To Assess the Pharmacokinetics, Safety and Tolerability of Selumetinib in Renal Impaired Subjects and Healthy Subjects
29 июня 2015 г. обновлено: AstraZeneca
An Open Label Comparative Study of the Pharmacokinetics, Safety and Tolerability of Selumetinib (AZD6244, ARRY 142886) (Hyd Sulfate) Following a Single Oral Dose in Subjects With Renal Impairment and Healthy Subjects
A study to assess the pharmacokinetics, safety and tolerability of Selumetinib (AZD6244, ARRY-142886) in subjects with renal impairment and healthy subjects
Обзор исследования
Подробное описание
An open label study to assess the pharmacokinetics, safety and tolerability of 50 mg single oral dose of Selumetinib (AZD6244, ARRY-142886) in subjects with renal impairment and healthy subjects
Тип исследования
Интервенционный
Регистрация (Действительный)
24
Фаза
- Фаза 1
Контакты и местонахождение
В этом разделе приведены контактные данные лиц, проводящих исследование, и информация о том, где проводится это исследование.
Места учебы
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Florida
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Orlando, Florida, Соединенные Штаты
- Research Site
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Критерии участия
Исследователи ищут людей, которые соответствуют определенному описанию, называемому критериям приемлемости. Некоторыми примерами этих критериев являются общее состояние здоровья человека или предшествующее лечение.
Критерии приемлемости
Возраст, подходящий для обучения
18 лет и старше (Взрослый, Пожилой взрослый)
Принимает здоровых добровольцев
Нет
Полы, имеющие право на обучение
Все
Описание
Inclusion Criteria all participants:
- Male and female (non childbearing potential) subjects aged 18 years or more with suitable veins for cannulation or repeated venipuncture.
Have a weight of at least 50 kg (110 lbs) and body mass index (BMI) between 18 and 40 kg/m2, inclusive.
Inclusion healthy volunteers only:
Must be in good health as determined by a medical history, physical examination, 12 lead ECG, clinical laboratory evaluations, and an ophthalmic examination performed before the administration of the investigational product.
Inclusion renal impaired patients only:
- Stable renal function
Exclusion Criteria all participants:
- Subjects of Japanese or non Japanese Asian ethnicity.
- Any one parent or grandparent (maternal or paternal) is Japanese or non-Japanese Asian (e.g. China, Taiwan, Korea, Philippines, Thailand, Vietnam and Malaysia). Asian Indians are acceptable.
- Subjects who smoke more than 10 cigarettes or the equivalent in tobacco per day
In the opinion of the investigator, any evidence of additional severe or uncontrolled systemic disease (eg, currently unstable or uncompensated hepatic, cardiovascular, or respiratory disease) or laboratory finding, physical examination, hematology, clinical chemistry, urinalysis, vital signs, or 12-lead ECG that makes it undesirable for the subject to participate in the study.
Exclusion renal impaired patients only:
- Subjects with an active renal transplant (subjects who have previously received a renal transplant and are currently undergoing dialysis due to transplant failure may be enrolled).
- Acute coronary syndrome within 6 months prior to administration of the investigational product.
Учебный план
В этом разделе представлена подробная информация о плане исследования, в том числе о том, как планируется исследование и что оно измеряет.
Как устроено исследование?
Детали дизайна
- Основная цель: Фундаментальная наука
- Распределение: Нерандомизированный
- Интервенционная модель: Параллельное назначение
- Маскировка: Нет (открытая этикетка)
Оружие и интервенции
Группа участников / Армия |
Вмешательство/лечение |
|---|---|
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Экспериментальный: HV selumetinib Stage 1
Healthy volunteer (HV)group to receive selumetinib 50mg (2x25mg) orally
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selumetinib 50 mg (2x25mg) administered by mouth as capsules
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Экспериментальный: ESRD selumetinib Stage 1
End stage renal disease (ESRD)patients to recieve selumetinib 50mg (2x25mg) orally
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selumetinib 50 mg (2x25mg) administered by mouth as capsules
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Экспериментальный: Selumetinib stage 2
If deemed necessary patients with mild and/or moderate and/or severe renal impairment will recieve selumetinib 50mg(2x25mg) orally
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selumetinib 50 mg (2x25mg) administered by mouth as capsules
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Что измеряет исследование?
