Hepatitis C, ChronicPhase 1NCT00793793

Safety, Antiviral Activity and PK of MRD of BI 201335 in Chronic Hepatitis C Patients Both Treatment Naive and -Experienced

A Phase 1 study testing BI201335 in people with Hepatitis C, Chronic, run by Boehringer Ingelheim at 16 sites in 4 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial summary

This study will investigate safety, antiviral activity, and pharmacokinetics of BI 201335 NA in HCV genotype 1 infected patients treated for 14 days monotherapy followed by BI 201335 NA combination therapy with PegIFN/RBV for an additional 14 days for treatment-naïve patients; or for 28 days as BI 201335 NA… Read more about this study

Who is it for?: Ages 18 years and older
Conditions the study is for: Hepatitis C, Chronic
What is being tested?: BI201335
Could I receive a placebo?: Yes, some participants may receive a placebo
How many people: 96 participants
Where: 16 sitesin 4 countries
Study dates: Sep 2007to 25 Jan 2011
Phase: Phase 1
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 years and older
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

1a. For treatment-naïve patients: no prior therapy with interferon, peginterferon, or ribavirin for acute or chronic hepatitis C infection
1b. For treatment-experienced patients: confirmed virological failure during or after combination treatment with an approved dose of alfa-2a or alfa-2b peginterferon combined with ribavirin; such patients must have received at least 12 weeks of therapy with a 90 day washout period prior to screening and must have documentation of medical history prior to enrolment in 1220.2 2. Age 18 years or older 3. Signed informed consent form prior to trial participation 4. Male or female with documented hysterectomy or menopausal female with last menstrual period at least 6 months prior to screening 5. Chronic hepatitis C infection of genotype 1, diagnosed by positive HCV serology test (HCV Ab positive) or detectable HCV RNA at least 6 months prior to screening 6. HCV viral load >= 100,000 IU/mL at screening 7. TSH and T4 within normal limits or adequately controlled thyroid function 8. Histological evidence within 36 months prior to study enrolment of any degree of chronic necroinflammatory activity or the presence of fibrosis (Ishak Grade 1-4 or Metavir Grade 1-3)

Who cannot join

Patients who have been previously treated with at least one dose of any protease inhibitor for acute or chronic hepatitis C infection
Evidence of liver disease due to causes other than chronic HCV infection
Positive ELISA for HIV-1 or HIV-2
Hepatitis B virus (HBV) infection based on presence of Hbs Ag or HBV DNA
Any previous liver biopsy consistent with cirrhosis
Decompensated liver diseases as evidenced by ascites, portal hypertension, jaundice or hepatic encephalopathy

Show all 24Show fewer

Haemophilia
Hemoglobinopathy (e.g., thalassemia major or sickle cell anemia)
Severe pre-existing psychiatric disease
Poorly controlled diabetes mellitus
Ischaemic heart disease
Chronic obstructive airway disease
Autoimmune disease; including autoimmune hepatitis
History of alcohol abuse within the past 12 months
Hyperbilirubinemia (conjugated bilirubin) >1.5x ULN
Alkaline phosphatase >1.5x ULN
ALT and AST levels >= 5 x ULN
Hemoglobin < 12.0 g/dL for women and < 13.0 g/dL for men
White blood cell count < 2000 cells/mm3
Absolute Neutrophil Count < 1500 cells/mm3
Platelet count < 100,000 cells/mm3
Prothrombin time INR (Institutional Normalized Ratio) prolonged to > 1.5 x ULN
Usage of any investigational drug within 30 days prior to enrolment; or the planned usage of an investigational drug during the course of the current study
Known hypersensitivity to study drugs

Trial locations and contacts

16 sites in 4 countries.

Country

City, postcode or hospital

16 sites in 4 countries

United States6 sites

1220.2.14 Boehringer Ingelheim Investigational Site
Austin, Texas
1220.2.17 Boehringer Ingelheim Investigational Site
Baltimore, Maryland
1220.2.11 Boehringer Ingelheim Investigational Site
New York, New York
1220.2.12 Boehringer Ingelheim Investigational Site
New York, New York
1220.2.10 Boehringer Ingelheim Investigational Site
San Francisco, California
1220.2.15 Boehringer Ingelheim Investigational Site
San Francisco, California

Other trials in United States

Germany5 sites

1220.2.49002 Boehringer Ingelheim Investigational Site
Berlin
1220.2.49005 Boehringer Ingelheim Investigational Site
Düsseldorf
1220.2.49006 Boehringer Ingelheim Investigational Site
Hanover
1220.2.49004 Boehringer Ingelheim Investigational Site
Kiel
1220.2.49003 Boehringer Ingelheim Investigational Site
Mainz

Other trials in Germany

France4 sites

1220.2.3304A Boehringer Ingelheim Investigational Site
Lyon
1220.2.3303A Boehringer Ingelheim Investigational Site
Marseille
1220.2.3301A Boehringer Ingelheim Investigational Site
Paris
1220.2.3302A Boehringer Ingelheim Investigational Site
Paris

Other trials in France

Spain1 site

1220.2.34001 Boehringer Ingelheim Investigational Site
Madrid

Other trials in Spain

About this study

Official title: Safety, Antiviral Activity, and Pharmacokinetics of Multiple Rising Oral Doses of BI 201335 NA in Treatment-naïve Patients With Chronic Hepatitis C Infection for 14 Days Monotherapy Followed by Combination With Pegylated Interferon and Ribavirin for an Additional 14 Days (Double-blind, Placebo Controlled), and in Treatment-experienced Patients With Chronic Hepatitis C Infection for 28 Days as Combination Therapy With Pegylated Interferon and Ribavirin (Open-label)

A secondary objective is to investigate antiviral activity, potential drug-drug interactions and safety of combination therapy of BI 201335 NA and PegIFN/RBV up to 28 days for treatment-naïve patients.

