Clinical trial NCT05166096: Comparative Pharmacokinetic, Pharmacodynamic, and Safety Study of 1 Dose Level of Aspirin for Injection and Oral Aspirin Tablets in Healthy Adult Human Subjects
Official title: A Phase 1, Open-Label, 2-Period, 2-Formulation, Within-Subject Crossover Comparative Pharmacokinetic, Pharmacodynamic, and Safety Study of 1 Dose Level of Aspirin for Injection and Oral Aspirin Tablets in Healthy Adult Human Subjects Under Fasting Conditions
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy
Lead sponsor: Rhoshan Pharmaceuticals Inc
Sponsor class: INDUSTRY
First posted: 2021-12-21
Enrollment: 24
Sex: ALL
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: BASIC_SCIENCE

Brief summary: The purpose of this study is to compare the safety, pharmacokinetics, and pharmacodynamic effects of aspirin administered intravenously with aspirin administered orally.


Eligibility criteria: Inclusion Criteria:

Each subject must meet all of the following criteria to be enrolled in this study:

1. The subject is male or female 18 to 55 years of age, inclusive
2. The subjects has a body mass index (BMI) 18 to 30 kg/m2, inclusive, at screening.
3. The subject is considered by the investigator to be in good general health as determined by medical history, clinical laboratory test results, vital sign measurements, 12-lead ECG results, and physical examination findings at screening.
4. The subject has a hemoglobin level within following acceptable range at Screening and Check-in: Male: 12.8 to 17.4 g/dL, Female: 10.8 to 15.0 g/dL
5. The subject has liver function tests within normal limits, or has results that do not show clinically significant abnormalities, as judged by the investigator at Screening and Check in.
6. The subject has estimated glomerular filtration rate (eGFR) ≥ 50 mL/min at Screening.
7. Female subjects of childbearing potential must use an acceptable method of birth control (i.e., diaphragm with spermicide, intrauterine device, condom with foam or vaginal spermicide, oral contraceptives, or abstinence) or be surgically sterile (i.e., hysterectomy, bilateral tubal ligation or bilateral oophorectomy), or postmenopausal (defined as amenorrhea 12 consecutive months and documented plasma FSH level \>40 IU/mL). Female subjects must have a negative pregnancy test at screening and before dosing with study drug.

   Male subjects with female partners of childbearing potential must be vasectomized, be willing to use an acceptable method of birth control, or to practice abstinence during the study.
8. The subject agrees to comply with all protocol requirements.
9. The subject is able to provide written informed consent.

Exclusion Criteria:

Subjects meeting any of the following criteria will be excluded from the study:

1. The subjects has had any major illness within 3 months before dosing with study drug or any significant ongoing chronic medical illness, as judged by the investigator.
2. The subjects has a history of active deep vein thrombosis and/or thromboembolic disorder, including history of hypothrombinemia and vitamin K deficiency.
3. The subject has a history of neuropsychiatric disease, hypertension, cardiac failure, cerebrovascular disease, chronic respiratory disease, asthma, nasal polyps associated with asthma, hepatic or renal impairment, recent dehydration (within last 30 days), gout thyrotoxicosis or systemic lupus erythematosus and other connective tissue disorders.
4. The subject has a history of gastrointestinal bleeding or has active gastrointestinal disease that could affect drug absorption.
5. The subject has a history of hemorrhagic disorder.
6. Prothrombin time or activated partial thromboplastin time level outside the normal range at screening and check-in.
7. The subject has an increased risk of bleeding including but not limited to: any history of a clinically significant bleeding problem, any recent (within 30 days preceding the first dose of study drug) major trauma, platelet count \<100,000 mm3
8. The subject has a history of glucose-6-phosphate dehydrogenase deficiency.
9. The subject has a recent history of tooth extraction within 3 weeks before dosing with study drug.
10. The subject is a smoker or has used nicotine-containing products (e.g., snuff, nicotine patch, nicotine chewing gum, mock cigarettes, inhalers, or "vape" devices) within 6 months before the first dose of study drug and throughout the study (including the washout period).
11. The subject has a history of alcohol abuse or drug addiction within 1 year prior to check-in or excessive alcohol consumption (regular alcohol intake \>21 units per week for male subjects and \>14 units of alcohol per week for female subjects), or use of alcohol 48 hours before dosing with study drug.
12. The subject has a positive test result for drugs of abuse, alcohol, or cotinine at screening or before dosing with study drug.
13. The subject has used any prescription (excluding hormonal birth control) or over-the-counter medications, including fish oil and other herbal or nutritional supplements and, in particular, aspirin (no aspirin-containing medications allowed at all), nonsteroidal anti-inflammatory agents (No NSAIDS allowed at all, and no acetaminophen, diclofenac, ketorolac allowed), or anticoagulation therapy within 14 days before dosing with study drug and throughout the entire study period (including the washout period).
14. The subject has received vaccination against Varicella zoster within 6 weeks before dosing with study drug.
15. The subject has a positive test result for COVID-19, hepatitis B surface antigen, hepatitis C virus antibody, or HIV type 1 or 2 antibodies at screening.
16. The subject has received the COVID-19 vaccine within 14 days before Day -3, or subjects who plan to receive a COVID-19 vaccine at any time during the study.
17. The subject has a history of relevant drug and/or food allergies (i.e., allergy to aspirin or any excipients, allergic skin reactions, or any significant food allergy that could preclude a standard diet in the clinical unit).
18. The subject has consumed grapefruit or grapefruit juice, Seville orange or Seville orange-containing products (e.g. marmalade), or alcohol-, caffeine-, poppy-, or xanthine-containing products within 48 hours.
19. The subject is involved in strenuous activity or contact sports within 24 hours before dosing with study drug and during the study.
20. The subject has donated blood or blood products \>450 mL within 30 days before dosing with study drug.
21. The subject has received study drug in another investigational study within 30 days or 5 half-lives, whichever is longer, before dosing with study drug.
22. In the opinion of the investigator, the subject is not suitable for entry into the study.

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Primary outcomes:
measure: Change in serum thromboxane B2 from baseline
timeFrame: 1 hour before dosing and 2, 5, 10, 20, 30,45, 60, and 180 minutes post dosing
Secondary outcomes:
measure: Urinary 11-dehydro-TXB2 levels
timeFrame: Every 12 hours from 72 hours prior to dosing to 72 hours after dosing.
measure: Urinary 2,3-dinor-6-keto-PGF1alpha
timeFrame: Every 12 hours from 72 hours prior to dosing to 72 hours after dosing.
measure: Acetylsalicylic Acid Plasma Pharmacokinetics
timeFrame: 1 hour prior to dosing, and 1,3,5,10,15,20,30, and 45 minutes and 1,1.5,2,3,6,8, and 24 hours post-dosing.
measure: Salicylic Acid Plasma Pharmacokinetics
timeFrame: 1 hour prior to dosing, and 1,3,5,10,15,20,30, and 45 minutes and 1,1.5,2,3,6,8, and 24 hours post-dosing.
Other outcomes:
Locations:
city: Austin
country: United States
facility: PPD Early Development
state: Texas
Study officials:
References: