Effects of Steady State Tipranavir/Ritonavir or Darunavir/Ritonavir or Ritonavir on Platelet Function, Coagulation and Fibrinolysis Biomarkers in Healthy Subjects

NCT02251795 | Completed Phase 1

• 1 other identifier: 1182.117
• Study Type: interventional
• Target: 52
• Locations: 0 countries
• Sites: N/A

Brief Summary

Study to determine the effect of steady-state plasma concentration of Tipranavir/ritonavir (TPV/r) on platelet aggregation in healthy subjects and investigate the effect of TPV/r at steady state plasma concentrations on other platelet functions and biomarkers of coagulation and fibrinolysis.

Conditions

Healthy

Outcome Measures

Primary Outcomes (1)

• Percent change from baseline in the area under the curve (AUC) of platelet aggregation in response to arachidonic acid (AA)

  calculated as the ratio of the AUC at steady state TPV plasma concentrations and the baseline AUC

  pre-dose, up to 48 h after drug administration

Secondary Outcomes (29)

• Changes in platelet aggregation in response to AA

  pre-dose, up to 48 h after drug administration

• Changes in platelet aggregation in response to collagen

  pre-dose, up to 48 h after drug administration

• Changes in platelet aggregation in response adenosine diphosphate (ADP)

  pre-dose, up to 48 h after drug administration

• Changes in closure Time (CT)

  pre-dose, up to 48 h after drug administration

• Changes in urinary thromboxane B2 metabolites

  pre-dose, up to 48 h after drug administration

Study Arms (3)

Tipranavir/Ritonavir

EXPERIMENTAL

500 mg Tipranavir / 200 mg Ritonavir 10 days BID

Drug: Tipranavir; Drug: Ritonavir; Drug: Aspirin

Darunavir/Ritonavir

ACTIVE COMPARATOR

600 mg Darunavir /100 mg Ritonavir 10 days BID

Drug: Ritonavir; Drug: Darunavir; Drug: Aspirin

Ritonavir

ACTIVE COMPARATOR

100 mg Ritonavir 10 days BID

Drug: Ritonavir; Drug: Aspirin

Interventions

Tipranavir DRUG

Also known as: APTIVUS®

Tipranavir/Ritonavir

Ritonavir DRUG

Also known as: Norvir®

Darunavir/Ritonavir; Ritonavir; Tipranavir/Ritonavir

Darunavir DRUG

Also known as: PREZISTA®

Darunavir/Ritonavir

Aspirin DRUG

single dose on day 2

Also known as: Acetylsalicylic acid

Darunavir/Ritonavir; Ritonavir; Tipranavir/Ritonavir

Eligibility Criteria

• Age: 18 Years - 50 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Ability and willingness to give written informed consent to participate in this study (i.e., prior to any study-specific procedures)
• Age ≥18 years and ≤50 years
• Female subjects of child-bearing potential were eligible if:
• They had used a barrier contraceptive method for at least 12 weeks before administration of study medication and had a negative serum pregnancy test result during the screening period (Day - 35 to Day -3); or,
• Were abstinent for more than 12 weeks before screening and had a negative serum pregnancy test result during the screening period (Day -35 to Day -3); or,
• Had a documented tubal ligation and had a negative serum pregnancy test result during the screening period (Day -35 to Day -3)
• Ability to swallow capsules without difficulty
• Reasonable probability of completing the study
• Findings from medical history, physical examination and 12-lead ECG indicating subject was healthy and suitable for the trial in the opinion of the investigator
• Agreement to abstain from alcohol consumption or drugs of abuse during the study
• Agreement to abstain from ingestion of grapefruit, grapefruit juice, Seville oranges, or orange marmalade from screening period to the end of the study
• Negative urine drug screen for drugs of abuse
• Non smoker
• Agreement to abstain from use of tobacco products from screening period to the end of the study
• Negative HIV-1 serology by ELISA testing

You may not qualify if:

• Female subjects who:
• had a positive serum pregnancy test during the screening period (Day -35 to Day -3) or during the study
• were breast feeding or planing to breast feed at any time from the screening period through 30 days after the last dose of the study drug
• were not willing to use a barrier method of contraception at any time from screening period through 30 days after the last dose of the study drug
• were taking any hormonal therapy for any reason such as birth control or replacement therapy
• Had used any investigational agent within 30 days prior to Visit 2
• Blood or plasma donations (\>100 mL total) for research or altruistic reasons within 30 days prior to Visit 2
• Had used aspirin or any non-steroidal anti-inflammatory agent (NSAID), and including COX-2 inhibitors, dipyridamole, clopidogrel, ticlopidine or other antiplatelet drugs within 14 days prior to Visit 2 or during the study
• Active peptic ulceration or history of peptic ulcer disease
• Known history of or suspected hypersensitivity to aspirin, any NSAID or any other component of the test drugs (Tipranavir, Darunavir, Ritonavir)
• Known hypersensitivity to antiretroviral drugs (marketed or experimental drug in clinical research studies)
• Active bleeding disorder or history of active bleeding disorder
• Active Intra cranial hemorrhage (ICH) or history of ICH
• Active coronary artery disease or history of coronary artery disease
• Alcohol abuse (more than 60 g/day)

Sponsors & Collaborators

• Boehringer Ingelheim: lead

MeSH Terms

Interventions

tipranavir; Ritonavir; Darunavir; Aspirin

Intervention Hierarchy (Ancestors)

Thiazoles; Sulfur Compounds; Organic Chemicals; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Sulfonamides; Amides; Carbamates; Acids, Acyclic; Carboxylic Acids; Sulfones; Furans; Salicylates; Hydroxybenzoates; Phenols; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons

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 25, 2014
• First Posted: September 29, 2014
• Study Start: August 1, 2007
• Primary Completion: June 1, 2008
• Last Updated: September 29, 2014

Record last verified: 2014-09