Chronic Hepatitis C Virus InfectionPhase 2NCT00851890
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
A Phase 2 study testing ABT-333, Pegylated interferon and Ribavirin in people with Chronic Hepatitis C Virus Infection, run by AbbVie (prior sponsor, Abbott) at 8 sites in 2 countries.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 70 years
- Conditions the study is for
- Chronic Hepatitis C Virus Infection
- What is being tested?
- ABT-333, Pegylated interferon and Ribavirin
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 30 participants
- Where
- 8 sitesin 2 countries
- Study dates
- Mar 2009to Jul 2009
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 70 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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.
Trial locations and contacts
8 sites in 2 countries.
8 sites in 2 countries
United States7 sites
Site Reference ID/Investigator# 16103
Anaheim, California, 92801
Site Reference ID/Investigator# 16105
Baton Rouge, Louisiana, 70808
Site Reference ID/Investigator# 16106
Chapel Hill, North Carolina, 27599-7584
Site Reference ID/Investigator# 16107
Dallas, Texas, 75203
Site Reference ID/Investigator# 16124
Los Angeles, California, 90048
Site Reference ID/Investigator# 16102
Orlando, Florida, 32803
Site Reference ID/Investigator# 16123
San Antonio, Texas, 78215
About this study
Official title: A Blinded, Randomized, Placebo-controlled 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
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.
Read the detailed description
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
- Chronic Hepatitis C Virus Infection
- Being tested
- ABT-333, Placebo for ABT-333, Pegylated interferon, Ribavirin
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ABT-333Drug
Also called dasabuvir
50 mg capsules
Placebo for ABT-333Other
Capsule
Pegylated interferonDrug
Syringe, 180 µg/0.5 mL for subcutaneous injections administered weekly
RibavirinDrug
200 mg tablet dosed at 1000 or 1200 mg daily divided twice a day
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: 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. Receives: 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. Receives: 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. Receives: Other: Placebo for ABT-333; Drug: Pegylated interferon; Drug: Ribavirin |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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:
- Mild - transient and easily tolerated;
- Moderate - caused discomfort and interrupted usual activities;
- 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.
Measured: 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
Serum hepatitis C virus ribonucleic acid (HCV RNA) levels (reported as log10 IU/mL) were determined 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 and the Day 28 or Final Visit value was the last HCV RNA measurement during the study. Data are reported as the least squares mean change from baseline ± standard error.
Measured: 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
Serum hepatitis C virus ribonucleic acid (HCV RNA) levels (measured in IU/mL) were determined 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. Data are reported as the percentage of participants.
Measured: 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
Serum hepatitis C virus ribonucleic acid (HCV RNA) levels (measured in IU/mL) were determined for each sample using a real-time reverse transcriptase polymerase chain reaction (RT-PCR) assay. The lower limit of quantification (LLOQ) was defined as HCV RNA levels ≤ 25 IU/mL. Data are reported as the percentage of participants.
Measured: 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
Serum hepatitis C virus ribonucleic acid (HCV RNA) levels (measured in IU/mL) were determined for each sample using a real-time reverse transcriptase polymerase chain reaction (RT-PCR) assay. The lower limit of detection (LLOD) was defined as a HCV RNA level equal to 10 IU/mL. Data are reported as the percentage of participants.
Measured: Day 28 or Final Visit
Number of Participants With Resistance-Associated Variants in Non-structural Viral Protein 5B (NS5B) Through Day 28
Samples from Days 1, 5, 10, 17, 24 and 28 were analyzed for the presence of resistance-associated amino acids using population sequencing and compared to the baseline non-structural viral protein 5B (NS5B) sequence to assess amino acid changes. The amino acid sequence of NS5B before the first dose of ABT-333 on Day 1 was defined as the baseline sequence. The number of participants with variants at resistance-associated amino acid positions in the post-baseline samples are presented.
Measured: Days 1, 5, 10, 17, 24 and 28
Number of Participants With Maximal Phenotypic Resistance to ABT-333 >10 Fold Relative to Baseline Through Day 28
Phenotypic resistance to ABT-333 was assessed by calculating the fold difference in the half maximal effective concentration (EC50) compared with the EC50 for the corresponding baseline sample, and the maximal fold change in EC50 from baseline over the Day 5-28 period. The resistance sample drawn before the first dose of ABT-333 on Day 1 was defined as the baseline sample. The number of participants with phenotypic resistance in the post-baseline samples are presented.
Measured: Days 1 through 28
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 Feb 2009 (estimated)
- Study startMar 2009
- Primary completionJul 2009
- Study completionJul 2009
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Chronic Hepatitis C Virus InfectionStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 30 participants (actual)
Sponsor and investigators
- Lead sponsor
- AbbVie (prior sponsor, Abbott)
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Daniel Cohen, MD, Study director, AbbVie
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00851890
- Sponsor's protocol ID
- M10-380
- Status last verified
- Dec 2014
- First submitted
- 24 Feb 2009
- Last updated
- 2 Jul 2018
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Publications
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.
