Clinical trial NCT01425970 (phase 2, status: terminated)
Conditions: hepatitis c
ICD codes: B18.2, B17.10, B17.11, B19.20, B19.21, B15.0, B15.9
Drugs: inx-08189, inx-08189, inx-08189, placebo matching with inx-08189, ribavirin, inx-08189, daclatasvir
SMILES: COC1=C2N=CN([C@@H]3O[C@H](COP(=O)(N[C@@H](C)C(=O)OCC(C)(C)C)OC4=C5C=CC=CC5=CC=C4)[C@@H](O)[C@@]3(C)O)C2=NC(N)=N1, COC1=C2N=CN([C@@H]3O[C@H](COP(=O)(N[C@@H](C)C(=O)OCC(C)(C)C)OC4=C5C=CC=CC5=CC=C4)[C@@H](O)[C@@]3(C)O)C2=NC(N)=N1, COC1=C2N=CN([C@@H]3O[C@H](COP(=O)(N[C@@H](C)C(=O)OCC(C)(C)C)OC4=C5C=CC=CC5=CC=C4)[C@@H](O)[C@@]3(C)O)C2=NC(N)=N1, CN1C(=O)C=C(N2CCC[C@@H](N)C2)N(CC2=C(C=CC=C2)C#N)C1=O, NC(=O)C1=NN(C=N1)[C@@H]1O[C@H](CO)[C@@H](O)[C@H]1O, COC1=C2N=CN([C@@H]3O[C@H](COP(=O)(N[C@@H](C)C(=O)OCC(C)(C)C)OC4=C5C=CC=CC5=CC=C4)[C@@H](O)[C@@]3(C)O)C2=NC(N)=N1, COC(=O)N[C@@H](C(C)C)C(=O)N1CCC[C@H]1C1=NC=C(N1)C1=CC=C(C=C1)C1=CC=C(C=C1)C1=CN=C(N1)[C@@H]1CCCN1C(=O)[C@@H](NC(=O)OC)C(C)C
Reason stopped: 
    termination of study was due to safety reasons
  
Eligibility criteria:

        For more information regarding BMS clinical trial participation, please visit
        www.BMSStudyConnect.com

        Inclusion Criteria:

        Amendment 4: Genotype 1, 10 subjects at site 401.

          -  Males and females, 18 to 65 years of age inclusive with a body mass index (BMI) of at
             least 18 kg/m2 but not exceeding 36 kg/m2

          -  Diagnosed with chronic HCV at least 6 months prior to Visit 1 with medical
             documentation (e.g., prior PCR result, prior liver biopsy, prior genotyping, etc.),
             with a positive HCV viral load of at least 50,000 IU/mL at Visit 1 (screening) as
             measured by quantitative PCR

          -  Chronic genotype 2 or 3 HCV infection (per polymerase chain reaction [PCR]
             methodology)

          -  HCV treatment-naïve where "treatment-naïve" is defined as no prior treatment with IFN
             alfa 2a or 2b, Pegylated IFN alfa-2a, Ribavirin, or any HCV direct-acting anti-viral
             drugs

          -  Liver biopsy consistent with chronic HCV infection but with a classification of
             non-cirrhotic (and without classification of 'transition to cirrhosis or borderline
             cirrhosis') as judged by a pathologist (defined as Knodell ≤ 3, Metavir ≤ 2, Ishak ≤
             4, or Batts &Ludwig ≤ 2 ) within the last two years and before Visit 2 (biopsy can be
             done after Visit 1 and before Visit 2, within the screening period)

          -  Negative urine drug screen for drugs of abuse and methadone (via central lab-provided
             dipstick at site) at screening (Visit 1) (note: subjects with a valid prescription for
             a drug which can be abused [e.g., benzodiazepine, opiates] can be enrolled on the
             judgment of the investigator)

          -  Females will have a negative serum beta human chorionic gonadotropin (βHCG) pregnancy
             test at screening and a negative urine dipstick pregnancy test on Study Day 0 (visit
             2)

          -  Agreement by both female subjects of childbearing potential and male subjects (who
             have not been surgically sterilized) to practice an acceptable method of birth
             control, which includes at least one barrier during the study and for at least 6
             months after the cessation of treatment. Surgical sterilization of either the female
             or the male partner must have occurred at least 6 months prior to the first dose and
             females must be post-menopausal for 2 years to be considered of non-child-bearing
             potential. Acceptable contraceptive methods include one of the following: Oral and
             implantable hormonal contraceptives by the female partner for at least 3 months prior
             to the first dose of Study Drug with additional use of a barrier method, IUD in place
             for at least 6 months prior to first dose with additional use of barrier method.
             Acceptable barrier methods include either diaphragm with spermicide, and condom with
             spermicide. (Note: Abstinence is not an acceptable method of birth control, subjects
             who indicate sexual inactivity must agree to utilize an acceptable method of birth
             control in the event of sexual activity)

