Safety Study of INX-08189, Pharmacokinetic and Pharmacodynamic With Ribavirin and Food Effect Study, in Chronically-infected Genotype 1 Hepatitis C Virus, Treatment-naïve Subjects

NCT01445795 | Completed Phase 1

• 2 other identifiers: AI472-006INH-189-006
• Study Type: interventional
• Target: 50
• Locations: 2 countries
• Sites: 2

Brief Summary

This study is to determine the safety and Pharmacokinetics (PK) and Pharmacodynamics (PD) of INH-08189 dosed once a day (QD), two times a day (BID) or adjunctively with Ribavirin and a study of the food effect in Chronically-infected Genotype 1 Hepatitis C Virus (HCV), Treatment-naïve subjects.

Conditions

Hepatitis C

Keywords

Inhibitex; Chronic Hepatitis; Hepatitis C Virus

Outcome Measures

Primary Outcomes (1)

• Change from baseline in HCV RNA 24 hours following the final dose of Study Drug (INX-08189/placebo)

  24 hours following the final dose of Study Drug

Secondary Outcomes (1)

• Change in HCV RNA over time during the 7 days of dosing and during the follow-up period and the maximum change from baseline in HCV RNA.

  HCV RNA will be measured at the following time points: Once each at Screening (Visit1), Study Day 10 (Visit 12), and Study Day 14 (Visit 13). Samples will be taken for HCV analysis pre-dose, and at 12, 24 and 48 hours after the first dose of Study Drug

Study Arms (8)

200 mg INX-08189 Fasted

EXPERIMENTAL

Cohort 1: 200 mg INX-08189 QD fasted for seven days

Drug: 200 mg INX-08189 Fasted

Placebo QD Fasted

PLACEBO COMPARATOR

Cohort 1: Placebo QD fasted for seven days

Drug: Placebo QD Fasted

100 mg INX-08189 with Ribavirin

EXPERIMENTAL

Cohort 2: 100 mg INX-08189 100 mg dosed with ribavirin x7 days (ribavirin will be dosed in a weight-based fashion as labeled BID, the AM dose will be taken 4 hours after INX-08189 so it may be taken with food)

Drug: 100 mg INX-08189 QD; Drug: ribavirin

Placebo QD dosed with ribavirin

ACTIVE COMPARATOR

Cohort 2: Placebo QD dosed with ribavirin x7 days (ribavirin will be dosed in a weight-based fashion as labeled BID)

Drug: Placebo QD

100 mg INX-08189 with a low-fat meal

EXPERIMENTAL

Cohort 3: 100 mg INX-08189 with a low-fat meal QD x7 days

Drug: 100 mg INX-08189 with low-fat meal

Placebo with low-fat meal

PLACEBO COMPARATOR

Cohort 3: Placebo administered with a low-fat meal QD for 7 days

Drug: Placebo with low-fat meal

100 mg INX-08189 Fasted

EXPERIMENTAL

Cohort 4: 100 mg INX-08189 BID fasted x7 days

Drug: 100 mg INX-08189 BID Fasted

Placebo BID Fasted

PLACEBO COMPARATOR

Cohort 4: Placebo BID fasted x7 days

Drug: Placebo BID Fasted

Interventions

200 mg INX-08189 Fasted DRUG

200 mg capsule INX-08189 fasted x7 days

200 mg INX-08189 Fasted

Placebo QD Fasted DRUG

Placebo capsule QD fasted x7 days

Placebo QD Fasted

100 mg INX-08189 QD DRUG

100 mg INX-08189 capsule QD x 7 days

100 mg INX-08189 with Ribavirin

Placebo QD DRUG

Placebo capsule Placebo QD dosed with ribavirin x7 days (ribavirin will be dosed in a weight-based fashion as labeled BID)

