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Evaluation HEC121120 Tolerance in Healthy Subjects and Patients With Chronic Hepatitis B, Pharmacokinetics Characteristics and Antiviral Activity of Ⅰ Phase of Study

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. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04536532
Recruitment Status : Not yet recruiting
First Posted : September 2, 2020
Last Update Posted : September 2, 2020
Sponsor:
Information provided by (Responsible Party):
Sunshine Lake Pharma Co., Ltd.

Brief Summary:
The Safety, Tolerability, Pharmacokinetics and antiviral activity Study of Anti hepatitis B virus treatment drug HEC121120 in Healthy subjects and in patients with chronic hepatitis B

Condition or disease Intervention/treatment Phase
Hepatitis B, Chronic Drug: HEC121120 tablets Drug: HEC121120 placebo tablets Drug: entecavir tablets Drug: entecavir placebo tablets Phase 1 Phase 2

Detailed Description:

This study consists of two parts: healthy subjects and chronic hepatitis B patients. Healthy subjects will conduct a single-dose, multiple-dose and food effect study.

I. Single-Dose Study:There will be a total of 6 dose cohorts(25 mg, 50 mg, 100 mg, 400 mg, 600 mg, 800 mg). 25 mg cohort as experimental cohort, plans to enroll 4 subjects (male or female) who will use HEC121120 tablets . The other else cohorts will include 10 subjects, of which 8 receives HEC121120 tablets and 2 receives placebo, regardless of gender. Each subject will only participate in one dose cohort. Each cohort will be divided into 2 group. The first group consists of 3 sentinels, two receiving active and one placebo. The second group will consist of the remainder of the cohort (6 active and 1 placebo) and, following review of the available safety data, will be dosed 24 hours after the sentinel group. Subjects can leave the pharmacy after their biological samples are collected on day 5. Subjects in each cohort will receive a single dose of HEC121120 or placebo in the fasted state on day 1, and safety evaluation is to be performed on day 2 and 5.

II. Food effect: There will be 1 dose cohort (200 mg), only to be admitted to the 100 mg dose cohort if a single dose has been completed and is safe and well tolerated. A total of 18 subjects were enrolled in this dose cohort, divided into two groups A and B (9 subjects in each group, 8 subjects in each group received HEC121120 and 1 received the placebo, with the ratio of male to female as close as possible. All subjects were required to participate in a single dose and food influence study on pharmacokinetics. Two cycles of cross-dose administration were performed, with a washout period of 7 days. Four sentinels were first enrolled in group A, and their safety indexes were evaluated by the investigator at least 24 h after administration. If tolerated, the remaining 5 sentinels could be enrolled in group A, and the remaining 4 sentinels could be enrolled in group B. The safety indexes were evaluated by the investigator at least 24 h after administration, if tolerated, the remaining 5 sentinels could be enrolled in group B.

III. Multi-Dose Study: There will be 1 dose(200 mg) cohort which will consist of 12 subjects, of which 10 receive HEC121120 tablets and 2 receive placebo, with the ratio of male to female as close as possible. All subjects will receive HEC121120 or placebo for 5 consecutive days (study doses, administration method (fasted or fed), dosing frequency, and dosing period are all to be determined based on data from the single-dose study and multiple-dose study). Subjects can leave pharmacy after their biological samples are collected. Safety evaluation is to be performed on day 3 and 7.

IV:Chronic hepatitis B patients: There will be a total of 3 dose cohorts (100、200、400 mg). Each cohort will consist of 14 subjects, of which 12 receive HEC121120 tablets and placebo(Entecavir simulation tablet), 2 receive Entecavir and placebo(HEC121120 simulation tablet). It is necessary to determine the administration method and dose for patients with chronic hepatitis B based on the results of the tolerance and PK study of healthy subjects. Each subject will only participate in one dose cohort.Initially, the drug frequency was set as once a day for 28 consecutive days. Safety and antiviral activity evaluation is to be performed on day 7, 14, 21±2, 29, 35±2.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 126 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Single-center, Randomized, Double-blind, Single and Multiple Dosing, Evaluation HEC121120 Tolerance in Healthy Subjects and Patients With Chronic Hepatitis B, Pharmacokinetics Characteristics and Antiviral Activity of Ⅰ Phase of Study
Estimated Study Start Date : September 30, 2020
Estimated Primary Completion Date : July 7, 2022
Estimated Study Completion Date : September 15, 2022

Resource links provided by the National Library of Medicine

Drug Information available for: Entecavir

Arm Intervention/treatment
Experimental: HEC121120 tablets
part 1(Health volunteer): single-Dose Study: There will be a total of 6 dose cohorts: 25 mg、50 mg、100 mg、400 mg、600 mg、800 mg food effect:200 mg multiple-dose study: 200 mg part 2(Patients with chronic hepatitis B): There will be a total of 3 dose cohorts:100、200、400 mg
Drug: HEC121120 tablets

single-Dose Study: Each dose of HEC121120 and placebo will be administered with approximately 240 mL of water in the morning after fasting for at least 10 hours overnight.

multiple-dose study/Patients with chronic hepatitis B:The study doses, administration method (fasted or fed), dosing frequency, and dosing period are all to be determined based on data from the single-dose study and/or multiple-dose study.


