A Phase I Study to Investigate the Effect of Hepatic Impairment on the Pharmacokinetics, Safety, and Tolerability of AZD4144
A Phase I, Multicentre, Single-Dose, Non-Randomised, Open-Label, Parallel-Group Study to Investigate the Effect of Hepatic Impairment on the Pharmacokinetics, Safety, and Tolerability of AZD4144
調査の概要
詳細な説明
This Phase I, open-label, parallel group study will investigate the single oral dose PK, safety, and tolerability of AZD4144 to male and female participants with mild, moderate, and severe hepatic impairment compared to matched controls with normal hepatic function.
Approximately 60 participants are planned to be screened to achieve up to 30 evaluable participants. For each of the 3 hepatic impairment groups, 6 participants are planned to complete the study. Initially, 6 participants with normal hepatic function will be recruited, matched on a group level regarding sex, age, and BMI to the participants with hepatic impairment. Additional participants with normal hepatic function, up to a total of 12, may be included if needed to meet the matching criteria.
研究の種類
入学 (推定)
段階
- フェーズ 1
連絡先と場所
研究連絡先
- 名前:AstraZeneca Clinical Study Information Center
- 電話番号:1-877-240-9479
- メール:information.center@astrazeneca.com
研究場所
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Arizona
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Mesa、Arizona、アメリカ、85210
- Research Site
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Florida
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Miami Lakes、Florida、アメリカ、33014
- Research Site
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Orlando、Florida、アメリカ、32809
- Research Site
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Texas
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Austin、Texas、アメリカ、78757
- Research Site
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-
参加基準
適格基準
就学可能な年齢
- 大人
- 高齢者
健康ボランティアの受け入れ
説明
Inclusion Criteria:
Healthy Matched Control Participants Only (Group 4):
• Must be medically healthy with no clinically significant medical history, physical examination, clinical laboratory profiles, vital signs, or 12-lead ECGs, as deemed by the investigator at screening and Day -1.
Hepatically-Impaired Participants Only (Groups 1, 2, and 3):
- Must have a diagnosis of chronic (≥ 6 months) and stable hepatic impairment (e.g., no clinically significant change in signs, symptoms, or laboratory parameters of hepatic disease status within 30 days prior to study screening, as determined by the investigator at screening and Day -1).
- Must be classified by the investigator as CP Class A (Group 1), CP Class B (Group 2), or CP Class C (Group 3) at screening.
- Participant must be stable on a concomitant medication and/or treatment regimen (defined as not starting a new treatment/medication[s] or a change in the dosage or frequency of the concomitant medication[s] within at least 2 weeks prior to screening).
All Groups:
- Body weight ≥ 50 kg and body mass index (BMI) within the range 18 to 45 kg/m2, inclusive.
- All Females of Childbearing Potential (FOCBP) must have a negative pregnancy test at screening and Day -1.
Exclusion Criteria:
- History of any clinically significant disease or disorder which, in the opinion of the investigator, may either put the participant at risk because of participation in the study, or influence the results or the participant's ability to participate in the study.
- Have Type 1 diabetes mellitus or T2DM (Group 4)
- Known history of primary immunodeficiency (congenital or acquired) or an underlying condition that predisposes to infection.
- History of long QT syndrome or prolonged QTcF.
- Presence of unstable medical or psychological conditions, or any evidence of additional severe or uncontrolled systemic disease (e.g., currently unstable or uncompensated renal, cardiovascular, or respiratory disease).
- Evidence of renal impairment at screening
- Current liver transplant or anticipated to receive liver transplant within 2 months of screening or Day -1 (Group 1, 2 and 3).
- Use of any of the prescription and non-prescription prohibited medications.
- Concomitant immunosuppressive, steroid treatment.
- Live or attenuated vaccines within 3 months prior to study intervention or live vaccinations planned during the trial.
- History of severe allergy/hypersensitivity of AZD4144 or any of the excipients of the product.
