A Phase I study to evaluate single and multiple (seven) oral doses of SRT2104 on the endotoxin induced inflammatory response in healthy male subjects

Conditions: Door endotoxine veroorzaakte inflammatie reactie
Inflammation
innate immunesystem
10002252

Registration Number: NL-OMON32755

Lead Sponsor: Sirtris Pharmaceuticals, Inc

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: Pending

Sex: Not specified

Target Recruitment: 24

Inclusion Criteria

A subject will be eligible for inclusion in this study only if all of the following criteria apply: ;1. Healthy, as determined by a responsible and experienced physician, based on a medical evaluation including medical history, physical examination and laboratory tests carried out within 28 days prior to day 1. A subject with a clinical abnormality or laboratory parameters outside the reference range for the population being studied may be included only if the Investigator and the Medical Monitor agree that the finding is unlikely to introduce additional risk factors and will not interfere with the study procedures.
2. Male between 18 and 35 years of age inclusive, at the time of signing the informed consent
3. Capable of giving written informed consent, which includes compliance with the requirements and restrictions listed in the consent form
4. No history of HIV 1 and 2, and hepatitis B and C
5. Normal 12 lead ECG without any clinically significant abnormality as judged by the Investigator and average QTcB or QTcF < 450 msec
6. Normal renal and liver function (normal serum creatinine and liver function tests (ALT, AST, Total bilirubin, alkaline phosphatase)
7. Subjects must agree with their partners to use double-barrier birth control or abstinence while participating in the study and for 12 weeks following the last dose of study drug

Exclusion Criteria

Subjects meeting any of the following exclusion criteria are not to be enrolled in the study:
As a result of the medical interview, physical examination or screening investigations, the Investigator or appropriately qualified designee considers the subject unfit for the study.;1. Subject has had a major illness in the past three months or any significant chronic medial illness that the investigator would deem unfavourable for enrolment including inflammatory diseases
2. Subjects with a history of any type of malignancy with the exception of successfully treated basal cell cancer of the skin
3. Subject has renal impairment
4. Subject has a past or current gastro-intestinal disease which may influence drug absorption
5. The subject has a known positive test for hepatitis C antibody or hepatitis B surface antigen
6. Current or chronic history of liver disease, or known hepatic or biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones).
7. The subject has a known positive test for HIV antibody 1 or 2
8. Subject has a history, within three years, of drug abuse (including benzodiazepines, opioids, amphetamine, cocaine, THC) or a positive drug results at the Screening visit
9. History of alcoholism and/or is drinking more than 3 drinks per day. Alcoholism is defined as an average weekly intake of >21 units for males or >14 units for females. One unit is equivalent to 8 g of alcohol: a half-pint (~240 mL) of beer, 1 glass (125 mL) of wine or 1 (25 mL) measure of spirits
10. The subject has participated in a clinical trial and has received an investigational product within three months of the first dosing day in the current study
11. Use of prescription or non-prescription drugs, and herbal and dietary supplements within 7 days unless in the opinion of the Investigator and Medical Monitor the medication will not interfere with the study procedures or compromise subject safety.
12. Subject has difficultly in donating blood or accessibility of a vein in left or right arm.
13. Subject has donated more than 350 mL of blood in last 3 months
14. Subject uses tobacco products
15. Any other issue that, in the opinion of the Principal Investigator, would could be harmful to the subject or compromise interpretation of the data

Study & Design

Study Type: Interventional

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
<p>Primary study endpoints include clinical signs and symptoms and laboratory<br /><br>parameters for inflammation (cytokines, activation of leukocytes, coagulation<br /><br>and vascular endothelium). </p><br>

Secondary Outcome Measures

Name	Time	Method
<p>Secondary endpoints include pharmacokinetics and safety recordings.<br /><br>Exploratory endpoints include lipid profiles, acute phase proteins, metabolic<br /><br>profiles and gene expression analysis from white blood cells. </p><br>