A Study of the Pharmacokinetic and Pharmacodynamic Responses in Healthy and Altered Human Cardiovascular Systems

• Status: Terminated
• Trial end date: 2020-02-29
• Target enrollment: 0
• Participant gender: Male

Summary

Unwanted effects on the cardiovascular system is one of the most common causes of safety related discontinuation of a drug. This study aims to develop an in silico model of the human cardiovascular system that can be used to predict unwanted cardiovascular effects of drugs. This will be achieved through a drug administration study that will generate comprehensive pharmacokinetic and pharmacodynamic data following the administration of the following drugs, all known to have effects on the cardiovascular system. Half the participants will receive: Placebo, Salbutamol, Nicardipine, Dobutamine and the other half will receive Placebo, Phenylephrine, Verapamil, Phentolamine.

• Phase: Phase 1
• Accepts Healthy Volunteers?: Accepts Healthy Volunteers

Details

• Lead Sponsor: Cambridge University Hospitals NHS Foundation Trust
• Collaborators: AstraZeneca; University of Cambridge
• Treatments: Albuterol; Dobutamine; Nicardipine; Oxymetazoline; Phentolamine; Phenylephrine; Verapamil

Criteria

Part A Inclusion Criteria

To be included in the study the patient must:

• Have given written informed consent to participate

• Male

• Be aged between 18 and 30 years at the time of first study appointment

• BMI <30

• Deemed healthy to partake in the study at the discretion of the investigator

Exclusion Criteria

The presence of any of the following will preclude patient inclusion:

• Less than 18 years old, >30 years old

• BMI >30

• On regular medications

• Known allergy to medications

• History of psychiatric, chronic cardiac / respiratory / renal disease

• Known diagnosis of diabetes

• Habitual smoker

• Screening heart rate of less than 60 beats per minute

• Screening heart rate of greater than 100 beats per minute

• Screening blood pressure of less than 100mmHg systolic and/or 55mmHg diastolic

• Any concomitant condition or circumstance that, at the discretion of the investigator, may affect the participant's ability to complete the study

• Current participation in another interventional research study

Part B Inclusion Criteria

To be included in the study the patient must:

• Have given written informed consent to participate

• Male

• Be aged over 18 years at the time of first study appointment

• Possess one of the following - known diagnosis of diabetes, known diagnosis of hypertension, obesity (BMI>30), aged >65

• Deemed healthy to partake in the study at the discretion of the investigator

Exclusion Criteria

The presence of any of the following will preclude patient inclusion:

• Less than 18 years old

• On regular medications that are contraindicated for co-use with the study drugs

• Known allergy to medications

• Screening heart rate of less than 60 beats per minute

• Screening heart rate of greater than 100 beats per minute

• Screening blood pressure of less than 100mmHg systolic and/or 55mmHg diastolic

• Any concomitant condition or circumstance that, at the discretion of the investigator, may affect the participant's ability to complete the study

• Current participation in another interventional research study

Part C Inclusion Criteria

To be included in the study the patient must:

• Have given written informed consent to participate

• Male

• Be aged over 18 years at the time of first study appointment

• Clinical diagnosis of autonomic dysfunction

• BMI<30

• Deemed healthy to partake in the study at the discretion of the investigator

Exclusion Criteria

The presence of any of the following will preclude patient inclusion:

• Less than 18 years old

• BMI >30

• On regular medication

• Known allergy to medications

• History of psychiatric, chronic cardiac / respiratory / renal disease

• Habitual smoker

• Screening heart rate of less than 60 beats per minute

• Screening heart rate of greater than 100 beats per minute

• Screening blood pressure of less than 100mmHg systolic and/or 55mmHg diastolic

• Any concomitant condition or circumstance that, at the discretion of the investigator, may affect the participant's ability to complete the study

• Current participation in another interventional research study