A Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Antiviral Activity of Multiple Doses of ABT-333 Alone and in Combination With Pegylated Interferon (pegIFN) and Ribavirin (RBV) in Subjects With Genotype 1 Chronic Hepatitis C Virus (HCV) Infection

NCT ID: NCT00851890

Last Updated: 2018-07-02

Study Results

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE2

Total Enrollment

30 participants

Study Classification

INTERVENTIONAL

Study Start Date

2009-03-31

Study Completion Date

2009-07-31

Brief Summary

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The purpose of this study was to assess the safety, tolerability, pharmacokinetics and antiviral activity of ABT-333 (also known as dasabuvir) in treatment-naïve, hepatitis C virus (HCV)-infected participants.

Detailed Description

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This was a Phase 2a, blinded, randomized, placebo-controlled clinical trial in hepatitis C virus (HCV)-infected adults with 2 planned sequential evaluations, Part 1 and Part 2. The study evaluated the safety, tolerability, antiviral activity, and pharmacokinetics of ABT-333 or placebo monotherapy, followed by 26 days of ABT-333 or placebo with pegylated interferon a-2a (pegIFN) and ribavirin (RBV) combination therapy. Review of safety and efficacy in Part 1 of the study showed similar response rates across ABT-333 doses so Part 2 of the study was not performed. The study also assessed emergence of resistant HCV in conjunction with kinetics of viral load decay and rebound in treatment-naïve, HCV-infected participants.

Conditions

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Chronic Hepatitis C Virus Infection

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

DOUBLE

Participants Investigators

Study Groups

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ABT-333 (300 mg) twice daily (BID) + pegIFN/RBV

Hepatitis C virus (HCV) positive, treatment-naive participants received 300 mg ABT-333 BID for 2 days followed by 300 mg ABT-333 BID with pegylated interferon/ribavirin (pegIFN/RBV) for 26 days. Pegylated interferon was administered at 180 μg subcutaneously once a week and RBV was dosed 1000 or 1200 mg daily divided twice a day.

Group Type EXPERIMENTAL

ABT-333

Intervention Type DRUG

50 mg capsules

Pegylated interferon

Intervention Type DRUG

Syringe, 180 µg/0.5 mL for subcutaneous injections administered weekly

Ribavirin

Intervention Type DRUG

200 mg tablet dosed at 1000 or 1200 mg daily divided twice a day

ABT-333 (600 mg) twice daily (BID) + pegIFN/RBV

Hepatitis C virus (HCV) positive, treatment-naive participants received 600 mg ABT-333 BID for 2 days followed by 600 mg ABT-333 BID with pegylated interferon/ribavirin (pegIFN/RBV) for 26 days. Pegylated interferon was administered at 180 μg subcutaneously once a week and RBV was dosed 1000 or 1200 mg daily divided twice a day.

Group Type EXPERIMENTAL

ABT-333

Intervention Type DRUG

50 mg capsules

Pegylated interferon

Intervention Type DRUG

Syringe, 180 µg/0.5 mL for subcutaneous injections administered weekly

Ribavirin

Intervention Type DRUG

200 mg tablet dosed at 1000 or 1200 mg daily divided twice a day

ABT-333 (1200 mg) once daily (QD) + pegIFN/RBV

Hepatitis C virus (HCV) positive, treatment-naive participants received 1200 mg ABT-333 QD for 2 days followed by 1200 mg ABT-333 QD with pegylated interferon/ribavirin (pegIFN/RBV) for 26 days. Pegylated interferon was administered at 180 μg subcutaneously once a week and RBV was dosed 1000 or 1200 mg daily divided twice a day.

Group Type EXPERIMENTAL

ABT-333

Intervention Type DRUG

50 mg capsules

Pegylated interferon

Intervention Type DRUG

Syringe, 180 µg/0.5 mL for subcutaneous injections administered weekly

Ribavirin

Intervention Type DRUG

200 mg tablet dosed at 1000 or 1200 mg daily divided twice a day

Placebo + pegIFN/RBV

Hepatitis C virus (HCV) positive, treatment-naïve participants received matching placebo once daily (QD) or twice daily (BID) for 2 days followed by placebo QD or BID with pegylated interferon/ribavirin (pegIFN/RBV) for 26 days. Pegylated interferon was administered at 180 μg subcutaneously once a week and RBV was dosed 1000 or 1200 mg daily divided twice a day.