Placebo QD dosed with ribavirin

100 mg INX-08189 with low-fat meal DRUG

INX-08189 100 mg capsule, with low-fat meal QD for seven days

100 mg INX-08189 with a low-fat meal

Placebo with low-fat meal DRUG

Placebo capsule administered with a low-fat meal QD for seven days

Placebo with low-fat meal

100 mg INX-08189 BID Fasted DRUG

100 mg INX-08189 BID fasted x7 days

100 mg INX-08189 Fasted

Placebo BID Fasted DRUG

Placebo BID fasted x7 days

Placebo BID Fasted

ribavirin DRUG

100 mg INX-08189 with Ribavirin

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Screening visit (Visit 1), subject criteria:
• 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 by at least 1 previous polymerase chain reaction (PCR) result prior to Visit 1 (screening), with a positive HCV viral load of least 100,000 IU/ml at Visit 1 (screening) as measured by quantitative PCR;
• HCV genotype 1 per laboratory testing report;
• HCV treatment-naïve where "treatment-naïve" is defined as no prior treatment with interferon alpha, pegylated interferon alpha, ribavirin, or any HCV direct acting anti-viral drugs;
• Liver biopsy consistent with chronic HCV infection but with a classification of non-cirrhotic as judged by a pathologist (defined as Knodell ≤ 3, Metavir ≤ 2, Ishak ≤ 4, or Batts \& Ludwig ≤ 2) within the last 2 years and before Visit 2 (biopsy can be done within the screening period);
• Negative urine drug screen for drugs of abuse (see Appendix B; note: methadone is not allowed);
• Females will have a negative serum beta human chorionic gonadotropin (βHCG) pregnancy test at screening and a negative urine dipstick pregnancy test upon entry to the clinical unit on Study Day -1;
• 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 1 barrier during the study and at least 6 months after cessation of treatment. Surgical sterilization of either the female or the male must have occurred at least 6 month prior to first dose and females must be post-menopausal for 2 years to be considered non-child-bearing potential.
• 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

You may not qualify if:

• screening visit (Visit1), subject criteria:
• Advanced liver disease, cirrhosis, or signs of decompensated liver disease such as variceal bleeding, ascites, hepatic encephalopathy, active jaundice defined by a total bilirubin \> 2, or other evidence of decompensated liver disease;
• Co-infection with hepatitis B virus (HBV)or human immunodeficiency virus (HIV) (positive test for hepatitis B surface antigen \[HBsAg\] or anti-HIV antibody \[Ab\]);
• Acute cardiac ischemia, unstable heart disease or clinically symptomatic cardiac abnormalities apparent on electrocardiogram (ECG) and physical exam, or a QTcF interval at Visit 1 of ≥ 450 ms by Fridericia's correction, or a personal or family history of Torsades de pointes;
• Use of the following medications concurrently or within the 30 days prior Screening (Visit 1) associated with QT prolongation: macrolides, antiarrhythmic agents, azoles, fluoroquinolones, and tricyclic anti-depressants (note: methadone use is not allowed);
• Use of immunosuppressive or immune-modulating agents (including 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 asthma and topical steroid for minor skin conditions allowed and washout period for PO/IM/IV corticosteroid use is 8 weeks; washout periods for other immunosuppressives determined by Medical Monitor);
• Use of strong Cytochrome P (CYP)3A4-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 \< 1,800 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, 1 re-test allowed for the purpose of qualifying for study);
• A history of abnormal thyroid function that is not adequately controlled (defined as thyroid stimulating hormone \[TSH\] levels \< 0.8 x lower limit of normal \[LLN\] or \> 1.2 x the upper limit of normal \[ULN\]);
• Serum creatinine concentration ≥ 1.5 times the upper limit of normal, or albumin ≤ 3 g/dl;
• Any history of suicide attempt, receipt of professional counseling for suicidal ideation or any current suicidal ideation, or other serious psychiatric disorders (ie, bipolar disorder, severe depression, psychosis) requiring or having required hospitalization or medication
• 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 within the past 2 years or an alcohol use pattern that will interfere with the study conduct;
• Drug abuse within the last 6 months.
• Current lactation or breastfeeding;

Sponsors & Collaborators

• Bristol-Myers Squibb: lead

Study Sites (2)

Unknown Facility

San Antonio, Texas, 78215, United States

Location

Unknown Facility

San Juan, 00927, Puerto Rico

Location

MeSH Terms

Conditions

Hepatitis C; Hepatitis, Chronic

Interventions

BMS-986094; Ribavirin

Condition Hierarchy (Ancestors)

Blood-Borne Infections; Communicable Diseases; Infections; Hepatitis, Viral, Human; Virus Diseases; Flaviviridae Infections; RNA Virus Infections; Hepatitis; Liver Diseases; Digestive System Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Ribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: FACTORIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 27, 2011
• First Posted: October 4, 2011
• Study Start: September 1, 2011
• Primary Completion: May 1, 2012
• Study Completion: May 1, 2012
• Last Updated: June 27, 2016

Record last verified: 2016-06

Locations

PR (1); US (1)