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Study of the Safety & PK of INX-08189 in Chronically-infected HCV, Treatment-naïve Subjects | Clinical Trials | Clareo Health

COMPLETEDPHASE1

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

A Multi-center, Sequential-cohort, Placebo-controlled, 7-day Treatment Period Study of the Safety and Pharmacokinetics of Multiple Ascending Oral Doses of INX-08189 in Chronically-infected Genotype 1 HCV, Treatment-naïve Subjects

NCT01250366•Bristol-Myers Squibb

View on ClinicalTrials.gov

Summary

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

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

Eligibility

Age

18 - 65 years

Sex

ALL

Healthy Volunteers

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;
+1 more criteria

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;
+8 more criteria

Locations (4)

Los Angeles, California, United States

Plymouth, Minnesota, United States

San Antonio, Texas, United States

San Juan, Puerto Rico

Key Dates

Start Date

October 1, 2010

Primary Completion Date

March 1, 2011

Completion Date

June 1, 2011

Last Updated

July 12, 2012

Enrollment

ACTUAL participants

Conditions

HCV (Genotype 1)

Interventions

INX-08189

DRUG

INX-08189

DRUG

INX-08189

DRUG

INX-08189

DRUG

INX-08189

DRUG

INX-08189

DRUG

INX-08189

DRUG

Placebo matching with INX-08189

DRUG

Ribavirin

DRUG