- ICH GCP
- US-Register für klinische Studien
- Klinische Studie NCT01014117
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
Studienübersicht
Status
Bedingungen
Intervention / Behandlung
Studientyp
Einschreibung (Tatsächlich)
Phase
- Phase 1
Kontakte und Standorte
Studienorte
-
-
-
Amsterdam, Niederlande, 1105 AZ
- GSK Investigational Site
-
-
Teilnahmekriterien
Zulassungskriterien
Studienberechtigtes Alter
Akzeptiert gesunde Freiwillige
Studienberechtigte Geschlechter
Beschreibung
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
Studienplan
Wie ist die Studie aufgebaut?
Designdetails
- Hauptzweck: Grundlegende Wissenschaft
- Zuteilung: Zufällig
- Interventionsmodell: Parallele Zuordnung
- Maskierung: Verdreifachen
Waffen und Interventionen
Teilnehmergruppe / Arm |
Intervention / Behandlung |
---|---|
Placebo-Komparator: 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. |
Das passende Placebo wird in Form von Hartgelatinekapseln geliefert, die jeweils eine entsprechende Menge Placebo enthalten.
|
Aktiver Komparator: 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.
|
Das passende Placebo wird in Form von Hartgelatinekapseln geliefert, die jeweils eine entsprechende Menge Placebo enthalten.
SRT2104 will be supplied as hard gelatin capsules, with each containing 250mg of SRT2104.
|
Aktiver Komparator: 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.
|
SRT2104 will be supplied as hard gelatin capsules, with each containing 250mg of SRT2104.
|
Was misst die Studie?
Primäre Ergebnismessungen
Ergebnis Maßnahme |
Zeitfenster |
---|---|
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).
Zeitfenster: 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.
|
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.
|
Sekundäre Ergebnismessungen
Ergebnis Maßnahme |
Zeitfenster |
---|---|
To determine PK of SRT2104 in normal healthy male subjects exposed to low-dose endotoxin (LPS).
Zeitfenster: 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.
|
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).
Zeitfenster: Safety will be monitored by AEs, VS, physical exam, labs and ECGs during the course of the study.
|
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.
Zeitfenster: 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.
|
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.
|
Mitarbeiter und Ermittler
Sponsor
Publikationen und hilfreiche Links
Allgemeine Veröffentlichungen
- 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.
Studienaufzeichnungsdaten
Haupttermine studieren
Studienbeginn (Tatsächlich)
Primärer Abschluss (Tatsächlich)
Studienabschluss (Tatsächlich)
Studienanmeldedaten
Zuerst eingereicht
Zuerst eingereicht, das die QC-Kriterien erfüllt hat
Zuerst gepostet (Schätzen)
Studienaufzeichnungsaktualisierungen
Letztes Update gepostet (Tatsächlich)
Letztes eingereichtes Update, das die QC-Kriterien erfüllt
Zuletzt verifiziert
Mehr Informationen
Begriffe im Zusammenhang mit dieser Studie
Andere Studien-ID-Nummern
- 114009
Plan für individuelle Teilnehmerdaten (IPD)
Planen Sie, individuelle Teilnehmerdaten (IPD) zu teilen?
Beschreibung des IPD-Plans
Studiendaten/Dokumente
-
Datensatzspezifikation
Informationskennung: 114009Informationskommentare: For additional information about this study please refer to the GSK Clinical Study Register
-
Einzelner Teilnehmerdatensatz
Informationskennung: 114009Informationskommentare: For additional information about this study please refer to the GSK Clinical Study Register
-
Statistischer Analyseplan
Informationskennung: 114009Informationskommentare: For additional information about this study please refer to the GSK Clinical Study Register
-
Studienprotokoll
Informationskennung: 114009Informationskommentare: For additional information about this study please refer to the GSK Clinical Study Register
-
Klinischer Studienbericht
Informationskennung: 114009Informationskommentare: For additional information about this study please refer to the GSK Clinical Study Register
-
Einwilligungserklärung
Informationskennung: 114009Informationskommentare: For additional information about this study please refer to the GSK Clinical Study Register
Diese Informationen wurden ohne Änderungen direkt von der Website clinicaltrials.gov abgerufen. Wenn Sie Ihre Studiendaten ändern, entfernen oder aktualisieren möchten, wenden Sie sich bitte an register@clinicaltrials.gov. Sobald eine Änderung auf clinicaltrials.gov implementiert wird, wird diese automatisch auch auf unserer Website aktualisiert .
Klinische Studien zur Sepsis
-
University of Kansas Medical CenterUniversity of KansasRekrutierungSepsis | Septischer Schock | Sepsis-Syndrom | Sepsis, schwer | Bakterielle Sepsis | Sepsis-BakterämieVereinigte Staaten
-
Jip GroenInBiomeRekrutierungMikrobielle Besiedlung | Neonatale Infektion | Neonatale Sepsis, früher Beginn | Mikrobielle Krankheit | Klinische Sepsis | Kultur-negative neonatale Sepsis | Neonatale Sepsis, später Beginn | Kulturpositive neonatale SepsisNiederlande
-
Karolinska InstitutetÖrebro University, SwedenAbgeschlossenSepsis | Sepsis-Syndrom | Sepsis, schwerSchweden
-
The University of QueenslandRoyal Brisbane and Women's HospitalUnbekannt
-
Ohio State UniversityAbgeschlossenSepsis, schwere Sepsis und septischer SchockVereinigte Staaten
-
Beckman Coulter, Inc.Biomedical Advanced Research and Development AuthorityRekrutierungSchwere Sepsis | Schwere Sepsis ohne septischen SchockVereinigte Staaten
-
University of LeicesterUniversity Hospitals, Leicester; The Royal College of AnaesthetistsAbgeschlossenSepsis | Septischer Schock | Schwere Sepsis | Sepsis-SyndromVereinigtes Königreich
-
Indonesia UniversityAbgeschlossenSchwere Sepsis mit septischem Schock | Schwere Sepsis ohne septischen SchockIndonesien
-
Weill Medical College of Cornell UniversityNational Heart, Lung, and Blood Institute (NHLBI); New York Presbyterian Hospital und andere MitarbeiterAbgeschlossenSepsis | Septischer Schock | Schwere Sepsis | Infektion | Sepsis-SyndromVereinigte Staaten
-
Inverness Medical InnovationsAbgeschlossenSepsis | Systemisches Entzündungsreaktionssyndrom | Schwere Sepsis | Sepsis-SyndromVereinigte Staaten
Klinische Studien zur Placebo
-
SamA Pharmaceutical Co., LtdUnbekanntAkute Bronchitis | Akute Infektion der oberen AtemwegeKorea, Republik von
-
National Institute on Drug Abuse (NIDA)AbgeschlossenCannabiskonsumVereinigte Staaten
-
AstraZenecaParexel; Spandauer Damm 130; 14050; Berlin, GermanyAbgeschlossenMännliche Probanden mit Typ-II-Diabetes (T2DM)Deutschland
-
Instituto de Investigación Hospital Universitario...Creaciones Aromáticas Industriales, S.A. (CARINSA)Abgeschlossen
-
Soroka University Medical CenterAbgeschlossen
-
Regado Biosciences, Inc.AbgeschlossenGesunder FreiwilligerVereinigte Staaten
-
Texas A&M UniversityNutraboltAbgeschlossenGlucose and Insulin Response
-
Longeveron Inc.BeendetHypoplastisches LinksherzsyndromVereinigte Staaten
-
Heptares Therapeutics LimitedAbgeschlossenPharmakokinetik | SicherheitsproblemeVereinigtes Königreich