Study to Determine the Pharmacokinetics on TPV/r in Subjects With Mild and Moderate Hepatic Insufficiency

NCT02249442 | Completed Phase 1

• 1 other identifier: 1182.32
• Study Type: interventional
• Target: 24
• Locations: 0 countries
• Sites: N/A

Brief Summary

To determine the pharmacokinetics of single-dose and steady-state Tipranavir/Ritonavir (TPV/r) 500/200 mg in subjects with mild to moderate hepatic insufficiency

Conditions

Hepatic Insufficiency

Outcome Measures

Primary Outcomes (4)

• AUC0-∞ (area under the concentration time curve of drug in plasma over the time interval from 0 extrapolated to infinity)

  Up to day 12 after first drug administration

• AUC0-12h (area under the concentration time curve of drug in plasma over the time interval from 0 to 12h)

  Up to 12 hours after drug administration

• Cmax (maximum concentration of drug in plasma)

  Up to day 12 after first drug administration

• Cp12h (drug concentration in plasma at 12 hours after administration) for the mild hepatic subjects

  Up to 12 hours (h) after drug administration

Secondary Outcomes (8)

• time from dosing to the maximum concentration (tmax)

  Up to day 12 after first drug administration

• elimination half-life (t1/2)

  Up to day 12 after first drug administration

• oral clearance (CL/F)

  Up to day 12 after first drug administration

• volume of distribution (Vz/F)

  Up to day 12 after first drug administration

• Relationship between pharmacokinetic parameters and baseline covariates

  Up to day 12 after first drug administration

Study Arms (2)

Scheme A, mild hepatic subjects

EXPERIMENTAL

multi-dose

Drug: Tipranavir (TPV); Drug: Ritonavir (r)

Scheme B, moderate hepatic subjects

EXPERIMENTAL

single dose

Drug: Tipranavir (TPV); Drug: Ritonavir (r)

Interventions

Tipranavir (TPV) DRUG

Scheme A, mild hepatic subjects; Scheme B, moderate hepatic subjects

Ritonavir (r) DRUG

Scheme A, mild hepatic subjects; Scheme B, moderate hepatic subjects

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Signed informed consent prior to trial participation.
• Male and female subjects with:
• Diagnostically established hepatic disease with mild hepatic insufficiency (defined as maximum ever Child-Pugh score ≤6) or
• Diagnostically established hepatic disease with moderate hepatic insufficiency (defined as maximum ever Child-Pugh score ≤9) for less than 5 years. Current Child-Pugh score must be less than 9 or
• Subjects matched by gender, race, age (±3 years), and weight (±3 kg) and cigarette smoking (matched where possible by +/- .25 pack years) to subjects with mild or moderate hepatic impairment already enrolled in the study.
• Body Mass Index (BMI) between 18 and 29 kg/m2
• Subjects ≥18 and ≤75 years old.
• Ability to swallow multiple large capsules without difficulty.
• Laboratory values that indicate adequate baseline organ function are required at the time of screening. All subjects (including healthy controls) should have all laboratory values less than or equal to Grade 1, based on the AIDS Clinical Trial Group (ACTG) Grading Scale.The following exceptions will be made only for subjects with mild or moderate hepatic insufficiency:
• Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) \<5 x upper limit normal (ULN) (≤ Grade 2)
• Alkaline Phosphatase \<2 x ULN
• Hemoglobin \>10.0 g / dL
• Platelets \>75,000 / μl
• Willingness to abstain from alcohol starting 2 days prior to administration of study drug up to the end of the study.
• Willingness to abstain from the following 72 hours prior to pharmacokinetic (PK) sampling: Garlic supplements, methylxanthine containing drinks (coffee, tea, cola, energy drinks, chocolate, etc.).

You may not qualify if:

• Female subjects who are of reproductive potential who:
• Have positive serum β-hCG (Human chorionic gonadotropin test for pregnancy) at Visit 1 or on Day 0.
• Have not been using a barrier contraceptive method for at least 3 months prior to Day 0 (Visit 2).
• Are not willing to use a reliable method of at least barrier contraception, during the trial and 60 days after completion/termination.
• Are breast-feeding.
• Participation in another trial with an investigational medicine within 60 days prior to Day 0 (Visit 2).
• Use of any medication listed in the protocol within 30 days prior to Day 0 (Visit 2).
• Use of any pharmacological contraceptive (including oral or patch) for one month prior to study initiation and for the duration of the study. Use of implantable or injectable contraceptive agents is excluded for at least six months prior to study start.
• Use of hormone replacement therapy with estrogen-based preparations for at least 1 month prior to study initiation and for the duration of the study.
• Administration of antimicrobial agents within 10 days prior to Day 0 (Visit 2) or during the trial.
• Subjects with a history of spontaneous bacterial peritonitis, advanced hepatic cirrhosis (including Child's-Pugh score \>8), active esophageal variceal disease, or asterixis.
• Subjects with active or untreated hepatocellular carcinoma or who test positive for serum alpha fetoprotein (\>10mg/dL).
• Subjects with active coagulopathy.
• Have serological evidence of exposure to, or infection with, HIV.
• Recent history of alcohol or substance abuse (within 6 months of study period).

Sponsors & Collaborators

• Boehringer Ingelheim: lead

Related Links

• Related Info

MeSH Terms

Conditions

Hepatic Insufficiency

Interventions

tipranavir; Ritonavir

Condition Hierarchy (Ancestors)

Liver Diseases; Digestive System Diseases

Intervention Hierarchy (Ancestors)

Thiazoles; Sulfur Compounds; Organic Chemicals; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Design

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

Study Record Dates

• First Submitted: September 23, 2014
• First Posted: September 25, 2014
• Study Start: October 1, 2003
• Primary Completion: June 1, 2004
• Last Updated: January 23, 2025

Record last verified: 2025-01

Data Sharing

• IPD Sharing: Will not share