A Study to Assess Disintegration of the New Aspirin Disintegrating Tablets

Study Overview
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Brief Summary
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The aim of this study is to assess disintegration of the new Aspirin disintegrating tablets

Official Title
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An Open Label, Randomized, Four-Way Crossover Trial to Assess the Disintegration, Gastric Emptying and Pharmacokinetic Parameters of a New Disintegrating Acetylsalicylic Acid 500 mg, 1000 mg Tablet Formulation and 2 Different Ibuprofen Tablets in Fasted Healthy Male Subjects

Conditions
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Moderate Pain

Intervention / Treatment
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* Drug: 500 mg acetylsalicylic acid (Aspirin, BAYE4465)
* Drug: 1000 mg acetylsalicylic acid (Aspirin, BAYE4465)
* Drug: 400 mg ibuprofen(Nurofen)
* Drug: 400 mg ibuprofen (Dolormin Extra)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy male volunteers aged 18 to 65 years included Verified diagnosis of healthy Non-smokers or passive smokers BMI in the range of 18.5 to 30 kg/m2 Subject has given written informed consent to participate in the trial prior to admission to the trial Exclusion Criteria: Blood donation within the last 90 days prior to planned randomization Any previous medication within 10 days before the planned administration of the radiolabelled Investigational Medicinal Product (rIMP) which, in the opinion of the physician responsible, will interfere with the study procedures or compromise safety Subject has any non-removable metal objects such as metal plates, screws etc. in their chest or abdominal area which, in the opinion of the physician responsible, could affect the study conduct. Vegetarian Subjects for whom participation in this study will exceed the limits of total radiation exposure allowed in any 12 month period (5 Millisievert), or will exceed 10 Millisievert over any three year period

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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Male

