Comparative Effects of Aspirin and NHP-544C

NCT02189122 | Completed Results DMC

• 1 other identifier: 140707
• Study Type: interventional
• Target: 61
• Locations: 1 country
• Sites: 1

Brief Summary

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

Conditions

Healthy

Outcome Measures

Primary Outcomes (6)

• 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

Study Arms (2)

Group 1:Aspirin/placebo

ACTIVE COMPARATOR

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; Drug: Aspirin 81 mg; Drug: Aspirin 162 mg; Drug: Placebo

Group 2:NHP-544C/placebo

ACTIVE COMPARATOR

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; Drug: NHP544-C 81 mg; Drug: NHP544C 162 mg; Drug: Placebo

Interventions

Bradykinin DRUG

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

Also known as: BK

Group 1:Aspirin/placebo; Group 2:NHP-544C/placebo

Aspirin 81 mg DRUG

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

Also known as: ASA 81 mg

Group 1:Aspirin/placebo

Aspirin 162 mg DRUG

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

Also known as: ASA 162 mg

Group 1:Aspirin/placebo

NHP544-C 81 mg DRUG

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

Group 2:NHP-544C/placebo

NHP544C 162 mg DRUG

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

Group 2:NHP-544C/placebo

Placebo DRUG

Subjects will take matching placebo for five days.

Group 1:Aspirin/placebo; Group 2:NHP-544C/placebo

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Vanderbilt University: lead

Study Sites (1)

Vanderbilt University Medical Center

Nashville, Tennessee, 37232, United States

Location

Related Publications (1)

• 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.

  PMID: 27069632 RESULT

MeSH Terms

Interventions

Bradykinin; Aspirin

Intervention Hierarchy (Ancestors)

Kinins; Intercellular Signaling Peptides and Proteins; Peptides; Amino Acids, Peptides, and Proteins; Neuropeptides; Oligopeptides; Proteins; Nerve Tissue Proteins; Autacoids; Inflammation Mediators; Biological Factors; Salicylates; Hydroxybenzoates; Phenols; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals

Results Point of Contact

• Title: Nancy J. Brown, M.D.
• Organization: VANDERBILT UNIVERSITY MEDICAL CENTER

nancy.j.brown@vanderbilt.edu

6153438701

Study Officials

• Nancy J Brown, MD

  Vanderbilt University Medical Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: M.D.; Professor of Medicine and Pharmacology

Study Record Dates

• First Submitted: July 10, 2014
• First Posted: July 14, 2014
• Study Start: July 1, 2014
• Primary Completion: July 1, 2015
• Study Completion: July 1, 2015
• Last Updated: July 12, 2016
• Results First Posted: June 3, 2016

Record last verified: 2016-06

Locations

US (1)