Conditions: Hepatitis C, Chronic
Being tested: BI201335, Placebo
Medical subject headings: Hepatitis C, Chronic

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

BI201335Drug
patient to receive rising doses of BI201335 solution qd +/- PegIFN/RBV fore 28 days
BI201335Drug
patient to receive rising doses of BI201335 solution qd +/- PegIFN/RBV fore 28 days
BI201335Drug
patient to receive rising doses of BI201335 solution qd +/- PegIFN/RBV fore 28 days
BI201335Drug
patient to receive 240mg solution BI201335 qd +/- PegIFN/RBV fore 28 days
PlaceboDrug

Study groups in NCT00793793
Study group	Role	What they receive
20mg	Experimental	patient to receive 20mg solution BI201335 qd +/- PegIFN/RBV fore 28 days Receives: Drug: BI201335
48mg	Experimental	patient to receive 48mg solution BI201335 qd +/- PegIFN/RBV fore 28 days Receives: Drug: BI201335
120mg	Experimental	patient to receive 120mg solution BI201335 qd +/- PegIFN/RBV fore 28 days Receives: Drug: BI201335
240mg	Experimental	patient to receive 240mg solution BI201335 qd +/- PegIFN/RBV fore 28 days Receives: Drug: BI201335
Placebo	Placebo comparator	Not described Receives: Drug: Placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

Efficacy: VR (Virologic Response) of >=2 log10 Reduction in Plasma Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) From Baseline at Any Time up to Day 14 (naïve Patients) or Day 28 (Experienced Patients)
Efficacy endpoint: VR (virologic response) of >=2 log10 reduction in Plasma Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) from baseline at any time up to Day 14 (naïve patients) or Day 28 (experienced patients).
Measured: Baseline and up to 4 weeks
Occurrence of Adverse Events (AEs) During BI201335 + Washout Period
Occurrence of Adverse Events (AEs) during BI201335 + washout period. For placebo patients include all AEs through 30 days after trial discontinuation.
Measured: from day 1 and up to 4 weeks + 4 days washout
Occurrence of Serious Adverse Events (SAEs) During BI201335 + Washout Period
Occurrence of Serious Adverse Events (SAEs)during BI201335 or BI201335+ washout period. For placebo patients include all SAEs through 30 days after trial discontinuation.
Measured: from day 1 and up to 4 weeks + 4 days washout
Occurrence of Laboratory Test Abnormalities and With Respect to Division of AIDS (DAIDS) Classification and Laboratory Test Values Change Over Time
Occurrence of laboratory test abnormalities and with respect to Division of AIDS (DAIDS) classification and laboratory test values change over time.
ALT=Alanine transaminase (SGPT), AST=Aspartate transaminase (SGOT).
Measured: Baseline and up to 4 weeks

Secondary outcomes (29)