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: Other
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Sequence 1: starting with BAYE4465 500 mg<br>Participants will participant four treatment periods with four different treatments. Treatment assignment adhere to Williams design | Drug: 500 mg acetylsalicylic acid (Aspirin, BAYE4465)<br>* Single intake of 1 tablet, 500mg<br>Drug: 1000 mg acetylsalicylic acid (Aspirin, BAYE4465)<br>* Single intake of 1 tablet, 1000mg<br>Drug: 400 mg ibuprofen(Nurofen)<br>* Single intake of 1 tablet, 400mg<br>Drug: 400 mg ibuprofen (Dolormin Extra)<br>* Single intake of 1 tablet, 400mg<br>|
| Experimental: Sequence 2: starting with BAYE4465 1000 mg<br>Participants will participant four treatment periods with four different treatments. Treatment assignment adhere to Williams design | Drug: 500 mg acetylsalicylic acid (Aspirin, BAYE4465)<br>* Single intake of 1 tablet, 500mg<br>Drug: 1000 mg acetylsalicylic acid (Aspirin, BAYE4465)<br>* Single intake of 1 tablet, 1000mg<br>Drug: 400 mg ibuprofen(Nurofen)<br>* Single intake of 1 tablet, 400mg<br>Drug: 400 mg ibuprofen (Dolormin Extra)<br>* Single intake of 1 tablet, 400mg<br>|
| Experimental: Sequence 3: starting with Nurofen<br>Participants will participant four treatment periods with four different treatments. Treatment assignment adhere to Williams design | Drug: 500 mg acetylsalicylic acid (Aspirin, BAYE4465)<br>* Single intake of 1 tablet, 500mg<br>Drug: 1000 mg acetylsalicylic acid (Aspirin, BAYE4465)<br>* Single intake of 1 tablet, 1000mg<br>Drug: 400 mg ibuprofen(Nurofen)<br>* Single intake of 1 tablet, 400mg<br>Drug: 400 mg ibuprofen (Dolormin Extra)<br>* Single intake of 1 tablet, 400mg<br>|
| Experimental: Sequence 4: starting with Dolormin Extra<br>Participants will participant four treatment periods with four different treatments. Treatment assignment adhere to Williams design | Drug: 500 mg acetylsalicylic acid (Aspirin, BAYE4465)<br>* Single intake of 1 tablet, 500mg<br>Drug: 1000 mg acetylsalicylic acid (Aspirin, BAYE4465)<br>* Single intake of 1 tablet, 1000mg<br>Drug: 400 mg ibuprofen(Nurofen)<br>* Single intake of 1 tablet, 400mg<br>Drug: 400 mg ibuprofen (Dolormin Extra)<br>* Single intake of 1 tablet, 400mg<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to complete tablet disintegration | The tablet is radiolabeled. Scintigraphy images of the abdominal area will be taken It is time until an image with no definable hot spot remaining is identified | Up to 4 hours | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Gastric empty time, if applicable | Gastric emptying time will be calculated by a qualified assessor based on the scintigraphy images | Up to 4 hours | 
| Time of colon arrival, if applicable | Time of colon arrival will be calculated by a qualified assessor based on the scintigraphy images | Up to 4 hours | 
| Small intestine transit time, if applicable | Small intestine transit time will be calculated by a qualified assessor based on the scintigraphy images | Up to 4 hours | 
| Time of onset of release of radiolabel | Time of onset of release of radiolabel will be calculated by a qualified assessor based on the scintigraphy images | Up to 4 hours | 
| Site of onset of release of radiolabel | Site of onset of release of radiolabel will be determined by a qualified assessor based on the scintigraphy images | Up to 4 hours | 
| Site of completion of release of radiolabel | Site of completion of release of radiolabel will be determined by a qualified assessor based on the scintigraphy images | Up to 4 hours | 
| Disintegration rate of the tablet estimated from the radioactivity remaining | Disintegration rate of the tablet estimated from the radioactivity rem will be calculated by a qualified assessor based on the scintigraphy images | Up to 4 hours | 
| Time of 50% disintegration of the tablet estimated from the radioactivity remaining | Time of 50% disintegration of the tablet estimated from the radioactivity remaining will be calculated by a qualified assessor based on the scintigraphy images | Up to 4 hours | 
| Gastric emptying kinetics of dispersed radioactive material (t50% and t90%) | Gastric emptying kinetics of dispersed radioactive material (t50% and t90%) will be calculated by a qualified assessor based on the scintigraphy images | Up to 4 hours | 
| AUC0-t | Area under the plasma concentration vs time curve from zero to the last data point | Prior to dosing (between 60-15 min), and 5, 9, 13, 18, 23, 28, 33, 38, 48, 58, 68, 78, 88, 118, 178 and 238 min post-dose | 
| Cmax | Maximum drug concentration in plasma after single dose administration | Prior to dosing (between 60-15 min), and 5, 9, 13, 18, 23, 28, 33, 38, 48, 58, 68, 78, 88, 118, 178 and 238 min post-dose | 
| AUC0-infinity | Area under the plasma concentration vs time curve from zero to infinity | Prior to dosing (between 60-15 min), and 5, 9, 13, 18, 23, 28, 33, 38, 48, 58, 68, 78, 88, 118, 178 and 238 min post-dose | 
| t1/2 | Half-life associated with the terminal slope | Prior to dosing (between 60-15 min), and 5, 9, 13, 18, 23, 28, 33, 38, 48, 58, 68, 78, 88, 118, 178 and 238 min post-dose | 
| tmax | Time to reach maximum drug concentration in the measured | Prior to dosing (between 60-15 min), and 5, 9, 13, 18, 23, 28, 33, 38, 48, 58, 68, 78, 88, 118, 178 and 238 min post-dose | 
| Cmax/AUC0-infinity |  | Prior to dosing (between 60-15 min), and 5, 9, 13, 18, 23, 28, 33, 38, 48, 58, 68, 78, 88, 118, 178 and 238 min post-dose |