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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT03032536




Registration number
NCT03032536
Ethics application status
Date submitted
24/01/2017
Date registered
26/01/2017

Titles & IDs
Public title
Study of the Relative Oral Bioavailability of AL-3778 Tablets and Drug Interaction With Entecavir or Tenofovir Disoproxil Fumarate in Healthy Volunteers
Scientific title
A Randomized, Open-label, Multi-part Study of the Relative Oral Bioavailability of AL-3778 Tablets and Drug Interaction With Entecavir or Tenofovir Disoproxil Fumarate in Healthy Volunteers
Secondary ID [1] 0 0
U1111-1187-4391
Secondary ID [2] 0 0
AL-3778-1002
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Hepatitis B 0 0
Chronic Hepatitis B 0 0
Viral Hepatitis B 0 0
Condition category
Condition code
Infection 0 0 0 0
Other infectious diseases
Oral and Gastrointestinal 0 0 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
Treatment: Drugs - AL-3778
Treatment: Drugs - Entecavir
Treatment: Drugs - Tenofovir disoproxil fumarate

Experimental: Treatments A, B, C - Part 1: Cross-Over

* Treatment A: AL-3778 6 x 100-mg capsules (fasted) once.
* Treatment B: AL-3778 2 x 300-mg tablets (fasted) once
* Treatment C: AL-3778 2 x 300-mg tablets (high-fat meal) once.

Experimental: Treatments D, E, F - Part 2 (optional): Cross-Over

* Treatment D: AL-3778 2×300-mg tablets (fasted) once.
* Treatment E: AL-3778 tablet Dose (fasted) once. Dose will match Treatment F dose and will be:
* 1000mg: 2 x 500-mg OR
* 800mg: 1 x 300-mg + 1 x 500-mg OR
* 700mg: 1 x 200-mg + 1 x 500-mg
* Treatment F: AL-3778 tablet Dose (high-fat meal) once. Dose will match Treatment E dose and will be:
* 1000mg: 2 x 500-mg OR
* 800mg: 1 x 300-mg + 1 x 500-mg OR
* 700mg: 1 x 200-mg + 1 x 500-mg

Experimental: Treatment G - Part 3: AL-3778 twice daily administered under fasted conditions for 14 days.

Dose will be determined by Part 1 and/or Part 2 and will be one of the following tablet dosages:

* 600mg: 2 x 300-mg OR
* 1000mg: 2 x 500-mg OR
* 800mg: 1 x 300-mg + 1 x 500-mg OR
* 700mg: 1 x 200-mg + 1 x 500-mg

Active comparator: Treatment H - Part 3: Entecavir 0.5 mg once daily administered under fasted conditions for 14 days

Experimental: Treatment I - Part 3: AL-3778 twice daily with entecavir 0.5 mg once daily both administered under fasted conditions for 14 days.

AL-3778 dose will be determined by Part 1 and/or Part 2 and will be one of the following tablet dosages:

* 600mg: 2 x 300-mg OR
* 1000mg: 2 x 500-mg OR
* 800mg: 1 x 300-mg + 1 x 500-mg OR
* 700mg: 1 x 200-mg + 1 x 500-mg

Active comparator: Treatment J - Part 3: Tenofovir disoproxil fumarate 300 mg once daily administered under fasted conditions for 14 days

Experimental: Treatment K - Part 3: AL-3778 twice daily and tenofovir disoproxil fumarate 300 mg once daily both administered under fasted conditions for 14 days.

AL-3778 dose will be determined by Part 1 and/or Part 2 and will be one of the following tablet dosages:

* 600mg: 2 x 300-mg OR
* 1000mg: 2 x 500-mg OR
* 800mg: 1 x 300-mg + 1 x 500-mg OR
* 700mg: 1 x 200-mg + 1 x 500-mg


Treatment: Drugs: AL-3778
AL-3778 tablets or capsules

Treatment: Drugs: Entecavir
Entecavir once daily for 14 days

Treatment: Drugs: Tenofovir disoproxil fumarate
Tenofovir disoproxil fumarate once daily for 14 days
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
AL-3778, entecavir, tenofovir: Maximum observed plasma concentration (Cmax)
Timepoint [1] 0 0
At 0, 0.5, 1, 2, 3, 4, 6, 8, 10, 12 hours after dosing on Day 1 and 14 and once per day on Day 8, 10, 12, and 22
Primary outcome [2] 0 0
AL-3778, entecavir, tenofovir: Area under the plasma concentration-time curve from time 0 to last measurable concentration (AUClast)
Timepoint [2] 0 0
At 0, 0.5, 1, 2, 3, 4, 6, 8, 10, 12 hours after dosing on Day 1 and 14 and once per day on Day 8, 10, 12, and 22
Primary outcome [3] 0 0
AL-3778, entecavir, tenofovir: Area under the plasma concentration-time curve from time 0 to extrapolated to infinity (AUC8)
Timepoint [3] 0 0
At 0, 0.5, 1, 2, 3, 4, 6, 8, 10, 12 hours after dosing on Day 1 and 14 and once per day on Day 8, 10, 12, and 22
Primary outcome [4] 0 0
AL-3778, entecavir, tenofovir: Maximum observed plasma concentration on Day 1 (Cmax. Day 1)
Timepoint [4] 0 0
At 0, 0.5, 1, 2, 3, 4, 6, 8, 10, 12 hours after dosing on Day 1
Primary outcome [5] 0 0
AL-3778, entecavir, tenofovir: Minimum observed plasma concentration on Day 1 (Cmin, Day 1)
Timepoint [5] 0 0
At 0, 0.5, 1, 2, 3, 4, 6, 8, 10, 12 hours after dosing on Day 1
Primary outcome [6] 0 0
AL-3778, entecavir, tenofovir: Area under the plasma concentration-time curve from time 0 to dosing interval on Day 1 (AUC0-?, Day 1)
Timepoint [6] 0 0
At 0, 0.5, 1, 2, 3, 4, 6, 8, 10, 12 hours after dosing on Day 1
Primary outcome [7] 0 0
AL-3778, entecavir, tenofovir: Minimum observed plasma concentration (C_min)
Timepoint [7] 0 0
At 0, 0.5, 1, 2, 3, 4, 6, 8, 10, 12 hours after dosing on Day 1 and 14 and once per day on Day 8, 10, 12, and 22
Secondary outcome [1] 0 0
AL-3778, entecavir, tenofovir: Predose plasma concentrations (C_0-h)
Timepoint [1] 0 0
At 0, 0.5, 1, 2, 3, 4, 6, 8, 10, 12 hours after dosing on Day 1 and 14 and once per day on Day 8, 10, 12, and 22
Secondary outcome [2] 0 0
AL-3778, entecavir, tenofovir: Last observed plasma concentration (C_last)
Timepoint [2] 0 0
At 0, 0.5, 1, 2, 3, 4, 6, 8, 10, 12 hours after dosing on Day 1 and 14 and once per day on Day 8, 10, 12, and 22
Secondary outcome [3] 0 0
AL-3778, entecavir, tenofovir: Time of the maximum observed plasma concentration (T_max)
Timepoint [3] 0 0
At 0, 0.5, 1, 2, 3, 4, 6, 8, 10, 12 hours after dosing on Day 1 and 14 and once per day on Day 8, 10, 12, and 22
Secondary outcome [4] 0 0
AL-3778, entecavir, tenofovir: Time to last measurable plasma concentration (T_last)
Timepoint [4] 0 0
At 0, 0.5, 1, 2, 3, 4, 6, 8, 10, 12 hours after dosing on Day 1 and 14 and once per day on Day 8, 10, 12, and 22
Secondary outcome [5] 0 0
AL-3778, entecavir, tenofovir: Apparent oral clearance (CL/F)
Timepoint [5] 0 0
At 0, 0.5, 1, 2, 3, 4, 6, 8, 10, 12 hours after dosing on Day 1 and 14 and once per day on Day 8, 10, 12, and 22
Secondary outcome [6] 0 0
AL-3778, entecavir, tenofovir: Apparent volume of distribution (Vz/F)
Timepoint [6] 0 0
At 0, 0.5, 1, 2, 3, 4, 6, 8, 10, 12 hours after dosing on Day 1 and 14 and once per day on Day 8, 10, 12, and 22
Secondary outcome [7] 0 0
AL-3778, entecavir, tenofovir: Apparent terminal half-life (t½)
Timepoint [7] 0 0
At 0, 0.5, 1, 2, 3, 4, 6, 8, 10, 12 hours after dosing on Day 1 and 14 and once per day on Day 8, 10, 12, and 22
Secondary outcome [8] 0 0
AL-3778, entecavir, tenofovir: Maximum observed plasma concentration on Day 14 (Cmax. Day 14)
Timepoint [8] 0 0
At 0, 0.5, 1, 2, 3, 4, 6, 8, 10, 12 hours after dosing on Day 14
Secondary outcome [9] 0 0
AL-3778, entecavir, tenofovir: Minimum observed plasma concentration on Day 14 (Cmin, Day 14)
Timepoint [9] 0 0
At 0, 0.5, 1, 2, 3, 4, 6, 8, 10, 12 hours after dosing on Day 14
Secondary outcome [10] 0 0
AL-3778, entecavir, tenofovir: Area under the plasma concentration-time curve from time 0 to dosing interval, tau, on Day 14 (AUC0-?, Day 14)
Timepoint [10] 0 0
At 0, 0.5, 1, 2, 3, 4, 6, 8, 10, 12 hours after dosing on Day 1 and 14
Secondary outcome [11] 0 0
Incidence, nature, and severity of adverse events
Timepoint [11] 0 0
Screening to Day 22
Secondary outcome [12] 0 0
Changes in Vital Signs during and after study drug administration
Timepoint [12] 0 0
Day 1 to Day 22
Secondary outcome [13] 0 0
changes in physical examinations during and after study drug administration
Timepoint [13] 0 0
Day 1 to Day 22
Secondary outcome [14] 0 0
changes in clinical laboratory results during and after study drug administration
Timepoint [14] 0 0
Day 1 to Day 22
Secondary outcome [15] 0 0
changes in electrocardiogram results during and after study drug administration
Timepoint [15] 0 0
Day 1 to Day 22