Maximum Viral Load Reduction From Baseline up to Day 14 for Treatment-naïve Patients and Day 28 Treatment for Treatment-experienced Patients
Maximum viral load reduction from baseline up to Day 14 for treatment-naïve patients and Day 28 treatment for treatment-experienced patients.
Measured: Baseline and up to 4 weeks
Change From Baseline in Viral Load on Day 14 for Treatment-naïve Patients and on Day 28 Treatment for Treatment-experienced Patients
Change from baseline in viral load on Day 14 for treatment-naïve patients and on Day 28 treatment for treatment-experienced patients.
Measured: Baseline and up to 4 weeks
Rapid Virologic Response (RVR)
Rapid virologic response (RVR): Plasma HCV RNA level below the limit of detection of the Roche COBAS Taqman HCV/HPS assay (10 IU/mL) on Day 28 for all patients.
Measured: week 4
Early Virologic Response (EVR)
Early Virologic Response (EVR): >=2 log10 reduction in plasma HCV RNA level from baseline at week 12 (day 84)
Measured: week 12
Complete EVR1 (cEVR1)
VL (Viral load) below the limit of quantification of the Roche COBAS Taqman HCV/HPS assay (25 IU/mL) at 4 weeks and below the limit of detection of the Roche COBAS Taqman HCV/HPS assay (10 IU/mL) at 12 weeks
Measured: week 4 and week 12
Complete EVR2 (cEVR2)
VL below the limit of detection at both 4 weeks and 12 weeks
Measured: week 4 and week 12
End of Treatment Response (ETR)
End of Treatment Response (ETR): Plasma HCV RNA level below the limit of detection of the Roche COBAS Taqman HCV/HPS assay (10 IU/mL) at week 48 (Day 336).
Measured: week 48
Sustained Virologic Response (SVR)
Sustained Virologic Response (SVR): Plasma HCV RNA level below the limit of detection of the Roche COBAS Taqman HCV/HPS assay (10 IU/mL) at week 72 (Day 504).
Measured: week 72
Achievement of an HCV RNA Level Below the Limit of Detection Over Time
Achievement of an HCV RNA level below the limit of detection of the Roche COBAS Taqman HCV/HPS assay (10 IU/mL) over time
Measured: from day 1 and up to 4 weeks
Achievement of an HCV RNA Level Below the Limit of Quantification Over Time
Achievement of an HCV RNA Level Below the Limit of quantification of the Roche COBAS Taqman HCV/HPS assay (25 IU/mL) Over Time
Measured: from day 1 and up to 4 weeks
Achievement of a >= 2 log10 Reduction in Plasma HCV RNA Level From Baseline Over Time
Achievement of a >= 2 log10 reduction in plasma HCV RNA level from baseline over time.
Measured: from day 1 and up to 4 weeks
Occurrence of AEs, by Action Taken With Regard to Study Medication
Occurrence of AEs, by action taken with regard to study medication.
Measured: from day 1 and up to 4 weeks
Occurrence of Discontinuations Due to AEs During BI201335 or BI201335+PegIFN/RBV Combination Treatment Period
Occurrence of discontinuations due to AEs during BI201335 or BI201335+PegIFN/RBV combination treatment period.
Measured: from day 1 and up to 4 weeks
PK (Pharmacokinetic) Parameter After the First Dose: Cmax ( Maximum Measured Concentration of the Analyte in Plasma)
PK (pharmacokinetic) parameter after the first dose: Cmax ( Maximum measured concentration of the analyte in plasma ).
.
Measured: Times of -0:15, 0:30, 1:00, 2:00, 3:00, 4:00, 6:00. 8:00. 12:00, and 16:00 h relative to first administration of trial medication (on day 1)
PK Parameter After the First Dose: Tmax (Time From (Last) Dosing to the Maximum Measured Concentration of the Analyte in Plasma)
PK parameter after the first dose: tmax (Time from (last) dosing to the maximum measured concentration of the analyte in plasma).
Measured: Times of -0:15, 0:30, 1:00, 2:00, 3:00, 4:00, 6:00. 8:00. 12:00, and 16:00 h relative to first administration of trial medication (on day 1)
PK Parameter After the First Dose: AUCτ,1 (Area Under the Concentration-time Curve of the Analyte in Plasma Over a Uniform Dosing Interval τ on Day 1)
PK parameter after the first dose: AUCτ,1 (Area under the concentration-time curve of the analyte in plasma over a uniform dosing interval τ on day 1).
Measured: Times of -0:15, 0:30, 1:00, 2:00, 3:00, 4:00, 6:00. 8:00. 12:00, and 16:00 h relative to first administration of trial medication (on day 1)
PK Parameter at Steady State After the Last Dose: Cmax,ss (Maximum Measured Concentration of the Analyte in Plasma at Steady State Over a Uniform Dosing Interval τ)
PK parameter at steady state after the last dose: Cmax,ss (Maximum measured concentration of the analyte in plasma at steady state over a uniform dosing interval τ).
Measured: Times of -0:05, 0:30, 1:00, 2:00, 3:00, 4:00, 6:00. 8:00. 12:00, 16:00, 24:00 h relative to last administration of trial medication (on day 28)
PK Parameter at Steady State After the Last Dose: Tmax,ss (Time From Last Dosing to the Maximum Measured Concentration of the Analyte in Plasma at Steady State )
PK parameter at steady state after the last dose: tmax,ss (Time from last dosing to the maximum measured concentration of the analyte in plasma at steady state ).
Measured: Times of -0:05, 0:30, 1:00, 2:00, 3:00, 4:00, 6:00. 8:00. 12:00, 16:00, 24:00 h relative to last administration of trial medication (on day 28)
PK Parameter at Steady State After the Last Dose: Cmin,ss (Minimum Measured Concentration of the Analyte in Plasma)
PK parameter at steady state after the last dose: Cmin,ss (Minimum measured concentration of the analyte in plasma).
Measured: Times of -0:05, 0:30, 1:00, 2:00, 3:00, 4:00, 6:00. 8:00. 12:00, 16:00, 24:00 h relative to last administration of trial medication (on day 28)
PK Parameter at Steady State After the Last Dose: AUCτ,ss (Area Under the Concentration-time Curve of the Analyte in Plasma at Steady State Over a Uniform Dosing Interval τ)
PK parameter at steady state after the last dose: AUCτ,ss ((Area under the concentration-time curve of the analyte in plasma at steady state over a uniform dosing interval τ).
Measured: Times of -0:05, 0:30, 1:00, 2:00, 3:00, 4:00, 6:00. 8:00. 12:00, 16:00, 24:00 h relative to last administration of trial medication (on day 28)
PK Parameter at Steady State After the Last Dose: t1/2,ss (Terminal Half-life of the Analyte in Plasma at Steady State )
PK parameter at steady state after the last dose: t1/2,ss (Terminal half-life of the analyte in plasma at steady state [h] )
Measured: Times of -0:05, 0:30, 1:00, 2:00, 3:00, 4:00, 6:00. 8:00. 12:00, 16:00, 24:00 h relative to last administration of trial medication (on day 28)
PK Parameter at Steady State After the Last Dose: MRTpo,ss (Mean Residence Time of the Analyte in the Body at Steady State After Oral Administration)
PK parameter at steady state after the last dose: MRTpo,ss (Mean residence time of the analyte in the body at steady state after oral administration [h] )
Measured: Times of -0:05, 0:30, 1:00, 2:00, 3:00, 4:00, 6:00. 8:00. 12:00, 16:00, 24:00 h relative to last administration of trial medication (on day 28)
PK Parameter at Steady State After the Last Dose: CL/F,ss (Apparent Clearance of the Analyte in Plasma at Steady State Following Multiple Oral Dose Administration )
PK parameter at steady state after the last dose (if applicable): CL/F,ss (ss Apparent clearance of the analyte in plasma at steady state following multiple oral dose administration [mL/min] )
Measured: Times of -0:05, 0:30, 1:00, 2:00, 3:00, 4:00, 6:00. 8:00. 12:00, 16:00, 24:00 h relative to last administration of trial medication (on day 28)
PK Parameter at Steady State After the Last Dose: Vz/F,ss (Apparent Volume of Distribution During the Terminal Phase z at Steady State Following an Oral Administration )
PK parameter at steady state after the last dose: Vz/F,ss (Apparent volume of distribution during the terminal phase z at steady state following an oral administration [L] )
Measured: Times of -0:05, 0:30, 1:00, 2:00, 3:00, 4:00, 6:00. 8:00. 12:00, 16:00, 24:00 h relative to last administration of trial medication (on day 28)
PK Parameter for Drug-drug Interaction (naïve Patients With ≥1 Log Reduction on Day 10): AUCτ,ss (Area Under the Concentration-time Curve of the Analyte in Plasma at Steady State Over a Uniform Dosing Interval τ )
PK parameter for drug-drug interaction (naïve patients with ≥1 log reduction on Day 10): AUCτ,ss ( Area under the concentration-time curve of the analyte in plasma at steady state over a uniform dosing interval τ ).
Measured: Times of -0:05, 0:30, 1:00, 2:00, 3:00, 4:00, 6:00. 8:00. 12:00, 16:00, 24:00 h relative to administration of trial medication in the morning of Day 14 (on day 14)
PK Parameter for Drug-drug Interaction (naïve Patients With ≥1 Log Reduction on Day 10): Cmax,ss
PK parameter for drug-drug interaction (naïve patients with ≥1 log reduction on Day 10): Cmax,ss.
Measured: Times of -0:05, 0:30, 1:00, 2:00, 3:00, 4:00, 6:00. 8:00. 12:00, 16:00, 24:00 h relative to administration of trial medication in the morning of Day 14 (on day 14)
PK Parameter for Drug-drug Interaction (naïve Patients With ≥1 Log Reduction on Day 10): Cmin, ss
PK parameter for drug-drug interaction (naïve patients with ≥1 log reduction on Day 10): Cmin, ss.
Measured: Times of -0:05, 0:30, 1:00, 2:00, 3:00, 4:00, 6:00. 8:00. 12:00, 16:00, 24:00 h relative to administration of trial medication in the morning of Day 14 (on day 14)
Accumulation Ratio of the Analyte in Plasma Following Multiple Doses Over a Uniform Dosing Interval: RAcmax
For TN patients, comparing exposure on Day 14 to the first dose on Day 1; for TE patients, comparing exposure on Day 28 to the first dose on Day 1.
Measured: Day 1, Day 14, and Day 28
Accumulation Ratio of the Analyte in Plasma Following Multiple Doses Over a Uniform Dosing Interval: RAauc
For TN patients, comparing exposure on Day 14 to the first dose on Day 1; for TE patients, comparing exposure on Day 28 to the first dose on Day 1.
Measured: Day 1, Day 14, and Day 28

