Study to Assess the Safety, Tolerability, Pharmacokinetics and Antiviral Activity of ABT-267 in HCV Infected Subjects

NCT01563536 | Completed Phase 2 Results

• 1 other identifier: M13-386
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 4

Brief Summary

The purpose of this study is to assess the safety, tolerability, pharmacokinetics, and antiviral activity of multiple, ascending doses of ABT-267 (also known as ombitasvir) administered as two-day monotherapy followed by ABT-267 in combination therapy with other direct-acting antiviral agents (DAAs) ABT-450 with ritonavir (ABT-450/r) and ABT-333 (also known as dasabuvir) plus ribavirin (RBV) in patients with chronic Hepatitis C virus (HCV) infection without cirrhosis.

Conditions

Chronic Hepatitis C Infection

Keywords

Hepatitis C,Genotype 1

Outcome Measures

Primary Outcomes (6)

• Maximum Plasma Concentration (Cmax) of ABT-267 Following Monotherapy on Day 1

  Blood samples were collected pre-dose (time 0) and at 2, 4, and 6 hours post-dose on Day 1 and pre-dose on Day 2 (ABT-267 monotherapy). The samples were analyzed for ABT-267 using validated analytical methods. Maximum plasma concentration (Cmax; measured in ng/mL) was estimated using noncompartmental analyses.

  Day 1 (pre-dose [time 0] and at 2, 4, and 6 hours post-dose) and Day 2 (pre-dose)

• Time of Maximum Plasma Concentration (Tmax) of ABT-267 Following Monotherapy on Day 1

  Blood samples were collected pre-dose (time 0) and at 2, 4, and 6 hours post-dose on Day 1 and pre-dose on Day 2 (ABT-267 monotherapy). The samples were analyzed for ABT-267 using validated analytical methods. Time of maximum plasma concentration (Tmax; measured in hours) was estimated using noncompartmental analyses.

  Day 1 (pre-dose [time 0] and at 2, 4, and 6 hours post-dose) and Day 2 (pre-dose)

• Area Under the Plasma Concentration-time Curve From Time 0 to 24 Hours (AUC[24]) of ABT-267 Following Monotherapy on Day 1

  Blood samples were collected pre-dose (time 0) and at 2, 4, and 6 hours post-dose on Day 1 and pre-dose on Day 2 (ABT-267 monotherapy). The samples were analyzed for ABT-267 using validated analytical methods. Area under the plasma concentration-time curve from time 0 to 24 hours (AUC\[24\]; measured in ng multiplied by hour/mL) was estimated using noncompartmental analyses.

  Day 1 (pre-dose [time 0] and at 2, 4, and 6 hours post-dose) and Day 2 (pre-dose)

• Plasma Concentration of ABT-267 Pre-dose (Ctrough) on Day 2 and Day 3

  Blood samples were collected pre-dose on Day 2 (prior to second dose of ABT-267 monotherapy) and pre-dose on Day 3 (prior to first dose of combination therapy). The samples were analyzed for ABT-267 using validated analytical methods. Pre-dose plasma concentrations on Day 2 and Day 3 (Ctrough, measured in ng/mL) are reported.

  Day 2 (pre-dose) and Day 3 (pre-dose)

• Number of Participants With Adverse Events (AEs)

  An adverse event was defined as any untoward medical occurrence in a patient or clinical investigation participant administered a pharmaceutical product and that did not necessarily have a causal relationship with this treatment. The investigator assessed the relationship of each AE to the use of direct-acting antiviral agents (DAAs), and rated the severity of each event as either: Mild: The AE was transient and easily tolerated by the participant; Moderate: The AE caused the participant discomfort and interrupted usual activities; Severe: The AE caused considerable interference with the participant's usual activities and could have been incapacitating or life-threatening. A serious adverse event was any event that resulted in death, was life-threatening, resulted in hospitalization or prolongation of hospitalization, resulted in a congenital anomaly or persistent or significant disability or was any other important medical event requiring medical or surgical intervention.

  All AEs were collected from the time of study drug administration to 30 days after last dose of study drug (16 weeks).

• Mean Maximal Decrease From Baseline in Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) During ABT-267 Monotherapy

  The baseline value was the last measurement before the first dose of ABT-267 monotherapy (Day 1). The maximal decrease during monotherapy was the change from baseline to the lowest log10 IU/mL HCV RNA level any time from the first dose of ABT-267 on Day 1 to the last log10 HCV RNA level before the first dose of ABT-267 combination therapy (Study Day 3).

