A Study Evaluating the Safety and Pharmacokinetics/Pharmacodynamics of HSK3486
A Single-center, Open-label, Randomized, Double-crossover, Propofol-controlled, Two-stage Study Evaluating the Safety and Pharmacokinetics/Pharmacodynamics of IV Maintenance Dose After An Initial Dose and IV Single Loade Dose Plus Maintenance Dose of HSK3486 Emulsion fo Injection in Healthy 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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Chengdu、中国
- West China Hospital,Sichuan University
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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 males or females with full capacity for civil conduct, aged ≥ 18 and ≤ 49 years old;
- Body weight > 45 kg, and body mass index (BMI) ≥ 19 and ≤26 kg/m2;
- Blood pressure between 90-140/60-90 mmHg; heart rate between 60-99 bpm; body temperature between 35.8-37.5 °C; respiration rate between 12-20 breaths per minute; SpO2 when inhaling > 95%;
- Normal physical examinations, laboratory examinations (routine blood test, blood biochemistry and routine urinalysis), and 12-Lead ECG, or abnormal but without clinical significance; no potential difficult airway (modified Mallampati score I-III);
- No previous history of major organ primary diseases, such as liver, kidneys, digestive tract, blood, and metabolic diseases; no history of malignant hyperthermia and other genetic conditions; no history of mental/neurological diseases; No history of epilepsy; no contraindications for deep sedation/general anesthesia; no clinically significant history of anesthesia accidents;
- Subjects must understand the procedures and methods of this study, and be willing to provide informed consent and to complete the trial in strict accordance with trial protocol.
Exclusion Criteria:
- Known sensitivity to propofol, excipients in propofol medium-/long-chain triglyceride emulsion injection, excipients in HSK3486 emulsion injection (soybean oil, glycerin, triglyceride, egg lecithin, sodium oleate, and sodium hydroxide); history of drug allergies (including anesthetics), allergic diseases, or those with hyperactive immune response;
- History of drug abuse or any signs of chronic benzodiazepines use (such as insomnia, anxiety, spasms) within 3 months prior to screening, or a positive urine drug test during screening;
- Participated in clinical trials involving any medications or medical devices within 3 months prior to screening, or subjects who have participated in 3 or more drug clinical trials within the past year;
- Serious infection, trauma or major surgery within 4 weeks before screening; or acute disease with clinical significance (determined by the investigator) within 2 weeks before screening, including GI diseases or infections (such as respiratory or CNS infections);
- In receipt of propofol, other sedatives/anesthetics and/or opioid analgesics or compounds containing analgesics within 3 days prior to screening;
- In receipt of prescription drugs, Chinese herbal medicines, over-the-counter drugs or food supplements (such as vitamins and calcium supplements) other than contraceptives, paracetamol, oral non-steroidal anti-inflammatory drugs, topical over-the-counter preparations, within 2 weeks prior to enrollment; unless the principal investigator (PI) and the sponsor agree that the medication has no effect on the safety and PK/PD results of the trial;
- History of cardiovascular diseases such as: postural hypotension, severe arrhythmia, heart failure, Adams-Stokes syndrome, unstable angina, myocardial infarction within 6 months before screening, tachycardia/bradycardia requiring medication, third-degree atrioventricular block or QTcF interval ≥ 450 ms (Fridericia's correction formula);
- Impaired respiratory function, history of obstructive pulmonary disease, history of asthma, sleep apnea syndromes; history of failed tracheal intubation; history of bronchospasm requiring treatment within 3 months prior to screening; acute upper respiratory tract infection, and with obvious symptoms such as fever, wheezing, nasal congestion and cough within 1 week prior to baseline;
- History of GI tract diseases: Gastrointestinal obstruction, active GI bleed, potential for reflux and aspiration;
Laboratory results that meet any of the following during screening/enrollment:
- Positive test for either HBsAg, HCV, HIV, or syphilis;
Abnormal hepatic or renal function confirmed after re-examination;
- ALT or AST > 1×ULN;
- Creatinine > 1×ULN;
- TBIL > 1.5×ULN;
- History of alcohol abuse within 3 months prior to screening, abuse defined as average of > 2 units of alcohol per day (1 unit = 360 mL beer or 45 mL liquor with 40% alcohol or 150 mL wine), or positive blood alcohol concentration during screening;
- Blood donation or blood loss ≥ 200 mL within 30 days before the trial; plasma donation or plasma exchange within 7 days before the trial;
- Subjects who continue to smoke, drink alcohol, or consume any food or beverages containing xanthine or caffeine, to participate in strenuous physical activities and other factors that may affect drug absorption, distribution, metabolism, and excretion within 2 days prior to enrollment; subjects who are unable to fast for 6 hours prior to dose administration;
- Subjects expected to have surgery or hospitalization during the trial;
- Women who are pregnant or breastfeeding; women of child-bearing potential or men who are unwilling to use contraception during the trial; subjects who are planning pregnancy within 1 month after the completion of the trial (including male subjects);
- Subjects judged by the investigator to be unsuitable for participating in this trial for any reason.