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

Sep 200725 Jan 2011

First posted19 Nov 2008 (estimated)
Study startSep 2007
Primary completionJan 2011
Study completion25 Jan 2011

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 (2)Papers the sponsor has linked to this study.
Other trials for Hepatitis C, ChronicStudies of the same condition, open and under way.
More trials run by Boehringer IngelheimThe sponsor's other registered studies.
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 1
Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Double blind
Enrolment: 96 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT00793793
Sponsor's protocol ID: 1220.2
Other IDs: 2007-001158-19
Status last verified: Aug 2018
First submitted: 23 Sep 2008
Last updated: 5 Sep 2018
Results posted: Yes, on ClinicalTrials.gov

Publications

Berger KL, Lagace L, Triki I, Cartier M, Marquis M, Lawetz C, Bethell R, Scherer J, Kukolj G. Viral resistance in hepatitis C virus genotype 1-infected patients receiving the NS3 protease inhibitor Faldaprevir (BI 201335) in a phase 1b multiple-rising-dose study. Antimicrob Agents Chemother. 2013 Oct;57(10):4928-36. doi: 10.1128/AAC.00822-13. Epub 2013 Jul 22.
PubMed 23877706
Manns MP, Bourliere M, Benhamou Y, Pol S, Bonacini M, Trepo C, Wright D, Berg T, Calleja JL, White PW, Stern JO, Steinmann G, Yong CL, Kukolj G, Scherer J, Boecher WO. Potency, safety, and pharmacokinetics of the NS3/4A protease inhibitor BI201335 in patients with chronic HCV genotype-1 infection. J Hepatol. 2011 Jun;54(6):1114-22. doi: 10.1016/j.jhep.2010.08.040. Epub 2010 Nov 11.
PubMed 21145839

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

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RecruitingObservational study
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Chronic Liver Disease and Cirrhosis, Liver Cancer
Active, not recruitingPhase 4
Sofosbuvir/Velpatasvir Treatment of Chronic Hepatitis C During Pregnancy
Hepatitis C, Chronic, Pregnancy; Infection
Enrolling by invitationObservational study
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All Hepatitis C, Chronic trials