PubMed 26597291
Study at a glance
From the registry record, last updated by the sponsor on 2 Jul 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Blinded, Randomized, Placebo-controlled 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
- ClinicalTrials.gov ID
- NCT00851890
- Acronym / sponsor ID
- M10-380
- Conditions
- Chronic Hepatitis C Virus Infection
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 30 participants (actual)
- Lead sponsor
- AbbVie (prior sponsor, Abbott)Industry (pharma, biotech, devices)
- Study start
- Mar 2009
- Primary completion
- Jul 2009 (actual)
- Study completion
- Jul 2009 (actual)
- First posted
- 26 Feb 2009 (estimated)
- Results
- Posted 8 Jan 2015
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| ABT-333 (300 mg) twice daily (BID) + pegIFN/RBV | Experimental | Drug: ABT-333, Drug: Pegylated interferon, Drug: RibavirinHepatitis 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. |
| ABT-333 (600 mg) twice daily (BID) + pegIFN/RBV | Experimental | Drug: ABT-333, Drug: Pegylated interferon, Drug: RibavirinHepatitis 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. |
| ABT-333 (1200 mg) once daily (QD) + pegIFN/RBV | Experimental | Drug: ABT-333, Drug: Pegylated interferon, Drug: RibavirinHepatitis 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. |
| Placebo + pegIFN/RBV | Placebo comparator | Other: Placebo for ABT-333, Drug: Pegylated interferon, Drug: RibavirinHepatitis 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. |
Who may qualify
- Ages
- 18 to 70 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- 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.
Key exclusion criteria (7 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| ABT-333Also: dasabuvir50 mg capsules | Drug | 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-333Capsule | Other | Placebo + pegIFN/RBV |
| Pegylated interferonSyringe, 180 µg/0.5 mL for subcutaneous injections administered weekly | Drug | 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 |
| Ribavirin200 mg tablet dosed at 1000 or 1200 mg daily divided twice a day | Drug | 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 |
Primary outcome
Mean Maximal Change From Baseline in Hepatitis C Virus Ribonucleic Acid (HCV RNA) Levels During ABT-333 Monotherapy Treatment
Time frame: Prior to the first dose on Day 1 to before first dose on Day 3
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.
Mean Maximal Change From Baseline in Hepatitis C Virus Ribonucleic Acid (HCV RNA) Levels Through Day 28
Time frame: Prior to the first dose on Day 1 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.
Maximum Plasma Concentration (Cmax) of ABT-333
Time frame: Pre-dose (time 0 hours); 2, 4, 8, 12, and 16 hours post-dose on Day 1; and pre-dose on Day 2
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.
Time to Maximum Plasma Concentration (Tmax) of ABT-333
Time frame: Pre-dose (time 0 hours); 2, 4, 8, 12, and 16 hours post-dose on Day 1; and pre-dose on Day 2
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.
Area Under the Plasma Concentration-time Curve From 0 to 12 Hours Post-dose (AUC12) of ABT-333
Time frame: Pre-dose (time 0 hours); 2, 4, 8, 12, and 16 hours post-dose on Day 1; and pre-dose on Day 2
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.
Serum Concentrations of Pegylated Interferon (pegIFN)
Time frame: 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
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.
Plasma Concentrations of Ribavirin (RBV)
Time frame: 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
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.
Number of Participants Having Treatment-emergent Adverse Events (AEs)
Time frame: AEs were collected from the time of study drug administration to 30 days after last dose of study drug (8 Weeks)
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.
6 secondary outcomes
Change From Baseline in Hepatitis C Virus Ribonucleic Acid (HCV RNA) Levels Through Day 28 or Final Visit
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: Day 28 or Final Visit
Number of Participants With Resistance-Associated Variants in Non-structural Viral Protein 5B (NS5B) Through Day 28
Time frame: Days 1, 5, 10, 17, 24 and 28
Number of Participants With Maximal Phenotypic Resistance to ABT-333 >10 Fold Relative to Baseline Through Day 28
Time frame: Days 1 through 28
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 2 Jul 2018.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 26597291Mensing 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.
- Related InfoLink provided by the sponsor.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Daniel Cohen, MD study director
AbbVie
8 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing ABT-333, Pegylated interferon and Ribavirin in people with Chronic Hepatitis C Virus Infection, run by AbbVie (prior sponsor, Abbott) at 8 sites in 2 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 8 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 2 Jul 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 8 sites in United States, Puerto Rico. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 8 Jan 2015). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Mean Maximal Change From Baseline in Hepatitis C Virus Ribonucleic Acid (HCV RNA) Levels During ABT-333 Monotherapy Treatment (time frame: Prior to the first dose on Day 1 to before first dose on Day 3). The study lists 8 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00851890, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 2 Jul 2018.