Effects of Tipranavir (With Ritonavir) Capsule and Liquid Formulation on Cytochrome P450 and P-glycoprotein Activity in Healthy Volunteers

NCT02243553 | Completed Phase 1

• 1 other identifier: 1182.101
• Study Type: interventional
• Target: 34
• Locations: 0 countries
• Sites: N/A

Brief Summary

Primary: To quantify the influence of single-dose and steady-state tipranavir/ritonavir 500/200 mg on intestinal and hepatic cytochrome P450 (CYP) and P-glycoprotein (P-gp) biomarkers, as a means of predicting drug interactions. The AUCs for biomarkers caffeine, warfarin, omeprazole, dextromethorphan, midazolam, and digoxin will be assessed.

Conditions

Healthy

Outcome Measures

Primary Outcomes (1)

• Area under plasma concentration-time curve (AUC) at steady state

  up to 72 hours

Secondary Outcomes (7)

• Plasma concentration after 12 hours (Cp12h)

  12 hours

• Maximum plasma concentration (Cmax)

  up to 12 hours

• Time of maximum concentration (Tmax)

  up to 72 hours

• Apparent terminal half-life (t1/2)

  up to 72 hours

• Area under plasma concentration-time curve (AUC) after single dose

  up to 72 hours

Study Arms (4)

Treatment A

EXPERIMENTAL

tipranavir (TPV) capsule + ritonavir (RTV) capsule + cocktail + digoxin oral

Drug: Tipranavir capsule; Drug: Ritonavir capsule; Drug: Caffeine; Drug: Warfarin sodium; Drug: Vitamin K; Drug: Omeprazole; Drug: Dextromethorphan hydrobromide; Drug: Midazolam injection; Drug: Midazolam oral solution; Drug: Digoxin tablet

Treatment B

EXPERIMENTAL

TPV capsule + RTV capsule + cocktail + digoxin injection

Drug: Tipranavir capsule; Drug: Ritonavir capsule; Drug: Caffeine; Drug: Warfarin sodium; Drug: Vitamin K; Drug: Omeprazole; Drug: Dextromethorphan hydrobromide; Drug: Midazolam injection; Drug: Midazolam oral solution; Drug: Digoxin injection

Treatment C

EXPERIMENTAL

TPV solution + RTV capsule + cocktail + digoxin oral

Drug: Tipranavir solution; Drug: Ritonavir capsule; Drug: Caffeine; Drug: Warfarin sodium; Drug: Vitamin K; Drug: Omeprazole; Drug: Dextromethorphan hydrobromide; Drug: Midazolam injection; Drug: Midazolam oral solution; Drug: Digoxin tablet

Treatment D

EXPERIMENTAL

TPV solution + RTV capsule + cocktail + digoxin injection

Drug: Tipranavir solution; Drug: Ritonavir capsule; Drug: Caffeine; Drug: Warfarin sodium; Drug: Vitamin K; Drug: Omeprazole; Drug: Dextromethorphan hydrobromide; Drug: Midazolam injection; Drug: Midazolam oral solution; Drug: Digoxin injection

