Address 66944 0
INC Research
159 Port Road,
Hindmarsh, SA 5007, Australia
Country 66944 0
Australia
Phone 66944 0
+61 8 7202 1500
Fax 66944 0
Email 66944 0
jemma.lawson@incresearch.com

No information has been provided regarding IPD availability


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

Documents added manually
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Documents added automatically
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