A Study to Determine the Safety, Tolerability, and Effects of GSK2374697 in Healthy Volunteers
A Single-blinded, Randomized, Placebo-controlled, Staggered-parallel, Escalating Dose Study to Investigate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of GSK2374697 in Healthy Volunteers
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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Minnesota
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Minneapolis、Minnesota、アメリカ、55404
- 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, laboratory tests and Holter monitoring. A subject with a clinical abnormality or laboratory parameters outside the reference range for the population being studied may be included if the investigator and the GSK Medical Monitor (or designee) agree that the finding is unlikely to introduce additional risk factors and will not interfere with the study procedures or objectives. Subjects with values outside the ranges noted below should be excluded from enrollment, unless the investigator and GSK medical monitor (or designee) agree that the value in question would not pose a significant safety risk for the subject or compromise the study objectives. Please see Section 7.1 for additional information.
- Male or female between 18 and 65 years of age inclusive, at the time of signing the informed consent.
- A female subject is eligible to participate if she is of:
Non-childbearing potential defined as pre-menopausal females with a documented tubal ligation or hysterectomy; or postmenopausal defined as 12 months of spontaneous amenorrhea [in questionable cases a blood sample with simultaneous follicle stimulating hormone (FSH) > 40 MlU/ml and estradiol < 40 pg/ml (<147 pmol/L) is confirmatory]. Females on hormone replacement therapy (HRT) and whose menopausal status is in doubt must discontinue HRT to allow confirmation of post-menopausal status prior to study enrollment. For most forms of HRT, at least 2- 4 weeks will elapse between the cessation of therapy and the blood draw; this interval depends on the type and dosage of HRT. Following confirmation of their post-menopausal status, they can resume use of HRT during the study.
- Body weight ≥ 50.0 kg and BMI within the range 19.9 - 35 kg/m2 (inclusive).
- Capable of giving written informed consent, which includes compliance with the requirements and restrictions listed in the consent form.
- Single or Average QTcB < 450 msec.
- AST, ALT, alkaline phosphatase and bilirubin ≤ 1.5xULN at screening and at baseline (isolated bilirubin >1.5xULN is acceptable if bilirubin is fractionated and direct bilirubin <35%).
Exclusion Criteria:
- A positive pre-study Hepatitis B surface antigen or positive Hepatitis C antibody result within 3 months of screening.
- A positive test for HIV antibody.
- History of chronic or acute pancreatitis. Note: Subjects with a lipase value above the upper limit of normal (ULN) at screening are excluded. If amylase result is above ULN and lipase is below ULN, an amylase isoenzyme analysis may be performed. If this additional test confirms that the pancreatic amylase isoenzyme fraction is not the cause of the elevation, the subject may enroll in the study.
- History of thyroid disease: personal or family history of thyroid cancer unless approved by the GSK medical monitor (or designee), and/or a history of uncorrected thyroid dysfunction or an abnormal thyroid function as assessed by TSH, and/or plasma calcitonin at screening > 50pg/mL.
- History of- or family history of a renal disorder that may compromise renal function
- Creatinine clearance < 80 mL/min. (estimated from serum creatinine (SCr) and demographic data using the Cockcroft-Gault calculation):
To calculate estimated Cockcroft-Gault GFR (mL/min) manually:
= (140 - age) * (weight in kg) * (0.85 if female) / (72 * Cr in mg/dL)
- History of regular alcohol consumption within 6 months of the study defined as:
An average weekly intake of >14 drinks for males or >7 drinks for females. One drink is equivalent to 12 g of alcohol: 12 ounces (360 ml) of beer, 5 ounces (150 ml) of wine or 1.5 ounces (45 ml) of 80 proof distilled spirits.
- Exposure to more than four new chemical entities within 12 months prior to the first dosing day, and prior exposure to any anti-diabetic drug in a clinical study will require approval from the GSK medical monitor (or designee) before a subject is considered eligible for enrollment. In addition, subject has participated in a clinical trial and has received an investigational (non-approved) product within the following time period prior to the first dosing day in the current study: 30 days, 5 half-lives or twice the duration of the biological effect of the investigational product (whichever is longer)
- History of sensitivity to any of the study medications, or components thereof or a history of drug or other allergy that, in the opinion of the investigator or GSK Medical Monitor (or designee), contraindicates their participation. Use of prescription or non-prescription drugs, including vitamins, herbal and dietary supplements (including St John's Wort) within 7 days (or 14 days if the drug is a potential enzyme inducer) or 5 half-lives (whichever is longer) prior to the first dose of study medication, unless in the opinion of the investigator and GSK Medical Monitor (or designee) the medication will not interfere with the study procedures or compromise subject safety.
- Where participation in the study would result in donation of blood or blood products in excess of approximately 500 mL within a 56 day period.
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:処理
- 割り当て:ランダム化
- 介入モデル:並列代入
- マスキング:ダブル
武器と介入
参加者グループ / アーム |
介入・治療 |
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アクティブコンパレータ:GSK2376497
single dose escalation or multiple-dose titration
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GSK2376497 Active Comparator
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プラセボコンパレーター:0.9% sodium chloride
placebo injection
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0.9% sodium chloride Placebo Comparator
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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 |
メジャーの説明 |
時間枠 |
---|---|---|
Number of subjects with adverse events after ascending single or titrated mulitple subcutaneous doses of GSK2374697
時間枠:up to 70 days post dose
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Adverse events, laboratory parameters, ECGs, and vital signs
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up to 70 days post dose
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pharmacokinetic parameters of GSK2374697, after ascending single or titrated multiple subcutaneous doses, in healthy subjects
時間枠:pre-dose, then 6, 12, 18, 24, 30, 36, 42, 48, 54, 60, and 66 hours after dose (this schedule is q6h through Day 3, up to just prior to Day 4). In addition, sampling continues out through Day 70, on specific days, q12h.
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Pharmacokinetics parameters: AUCs, Cmax, tmax, elimination half-life (t½), lag time (tlag), apparent clearance (CL/F) and apparent volume of distribution (V/F), area under the plasma drug concentration versus time curve on Days 1 through end of study (up to 70 Days)
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pre-dose, then 6, 12, 18, 24, 30, 36, 42, 48, 54, 60, and 66 hours after dose (this schedule is q6h through Day 3, up to just prior to Day 4). In addition, sampling continues out through Day 70, on specific days, q12h.
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二次結果の測定
結果測定 |
メジャーの説明 |
時間枠 |
---|---|---|
pharmacodynamic effects of GSK2374697 in healthy subjects after meal challenge
時間枠:On 2 days
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Fasting, 2h, and Cmax parameters on Day -1 and approximately Day 6 (or Day 16)
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On 2 days
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dose proportionality of GSK2374697
時間枠:up to 70 days post dose
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Pharmacokinetics parameters based on single and/or titrated multiple subcutaneous doses of GSK2374697
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up to 70 days post dose
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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
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
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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注釈付き症例報告書
情報識別子:114403情報コメント:For additional information about this study please refer to the GSK Clinical Study Register
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データセット仕様
情報識別子:114403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:114403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:114403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:114403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:114403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:114403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。