Effect of SRT2104 on Endotoxin-induced Inflammation

This study has been completed.
Sponsor:
Information provided by:
GlaxoSmithKline
ClinicalTrials.gov Identifier:
NCT01014117
First received: November 12, 2009
Last updated: February 17, 2011
Last verified: February 2011

November 12, 2009
February 17, 2011
December 2009
May 2010   (final data collection date for primary outcome measure)
To determine if a single or 7 daily doses of SRT2104 attenuates the inflammatory response in normal healthy male subjects after exposure to low-dose endotoxin (LPS). [ Time Frame: Measurements of inflammation will be conducted on plasma samples obtained on Day7 at -3, 0, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8 and 12hrs. Samples will also be taken on Day8, approximately 24hrs after dosing on Day7. ]
Same as current
Complete list of historical versions of study NCT01014117 on ClinicalTrials.gov Archive Site
  • To determine PK of SRT2104 in normal healthy male subjects exposed to low-dose endotoxin (LPS). [ Time Frame: Plasma samples will be collected at pre-dose, 15min, 30min, and 1, 2, 3, 4, 8, and 12hrs post-dose on Day1 and Day7. Plasma samples will also be collected on Day2 and Day8 and at 24hrs post-dose Day1 and Day7, respectively. ]
  • To determine the safety profile of SRT2104 in healthy male subjects exposed to low-dose endotoxin (LPS). [ Time Frame: Safety will be monitored by AEs, VS, physical exam, labs and ECGs during the course of the study. ]
  • To determine the effect of SRT2104 on other parameters following low-dose endotoxin (LPS) exposure in humans e.g., lipid profile, serum amyloid phospholipids, metabolic profiles and gene expression analysis etc. [ Time Frame: Blood samples will be collected for exploratory gene expression analysis pre-dose on Days1 and 7, and 4hrs after LPS exposure on Day7. Samples for other parameters will be collected during fasting, pre-dose on Days1 and 7 and 24hrs post-dose on Day8. ]
Same as current
Not Provided
Not Provided
 
Effect of SRT2104 on Endotoxin-induced Inflammation
A Phase I Study to Evaluate Single and Multiple (Seven) Oral Doses of SRT2104 on the Endotoxin Induced Inflammatory Response in Healthy Male Subjects

SRT2104 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 SRT2104 may be a novel compound for the treatment of inflammatory disorders in man.

Not Provided
Interventional
Phase 1
Allocation: Randomized
Endpoint Classification: Pharmacokinetics/Dynamics Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator)
Primary Purpose: Basic Science
Sepsis
  • Drug: Placebo
    Matching placebo will be supplied as hard gelatin capsules, with each containing an appropriate amount of placebo.
  • Drug: SRT2104
    SRT2104 will be supplied as hard gelatin capsules, with each containing 250mg of SRT2104.
  • Placebo Comparator: Placebo

    The Placebo treatment group will be administered eight oral placebo capsules once daily for 7 days.

    A trained investigative site member will administer the test material to subjects on Day 1, 2, and 7. On Days 1, 2 and 7 the subjects will receive SRT2104 or placebo approximately 15min following the consumption of a standardized meal at the study center. During non-clinic days, the subject will self-administer the test material approximately 15 min following consumption of a standardized meal at home. Test material should be administered with approximately 400mL of water. On Days 1 and 7, dosing will occur at approximately 7AM. Dosing on Days 2-6 will occur before 9AM. Subjects must wait at least 1-2 hrs after dosing before consuming additional calories on all dosing days.

    Intervention: Drug: Placebo
  • Active Comparator: Placebo and 2.0g SRT2104
    This treatment group will be administered eight oral placebo capsules once daily for 6 days followed by 2.0g SRT2104 administered as eight oral SRT2104 capsules on Day 7. A trained investigative site member will administer the test material to subjects on Day 1, 2, and 7. On Days 1, 2 and 7 the subjects will receive SRT2104 or placebo approximately 15min following the consumption of a standardized meal at the study center. During non-clinic days, the subject will self-administer the test material approximately 15 min following consumption of a standardized meal at home. Test material should be administered with approximately 400mL of water. On Days 1 and 7, dosing will occur at approximately 7AM. Dosing on Days 2-6 will occur before 9AM. Subjects must wait at least 1-2 hrs after dosing before consuming additional calories on all dosing days.
    Interventions:
    • Drug: Placebo
    • Drug: SRT2104
  • Active Comparator: 2.0g SRT2104
    The 2.0g SRT2104 treatment group will be administered eight oral SRT2104 capsules once daily for 7 days. A trained investigative site member will administer the test material to subjects on Day 1, 2, and 7. On Days 1, 2 and 7 the subjects will receive SRT2104 or placebo approximately 15min following the consumption of a standardized meal at the study center. During non-clinic days, the subject will self-administer the test material approximately 15 min following consumption of a standardized meal at home. Test material should be administered with approximately 400mL of water. On Days 1 and 7, dosing will occur at approximately 7AM. Dosing on Days 2-6 will occur before 9AM. Subjects must wait at least 1-2 hrs after dosing before consuming additional calories on all dosing days.
    Intervention: Drug: SRT2104
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
41
May 2010
May 2010   (final data collection date for primary outcome measure)

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 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
  • 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
  • No history of HIV 1 and 2, and hepatitis B and C
  • Normal 12 lead ECG without any clinically significant abnormality as judged by the Investigator and average QTcB or QTcF < 450 msec
  • Normal renal and liver function (normal serum creatinine and liver function tests (ALT, AST, Total bilirubin, alkaline phosphatase)
  • 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:

  • 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
  • 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
  • Subjects with a history of any type of malignancy with the exception of successfully treated basal cell cancer of the skin
  • Subject has renal impairment
  • Subject has a past or current gastro-intestinal disease which may influence drug absorption
  • The subject has a known positive test for hepatitis C antibody or hepatitis B surface antigen
  • Current or chronic history of liver disease, or known hepatic or biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones)
  • The subject has a known positive test for HIV antibody 1 or 2
  • 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 first dosing day 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 other issue that, in the opinion of the Principal Investigator, would could be harmful to the subject or compromise interpretation of the data
Male
18 Years to 35 Years
Yes
Contact information is only displayed when the study is recruiting subjects
Netherlands
 
NCT01014117
114009
No
Cheri Hudson; Clinical Disclosure Advisor, GSK Clinical Disclosure
GlaxoSmithKline
Not Provided
Study Director: GSK Clinical Trials GlaxoSmithKline
GlaxoSmithKline
February 2011

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP