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
調査の概要
研究の種類
入学 (実際)
段階
- フェーズ 1
連絡先と場所
研究場所
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Amsterdam、オランダ、1105 AZ
- GSK Investigational Site
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参加基準
適格基準
就学可能な年齢
健康ボランティアの受け入れ
受講資格のある性別
説明
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
研究計画
研究はどのように設計されていますか?
デザインの詳細
- 主な目的:基礎科学
- 割り当て:ランダム化
- 介入モデル:並列代入
- マスキング:トリプル
武器と介入
参加者グループ / アーム |
介入・治療 |
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プラセボコンパレーター: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. |
適合するプラセボはハードゼラチンカプセルとして提供され、それぞれに適切な量のプラセボが含まれます。
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アクティブコンパレータ: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.
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適合するプラセボはハードゼラチンカプセルとして提供され、それぞれに適切な量のプラセボが含まれます。
SRT2104 will be supplied as hard gelatin capsules, with each containing 250mg of SRT2104.
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アクティブコンパレータ: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.
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SRT2104 will be supplied as hard gelatin capsules, with each containing 250mg of SRT2104.
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この研究は何を測定していますか?
主要な結果の測定
結果測定 |
時間枠 |
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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).
時間枠: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.
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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.
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二次結果の測定
結果測定 |
時間枠 |
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To determine PK of SRT2104 in normal healthy male subjects exposed to low-dose endotoxin (LPS).
時間枠: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.
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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.
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To determine the safety profile of SRT2104 in healthy male subjects exposed to low-dose endotoxin (LPS).
時間枠:Safety will be monitored by AEs, VS, physical exam, labs and ECGs during the course of the study.
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Safety will be monitored by AEs, VS, physical exam, labs and ECGs during the course of the study.
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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.
時間枠: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.
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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.
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協力者と研究者
スポンサー
出版物と役立つリンク
一般刊行物
- 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.
研究記録日
主要日程の研究
研究開始 (実際)
一次修了 (実際)
研究の完了 (実際)
試験登録日
最初に提出
QC基準を満たした最初の提出物
最初の投稿 (見積もり)
学習記録の更新
投稿された最後の更新 (実際)
QC基準を満たした最後の更新が送信されました
最終確認日
詳しくは
本研究に関する用語
その他の研究ID番号
- 114009
個々の参加者データ (IPD) の計画
個々の参加者データ (IPD) を共有する予定はありますか?
IPD プランの説明
試験データ・資料
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データセット仕様
情報識別子:114009情報コメント:For additional information about this study please refer to the GSK Clinical Study Register
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個人参加者データセット
情報識別子:114009情報コメント:For additional information about this study please refer to the GSK Clinical Study Register
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統計分析計画
情報識別子:114009情報コメント:For additional information about this study please refer to the GSK Clinical Study Register
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研究プロトコル
情報識別子:114009情報コメント:For additional information about this study please refer to the GSK Clinical Study Register
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臨床研究報告書
情報識別子:114009情報コメント:For additional information about this study please refer to the GSK Clinical Study Register
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インフォームド コンセント フォーム
情報識別子:114009情報コメント:For additional information about this study please refer to the GSK Clinical Study Register
この情報は、Web サイト clinicaltrials.gov から変更なしで直接取得したものです。研究の詳細を変更、削除、または更新するリクエストがある場合は、register@clinicaltrials.gov。 までご連絡ください。 clinicaltrials.gov に変更が加えられるとすぐに、ウェブサイトでも自動的に更新されます。
プラセボの臨床試験
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Palacky University完了
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Universidade Federal do ParaConselho Nacional de Desenvolvimento Científico e Tecnológico完了
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Advice Pharma Group srl積極的、募集していない肥満 | 栄養障害 | 体重 | 減量 | 食生活 | 太りすぎと肥満 | 健康行動 | ダイエット、健康 | ダイエット習慣 | ライフスタイル | 栄養、健康 | 行動障害イタリア
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University Hospital, Strasbourg, France積極的、募集していない