Study at a glance

From the registry record, last updated by the sponsor on 5 Sep 2018. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: Safety, Antiviral Activity, and Pharmacokinetics of Multiple Rising Oral Doses of BI 201335 NA in Treatment-naïve Patients With Chronic Hepatitis C Infection for 14 Days Monotherapy Followed by Combination With Pegylated Interferon and Ribavirin for an Additional 14 Days (Double-blind, Placebo Controlled), and in Treatment-experienced Patients With Chronic Hepatitis C Infection for 28 Days as Combination Therapy With Pegylated Interferon and Ribavirin (Open-label)
ClinicalTrials.gov ID: NCT00793793
Acronym / sponsor ID: 1220.2
Conditions: Hepatitis C, Chronic
Phase: Phase 1
Study type: Interventional
Recruitment status: Completed
Enrolment: 96 participants (actual)
Lead sponsor: Boehringer IngelheimIndustry (pharma, biotech, devices)
Study start: Sep 2007
Primary completion: Jan 2011 (actual)
Study completion: 25 Jan 2011 (actual)
First posted: 19 Nov 2008 (estimated)
Results: Posted 17 Sep 2015

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Double blind
Number of arms: 5

Arm	Type	Receives
20mg	Experimental	Drug: BI201335patient to receive 20mg solution BI201335 qd +/- PegIFN/RBV fore 28 days
48mg	Experimental	Drug: BI201335patient to receive 48mg solution BI201335 qd +/- PegIFN/RBV fore 28 days
120mg	Experimental	Drug: BI201335patient to receive 120mg solution BI201335 qd +/- PegIFN/RBV fore 28 days
240mg	Experimental	Drug: BI201335patient to receive 240mg solution BI201335 qd +/- PegIFN/RBV fore 28 days
Placebo	Placebo comparator	Drug: Placebo

Who may qualify

Ages: 18 years and older
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (2 listed)

1a. For treatment-naïve patients: no prior therapy with interferon, peginterferon, or ribavirin for acute or chronic hepatitis C infection
1b. For treatment-experienced patients: confirmed virological failure during or after combination treatment with an approved dose of alfa-2a or alfa-2b peginterferon combined with ribavirin; such patients must have received at least 12 weeks of therapy with a 90 day washout period prior to screening and must have documentation of medical history prior to enrolment in 1220.2 2. Age 18 years or older 3. Signed informed consent form prior to trial participation 4. Male or female with documented hysterectomy or menopausal female with last menstrual period at least 6 months prior to screening 5. Chronic hepatitis C infection of genotype 1, diagnosed by positive HCV serology test (HCV Ab positive) or detectable HCV RNA at least 6 months prior to screening 6. HCV viral load >= 100,000 IU/mL at screening 7. TSH and T4 within normal limits or adequately controlled thyroid function 8. Histological evidence within 36 months prior to study enrolment of any degree of chronic necroinflammatory activity or the presence of fibrosis (Ishak Grade 1-4 or Metavir Grade 1-3)

Key exclusion criteria (24 listed)

Patients who have been previously treated with at least one dose of any protease inhibitor for acute or chronic hepatitis C infection
Evidence of liver disease due to causes other than chronic HCV infection
Positive ELISA for HIV-1 or HIV-2
Hepatitis B virus (HBV) infection based on presence of Hbs Ag or HBV DNA
Any previous liver biopsy consistent with cirrhosis

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
BI201335patient to receive rising doses of BI201335 solution qd +/- PegIFN/RBV fore 28 days	Drug	240mg
BI201335patient to receive rising doses of BI201335 solution qd +/- PegIFN/RBV fore 28 days	Drug	120mg
BI201335patient to receive rising doses of BI201335 solution qd +/- PegIFN/RBV fore 28 days	Drug	48mg
BI201335patient to receive 240mg solution BI201335 qd +/- PegIFN/RBV fore 28 days	Drug	20mg
Placebo	Drug	Placebo

Primary outcome

Efficacy: VR (Virologic Response) of >=2 log10 Reduction in Plasma Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) From Baseline at Any Time up to Day 14 (naïve Patients) or Day 28 (Experienced Patients)
Time frame: Baseline and up to 4 weeks
Efficacy endpoint: VR (virologic response) of >=2 log10 reduction in Plasma Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) from baseline at any time up to Day 14 (naïve patients) or Day 28 (experienced patients).
Occurrence of Adverse Events (AEs) During BI201335 + Washout Period
Time frame: from day 1 and up to 4 weeks + 4 days washout
Occurrence of Adverse Events (AEs) during BI201335 + washout period. For placebo patients include all AEs through 30 days after trial discontinuation.
Occurrence of Serious Adverse Events (SAEs) During BI201335 + Washout Period
Time frame: from day 1 and up to 4 weeks + 4 days washout
Occurrence of Serious Adverse Events (SAEs)during BI201335 or BI201335+ washout period. For placebo patients include all SAEs through 30 days after trial discontinuation.
Occurrence of Laboratory Test Abnormalities and With Respect to Division of AIDS (DAIDS) Classification and Laboratory Test Values Change Over Time
Time frame: Baseline and up to 4 weeks
Occurrence of laboratory test abnormalities and with respect to Division of AIDS (DAIDS) classification and laboratory test values change over time. ALT=Alanine transaminase (SGPT), AST=Aspartate transaminase (SGOT).

