The Safety and Dose-range Study of Metacavir Enteric-coated Capsules in Patients With Chronic Hepatitis B

A Randomized,Double-blind,Double-dummy,Multiple-dose Parallel Control,Multiple Centers Study to Assess the Safety and Dose-range of Metacavir Enteric-coated Capsules for Patients With Chronic Hepatitis B

The study objective is to evaluate the safety and effectiveness of different doses of Metacavir Enteric-coated Capsules in treatment of chronic hepatitis B,as well as to find an appropriate clinical dosage by comparing the effect of different doses of treatment,in order to provide references of clinical trial of the next phase.

Study Overview

• Status: Unknown
• Conditions: Chronic Hepatitis B
• Intervention / Treatment: Drug: Metacavir Enteric-coated Capsules 80mg; Drug: Metacavir Enteric-coated Capsules Placebo 240mg; Drug: Adefovir Dipivoxil Capsule Placebo 10mg; Drug: Metacavir Enteric-coated Capsules 160mg; Drug: Metacavir Enteric-coated Capsules Placebo 160mg; Drug: Metacavir Enteric-coated Capsules 320mg; Drug: Metacavir Enteric-coated Capsules Placebo 320mg; Drug: Adefovir Dipivoxil Capsule10mg

Detailed Description

180 eligible subjects will be included.According to the set grouping method of dose escalation.Subjects will be randomized in a 1:1:1:1 proportion of Metacavir Enteric-coated Capsules(80mg/160mg/320mg) group,positive control group or placebo control group.Each group has 36 subjects.

1.Subjects will use the study medication(2 hours before or after meal,once a day) from Visit 3 to Visit 5.

1. Metacavir Enteric-coated Capsules 80mg Group:Metacavir Enteric-coated Capsules 80mg,Metacavir Enteric-coated Capsules Placebo 240mg,Adefovir Dipivoxil Capsule Placebo 10mg;
2. Metacavir Enteric-coated Capsules 160mg Group:Metacavir Enteric-coated Capsules 160mg,Metacavir Enteric-coated Capsules Placebo 160mg,Adefovir Dipivoxil Capsule Placebo 10mg;
3. Metacavir Enteric-coated Capsules 320mg Group:Metacavir Enteric-coated Capsules 320mg,Adefovir Dipivoxil Capsule Placebo 10mg;
4. Positive Control(Adefovir Dipivoxil Capsule) Group:Metacavir Enteric-coated Capsules Placebo 320mg,Adefovir Dipivoxil Capsule 10mg;
5. Placebo Control Group:Metacavir Enteric-coated Capsules Placebo 320mg,Adefovir Dipivoxil Capsule Placebo 10mg;

• Study Type: Interventional
• Enrollment (Anticipated): 180
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Maorong Wang; Phone Number: 025-80864021

Study Locations

• China
  • Jiangsu
    • Nanjing, Jiangsu, China
      • Recruiting
      • 81 Military Hospital of China
      • Contact: Maorong Wang; Phone Number: 025-80864021
      • Principal Investigator: Maorong Wang

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Are at least 18 years of age and no older than 65;
• Subjects,with an established clinical history of HBV at Screening,has a positive HBsAg test(>6months) regardless of a positive/negative HBeAg test;
• At Screening,HBV-DNA>10^5 copies/ml in HBeAg positive or HBV-DNA>10^4 copies/ml in HBeAg negative(HBV-DNA was evaluated by polymerase chain reaction fluorescent labeling.);
• Subjects with abnormal liver function test defined as alanine aminotransferase(ALT) was 2~10 times upper limit of normal in HBeAg positive or 1.5~10 times upper limit of normal in HBeAg negative;
• Subjects who are willing to require any other treatment for anti-hepatitis B during the study period;
• Subjects who are willing to take measures for effective non-pharmaceutical contraception;
• Given their signed written informed consent to participate;

Exclusion Criteria:

• Subjects with hepatitis C(HCV),hepatitis D(HDV),autoimmune hepatitis,hereditary liver disease or any other active hepatitis;
• A positive human immunodeficiency virus(HIV) test result;
• Subjects,who in the opinion of the investigator,have a current diagnosis of hepatocellular carcinoma or serum α-fetoprotein(AFP)>100ug/L;
• Subjects with severe hepatitis or decompensated liver disease defined as hepatic encephalopathy,ascites,low protein blood syndrome(albumin ≤30g/l) or variceal bleeding;
• Serum Creatinine(SCr) exceeds upper limit of normal;
• At Screening,ALT>10 times upper limit of normal,Total Bilirubin(TBIL)>double upper limit of normal or transient hepatic decompensation caused by condition aggravation;
• Subjects who required treatment with nucleoside antiviral drugs such as lamivudine,Adefovir dipivoxil,Telbivudine,Tenofovir disoproxil or Entecavir before Screening;
• Subjects who require treatment with interferon-α，thymosin α-1 or other antiviral therapy,immunosuppressive agents,immune modulators within 6 months before Screening;
• Subjects with cardiac disease,hematological system disease,cancer,impaired immunity or psychiatric disease;
• Hemoglobin<10g/dl,white blood cell count<3.5 10^9/L,platelets<80 10^9/L;
• Subjects,who in the opinion of the investigator,have a current diagnosis of pancreatitis pre-dose within 24 weeks;
• History of hypersensitivity or allergy to any of the study drugs;
• Subjects who participate in other clinical trials within 3 months prior to Screening;
• Women who are pregnant or lactating or planning a pregnancy recently;
• Subjects in the opinion of the investigator,could not participate in the study.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

