Phase II Pharmacokinetic and Pharmacodynamic Study of DEX in Subjects Aged 12 Months Through <24 Months
2015年6月29日 更新者：Hospira, now a wholly owned subsidiary of Pfizer
A Phase II, Randomized, Open-Label, Single Center, Pharmacokinetic and Pharmacodynamic Study of Dexmedetomidine in Pediatric Subjects Aged 12 Months Through <24 Months
The purpose of this study is to investigate the pharmacokinetic, pharmacodynamic, and safety of dexmedetomidine at 2 different dose levels in pediatric subjects, aged 12 months through <24 months, administered as an intravenous loading dose followed by continuous infusion for a minimum of 6 hours and up to 24 hours in an intensive care setting.
調査の概要
詳細な説明
Phase II, randomized, open-label, single-center, study evaluating the pharmacokinetics and pharmacodynamics of dexmedetomidine in pediatric subjects across two dose levels (Dose Level 1 consists of a 0.7 mcg/kg loading dose immediately followed by a 0.5 mcg/kg/hr maintenance infusion; Dose Level 2 consists of a 1.0 mcg/kg loading dose immediately followed by a 0.75 mcg/kg/hr maintenance infusion).
The study population will consist of intubated and mechanically ventilated pediatric subjects who require sedation in an intensive care setting for a minimum of 6 hours but not to exceed 24 hours.
Subjects eligible for enrollment are 12 months to <24 months of age.
研究の種類
介入
入学 (実際)
5
段階
- フェーズ2
連絡先と場所
このセクションには、調査を実施する担当者の連絡先の詳細と、この調査が実施されている場所に関する情報が記載されています。
研究場所
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Pennsylvania
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Pittsburgh、Pennsylvania、アメリカ、15224
- Children's Hospital of Pittusburgh of UPMC
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参加基準
研究者は、適格基準と呼ばれる特定の説明に適合する人を探します。これらの基準のいくつかの例は、人の一般的な健康状態または以前の治療です。
適格基準
就学可能な年齢
1年～1年 (子)
健康ボランティアの受け入れ
いいえ
受講資格のある性別
全て
説明
Inclusion Criteria:
- Subject is 12 months to <24 months of age at screening.
- Subject is intubated and mechanically ventilated in an intensive care setting and is anticipated to require a minimum of 6 hours of continuous IV sedation.
- Subject has adequate renal function, defined as: Serum creatinine ≤1.0 mg/dL.
- The subject's parent(s) or legal guardian(s) must voluntarily sign and date the informed consent document approved by the Institutional Review Board.
Exclusion Criteria:
Pediatric subjects with neurological conditions that prohibit an evaluation of sedation such as:
- Diminished consciousness from increased intracranial pressure
- Extensive brain surgery (surgery requiring intracranial pressure monitor)
- Diminished cognitive function per Principal Investigator (PI) discretion
- Subjects with immobility from neuromuscular disease or continuous infusion of neuromuscular blocking agents.
- Subjects with second degree or third degree heart block unless subject has a permanent pacemaker or pacing wires are in situ.
- Subjects who have hepatic impairment as defined by a serum glutamic-pyruvic transaminase/alanine aminotransferase (SGPT/ALT) >90 U/L at the time of screening.
- Subjects who have hypotension, based on repeat assessments within 15 minutes preceding the start of study drug, defined as: Systolic blood pressure (SBP) <70 mmHg.
- Pre-existing bradycardia based on repeated assessments within 15 minutes preceding the start of study drug, defined as: Heart rate (HR) <70 bpm.
- Subject who have acute thermal burns involving more than 15 percent total body surface area.
- Subjects who have a known allergy to dexmedetomidine, midazolam or fentanyl.
- Subject who has received dexmedetomidine within 15 hours prior to the start of study drug.
- Subjects with a life expectancy that is <72 hours.
- Subjects that are expected to have hemodialysis (continuous hemofiltration), peritoneal dialysis or extracorporeal membrane oxygenation (ECMO) treatments within 48 hours prior to the start of study drug or during the duration of the study.
- Subjects who have been treated with α-2 agonists/antagonists within 2 weeks.
- Subjects with a spinal cord injury above T5 (5th Thoracic Vertebra).
- Subjects who have received another investigational drug as part of an investigational drug study within the past 30 days.
- Subjects who, in the opinion of the investigator, may not be able to comply with the safety monitoring requirements of this clinical study.
