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Open Label Single Dose Phase I Trial of BI 201335 to Study Pharmacokinetics and Safety in Patients With Compensated Liver Cirrhosis

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ClinicalTrials.gov Identifier: NCT01909778
Recruitment Status : Completed
First Posted : July 29, 2013
Results First Posted : August 10, 2015
Last Update Posted : August 10, 2015
Sponsor:
Information provided by (Responsible Party):
Boehringer Ingelheim

Brief Summary:
This trial was intended to investigate the pharmacokinetics, safety and tolerability of BI 201335 NA soft-gel capsules in patients with compensated liver cirrhosis, i.e. grade A according to Child-Pugh classification (< 7 points).

Condition or disease Intervention/treatment Phase
Hepatitis C Liver Cirrhosis Drug: BI 201335 Phase 1

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 2 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: An Open Label Single Dose Phase I Trial of 120 mg and 240 mg BI 201335 Soft Gel Capsules to Study Pharmacokinetic Properties and Safety in Patients With Compensated Liver Cirrhosis in Historical Comparison With 1220.2
Study Start Date : June 2008
Actual Primary Completion Date : October 2008
Actual Study Completion Date : October 2008

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Cirrhosis

Arm Intervention/treatment
Experimental: BI 201335
BI 201335 two single oral doses, separated by 14 days washout period
Drug: BI 201335
single oral doses




Primary Outcome Measures :
  1. AUC 0-∞ [ Time Frame: -0:15, 1:00, 2:00, 3:00, 4:00, 5:00, 6:00, 8:00, 12:00, 16:00, 20:00, 24:00, 48:00, 72:00, 96:00, 120:00 h (hours) after drug administration on day 1 and day 15 ]
    Area under the concentration-time curve of the analyte in plasma over the time interval from 0 extrapolated to infinity (AUC 0-∞).

  2. Cmax [ Time Frame: -0:15, 1:00, 2:00, 3:00, 4:00, 5:00, 6:00, 8:00, 12:00, 16:00, 20:00, 24:00, 48:00, 72:00, 96:00, 120:00 h after drug administration on day 1 and day 15 ]
    Maximum plasma concentration (Cmax). Individual Cmax values will be directly determined from the plasma concentration time profiles.


Secondary Outcome Measures :
  1. Tmax [ Time Frame: -0:15, 1:00, 2:00, 3:00, 4:00, 5:00, 6:00, 8:00, 12:00, 16:00, 20:00, 24:00, 48:00, 72:00, 96:00, 120:00 h after drug administration on day 1 and day 15 ]
    Time at which the maximum plasma concentration occurs (tmax). Individual tmax values will be directly determined from the plasma concentration time profiles.

  2. AUC0-tz [ Time Frame: -0:15, 1:00, 2:00, 3:00, 4:00, 5:00, 6:00, 8:00, 12:00, 16:00, 20:00, 24:00, 48:00, 72:00, 96:00, 120:00 h after drug administration on day 1 and day 15 ]
    Area under the concentration-time curve over the time interval from 0 to the last quantifiable plasma concentration (AUC0-tz).

  3. t1/2 [ Time Frame: -0:15, 1:00, 2:00, 3:00, 4:00, 5:00, 6:00, 8:00, 12:00, 16:00, 20:00, 24:00, 48:00, 72:00, 96:00, 120:00 h after drug administration on day 1 and day 15 ]
    Elimination half-life (t1/2). The terminal half-life will be calculated from the terminal rate constant.

  4. CL/F [ Time Frame: -0:15, 1:00, 2:00, 3:00, 4:00, 5:00, 6:00, 8:00, 12:00, 16:00, 20:00, 24:00, 48:00, 72:00, 96:00, 120:00 h after drug administration on day 1 and day 15 ]

    Apparent clearance of the analyte in plasma following extravascular administration (CL/F).

    The apparent clearance after oral administration will be determined according to the following equation: CL or CL/F=dose/AUC0-∞. (F=absolute bioavailability factor)


  5. Vz/F [ Time Frame: -0:15, 1:00, 2:00, 3:00, 4:00, 5:00, 6:00, 8:00, 12:00, 16:00, 20:00, 24:00, 48:00, 72:00, 96:00, 120:00 h after drug administration on day 1 and day 15 ]
    Apparent volume of distribution during the terminal phase (Vz/F) following an extravascular dose (at steady state).

  6. MRTpo [ Time Frame: -0:15, 1:00, 2:00, 3:00, 4:00, 5:00, 6:00, 8:00, 12:00, 16:00, 20:00, 24:00, 48:00, 72:00, 96:00, 120:00 h after drug administration on day 1 and day 15 ]
    Mean residence time of the analyte in the body after oral administration (MRTpo).

