Effect of SRT2379 on Endotoxin-Induced Inflammation

SRT2379 is a potent small molecule activator of SIRT1 that has been found to inhibit systemic inflammation induced by intravenous injection of lipopolysaccharide (LPS) in mice. The objective of this study is to test if SRT2379 may be a novel compound for the treatment of inflammatory disorders in man.


Eligibility Criteria:
Inclusion Criteria:

* 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 21 days prior to dosing.
* Male between 18 and 35 years of age inclusive, at the time of signing the informed consent
* Capable of giving written informed consent, which includes compliance with the requirements and restrictions listed in the consent form
* Chemistry panel, including renal and liver functions tests, without any clinically relevant abnormality
* Subjects must agree with their partners to use double-barrier birth control or abstinence while participating in the study and for 7 days following the dose of study drug

Exclusion Criteria:

* Subject has had a major illness in the past 3 months or any significant chronic medical illness that the investigator would deem unfavorable for enrollment including inflammatory diseases
* Subjects with a history of any type of malignancy with the exception of successfully treated basal cell cancer of the skin
* Subject has a past or current gastrointestinal disease which may influence drug absorption
* The subject has a known positive test for hepatitis C antibody, hepatitis B surface antigen or HIV
* Current or chronic history of liver disease, or known hepatic or biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones)
* 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
* 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
* The subject has participated in a clinical trial and has received an investigational product within three months of the dosing in the current study
* 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
* Subject has difficultly in donating blood or accessibility of a vein in left or right arm
* Subject has donated more than 350 mL of blood in last 3 months
* Subject uses tobacco products
* Any clinically relevant abnormality noted on the 12-lead ECG as judged by the investigator or an average QTcB or QTcF \> 450 msec
* Any other issue that, in the opinion of the Principal Investigator, would could be harmful to the subject or compromise interpretation of the data
* Prior participation in a trial where the subject received IV LPS