29 secondary outcomes

Maximum Viral Load Reduction From Baseline up to Day 14 for Treatment-naïve Patients and Day 28 Treatment for Treatment-experienced Patients
Time frame: Baseline and up to 4 weeks
Change From Baseline in Viral Load on Day 14 for Treatment-naïve Patients and on Day 28 Treatment for Treatment-experienced Patients
Time frame: Baseline and up to 4 weeks
Rapid Virologic Response (RVR)
Time frame: week 4
Early Virologic Response (EVR)
Time frame: week 12
Complete EVR1 (cEVR1)
Time frame: week 4 and week 12
Complete EVR2 (cEVR2)
Time frame: week 4 and week 12
End of Treatment Response (ETR)
Time frame: week 48
Sustained Virologic Response (SVR)
Time frame: week 72
Achievement of an HCV RNA Level Below the Limit of Detection Over Time
Time frame: from day 1 and up to 4 weeks
Achievement of an HCV RNA Level Below the Limit of Quantification Over Time
Time frame: from day 1 and up to 4 weeks
Achievement of a >= 2 log10 Reduction in Plasma HCV RNA Level From Baseline Over Time
Time frame: from day 1 and up to 4 weeks
Occurrence of AEs, by Action Taken With Regard to Study Medication
Time frame: from day 1 and up to 4 weeks
Occurrence of Discontinuations Due to AEs During BI201335 or BI201335+PegIFN/RBV Combination Treatment Period
Time frame: from day 1 and up to 4 weeks
PK (Pharmacokinetic) Parameter After the First Dose: Cmax ( Maximum Measured Concentration of the Analyte in Plasma)
Time frame: Times of -0:15, 0:30, 1:00, 2:00, 3:00, 4:00, 6:00. 8:00. 12:00, and 16:00 h relative to first administration of trial medication (on day 1)
PK Parameter After the First Dose: Tmax (Time From (Last) Dosing to the Maximum Measured Concentration of the Analyte in Plasma)
Time frame: Times of -0:15, 0:30, 1:00, 2:00, 3:00, 4:00, 6:00. 8:00. 12:00, and 16:00 h relative to first administration of trial medication (on day 1)
PK Parameter After the First Dose: AUCτ,1 (Area Under the Concentration-time Curve of the Analyte in Plasma Over a Uniform Dosing Interval τ on Day 1)
Time frame: Times of -0:15, 0:30, 1:00, 2:00, 3:00, 4:00, 6:00. 8:00. 12:00, and 16:00 h relative to first administration of trial medication (on day 1)
PK Parameter at Steady State After the Last Dose: Cmax,ss (Maximum Measured Concentration of the Analyte in Plasma at Steady State Over a Uniform Dosing Interval τ)
Time frame: Times of -0:05, 0:30, 1:00, 2:00, 3:00, 4:00, 6:00. 8:00. 12:00, 16:00, 24:00 h relative to last administration of trial medication (on day 28)
PK Parameter at Steady State After the Last Dose: Tmax,ss (Time From Last Dosing to the Maximum Measured Concentration of the Analyte in Plasma at Steady State )
Time frame: Times of -0:05, 0:30, 1:00, 2:00, 3:00, 4:00, 6:00. 8:00. 12:00, 16:00, 24:00 h relative to last administration of trial medication (on day 28)
PK Parameter at Steady State After the Last Dose: Cmin,ss (Minimum Measured Concentration of the Analyte in Plasma)
Time frame: Times of -0:05, 0:30, 1:00, 2:00, 3:00, 4:00, 6:00. 8:00. 12:00, 16:00, 24:00 h relative to last administration of trial medication (on day 28)
PK Parameter at Steady State After the Last Dose: AUCτ,ss (Area Under the Concentration-time Curve of the Analyte in Plasma at Steady State Over a Uniform Dosing Interval τ)
Time frame: Times of -0:05, 0:30, 1:00, 2:00, 3:00, 4:00, 6:00. 8:00. 12:00, 16:00, 24:00 h relative to last administration of trial medication (on day 28)
PK Parameter at Steady State After the Last Dose: t1/2,ss (Terminal Half-life of the Analyte in Plasma at Steady State )
Time frame: Times of -0:05, 0:30, 1:00, 2:00, 3:00, 4:00, 6:00. 8:00. 12:00, 16:00, 24:00 h relative to last administration of trial medication (on day 28)
PK Parameter at Steady State After the Last Dose: MRTpo,ss (Mean Residence Time of the Analyte in the Body at Steady State After Oral Administration)
Time frame: Times of -0:05, 0:30, 1:00, 2:00, 3:00, 4:00, 6:00. 8:00. 12:00, 16:00, 24:00 h relative to last administration of trial medication (on day 28)
PK Parameter at Steady State After the Last Dose: CL/F,ss (Apparent Clearance of the Analyte in Plasma at Steady State Following Multiple Oral Dose Administration )
Time frame: Times of -0:05, 0:30, 1:00, 2:00, 3:00, 4:00, 6:00. 8:00. 12:00, 16:00, 24:00 h relative to last administration of trial medication (on day 28)
PK Parameter at Steady State After the Last Dose: Vz/F,ss (Apparent Volume of Distribution During the Terminal Phase z at Steady State Following an Oral Administration )
Time frame: Times of -0:05, 0:30, 1:00, 2:00, 3:00, 4:00, 6:00. 8:00. 12:00, 16:00, 24:00 h relative to last administration of trial medication (on day 28)
PK Parameter for Drug-drug Interaction (naïve Patients With ≥1 Log Reduction on Day 10): AUCτ,ss (Area Under the Concentration-time Curve of the Analyte in Plasma at Steady State Over a Uniform Dosing Interval τ )
Time frame: Times of -0:05, 0:30, 1:00, 2:00, 3:00, 4:00, 6:00. 8:00. 12:00, 16:00, 24:00 h relative to administration of trial medication in the morning of Day 14 (on day 14)
PK Parameter for Drug-drug Interaction (naïve Patients With ≥1 Log Reduction on Day 10): Cmax,ss
Time frame: Times of -0:05, 0:30, 1:00, 2:00, 3:00, 4:00, 6:00. 8:00. 12:00, 16:00, 24:00 h relative to administration of trial medication in the morning of Day 14 (on day 14)
PK Parameter for Drug-drug Interaction (naïve Patients With ≥1 Log Reduction on Day 10): Cmin, ss
Time frame: Times of -0:05, 0:30, 1:00, 2:00, 3:00, 4:00, 6:00. 8:00. 12:00, 16:00, 24:00 h relative to administration of trial medication in the morning of Day 14 (on day 14)
Accumulation Ratio of the Analyte in Plasma Following Multiple Doses Over a Uniform Dosing Interval: RAcmax
Time frame: Day 1, Day 14, and Day 28
Accumulation Ratio of the Analyte in Plasma Following Multiple Doses Over a Uniform Dosing Interval: RAauc
Time frame: Day 1, Day 14, and Day 28

