Effect of Multiple Dose Levels of SRT2379 on Endotoxin-Induced Inflammation

NCT ID: NCT01416376

Last Updated: 2017-06-15

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 39 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2011-08-30
• Study Completion Date: 2011-12-12

Brief Summary

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 determine the effect of a single administration of SRT2379, at multiple-dose levels, on the inflammatory response to low dose endotoxin.

Conditions

Sepsis

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: BASIC_SCIENCE
• Blinding Strategy: DOUBLE

Study Groups

50mg SRT2379

Single oral administration of 50mg SRT2379

Group Type: ACTIVE_COMPARATOR

Placebo

Intervention Type: DRUG

For the placebo capsules, the SRT2379 drug substance will be replaced by microcrystalline cellulose (Avicel PH200) to visually match the SRT2379 investigational product.

250mg SRT2379

Single oral administration of 250mg SRT2379

Group Type: ACTIVE_COMPARATOR

Placebo

Intervention Type: DRUG

For the placebo capsules, the SRT2379 drug substance will be replaced by microcrystalline cellulose (Avicel PH200) to visually match the SRT2379 investigational product.

1000mg SRT2379

Single oral administration of 1000mg SRT2379

Group Type: ACTIVE_COMPARATOR

SRT2379

Intervention Type: DRUG

SRT2379 is supplied as hard gelatin capsules containing either 25mg or 250mg free-base equivalent of SRT23790 drug substance as its succinate salt.

Placebo

Single oral administration of placebo

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

For the placebo capsules, the SRT2379 drug substance will be replaced by microcrystalline cellulose (Avicel PH200) to visually match the SRT2379 investigational product.

Interventions

SRT2379

SRT2379 is supplied as hard gelatin capsules containing either 25mg or 250mg free-base equivalent of SRT23790 drug substance as its succinate salt.

Intervention Type: DRUG

Placebo

For the placebo capsules, the SRT2379 drug substance will be replaced by microcrystalline cellulose (Avicel PH200) to visually match the SRT2379 investigational product.

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• Healthy, as determined by a responsible and experienced physician, based on a medical evaluation including medical history, physical examination (PE) and laboratory tests carried out within 21 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 and able to comply with the requirements and restrictions listed in the informed consent form

• Chemistry panel, including renal and liver function tests, without any clinically relevant abnormality as judged by the Investigator
• Subjects must agree to use double-barrier birth control or abstinence while participating in the study and for 7 days following the last 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 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 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 human immunodeficiency virus (HIV) antibody 1 or 2

• 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 3 years, of drug abuse (including benzodiazepines, opioids, amphetamine, cocaine, THC, methamphetamine) or a positive drug result at the Screening visit
• History of alcoholism and/or is drinking more than 3 units of alcohol per day. Alcoholism is defined as an average weekly intake of >21 units for males. 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 received an investigational product within three months of the first dosing day in the current study; Note: any subject who has participated in a prior human endotoxemia study with SRT2379 or SRT2104 would be excluded from participation in this trial.
• Use of prescription or non-prescription drugs and herbal and dietary supplements within 7 days unless in the opinion of the Investigator the medication will not interfere with the study procedures or compromise subject safety
• Subject has difficulty donating blood or limited accessibility of a vein in left and 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 Investigator , could be harmful to the subject or compromise interpretation of the data
• Prior participation in a trial where the subject received intravenous endotoxin (LPS) infusion

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 35 Years
• Eligible Sex: MALE
• Accepts Healthy Volunteers: Yes

Sponsors

GlaxoSmithKline

INDUSTRY

Sponsor Role: collaborator

Sirtris, a GSK Company

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

GSK Clinical Trials

Role: STUDY_DIRECTOR

GlaxoSmithKline

Locations

GSK Investigational Site

Amsterdam, , Netherlands

Countries

Netherlands

Study Documents

Document Type: Clinical Study Report

For additional information about this study please refer to the GSK Clinical Study Register

View Document

Document Type: Dataset Specification

For additional information about this study please refer to the GSK Clinical Study Register

View Document

Document Type: Individual Participant Data Set

For additional information about this study please refer to the GSK Clinical Study Register

View Document

Document Type: Statistical Analysis Plan

For additional information about this study please refer to the GSK Clinical Study Register

View Document

Document Type: Study Protocol

For additional information about this study please refer to the GSK Clinical Study Register

View Document

Document Type: Informed Consent Form

For additional information about this study please refer to the GSK Clinical Study Register

View Document

Related Links

https://www.clinicalstudydatarequest.com

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

Other Identifiers

115830

Identifier Type: -

Identifier Source: org_study_id