研究計画
このセクションでは、研究がどのように設計され、研究が何を測定しているかなど、研究計画の詳細を提供します。
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：なし（オープンラベル）
武器と介入
参加者グループ / アーム |
介入・治療 |
|---|---|
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実験的：Dose level 1
Dexmedetomidine 0.7 mcg/kg loading dose and 0.5 mcg/kg/hr maintenance infusion
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For sedation according to protocol
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実験的：Dose level 2
Dexmedetomidine 1.0 mcg/kg loading dose and 0.75 mcg/kg/hr maintenance infusion
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For sedation according to protocol
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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 |
|---|---|---|
|
Area Under the Plasma Concentration-time Curve (AUC0-∞)
時間枠：30 minutes prior to loading dose (LD); 5 minutes before finishing LD; 0.5, 1, 2 and 4-6 hours during maintenance infusion (MI); 30 minutes prior (within 24 hours of start of MI) and 10 minutes, 0.5, 1, 2, 4 and 10 hours end of MI
|
Area under the plasma concentration-time curve of dexmedetomidine at 0 to Infinity hours
|
30 minutes prior to loading dose (LD); 5 minutes before finishing LD; 0.5, 1, 2 and 4-6 hours during maintenance infusion (MI); 30 minutes prior (within 24 hours of start of MI) and 10 minutes, 0.5, 1, 2, 4 and 10 hours end of MI
|
|
Observed Peak Plasma Concentration (Cmax)
時間枠：30 minutes prior to loading dose (LD); 5 minutes before finishing LD; 0.5, 1, 2 and 4-6 hours during maintenance infusion (MI); 30 minutes prior (within 24 hours of start of MI) and 10 minutes, 0.5, 1, 2, 4 and 10 hours end of MI
|
Maximum observed concentration of dexmedetomidine in plasma
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30 minutes prior to loading dose (LD); 5 minutes before finishing LD; 0.5, 1, 2 and 4-6 hours during maintenance infusion (MI); 30 minutes prior (within 24 hours of start of MI) and 10 minutes, 0.5, 1, 2, 4 and 10 hours end of MI
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Steady State Concentration (Css)
時間枠：30 minutes prior to loading dose (LD); 5 minutes before finishing LD; 0.5, 1, 2 and 4-6 hours during maintenance infusion (MI); 30 minutes prior (within 24 hours of start of MI) and 10 minutes, 0.5, 1, 2, 4 and 10 hours end of MI
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Concentration of dexmedetomidine at steady state in plasma
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30 minutes prior to loading dose (LD); 5 minutes before finishing LD; 0.5, 1, 2 and 4-6 hours during maintenance infusion (MI); 30 minutes prior (within 24 hours of start of MI) and 10 minutes, 0.5, 1, 2, 4 and 10 hours end of MI
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Terminal Elimination Half-life (t1/2)
時間枠：30 minutes prior to loading dose (LD); 5 minutes before finishing LD; 0.5, 1, 2 and 4-6 hours during maintenance infusion (MI); 30 minutes prior (within 24 hours of start of MI) and 10 minutes, 0.5, 1, 2, 4 and 10 hours end of MI
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Terminal elimination half-life of dexmedetomidine.
Half-life is the time required for plasma concentration of the drug to decrease by 50%.
|
30 minutes prior to loading dose (LD); 5 minutes before finishing LD; 0.5, 1, 2 and 4-6 hours during maintenance infusion (MI); 30 minutes prior (within 24 hours of start of MI) and 10 minutes, 0.5, 1, 2, 4 and 10 hours end of MI
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Time to Reach Maximum Plasma Concentration (Tmax)
時間枠：30 minutes prior to loading dose (LD); 5 minutes before finishing LD; 0.5, 1, 2 and 4-6 hours during maintenance infusion (MI); 30 minutes prior (within 24 hours of start of MI) and 10 minutes, 0.5, 1, 2, 4 and 10 hours end of MI
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Observed time to reach maximum plasma concentration of dexmedetomidine, expressed in hours
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30 minutes prior to loading dose (LD); 5 minutes before finishing LD; 0.5, 1, 2 and 4-6 hours during maintenance infusion (MI); 30 minutes prior (within 24 hours of start of MI) and 10 minutes, 0.5, 1, 2, 4 and 10 hours end of MI
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Weight-Adjusted Plasma Clearance (CLw)
時間枠：30 minutes prior to loading dose (LD); 5 minutes before finishing LD; 0.5, 1, 2 and 4-6 hours during maintenance infusion (MI); 30 minutes prior (within 24 hours of start of MI) and 10 minutes, 0.5, 1, 2, 4 and 10 hours end of MI
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Weight-Adjusted Plasma Clearance of dexmedetomidine after intravenous administration.
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30 minutes prior to loading dose (LD); 5 minutes before finishing LD; 0.5, 1, 2 and 4-6 hours during maintenance infusion (MI); 30 minutes prior (within 24 hours of start of MI) and 10 minutes, 0.5, 1, 2, 4 and 10 hours end of MI
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Plasma Clearance (CL)
時間枠：30 minutes prior to loading dose (LD); 5 minutes before finishing LD; 0.5, 1, 2 and 4-6 hours during maintenance infusion (MI); 30 minutes prior (within 24 hours of start of MI) and 10 minutes, 0.5, 1, 2, 4 and 10 hours end of MI
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Clearance of dexmedetomidine after intravenous administration.
