Clinical trial NCT00905632: 4 Week Combination of BI 207127 NA With Peg-IFN and Ribavirin in Chronic HCV Patients
Official title: Safety, Antiviral Activity, and Pharmacokinetics of BI 207127 NA Administered in Combination With Peg-IFN and Ribavirin in Chronic HCV-infected Patients for 4 Weeks, a Randomised, Double-blind, Placebo Controlled Study
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Hepatitis C, Chronic
Lead sponsor: Boehringer Ingelheim
Sponsor class: INDUSTRY
First posted: 2009-05-20
Enrollment: 75
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The main purpose of this clinical trial with BI 207127 is to see the effect of 4 week combination of BI 207127 with Peginterferon alfa (Peg-IFN) and Ribavirin (RBV) on hepatitis C virus (HCV) virus load and how safe BI 207127 is in this combination in HCV infected patients.


Eligibility criteria: Inclusion criteria:

1. HCV genotype 1
2. HCV viral load \>100,000 IU/mL
3. histology or fibroscan to rule out cirrhosis
4. Absence of retinopathy
5. treatment naive patients and treatment experienced patients
6. Age 18 - 70 years
7. Male OR female with documented hysterectomy OR postmenopausal

Exclusion criteria:

1. Fertile males not willing to use an adequate form of contraception
2. Pretreatment with any HCV-polymerase inhibitor
3. Any concurrent disease if clinically significant based on the investigator's medical assessment
4. Current alcohol or drug abuse, or history of the same
5. Positive test for HIV or HBs
6. History of malignancy
7. Planned or concurrent usage of any other pharmacological therapy including any antiviral therapy or vaccination
8. Usage of any investigational drug within thirty (30) days prior to enrolment or 5 halflives, whichever is longer
9. Any clinically significant laboratory abnormalities based on the investigator's medical assessment at screening
10. Patients treated with any interferon (approved or investigational) or Peg-IFN and/or Ribavirin within 3 months prior to screening
11. Known hypersensitivity to drugs or excipients; Further exclusion criteria apply