5

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Metacavir Enteric-coated Capsule 80mg; Metacavir Enteric-coated Capsules 80mg; Metacavir Enteric-coated Capsules Placebo 240mg; Adefovir Dipivoxil Capsule Placebo 10mg;	Drug: Metacavir Enteric-coated Capsules 80mg; Metacavir Enteric-coated Capsules 80mg; Drug: Metacavir Enteric-coated Capsules Placebo 240mg; Metacavir Enteric-coated Capsules Placebo 240mg; Drug: Adefovir Dipivoxil Capsule Placebo 10mg; Adefovir Dipivoxil Capsule Placebo 10mg
Active Comparator: Metacavir Enteric-coated Capsules 160mg; Metacavir Enteric-coated Capsules 160mg; Metacavir Enteric-coated Capsules Placebo 160mg; Adefovir Dipivoxil Capsule Placebo 10mg;	Drug: Adefovir Dipivoxil Capsule Placebo 10mg; Adefovir Dipivoxil Capsule Placebo 10mg; Drug: Metacavir Enteric-coated Capsules 160mg; Metacavir Enteric-coated Capsules 160mg; Drug: Metacavir Enteric-coated Capsules Placebo 160mg; Metacavir Enteric-coated Capsules Placebo 160mg
Placebo Comparator: Metacavir Enteric-coated Capsules 320mg; Metacavir Enteric-coated Capsules 320mg; Adefovir Dipivoxil Capsule Placebo 10mg	Drug: Adefovir Dipivoxil Capsule Placebo 10mg; Adefovir Dipivoxil Capsule Placebo 10mg; Drug: Metacavir Enteric-coated Capsules 320mg; Metacavir Enteric-coated Capsules 320mg
Active Comparator: Adefovir Dipivoxil Capsule; Metacavir Enteric-coated Capsules Placebo 320mg; Adefovir Dipivoxil Capsule 10mg;	Drug: Metacavir Enteric-coated Capsules Placebo 320mg; Metacavir Enteric-coated Capsules Placebo 320mg; Drug: Adefovir Dipivoxil Capsule10mg; Adefovir Dipivoxil Capsule10mg
Placebo Comparator: Placebo; Metacavir Enteric-coated Capsules Placebo 320mg; Adefovir Dipivoxil Capsule Placebo 10mg;	Drug: Adefovir Dipivoxil Capsule Placebo 10mg; Adefovir Dipivoxil Capsule Placebo 10mg; Drug: Metacavir Enteric-coated Capsules 320mg; Metacavir Enteric-coated Capsules 320mg; Drug: Metacavir Enteric-coated Capsules Placebo 320mg; Metacavir Enteric-coated Capsules Placebo 320mg

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The change from baseline in the logarithms of measurement data of HBV-DNA at Week 12 of treatment.	The change from baseline in the logarithms of measurement data of HBV-DNA at Week 12 of treatment.（Unit：log10)	12 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of treatment-chronic hepatitis B	The proportion of subjects whose HBV-DNA are down to double logarithms at Week 12 of treatment.(Unit：%); The proportion of subjects whose HBV-DNA are not detected or less than upper limit of normal at Week 12 of treatment.(Unit：%); The proportion of subjects (HBeAg positive at baseline) whose is changed at Week 12 of treatment.(Unit：%); The proportion of subjects whose HBsAg is changed to negative at Week 12 of treatment.(Unit：%)	12 weeks
Incidence of Adverse Events(AEs)		48 weeks

Collaborators and Investigators

• Sponsor: Guangzhou Yipinhong Pharmaceutical CO.,LTD
• Investigators: Principal Investigator: Maorong Wang, 81 Military Hospital of China; Principal Investigator: Yonggang Li, Beijing 302 Hospital; Principal Investigator: Yanlin Yu, Wannan Medical College Yijishan Hospital; Principal Investigator: Jun Li, The First Affiliated Hospital with Nanjing Medical University

Study record dates

Study Major Dates

• Study Start: December 1, 2012
• Primary Completion (Anticipated): December 1, 2018

Study Registration Dates

• First Submitted: September 1, 2016
• First Submitted That Met QC Criteria: November 14, 2016
• First Posted (Estimate): November 17, 2016

Study Record Updates

• Last Update Posted (Estimate): November 22, 2016
• Last Update Submitted That Met QC Criteria: November 21, 2016
• Last Verified: August 1, 2016

More Information

Terms related to this study

• Keywords: Chronic Hepatitis B
• Additional Relevant MeSH Terms: Digestive System Diseases; RNA Virus Infections; Virus Diseases; Infections; Blood-Borne Infections; Communicable Diseases; Liver Diseases; Hepatitis, Viral, Human; Hepadnaviridae Infections; DNA Virus Infections; Enterovirus Infections; Picornaviridae Infections; Hepatitis B; Hepatitis; Hepatitis A; Hepatitis B, Chronic; Hepatitis, Chronic; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Reverse Transcriptase Inhibitors; Nucleic Acid Synthesis Inhibitors; Enzyme Inhibitors; Adefovir; Adefovir dipivoxil
• Other Study ID Numbers: PNA-20140110-v2