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Trial record 5 of 5 for:    "Viral Hepatitis" | "Entecavir"

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

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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.

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).

Condition or disease Intervention/treatment Phase
Hepatitis B Chronic Hepatitis B Viral Hepatitis B Drug: AL-3778 Drug: Entecavir Drug: Tenofovir disoproxil fumarate Phase 1

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 54 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official 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
Actual Study Start Date : January 31, 2017
Actual Primary Completion Date : June 28, 2017
Actual Study Completion Date : June 28, 2017

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Drug Reactions

Arm Intervention/treatment
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.
Drug: AL-3778
AL-3778 tablets or capsules
Other Name: NVR 3-778, JNJ-63595948, ALS-003778

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
Drug: AL-3778
AL-3778 tablets or capsules
Other Name: NVR 3-778, JNJ-63595948, ALS-003778

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
Drug: AL-3778
AL-3778 tablets or capsules
Other Name: NVR 3-778, JNJ-63595948, ALS-003778

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

Active Comparator: Treatment J
Part 3: Tenofovir disoproxil fumarate 300 mg once daily administered under fasted conditions for 14 days
Drug: Tenofovir disoproxil fumarate
Tenofovir disoproxil fumarate once daily for 14 days
Other Name: Viread

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
Drug: AL-3778
AL-3778 tablets or capsules
Other Name: NVR 3-778, JNJ-63595948, ALS-003778

Drug: Tenofovir disoproxil fumarate
Tenofovir disoproxil fumarate once daily for 14 days
Other Name: Viread




Primary Outcome Measures :
  1. 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 ]
  2. 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 ]
  3. 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 ]
  4. 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 ]
  5. 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 ]
  6. 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 ]
  7. 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 ]

Secondary Outcome Measures :
  1. 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 ]
  2. 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 ]
  3. 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 ]
  4. 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 ]
  5. 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 ]
  6. 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 ]
  7. 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 ]
  8. 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 ]
  9. 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 ]
  10. 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 ]
  11. Incidence, nature, and severity of adverse events [ Time Frame: Screening to Day 22 ]
  12. Changes in Vital Signs during and after study drug administration [ Time Frame: Day 1 to Day 22 ]
  13. changes in physical examinations during and after study drug administration [ Time Frame: Day 1 to Day 22 ]
  14. changes in clinical laboratory results during and after study drug administration [ Time Frame: Day 1 to Day 22 ]
  15. changes in electrocardiogram results during and after study drug administration [ Time Frame: Day 1 to Day 22 ]


Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years to 60 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03032536


Locations
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New Zealand
Auckland Clinical Studies
Auckland, New Zealand, 1010
Christchurch Clinical Studies Trust
Christchurch, New Zealand, 8011
Sponsors and Collaborators
Alios Biopharma Inc.
Investigators
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Study Director: William D Kennedy, MD Alios Biopharma Inc.

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Responsible Party: Alios Biopharma Inc.
ClinicalTrials.gov Identifier: NCT03032536     History of Changes
Other Study ID Numbers: AL-3778-1002
U1111-1187-4391 ( Registry Identifier: WHO )
First Posted: January 26, 2017    Key Record Dates
Last Update Posted: October 16, 2017
Last Verified: October 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: Data will be provided per regulatory requirements.

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Entecavir
Hepatitis A
Hepatitis B
Hepatitis B, Chronic
Hepatitis
Liver Diseases
Digestive System Diseases
Hepatitis, Viral, Human
Virus Diseases
Enterovirus Infections
Picornaviridae Infections
RNA Virus Infections
Hepadnaviridae Infections
DNA Virus Infections
Hepatitis, Chronic
Tenofovir
Antiviral Agents
Anti-Infective Agents
Reverse Transcriptase Inhibitors
Nucleic Acid Synthesis Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Anti-Retroviral Agents
Anti-HIV Agents