INC280 in Healthy Subjects With Impaired Hepatic Function and Subjects With Normal Hepatic Function
An Open Label, Single-dose, Multi-center, Parallel-group, Two-staged Study to Evaluate Pharmacokinetics of Oral cMET Inhibitor INC280 in Non-Cancer Subjects With Impaired Hepatic Function and Non-Cancer Subjects With Normal Hepatic Function
This is a phase I, multi-center, open-label, single oral dose, parallel group study to evaluate the pharmacokinetics and safety of INC280 in non-cancer subjects with impaired hepatic function and non-cancer subjects with normal hepatic function.The study population will be healthy male and postmenopausal or sterile female subjects who meet all of the inclusion and none of the exclusion criteria. Subjects will be assigned to groups according to their hepatic function: normal (Group 1), mild (Group 2), moderate (Group 3), and severe (Group 4) impairment. This study consists of a two-staged design with interim analysis. In Stage 1, subjects in Groups 1, 2 and 3 will be enrolled. Upon completion of Stage 1, an interim analysis will be conducted. Depending on the results of the analysis, either the study will conclude with no further enrollment or Stage 2 will commence with enrollment of Group 4.
A minimum of 6 evaluable subjects per group will be enrolled.Once enrolled in the study, participants will be confined to the facility for 4 days, given a single dose of INC280 and monitored for pharmacokinetic and safety assessments.
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
-
-
Florida
-
Miami、Florida、アメリカ、33136
- University of Miami Miller School of Medicine Clinical Resea Oncology
-
Miami、Florida、アメリカ、33142
- Clinical Pharmacology of Miami, LLC.
-
Orlando、Florida、アメリカ、32086
- Orlando Clinical Research Center
-
-
Minnesota
-
Minneapolis、Minnesota、アメリカ、55404
- DaVita Clinical Research
-
-
North Carolina
-
Durham、North Carolina、アメリカ、27710
- Duke University Medical Center Oncology
-
-
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 (all groups):
- Female subjects must be postmenopausal or sterile
- Good health, as determined by absence of clinically significant findings in medical history, physical examination, vital signs, and ECGs, unless it is consistent with known clinical disease for hepatic impairment subjects
- Adequate organ function and normal laboratory tests, unless it is consistent with known clinical disease for hepatic impairment subjects
- Body Mass Index (BMI) of 18- 36 kg/m2, with body weight ≥ 50 kg
Inclusion Criteria (hepatic impairment groups):
- Confirmed liver disease
- Stable comorbidities are allowed as long as generally considered healthy
- Subjects with hepatic impairment must meet the following laboratory values:
- Aspartate transaminase (AST) ≤ 5 x ULN
- Alanine transaminase (ALT) ≤ 5 x ULN
- Total bilirubin ≤ 3 x ULN (≤ 5 x XULN for subjects with severe hepatic impairment [group 4])
- Calculated creatinine clearance (using Cockcroft-Gault formula) ≥ 45 mL/min
- Platelets > 50 x 10^9/L. Subjects with severe hepatic impairment can be enrolled if platelet count > 40 x 10^9/L
Exclusion Criteria (all groups):
- History or presence of clinically significant ECG abnormalities or clinically significant cardiovascular disease
- Immunocompromised subjects, including HIV
- Use of drugs known to affect CYP3A4
- Use of QT-prolonging drugs
- Use of any other drugs, unless they are required to treat the hepatic impairment subject's disease
- Use of proton pump inhibitors (PPI) medications within 7 days prior to dosing and during the current study until last day of confinement
Exclusion Criteria (normal hepatic function group):
- A positive Hepatitis B surface antigen (HBsAg) or Hepatitis C test result
Exclusion Criteria (hepatic impairment groups):
- Active Grade 3 or 4 hepatic encephalopathy within 4 weeks of study entry
- Clinical evidence of severe ascites
- Ascites requiring paracentesis within 3 weeks prior to dosing
Other protocol-defined inclusion/exclusion criteria may apply.
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：正常な肝機能
肝機能が正常な者
|
Single 200 mg dose INC280
|
|
実験的：軽度の肝障害
軽度の肝障害のある者
|
Single 200 mg dose INC280
|
|
実験的：中等度の肝障害
中等度の肝障害のある者
|
Single 200 mg dose INC280
|
|
実験的：Severe hepatic impairment
Subjects with severe hepatic impairment
|
Single 200 mg dose INC280
|
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 |
|---|---|---|
|
AUClast of INC280
時間枠：Up to 72 hours post-dose
|
INC280 pharmacokinetic parameters
|
Up to 72 hours post-dose
|
|
AUCinf of INC280
時間枠：Up to 72 hours post-dose
|
INC280 pharmacokinetic parameters
|
Up to 72 hours post-dose
|
|
Cmax of INC280
時間枠：Up to 72 hours post-dose
|
INC280 pharmacokinetic parameters
|
Up to 72 hours post-dose
|
|
Tmax of INC280
時間枠：Up to 72 hours post-dose
|
INC280 pharmacokinetic parameters
|
Up to 72 hours post-dose
|
|
T1/2 of INC280
時間枠：Up to 72 hours post-dose
|
INC280 pharmacokinetic parameters
|
Up to 72 hours post-dose
|
|
CL/F of INC280
時間枠：Up to 72 hours post-dose
|
INC280 pharmacokinetic parameters
|
Up to 72 hours post-dose
|
|
Vz/F of INC280
時間枠：Up to 72 hours post-dose
|
INC280 pharmacokinetic parameters
|
Up to 72 hours post-dose
|
二次結果の測定
結果測定 |
メジャーの説明 |
時間枠 |
|---|---|---|
|
Adverse events based on the CTCAE v4.03 grade (severity) and frequency, and other safety data (e.g., ECG, laboratory results)
時間枠：Up to 30 days
|
Safety
|
Up to 30 days
|
|
Unbound fraction and AUClast based on unbound concentration in plasma
時間枠：3 hours post-dose
|
To assess the plasma protein binding of INC280
|
3 hours post-dose
|
|
Unbound fraction and AUCinf based on unbound concentration in plasma
時間枠：3 hours post-dose
|
To assess the plasma protein binding of INC280
|
3 hours post-dose
|
|
Unbound fraction and Cmax based on unbound concentration in plasma
時間枠：3 hours post-dose
|
To assess the plasma protein binding of INC280
|
3 hours post-dose
|
|
Unbound fraction and Tmax based on unbound concentration in plasma
時間枠：3 hours post-dose
|
To assess the plasma protein binding of INC280
|
3 hours post-dose
|
|
Unbound fraction and T1/2 based on unbound concentration in plasma
時間枠：3 hours post-dose
|
To assess the plasma protein binding of INC280
|
3 hours post-dose
|
|
Unbound fraction and CL/F based on unbound concentration in plasma
時間枠：3 hours post-dose
|
To assess the plasma protein binding of INC280
|
3 hours post-dose
|
|
Unbound fraction and Vz/F based on unbound concentration in plasma
時間枠：3 hours post-dose
|
To assess the plasma protein binding of INC280
|
3 hours post-dose
|
協力者と研究者
スポンサー
捜査官
- スタディディレクター：NovartisPharmaceuticals、NovartisPharmaceuticals
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
その他の研究ID番号
- CINC280A2106
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?
医薬品およびデバイス情報、研究文書
米国FDA規制医薬品の研究
米国FDA規制機器製品の研究
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。