Primary outcomes:
measure: Number of Participants With Virologic Response Defined as >= 3 Log Drop in Viral Load From Baseline at Day 28 With no Evidence of Virologic Rebound During These 28 Days. Virologic Rebound is Defined as >= 1 Log Increase in Viral Load From Nadir.
timeFrame: Baseline and 4 weeks
Secondary outcomes:
measure: Viral Load (Log10) at Each Visit up to Day 28, Change From Baseline
timeFrame: Baseline and days 1, 2, 4, 8, 15, 22 and 28
measure: Viral Load at Each Visit up to Day 28
timeFrame: Baseline and days 8, 15, 22 and 28
measure: Number of Participants With Virologic Response at Day 28
timeFrame: day 28
measure: Number of Participants With Rapid Virological Response
timeFrame: 4 weeks
measure: Number of Participants With Early Virological Response
timeFrame: Baseline and week 12
measure: Number of Participants With End of Treatment Response
timeFrame: Week 12
measure: Number of Participants With Sustained Virological Response
timeFrame: Until end of treatment, up to 570 days
measure: Plasma Concentration Time Profiles of BI 207127
timeFrame: 0.5 hours (h), 3h, 8h, 15h, 23.917h, 503.917h, 649h, 652h, 656h and 672h after drug administration
measure: Plasma Concentration Time Profiles of CD 6168
timeFrame: 0.5 hours (h), 3h, 8h, 15h, 23.917h, 503.917h, 649h, 652h, 656h and 672h after drug administration
measure: Cmax of BI 207127 and CD 6168 in Plasma After First Dose and After Last Dose (Steady State)
timeFrame: 5 min before drug admin and 30min, 1 hour (h), 2h, 3h, 4h, 5h 55min, 8h, 10h, 11h 55min and 15h after drug administration on day 1: 5 min before drug admin and 30min, 1h, 2h, 3h, 4h, 6h, 8h, 10h, 12h, 24h and 48h after admin on day 28
measure: Tmax of BI 207127 and CD 6168 in Plasma After First Dose and After Last Dose (Steady State)
timeFrame: 5 min before drug admin and 30min, 1 hour (h), 2h, 3h, 4h, 5h 55min, 8h, 10h, 11h 55min and 15h after drug administration on day 1: 5 min before drug admin and 30min, 1h, 2h, 3h, 4h, 6h, 8h, 10h, 12h, 24h and 48h after admin on day 28
measure: AUC0-6 of BI 207127 and CD 6168 in Plasma After First Dose and After Last Dose (Steady State)
timeFrame: 30min, 1 hour (h), 2h, 3h, 4h and 5h 55min after drug administration on day 1: 30min, 1h, 2h, 3h, 4h and 6h after admin on day 28
measure: Cpre Pharmacokinetic Parameter of BI 207127 and CD 6168
timeFrame: 5 minutes before drug administration on days 1, 2, 4, 8, 15, 22 and 27
measure: C6,ss Pharmacokinetic Parameters of BI 207127 and CD 6168 at Steady State After the Last Dose
timeFrame: 654 hours after drug administration on day 28
measure: AUC0-infinity,ss Pharmacokinetic Parameters of BI 207127 and CD 6168 at Steady State After the Last Dose
timeFrame: 5 min before drug admin and 30min, 1h, 2h, 3h, 4h, 6h, 8h, 10h, 12h, 24h and 48h after admin on day 28
measure: λz Pharmacokinetic Parameters of BI 207127 and CD 6168 at Steady State After the Last Dose
timeFrame: 5 min before drug admin and 30min, 1h, 2h, 3h, 4h, 6h, 8h, 10h, 12h, 24h and 48h after admin on day 28
measure: t1/2,ss and MRTpo,ss Pharmacokinetic Parameters of BI 207127 and CD 6168 at Steady State After the Last Dose
timeFrame: 5 min before drug admin and 30min, 1h, 2h, 3h, 4h, 6h, 8h, 10h, 12h, 24h and 48h after admin on day 28
measure: RA,Cmax Pharmacokinetic Parameters of BI 207127 and CD 6168 at Steady State After the Last Dose
timeFrame: 5 min before drug admin and 30min, 1h, 2h, 3h, 4h, 6h, 8h, 10h, 12h, 24h and 48h after admin on day 28
measure: Number of Participants With Clinical Relevant Abnormalities for Vital Signs, Body Temperature, Physical Examination, Blood Chemistry, Haematology, Coagulation, Urinalysis and ECG
timeFrame: From the start of the study to Day 30 (2 days after last dose)
measure: Number of Participants With Discontinuations Due to AEs
timeFrame: 4 weeks
Other outcomes:
Locations:
city: Grenoble cédex 9
country: France
facility: 1241.7.3307A CHU de Grenoble
city: Lille
country: France
facility: 1241.7.3303A Hôpital Claude Huriez
city: Lyon cedex 02
country: France
facility: 1241.7.3302A Hopital de l'Hotel Dieu
city: Montpellier
country: France
facility: 1241.7.3301A Hôpital Saint Eloi
city: Nice Cedex 3
country: France
facility: 1241.7.3305A HOP Archet 2
city: Pessac Cedex
country: France
facility: 1241.7.3306A Hôpital Haut-Lévêque
city: Vandoeuvre
country: France
facility: 1241.7.3304A HOP de Brabois
city: Aachen
country: Germany
facility: 1241.7.49010 Boehringer Ingelheim Investigational Site
city: Berlin
country: Germany
facility: 1241.7.49012 Boehringer Ingelheim Investigational Site
city: Essen
country: Germany
facility: 1241.7.49004 Boehringer Ingelheim Investigational Site
city: Freiburg
country: Germany
facility: 1241.7.49011 Boehringer Ingelheim Investigational Site
city: Hamburg
country: Germany
facility: 1241.7.49001 Boehringer Ingelheim Investigational Site
city: Mainz
country: Germany
facility: 1241.7.49013 Boehringer Ingelheim Investigational Site
city: Regensburg
country: Germany
facility: 1241.7.49009 Boehringer Ingelheim Investigational Site
city: Ulm
country: Germany
facility: 1241.7.49002 Boehringer Ingelheim Investigational Site
city: Basel
country: Switzerland
facility: 1241.7.41003 Boehringer Ingelheim Investigational Site
city: Lugano
country: Switzerland
facility: 1241.7.41004 Boehringer Ingelheim Investigational Site
city: St. Gallen
country: Switzerland
facility: 1241.7.41001 Boehringer Ingelheim Investigational Site
Study officials:
affiliation: Boehringer Ingelheim
name: Boehringer Ingelheim
role: STUDY_CHAIR
References:
citation: Larrey D, Lohse AW, de Ledinghen V, Trepo C, Gerlach T, Zarski JP, Tran A, Mathurin P, Thimme R, Arasteh K, Trautwein C, Cerny A, Dikopoulos N, Schuchmann M, Heim MH, Gerken G, Stern JO, Wu K, Abdallah N, Girlich B, Scherer J, Berger F, Marquis M, Kukolj G, Bocher W, Steffgen J. Rapid and strong antiviral activity of the non-nucleosidic NS5B polymerase inhibitor BI 207127 in combination with peginterferon alfa 2a and ribavirin. J Hepatol. 2012 Jul;57(1):39-46. doi: 10.1016/j.jhep.2012.02.015. Epub 2012 Mar 10.