A study of the safety of combining BIT225 with pegylated interferon and ribavirin, in patients with hepatitis C virus infection, including measurement of the concentration and distribution of BIT225 in the body and antiviral activity.
- Conditions
- Hepatitis C Virus InfectionInfection - Other infectious diseasesOral and Gastrointestinal - Other diseases of the mouth, teeth, oesophagus, digestive system including liver and colon
- Registration Number
- ACTRN12612000828820
- Lead Sponsor
- Biotron Limited
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Completed
- Sex
- All
- Target Recruitment
- 24
1. Males or females, aged 18 to 55 years
2. Chronic hepatitis C infection (defined as persistent HCV infection as diagnosed by detection of HCV RNA in the blood at least 6 months from initial detection).
3. Serologic evidence of HCV infection by anti-HCV antibody test.
4. Documentation of HCV genotype 1-infection at any time prior to entry. A laboratory report must be used for documentation. Those without known genotype at screening will have a screening genotype performed.
5. HCV RNA of >/= 105 IU/mL as measured by the ROCHE COBAS Amplicor Monitor 'registered trademark' version 2.0 method within 60 days of Entry
6. ALT (SGOT) , AST (SGPT), and alkaline phosphatase less than or equal to 5 times upper level of normal within 60 days of Entry.
7. For females of reproductive potential (defined as women who have not been post-menopausal for at least 24 consecutive months, i.e., who have had menses within the preceding 24 months, or women who have not undergone surgical sterilization, specifically hysterectomy, or bilateral oophorectomy and/or tubal ligation), must have a negative serum or urine pregnancy test with a sensitivity of at least 50mlU/mL within 60 days prior to study entry.
A negative serum or urine pregnancy test result is also required within 24 hours prior to the initiation of study treatment (Day -1)
All subjects must agree not to participate in a conception process (e.g., active attempt to become pregnant or to impregnate, sperm donation, in vitro fertilization).
If participating in sexual activity that could lead to pregnancy, the subject must agree to use two reliable methods of contraception simultaneously while receiving study treatment and for 6 weeks after stopping study treatment.
8. Subjects who are not of reproductive potential (women who have been post-menopausal for at least 24 consecutive months or have undergone hysterectomy, salpingotomy, and/or bilateral oophorectomy or men who have documented azoospermia) are eligible without requiring the use of contraceptives.
9. Provide written informed consent to participate in the study and be willing to comply with the study procedures.
10. Naive to therapy for HCV, including any interferon or ribavirin.
1. Patients who have received an investigational drug for HCV.
2. Positive results for Hepatitis B (Hepatitis B surface antigen) and HIV antibody at Screening.
3. History or presence of other evidence of a medical condition associated with chronic liver disease (e.g., chronic or acute hepatitis B, acute hepatitis A, hemochromatosis, autoimmune hepatitis, Wilson’s disease, Gilbert’s syndrome, homozygote alpha1-antitrypsin deficiency, alcoholic liver disease, and toxin exposures).
4. Bridging cirrhosis or cirrhosis confirmed on a biopsy obtained within the past 36 months as judged by a local pathologist. Note: patients with Metavir (or equivalent index) stage 3 fibrosis on a previous biopsy or patients with no previous biopsy will require an abdominal ultrasound within 6 months of first dose showing no evidence of cirrhosis
5. History or signs of decompensated liver disease manifested by presence of Child-Pugh class B or C, ascites, variceal bleeding, or hepatic encephalopathy, spontaneous bacterial peritonitis, or other clinical signs of portal hypertension or hepatic insufficiency
6. History or other evidence of clinically significant renal disease.
7. Pregnancy or breast feeding, male partners of pregnant females.
8. Abnormal haematological and biochemical parameters within 60 days of Entry:
a. Absolute neutrophil count <1000/mm3
b. Haemoglobin <11 g/dL in females or 13 g/dL in males
c. Platelet count <150,000/mm3
d. International normalized ratio (INR) >1,5
e. Total bilirubin within normal reference range
f. Creatinine > 1.5 mg/dL
Estimated creatinine clearance < 80 mL/minute at Screening. Value will be calculated using the Cockcroft-Gault formula.
9. Screening ECG QTcB value >/= 450 ms.
10. The consumption / administration of prohibited concomitant medication (prescribed, over-the-counter or complementary) at the time of the Screening visit. Any medication taken from 28 days prior to first dose through to the end of the participation in the study must be approved by the Biotron Medical Monitor in consultation with the Investigator.
11. Active drug or alcohol use or dependence that, in the opionion of the site investigator, would interfere with adherence to study requirements.
12. A positive result on urine screen for drugs of abuse and alcohol breath test at Screening or Day -1 which in the opinion of the Investigator should preclude them from participation in the study.
13. History of severe psychiatric disease, which in the opinion of the Investigator should preclude them from participation in the study. Uncontrolled or active depression or other psychiatric disorder such as untreated Grade >/=3 psychiatric disorder, Grade >/=3 disorder not amenable to medical intervention, or any hospitalization within the past 52 weeks that in the opinion of the site investigator might preclude tolerability of study requirements.
14. Any prior suicide attempt.
15. History of immunologically mediated disease (e.g., inflammatory bowel disease, idiopathic thrombocytopenic purpura, lupus erythematosus, autoimmune haemolytic anaemia, scleroderma, severe psoriasis, rheumatoid arthritis requiring more than intermittent non-steroidal anti-inflammatory medications for management, etc.) that may be exacerbated by interferon use.
16. History or other evidence of chronic pulmonary disease associated with functional limitation.
17. History of documented or presumed coronary art
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Evaluate the safety and tolerability of 200 and 400 mg of BIT225 twice daily compared with placebo in combination with PEG-IFN and RBV in patients with chronic HCV infection that are treatment-naive to antiviral treatment with ribavirin and/or interferon. Safety and tolerability will be assessed by comparison to placebo of treatment emergent untoward medical changes, e.g. nausea, vomitting or loss of weight, and changes in clinical laboratory assessments, vital signs and ECG.[Medical changes will be evaluated daily, clinical laboratory assessments, vital signs and ECG weekly, over the 28 days of dosing.]
- Secondary Outcome Measures
Name Time Method