Effect of SRT2379 on Endotoxin-Induced Inflammation

A Phase I Study to Evaluate a Single Oral Dose of SRT2379 on the Endotoxin Induced Inflammatory Response in Healthy Male Subjects

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.

Study Overview

• Status: Completed
• Conditions: Sepsis
• Intervention / Treatment: Drug: Placebo; Drug: SRT2379

• Study Type: Interventional
• Enrollment (Actual): 17
• Phase: Phase 1

Contacts and Locations

Study Locations

• Netherlands
  • Amsterdam, Netherlands, 1105 AZ
    • GSK Investigational Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 35 years (Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: Male

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
To determine if a single dose of SRT2379 attenuates the inflammatory response in normal healthy male subjects after exposure to low-dose endotoxin (LPS).	24 hours

Secondary Outcome Measures

Outcome Measure	Time Frame
To determine PK of SRT2379 in normal healthy male subjects exposed to low-dose endotoxin (LPS).	24 hours
To determine the safety profile of SRT2379 in healthy male subjects exposed to low-dose endotoxin (LPS).	10 days

Collaborators and Investigators

• Sponsor: Sirtris, a GSK Company
• Collaborators: GlaxoSmithKline

Publications and helpful links

Helpful Links

• Researchers can use this site to request access to anonymised patient level data and/or supporting documents from clinical studies to conduct further research.

Study record dates

Study Major Dates

• Study Start (Actual): February 17, 2011
• Primary Completion (Actual): April 26, 2011
• Study Completion (Actual): April 26, 2011

Study Registration Dates

• First Submitted: December 16, 2010
• First Submitted That Met QC Criteria: December 16, 2010
• First Posted (Estimate): December 17, 2010

Study Record Updates

• Last Update Posted (Actual): August 4, 2017
• Last Update Submitted That Met QC Criteria: August 2, 2017
• Last Verified: August 1, 2017

More Information

Terms related to this study

• Other Study ID Numbers: 115083

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Patient-level data for this study will be made available through www.clinicalstudydatarequest.com following the timelines and process described on this site.

Study Data/Documents

1. Individual Participant Data Set
   Information identifier: 115083
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
2. Statistical Analysis Plan
   Information identifier: 115083
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
3. Dataset Specification
   Information identifier: 115083
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
4. Annotated Case Report Form
   Information identifier: 115083
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
5. Informed Consent Form
   Information identifier: 115083
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
6. Clinical Study Report
   Information identifier: 115083
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
7. Study Protocol
   Information identifier: 115083
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register