SepsisPhase 1NCT01014117

Effect of SRT2104 on Endotoxin-induced Inflammation

A Phase 1 study testing SRT2104 in people with Sepsis, run by GlaxoSmithKline at 1 site in Netherlands.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Trial summary

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. Read more about this study

Who is it for?: Ages 18 to 35 years, men onlyHealthy volunteers can take part
Conditions the study is for: Sepsis
What is being tested?: SRT2104
Type of treatment: Pill or oral medicine
Could I receive a placebo?: Yes, some participants may receive a placebo
How many people: 41 participants
Where: 1 siteNetherlands
Study dates: 9 Dec 2009to 10 May 2010
Phase: Phase 1
Are there results?: None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 to 35 years
Men only
Healthy volunteers accepted
Adult

Who may be able to join

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

Who cannot join

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

Show all 16Show fewer

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

Trial locations and contacts

1 site in 1 country.

Netherlands1 site

GSK Investigational Site
Amsterdam, 1105 AZ

Other trials in Netherlands

About this study

Official title: A Phase I Study to Evaluate Single and Multiple (Seven) Oral Doses of SRT2104 on the Endotoxin Induced Inflammatory Response in Healthy Male Subjects

Conditions: Sepsis
Being tested: Placebo, SRT2104
Medical subject headings: Sepsis

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

PlaceboDrug
Matching placebo will be supplied as hard gelatin capsules, with each containing an appropriate amount of placebo.
SRT2104Drug
SRT2104 will be supplied as hard gelatin capsules, with each containing 250mg of SRT2104.

Study groups in NCT01014117
Study group	Role	What they receive
Placebo	Placebo comparator	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. Receives: Drug: Placebo
Placebo and 2.0g SRT2104	Active comparator	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. Receives: Drug: Placebo; Drug: SRT2104
2.0g SRT2104	Active comparator	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. Receives: Drug: SRT2104

What is being measured

The primary outcome is the main question the study is designed to answer.

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).
Measured: 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.

Secondary outcomes (3)

To determine PK of SRT2104 in normal healthy male subjects exposed to low-dose endotoxin (LPS).
Measured: 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).
Measured: 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.
Measured: 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.

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

9 Dec 200910 May 2010

First posted16 Nov 2009 (estimated)
Study start9 Dec 2009
Primary completion10 May 2010
Study completion10 May 2010

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Publications (2)Papers the sponsor has linked to this study.
Other trials for SepsisStudies of the same condition, open and under way.
More trials run by GlaxoSmithKlineThe sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 1
Primary purpose: Basic science
Allocation: Randomised
Intervention model: Parallel groups
Masking: Triple blind
Who is masked: Participant, Care provider, Investigator
Enrolment: 41 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT01014117
Sponsor's protocol ID: 114009
Status last verified: Jun 2017
First submitted: 12 Nov 2009
Last updated: 22 Jun 2017
Results posted: No
Data monitoring committee: No
Individual data sharing: Yes: Patient-level data for this study will be made available through www.clinicalstudydatarequest.com following the timelines and process described on this site.

Publications

van der meer, AJ, Scicluno, B, Lin, J, Jacobson, EW, Vlasuk, GP, van der Poll. The first demonstration of clinical activity by a small molcule SIRT1 activator: SRT 2104 reduces cytokine release and coagulation activation in a human enotoxin model. [Inflammation Research]. 2011;60(Supplement 1):S1-321.
van der Meer AJ, Scicluna BP, Moerland PD, Lin J, Jacobson EW, Vlasuk GP, van der Poll T. The Selective Sirtuin 1 Activator SRT2104 Reduces Endotoxin-Induced Cytokine Release and Coagulation Activation in Humans. Crit Care Med. 2015 Jun;43(6):e199-202. doi: 10.1097/CCM.0000000000000949.
PubMed 25978169

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

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Study at a glance

From the registry record, last updated by the sponsor on 22 Jun 2017. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: A Phase I Study to Evaluate Single and Multiple (Seven) Oral Doses of SRT2104 on the Endotoxin Induced Inflammatory Response in Healthy Male Subjects
ClinicalTrials.gov ID: NCT01014117
Acronym / sponsor ID: 114009
Conditions: Sepsis
Phase: Phase 1
Study type: Interventional
Recruitment status: Completed
Enrolment: 41 participants (actual)
Lead sponsor: GlaxoSmithKlineIndustry (pharma, biotech, devices)
Study start: 9 Dec 2009 (actual)
Primary completion: 10 May 2010 (actual)
Study completion: 10 May 2010 (actual)
First posted: 16 Nov 2009 (estimated)
Results: Not posted in the source record

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Study design

Primary purpose: Basic science
Allocation: Randomised
Intervention model: Parallel groups
Masking: Triple blind (participant, care provider, investigator)
Number of arms: 3

Arm	Type	Receives
Placebo	Placebo comparator	Drug: PlaceboThe 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.
Placebo and 2.0g SRT2104	Active comparator	Drug: Placebo, Drug: SRT2104This 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.
2.0g SRT2104	Active comparator	Drug: SRT2104The 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.

Who may qualify

Ages: 18 to 35 years
Sex: Male only
Healthy volunteers: Accepted
Age groups: Adult

Key inclusion criteria (7 listed)

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

Key exclusion criteria (16 listed)

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

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
PlaceboMatching placebo will be supplied as hard gelatin capsules, with each containing an appropriate amount of placebo.	Drug	Placebo, Placebo and 2.0g SRT2104
SRT2104SRT2104 will be supplied as hard gelatin capsules, with each containing 250mg of SRT2104.	Drug	2.0g SRT2104, Placebo and 2.0g SRT2104

Primary outcome

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.

3 secondary outcomes

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.

Results and safety

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 22 Jun 2017.
Backgroundvan der meer, AJ, Scicluno, B, Lin, J, Jacobson, EW, Vlasuk, GP, van der Poll. The first demonstration of clinical activity by a small molcule SIRT1 activator: SRT 2104 reduces cytokine release and coagulation activation in a human enotoxin model. [Inflammation Research]. 2011;60(Supplement 1):S1-321.
Derived from this study: PubMed 25978169van der Meer AJ, Scicluna BP, Moerland PD, Lin J, Jacobson EW, Vlasuk GP, van der Poll T. The Selective Sirtuin 1 Activator SRT2104 Reduces Endotoxin-Induced Cytokine Release and Coagulation Activation in Humans. Crit Care Med. 2015 Jun;43(6):e199-202. doi: 10.1097/CCM.0000000000000949.
Results for study 114009 can be found on the GSK Clinical Study Register.Link provided by the sponsor.
Researchers can use this site to request access to anonymised patient level data and/or supporting documents from clinical studies to conduct further research.Link provided by the sponsor.
Individual participant dataSharing planned: Yes. Patient-level data for this study will be made available through www.clinicalstudydatarequest.com following the timelines and process described on this site.

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

GSK Clinical Trials study director

GlaxoSmithKline

1 site in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing SRT2104 in people with Sepsis, run by GlaxoSmithKline at 1 site in Netherlands.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 7 inclusion and 16 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 22 Jun 2017. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in Netherlands. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the 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.). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01014117, which also lists 2 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 22 Jun 2017; AzTrials last refreshed its copy on 6 Nov 2026.