Pharmacokinetic of Tadalafil Co-administered With Tipranavir/Ritonavir to Healthy Male Volunteers

Assessment of Single-dose Oral Tadalafil Pharmacokinetic Characteristics When Simultaneously Co-administered With Single-dose and Steady-state Tipranavir/Ritonavir 500 mg/200 mg to Healthy Male Volunteers

Study to assess the effects of single-dose and steady-state tipranavir/ritonavir 500 mg/200 mg on the single-dose pharmacokinetics of tadalafil 10 mg

Study Overview

• Status: Completed
• Conditions: Healthy
• Intervention / Treatment: Drug: Tadalafil; Drug: Tipranavir; Drug: Ritonavir

• Study Type: Interventional
• Enrollment (Actual): 17
• Phase: Phase 1

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: Male

Description

Inclusion Criteria:

1. Signed informed consent
2. Healthy male subjects aged between 18 years and 55 years inclusive
3. Weighing at least 40 kg
4. Volunteers must be hospitalized on day of pharmacokinetic assessments for each regimen
5. Volunteers must be willing to complete all study-related activities
6. Each volunteer must have a valid social security regimen
7. Each volunteer must have acceptable medical history, physical examination and laboratory test
8. Volunteers with negative HIV serology

Exclusion Criteria:

1. 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. (If heparin is used during pharmacokinetic (PK) sampling, subjects with a history of sensibility to heparin or heparin-induced thrombocytopenia should not be enrolled)
2. Any finding of the medical examination (including blood pressure, pulse rate, and electrocardiogram) deviating from normal and of clinical relevance
3. Gastrointestinal, hepatic, renal, respiratory, cardiovascular, metabolic, immunologic, haematological, oncological or hormonal disorders
4. Known elevated liver enzymes in past clinical trials with any compound (experimental or marketed)
5. Clinically relevant laboratory abnormalities and all abnormal laboratory values >Grade 1, based on the Division of AIDS Grading Scale
6. Subjects with a history of any illness or allergy that, in the opinion of the investigator, might confound the results of the study or pose additional risk in administering tipranavir, ritonavir or tadalafil to the subject
7. Volunteers who are using any form of organic nitrate, either regularly and/or intermittently (contraindication to use tadalafil)
8. Hypersensitivity to tadalafil, tipranavir, ritonavir or their excipients
9. Concurrent treatment with other experimental compounds
10. Inadequate venous access
11. Contraindications to tadalafil: Volunteers with mild or moderate hepatic impairment, Renal insufficiency or Cardiovascular disease (patients with a myocardial infarction within the last 90 days, unstable angina or angina occurring during sexual intercourse, patients with New York Heart Association Class 2 or greater heart failure in the last 6 months, patients with uncontrolled arrhythmias, hypotension (<90/50 mm Hg), or uncontrolled hypertension (>170/100 mm Hg), and patients with a stroke within the last 6 months)
12. Clinically unacceptable result at the screening physical examination
13. Use of investigational medications within 30 days before study entry
14. Patients hospitalized in a medical or social establishment, for any other reason than research
15. People deprived of judicial or administrative freedom.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Sequential treatment	Drug: Tadalafil; administered days 1, 8 and 16; Drug: Tipranavir; administered days 8-18; Drug: Ritonavir; administered days 8-18

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Maximum Plasma Concentration (Cmax) for Tadalafil	up to 72 hours after drug administration
Plasma Concentration (Cp12h) for Tadalafil	12 hours after drug administration
Area Under Plasma Concentration-time Curve (AUC0-72h) for Tadalafil	up to 72 hours after drug administration
AUC0-∞ for Tadalafil	up to 72 hours after drug administration

Secondary Outcome Measures

Outcome Measure	Time Frame
Number of subjects with adverse events	up to 42 days
Cmax for Tipranavir and Ritonavir	up to 12 hours after drug administration
Cp12 for Tipranavir and Ritonavir	12 hours after drug administration
AUC0-12hTipranavir and Ritonavir	12 hours after drug administration
Time of Maximum Concentration	up to 72 hours after drug administration
Elimination half-life (t1/2)	up to 72 hours after drug administration
Total body clearance (Cl/F)	up to 72 hours after drug administration
Volume of distribution,	up to 72 hours after drug administration

Collaborators and Investigators

• Sponsor: Boehringer Ingelheim

Publications and helpful links

Helpful Links

• Related Info

Study record dates

Study Major Dates

• Study Start: December 1, 2005
• Primary Completion (Actual): March 1, 2006

Study Registration Dates

• First Submitted: September 30, 2014
• First Submitted That Met QC Criteria: September 30, 2014
• First Posted (Estimate): October 1, 2014

Study Record Updates

• Last Update Posted (Estimate): October 1, 2014
• Last Update Submitted That Met QC Criteria: September 30, 2014
• Last Verified: September 1, 2014

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Molecular Mechanisms of Pharmacological Action; Vasodilator Agents; Anti-Infective Agents; Urological Agents; Antiviral Agents; Enzyme Inhibitors; Anti-HIV Agents; Anti-Retroviral Agents; Protease Inhibitors; Cytochrome P-450 CYP3A Inhibitors; Cytochrome P-450 Enzyme Inhibitors; HIV Protease Inhibitors; Viral Protease Inhibitors; Phosphodiesterase Inhibitors; Phosphodiesterase 5 Inhibitors; Ritonavir; Tipranavir; Tadalafil
• Other Study ID Numbers: 1182.83