Comparative Effects of Aspirin and NHP-544C

NCT ID: NCT02189122

Last Updated: 2016-07-12

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 61 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2014-07-31
• Study Completion Date: 2015-07-31

Brief Summary

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

Conditions

Healthy

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: BASIC_SCIENCE
• Blinding Strategy: DOUBLE

Study Groups

Group 1:Aspirin/placebo

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.

Group Type: ACTIVE_COMPARATOR

Bradykinin

Intervention Type: DRUG

Bradykinin will be given intravenously in graded doses. Each dose will be given for 15 minutes.

Aspirin 81 mg

Intervention Type: DRUG

Subjects will take Aspirin 81 mg per day for five days.

Aspirin 162 mg

Intervention Type: DRUG

Subjects will take aspirin 162 mg per day for 5 days.

Placebo

Intervention Type: DRUG

Subjects will take matching placebo for five days.

Group 2:NHP-544C/placebo

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.

Group Type: ACTIVE_COMPARATOR

Bradykinin

Intervention Type: DRUG

Bradykinin will be given intravenously in graded doses. Each dose will be given for 15 minutes.

NHP544-C 81 mg

Intervention Type: DRUG

Subjects will take NHP544C 81 mg per day for five days.

NHP544C 162 mg

Intervention Type: DRUG

Subjects will take NHP544C 162 mg once a day for five days.

Placebo

Intervention Type: DRUG

Subjects will take matching placebo for five days.

Interventions

Bradykinin

Bradykinin will be given intravenously in graded doses. Each dose will be given for 15 minutes.

Intervention Type: DRUG

Aspirin 81 mg

Subjects will take Aspirin 81 mg per day for five days.

Intervention Type: DRUG

Aspirin 162 mg

Subjects will take aspirin 162 mg per day for 5 days.

Intervention Type: DRUG

NHP544-C 81 mg

Subjects will take NHP544C 81 mg per day for five days.

Intervention Type: DRUG

NHP544C 162 mg

Subjects will take NHP544C 162 mg once a day for five days.

Intervention Type: DRUG

Placebo

Subjects will take matching placebo for five days.

Intervention Type: DRUG

Other Intervention Names

BK; ASA 81 mg; ASA 162 mg

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 55 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Vanderbilt University

OTHER

Sponsor Role: lead

Responsible Party

Nancy J. Brown

M.D.; Professor of Medicine and Pharmacology

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Nancy J Brown, MD

Role: PRINCIPAL_INVESTIGATOR

Vanderbilt University Medical Center

Locations

Vanderbilt University Medical Center

Nashville, Tennessee, United States

Countries

United States

References

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.

Reference Type: RESULT

PMID: 27069632 (View on PubMed)

Other Identifiers

140707

Identifier Type: -

Identifier Source: org_study_id