Clinical trial NCT02189122: Comparative Effects of Aspirin and NHP-544C
Official title: Comparative Effects of Rapid-Release Aspirin and NHP-544C on Basal and Bradykinin Stimulated Prostacyclin Production
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Healthy
Lead sponsor: Vanderbilt University
Sponsor class: OTHER
First posted: 2014-07-14
Enrollment: 61
Sex: ALL
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: BASIC_SCIENCE

Brief summary: The investigators will compare the effects of rapid release aspirin and NHP-544C on the prostacyclin response to intravenous bradykinin.


Eligibility criteria: Inclusion Criteria:

1. Ages of 18 and 55 years, inclusive
2. No significant medical issues without significant abnormal findings at the baseline physical examination
3. Body mass index (BMI) between 18.0 and 30.0kg/m2 (weight (kg)/\[height(m)\]2)
4. 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
5. Ability to understand the requirements of the study and a willingness to comply with all study procedures

Exclusion Criteria:

1. 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
2. Participation in an investigational drug study within the 30 days prior to CRC admission
3. 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
4. History of metabolic, renal, hepatic, hemorrhagic stroke, gastrointestinal bleed, cardiovascular disease, central nervous system disorder, or peptic ulcer disease or other chronic bleeding disorder
5. History of gastrointestinal disorder that could result in incomplete absorption of the study drug
6. Malignancy, or neurologic or psychiatric disorder
7. Abnormal laboratory value(s) determined to be clinically significant (in the opinion of the Investigator)
8. History of illicit drug abuse in the past year or current evidence of such abuse in the opinion of the investigator
9. Pregnancy or lactation
10. Acute illness within 1 week of CRC admission
11. Significant loss of blood or blood or plasma donation within 30 days of drug administration
12. Hypersensitivity or allergy to NSAIDs, aspirin, ethylcellulose, polyvidone, castor oil, magnesium stearate, tartaric acid, colloidal anhydrous silica, talc, gelatin, titanium dioxide, erythrosine, or indigotin
13. History of aspirin resistance
14. 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
15. Alcohol consumption within 3 days of Day 1
16. Difficulty swallowing oral medications
17. Consumption of coffee or caffeine-containing beverages exceeding the equivalent of five 8-oz cups of coffee per day on average

Primary outcomes:
measure: Urine Thromboxane Concentrations at Placebo ASA or Placebo NHP-544C Dose
timeFrame: 24 hour collection
measure: Urine Thromboxane Concentrations at 81mg ASA or NHP-544C Dose
timeFrame: 24 hour collection
measure: Urine Thromboxane Concentrations at 162.5 mg ASA or NHP-544C Dose
timeFrame: 24 hour collection
measure: Urine Prostacyclin Concentrations at Placebo ASA or Placebo NHP-544C Dose
timeFrame: 24 hour collection
measure: Urine Prostacyclin Concentrations at 81 mg ASA or NHP-544C Dose
timeFrame: 24 hour collection
measure: Urine Prostacyclin Concentrations at 162.5 mg ASA or NHP-544C Dose
timeFrame: 24 hour collection
Secondary outcomes:
Other outcomes:
Locations:
city: Nashville
country: United States
facility: Vanderbilt University Medical Center
state: Tennessee
Study officials:
affiliation: Vanderbilt University Medical Center
name: Nancy J Brown, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Gamboa JL, Devin JK, Ramirez CE, Yu C, Nian H, Lee RH, Brown NJ. Comparative effects of immediate-release and extended-release aspirin on basal and bradykinin-stimulated excretion of thromboxane and prostacyclin metabolites. Pharmacol Res Perspect. 2016 Feb 23;4(2):e00221. doi: 10.1002/prp2.221. eCollection 2016 Apr.