NCT02251795已完成1 期
Effects of Steady State Tipranavir/Ritonavir or Darunavir/Ritonavir or Ritonavir on Platelet Function, Coagulation and Fibrinolysis Biomarkers in Healthy Subjects
适应症
干预措施
相关药物
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 52
- 主要终点
- Percent change from baseline in the area under the curve (AUC) of platelet aggregation in response to arachidonic acid (AA)
研究概览
简要总结
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 50 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •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
- •Agreement to abstain from use of tobacco products from screening period to the end of the study
- •Negative HIV-1 serology by ELISA testing
- •Negative Hepatitis B surface Antigen test (HBsAg)
- •Negative Hepatitis C Virus antibody (anti-HCV) test by Enzyme Immunoassay
- •Platelet count ≥125,000/mm3
- •Hemoglobin ≥11.0 g/dL
- •Prothrombin time ≤1.0 x upper limit of normal (ULN)
- •Activated Partial thromboplastin time ≤1.0 x ULN
排除标准
- •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)
- •Any indication for current use of aspirin or any NSAID or indication for such use from Visit 2 to Visit 18
- •Had used any over-the-counter medication within 7 days prior to Visit 2, or current use of any prescription drug
- •Subjects who had an abnormal laboratory result of Grade 1 or greater, as defined by the Division of AIDS Table for Grading the Severity of Adult and Pediatric Adverse Events (DAIDS), (result must have been available at least 3 days prior to Visit 2-Day 1), except the following screening laboratory values:
- •serum potassium, serum sodium, serum phosphate and uric acid, where central laboratory reference ranges will be used to determine eligibility rather than DAIDS table; or,
- •amylase or creatinine results of Grade 1 on DAIDS table if these results are considered clinically not significant by investigator; or
- •other marginally abnormal laboratory values not considered clinically significant by investigator and approved by clinical monitor
- •History of any illness that in the opinion of the investigator might confound the results of the study or pose additional risks in administering aspirin, Tipranavir, Darunavir, or Ritonavir
- •Hypersensitivity to sulphonamide drugs
- •Had used proton pump inhibitors during 14 days prior to Visit 2
- •Vitamin E intake in excess of 60 mg/day within 30 days prior to Visit 2
- •Vitamin E supplementation in excess of 60 mg/day during the study (Vitamin E content of multivitamin tablets is allowed)
研究组 & 干预措施
Tipranavir/Ritonavir
Experimental
500 mg Tipranavir / 200 mg Ritonavir 10 days BID
干预措施: Tipranavir (Drug)
Tipranavir/Ritonavir
Experimental
500 mg Tipranavir / 200 mg Ritonavir 10 days BID
干预措施: Ritonavir (Drug)
Tipranavir/Ritonavir
Experimental
500 mg Tipranavir / 200 mg Ritonavir 10 days BID
干预措施: Aspirin (Drug)
Darunavir/Ritonavir
Active Comparator
600 mg Darunavir /100 mg Ritonavir 10 days BID
干预措施: Ritonavir (Drug)
Darunavir/Ritonavir
Active Comparator
600 mg Darunavir /100 mg Ritonavir 10 days BID
干预措施: Darunavir (Drug)
Darunavir/Ritonavir
Active Comparator
600 mg Darunavir /100 mg Ritonavir 10 days BID
干预措施: Aspirin (Drug)
Ritonavir
Active Comparator
100 mg Ritonavir 10 days BID
干预措施: Ritonavir (Drug)
Ritonavir
Active Comparator
100 mg Ritonavir 10 days BID
干预措施: Aspirin (Drug)
结局指标
主要结局
Percent change from baseline in the area under the curve (AUC) of platelet aggregation in response to arachidonic acid (AA)
时间窗: pre-dose, up to 48 h after drug administration
calculated as the ratio of the AUC at steady state TPV plasma concentrations and the baseline AUC
次要结局
- Changes in fibrinogen(Baseline, up to day 30)
- Area under the curve from 0-12 hours (AUC0-12h)(up to 12 hours after drug administration)
- Changes in factor II(Baseline, up to day 30)
- Changes in factor IX(Baseline, up to day 30)
- Time from dosing to the maximum measured concentration of the analyte in plasma (Tmax)(up to 48 h after drug administration)
- Terminal half-life (t1/2)(pre-dose, up to 48 h after drug administration)
- Changes in factor X(Baseline, up to day 30)
- Changes in platelet aggregation in response to AA(pre-dose, up to 48 h after drug administration)
- Total clearance of the analyte in plasma (CL/F)(pre-dose, up to 48 h after drug administration)
- Number of subjects with treatment-emergent adverse events(up to 96 days)
- 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 von anti-thrombin III antigen(Baseline, up to day 30)
- Changes in anti-thrombin III activity(Baseline, up to day 30)
- Number of subjects with abnormal findings in laboratory tests(up to day 61)
- Changes in plasminogen activity(Baseline, up to day 30)
- Changes in alpha 2-antiplasmin(Baseline, up to day 30)
- Changes in D-dimer(Baseline, up to day 30)
- Changes in Plasminogen Activator Inhibitor (PAI-1)(Baseline, up to day 30)
- Changes in urinary thromboxane B2 metabolites(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 bleeding time(Baseline, up to day 30)
- Changes in activated partial thromboplastin time (aPTT)(Baseline, up to day 30)
- Changes in prothrombin time (PT)(Baseline, up to day 30)
- Changes in von Willebrand antigen(Baseline, up to day 30)
- Changes in factor VII(Baseline, up to day 30)
- Maximum measured concentration of the analyte in plasma (Cmax)(pre-dose, up to 48 h after drug administration)
- Serum concentration at 12 hours (Cp12h)(12 hours after drug administration)
- Apparent volume of distribution (V/F)(pre-dose, up to 48 h after drug administration)
研究者
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