          -  Willing and able to complete all study visits and procedures, and able to effectively
             communicate with the investigator and other testing center personnel

          -  Signed informed consent form (ICF) executed prior to protocol screening assessments

        Exclusion Criteria:

          -  Signs or symptoms of decompensated liver disease such as variceal bleeding, ascites,
             hepatic encephalopathy, active jaundice defined by an indirect bilirubin > 2, Alanine
             transaminase (ALT) or Aspartate aminotransferase (AST) laboratory values ≥ 10 times
             the upper limit of normal, or other evidence of decompensated liver disease, or
             hepatocellular carcinoma

          -  Chronic liver disease other than HCV not limited to Hepatitis B virus (HBV) [positive
             test for hepatitis B surface antigen (HBsAg)], hemochromatosis, auto-immune hepatitis,
             alcoholic liver disease or non-alcoholic fatty liver disease

          -  History of liver transplantation

          -  Co-infection with Human immunodeficiency virus (HIV) [positive test for anti-HIV Ab]
             or use of didanosine

          -  History of a heart attack, cardiac ischemia, heart disease, clinically symptomatic
             cardiac abnormalities, or blood clots, based on medical history or apparent on
             physical exam

          -  QTcF interval at Visit 1 of greater than or equal to 450 ms by Fridericia's
             correction, or a personal or family history of Torsades de Pointe

          -  History or presence of sarcoidosis or pancreatitis

          -  History or presence of severe pulmonary function impairment including severe (> GOLD
             stage III) chronic obstructive pulmonary obstructive disease, and moderate to severe
             asthma

          -  Uncontrolled diabetes mellitus as evidenced by HbA1C ≥ 8.5% at screening (Visit 1)

          -  Use of the following medications concurrently or within the 30 days prior to Screening
             (Visit 1) associated with QT prolongation: macrolides, antiarrhythmic agents, azoles,
             fluoroquinolones, and tricyclic anti-depressants (specifically excluded medication
             will be listed in protocol Section 6.8)

          -  Use of immunosuppressive or immune-modulating agents (including azathioprine,
             corticosteroids and immunosuppressive agents) or presence of an
             immunologically-mediated autoimmune disease (other than asthma) or history of solid
             organ or bone marrow transplantation (note: inhaled steroids for mild/moderate asthma
             and topical steroid for minor skin conditions allowed and washout period for per Oral
             (PO)/Intramuscular (IM)/ Intravenous (IV) corticosteroid use is 8 weeks; washout
             periods for other immunosuppressives determined by Medical Monitor)

          -  Use of strong CYP3A4-inhibiting protease inhibitors (specifically Atazanavir,
             Indinavir, Nelfinavir, Saquinavir, and Ritonavir), strong CYP3A4 inhibitors
             (specifically Clarithromycin, Itraconazole, Ketoconazole, Nefazodone, Telithromycin),
             or strong CYP3A4 inducers (specifically Rifampin, Efavirenz, Etravirine,
             Phenobarbital, Phenytoin, and Carbamazepine)

          -  Absolute neutrophil count of < 1800 cells/mm3, or platelet count < 130,000 cells/mm3,
             or hemoglobin < 12 g/dl for women and < 13 g/dl for men, or a history of anemia,
             sickle cell anemia, or thalassemia; (note: if baseline value within 5% of minimum
             qualifying value, one re-test allowed for the purpose of qualifying for study)

          -  A history or presence of abnormal thyroid function that is not adequately controlled
             [defined as Thyroid-stimulating hormone (TSH) levels less than 0.8 x lower limit of
             normal (LLN) or greater than 1.2 x the upper limit of normal (ULN)]

          -  Creatinine clearance < 50 mL/minute, serum creatinine concentration ≥ 1.5 times the
             ULN, or albumin ≤ 3 g/dl

          -  Presence or history of bipolar disorder, schizophrenia, psychosis, or unstable
             psychiatric condition, or hospitalization for psychiatric condition, or suicide
             attempt. (Note: Subjects with psychiatric conditions need to be adequately treated and
             on stable doses of appropriate medications for at least 3 months prior to Visit 1.
             History of suicidal ideation within prior 3 months is exclusionary)

          -  Any malignancy within the last 5 years other than treated cervical carcinoma in situ
             or treated basal cell carcinoma with no more than 20% risk of recurrence within 2
             years

          -  Alcohol abuse by the assessment of the investigator within the past 2 years or an
             alcohol use pattern that will interfere with the study conduct

          -  Drug abuse by the assessment of the investigator within the last six months

          -  Pregnancy, current lactation in female subjects, or male subjects with partners who
             are pregnant, or females intending to become pregnant

          -  Major surgery within 30 days prior to Visit 1

          -  Participation in another clinical trial of an investigational drug or device within 6
             months prior to Visit 1 unless that prior participation involved exposure only to
             placebo by clear and available documentation

          -  Donation of blood or plasma within 30 days prior to Visit 1 (not including routine
             laboratory assessments)