Study of Effects and Safety Between Adefovir Dipivoxil Plus Polyene Phosphatidylcholine Versus Adefovir Dipivoxil Alone in Chronic Hepatitis B Patients

• Register: ClinicalTrials.gov
• Last refreshed on: 17 October 2012
• Main ID: NCT01436539
• Date of registration: 13/09/2011
• Primary sponsor: Jun Cheng
• Public title: Study of Effects and Safety Between Adefovir Dipivoxil Plus Polyene Phosphatidylcholine Versus Adefovir Dipivoxil Alone in Chronic Hepatitis B Patients
• Scientific title: A Multi-center, Open Label, Randomized Study of Effects and Safety Between Adefovir Dipivoxil Plus Polyene Phosphatidylcholine Capsule Versus Adefovir Dipivoxil Alone in Chronic Hepatitis B Patients
• Date of first enrolment: September 2011
• Target sample size: 300
• Recruitment status: Not yet recruiting
• URL: http://clinicaltrials.gov/show/NCT01436539
• Study type: Interventional
• Study design: Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Countries of recruitment

China

Key inclusion & exclusion criteria

Inclusion Criteria:

- Males and females between the age of 18 to 65 years with chronic hepatitis B.

- HBsAg positive for a minimum of 6 months.

- HBV DNA =4 log10 copies/ml, and = 6 log10 copies/mL

- Alanine aminotransferase (ALT) = 2 times the upper limit of normal(ULN) and =10 times
ULN, and documented ALT abnormal within 6 month prior to the study screening.

- Had a liver biopsy performed within 6 months prior to randomization and has readable
biopsy slides or agrees to have a biopsy performed prior to entry.

- Willing and able to provide written informed consent.

Exclusion Criteria:

- Received any nucleoside, nucleotide or interferon therapy within 6 months prior to
the screening.

- Previous treatment with lamivudine, adefovir, entecavir or telbivudine and occurred
viral breakthrough or genotype resistance.

- Received immunosuppressive agents or other immunoregulates (including
thymosin),systemic cytotoxic drugs, other antiviral agents including Chinese herb
medicine within 6 months prior to the screening.

- Active alcohol intake( more than 20g/d for female or more than 30g/d for male) or
drug abuse within 1 year prior to screening. Alcohol or drug abuse considered by the
investigator to be sufficient to hinder compliance with treatment, participation in
the study or interpretation of results.

- ALT is greater than 10 times ULN at screening or has the history of transient
decompensated liver disease due to acute exacerbation.

- Any of the laboratory test at screening as the following :

- serum creatinine > 1.5 mg/dl ;

- prothrombin time = 4 seconds prolonged or PTA <60%;

- serum albumin<32 g/L;

- serum bilirubin>3.0mg/dL;

- Hemoglobin<11g/dL(males) or <10 g/dL(females), white blood cells count<3.5 x
10^9/L, absolute neutrophil count <1.5 x 10^9/L, platelets<80 x 10^9/L.

- Patient is coinfected with HCV, HDV or HIV.

- Hepatocellular carcinoma (HCC), or the presence of a mass on imaging studies of the
liver that is suggest of HCC, or an alpha-fetoprotein (AFP)> 500ng/mL.

- Decompensated liver disease as defined by serum bilirubin >3mg/dL, prothrombin time=
4 seconds prolonged, a serum albumin<32g/L, or a history of ascites, variceal
bleeding or hepatic encephalopathy.

- Presence of other causes of liver disease (i.e.alcoholic liver disease,autoimmune
hepatitis, hemochromatosis, Wilson disease, nonalcoholic steatohepatitis,
alpha-1anti-trypsin deficiency).

- Any serious or active medical or psychiatric illnesses other than hepatitis B which,
in the opinion of the investigator, would interfere with patient treatment,
assessment or compliance with the protocol. This would include, may not limit to,
renal, cardiac, pulmonary, vascular, neurogenic, digestive, metabolic (diabetes,
thyroid disorders, adrenal disease), immunodeficiency disorders, active infection or
cancer.

- BMI=30.

- Patient is pregnant or breast-feeding.

- Planned for liver transplantation or previous liver transplantation.

- Need take hepatotoxic drugs (e.g.,dapsone, erythromycin, fluconazole, rifampin, etc)
and nephrotoxic drugs (e.g., NSAIDs, aminoglycosides, amphotericin B, foscarnet,
etc.) for long time.

- History of hypersensitivity to nucleoside analogues.

- Previous (or planned) participation in an investigational trial involving
administration of investigational compound within 12 weeks prior to the study
screening.

- Poor compliance of the patient considered by investigator.



Age minimum: 18 Years
Age maximum: 65 Years
Gender: Both

Health Condition(s) or Problem(s) studied

Chronic Hepatitis B

Intervention(s)

Drug: Adefovir Dipivoxil

Drug: Adefovir Dipivoxil and polyene phosphatidylcholine

Primary Outcome(s)

Proportions of subjects with histological response in treatment and control group. [Time Frame: at week 48]

Secondary Outcome(s)

ALT normalization rate and range [Time Frame: at week 12 and 48]

Frequency of adverse events [Time Frame: up to 60 weeks]

Frequency of discontinuations from study drug due to adverse events or laboratory abnormalities. [Time Frame: up to 60 weeks]

Frequency of serious adverse events [Time Frame: up to 60 weeks]

HBeAg loss and HBe seroconversion [Time Frame: at week 12 and 48]

HBsAg loss and HBs seroconversion [Time Frame: at week 12 and 48]

Improvement in symptoms score [Time Frame: at week 12, 24 and 48]

Liver stiffness values reduction from baseline by Fibroscan [Time Frame: at week 48]

Mean log10 reduction from baseline in HBVDNA [Time Frame: at week 12, 24, 48]

Proportions of subjects in each group who achieve: HBV DNA < 300 copies/mL [Time Frame: at week 48]

Secondary ID(s)

Ditan-2011-01

Source(s) of Monetary Support

Please refer to primary and secondary sponsors

Secondary Sponsor(s)

Fujian Cosunter Pharmaceutical Co. Ltd

Sanofi-Aventis