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:クロスオーバー割り当て
- 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:HSK3486
First-stage: 1mg/kg/h, 0.4mg/kg/h; Second-stage:Single loading dose: 0.2mg/kg, maintenance dose: 0.35mg/kg/h,
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First-stage:after an initial dose of 1mg/kg/h, If the BIS is in the range of 80 to 60 and the continuous RASS score = 3 or one time RASS score ≤ -4, the 0.4 mg/kg/h maintenance dose is administered. The total infusion time was 4h. Second-stage: a single loading dose of 0.2 mg/kg given over 1 minute, then a continuous infusion of maintenance dose 0.35 mg/kg/h for a total infusion time of 12h. |
アクティブコンパレータ:Propofol
First-stage: 5mg/kg/h, 2mg/kg/h; Second-stage:Single load ing dose: 1mg/kg, maintenance dose: 1.75mg/kg/h
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First-stage: after an initial dose of 5mg/kg/h, If the BIS is in the range of 80 to 60 and the continuous RASS score = 3 or one time RASS score ≤ -4, the 0.4 mg/kg/h maintenance dose is administered. The total infusion time was 4h. Second-stage: loading dose of 1mg/kg given over 1 minute, then a continuous infusion of maintenance dose 1.75 mg/kg/h for a total infusion time of 12h. |
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 |
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血圧(収縮期、拡張期、平均動脈圧)
時間枠:スクリーニングから投与後3日まで
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安全エンドポイント
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スクリーニングから投与後3日まで
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heart rate
時間枠:from the screening to 3 days post-dose
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safety endpoits
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from the screening to 3 days post-dose
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respiratory rate
時間枠:from the screening to 3 days post-dose
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safety endpoits
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from the screening to 3 days post-dose
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blood oxygen saturation
時間枠:from the screening to 3 days post-dose
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safety endpoits
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from the screening to 3 days post-dose
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Number of patients with adverse events
時間枠:from the baseline to 3 days post-dose
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safety endpoits
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from the baseline to 3 days post-dose
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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 |
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総クリアランス
時間枠:・1日目の投与30分前から投与24時間後まで
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・1日目の投与30分前から投与24時間後まで
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流通量
時間枠:・1日目の投与30分前から投与24時間後まで
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・1日目の投与30分前から投与24時間後まで
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Richmond Agitation Sedation Scale( scores:+4~-5)
時間枠:-30 minutes before administration until the subject is completely awakened post administration on day 1
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Change from baseline in Richmond Agitation Sedation Scale(RASS) score
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-30 minutes before administration until the subject is completely awakened post administration on day 1
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Bispectral index
時間枠:-30 minutes before administration until the subject is completely awakened post administration on day 1
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-30 minutes before administration until the subject is completely awakened post administration on day 1
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Sedation/anesthesia satisfaction, satisfaction assessment of subjects, anesthesiologists, and endoscopic physicians
時間枠:-30 minutes before administration until the subject is completely awakened post administration on day 1
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-30 minutes before administration until the subject is completely awakened post administration on day 1
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Terminal elimination half life
時間枠:-30 minutes before administration until 24 hours post administration on day 1
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-30 minutes before administration until 24 hours post administration on day 1
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plasma concentration at the end of infusion
時間枠:-30 minutes before administration until 24 hours post administration on day 1
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-30 minutes before administration until 24 hours post administration on day 1
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その他の成果指標
結果測定 |
時間枠 |
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area under curve from time 0 to the last measurable blood sampling time (AUC0-last)
時間枠:-30 minutes before administration until 24 hours post administration on day 1
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-30 minutes before administration until 24 hours post administration on day 1
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area under curve from time 0 to infinite time (AUC0-inf)
時間枠:-30 minutes before administration until 24 hours post administration on day 1
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-30 minutes before administration until 24 hours post administration on day 1
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Peak concentration
時間枠:-30 minutes before administration until 24 hours post administration on day 1
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-30 minutes before administration until 24 hours post administration on day 1
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time to peak observed (Tmax)
時間枠:-30 minutes before administration until 24 hours post administration on day 1
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-30 minutes before administration until 24 hours post administration on day 1
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協力者と研究者
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 (実際)
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
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。
HSK3486の臨床試験
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Sichuan Haisco Pharmaceutical Group Co., LtdThe First Hospital of Jilin University完了
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Sichuan Haisco Pharmaceutical Group Co., Ltd完了
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Sichuan Haisco Pharmaceutical Group Co., LtdThe First Affiliated Hospital of Zhengzhou University完了
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Sichuan Haisco Pharmaceutical Group Co., Ltd完了
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Sichuan Haisco Pharmaceutical Group Co., Ltd引きこもった
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Sichuan Haisco Pharmaceutical Group Co., Ltd完了
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Sichuan Haisco Pharmaceutical Group Co., LtdThe First Hospital of Jilin University完了
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Sichuan Haisco Pharmaceutical Group Co., Ltd完了
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University of Medicine and Dentistry of New Jersey引きこもった
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Sichuan Haisco Pharmaceutical Group Co., Ltd完了