Placebo Comparator: HEC121120 placebo tablets
part 1(Health volunteer): single-Dose Study: There will be a total of 6 dose cohorts: 25 mg、50 mg、100 mg、400 mg、600 mg、800 mg food effect:200 mg multiple-dose study: 200 mg part 2(Patients with chronic hepatitis B): There will be a total of 3 dose cohorts:100、200、400 mg
Drug: HEC121120 placebo tablets

single-Dose Study: Each dose of HEC121120 and placebo will be administered with approximately 240 mL of water in the morning after fasting for at least 10 hours overnight.

multiple-dose study/Patients with chronic hepatitis B:The study doses, administration method (fasted or fed), dosing frequency, and dosing period are all to be determined based on data from the single-dose study and/or multiple-dose study.


Active Comparator: entecavir tablets
part 2(Patients with chronic hepatitis B): 0.5 mg
Drug: entecavir tablets
Patients with chronic hepatitis B:Administered Entecavir orally once daily for consecutive 28 days in fasted state

Placebo Comparator: entecavir placebo tablets
part 2(Patients with chronic hepatitis B): 0.5 mg
Drug: entecavir placebo tablets
Patients with chronic hepatitis B:Administered Entecavir placebo orally once daily for consecutive 28 days in fasted state




Primary Outcome Measures :
  1. Adverse Events [ Time Frame: Time Frame: From Days 1-35 ]
    Incidence of adverse events

  2. Cmax [ Time Frame: Time Frame: Day 1-7 ]
    Maximum plasma concentration of study drugs

  3. AUC [ Time Frame: Time Frame: Day 1-7 ]
    Maximum plasma concentration of study drugs

  4. HBV DNA [ Time Frame: Time Frame: Day 29-35 ]
    Hepatitis B virus DNA



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 65 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

Health volunteer

Inclusion Criteria:

  1. Sign the informed consent form before the trial and fully understand the contents of the trial, the process and possible adverse reactions.
  2. Be able to complete the study according to the trail protocol.
  3. Subjects (including partners) have no pregnancy plan within 6 months after the last dose of study drug and voluntarily take effective contraceptive measures.
  4. subjects and must be 18 to 45 years of age inclusive.
  5. Body weight ≥ 45 kg and body mass index(BMI)between 18 and 28 kg / m^2, inclusive.
  6. Physical examination and vital signs without clinically significant abnormalities.

Exclusion Criteria:

  1. Use of >5 cigarettes per day during the past 3 months.
  2. Known history of allergy to study drugs,or allergies constitution ( multiple drug and food allergies).
  3. History of alcohol abuse (14 units of alcohol per week: 1 unit = 285 mL of beer, or 25 mL of spirits or 100 mL of wine).
  4. Donation or loss of blood over 450 mL within 3 months prior to screening. 5.12-lead ECG with clinically significant.

6.Positive for Viral hepatitis (including hepatitis B and C), HIV and syphilis. 7.Subjects deemed unsuitable by the investigator for any other reason.

Patients with chronic hepatitis B

Inclusion Criteria:

  1. Sign the informed consent form before the trial and fully understand the contents of the trial, the process and possible adverse reactions.
  2. Be able to complete the study according to the trail protocol.
  3. Subjects (including partners) have no pregnancy plan within 6 months after the last dose of study drug and voluntarily take effective contraceptive measures.
  4. subjects and must be 18 to 65 years of age inclusive.
  5. Body mass index(BMI)between 18 and 32 kg / m^2, inclusive.
  6. There is evidence of hepatitis B infection for more than 6 months。
  7. HBV DNA copies≥2.0×10^4 IU/mL.
  8. ALT≤5×ULN,TBIL≤2×ULN
  9. No cirrhosis.

Exclusion Criteria:

  1. Use of >5 cigarettes per day during the past 3 months.
  2. Known history of allergy to study drugs,or allergies constitution ( multiple drug and food allergies).
  3. Female subjects were lactating or had positive serum pregnancy results during the screening or testing period.
  4. Donation or loss of blood over 450 mL within 3 months prior to screening. 5.12-lead ECG with clinically significant.

6.Positive for Viral hepatitis C, HIV and syphilis. 7. AFP>50 ng/mL. 8. eGFR<60 mL/min/1.73m^2 9.Subjects deemed unsuitable by the investigator 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): NCT04536532


Contacts
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Contact: Yanhua Ding, Doctor 18186879768 dingyanhua2003@126.com

Sponsors and Collaborators
Sunshine Lake Pharma Co., Ltd.
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Responsible Party: Sunshine Lake Pharma Co., Ltd.
ClinicalTrials.gov Identifier: NCT04536532    
Other Study ID Numbers: HEC121120-P-01
First Posted: September 2, 2020    Key Record Dates
Last Update Posted: September 2, 2020
Last Verified: August 2020

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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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
Entecavir
Antiviral Agents
Anti-Infective Agents