The Effect of Exercise on Pharmacodynamics and Pharmacokinetics of a Single Dose of Unfractionated Heparin

Study Overview
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Brief Summary
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The aim of this project is to assess the influence of exercise on pharmacokinetics (PK) and pharmacodynamics (PD) of a single dose of subcutaneously (sc) administered unfractionated heparin (UFH). It is hypothesized that exercise will increase the systemic exposure (PK) and therefore the clinical effects (PD) of the sc administered UFH. To assess this, healthy male volunteers will be included in a controlled, randomized, crossover study, where they, on four separate days, will have UFH injected sc in the thigh, followed by different exercise interventions (one per experimental day). Blood sampling, with the aim of assessing PK and PD will be performed during the following hours.

Official Title
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The Effect of Exercise on Pharmacodynamics and Pharmacokinetics of a Single Dose of Unfractionated Heparin: A Randomized, Controlled, Cross-over Study

Conditions
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Blood Coagulation Disorder

Intervention / Treatment
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* Drug: Unfractionated heparin
* Behavioral: Double-legged cycle ergometer exercise
* Behavioral: Single-legged cycle ergometer exercise, with unfractionated heparin injection in the exercising leg
* Behavioral: Single-legged cycle ergometer exercise, with unfractionated heparin injection in the non-exercising leg
* Behavioral: No exercise


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Body weight 50 kg or more Body Mass Index 18.5-25 kg/m2 Acceptance of not drinking alcohol for 24 hours before to 24 hours after dosing of study drug Acceptance of not performing physical activity for 24 hours before to 24 hours after dosing of study drug Signed informed consent form Exclusion Criteria: History or sign of bleeding disorders History or sign of kidney disease History or sign of liver disease Average systolic blood pressure <100 mmHg or >140 mmHg and/or average diastolic blood pressure <60 mmHg or >90 mmHg (average of three measurements performed at screening). Daily pharmaceutical treatment Contraindication to increased levels of physical activity (10) Smoking or other regular use of any form of nicotine products during the study period and the previous 3 months. Current or prior participation (within 3 months before screening) in other clinical trials that might affect the results of this study (judged by the investigator). Previous treatment with heparins Low levels of anti-thrombin (P-antitrombin(enz.) <0,80 kIU/L)

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 50 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: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Unfractionated heparin + No exercise<br>15,000 units of unfractionated heparin will be administered in the thigh. No exercise will be performed afterwards. | Drug: Unfractionated heparin<br>* 15,000 units of unfractionated heparin administered in the thigh<br>Behavioral: No exercise<br>* No exercise<br>|
| Experimental: Unfractionated heparin + Double-legged cycle ergometer exercise<br>15,000 units of unfractionated heparin will be administered in the thigh. Double-legged cycle ergometer exercise will be performed for 1 hour afterwards | Drug: Unfractionated heparin<br>* 15,000 units of unfractionated heparin administered in the thigh<br>Behavioral: Double-legged cycle ergometer exercise<br>* One hour of double-leg cycle ergometer exercise<br>|
| Experimental: Unfractionated heparin + Single-legged ipsilateral cycle ergometer exercise<br>15,000 units of unfractionated heparin will be administered in the thigh. Single-legged cycle ergometer exercise in leg where unfractionated heparin injection is given will be performed for 1 hour afterwards | Drug: Unfractionated heparin<br>* 15,000 units of unfractionated heparin administered in the thigh<br>Behavioral: Single-legged cycle ergometer exercise, with unfractionated heparin injection in the exercising leg<br>* One hour of single-leg cycle ergometer exercise, after unfractionated heparin injection in the ipsilateral leg<br>|
| Experimental: Unfractionated heparin + Single-legged contralateral cycle ergometer exercise<br>15,000 units of unfractionated heparin will be administered in the thigh. Single-legged cycle ergometer exercise in contralateral leg to where unfractionated heparin injection is given will be performed for 1 hour afterwards | Drug: Unfractionated heparin<br>* 15,000 units of unfractionated heparin administered in the thigh<br>Behavioral: Single-legged cycle ergometer exercise, with unfractionated heparin injection in the non-exercising leg<br>* One hour of single-leg cycle ergometer exercise, after unfractionated heparin injection in the ipsilateral leg<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Difference between interventions in change in incremental activated partial thromboplastin time (aPTT) |  | Peak aPTT for 1-8 hours after unfractionated heparin (UFH) injection | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Difference between interventions in change in incremental plasma heparin |  | Peak plasma heparin for 1-8 hours after UFH injection | 
| Difference between interventions in mean incremental aPTT |  | 1-8 hours after UFH injection | 
| Difference between interventions in mean incremental plasma heparin |  | 1-8 hours after UFH injection | 
| Difference between interventions in change in aPTT |  | 4 hours after UFH injection | 
| Difference between interventions in change in plasma heparin |  | 4 hours after UFH injection | 
| Difference between interventions in mean incremental natriuretic peptides |  | 1-8 hours after UFH injection | 
| Difference between interventions in mean incremental follistatin |  | 1-8 hours after UFH injection |