A Multiple Daily Oral Dose Study of DUR-928 in Healthy Volunteers

• Register: ANZCTR
• Last refreshed on: 13 January 2020
• Main ID: ACTRN12615000267550
• Date of registration: 20/03/2015
• Prospective Registration: Yes
• Primary sponsor: INC Research
• 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
• Date of first enrolment: 23/03/2015
• Target sample size: 28
• Recruitment status: Completed
• URL: https://anzctr.org.au/ACTRN12615000267550.aspx
• Study type: Interventional
• Study design: Purpose: Treatment; Allocation: Randomised controlled trial; Masking: Blinded (masking used);Assignment: Parallel;Type of endpoint: Safety;
• Phase: Phase 1

Countries of recruitment

Australia

Contacts

• Name: Ms Jemma Lawson

• Name: Ms Jemma Lawson

Key inclusion & exclusion criteria

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.

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


Age minimum: 19 Years
Age maximum: 55 Years
Gender: Both males and females

Health Condition(s) or Problem(s) studied

Oral and Gastrointestinal - Other diseases of the mouth, teeth, oesophagus, digestive system including liver and colon

Metabolic and Endocrine - Other metabolic disorders

Treatment of Fatty Liver Disease;
Treatment of Fatty Liver Disease

Intervention(s)

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

Primary Outcome(s)

To evaluate the safety of multiple doses of DUR-928 in healthy volunteers at steady state. [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).
]

To evaluate the pharmacokinetics of multiple doses of DUR-928 in healthy volunteers at steady state. [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(s)

Evaluate dose proportionality of DUR-928 at steady state. [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).]

To determine any dose limiting adverse drug effects at steady state following multiple oral dosing of DUR 928 in healthy volunteers.
[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.]

To evaluate the effect of a standard meal on the pharmacokinetics of DUR-928. [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).]

Secondary ID(s)

Nil known

Source(s) of Monetary Support

DURECT Corporation

Ethics review

Status: Approved
Approval date:
Contact:

Alfred Hospital Ethics Committee