Comparative Effects of Aspirin and NHP-544C

Study Overview
=================
Brief Summary
-----------------
The investigators will compare the effects of rapid release aspirin and NHP-544C on the prostacyclin response to intravenous bradykinin.

Official Title
-----------------
Comparative Effects of Rapid-Release Aspirin and NHP-544C on Basal and Bradykinin Stimulated Prostacyclin Production

Conditions
-----------------
Healthy

Intervention / Treatment
-----------------
* Drug: Bradykinin
* Drug: Aspirin 81 mg
* Drug: Aspirin 162 mg
* Drug: NHP544-C 81 mg
* Drug: NHP544C 162 mg
* Drug: Placebo


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Ages of 18 and 55 years, inclusive No significant medical issues without significant abnormal findings at the baseline physical examination Body mass index (BMI) between 18.0 and 30.0kg/m2 (weight (kg)/[height(m)]2) For women - negative pregnancy test on Period 1, Day -1, or surgically sterilized, or is at least two years post-menopausal prior to randomization. Females of childbearing potential must be practicing an acceptable method of birth control to be eligible. Acceptable forms of birth control include: condom plus spermicide or condom plus other form of birth control including hormonal method (IUD, patch, ring, implant, or injectable), sterilization of partner, or non-hormonal IUD. The use of oral contraceptives is allowed during the study, but the subject must be on a stable dose for 30 days prior to the trial and throughout all four dosing periods Ability to understand the requirements of the study and a willingness to comply with all study procedures Exclusion Criteria: Clinically significant and relevant medical history (including failure of a major organ system) or current medical illness, and is deemed by the Principal Investigator to be unsuitable to participate in the study Participation in an investigational drug study within the 30 days prior to CRC admission Use of aspirin or other NSAID within 14 days of Day 1 of the study. All other medications, prescription (with the exception of contraceptives), over-the-counter (OTC), herbal, and vitamin supplements must be discontinued 7 days prior to Day 1. If subjects are taking prescription medication, or OTC medication at the direction of a health care provider, that provider must confirm that it is acceptable for them to stop dosing for the duration of the study History of metabolic, renal, hepatic, hemorrhagic stroke, gastrointestinal bleed, cardiovascular disease, central nervous system disorder, or peptic ulcer disease or other chronic bleeding disorder History of gastrointestinal disorder that could result in incomplete absorption of the study drug Malignancy, or neurologic or psychiatric disorder Abnormal laboratory value(s) determined to be clinically significant (in the opinion of the Investigator) History of illicit drug abuse in the past year or current evidence of such abuse in the opinion of the investigator Pregnancy or lactation Acute illness within 1 week of CRC admission Significant loss of blood or blood or plasma donation within 30 days of drug administration Hypersensitivity or allergy to NSAIDs, aspirin, ethylcellulose, polyvidone, castor oil, magnesium stearate, tartaric acid, colloidal anhydrous silica, talc, gelatin, titanium dioxide, erythrosine, or indigotin History of aspirin resistance History of alcohol abuse within past year. Current alcohol use should not exceed 14 standard alcoholic drinks per week. A drink is defined as 1.5 ounces (oz.) liquor, 12 oz. beer, or 6 oz. wine Alcohol consumption within 3 days of Day 1 Difficulty swallowing oral medications Consumption of coffee or caffeine-containing beverages exceeding the equivalent of five 8-oz cups of coffee per day on average

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 55 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Basic Science
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Group 1:Aspirin/placebo<br>Group 1 will be randomized to the order in which they receive rapid-release aspirin (ASA), 81 mg), ASA 162.5 mg, and identical-appearing placebo for 5 days. Bradykinin will be given intravenously in graded doses on the fifth day of each treatment period. | Drug: Bradykinin<br>* Bradykinin will be given intravenously in graded doses. Each dose will be given for 15 minutes.<br>* Other names: BK;Drug: Aspirin 81 mg<br>* Subjects will take Aspirin 81 mg per day for five days.<br>* Other names: ASA 81 mg;Drug: Aspirin 162 mg<br>* Subjects will take aspirin 162 mg per day for 5 days.<br>* Other names: ASA 162 mg;Drug: Placebo<br>* Subjects will take matching placebo for five days.<br>|
| Active Comparator: Group 2:NHP-544C/placebo<br>Group 2 will be randomized to the order in which they receive NHP-544C 81 mg, NPH-544C 162.5 mg and identical-appearing placebo for five days. Bradykinin will be given intravenously in graded doses on the fifth day of each treatment period. | Drug: Bradykinin<br>* Bradykinin will be given intravenously in graded doses. Each dose will be given for 15 minutes.<br>* Other names: BK;Drug: NHP544-C 81 mg<br>* Subjects will take NHP544C 81 mg per day for five days.<br>Drug: NHP544C 162 mg<br>* Subjects will take NHP544C 162 mg once a day for five days.<br>Drug: Placebo<br>* Subjects will take matching placebo for five days.<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Urine Thromboxane Concentrations at Placebo ASA or Placebo NHP-544C Dose |  | 24 hour collection | 
| Urine Thromboxane Concentrations at 81mg ASA or NHP-544C Dose |  | 24 hour collection | 
| Urine Thromboxane Concentrations at 162.5 mg ASA or NHP-544C Dose |  | 24 hour collection | 
| Urine Prostacyclin Concentrations at Placebo ASA or Placebo NHP-544C Dose |  | 24 hour collection | 
| Urine Prostacyclin Concentrations at 81 mg ASA or NHP-544C Dose |  | 24 hour collection | 
| Urine Prostacyclin Concentrations at 162.5 mg ASA or NHP-544C Dose |  | 24 hour collection |