Study of the Safety & PK of INX-08189 in Chronically-infected HCV, Treatment-naïve Subjects

NCT ID: NCT01250366

Last Updated: 2012-07-12

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE1

Total Enrollment

70 participants

Study Classification

INTERVENTIONAL

Study Start Date

2010-10-31

Study Completion Date

2011-06-30

Brief Summary

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The purpose of this study is to determine the Safety and Pharmacokinetics of Multiple Ascending Oral Doses of INX-08189 in Chronically-infected Genotype 1 HCV, Treatment-naïve Subjects.

Detailed Description

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This is a multi-center, sequential-cohort, double-blind, placebo-controlled, multiple ascending dose, 7-day treatment study in chronically-infected genotype 1 HCV, treatment-naïve subjects.

Primary Objectives include:

Safety

• to evaluate the safety of ascending oral doses of INX-08189 given once a day for seven (7) days in chronically-infected genotype 1 HCV, treatment-naïve subjects

Pharmacokinetic

• to characterize the pharmacokinetic (PK) profile of multiple ascending oral doses of INX-08189 in chronically-infected genotype 1 HCV, treatment-naïve subjects

Pharmacodynamic

• to evaluate the relationship between the metrics of the reduction from baseline in serum HCV RNA and PK parameters of INX-08189 and the metabolite INX-08032

Efficacy

• to measure the maximal reduction in plasma HCV RNA by ascending oral dose level of INX-08189 given once a day for seven (7) days in chronically-infected genotype 1 HCV, treatment-naïve subjects

Conditions

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HCV (Genotype 1)

Keywords

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Safety and Pharmacokinetics

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

FACTORIAL

Primary Study Purpose

TREATMENT

Blinding Strategy

TRIPLE

Participants Caregivers Investigators

Study Groups

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Arm 1: INX-08189 (9 mg) or Placebo

Group Type EXPERIMENTAL

INX-08189

Intervention Type DRUG

Capsules, Oral, 9 mg, Once Daily, 7 Days

Placebo matching with INX-08189

Intervention Type DRUG

Capsules, Oral, 0 mg, Once daily, 7 days

Arm 2: INX-08189 (25 mg) or Placebo

Group Type EXPERIMENTAL

INX-08189

Intervention Type DRUG

Capsule, Oral, 25 mg, Once Daily, 7 days

Placebo matching with INX-08189

Intervention Type DRUG

Capsules, Oral, 0 mg, Once daily, 7 days

Arm 3: INX-08189 (50 mg + 9 mg) or Placebo

Group Type EXPERIMENTAL

INX-08189

Intervention Type DRUG

Capsules, Oral, 50 mg, Single Dose, 1 day

INX-08189

Intervention Type DRUG

Capsules, Oral, 9 mg, Once daily, 6 days

Placebo matching with INX-08189

Intervention Type DRUG

Capsules, Oral, 0 mg, Once daily, 7 days

Arm 4: INX-08189 (50 mg) or Placebo

Group Type EXPERIMENTAL

INX-08189

Intervention Type DRUG

Capsules, Oral, 50 mg, Once daily, 7 days

Placebo matching with INX-08189

Intervention Type DRUG

Capsules, Oral, 0 mg, Once daily, 7 days

Arm 5: INX-08189 (9 mg) or Placebo + Ribavirin

Group Type EXPERIMENTAL

INX-08189

Intervention Type DRUG

Capsules, Oral, 9 mg, Once daily, 7 days

Placebo matching with INX-08189

Intervention Type DRUG

Capsules, Oral, 0 mg, Once daily, 7 days

Ribavirin

Intervention Type DRUG

Capsules, Oral, 1000 or 1200 mg daily (delivered in weight-adjusted am/pm divided dose), 7 days

Arm 6: INX-08189 (25 mg) or Placebo + Ribavirin

Group Type EXPERIMENTAL

INX-08189

Intervention Type DRUG

Capsule, Oral, 25 mg, Once Daily, 7 days

Placebo matching with INX-08189

Intervention Type DRUG

Capsules, Oral, 0 mg, Once daily, 7 days

Ribavirin

Intervention Type DRUG

Capsules, Oral, 1000 or 1200 mg daily (delivered in weight-adjusted am/pm divided dose), 7 days

Arm 7: INX-08189 (100 mg) or Placebo

Group Type EXPERIMENTAL

INX-08189

Intervention Type DRUG

Capsules, Oral, 100 mg, Once daily, 7 days

Placebo matching with INX-08189

Intervention Type DRUG

Capsules, Oral, 0 mg, Once daily, 7 days

Interventions

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INX-08189

Capsules, Oral, 9 mg, Once Daily, 7 Days

Intervention Type DRUG

INX-08189

Capsule, Oral, 25 mg, Once Daily, 7 days

Intervention Type DRUG

INX-08189

Capsules, Oral, 50 mg, Single Dose, 1 day

Intervention Type DRUG

INX-08189

Capsules, Oral, 9 mg, Once daily, 6 days

Intervention Type DRUG

INX-08189

Capsules, Oral, 50 mg, Once daily, 7 days

Intervention Type DRUG

INX-08189

Capsules, Oral, 9 mg, Once daily, 7 days

Intervention Type DRUG

INX-08189

Capsules, Oral, 100 mg, Once daily, 7 days

Intervention Type DRUG

Placebo matching with INX-08189

Capsules, Oral, 0 mg, Once daily, 7 days

Intervention Type DRUG

Ribavirin

Capsules, Oral, 1000 or 1200 mg daily (delivered in weight-adjusted am/pm divided dose), 7 days

