Effect of SRT2379 on Endotoxin-Induced Inflammation

This study has been completed.
Sponsor:
Collaborator:
GlaxoSmithKline
Information provided by:
GlaxoSmithKline
ClinicalTrials.gov Identifier:
NCT01262911
First received: December 16, 2010
Last updated: July 26, 2011
Last verified: July 2011
  Purpose

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.


Condition Intervention Phase
Sepsis
Drug: SRT2379
Drug: Placebo
Phase 1

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Pharmacokinetics/Dynamics Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Basic Science
Official Title: A Phase I Study to Evaluate a Single Oral Dose of SRT2379 on the Endotoxin Induced Inflammatory Response in Healthy Male Subjects

Further study details as provided by GlaxoSmithKline:

Primary Outcome Measures:
  • To determine if a single dose of SRT2379 attenuates the inflammatory response in normal healthy male subjects after exposure to low-dose endotoxin (LPS). [ Time Frame: 24 hours ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • To determine PK of SRT2379 in normal healthy male subjects exposed to low-dose endotoxin (LPS). [ Time Frame: 24 hours ] [ Designated as safety issue: No ]
  • To determine the safety profile of SRT2379 in healthy male subjects exposed to low-dose endotoxin (LPS). [ Time Frame: 10 days ] [ Designated as safety issue: No ]

Enrollment: 17
Study Start Date: February 2011
Study Completion Date: March 2011
Primary Completion Date: March 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: 1.0 g SRT2379
Single dose of 1.0g of SRT2379
Drug: SRT2379
SRT2379 will be supplied as hard gelatin capsules, with each containing 250mg.
Placebo Comparator: 1.0 g Placebo
Single dose of 1.0g of placebo
Drug: Placebo
Matching placebo will be supplied as hard gelatin capsules, with each containing an appropriate amount of placebo.

  Eligibility

Ages Eligible for Study:   18 Years to 35 Years
Genders Eligible for Study:   Male
Accepts Healthy Volunteers:   Yes
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01262911

Locations
Netherlands
GSK Investigational Site
Amsterdam, Netherlands, 1105 AZ
Sponsors and Collaborators
Sirtris, a GSK Company
GlaxoSmithKline
Investigators
Study Director: GSK Clinical Trials GlaxoSmithKline
  More Information

No publications provided

Responsible Party: Cheri Hudson; Clinical Disclosure Advisor, GSK Clinical Disclosure
ClinicalTrials.gov Identifier: NCT01262911     History of Changes
Other Study ID Numbers: 115083
Study First Received: December 16, 2010
Last Updated: July 26, 2011
Health Authority: Netherlands: Centrale Commissie Mensgebonden Onderzoek

ClinicalTrials.gov processed this record on October 21, 2014