Clearance is the rate at which the drug is removed from the plasma after the dose.
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30 minutes prior to loading dose (LD); 5 minutes before finishing LD; 0.5, 1, 2 and 4-6 hours during maintenance infusion (MI); 30 minutes prior (within 24 hours of start of MI) and 10 minutes, 0.5, 1, 2, 4 and 10 hours end of MI
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Volume of Distribution (Vd)
時間枠：30 minutes prior to loading dose (LD); 5 minutes before finishing LD; 0.5, 1, 2 and 4-6 hours during maintenance infusion (MI); 30 minutes prior (within 24 hours of start of MI) and 10 minutes, 0.5, 1, 2, 4 and 10 hours end of MI
|
Volume of distribution of dexmedetomidine after intravenous administration.
Volume of distribution measures how much the drug spreads through the body after the dose.
|
30 minutes prior to loading dose (LD); 5 minutes before finishing LD; 0.5, 1, 2 and 4-6 hours during maintenance infusion (MI); 30 minutes prior (within 24 hours of start of MI) and 10 minutes, 0.5, 1, 2, 4 and 10 hours end of MI
|
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Weight-Adjusted Volume of Distribution (Vdw)
時間枠：30 minutes prior to loading dose (LD); 5 minutes before finishing LD; 0.5, 1, 2 and 4-6 hours during maintenance infusion (MI); 30 minutes prior (within 24 hours of start of MI) and 10 minutes, 0.5, 1, 2, 4 and 10 hours end of MI
|
Weight-Adjusted Volume of distribution of dexmedetomidine after intravenous administration.
|
30 minutes prior to loading dose (LD); 5 minutes before finishing LD; 0.5, 1, 2 and 4-6 hours during maintenance infusion (MI); 30 minutes prior (within 24 hours of start of MI) and 10 minutes, 0.5, 1, 2, 4 and 10 hours end of MI
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Average Total Faces, Legs, Activity, Cry, and Consolability (FLACC) Score
時間枠：Prior to loading dose and every hour during the maintenance infusion; within 5 minutes after any fentanyl administration during DEX infusion or every 4 hours in case of continuous fentanyl infusion; within 5 minutes prior and after titration of fentanyl
|
FLACC scale is a 5 category observational measure to assess pediatric pain on face, legs, activity, cry and consolability.
Responses in each category are scored between 0 to 2 (0 = normal, relaxed to 2 = upset, rigid), for a maximum total score of 10.
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Prior to loading dose and every hour during the maintenance infusion; within 5 minutes after any fentanyl administration during DEX infusion or every 4 hours in case of continuous fentanyl infusion; within 5 minutes prior and after titration of fentanyl
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Absolute Time That Subject is in UMSS Range 2-4 During Treatment Period
時間枠：During the treatment (6 to 24 hours)
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The level of sedation will be assessed using the University of Michigan Sedation Scale (UMSS). Score 0 (awake/alert); Score 1 (sleepy/responds appropriately); Score 2 (somnolent/arouses to light stimuli); Score 3 (deep sleep/arouses to deeper physical stimuli); Score 4 (unarousable). The UMSS scores obtained just prior the loading dose (LD) and 5 and 10 minutes during LD; 0, 5, 10, 15, 30, and 60 minutes and thereafter every 4 hours of the maintenance infusion; within 5 minutes of obtaining each pharmacokinetic sample; within 5 minutes prior and after any midazolam rescue during dexmedetomidine infusion period. |
During the treatment (6 to 24 hours)
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Number of Subjects Who Received Rescue Medication for Sedation and Analgesic
時間枠：During the treatment (6 to 24 hours)
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Participants who received rescue medication midazolam for sedation and/or fentanyl for analgesic during study drug Infusion
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During the treatment (6 to 24 hours)
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協力者と研究者
ここでは、この調査に関係する人々や組織を見つけることができます。
捜査官
- 主任研究者：Constantinos Chrysostomou, MD、Children's Hospital of Pittusburgh of UPMC
研究記録日
これらの日付は、ClinicalTrials.gov への研究記録と要約結果の提出の進捗状況を追跡します。研究記録と報告された結果は、国立医学図書館 (NLM) によって審査され、公開 Web サイトに掲載される前に、特定の品質管理基準を満たしていることが確認されます。
主要日程の研究
研究開始
2011年6月1日
一次修了 (実際)
2011年8月1日
研究の完了 (実際)
2011年8月1日
試験登録日
最初に提出
2011年6月20日
QC基準を満たした最初の提出物
2011年6月22日
最初の投稿 (見積もり)
2011年6月23日
学習記録の更新
投稿された最後の更新 (見積もり)
2015年7月24日
QC基準を満たした最後の更新が送信されました
2015年6月29日
最終確認日
2015年6月1日
詳しくは
本研究に関する用語
追加の関連 MeSH 用語
その他の研究ID番号
- DEX-11-01
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。