The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been endorsed by the ANZCTR. Before participating in a study, talk to your health care provider and refer to this information for consumers
Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT03239353




Registration number
NCT03239353
Ethics application status
Date submitted
27/07/2017
Date registered
1/08/2017
Date last updated
25/06/2018

Titles & IDs
Public title
A Phase 1 Study to Evaluate the Safety and Pharmacokinetics of Entecavir Extended Release (XR) in Healthy Subjects
Scientific title
A Phase 1, Randomized, Partially-Blind, Parallel-Group, Active and Placebo Controlled Study to Evaluate the Safety and Pharmacokinetics of Single Oral Doses of Entecavir Extended Release (XR) in Healthy Subjects
Secondary ID [1] 0 0
UAP008C001
Universal Trial Number (UTN)
Trial acronym
Linked study record

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

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Entecavir

Active Comparator: 1.5 mg ETV XR tablet -

Active Comparator: 3 mg ETV XR tablet -

Active Comparator: 6 mg ETV XR tablet -

Placebo Comparator: Placebo-to-match 1.5 mg ETV XR tablet -

Other: 0.5 mg ETV IR tablet -


Treatment: Drugs: Entecavir
Study drug (entecavir or placebo) will be administered with 240 mL of water following an overnight fast (no food or drink, except water, for at least 10 hours). Subjects will be required to fast (no food or beverages other than water) until after collection of the 4-hour blood draw.

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

Outcomes
Primary outcome [1] 0 0
To characterize the Pharmacokinetics (PK) of ETV XR tablet after single oral doses in healthy subjects. - Peak Plasma Concentration(Cmax)
Timepoint [1] 0 0
22 days
Primary outcome [2] 0 0
To characterize the Pharmacokinetics (PK) of ETV XR tablet after single oral doses - Area under the plasma concentration versus time curve (AUC)
Timepoint [2] 0 0
22 days
Primary outcome [3] 0 0
To characterize the Pharmacokinetics (PK) of ETV XR tablet after single oral doses - peak time (Tmax)
Timepoint [3] 0 0
22 days
Primary outcome [4] 0 0
To characterize the Pharmacokinetics (PK) of ETV XR tablet after single oral doses - Relative bioavailability (Frelative)
Timepoint [4] 0 0
22 days
Primary outcome [5] 0 0
To characterize the Pharmacokinetics (PK) of ETV XR tablet after single oral doses - half life (t1/2)
Timepoint [5] 0 0
22 days
Secondary outcome [1] 0 0
To assess ETV XR tablet in healthy subjects. - adverse events
Timepoint [1] 0 0
22 days
Secondary outcome [2] 0 0
To assess ETV XR tablet in healthy subjects. - laboratory abnormalities
Timepoint [2] 0 0
22 day
Secondary outcome [3] 0 0
To assess ETV XR tablet in healthy subjects. - vital signs
Timepoint [3] 0 0
22 days
Secondary outcome [4] 0 0
To assess ETV XR tablet in healthy subjects. - 12-lead electrocardiograms (ECGs)
Timepoint [4] 0 0
22 days
Secondary outcome [5] 0 0
To evaluate the dose linearity of ETV XR tablet - 1.5mg, 3mg and 6mg PK linearity
Timepoint [5] 0 0
60 days

Eligibility
Key inclusion criteria
Inclusion criteria:

Subjects will be considered for enrollment in the study if they meet all of the inclusion
criteria and none of the exclusion criteria.

1. Male or female aged between 18 and 55 years (inclusive). Body weight = 50 kg for
males, and =45 kg for females and Body Mass Index (BMI) between 18 and 28 kg/m2
(inclusive), BMI(kg/m2) = body weight(kg)/{height(m)}2;

2. Ability to fully understand the purpose, characteristic, method and the possible
adverse effects of the trial, and voluntarily signed Informed Consent obtained before
any trial-related procedures are performed;

3. Ability to comply with the requirements of this trial protocol, including refrain from
strenuous exercise/activity 3 days prior to Day -1 (admission) and for 3 days prior to
the Day 8, Day 15 and the final follow-up visit on Day 22through the duration of the
study

4. Have a creatinine clearance (CLCr) = 80 mL/min;

5. Male subjects and female subjects of child bearing potential must be willing to
practice effective contraception during the study and been willing and able to
continue contraception for 90 days after their dose of the study treatment;

6. Male subjects must refrain from sperm donation from Day -1 through completion of the
study and continuing for at least 90 days from the date of last dose of study drug;

