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

NCT00851890 | Completed Phase 2 Results

• 1 other identifier: M10-380
• Study Type: interventional
• Target: 30
• Locations: 2 countries
• Sites: 8

Brief Summary

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.

Conditions

Chronic Hepatitis C Virus Infection

Outcome Measures

Primary Outcomes (8)

• Mean Maximal Change From Baseline in Hepatitis C Virus Ribonucleic Acid (HCV RNA) Levels During ABT-333 Monotherapy Treatment

  Serum hepatitis C virus ribonucleic acid (HCV RNA) levels (reported as log10 IU/mL) were determined for each sample using a real-time reverse transcriptase polymerase chain reaction (RT-PCR) assay. The baseline value was the HCV RNA measurement before the first dose of ABT-333 on Day 1. The maximal change during monotherapy was nadir minus the baseline log10 HCV RNA level. Nadir was defined as the lowest log10 HCV RNA level any time after the first dose of study drug on Day 1 through the last log10 HCV RNA level before the first dose of study drug on Day 3. Data are reported as the least squares mean change from nadir ± standard error.

  Prior to the first dose on Day 1 to before first dose on Day 3

• Mean Maximal Change From Baseline in Hepatitis C Virus Ribonucleic Acid (HCV RNA) Levels Through Day 28

  Serum hepatitis C virus ribonucleic acid (HCV RNA) levels (reported as log10 IU/mL) were determined for each sample using a real-time reverse transcriptase polymerase chain reaction (RT-PCR) assay. The baseline value was the HCV RNA measurement before the first dose of ABT-333 on Day 1. The maximal change during treatment was nadir minus the baseline log10 HCV RNA level. Nadir was defined as the lowest log10 HCV RNA level any time after the first dose of study drug on Day 1 through the last log10 HCV RNA level on Day 28. Data are reported as the least squares mean change from nadir ± standard error.

  Prior to the first dose on Day 1 through Day 28

• Maximum Plasma Concentration (Cmax) of ABT-333

  Blood samples were collected pre-dose (time 0 hours); 2, 4, 8, 12, and 16 hours after the morning dose on Day 1; and pre-dose on Day 2. The samples were analyzed for the concentration of ABT-333 using validated analytical methods. The maximum plasma concentration (Cmax; measured in ng/mL) is the highest concentration that a drug achieves in the blood after administration in a dosing interval. The Cmax of ABT-333 was estimated using non-compartmental methods and data are reported as the mean ± standard deviation.

  Pre-dose (time 0 hours); 2, 4, 8, 12, and 16 hours post-dose on Day 1; and pre-dose on Day 2

• Time to Maximum Plasma Concentration (Tmax) of ABT-333

  Blood samples were collected pre-dose (time 0 hours); 2, 4, 8, 12, and 16 hours after the morning dose on Day 1; and pre-dose on Day 2. The samples were analyzed for the concentration of ABT-333 using validated analytical methods. The time to maximum plasma concentration (Tmax; measured in hours) is the time it takes for a drug to achieve Cmax. The Tmax of ABT-333 was estimated using non-compartmental methods and data are reported as the mean ± standard deviation.

  Pre-dose (time 0 hours); 2, 4, 8, 12, and 16 hours post-dose on Day 1; and pre-dose on Day 2

• Area Under the Plasma Concentration-time Curve From 0 to 12 Hours Post-dose (AUC12) of ABT-333

  Blood samples were collected pre-dose (time 0 hours); 2, 4, 8, 12, and 16 hours after the morning dose on Day 1; and pre-dose on Day 2. The samples were analyzed for the concentration of ABT-333 using validated analytical methods. The area under the plasma concentration-time curve (AUC; measured in ng\*hr/mL) measures the total exposure of a drug in blood plasma. The AUC12 of ABT-333 was estimated using non-compartmental methods and data are reported as the mean ± standard deviation.

  Pre-dose (time 0 hours); 2, 4, 8, 12, and 16 hours post-dose on Day 1; and pre-dose on Day 2

• Serum Concentrations of Pegylated Interferon (pegIFN)

  Blood samples were collected prior to the morning dose on Day 3; 4 hours after the morning dose on Day 3; prior to the morning dose on Days 4 and 5; and single samples were collected on Days 10, 17, 24, and 28. The samples were analyzed for the concentration of pegIFN (measured in ng/mL) using validated analytical methods and estimated using non-compartmental methods. Data are reported as the mean ± standard deviation.

  Prior to the morning dose on Day 3; 4 hours after the morning dose on Day 3; prior to the morning dose on Days 4 and 5; and single samples were collected on Days 10, 17, 24, and 28

• Plasma Concentrations of Ribavirin (RBV)

  Blood samples were collected prior to the morning dose on Day 3; 4 hours after the morning dose on Day 3; prior to the morning dose on Days 4 and 5; and single samples were collected on Days 10, 17, 24, and 28. The samples were analyzed for the concentration of RBV (measured in ng/mL) using validated analytical methods and estimated using non-compartmental methods. Data are reported as the mean ± standard deviation.

