Pharmacokinetics (PK) of Tipranavir/Ritonavir, Ribavirin, Pegylated Interferon (Peg INF) in Hepatitis C (HCV) Subjects With Mild Hepatic Impairment and in HCV, Hepatitis B (HBV), Hepatitis D Infected Subjects or Alcoholic Cirrhosis With Moderate Hepatic Impairment

NCT02259855 | Completed Phase 1

• 1 other identifier: 1182.59
• Study Type: interventional
• Target: 36
• Locations: 0 countries
• Sites: N/A

Brief Summary

The primary objectives were:

• To determine the effects of steady state TPV co-administered with low dose RTV on steady state PegIFN and RBV in HIV negative subjects with mild hepatic impairment (scheme A)
• To determine the effects of steady state of pegylated interferon (PegIFN) and RBV on steady state pharmacokinetics of TPV co-administered with low dose RTV in HIV negative subjects with mild hepatic impairment (scheme A)
• To determine the pharmacokinetics of single dose and steady state TPV/r 500/200 mg in subjects with moderate hepatic insufficiency (scheme B)

Conditions

Hepatic Insufficiency

Outcome Measures

Primary Outcomes (6)

• Area under the concentration-time curve from 0 to 12 hours of ribavirin (RBV), tipranavir (TPV) and ritonavir (RTV) in the plasma (AUC0-12h)

  Pre-dose, up to 120 hours after start of treatment

• Area under the concentration-time curve from 0 to 24 hours of pegylated interferon (Peg IFN) in the plasma (AUC0-24h)

  Pre-dose, up to 120 hours after start of treatment

• Maximum measured concentration of RBV, Peg INF, TPV and RTV in the plasma (Cmax)

  Pre-dose, up to 120 hours after start of treatment

• Measured concentration of RBV, TPV and RTV in the plasma at 12 hours (Cp12h)

  Pre-dose, up to 120 hours after start of treatment

• Measured concentration of Peg INF in the plasma at 24 hours (Cp24h)

  Pre-dose, up to 120 hours after start of treatment

• Area under the concentration-time curve from 0 extrapolated to infinity of TPV and RTV in the plasma (AUC0-∞)

  Pre-dose, up to 120 hours after start of treatment

Secondary Outcomes (9)

• Time from dosing to the maximum concentration of the analytes in the plasma (tmax)

  Pre-dose, up to 120 hours after start of treatment

• Terminal half-life of the analytes in the plasma (t1/2)

  Pre-dose, up to 120 hours after start of treatment

• Apparent clearance of the analytes in the plasma after extra vascular administration (CL/F)

  Pre-dose, up to 120 hours after start of treatment

• Apparent volume of distribution of the analytes in the plasma (Vz/F)

  Pre-dose, up to 120 hours after start of treatment

• Number of patients with clinically significant changes in laboratory values

  up to 3 weeks after start of treatment

Study Arms (3)