7. Subjects must refrain from blood donation from Screening through completion of the
study and continuing for at least 30 days from date of last dose of study drug;

8. AST, ALT and bilirubin = 1.5xULN (isolated bilirubin > 1.5xULN is acceptable if
bilirubin is fractionated and direct bilirubin <35%);

9. Must, in the opinion of the Investigator, be in good health based upon medical
history, physical examination (including vital signs), and screening laboratory
evaluations (hematology, chemistry, and urinalysis must fall within the normal range
of the central laboratory reference ranges unless the results have been determined by
the Investigator to have no clinical significance).
Minimum age
18 Years
Maximum age
55 Years
Gender
Both males and females
Can healthy volunteers participate?
Yes
Key exclusion criteria
Exclusion criteria:

A subject meeting any of the following criteria will be excluded from the study:

1. Current or a history of any clinically significant medical illness or medical
disorders the investigator considers should exclude including (but not limited to)
neurological disease, cardiovascular disease, hepatic or renal disease,
gastrointestinal tract disease (such as dysphagia, gastrointestinal ulcers),
respiratory disease, metabolism, skeletal system diseases or other condition known to
interfere with absorption, distribution, metabolism, or excretion of drugs;

2. Has a positive result from serology examination for hepatitis B virus (HBV), hepatitis
C virus (HCV), or human immunodeficiency virus (HIV);

3. There are drug-dependent or drug abuse history, or urine drug abuse screening
positive;

4. Subject smoked more than 5 cigarettes or other tobacco or nicotine-containing products
within 1 month prior to dosing and is unwilling to abstain from smoking for 48 hours
prior to check-in (Day -1)ing, for the duration of the confinement period and at each
follow-up visit;

5. Has used an alcohol consumption of more than 14 units of alcohol per week (1 unit of
alcohol is equivalent to 360 mL of beer or 45 mL of spirits with 40 % of alcohol or
150 mL of wine) within 6 months prior to screening or taking products containing
alcohol 48 hours prior to IMP administration;

6. Participated in any drug or medical device clinical trial within 3 months prior to
screening;

7. Pregnant or breastfeeding women or pregnancy testing is positive;

8. Have taken any prescription medications, over-the-counter medications, supplements or
herbal products within 14 days, or 5 half-lives (whichever is longer), of study drug
dosing, with the exception of paracetamol and hormonal contraceptive medications,
unless in the opinion of the Investigator and/or Medical Monitor that the substance
would not have any material impact on participant safety or the quality of study data;

9. Donated blood greater than 400 mL or significant blood loss equivalent to 400 mL or
received blood transfusion within 3 months of screening; Or donated blood greater than
200 ml or significant blood loss equivalent to 200 mL within 1 months prior to
screening;

10. Has infectious diseases within four weeks at screening (in the opinion of the
investigator would pose a risk for participation in this study), severe trauma, or a
history of major surgery within 3 months;

11. Cannot tolerate venepuncture or cannulation;

12. Consumption of grapefruit, grapefruit juice, cranberries, or products containing
Seville oranges (fruit juices, marmalade, jam, etc) within 7 days prior to study drug
dosing; consumption of caffeine-containing products within 48 hours of study drug
dosing;

13. Have been vaccinated within 90 days of study dosing, with the exception of licensed
intranasal or intramuscular influenza vaccine = 14 days prior to dosing.

14. Have severe multiple allergies and / or severe allergies (including latex / heparin
allergy) history, or has hypersensitivity or significant intolerance to prescription
drugs or over-the-counter drugs or food;

15. Subjects who, in the opinion of the Investigator, should not participate in the study.

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
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s

Intervention assignment
Parallel
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)
WA
Recruitment hospital [1] 0 0
Linear Clinical Research Ltd - Nedlands
Recruitment postcode(s) [1] 0 0
6009 - Nedlands

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Aucta Pharmaceuticals, Inc
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
This is a phase 1, randomized, parallel-group, single-center study in healthy adult subjects.
The study will be conducted in two parts sequentially:

Part 1 is an open-label, two-arm, active-controlled design to evaluate the PK and safety of
single oral dose of ETV XR tablet (1.5 mg) in healthy subjects. Part 1 will consist of 16
healthy subjects.

Part 2 is a double-blind, three-arm, placebo-controlled design to evaluate the PK and safety
of higher oral doses of ETV XR tablet (3 mg and 6 mg) in healthy subjects. Part 2 will
consist of 24 healthy subjects.
Trial website
https://clinicaltrials.gov/show/NCT03239353
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Address 0 0
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

No data has been provided for results reporting
Summary results
Other publications