Naproxen Sodium/ASA Platelet Study

Study Overview
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Brief Summary
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To determine if administration of naproxen sodium 220 mg maintains the platelet inhibitory effect of a low dose Immediate Release Aspirin (IR ASA) regimen.

Official Title
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A Randomized, Open Label, Parallel Group Study to Investigate the Effects on Serum Thromboxane by the Addition of Naproxen Sodium to Aspirin Therapy Versus Aspirin Therapy Alone

Conditions
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Hematology

Intervention / Treatment
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* Drug: Naproxen Sodium (Aleve, BAY117031)
* Drug: Acetylsalicylic Acid (Aspirin, BAYE4465)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy, ambulatory, male and female volunteers between 18 - 70 years of age with a Body Mass Index (BMI) of approximately 18 to 30 kg/m2, and a total body weight > 50 kg (110 lbs) Female subjects of childbearing potential must be using a medically acceptable form of birth control for at least 1 month prior to screening (3 months on oral contraceptives), e.g., oral or patch contraceptives, intrauterine device, Depo-Provera®, or a double barrier and have a negative pregnancy test at Screening and immediately prior to investigational product administration on Day 1 and Day 6. Female subjects of non-childbearing potential must be amenorrheic for at least 2 years or had a hysterectomy and/or bilateral oophorectomy Results of screening and clinical laboratory tests are within normal range or considered not clinically significant by the Principal Investigator and the Sponsor Be willing and able to participate in all scheduled visits, treatment plan, laboratory tests and other trial procedures according to the protocol Provide a personally signed and dated informed consent indicating that the subject has been informed of all pertinent aspects of the trial. Exclusion Criteria: History of hypersensitivity or asthma type symptoms with use of aspirin, naproxen sodium and similar pharmacological agents or components of the products Females who are pregnant or lactating Any disorder of the Aspirin Triad Syndrome (i.e., asthma, rhinitis or nasal polyps), or have chronic urticaria Eighteen to twenty years old with a viral infection, with or without fever within one month prior to start of Run-in Period History of gastrointestinal bleeding or perforation, related to previous NSAID therapy. Active, or history of recurrent peptic ulcer/hemorrhage (two or more distinct episodes of proven ulceration or bleeding) Evidence or history of clinically significant hematological, renal, endocrine, pulmonary, gastrointestinal, cardiovascular, hepatic, psychiatric, neurologic, infectious diseases or malignancies Any abnormal laboratory value or physical finding that according to the Investigator that may interfere with the interpretation of the study results or be indicative of an underlying disease state Have taken any medications including NSAIDs (except acceptable forms of birth control) within 7 days prior to the start of the Run-in Period or throughout the study, unless in the opinion of the Investigator and the Sponsor, the medication will not interfere with the study procedures, data integrity, data interpretation or compromise the safety of the subject Have taken antiplatelet or anticoagulant drugs within 30 days prior to start of the Run-in Period or during their participation in the study Have donated blood or blood components within 30 days prior to study entry