Interventions

Tipranavir capsule DRUG

Treatment A; Treatment B

Tipranavir solution DRUG

Treatment C; Treatment D

Ritonavir capsule DRUG

Treatment A; Treatment B; Treatment C; Treatment D

Caffeine DRUG

Treatment A; Treatment B; Treatment C; Treatment D

Warfarin sodium DRUG

Treatment A; Treatment B; Treatment C; Treatment D

Vitamin K DRUG

Treatment A; Treatment B; Treatment C; Treatment D

Omeprazole DRUG

Treatment A; Treatment B; Treatment C; Treatment D

Dextromethorphan hydrobromide DRUG

Treatment A; Treatment B; Treatment C; Treatment D

Midazolam injection DRUG

Treatment A; Treatment B; Treatment C; Treatment D

Midazolam oral solution DRUG

Treatment A; Treatment B; Treatment C; Treatment D

Digoxin tablet DRUG

Treatment A; Treatment C

Digoxin injection DRUG

Treatment B; Treatment D

Eligibility Criteria

• Age: 18 Years - 45 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Signed informed consent
• Healthy subjects aged between 18 years and 45 years inclusive
• Weighing at least 50 kg
• Volunteers must be hospitalized on Days 1-4, 7-9, and 17-20 for pharmacokinetic assessments for each biomarker and TPV/r (Days 7-9 and 17-20)
• Volunteers must be willing to complete all study-related activities
• Each volunteer must have a valid social security number
• Each volunteer must have acceptable medical history, physical examination and laboratory test

You may not qualify if:

• History or presence of allergy to the study drugs or their components or drugs of their class, or a history of drug or other allergy that, in the opinion of the physician responsible, contraindicates their participation
• Any finding of the medical examination (including blood pressure, pulse rate and electrocardiogram) deviating from normal and of clinical relevance
• History or diagnosis of any significant medical conditions: Including but not limited to gastrointestinal, hepatic, renal, respiratory, cardiovascular, metabolic, immunologic, hematological, psychiatric, neurological, oncological or hormonal disorders
• Known elevated liver enzymes in past clinical trials with any compound (experimental or marketed)
• Clinically relevant laboratory abnormalities (e.g. Hgb\<11g/dL, Hct\<30g/dL, total cholesterol \>240mg/dL, triglycerides \>500mg/dL, fasting glucose \>130mg/dL, liver function tests \>2.5x upper limit of normal, baseline international normalized ratio \>1.2)
• History of evidence of clinically significant hepatic, cardiac, pulmonary, endocrine, immunological, gastrointestinal, hematological, vascular or collagen disease
• History of alcohol abuse or use of any illicit drugs
• Unable to abstain from more than one beer or alcohol equivalent per day for the duration of the study
• Use of tobacco products and/or history of smoking within the past 2 months
• Pregnant or breast feeding
• Sexually active women of childbearing age who do not use an acceptable barrier method of birth control
• Hypersensitivity to caffeine, warfarin, vitamin K, omeprazole, dextromethorphan, midazolam, tipranavir, ritonavir or their excipients
• Concomitant treatment with other experimental compounds
• Concomitant administration of any prescription or over the counter medications known to alter P450 enzyme or P-gp activity
• Concomitant administration of any prescription or over the counter medications known to be highly dependent on P450 or P-gp for clearance for which elevated plasma concentrations are known to be associated with serious toxicity

Sponsors & Collaborators

• Boehringer Ingelheim: lead

MeSH Terms

Interventions

tipranavir; Ritonavir; Caffeine; Warfarin; Vitamin K; Omeprazole; Dextromethorphan; Midazolam; Digoxin

Intervention Hierarchy (Ancestors)

Thiazoles; Sulfur Compounds; Organic Chemicals; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Xanthines; Alkaloids; Purinones; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; 4-Hydroxycoumarins; Coumarins; Benzopyrans; Pyrans; Naphthoquinones; Naphthalenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Phytol; Diterpenes; Terpenes; Polycyclic Compounds; 2-Pyridinylmethylsulfinylbenzimidazoles; Sulfoxides; Pyridines; Benzimidazoles; Morphinans; Opiate Alkaloids; Heterocyclic Compounds, Bridged-Ring; Heterocyclic Compounds, 4 or More Rings; Phenanthrenes; Benzodiazepines; Benzazepines; Digitalis Glycosides; Cardenolides; Cardiac Glycosides; Cardanolides; Steroids; Fused-Ring Compounds; Glycosides; Carbohydrates

Study Design

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

Study Record Dates

• First Submitted: September 1, 2014
• First Posted: September 18, 2014
• Study Start: January 1, 2006
• Primary Completion: July 1, 2006
• Last Updated: September 18, 2014

Record last verified: 2014-08