Efficacy and Safety of All-Oral Combination of Narlaprevir/Ritonavir and Daclatasvir in Treatment-Naїve Patients With Chronic Hepatitis C Genotype 1b

Inclusion Criteria

• •Subjects who meet all of the following criteria are eligible for participation in the study:
• •Are willing and able to provide written informed consent.
• •Have confirmed chronic HCV infection as documented by:
• •1. positive anti-HCV antibody (Ab) test or
• •2. positive HCV RNA or
• •3. positive HCV genotyping test at least 6 months prior to the Baseline/Day 1 visit.
• •Have HCV genotype 1b at screening as determined by the Central Laboratory. Any non definitive results must exclude the subject from study participation.
• •Minimum HCV-RNA level of ≥10,000 IU at baseline.
• •No evidence of cirrhosis; availability at Baseline of at least one of the following tests, negative results:
• •1. Liver biopsy within 2 years of screening showing absence of cirrhosis;
• •2. Fibroscan with a result of ≤ 12.5 kPa within 6 months of baseline/Day1;
• •3. FibroTest score of ≤ 0.48 AND APRI of ≤ 1 performed during screening. In the absence of a definitive diagnosis of the presence or absence of cirrhosis by the above criteria, a liver biopsy was required. Liver biopsy results supersede the results obtained by Fibroscan or FibroTest.
• •Have a screening electrocardiogram (ECG) without clinically significant abnormalities (P wave \< 0.1 s; PQ interval 0,12-0,2 s; QRS complex 0,06-0,1 s; QT interval 0,35-0,49 s).
• •Must have the following laboratory parameters at screening:
• •1. alanine aminotransferase (ALT) ≤ 10 x the upper limit of normal (ULN);
• •2. aspartate aminotransferase (AST) ≤ 10 x ULN;
• •3. Hemoglobin ≥ 12g/dL for male, ≥ 11g/dL for female subjects;
• •4. Platelets ≥ 50,000cells/mm3;
• •5. International normalized ratio (INR) ≤ 1.5 x ULN unless subject has known hemophilia or is stable on an anticoagulant regimen affecting INR;
• •6. Albumin ≥ 3g/dL;
• •7. Direct bilirubin ≤ 1.5 x ULN;
• •8. Hemoglobin A1c (HbA1c) ≤ 10%;
• •9. Creatinine clearance (CLcr) ≥ 60 mL/min, as calculated by the Cockcroft-Gault equation;
• •10. Have not been treated with any investigational drug or device within 30 days of the screening visit.
• •A female subject is eligible to enter the study if it is confirmed that she is:
• •1. Not pregnant or nursing;
• •2. Of non-childbearing potential (i.e., women who have had a hysterectomy, both ovaries removed, or medically documented ovarian failure, or are postmenopausal women \>50 years of age with cessation \[for ≥12 months\] of previously occurring menses), or
• •3. Of childbearing potential (i.e., women who had not had a hysterectomy, both ovaries removed, or medically documented ovarian failure). Women ≤ 50 years of age with amenorrhea are considered to be of childbearing potential. These women must have a negative serum pregnancy test at screening and a negative urine pregnancy test on the baseline/Day 1 visit prior to enrollment. They must also agree to one of the following from 3 weeks prior to baseline/Day 1 until 6 months after last dose of the investigational drugs:
• •1. Complete abstinence from intercourse. Periodic abstinence from intercourse (e.g., calendar, ovulation, sympto thermal, post-ovulation methods) is not permitted Or
• •2. Consistent and correct use of 1 of the following methods of birth control listed below in addition to a male partner who correctly uses a condom from the date of screening until 6 months after the last dose of the investigational drugs:
• •* intrauterine device (IUD) with a failure rate of \< 1% per year;
• •* female barrier method: cervical cap or diaphragm with spermicidal agent;
• •* tubal sterilization;
• •* vasectomy in male partner; Women of childbearing potential must not rely on hormone-containing contraceptives as a form of birth control during the study. Female subjects using a hormone-containing contraceptive prior to screening must stop their contraceptive regimen use from the date of screening until 6 months after their last dose of investigational drugs.
• •All male study participants must agree to consistently and correctly use a condom, while their female partner agrees to use either 1 of the non hormonal methods of birth control listed above or a hormone-containing contraceptive listed below, from the date of screening until 6 months after their last dose of investigational drugs:
• •* implants of levonorgestrel;
• •* injectable progesterone;
• •* oral contraceptives (either combined or progesterone only);
• •* contraceptive vaginal ring;
• •* transdermal contraceptive patch;
• •Male subjects must agree to refrain from sperm donation for at least 6 months after the last dose of investigational drugs.
• •Are in generally good health as determined by the investigator.
• •Are able to comply with the dosing instructions for study drug administration and are able to complete the study schedule of assessments.