Mild hepatic insufficiency

EXPERIMENTAL

Drug: Tipranavir; Drug: Ritonavir; Drug: Pegylated interferon; Drug: Ribavirin

Moderate hepatic insufficiency

EXPERIMENTAL

Drug: Tipranavir; Drug: Ritonavir

Healthy subjects

EXPERIMENTAL

Drug: Tipranavir; Drug: Ritonavir

Interventions

Tipranavir DRUG

Healthy subjects; Mild hepatic insufficiency; Moderate hepatic insufficiency

Ritonavir DRUG

Healthy subjects; Mild hepatic insufficiency; Moderate hepatic insufficiency

Pegylated interferon DRUG

Mild hepatic insufficiency

Ribavirin DRUG

Mild hepatic insufficiency

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age ≥18 and Age ≤ 75 years
• BMI ≥18 and BMI ≤ 29 kg/m2 (Body Mass Index) at screening visit
• Signed and dated written informed consent prior to admission to the study in accordance with good clinical practice (GCP) and the local legislation
• Ability to swallow multiple large capsules without difficulty
• Serologic evidence of chronic hepatitis C infection by an antibody test and HCV branched DNA (bDNA) for subjects with mild hepatic impairment (Scheme A)
• Serologic evidence of chronic hepatitis C, B and/or delta infection by an antibody test and HCV bDNA, HBV RNA polymerase chain reaction (PCR) for subjects with moderate hepatic impairment (Child Pugh B)
• Alcoholic cirrhosis, for subjects with moderate hepatic impairment (Child Pugh B). Patients had to stop the alcohol consumption at least 1 month before the screening without any evidence of acute alcoholic hepatitis
• Subjects HCV positive with mild hepatic insufficiency were to be on stable treatment with PegIFN and ribavirin since at least 12 weeks prior to study entry
• Subjects with mild hepatic insufficiency were to be viral non-responders with less than a 2 log reduction in HCV RNA, compared to baseline (HCV treatment initiation) and have positive HCV RNA after 12 weeks therapy with PegIFN/RBV
• Subjects with:
• stable mild hepatic insufficiency treated by PegIFN and RBV
• moderate hepatic insufficiency \[Child-Pugh Class B (score 7-9)\]
• All fertile males or females, and their respective partner(s) were to be using two forms of effective contraception during ribavirin treatment and during the 6 months after its end. All other women must agree to use an effective form of contraception during the entire duration of the study. This may include condoms, diaphragms or implants. This did not apply to those surgically sterilized or in a post menopausal state
• Laboratory values that indicated adequate baseline organ function were required at the time of screening. All subjects with mild and moderate hepatic insufficiency should have all laboratory values less than or equal to grade 2, based on division of aids (DAIDS) Grading Scale. The following exceptions were made:
• Alanine transaminase (ALT) and/or aspartate aminotransferase (AST) \< 3 x upper limit of normal (ULN)

You may not qualify if:

• Use of any medication listed in the protocol within 30 days prior to Day 1
• Participation in another trial with an investigational medicine within 2 months prior to Day 1
• Absolute neutrophil count (ANC) \< 750 cells/mm³ at screening
• Serum creatine level \> 1.5 times upper the limit of normal at screening
• History of acute illness within 60 days prior to Day 1
• Subject with mild hepatic impairment (scheme A), HIV, HBV, hepatitis Delta positive and/or alcoholic cirrhosis
• Subject with moderate hepatic impairment (CPB), HIV positive
• Subject control, HIV hepatitis positive and alcoholic cirrhosis
• Subjects HIV positive, HBV positive and, for subjects controls HCV positive
• Active bleeding from oesophageal varices or other conditions consistent with active decompensated liver disease, active spontaneous bacterial peritonitis, active oesophageal variceal disease or active liver encephalopathy
• Subjects with Child-Pugh Class C (score \> 9)
• Alcohol abuse within 1 month prior to screening or during the study
• Other substance abuse within 6 months prior to screening or during the study
• Subjects with a history of any illness or allergy (including drug allergy) that, in the opinion of the investigator, might confound the results of the study or pose additional risk in administering TPV and RTV
• Subjects who have taken (within 7 days prior to Day 1) any over-the-counter or prescription medication that, in the opinion of the investigator in consultation with the Boehringer Ingelheim France (BIF) clinical monitor, might interfere with absorption, distribution, or metabolism of the study medications

Sponsors & Collaborators

• Boehringer Ingelheim: lead

Related Links

• Related Info

MeSH Terms

Conditions

Hepatic Insufficiency

Interventions

tipranavir; Ritonavir; Ribavirin

Condition Hierarchy (Ancestors)

Liver Diseases; Digestive System Diseases

Intervention Hierarchy (Ancestors)

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

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 24, 2014
• First Posted: October 9, 2014
• Study Start: January 1, 2006
• Primary Completion: October 1, 2008
• Last Updated: January 22, 2025

Record last verified: 2025-01

Data Sharing

• IPD Sharing: Will not share