An Explorative Study on the Pharmacokinetics and Pharmacodynamics of Sunitinib in Healthy Volunteers

University of Cologne

Status and phase

Completed

Phase 1

Conditions

Blood Pressure

Treatments

Drug: sunitinib (Sutent)

Study type

Interventional

Funder types

Other

Identifiers

NCT00904657

Uni-Koeln-1127

Details and patient eligibility

About

The study is conducted:

to investigate the influence of sunitinib (study drug) on the plasma biomarkers VEGF-A, VEGF-C, soluble VEGFR-2, and soluble VEGFR-3 (vessel endothelial growth factors) and on the blood pressure;
to generate a pharmacokinetic/pharmacodynamic model for sunitinib using biomarkers.

Enrollment

12 patients

Sex

All

Ages

18 to 55 years old

Volunteers

Accepts Healthy Volunteers

Inclusion criteria

Caucasian
Male/Female
Age: 18-55 years
Body weight of 60 kg or higher, Body Mass Index 19 - 27 kg/m2
Considered to be healthy on the basis of extensive pre-study screening
Willing and capable to confirm written consent to enrolment after ample information has been provided

Exclusion criteria

Ongoing healing of wound or parenchymal tissue requiring angiogenesis
Any skin abnormality and/or neurodermatitis and /or chronic skin disease
A history of haemorrhage
A history of any gastrointestinal event with persisting clinical relevance
A history of pancreatitis
History of cerebrovascular accident or transient ischemic attack or seizures
History of pulmonary embolism
History of venous thromboembolic events
History of hypertension
A history of cardiac events within 12 months prior to sunitinib administration such as myocardial infarction (including severe/unstable angina), coronary/peripheral artery bypass graft
Any relevant clinical abnormality (as based on extensive medical history, amination, vital signs and 12-lead ECG)
Inadequate cardiac function [left ventricular ejection fraction (LVEF) < lower limit of normal (LLN) as assessed by echocardiography (ECHO)]
A history of any surgical abdominal intervention (including appendectomy) or of peritonitis
Bronchial asthma, COPD, or actual obstructive bronchitis
Hypothyroidism /hyperthyroidism
Cardiac insufficiency
Liver disease
Cardiac dysrhythmia (e.g., prolongation of the QT interval)
Diabetes mellitus
Chronic infections
Relevant acute infections or with actual therapy-requiring allergies (including drug allergies) within the last two weeks
Suspicion of hypersensitivity to sunitinib or to any of the excipients
Any clinically relevant laboratory abnormality
Subjects receiving any medication within 2 weeks prior to study start or during the study (exceptions possible upon decision of Principal Investigator, e.g., paracetamol (acetaminophen) single dose for acute pain or topical aciclovir for herpes simplex)
Subjects who have taken a drug with a long half-life (> 24 hours) within four weeks before the first trial day
Subjects who received chronic drug treatment (> 3 days) within eight weeks before the first trial day
Subjects who participated in a clinical trial within the last 3 months before the start of the present study
Subjects who donated blood or plasma within the last 12 weeks before the start of the present study
Subjects who smoke, i.e., subjects who smoked one or more cigarettes during the last six months
Subjects who are known or suspected to be (social) drug dependent, incl. those drinking more than 30 g alcohol per day
Subjects with a history of alcohol or recreational drug addiction
Subjects with a history of any severe disease that might interfere with the study objectives (e.g. psychiatric disease, epilepsy)
Subjects who are not willing or able to abstain from alcohol, methylxanthine-containing beverages and foods, and grapefruit flesh/juice for 72 hours before first study drug administration until 2 weeks after last study drug administration
Subjects who adhere to a special diet (e.g., vegetarians) or lifestyle (including working at night and extreme physical activities such as competitive sports and weight lifting) that might interfere with the investigation
Subjects planning elective hospital treatment within two months after last intake of trial medication
Subjects who are known or suspected not to comply with the study directives and/or known or suspected not to be reliable or trustworthy
Subjects who are known or suspected not to be capable of understanding and evaluating the information that is given to them as part of the formal information policy (informed consent), in particular regarding the foreseeable risks and discomfort to which they will be exposed
Subjects with anticipated problems of successfully placing an indwelling venous catheter at a forearm
Female subjects only:
- positive results in pregnancy test
- pregnant and lactating women
- subjects who do not use or does not agree to use appropriate contraceptive methods during the study and two months after the study
Male subjects only: they have to accept not to procreate children during the study and two months after the study