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

NCT06174961 | Completed Phase 4

• 1 other identifier: 2023-000150-20
• Study Type: interventional
• Target: 23
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Blood Coagulation Disorder

Outcome Measures

Primary Outcomes (1)

• Difference between interventions in change in incremental activated partial thromboplastin time (aPTT)

  Peak aPTT for 1-8 hours after unfractionated heparin (UFH) injection

Secondary Outcomes (7)

• 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

Study Arms (4)

Unfractionated heparin + No exercise

EXPERIMENTAL

15,000 units of unfractionated heparin will be administered in the thigh. No exercise will be performed afterwards.

Drug: Unfractionated heparin; Behavioral: No exercise

Unfractionated heparin + Double-legged cycle ergometer exercise

EXPERIMENTAL

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; Behavioral: Double-legged cycle ergometer exercise

Unfractionated heparin + Single-legged ipsilateral cycle ergometer exercise

EXPERIMENTAL

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; Behavioral: Single-legged cycle ergometer exercise, with unfractionated heparin injection in the exercising leg

Unfractionated heparin + Single-legged contralateral cycle ergometer exercise

EXPERIMENTAL

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; Behavioral: Single-legged cycle ergometer exercise, with unfractionated heparin injection in the non-exercising leg

Interventions

Unfractionated heparin DRUG

15,000 units of unfractionated heparin administered in the thigh

Unfractionated heparin + Double-legged cycle ergometer exercise; Unfractionated heparin + No exercise; Unfractionated heparin + Single-legged contralateral cycle ergometer exercise; Unfractionated heparin + Single-legged ipsilateral cycle ergometer exercise

Double-legged cycle ergometer exercise BEHAVIORAL

One hour of double-leg cycle ergometer exercise

Unfractionated heparin + Double-legged cycle ergometer exercise

Single-legged cycle ergometer exercise, with unfractionated heparin injection in the exercising leg BEHAVIORAL

One hour of single-leg cycle ergometer exercise, after unfractionated heparin injection in the ipsilateral leg

Unfractionated heparin + Single-legged ipsilateral cycle ergometer exercise

Single-legged cycle ergometer exercise, with unfractionated heparin injection in the non-exercising leg BEHAVIORAL

One hour of single-leg cycle ergometer exercise, after unfractionated heparin injection in the ipsilateral leg

Unfractionated heparin + Single-legged contralateral cycle ergometer exercise

No exercise BEHAVIORAL

No exercise

Unfractionated heparin + No exercise

Eligibility Criteria

• Age: 18 Years - 50 Years
• Sex: male
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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)

Sponsors & Collaborators

• Kristian Karstoft: lead

Study Sites (1)

Bispebjerg-Frederiksberg Hospital, Department of Clinical Pharmacology

Copenhagen, 2400, Denmark

Location

MeSH Terms

Conditions

Blood Coagulation Disorders

Interventions

Heparin

Condition Hierarchy (Ancestors)

Hematologic Diseases; Hemic and Lymphatic Diseases

Intervention Hierarchy (Ancestors)

Glycosaminoglycans; Polysaccharides; Carbohydrates

Study Officials

• Kristian Karstoft, MD, DMSc

  Bispebjerg-Frederiksberg Hospital, Department of Clinical Pharmacology

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Chief Physician, Principal Investigator, MD, PhD, DMSc

Study Record Dates

• First Submitted: December 8, 2023
• First Posted: December 18, 2023
• Study Start: September 22, 2023
• Primary Completion: February 13, 2024
• Study Completion: May 1, 2024
• Last Updated: June 26, 2024

Record last verified: 2024-06

Locations

DK (1)