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: IR ASA co-administered with naproxen sodium<br>Confirmed eligible participants were randomized to be administered immediate release acetylsalicylic acid (IR ASA, Aspirin, BAYE4465) 81 mg once daily (qd) in parallel with naproxen sodium (Aleve, BAY117031) 220 mg qd for 10 consecutive days. A 3-day IR ASA 81 mg qd Run-Out period was followed. | Drug: Naproxen Sodium (Aleve, BAY117031)<br>* Naproxen sodium 220 mg qd or bid<br>Drug: Acetylsalicylic Acid (Aspirin, BAYE4465)<br>* ASA 81 mg qd<br>|
| Experimental: IR ASA 30 min after naproxen sodium<br>Confirmed eligible participants were randomized to be administered immediate release acetylsalicylic acid (IR ASA, Aspirin, BAYE4465) 81 mg qd 30 minutes after naproxen sodium (Aleve, BAY117031) 220 mg qd for 10 consecutive days. A 3-day IR ASA 81 mg qd Run-Out period was followed. | Drug: Naproxen Sodium (Aleve, BAY117031)<br>* Naproxen sodium 220 mg qd or bid<br>Drug: Acetylsalicylic Acid (Aspirin, BAYE4465)<br>* ASA 81 mg qd<br>|
| Experimental: IR ASA 8 hours after naproxen sodium<br>Confirmed eligible participants were randomized to be administered immediate release acetylsalicylic acid (IR ASA, Aspirin, BAYE4465) 81 mg qd 8 hours after naproxen sodium (Aleve, BAY117031) 220 mg qd for 10 consecutive days. A 3-day IR ASA 81 mg qd Run-Out period was followed. | Drug: Naproxen Sodium (Aleve, BAY117031)<br>* Naproxen sodium 220 mg qd or bid<br>Drug: Acetylsalicylic Acid (Aspirin, BAYE4465)<br>* ASA 81 mg qd<br>|
| Active Comparator: IR ASA only<br>Confirmed eligible participants were randomized to be administered immediate release acetylsalicylic acid (IR ASA, Aspirin, BAYE4465) 81 mg qd. A 3-day IR ASA 81 mg qd Run-Out period was followed. | Drug: Acetylsalicylic Acid (Aspirin, BAYE4465)<br>* ASA 81 mg qd<br>|
| Experimental: IR ASA 30 min before naproxen sodium<br>Confirmed eligible participants were randomized to be administered immediate release acetylsalicylic acid (IR ASA, Aspirin, BAYE4465) 81 mg qd 30 minutes before naproxen sodium (Aleve, BAY117031) 220 mg qd for 10 consecutive days. A 3-day IR ASA 81 mg qd Run-Out period was followed. | Drug: Naproxen Sodium (Aleve, BAY117031)<br>* Naproxen sodium 220 mg qd or bid<br>Drug: Acetylsalicylic Acid (Aspirin, BAYE4465)<br>* ASA 81 mg qd<br>|
| Experimental: IR ASA 30 min after first dose of naproxen sodium bid<br>Confirmed eligible participants were randomized to be administered immediate release acetylsalicylic acid (IR ASA, Aspirin, BAYE4465) 81 mg qd 30 minutes after first dose of naproxen sodium (Aleve, BAY117031) 220 mg, followed by second dose of naproxen sodium 220 mg 12 hours after first dose, for 10 consecutive days. A 3-day IR ASA 81 mg qd Run-Out period was followed. | Drug: Naproxen Sodium (Aleve, BAY117031)<br>* Naproxen sodium 220 mg qd or bid<br>Drug: Acetylsalicylic Acid (Aspirin, BAYE4465)<br>* ASA 81 mg qd<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Inhibition of Serum Thromboxane B2 (TXB2) on Day 16 at 24 Hour Post IR ASA 81 mg Administration | Inhibition of serum TXB2 at specified time point was calculated using the percentage of reduction from baseline as follows: Inhibition (%) = 100 × (Baseline Value - Post-baseline Value) / Baseline Value. For primary analysis, the mean and the lower bound of the corresponding one-sided 95% Confidence Interval (CI) were calculated. | At hour 24 on Day 16 post treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Inhibition of Serum TXB2 on Days 7, 16, 17, and 19 of the In-house Treatment Period at 1, 3, 6, 12, 18, and 24 Hours (Except at 24 Hours on Day 16) Post IR ASA 81 mg Administration | Inhibition of serum TXB2 at each time point were calculated using the percentage of reduction from baseline as follows: Inhibition (%) = 100 × (Baseline Value - Post-baseline Value) / Baseline Value. For primary analysis, the mean and the lower bound of the corresponding one-sided 95% CI were calculated. | At 1, 3, 6, 12, 18, and 24 hours on Days 7, 16, 17, and 19 (except 24 hours on Day 16) | 
| Inhibition of Arachidonic Acid (AA)-Induced Platelet Aggregation on Days 7, 16, 17, and 19 at 1, 3, 6, 12, 18, and 24 Hours Post IR ASA 81 mg Administration | Inhibition of AA-induced platelet aggregation at each time point were calculated using the percentage of reduction from baseline as follows: Inhibition (%) = 100 × (Baseline Value - Post-baseline Value) / Baseline Value. For primary analysis, the mean and the lower bound of the corresponding one-sided 95% CI were calculated. The platelet aggregation change-from-baseline scores range broadly in large part due to inclusion of participants with low baseline platelet aggregation scores. | At 1, 3, 6, 12, 18, and 24 hours on Days 7, 16, 17, and 19 | 
| Inhibition of TXB2 Using Platelet-rich Plasma (PRP) on Days 7, 16, 17, and 19 of the In-house Treatment Period at 1, 3, 6, 12, 18, and 24 Hours Post IR ASA 81 mg Administration | Inhibition of plasma TXB2 at each time point were calculated using the percentage of reduction from baseline as follows: Inhibition (%) = 100 × (Baseline Value - Post-baseline Value) / Baseline Value. For primary analysis, the mean and the lower bound of the corresponding one-sided 95% CI were calculated. | At 1, 3, 6, 12, 18, and 24 hours on Days 7, 16, 17, and 19 |