Eligibility
Key inclusion criteria
Main Inclusion Criteria for All Subjects:

1. Subject has provided written consent.
2. In the investigator's opinion, the subject is able to understand and comply with protocol requirements, instructions, and study restrictions and is likely to complete the study as planned.
3. Subject is in good health as deemed by the investigator, based on the totality of findings following a medical evaluation, including medical history, physical examination, laboratory tests and ECG.
4. Male or female, 18-60 years of age.
5. Body mass index 18-30 kg/m2, inclusive. The minimum weight is 50 kg.
6. A female subject is eligible to participate in this study if she is of non-childbearing potential (defined as females with a documented tubal ligation, bilateral oophorectomy or hysterectomy) or postmenopausal (defined as 12 months of spontaneous amenorrhea and follicle stimulating hormone level within the laboratory's reference range for postmenopausal females). A post-menopausal female receiving hormone replacement therapy who is willing to discontinue hormone therapy 28 days before study drug dosing and agrees to remain off hormone replacement therapy for the duration of the study may be eligible for study participation.
7. If male, subject is surgically sterile or practicing required forms of birth control until 6 months after the last dose of the study drug(s). Males must agree to refrain from sperm donation from check-in through 6 months after the last dose of the study drug(s).
8. Subject has been a nonsmoker and has not used nicotine or nicotine-containing products for at least 6 months.
9. Subjects who participated in Part 1 and/or Part 2 may participate in subsequent Part(s) upon satisfactory completion of a posttreatment visit, 7 days (+2 days) following the subject's last dose, and provided they continue to meet all of the inclusion criteria and none of the exclusion criteria.

Main exclusion criteria:

1. Subject is mentally or legally incapacitated, has significant emotional problems at the time of prestudy (screening) visit or expected during the conduct of the study or has a history of a clinically significant psychiatric disorder over the last 5 to 10 years.
2. Subject has a history of any illness that, in the opinion of the investigator, would confound the objectives or results of the study or poses an additional risk to the subject by their participation in the study.
3. Subject has an estimated creatinine clearance of =80 mL/min based on the Cockcroft-Gault equation; An actual creatinine clearance, as determined by a 24-hour urine collection, may be used in place of, or in conjunction with, the Cockcroft-Gault equation; subjects who have an actual or estimated creatinine clearance within 10% of 80 mL/min may be enrolled in the study at the discretion of the investigator.
4. Pregnant or nursing (lactating) females, confirmed by a positive human chorionic gonadotropin laboratory test or females contemplating pregnancy. Men whose female partners are pregnant or contemplating pregnancy from the date of screening until 6 months after their last dose of study drugs.
5. Clinically significant cardiovascular, respiratory, skeletal, renal, gastrointestinal, hematologic, hepatic, immunological, neurologic, endocrine, genitourinary abnormalities or disease or any other medical illness as determined by the investigator or Sponsor's Medical Monitor.
6. Subject has a history of malignancy except completely excised basal cell carcinoma or squamous cell carcinoma of the skin.
7. Subject lacks or has poor peripheral venous access.
8. Positive screening result for hepatitis B, hepatitis C and/or HIV serology.
9. Any condition that, in the opinion of the investigator, would compromise the study's objectives or the well-being of the subject or prevent the subject from meeting the study requirements.
10. Clinically significant abnormal ECG findings. Particularly, a history or family history of prolonged QT syndrome (eg, torsade de pointes) or sudden cardiac death.
11. ECG with PR >200 ms, QRS >120 ms, QTcF >450 ms, as assessed by triplicate 12-lead ECG at the screening visit.
12. Subject has had major surgery, or clinically significant blood loss or elective blood donation of significant volume (ie, >500 mL) within 60 days of first dose of study drug; >1 unit of plasma within 7 days of first dose of study drug.
13. Abnormal heart rate, respiratory rate, temperature or blood pressure values outside of the normal range (evaluated in a semi-recumbent or recumbent position after 5 minutes of rest). One repeat measurement after an additional 5 minutes of rest is permitted.
14. Evidence of active infection.
15. Unwilling to abstain from alcohol for at least 48 hours prior to the start of dosing through the study completion visit.
16. History of regular alcohol intake >7 units per week of alcohol for females and >14 units per week for males (one unit is defined as 10 g alcohol) within 3 months of the screening visit.
17. The subject has a positive screening or Day -1 drugs of abuse screen.
18. The use of concomitant medications, including prescription, over the counter medications, and herbal medications (such as St. John's Wort [Hypericum perforatum]) within 30 days prior to the first dose of study medication is excluded, unless approved by the Sponsor's Medical Monitor. Occasional use of ibuprofen/paracetamol/ acetaminophen is permitted.
19. Subject has received an investigational drug (including investigational vaccines) or used an invasive investigational medical device within 90 days before the planned study drug.
20. Subject has a history of significant multiple and/or severe allergies, or has had an anaphylactic reaction or significant intolerability to prescription or non-prescription drugs or food.
21. Hypersensitivity to the active substances or to any of the excipients of AL-3778, entecavir or tenofovir disoproxil fumarate.
22. Subject has known allergy to heparin or history of heparin-induced thrombocytopenia.
23. Abnormal biochemistry or hematology laboratory results obtained at screening determined to be clinically significant by the Investigator. Screening ALT, AST, GGT, albumin, and total bilirubin must be within normal ranges. Creatine kinase >1.5 x ULN is exlusionary
24. Unwillingness or inability to comply with the study protocol for any other reason.
Minimum age
18 Years
Maximum age
60 Years
Sex
Both males and females
Can healthy volunteers participate?
Yes
Key exclusion criteria

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
Parallel
Other design features
Phase
Phase 1
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Stopped early
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
31/01/2017
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
28/06/2017
Sample size
Target
Accrual to date
Final
54
Recruitment in Australia
Recruitment state(s)
Recruitment outside Australia
Country [1] 0 0
New Zealand
State/province [1] 0 0
Auckland
Country [2] 0 0
New Zealand
State/province [2] 0 0
Christchurch

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Alios Biopharma Inc.
Address
Country

Ethics approval
Ethics application status

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

Contacts
Principal investigator
Name 0 0
William D Kennedy, MD
Address 0 0
Alios Biopharma Inc.
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

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
Yes
What data in particular will be shared?
Data will be provided per regulatory requirements.
When will data be available (start and end dates)?
Available to whom?
Available for what types of analyses?
How or where can data be obtained?


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

No documents have been uploaded by study researchers.


Results not provided in https://clinicaltrials.gov/study/NCT03032536