Первичные показатели результатов
Мера результата |
Мера Описание |
Временное ограничение |
|---|---|---|
|
Description of the pharmacokinetic(PK) profile in terms of maximum observed plasma concentration (Cmax)
Временное ограничение: Samples taken at predose, 30min, 1h, 1h30min, 2h, 2h 30min, 3h, 3h 30min, 4h, 5h,6h,7h,8h,12h,18h,24h,36h,48h and 76h
|
This will be taken at visit 2 for Healthy volunteers and at visit 2 and 3 for patients with end stage renal disease
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Samples taken at predose, 30min, 1h, 1h30min, 2h, 2h 30min, 3h, 3h 30min, 4h, 5h,6h,7h,8h,12h,18h,24h,36h,48h and 76h
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Description of PK profile in terms of area under plasma concentration-time curve from zero extrapolated to infinity (AUC)
Временное ограничение: Samples taken at predose, 30min, 1h, 1h30min, 2h, 2h 30min, 3h, 3h 30min, 4h, 5h,6h,7h,8h,12h,18h,24h,36h,48h and 76h
|
This will be taken at visit 2 for Healthy volunteers and at visit 2 and 3 for patients with end stage renal disease
|
Samples taken at predose, 30min, 1h, 1h30min, 2h, 2h 30min, 3h, 3h 30min, 4h, 5h,6h,7h,8h,12h,18h,24h,36h,48h and 76h
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Description of PK profile in terms of area under plasma concentration-time curve to time of last measurable concentration (AUC[0-t]) for selumetinib if AUC is not reportable in more than 80% of subjects
Временное ограничение: Samples taken at predose, 30min, 1h, 1h30min, 2h, 2h 30min, 3h, 3h 30min, 4h, 5h,6h,7h,8h,12h,18h,24h,36h,48h and 76h
|
This will be taken at visit 2 for Healthy volunteers and at visit 2 and 3 for patients with end stage renal disease
|
Samples taken at predose, 30min, 1h, 1h30min, 2h, 2h 30min, 3h, 3h 30min, 4h, 5h,6h,7h,8h,12h,18h,24h,36h,48h and 76h
|
Вторичные показатели результатов
Мера результата |
Мера Описание |
Временное ограничение |
|---|---|---|
|
Description of the safety profile in terms of adverse events, physical examinations, ophthalmologic assessments, vital signs, clinical laboratory assessments and 12-lead electrocardiograms.
Временное ограничение: From screening until follow up. Approximately 6 weeks for healthy volunteers and 8 weeks for renal patients
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From screening until follow up. Approximately 6 weeks for healthy volunteers and 8 weeks for renal patients
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Description of the PK profile in terms of time to reach maximum observed concentration administration (tmax)
Временное ограничение: Samples taken at predose, 30min, 1h, 1h30min, 2h, 2h 30min, 3h, 3h 30min, 4h, 5h,6h,7h,8h,12h,18h,24h,36h,48h and 76h
|
This will be taken at visit 2 for Healthy volunteers and at visit 2 and 3 for patients with end stage renal disease
|
Samples taken at predose, 30min, 1h, 1h30min, 2h, 2h 30min, 3h, 3h 30min, 4h, 5h,6h,7h,8h,12h,18h,24h,36h,48h and 76h
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Description of PK profile in terms of area under the plasma concentration time curve from zero to 12 hours postdose (AUC[0-12])
Временное ограничение: Samples taken at predose, 30min, 1h, 1h30min, 2h, 2h 30min, 3h, 3h 30min, 4h, 5h,6h,7h,8h, and12h
|
This will be taken at visit 2 for Healthy volunteers and at visit 2 and 3 for patients with end stage renal disease
|
Samples taken at predose, 30min, 1h, 1h30min, 2h, 2h 30min, 3h, 3h 30min, 4h, 5h,6h,7h,8h, and12h
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Description of PK profile in terms of terminal rate constant (λz), terminal elimination half-life (t1/2), apparent oral clearance (CL/F)
Временное ограничение: Samples taken at predose, 30min, 1h, 1h30min, 2h, 2h 30min, 3h, 3h 30min, 4h, 5h,6h,7h,8h,12h,18h,24h,36h,48h and 76h
|
This will be taken at visit 2 for Healthy volunteers and at visit 2 and 3 for patients with end stage renal disease
|
Samples taken at predose, 30min, 1h, 1h30min, 2h, 2h 30min, 3h, 3h 30min, 4h, 5h,6h,7h,8h,12h,18h,24h,36h,48h and 76h
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Description of PK profile in terms of apparent volume of distribution at steady state (Vss/F) and apparent volume of distribution during the terminal phase (Vz/F)
Временное ограничение: Samples taken at predose, 30min, 1h, 1h30min, 2h, 2h 30min, 3h, 3h 30min, 4h, 5h,6h,7h,8h,12h,18h,24h,36h,48h and 76h
|
This will be taken at visit 2 for Healthy volunteers and at visit 2 and 3 for patients with end stage renal disease
|
Samples taken at predose, 30min, 1h, 1h30min, 2h, 2h 30min, 3h, 3h 30min, 4h, 5h,6h,7h,8h,12h,18h,24h,36h,48h and 76h
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Description of PK profile in terms of mean residence time (MRT) and fraction unbound (fu), free Cmax (Cmax, u), free AUC (AUCu), free AUC(0-t) (AUC[0-t],u) and unbound CL/F (CL/Fu)
Временное ограничение: Samples taken at predose, 30min, 1h, 1h30min, 2h, 2h 30min, 3h, 3h 30min, 4h, 5h,6h,7h,8h,12h,18h,24h,36h,48h and 76h
|
This will be taken at visit 2 for Healthy volunteers and at visit 2 and 3 for patients with end stage renal disease