Results and safety

Results posted to the registry on 17 Sep 2015, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Treatment Naive (TN): Placebo	8	8
Treatment Naive(TN): 20mg Per Day (QD)	6	5
TN: 48mg QD	7	5
TN: 120mg QD	7	4
TN: 240mg QD	6	4
Treatment Experienced (TE) Non-cirrhotic: 48 mg QD	6	4
TE Non-cirrhotic: 120 mg QD	7	3
TE Non-cirrhotic: 240 mg QD	6	6
TE Non-cirrhotic: 240 mg QD Soft Gel Capsule (SGC)	15	6
TE Non-cirrhotic: 240 mg Twice a Day (BID) SGC	15	6
TE With Cirrhosis: 240 mg QD SGC	6	3
TE With Cirrhosis: 240 mg BID SGC	7	1

Primary outcome: Efficacy: VR (Virologic Response) of >=2 log10 Reduction in Plasma Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) From Baseline at Any Time up to Day 14 (naïve Patients) or Day 28 (Experienced Patients)

Time frame: Baseline and up to 4 weeks. Number (95% Confidence Interval). Unit: percentage of responders

Measure	TN: Placebo n = 8	Treatment Naive(TN): 20mg QD n = 6	TN: 48mg QD n = 7	TN: 120mg QD n = 7	TN: 240mg QD n = 6	Treatment Experienced (TE) Non-cirrhotic: 48 mg QD n = 6	TE Non-cirrhotic: 120 mg QD n = 7	TE Non-cirrhotic: 240 mg QD n = 6	TE Non-cirrhotic: 240 mg QD Soft Gel Capsule (SGC) n = 15	TE Non-cirrhotic: 240 mg BID SGC n = 15	TE With Cirrhosis: 240 mg QD SGC n = 6	TE With Cirrhosis: 240 mg BID SGC n = 7
Value	0.00 (0.000 to 33.627)	83.33 (42.128 to 96.331)	100.00 (63.058 to 100.000)	100.00 (63.058 to 100.000)	100.00 (59.038 to 100.000)	100.00 (59.038 to 100.000)	100.00 (63.058 to 100.000)	100.00 (59.038 to 100.000)	100.00 (79.409 to 100.000)	100.00 (79.409 to 100.000)	100.00 (59.038 to 100.000)	100.00 (63.058 to 100.000)

Population analysed: Full Analysis Set (FAS): All randomized TN patients and treatment experienced patients who were dispensed trial medication and were documented to have taken at least 1 dose of trial medication.

Primary outcome: Occurrence of Adverse Events (AEs) During BI201335 + Washout Period

Time frame: from day 1 and up to 4 weeks + 4 days washout. Number. Unit: percentage of participants with AEs

Measure	TN: Placebo n = 8	Treatment Naive(TN): 20mg QD n = 6	TN: 48mg QD n = 7	TN: 120mg QD n = 7	TN: 240mg QD n = 6	Treatment Experienced (TE) Non-cirrhotic: 48 mg QD n = 6	TE Non-cirrhotic: 120 mg QD n = 7	TE Non-cirrhotic: 240 mg QD n = 6	TE Non-cirrhotic: 240 mg QD Soft Gel Capsule (SGC) n = 15	TE Non-cirrhotic: 240 mg BID SGC n = 15	TE With Cirrhosis: 240 mg QD SGC n = 6	TE With Cirrhosis: 240 mg BID SGC n = 7
Value	62.5	100.0	100.0	57.1	100.0	100.0	100.0	100.0	100.0	100.0	100.0	100.0

Population analysed: Treated Set (TS): This patient set included all patients who were dispensed trial medication and were documented to have taken at least 1 dose of investigational treatment regardless of randomization.

