Working…
COVID-19 is an emerging, rapidly evolving situation.
Get the latest public health information from CDC: https://www.coronavirus.gov.

Get the latest research information from NIH: https://www.nih.gov/coronavirus.
ClinicalTrials.gov
ClinicalTrials.gov Menu

Study of the Relative Oral Bioavailability of AL-3778 Tablets and Drug Interaction With Entecavir or Tenofovir Disoproxil Fumarate in Healthy Volunteers

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 evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03032536
Recruitment Status : Terminated (Sponsor decision.)
First Posted : January 26, 2017
Last Update Posted : October 16, 2017
Sponsor:
Information provided by (Responsible Party):
Alios Biopharma Inc.

Tracking Information
First Submitted Date  ICMJE January 24, 2017
First Posted Date  ICMJE January 26, 2017
Last Update Posted Date October 16, 2017
Actual Study Start Date  ICMJE January 31, 2017
Actual Primary Completion Date June 28, 2017   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: January 27, 2017)
  • AL-3778, entecavir, tenofovir: Maximum observed plasma concentration (Cmax) [ Time Frame: 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 ]
  • AL-3778, entecavir, tenofovir: Area under the plasma concentration-time curve from time 0 to last measurable concentration (AUClast) [ Time Frame: 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 ]
  • AL-3778, entecavir, tenofovir: Area under the plasma concentration-time curve from time 0 to extrapolated to infinity (AUC∞) [ Time Frame: 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 ]
  • AL-3778, entecavir, tenofovir: Maximum observed plasma concentration on Day 1 (Cmax. Day 1) [ Time Frame: At 0, 0.5, 1, 2, 3, 4, 6, 8, 10, 12 hours after dosing on Day 1 ]
  • AL-3778, entecavir, tenofovir: Minimum observed plasma concentration on Day 1 (Cmin, Day 1) [ Time Frame: At 0, 0.5, 1, 2, 3, 4, 6, 8, 10, 12 hours after dosing on Day 1 ]
  • AL-3778, entecavir, tenofovir: Area under the plasma concentration-time curve from time 0 to dosing interval on Day 1 (AUC0-Τ, Day 1) [ Time Frame: At 0, 0.5, 1, 2, 3, 4, 6, 8, 10, 12 hours after dosing on Day 1 ]
  • AL-3778, entecavir, tenofovir: Minimum observed plasma concentration (C_min) [ Time Frame: 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 ]
Original Primary Outcome Measures  ICMJE
 (submitted: January 24, 2017)
  • AL-3778, entecavir, tenofovir: Maximum observed plasma concentration (Cmax) [ Time Frame: Day 1 to Day 22 ]
  • AL-3778, entecavir, tenofovir: Area under the plasma concentration-time curve from time 0 to last measurable concentration (AUClast) [ Time Frame: Day 1 to Day 22 ]
  • AL-3778, entecavir, tenofovir: Area under the plasma concentration-time curve from time 0 to extrapolated to infinity (AUC∞) [ Time Frame: Day 1 to Day 22 ]
  • AL-3778, entecavir, tenofovir: Maximum observed plasma concentration on Day 1 (Cmax. Day 1) [ Time Frame: Day 1 ]
  • AL-3778, entecavir, tenofovir: Minimum observed plasma concentration on Day 1 (Cmin, Day 1) [ Time Frame: Day 1 ]
  • AL-3778, entecavir, tenofovir: Area under the plasma concentration-time curve from time 0 to dosing interval on Day 1 (AUC0-Τ, Day 1) [ Time Frame: Day 1 ]
  • AL-3778, entecavir, tenofovir: Minimum observed plasma concentration (Cmin) [ Time Frame: Day 1 to Day 22 ]
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: January 27, 2017)
  • AL-3778, entecavir, tenofovir: Predose plasma concentrations (C_0-h) [ Time Frame: 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 ]
  • AL-3778, entecavir, tenofovir: Last observed plasma concentration (C_last) [ Time Frame: 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 ]
  • AL-3778, entecavir, tenofovir: Time of the maximum observed plasma concentration (T_max) [ Time Frame: 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 ]
  • AL-3778, entecavir, tenofovir: Time to last measurable plasma concentration (T_last) [ Time Frame: 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 ]
  • AL-3778, entecavir, tenofovir: Apparent oral clearance (CL/F) [ Time Frame: 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 ]
  • AL-3778, entecavir, tenofovir: Apparent volume of distribution (Vz/F) [ Time Frame: 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 ]
  • AL-3778, entecavir, tenofovir: Apparent terminal half-life (t½) [ Time Frame: 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 ]
  • AL-3778, entecavir, tenofovir: Maximum observed plasma concentration on Day 14 (Cmax. Day 14) [ Time Frame: At 0, 0.5, 1, 2, 3, 4, 6, 8, 10, 12 hours after dosing on Day 14 ]
  • AL-3778, entecavir, tenofovir: Minimum observed plasma concentration on Day 14 (Cmin, Day 14) [ Time Frame: At 0, 0.5, 1, 2, 3, 4, 6, 8, 10, 12 hours after dosing on Day 14 ]
  • AL-3778, entecavir, tenofovir: Area under the plasma concentration-time curve from time 0 to dosing interval, tau, on Day 14 (AUC0-Τ, Day 14) [ Time Frame: At 0, 0.5, 1, 2, 3, 4, 6, 8, 10, 12 hours after dosing on Day 1 and 14 ]
  • Incidence, nature, and severity of adverse events [ Time Frame: Screening to Day 22 ]
