Comparative Effects of Aspirin and NHP-544C

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

Status

Completed

Phases

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT02189122

Enrollment

Registered

2014-07-14

Start date

2014-07-31

Completion date

2015-07-31

Last updated

2016-07-12

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Healthy

Brief summary

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

Interventions

DRUGBradykinin

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

DRUGAspirin 81 mg

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

DRUGAspirin 162 mg

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

DRUGNHP544-C 81 mg

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

DRUGNHP544C 162 mg

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

DRUGPlacebo

Subjects will take matching placebo for five days.

Study design

Allocation

RANDOMIZED

Intervention model

PARALLEL

Primary purpose

BASIC_SCIENCE

Masking

DOUBLE (Subject, Investigator)

Eligibility

Sex/Gender

ALL

Age

18 Years to 55 Years

Healthy volunteers

Yes

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

Design outcomes

Primary

Measure	Time frame
Urine Prostacyclin 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 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

Countries

United States

Participant flow

Pre-assignment details

Twenty-five enrolled participants were excluded prior to randomization to study group because they did not meet inclusion or exclusion criteria.

Participants by arm

Arm	Count
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.	18
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.	18
Total	36

Baseline characteristics

Characteristic	Group 1:Aspirin/Placebo	Total	Group 2:NHP-544C/Placebo
11-dehydrothromboxane B2	0.180 ng/mg creatinine	.206 ng/mg creatinine	.214 ng/mg creatinine
2,3-dinor-6-keto-PGF1alpha	.1 ng/mg creatinine	.121 ng/mg creatinine	.139 ng/mg creatinine
Age, Continuous	27.4 years	27.1 years	26.5 years
Ethnicity (NIH/OMB) Hispanic or Latino	3 Participants	4 Participants	1 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	15 Participants	32 Participants	17 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) Asian	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) Black or African American	0 Participants	3 Participants	3 Participants
Race (NIH/OMB) More than one race	0 Participants	1 Participants	1 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) White	18 Participants	32 Participants	14 Participants
Sex: Female, Male Female	8 Participants	21 Participants	13 Participants
Sex: Female, Male Male	10 Participants	15 Participants	5 Participants

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk
deaths Total, all-cause mortality	— / —	— / —
other Total, other adverse events	7 / 18	6 / 18
serious Total, serious adverse events	0 / 18	0 / 18