Primary outcome: Occurrence of Serious Adverse Events (SAEs) During BI201335 + Washout Period

Time frame: from day 1 and up to 4 weeks + 4 days washout. Number. Unit: percentage of participants with SAEs

Measure	TN: Placebo n = 8	Treatment Naive(TN): 20mg QD n = 6	TN: 48mg QD n = 7	TN: 120mg QD n = 7	TN: 240mg QD n = 6	Treatment Experienced (TE) Non-cirrhotic: 48 mg QD n = 6	TE Non-cirrhotic: 120 mg QD n = 7	TE Non-cirrhotic: 240 mg QD n = 6	TE Non-cirrhotic: 240 mg QD Soft Gel Capsule (SGC) n = 15	TE Non-cirrhotic: 240 mg BID SGC n = 15	TE With Cirrhosis: 240 mg QD SGC n = 6	TE With Cirrhosis: 240 mg BID SGC n = 7
Value	0.0	16.7	14.3	0.0	0.0	0.0	0.0	0.0	0.0	0.0	0.0	28.6

Population analysed: TS

Primary outcome: Occurrence of Laboratory Test Abnormalities and With Respect to Division of AIDS (DAIDS) Classification and Laboratory Test Values Change Over Time

Time frame: Baseline and up to 4 weeks. Number. Unit: participants with grade 3 or 4 abnormal

Measure	TN: Placebo n = 8	Treatment Naive(TN): 20mg QD n = 6	TN: 48mg QD n = 7	TN: 120mg QD n = 7	TN: 240mg QD n = 6	Treatment Experienced (TE) Non-cirrhotic: 48 mg QD n = 6	TE Non-cirrhotic: 120 mg QD n = 7	TE Non-cirrhotic: 240 mg QD n = 6	TE Non-cirrhotic: 240 mg QD Soft Gel Capsule (SGC) n = 15	TE Non-cirrhotic: 240 mg BID SGC n = 15	TE With Cirrhosis: 240 mg QD SGC n = 6	TE With Cirrhosis: 240 mg BID SGC n = 7
ALT/GPT SGPT increase, with grade 3 or 4 abnormal	0	0	1	0	0	0	0	0	0	0	1	0
AST/GOT SGOT increase, with grade 3 or 4 abnormal	0	0	1	0	0	0	0	0	0	0	2	1
Lipase increase, with grade 3 or 4 abnormal	0	0	0	0	0	0	0	0	0	1	0	0
Bilirubin total increa, with grade 3 or 4 abnormal	0	0	0	1	2	0	0	1	8	12	5	5
Uric acid increase, with grade 3 or 4 abnormal	0	0	0	0	0	0	0	0	0	0	0	1
Triglyceride increase, with grade 3 or 4 abnormal

29 secondary outcomes are reported in the full results.

Adverse events

Time frame: day 1 and up to 4 weeks + washout. Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Treatment Naive (TN): Placebo	0 of 8 (0%)	5 of 8 (62.5%)	Not reported
Treatment Naive(TN): 20mg QD	1 of 6 (16.7%)	6 of 6 (100%)	Not reported
TN: 48mg QD	1 of 7 (14.3%)	7 of 7 (100%)	Not reported
TN: 120mg QD	0 of 7 (0%)	4 of 7 (57.1%)	Not reported
TN: 240mg QD	0 of 6 (0%)	6 of 6 (100%)	Not reported
Treatment Experienced (TE) Non-cirrhotic: 48 mg QD	0 of 6 (0%)	6 of 6 (100%)	Not reported
TE Non-cirrhotic: 120 mg QD	0 of 7 (0%)	7 of 7 (100%)	Not reported
TE Non-cirrhotic: 240 mg QD	0 of 6 (0%)	6 of 6 (100%)	Not reported
TE Non-cirrhotic: 240 mg QD Soft Gel Capsule (SGC)	0 of 15 (0%)	15 of 15 (100%)	Not reported
TE Non-cirrhotic: 240 mg BID SGC	0 of 15 (0%)	15 of 15 (100%)	Not reported
TE With Cirrhosis: 240 mg QD SGC	0 of 6 (0%)	6 of 6 (100%)	Not reported
TE With Cirrhosis: 240 mg BID SGC	2 of 7 (28.6%)	7 of 7 (100%)	Not reported

Limitations and caveats (from the sponsor): Additional secondary endpoints were listed in the original protocol. Those endpoints are of exploratory nature only and were not considered relevant for trial conclusions. For more information see tab "Full Text Review", section "More Information".

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 5 Sep 2018.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Derived from this study: PubMed 23877706Berger KL, Lagace L, Triki I, Cartier M, Marquis M, Lawetz C, Bethell R, Scherer J, Kukolj G. Viral resistance in hepatitis C virus genotype 1-infected patients receiving the NS3 protease inhibitor Faldaprevir (BI 201335) in a phase 1b multiple-rising-dose study. Antimicrob Agents Chemother. 2013 Oct;57(10):4928-36. doi: 10.1128/AAC.00822-13. Epub 2013 Jul 22.
Derived from this study: PubMed 21145839Manns MP, Bourliere M, Benhamou Y, Pol S, Bonacini M, Trepo C, Wright D, Berg T, Calleja JL, White PW, Stern JO, Steinmann G, Yong CL, Kukolj G, Scherer J, Boecher WO. Potency, safety, and pharmacokinetics of the NS3/4A protease inhibitor BI201335 in patients with chronic HCV genotype-1 infection. J Hepatol. 2011 Jun;54(6):1114-22. doi: 10.1016/j.jhep.2010.08.040. Epub 2010 Nov 11.
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.

Boehringer Ingelheim study chair

Boehringer Ingelheim

16 sites in 4 countries: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing BI201335 in people with Hepatitis C, Chronic, run by Boehringer Ingelheim at 16 sites in 4 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 2 inclusion and 24 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 5 Sep 2018. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 16 sites in United States, Germany, France, Spain. 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 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

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 17 Sep 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?

Efficacy: VR (Virologic Response) of >=2 log10 Reduction in Plasma Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) From Baseline at Any Time up to Day 14 (naïve Patients) or Day 28 (Experienced Patients) (time frame: Baseline and up to 4 weeks). The study lists 4 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 NCT00793793, which also lists 2 linked publications.

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 5 Sep 2018.