- Has received another new chemical entity (defined as a compound which has not been approved for marketing) within 30 days prior to study intervention in this study or, if known, 5 half-lives from last dose in the previous study to study intervention in this study, whichever is longest.
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:非ランダム化
- 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 |
|---|---|
|
実験的:グループ1
軽度の肝障害のある参加者(CPクラスA、スコア5または6)
|
Single oral dose of AZD4144 in participants from all groups
|
|
実験的:グループ2
中等度の肝機能障害(CPクラスB、スコア7~9点)を有する参加者。
|
Single oral dose of AZD4144 in participants from all groups
|
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実験的:Group 3
Participants with severe hepatic impairment (CP Class C, score of 10 to 15).
|
Single oral dose of AZD4144 in participants from all groups
|
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実験的:Group 4
Participants with normal hepatic function matched on a group level regarding sex, age, and BMI to the impaired groups
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Single oral dose of AZD4144 in participants from all groups
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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 |
|---|---|---|
|
PK parameters AUCinf
時間枠:Day 0 through Day 7 or 9
|
area under the concentration-time curve from zero to infinity
|
Day 0 through Day 7 or 9
|
|
PK parameter AUClast
時間枠:Day 0 through Day 7 or 9
|
area under the concentration-time curve from zero to the last measurable concentration
|
Day 0 through Day 7 or 9
|
|
PK parameters AUC(0-144)
時間枠:Day 0 through Day 7
|
area under the curve from time zero to time 144hours post dose
|
Day 0 through Day 7
|
|
PK parameter Cmax
時間枠:Day 0 through Day 7 or 9
|
maximum observed plasma concentration
|
Day 0 through Day 7 or 9
|
二次結果の測定
結果測定 |
メジャーの説明 |
時間枠 |
|---|---|---|
|
PK parameters tmax
時間枠:Day 0 through Day 7 or 9
|
time to reach maximum observed plasma concentration
|
Day 0 through Day 7 or 9
|
|
PK Parameters t1/2λz
時間枠:Day 0 through Day 7 or 9
|
half-life associated with terminal slope (λz)
|
Day 0 through Day 7 or 9
|
|
PK Parameters CL/F
時間枠:Day 0 through Day 7 or 9
|
apparent total body clearance of drug from plasma after extravascular administration
|
Day 0 through Day 7 or 9
|
|
PK Parameters Vz/F
時間枠:Day 0 through Day 7 or 9
|
apparent volume of distribution during the terminal phase after extravascular administration.
|
Day 0 through Day 7 or 9
|
|
PK Parameters CLNR/F
時間枠:Day 0 through Day 7 or 9
|
non-renal clearance of drug from plasma
|
Day 0 through Day 7 or 9
|
|
PK parameters CLR from urine concentrations
時間枠:Day 0 through Day 3
|
renal clearance from urine concentration
|
Day 0 through Day 3
|
|
PK parameters Ae determined from urine concentration
時間枠:Day 0 through Day 3
|
amount of unchanged drug excreted into the urine
|
Day 0 through Day 3
|
|
PK parameters fe determined from urine concentration
時間枠:Day 0 through Day 3
|
Percentage of unchanged drug excreted into the urine
|
Day 0 through Day 3
|
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PK Parameters tlast
時間枠:Day 0 through Day 7 or 9
|
time of last quantifiable concentration
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Day 0 through Day 7 or 9
|
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PK Parameters λz
時間枠:Day 0 through Day 7 or 9
|
terminal elimination rate constant
|
Day 0 through Day 7 or 9
|
|
PK Parameters AUC(0-24)
時間枠:Day 0 through Day 1
|
area under the plasma concentration-time curve from time 0 to 24 hours postdose
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Day 0 through Day 1
|
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PK Parameters AUC(0-72)
時間枠:Day 0 through Day 3
|
area under the plasma concentration-time curve from time 0 to 72 hours postdose
|
Day 0 through Day 3
|
協力者と研究者
スポンサー
研究記録日
主要日程の研究
研究開始 (推定)
一次修了 (推定)
研究の完了 (推定)
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
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