  Prior to the morning dose on Day 3; 4 hours after the morning dose on Day 3; prior to the morning dose on Days 4 and 5; and single samples were collected on Days 10, 17, 24, and 28

• Number of Participants Having Treatment-emergent Adverse Events (AEs)

  An AE was any untoward medical occurrence that did not have a causal relationship with treatment. An Adverse Drug Reaction (ADR) was any noxious and undesired reaction related to the experimental drug or experiment. A serious adverse event (SAE) was an AE that resulted in death, was life-threatening, resulted in or prolonged hospitalization, resulted in congenital anomaly, was persistent or caused significant disability/incapacity, spontaneous or elective abortion, or required intervention to prevent a serious outcome. AEs were rated for severity as either: 1. Mild - transient and easily tolerated; 2. Moderate - caused discomfort and interrupted usual activities; 3. Severe - caused considerable interference with usual activities, may be incapacitating or life-threatening. AEs related to direct-acting antiviral agents (DAAs) were assessed as being either probably or possibly related by the investigator.

  AEs were collected from the time of study drug administration to 30 days after last dose of study drug (8 Weeks)

Secondary Outcomes (6)

• Change From Baseline in Hepatitis C Virus Ribonucleic Acid (HCV RNA) Levels Through Day 28 or Final Visit

  Day 28 and Final Visit

• Percentage of Participants With at Least a 2 log10 Maximal Decrease in Hepatitis C Virus Ribonucleic Acid (HCV RNA) Levels During ABT-333 Treatment

  Prior to the first dose on Day 1 and Day 28

• Percentage of Participants With Hepatitis C Virus Ribonucleic Acid (HCV RNA) Levels ≤ 25 IU/mL (the Lower Limit of Quantitation [LLOQ]) at Day 28 or Final Visit

  Day 28 or Final Visit

• Percentage of Participants With Hepatitis C Virus Ribonucleic Acid (HCV RNA) Levels ≤ 10 IU/mL (Lower Limit of Detection [LLOD]) at Day 28 or Final Visit

  Day 28 or Final Visit

• Number of Participants With Resistance-Associated Variants in Non-structural Viral Protein 5B (NS5B) Through Day 28

  Days 1, 5, 10, 17, 24 and 28

Study Arms (4)

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

EXPERIMENTAL

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.

Drug: ABT-333; Drug: Pegylated interferon; Drug: Ribavirin

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

EXPERIMENTAL

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.

Drug: ABT-333; Drug: Pegylated interferon; Drug: Ribavirin

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

EXPERIMENTAL

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.

Drug: ABT-333; Drug: Pegylated interferon; Drug: Ribavirin

Placebo + pegIFN/RBV

PLACEBO COMPARATOR

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.

Other: Placebo for ABT-333; Drug: Pegylated interferon; Drug: Ribavirin

Interventions

ABT-333 DRUG

50 mg capsules

Also known as: dasabuvir

ABT-333 (1200 mg) once daily (QD) + pegIFN/RBV; ABT-333 (300 mg) twice daily (BID) + pegIFN/RBV; ABT-333 (600 mg) twice daily (BID) + pegIFN/RBV

Placebo for ABT-333 OTHER

Capsule

Placebo + pegIFN/RBV

Pegylated interferon DRUG

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

ABT-333 (1200 mg) once daily (QD) + pegIFN/RBV; ABT-333 (300 mg) twice daily (BID) + pegIFN/RBV; ABT-333 (600 mg) twice daily (BID) + pegIFN/RBV; Placebo + pegIFN/RBV

Ribavirin DRUG

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

ABT-333 (1200 mg) once daily (QD) + pegIFN/RBV; ABT-333 (300 mg) twice daily (BID) + pegIFN/RBV; ABT-333 (600 mg) twice daily (BID) + pegIFN/RBV; Placebo + pegIFN/RBV

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• AbbVie (prior sponsor, Abbott): lead

Study Sites (8)

Site Reference ID/Investigator# 16103

Anaheim, California, 92801, United States

Location

Site Reference ID/Investigator# 16124

Los Angeles, California, 90048, United States

Location

Site Reference ID/Investigator# 16102

Orlando, Florida, 32803, United States

Location

Site Reference ID/Investigator# 16105

Baton Rouge, Louisiana, 70808, United States

Location

Site Reference ID/Investigator# 16106

Chapel Hill, North Carolina, 27599-7584, United States

Location

Site Reference ID/Investigator# 16107

Dallas, Texas, 75203, United States

Location

Site Reference ID/Investigator# 16123

San Antonio, Texas, 78215, United States

Location

Site Reference ID/Investigator# 16182

Santurce, 00909, Puerto Rico

Location

Related Publications (1)

• 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.

  PMID: 26597291 BACKGROUND

Related Links

• Related Info

MeSH Terms

Interventions

dasabuvir; Ribavirin

Intervention Hierarchy (Ancestors)

Ribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides

Results Point of Contact

• Title: Global Medical Services
• Organization: AbbVie (prior sponsor, Abbott)

800-633-9110

Study Officials

• Daniel Cohen, MD

  AbbVie

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 24, 2009
• First Posted: February 26, 2009
• Study Start: March 1, 2009
• Primary Completion: July 1, 2009
• Study Completion: July 1, 2009
• Last Updated: July 2, 2018
• Results First Posted: January 8, 2015

Record last verified: 2014-12

Locations

PR (1); US (7)