Comparative Effects of Aspirin and NHP-544C | NCT02189122

NCT02189122

Protocol Section

Identification Module

Results Section

Participant Flow Module

Annotation Section

No data available

No data is available for this block.

Document Section

No data available

No data is available for this block.

Derived Section

Miscellaneous Info Module

Status Module

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
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

Name	Type	Description	Arm Group Labels	Other Names
Bradykinin	Drug	Bradykinin will be given intravenously in graded doses. Each dose will be given for 15 minutes.	Group 1:Aspirin/placebo Group 2:NHP-544C/placebo

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

Eligibility Module

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

Name	Affiliation	Role
Nancy J Brown, MD	Vanderbilt University Medical Center	Principal Investigator

Facility	Status	City	State	ZIP	Country	Contacts
Vanderbilt University Medical Center		Nashville	Tennessee	37232	United States

PubMed Identifier	Type	Citation	Retractions
27069632	Result	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.

Arm/Group Information

ID	Title	Description
FG000	Group 1:Aspirin/Placebo	Group 1 will be randomized to receive rapid release aspirin (ASA, 81 mg), ASA 162.5 mg, or identical-appearing placebo for 5 days. Bradykinin will be given intravenously in graded doses on the fifth day of study. Bradykinin: Bradykinin will be given intravenously in graded doses. Each dose will be given for 15 minutes. Aspirin 81 mg: Subjects will take Aspirin 81 mg per day for five days. Aspirin 162 mg: Subjects will take aspirin 162 mg per day for 5 days. Placebo: Subjects will take matching placebo for five days. Three subjects participated in each possible sequence with the following exceptions: Four subjects participated in the sequence Aspirin 81 mg, Aspirin 162.5 mg, placebo; two subjects participated in the sequence placebo, Aspirin 162.5 mg, Aspirin 81 mg.
FG001	Group 2:NHP-544C/Placebo	Group 2 will be randomized to receive NHP-544C 81 mg, NPH-544C 162.5 mg or placebo. Bradykinin will be given intravenously in graded doses on the fifth day of study drug. Bradykinin: Bradykinin will be given intravenously in graded doses. Each dose will be given for 15 minutes. NHP544-C 81 mg: Subjects will take NHP544C 81 mg per day for five days. NHP544C 162 mg: Subjects will take NHP544C 162 mg once a day for five days. Placebo: Subjects will take matching placebo for five days. Three subjects participated in each possible sequence with the following exceptions: Four subjects participated in the sequence NHP544C 81 mg, NHP544C 162 mg, placebo; two subjects participated in the sequence NHP544C 162 mg, placebo, NHP544C 81 mg.

Baseline Characteristics Module

Arm/Group Information

ID	Title	Description
BG000	Group 1:Aspirin/Placebo	Group 1 will be randomized to receive rapid release aspirin (ASA, 81 mg), ASA 162.5 mg, or identical-appearing placebo for 5 days. Bradykinin will be given intravenously in graded doses on the fifth day of study. Bradykinin: Bradykinin will be given intravenously in graded doses. Each dose will be given for 15 minutes. Aspirin 81 mg: Subjects will take Aspirin 81 mg per day for five days. Aspirin 162 mg: Subjects will take aspirin 162 mg per day for 5 days. Placebo: Subjects will take matching placebo for five days.

Units	Counts
Participants	BG000

Title	Description	Population Description	Parameter Type	Dispersion Type	Unit of Measure	Calculate Percentage	Denominator Units Selected	Denominators	Classes
Age, Continuous			Mean

Outcome Measures Module

Outcome Measures

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Primary

Urine Thromboxane Concentrations at Placebo ASA or Placebo NHP-544C Dose

Posted

Median

Inter-Quartile Range

ng/mg creatinine

24 hour collection

ID	Title	Description
OG000	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. Bradykinin: Bradykinin will be given intravenously in graded doses. Each dose will be given for 15 minutes. Aspirin 81 mg: Subjects will take Aspirin 81 mg per day for five days. Aspirin 162 mg: Subjects will take aspirin 162 mg per day for 5 days. Placebo: Subjects will take matching placebo for five days.
OG001	Group 2:NHP-544C/Placebo

Adverse Events Module

Arm/Groups

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Group 1:Aspirin/Placebo	Group 1 will be randomized to receive rapid release aspirin (ASA, 81 mg), ASA 162.5 mg, or identical-appearing placebo for 5 days. Bradykinin will be given intravenously in graded doses on the fifth day of study. Bradykinin: Bradykinin will be given intravenously in graded doses. Each dose will be given for 15 minutes. Aspirin 81 mg: Subjects will take Aspirin 81 mg per day for five days. Aspirin 162 mg: Subjects will take aspirin 162 mg per day for 5 days. Placebo: Subjects will take matching placebo for five days.

Term	Organ System	Source Vocabulary	Assessment Type	Notes	Statistical Information
ST T wave changes following bradykinin infusion	Cardiac disorders		Systematic Assessment

Title	Organization	Phone	Extension	Email
Nancy J. Brown, M.D.	VANDERBILT UNIVERSITY MEDICAL CENTER	6153438701		nancy.j.brown@vanderbilt.edu

ID	Term
D001920	Bradykinin
D001241	Aspirin

ID	Term
D007705	Kinins
D036341	Intercellular Signaling Peptides and Proteins
D010455	Peptides
D000602	Amino Acids, Peptides, and Proteins

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.

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

NHP544-C 81 mg: Subjects will take NHP544C 81 mg per day for five days.

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

Placebo: Subjects will take matching placebo for five days.