Group Type PLACEBO_COMPARATOR

Placebo for ABT-333

Intervention Type OTHER

Capsule

Pegylated interferon

Intervention Type DRUG

Syringe, 180 µg/0.5 mL for subcutaneous injections administered weekly

Ribavirin

Intervention Type DRUG

200 mg tablet dosed at 1000 or 1200 mg daily divided twice a day

Interventions

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ABT-333

50 mg capsules

Intervention Type DRUG

Placebo for ABT-333

Capsule

Intervention Type OTHER

Pegylated interferon

Syringe, 180 µg/0.5 mL for subcutaneous injections administered weekly

Intervention Type DRUG

Ribavirin

200 mg tablet dosed at 1000 or 1200 mg daily divided twice a day

Intervention Type DRUG

Other Intervention Names

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dasabuvir

Eligibility Criteria

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Inclusion Criteria

* Participant has provided written consent.
* If female, participant is postmenopausal or surgically sterile.
* If male, must be practicing two effective methods of birth control.
* Participant is hepatitis C virus (HCV) genotype 1 with HCV ribonucleic acid levels \>50,000 IU/mL.
* Participants must demonstrate chronic hepatitis C infection for at least 6 months prior to study enrollment.
* Participants must have a liver biopsy with histology consistent with HCV-induced liver damage, and with no evidence of cirrhosis or liver pathology due to any cause other than chronic HCV.
* Condition of general good health other then HCV infection.
* Participants with a history of thyroid disease must have a thyroid stimulating hormone (TSH) value in the normal range.

Exclusion Criteria

* No prior history of receiving therapy for HCV infection.
* Positive test result for hepatitis A virus immunoglobulin M (HAV-IgM), hepatitis B surface antigen (HBsAg), or human immunodeficiency virus antibody (HIV Ab).
* Pregnant or breastfeeding females or male partners of women who are pregnant.
* History of seizures or cancer.
* History of major depressive disorder within 2 years.
* Any current or past history of cirrhosis.
* Any cause of liver disease other than chronic HCV infection.
Minimum Eligible Age

18 Years

Maximum Eligible Age

70 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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AbbVie (prior sponsor, Abbott)

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Daniel Cohen, MD

Role: STUDY_DIRECTOR

AbbVie

Locations

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Site Reference ID/Investigator# 16103

Anaheim, California, United States

Site Status

Site Reference ID/Investigator# 16124

Los Angeles, California, United States

Site Status

Site Reference ID/Investigator# 16102

Orlando, Florida, United States

Site Status

Site Reference ID/Investigator# 16105

Baton Rouge, Louisiana, United States

Site Status

Site Reference ID/Investigator# 16106

Chapel Hill, North Carolina, United States

Site Status

Site Reference ID/Investigator# 16107

Dallas, Texas, United States

Site Status

Site Reference ID/Investigator# 16123

San Antonio, Texas, United States

Site Status

Site Reference ID/Investigator# 16182

Santurce, , Puerto Rico

Site Status

Countries

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United States Puerto Rico

References

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Mensing S, Polepally AR, Konig D, Khatri A, Liu W, Podsadecki TJ, Awni WM, Menon RM, Dutta S. Population Pharmacokinetics of Paritaprevir, Ombitasvir, Dasabuvir, Ritonavir, and Ribavirin in Patients with Hepatitis C Virus Genotype 1 Infection: Combined Analysis from 9 Phase 1b/2 Studies. AAPS J. 2016 Jan;18(1):270-80. doi: 10.1208/s12248-015-9846-1. Epub 2015 Nov 23.

Reference Type BACKGROUND
PMID: 26597291 (View on PubMed)

Related Links

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Other Identifiers

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M10-380

Identifier Type: -

Identifier Source: org_study_id

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