Intervention Type DRUG

Eligibility Criteria

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Inclusion Criteria

At the screening visit (Visit 1), subjects will meet the following criteria:

1. Males \& females, 18 - 65 years of age inclusive(BMI of at least 18kg/m2 not exceeding 36kg/m2);
2. Diagnosis of chronic HCV by 1 previous PCR result prior to screening, with a positive HCV viral load of at least 100,000IU/ml at screening measured by quantitative PCR;
3. HCV genotype 1 per central lab testing report;
4. HCV treatment-naïve (defined as no prior treatment with interferon, pegylated interferon, ribavirin, or any HCV direct acting anti-viral drugs);
5. Liver biopsy consistent with chronic HCV infection but non-cirrhotic as judged by a pathologist (Knodell \< 3, Metavir \<2, Ishak \<4, or Batts \& Ludwig \<2) within the last 2 years \& before Visit 2 (biopsy can be done within screening period);
6. Negative urine drug screen for drugs of abuse at screening and Study Day -1 (methadone use allowed);
7. Females will have a negative serum βHCG pregnancy test at screening \& negative urine dipstick pregnancy test upon entry to clinical unit on Study Day -1;
8. Agreement by both females of childbearing potential \& males(who have not been surgically sterilized) to practice an acceptable method of birth control. Surgical sterilization of either female or male partner must have occurred at least 6 month prior to first dose \& females must be post-menopausal for 2 years to be considered of non-child-bearing potential. Acceptable contraceptive methods include 1 of the following: Oral \& implantable hormonal contraceptives by female at least 3 months prior to the 1st dose of Study Drug, IUD in place at least 6 months prior to first dose, barrier methods either diaphragm or condom with spermicide. (Abstinence is not an acceptable method of birth control, subjects who indicate sexual inactivity must agree to utilize birth control in the event of sexual activity);
9. Willing \& able to complete all study visits and procedures, \& able to communicate with the investigator \& other personnel;
10. Signed informed consent form (ICF) executed prior to protocol screening assessments

Exclusion Criteria

At the screening visit subjects will not meet any of the following criteria:

1. Advanced liver disease, cirrhosis, or with signs of decompensated liver disease such as variceal bleeding, ascites, hepatic encephalopathy, active jaundice (total bilirubin \> 2, or other evidence of decompensated liver disease;
2. Co-infection with HBV or HIV (positive test for HBsAg or anti-HIV Ab);
3. Acute cardiac ischemia, unstable heart disease or clinically symptomatic cardiac abnormalities apparent on ECG \& PE, or a QTcB interval at Visit 1 of ≥ to 450ms by Bazette's correction, or personal or family history of Torsades de pointes;
4. Use of the following medications concurrently or within the 30 days prior to Screening associated with QT prolongation: macrolides, antiarrhythmic agents, azoles, fluoroquinolones, \& tricyclic anti-depressants (methadone use allowed);
5. Use of immunosuppressive or immune-modulating agents (including corticosteroids \& immunosuppressive agents) or presence of an immunologically-mediated autoimmune disease (other than asthma) or history of organ transplantation (inhaled steroids for asthma \& topical steroid for minor skin conditions allowed);
6. Use of strong CYP3A4-inhibiting protease inhibitors (specifically atazanavir, indinavir, nelfinavir, saquinavir, \& ritonavir), strong CYP3A4 inhibitors (specifically clarithromycin, itraconazole, ketoconazole, nefazodone, telithromycin), or strong CYP3A4 inducers (specifically rifampin, efavirenz, etravirine, phenobarbital, phenytoin, \& carbamazepine);
7. Absolute NEUT count of \<1800 cells/mm3 (or \< 1500 cells/mm3 for African Americans), or platelet count \<130,000 cells/mm3, or hemoglobin \<11g/dl for women and \<13g/dl for men;
8. A history of abnormal thyroid function not adequately controlled (defined as TSH levels \< 0.8 x LLN or \> 1.2 x the ULN);
9. Serum creatinine concentration \> 1.5 times the upper limit of normal, or albumin \< 3g/dl;
10. Presence or history of severe, or uncontrolled, or hospitalization-requiring psychiatric disease including severe depression, suicide attempts or any severity of psychosis;
11. 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;
12. Alcohol abuse (investigator assessment) within the past 2 years or an alcohol use pattern that will interfere with the study conduct;
13. Drug abuse (investigator assessment)within the last 6 months with exception of methadone;
14. Current lactation or breastfeeding;
15. Major surgery within 30 days prior Visit 1;
16. Participation in another clinical trial of an investigational drug or device within 6 months prior to visit 1;
17. Donation of blood or plasma within 30 days prior to Visit 1
Minimum Eligible Age

18 Years

Maximum Eligible Age

65 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Bristol-Myers Squibb

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Locations

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Los Angeles, California, United States

Site Status

Plymouth, Minnesota, United States

Site Status

San Antonio, Texas, United States

Site Status

San Juan, , Puerto Rico

Site Status

Countries

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United States Puerto Rico

Other Identifiers

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INH-189-002

Identifier Type: OTHER

Identifier Source: secondary_id

AI472-002

Identifier Type: -

Identifier Source: org_study_id