|
Samples taken at predose, 30min, 1h, 1h30min, 2h, 2h 30min, 3h, 3h 30min, 4h, 5h,6h,7h,8h,12h,18h,24h,36h,48h and 76h
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Description of PK profile in terms of the amount of drug excreted in urine (Ae) the fraction of dose excreted in urine (fe), renal clearance (CLR) for selumetinib and AUC, Cmax, tmax, t1/2, λz, AUC(0-12) and AUC(0-t)
Временное ограничение: The urine collection intervals will be from -12 to 0 (predose), and 0 to 6, 6 to 12, 12 to 24, 24 to 36, 36 to
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These collection will be taken on visit 2 for the healthy volunteers and on visit 2 and 3 if the patients can produce urine
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The urine collection intervals will be from -12 to 0 (predose), and 0 to 6, 6 to 12, 12 to 24, 24 to 36, 36 to
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Description of the PK profile in terms of the metabolite to parent AUC and Cmax ratios (MRAUC and MRCmax)
Временное ограничение: Samples taken at predose, 30min, 1h, 1h30min, 2h, 2h 30min, 3h, 3h 30min, 4h, 5h,6h,7h,8h,12h,18h,24h,36h,48h and 76h
|
These samples will be taken on visit 2 for the healthy volunteers and on both visit 2 and visit 3
|
Samples taken at predose, 30min, 1h, 1h30min, 2h, 2h 30min, 3h, 3h 30min, 4h, 5h,6h,7h,8h,12h,18h,24h,36h,48h and 76h
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Description of the PK profile in terms of Ae, fe, and CLR for N-desmethyl selumetinib (and the amide metabolite, if deemed appropriate)
Временное ограничение: Samples taken at predose, 30min, 1h, 1h30min, 2h, 2h 30min, 3h, 3h 30min, 4h, 5h,6h,7h,8h,12h,18h,24h,36h,48h and 76h
|
Samples taken at predose, 30min, 1h, 1h30min, 2h, 2h 30min, 3h, 3h 30min, 4h, 5h,6h,7h,8h,12h,18h,24h,36h,48h and 76h
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Description of the PK profile in terms of time-matched area under the plasma concentration time curve from 1 to 5 hours postdose (AUC[1-5])
Временное ограничение: Sample taken predose, at 1h just before dialyse and at 5h after the end of the dialyse
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This will only be taken at the visit when dose is given 1h before dialyse start
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Sample taken predose, at 1h just before dialyse and at 5h after the end of the dialyse
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Description of the PK profile in terms of cumulative amount extracted during dialysis (Ad[1-5]), and dialysis clearance (CLD)
Временное ограничение: Samples taken from dialysate collections over 1 hour intervals throughout the entire (approximately 4 hours) dialysis period ie, 0 to 1, 1 to 2, 2 to 3, 3
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This will only be collected during visit 2 and only on end stage renal disease patients
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Samples taken from dialysate collections over 1 hour intervals throughout the entire (approximately 4 hours) dialysis period ie, 0 to 1, 1 to 2, 2 to 3, 3
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Соавторы и исследователи
Здесь вы найдете людей и организации, участвующие в этом исследовании.
Спонсор
Следователи
- Главный следователь: Thomas C Marbury, MD, Orlando Clinical Research Centre, US
- Директор по исследованиям: Ian Smith, MD, Astrazeneca United kingdom
Публикации и полезные ссылки
Лицо, ответственное за внесение сведений об исследовании, добровольно предоставляет эти публикации. Это может быть что угодно, связанное с исследованием.
Полезные ссылки
Даты записи исследования
Эти даты отслеживают ход отправки отчетов об исследованиях и сводных результатов на сайт ClinicalTrials.gov. Записи исследований и сообщаемые результаты проверяются Национальной медицинской библиотекой (NLM), чтобы убедиться, что они соответствуют определенным стандартам контроля качества, прежде чем публиковать их на общедоступном веб-сайте.
Изучение основных дат
Начало исследования
1 марта 2014 г.
Первичное завершение (Действительный)
1 июля 2014 г.
Завершение исследования (Действительный)
1 июля 2014 г.
Даты регистрации исследования
Первый отправленный
13 февраля 2014 г.
Впервые представлено, что соответствует критериям контроля качества
13 февраля 2014 г.
Первый опубликованный (Оценивать)
14 февраля 2014 г.
Обновления учебных записей
Последнее опубликованное обновление (Оценивать)
30 июня 2015 г.
Последнее отправленное обновление, отвечающее критериям контроля качества
29 июня 2015 г.
Последняя проверка
1 июня 2015 г.
Дополнительная информация
Термины, связанные с этим исследованием
Ключевые слова
Другие идентификационные номера исследования
- D1532C00081
Эта информация была получена непосредственно с веб-сайта clinicaltrials.gov без каких-либо изменений. Если у вас есть запросы на изменение, удаление или обновление сведений об исследовании, обращайтесь по адресу register@clinicaltrials.gov. Как только изменение будет реализовано на clinicaltrials.gov, оно будет автоматически обновлено и на нашем веб-сайте. .