  7. Assessment of Tolerability by Investigator [ Time Frame: Day 6 of period 1 and 2 ]
    The investigator has assessed tolerability based on adverse events and the laboratory evaluation. Tolerability was assessed by the investigator according to the categories 1="good", 2="satisfactory", 3="not satisfactory", and 4="bad".

  8. Clinical Relevant Abnormalities for Vital Signs, Blood Chemistry, Haematology, Urinanalysis and ECG [ Time Frame: from intake of the second dose Faldaprevir up to 9 days ]
    Clinical Relevant Abnormalities for Vital Signs, Blood Chemistry, Haematology, Urinanalysis and ECG. New abnormal findings or worsening of baseline conditions were reported as Adverse Events.



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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion criteria:

  1. Patients with liver cirrhosis, that is histologically proven in a previous liver biopsy; possible aetiologies are: cured HCV infection, former alcohol abuse, genetic haemochromatosis, non-alcoholic steatohepatitis or others.
  2. Compensated liver disease, as indicated by Prothrombin time or INR prolonged to <1.7 x ULN, serum bilirubin < 2 mg/dl, albumin > 3.5 g/dl, no ascites or encephalopathy (Child-Pugh grade A, score < 7)
  3. Age 18 years or older
  4. Male patients, or female with documented hysterectomy, ovariectomy or tubal ligation OR menopausal female with last menstrual period at least 12 months prior to screening OR female of childbearing potential with a negative serum pregnancy test at screening and day 1 and willing to ensure consistent and correct contraception
  5. Written informed consent prior to study enrolment which must be consistent with international conference on harmonisation ¿ good clinical practice (ICH-GCP) and local legislation.

Exclusion criteria:

  1. Serological evidence of active HBV, HCV or HIV infection (i.e. seropositivity for HBs antigen, anti-HIV-1 or -2 antibodies; if anti-HCV antibody positive, patients must have documented negative HCV RNA for at least 12 months)
  2. Usage of any drug within 7 days or 5 halftimes, whichever is longer, prior to treatment; or the planned usage of a drug during the course of the current study
  3. Usage of any investigational drug within 30 days prior to treatment; or the planned usage of an investigational drug during the course of the current study
  4. Decompensated liver disease within past 12 months, as indicated by variceal bleeding, ascites, encephalopathy, Prothrombin time or INR prolonged to > 1,7 x ULN, serum bilirubin > 2 mg/dl or albumin < 3,5 g/dl (i.e. Child-Pugh grade B)
  5. ALT or AST levels > 5xULN, Alkaline Phosphatase > 2xULN
  6. Liver cirrhosis due to primary or secondary biliary cirrhosis, sclerosing cholangitis, vanishing bile duct disease
  7. History of alcohol abuse within the past 3 months
  8. Known hypersensitivity to any content of the study drug
  9. Pregnant or breast feeding females
  10. Females of childbearing potential who are not willing to ensure consistent and correct use of condoms and at least one additional medically accepted method of contraception (diaphragm with spermicidal substance, cervical caps) or who are unwilling to comply to complete abstinence, from the date of screening until 6 months after the last dose of study drug
  11. AFP value > 100 ng/ml; if AFP is > 20 and <= 100 ng/ml, patients can be included if liver cancer is excluded by two congruent imaging studies (i.e. ultrasound plus CT scan or MRI)
  12. Evidence of chronic kidney failure (i.e. serum creatinine > ULN)
  13. Haemoglobinopathy (e.g., thalassaemia major or sickle cell anaemia)
  14. Concomitant intercurrent illnesses including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness or social situation that would limit compliance with trial requirement or which are considered relevant for the evaluation of the pharmacokinetic parameters or safety of the trial drug.
  15. Active or suspected malignancy or history of malignancy within the last 2 years (with the exception of appropriately treated basal cell carcinoma or in situ carcinoma of the uterine cervix)

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01909778


Locations
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Germany
1220.15.49006 Boehringer Ingelheim Investigational Site
Mainz, Germany
Sponsors and Collaborators
Boehringer Ingelheim
Investigators
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Study Chair: Boehringer Ingelheim Boehringer Ingelheim

Additional Information:
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Responsible Party: Boehringer Ingelheim
ClinicalTrials.gov Identifier: NCT01909778     History of Changes
Other Study ID Numbers: 1220.15
2007-007776-42 ( EudraCT Number: EudraCT )
First Posted: July 29, 2013    Key Record Dates
Results First Posted: August 10, 2015
Last Update Posted: August 10, 2015
Last Verified: August 2015
Additional relevant MeSH terms:
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Hepatitis C
Liver Cirrhosis
Fibrosis
Hepatitis
Liver Diseases
Digestive System Diseases
Hepatitis, Viral, Human
Virus Diseases
Flaviviridae Infections
RNA Virus Infections
Pathologic Processes