  Pre-dose on Days 1, 2, and 3

Secondary Outcomes (5)

• Percentage of Participants With Sustained Virologic Response 12 Weeks and 24 Weeks After Combination Therapy

  12 and 24 weeks after last dose of combination study drug

• Percentage of Participants With Rapid Virologic Response

  4 weeks

• Percentage of Participants With End-of-Treatment Response

  12 weeks

• Percentage of Participants With Extended Rapid Virologic Response

  Weeks 4 to 12

• Mean Change in Viral Load From Baseline to Pre-dose on Day 2 and Day 3 of ABT-267 Monotherapy

  Predose on Days 1, 2, and 3

Other Outcomes (1)

• Resistance-Associated Variants and Phenotypic Resistance

  Day 1 Pre-dose (Baseline) and Day 3 Pre-dose

Study Arms (2)

ABT-267 1.5 mg, then ABT-267, ABT-450/r, ABT-333, plus RBV

EXPERIMENTAL

ABT-267 (1.5 mg once daily) as monotherapy for 2 days, then ABT-267 (1.5 mg once daily), ABT-450/r (150 mg/ 100 mg once daily) and ABT-333 (400 mg twice daily), plus weight-based RBV (dosed 1,000 or 1,200 mg daily divided twice a day) combination therapy for 12 weeks

Drug: ABT-267; Drug: ABT-450; Drug: ABT-333; Drug: Ritonavir; Drug: Ribavirin

ABT-267 25 mg, then ABT-267, ABT-450/r, ABT-333, plus RBV

EXPERIMENTAL

ABT-267 (25 mg once daily) as monotherapy for 2 days, then ABT-267 (25 mg once daily), ABT-450/r (150 mg/ 100 mg once daily) and ABT-333 (400 mg twice daily), plus weight-based RBV (dosed 1,000 or 1,200 mg daily divided twice a day) combination therapy for 12 weeks

Drug: ABT-267; Drug: ABT-450; Drug: ABT-333; Drug: Ritonavir; Drug: Ribavirin

Interventions

ABT-267 DRUG

Tablet

Also known as: ombitasvir

ABT-267 1.5 mg, then ABT-267, ABT-450/r, ABT-333, plus RBV; ABT-267 25 mg, then ABT-267, ABT-450/r, ABT-333, plus RBV

ABT-450 DRUG

Tablet

ABT-267 1.5 mg, then ABT-267, ABT-450/r, ABT-333, plus RBV; ABT-267 25 mg, then ABT-267, ABT-450/r, ABT-333, plus RBV

ABT-333 DRUG

Tablet

Also known as: dasabuvir

ABT-267 1.5 mg, then ABT-267, ABT-450/r, ABT-333, plus RBV; ABT-267 25 mg, then ABT-267, ABT-450/r, ABT-333, plus RBV

Ritonavir DRUG

Capsule

ABT-267 1.5 mg, then ABT-267, ABT-450/r, ABT-333, plus RBV; ABT-267 25 mg, then ABT-267, ABT-450/r, ABT-333, plus RBV

Ribavirin DRUG

Tablet

ABT-267 1.5 mg, then ABT-267, ABT-450/r, ABT-333, plus RBV; ABT-267 25 mg, then ABT-267, ABT-450/r, ABT-333, plus 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:

• Male or female between the age of 18 and 70 years, inclusive, at time of enrollment.
• Subject has never received antiviral treatment for hepatitis C virus (HCV) infection.
• Body mass index (BMI) is ≥ 18 to \< 38 kg/m\^2. BMI is calculated as weight measured in kilograms (kg) divided by the square of height measured in meters (m).
• Chronic HCV genotype 1-infection for at least 6 months prior to study enrollment.
• Subject has plasma HCV RNA level \> 10,000 IU/mL at screening

You may not qualify if:

• History of severe, life-threatening or other significant sensitivity to any drug.
• Females who are or plan to become pregnant or breastfeeding or males whose partner is pregnant or planning to become pregnant.
• Recent history of drug or alcohol abuse that could preclude adherence to the protocol.
• Positive test result for hepatitis B surface antigen or anti-human immunodeficiency virus (HIV) antibodies.
• Any current or past clinical evidence of cirrhosis (e.g., ascites, esophageal varices), or a liver biopsy or FibroTest/aspartate aminotransferase to platelet ratio (APRI) or FibroScan® showing cirrhosis or extensive bridging fibrosis.

Sponsors & Collaborators

• AbbVie (prior sponsor, Abbott): lead

Study Sites (4)

Site Reference ID/Investigator# 68002

Bakersfield, California, 93301, United States

Location

Site Reference ID/Investigator# 67383

Orlando, Florida, 32809, United States

Location

Site Reference ID/Investigator# 67382

Annapolis, Maryland, 21401, United States

Location

Site Reference ID/Investigator# 67385

Poughkeepsie, New York, 12601, United States

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

ombitasvir; paritaprevir; dasabuvir; Ritonavir; Ribavirin

Intervention Hierarchy (Ancestors)

Thiazoles; Sulfur Compounds; Organic Chemicals; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Ribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides

Results Point of Contact

• Title: Global Medical Services
• Organization: AbbVie

800-633-9110

Study Officials

• Andrew L Campbell, 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: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 27, 2012
• First Posted: March 27, 2012
• Study Start: February 1, 2012
• Primary Completion: April 1, 2012
• Study Completion: June 1, 2013
• Last Updated: July 2, 2018
• Results First Posted: January 8, 2015

Record last verified: 2014-12

Locations

US (4)