  • Changes in Vital Signs during and after study drug administration [ Time Frame: Day 1 to Day 22 ]
  • changes in physical examinations during and after study drug administration [ Time Frame: Day 1 to Day 22 ]
  • changes in clinical laboratory results during and after study drug administration [ Time Frame: Day 1 to Day 22 ]
  • changes in electrocardiogram results during and after study drug administration [ Time Frame: Day 1 to Day 22 ]
Original Secondary Outcome Measures  ICMJE
 (submitted: January 24, 2017)
  • AL-3778, entecavir, tenofovir: Predose plasma concentrations (C0h) [ Time Frame: Day 1 to Day 22 ]
  • AL-3778, entecavir, tenofovir: Last observed plasma concentration (Clast) [ Time Frame: Day 1 to Day 22 ]
  • AL-3778, entecavir, tenofovir: Time of the maximum observed plasma concentration (Tmax) [ Time Frame: Day 1 to Day 22 ]
  • AL-3778, entecavir, tenofovir: Time to last measurable plasma concentration (Tlast) [ Time Frame: Day 1 to Day 22 ]
  • AL-3778, entecavir, tenofovir: Apparent oral clearance (CL/F) [ Time Frame: Day 1 to Day 22 ]
  • AL-3778, entecavir, tenofovir: Apparent volume of distribution (Vz/F) [ Time Frame: Day 1 to Day 22 ]
  • AL-3778, entecavir, tenofovir: Apparent terminal half-life (t½) [ Time Frame: Day 1 to Day 22 ]
  • AL-3778, entecavir, tenofovir: Maximum observed plasma concentration on Day 14 (Cmax. Day 14) [ Time Frame: Day 14 ]
  • AL-3778, entecavir, tenofovir: Minimum observed plasma concentration on Day 14 (Cmin, Day 14) [ Time Frame: Part 3 ]
  • AL-3778, entecavir, tenofovir: Area under the plasma concentration-time curve from time 0 to dosing interval, tau, on Day 14 (AUC0-Τ, Day 14) [ Time Frame: Day 1 to Day 14 ]
  • Incidence, nature, and severity of adverse events [ Time Frame: Screening to Day 22 ]
  • Changes in Vital Signs during and after study drug administration [ Time Frame: Day 1 to Day 22 ]
  • changes in physical examiniations during and after study drug administration [ Time Frame: Day 1 to Day 22 ]
  • changes in clinical laboratory results during and after study drug administration [ Time Frame: Day 1 to Day 22 ]
  • changes in electrocardiogram results during and after study drug administration [ Time Frame: Day 1 to Day 22 ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Study of the Relative Oral Bioavailability of AL-3778 Tablets and Drug Interaction With Entecavir or Tenofovir Disoproxil Fumarate in Healthy Volunteers
Official Title  ICMJE 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
Brief Summary This is an open-label, randomized, multi-part study to evaluate the relative oral bioavailability of a tablet formulation of AL-3778 (formerly NVR 3-778) administered under fasted and fed conditions (Parts 1 and 2) and the drug-drug interaction between AL-3778 and entecavir or tenofovir disoproxil fumarate (Part 3).
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Hepatitis B
  • Chronic Hepatitis B
  • Viral Hepatitis B
Intervention  ICMJE
  • Drug: AL-3778
    AL-3778 tablets or capsules
    Other Name: NVR 3-778, JNJ-63595948, ALS-003778
  • Drug: Entecavir
    Entecavir once daily for 14 days
  • Drug: Tenofovir disoproxil fumarate
    Tenofovir disoproxil fumarate once daily for 14 days
    Other Name: Viread
Study Arms  ICMJE
  • 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.
    Intervention: Drug: AL-3778
  • 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
    Intervention: Drug: AL-3778
  • 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
    Intervention: Drug: AL-3778
  • Active Comparator: Treatment H
    Part 3: Entecavir 0.5 mg once daily administered under fasted conditions for 14 days
    Intervention: Drug: Entecavir
  • 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
    Interventions:
    • Drug: AL-3778
    • Drug: Entecavir
  • Active Comparator: Treatment J
    Part 3: Tenofovir disoproxil fumarate 300 mg once daily administered under fasted conditions for 14 days
    Intervention: Drug: Tenofovir disoproxil fumarate
  • 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
    Interventions:
    • Drug: AL-3778
    • Drug: Tenofovir disoproxil fumarate
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Terminated
Actual Enrollment  ICMJE
 (submitted: October 13, 2017)
54
Original Estimated Enrollment  ICMJE
 (submitted: January 24, 2017)
114
Actual Study Completion Date  ICMJE June 28, 2017
Actual Primary Completion Date June 28, 2017   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 60 Years   (Adult)
Accepts Healthy Volunteers  ICMJE Yes
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE New Zealand
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03032536
Other Study ID Numbers  ICMJE AL-3778-1002
U1111-1187-4391 ( Registry Identifier: WHO )
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: Yes
Plan Description: Data will be provided per regulatory requirements.
Responsible Party Alios Biopharma Inc.
Study Sponsor  ICMJE Alios Biopharma Inc.
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: William D Kennedy, MD Alios Biopharma Inc.
PRS Account Alios Biopharma Inc.
Verification Date October 2017

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP