GSK1550188 A 52 Week Study of Belimumab Versus Placebo in the Treatment of Subjects With Systemic Lupus Erythematosus (SLE) Located in Northeast Asia
20 сентября 2019 г. обновлено: GlaxoSmithKline
The purpose of this study is to evaluate the efficacy and safety of belimumab in addition to standard therapy compared to placebo in subjects in Northeast Asia with systemic lupus erythematosus (SLE) over a 52 week period.
Обзор исследования
Статус
Завершенный
Условия
Вмешательство/лечение
Подробное описание
The purpose of this study is to demonstrate the efficacy and safety of belimumab 10mg/kg administered intravenously (IV) every 4 weeks compared to placebo, in patients with SLE when added to standard of care therapy, as measured by the SLE Responder Index (SRI) at 52 weeks, defined by a composite endpoint using SELENA SLEDAI score, Physician's Global Assessment (PGA) and BILAG A and B organ domain scores.
Тип исследования
Интервенционный
Регистрация (Действительный)
709
Фаза
- Фаза 3
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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Beijing, Китай, 100044
- GSK Investigational Site
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Beijing, Китай, 100029
- GSK Investigational Site
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Beijing, Китай, 100032
- GSK Investigational Site
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Chongqing, Китай, 400038
- GSK Investigational Site
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Shanghai, Китай, 200025
- GSK Investigational Site
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Shanghai, Китай, 200433
- GSK Investigational Site
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Shanghai, Китай, 200001
- GSK Investigational Site
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Shanghai, Китай, 200003
- GSK Investigational Site
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Tianjin, Китай, 300052
- GSK Investigational Site
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Anhui
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Hefei, Anhui, Китай, 230001
- GSK Investigational Site
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Guangdong
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Guangzhou, Guangdong, Китай, 510080
- GSK Investigational Site
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Guangzhou, Guangdong, Китай, 510630
- GSK Investigational Site
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Guangzhou, Guangdong, Китай, 510260
- GSK Investigational Site
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Heilongjiang
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Harbin, Heilongjiang, Китай, 150001
- GSK Investigational Site
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Hunan
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Changsha, Hunan, Китай, 410011
- GSK Investigational Site
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Changsha, Hunan, Китай, 410008
- GSK Investigational Site
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Jiangsu
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Nanjing, Jiangsu, Китай, 210029
- GSK Investigational Site
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Suzhou, Jiangsu, Китай, 215006
- GSK Investigational Site
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Shaanxi
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Xian, Shaanxi, Китай, 710032
- GSK Investigational Site
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Shandong
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Jinan, Shandong, Китай, 250012
- GSK Investigational Site
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Sichuan
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Chengdu, Sichuan, Китай, 610041
- GSK Investigational Site
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Yunnan
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Kunming, Yunnan, Китай, 650101
- GSK Investigational Site
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Zhejiang
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Hangzhou, Zhejiang, Китай, 310009
- GSK Investigational Site
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Busan, Корея, Республика
- GSK Investigational Site
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Daegu, Корея, Республика, 700-721
- GSK Investigational Site
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Incheon, Корея, Республика, 400-711
- GSK Investigational Site
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Seoul, Корея, Республика, 137-701
- GSK Investigational Site
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Seoul, Корея, Республика, 110-744
- GSK Investigational Site
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Seoul, Корея, Республика
- GSK Investigational Site
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Seoul, Корея, Республика, 133-792
- GSK Investigational Site
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Suwon, Kyonggi-do, Корея, Республика, 443-721
- GSK Investigational Site
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Chiba, Япония, 275-8580
- GSK Investigational Site
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Ehime, Япония, 791-0295
- GSK Investigational Site
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Fukuoka, Япония, 807-8555
- GSK Investigational Site
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Fukuoka, Япония, 810-8563
- GSK Investigational Site
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Hiroshima, Япония, 730-8619
- GSK Investigational Site
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Hiroshima, Япония, 739-0002
- GSK Investigational Site
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Hokkaido, Япония, 060-8648
- GSK Investigational Site
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Hokkaido, Япония, 060-8604
- GSK Investigational Site
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Hyogo, Япония, 675-8545
- GSK Investigational Site
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Miyagi, Япония, 980-8574
- GSK Investigational Site
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Nagasaki, Япония, 852-8501
- GSK Investigational Site
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Nagasaki, Япония, 857-1195
- GSK Investigational Site
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Okayama, Япония, 710-0824
- GSK Investigational Site
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Okinawa, Япония, 901-0243
- GSK Investigational Site
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Tochigi, Япония, 321-0293
- GSK Investigational Site
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Tokyo, Япония, 113-8431
- GSK Investigational 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:
- Age 18 years and older.
- Have a clinical diagnosis of SLE according to the American College of Rheumatology (ACR) classification criteria.
- Have active SLE disease.
- Have positive anti-nuclear antibody (ANA) test results.
- Are on a stable SLE treatment regimen.
- Females of childbearing age are willing to use appropriate contraception
Exclusion Criteria:
- Have received treatment with any B cell targeted therapy at any time.
- Have received a biologic investigational agent in the past year.
- Have received 3 or more courses of systemic corticosteroids in the past year.
- Have received intravenous (IV) cyclophosphamide within 180 days prior to Day 0.
- Have severe lupus kidney disease.
- Have active central nervous system (CNS) lupus.
- Have had a major organ transplant.
- Have significant unstable or uncontrolled acute or chronic diseases or conditions not due to SLE.
- Have a planned surgical procedure.
- Cancer within the last 5 years, except for adequately treated skin cancer, or carcinoma in situ of the uterine cervix.
- Have required management of acute or chronic infections in the past 60 days.
- Have current drug or alcohol abuse or dependence.
- Have a historically positive test, or test positive at screening for HIV, Hepatitis B, or Hepatitis C.
- Have an IgA deficiency.
- Have severe laboratory Abnormalities.
- Have had anaphylactic reaction to X-ray contrast agents or biologic agents.
- Suicidal behavior or ideation.
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: Уход
- Распределение: Рандомизированный
- Интервенционная модель: Параллельное назначение
- Маскировка: Четырехместный
Оружие и интервенции
Группа участников / Армия |
Вмешательство/лечение |
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Плацебо Компаратор: Плацебо
плацебо
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Administered intravenously.
Dosing at Weeks 0, 2, and 4, and then every 4 weeks through Week 48, with a final evaluation at Week 52.
All study subjects will receive standard SLE therapies during the study.
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Экспериментальный: Белимумаб
10мг/кг
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10mg/kg administered intravenously.
Dosing at Weeks 0, 2, and 4, then every 4 weeks through Week 48, with a final evaluation at Week 52.
All study subjects will receive standard SLE therapies during the study.
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Что измеряет исследование?
Первичные показатели результатов
Мера результата |
Мера Описание |
Временное ограничение |
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Percent of Participants Achieving Systemic Lupus Erythematosus (SLE) Responder Index (SRI) Response Rate at Week 52 for Double-blind Phase.
Временное ограничение: Week 52
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SRI response is a composite index, defined as the percent of participants with >=4 point reduction from Baseline in safety of estrogen in lupus national assessment (SELENA) systemic lupus erythematosus disease activity index (SLEDAI) score and no worsening (increase of < 0.30 points from Baseline) in physicians global assessment (PGA) and no new British isles lupus assessment group (BILAG) A organ domain score or 2 new BILAG B organ domain scores compared with Baseline at the time of assessment (at Week 52 of the blinded period).
A SELENA SLEDAI score of 0 would suggest no lupus activity; while a score of 105 is the maximum calculable if all items were scored as being present from active lupus.
PGA ranges from 0 (no activity) to 3 (severe activity).
BILAG has no range.
The higher thresholds of SELENA SLEDAI improvement (i.e., SRI5, SRI6, and SRI7) indicates a higher response (SRI5 is a 5 point SELENA SLEDAI reduction, SRI6 is a 6 point reduction, and SRI7 is a 7 point reduction).
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Week 52
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Вторичные показатели результатов
Мера результата |
Мера Описание |
Временное ограничение |
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Percent of Participants With >=4 Point Reduction From Baseline in SELENA SLEDAI Score at Week 52 for Double-blind Phase.
Временное ограничение: Baseline (Day 0) and Week 52
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The SELENA SLEDAI score is a weighted index for assessing SLE disease activity in which signs and symptoms, laboratory tests and physician's assessment for each of 9 organ system were given a weighted score and summed if present at the time of the visit or in the preceding 10 days.
A SELENA SLEDAI score of 0 would suggest no lupus activity; while a score of 105 is the maximum calculable if all items were scored as being present from active lupus.
A decrease of 4 points or more equates to a clinically meaningful improvement.
The Baseline value of a variable is defined as the value of the variable measured at Day 0 prior to dosing.
In case of multiple results on Day 0 prior to dosing, the latest result was used.
If a Day 0 value was not available, the last available value prior to Day 0 was used.
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Baseline (Day 0) and Week 52
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Percent of Participants With SRI7 Response at Week 52 for Double-blind Phase.
Временное ограничение: Baseline (Day 0) and Week 52
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SRI7 response is defined as the percent of participants with >=7 point reduction from Baseline in SELENA SLEDAI score and no worsening (increase of < 0.30 points from Baseline) in PGA and no new BILAG A organ domain score or 2 new BILAG B organ domain scores compared with Baseline at the time of assessment (at Week 52 of the blinded period).
A SELENA SLEDAI score of 0 would suggest no lupus activity; while a score of 105 is the maximum calculable if all items were scored as being present from active lupus.
PGA ranges from 0 (no activity) to 3 (severe activity).
BILAG has no range.
The higher thresholds of SELENA SLEDAI improvement (i.e., SRI5, SRI6, and SRI7) indicates a higher response (SRI5 is a 5 point SELENA SLEDAI reduction, SRI6 is a 6 point reduction, and SRI7 is a 7 point reduction).
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Baseline (Day 0) and Week 52
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Number of Days of Daily Prednisone Dose <=7.5 mg/Day and/or Reduced by 50 Percent From Baseline Over 52 Weeks for Double-blind Phase.
Временное ограничение: Week 52
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Number of days of daily prednisone dose <=7.5 mg/day and/or reduced by 50 percent over time through each scheduled visit during the blinded period were compared between belimumab and placebo using Rank ANCOVA model which was used for comparing belimumab and placebo.
The independent variables in the model included treatment group, Baseline prednisone dose level, country, Baseline SELENA SLEDAI score (<=9 vs. >=10) and complement levels (low C3 and/or C4 vs. no low C3 or C4).
This analysis was perfomed on the participants who used prednisone >7.5 mg/day at Baseline.
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Week 52
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Time to First Severe SLE Flare Index (SFI) Flare Over 52 Weeks for Double-blind Phase.
Временное ограничение: 52 weeks
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Time to first severe SLE flare is defined as the number of days from first treatment until the participant had an event (event date-treatement start date +1).
If a participant had a severe SFI flare and received protocol restricted medication then the event date was the earliest of the first severe SFI flare date, and the treatment failure date.
Analysis of severe SFI flare was performed on the modified SELENA SLEDAI SLE flare index in which the modification excluded severe flares that were triggered only by an increase in SELENA SLEDAI score to >12.
Analysis was from Cox proportional hazards model for the comparison between belimumab and placebo adjusting for country, Baseline SELENA SLEDAI score (<=9 vs. >=10) and complement levels (low C3 and/or C4 vs. no low C3 or C4).
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52 weeks
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Percent of Participants Achieving SLE SRI Response Rate for Open-label (OL) Phase
Временное ограничение: Weeks 24 and 48 for Years 2, 3, 4, 5 and 6
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SRI response is a composite index, defined as the percent of participants with >=4 point reduction from Baseline in SELENA SLEDAI score and no worsening (increase of < 0.30 points from Baseline) in PGA and no new BILAG A organ domain score or 2 new BILAG B organ domain scores compared with Baseline at time of assessment.
Excludes participants with a SELENA SLEDAI score <4 at baseline.
Participants randomized to belimumab in double-blinded (DB) phase, Baseline is last available value before first belimumab dose received in DB phase.
Participants randomized to placebo in DB phase, Baseline is last available value before receiving first belimumab dose in OL phase.
Observed case data are presented.Year 6 Week 48 is the Exit Visit obtained by slotting the Exit Visit to Week 48.
A SELENA SLEDAI score of 0 (no lupus activity) and a score of 105 (maximum).
PGA ranges from 0 (no activity) to 3 (severe activity).
BILAG has no range.
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Weeks 24 and 48 for Years 2, 3, 4, 5 and 6
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Соавторы и исследователи
Здесь вы найдете людей и организации, участвующие в этом исследовании.
Спонсор
Соавторы
Публикации и полезные ссылки
Лицо, ответственное за внесение сведений об исследовании, добровольно предоставляет эти публикации. Это может быть что угодно, связанное с исследованием.
Общие публикации
- Hannon CW, McCourt C, Lima HC, Chen S, Bennett C. Interventions for cutaneous disease in systemic lupus erythematosus. Cochrane Database Syst Rev. 2021 Mar 9;3(3):CD007478. doi: 10.1002/14651858.CD007478.pub2.
- Gupta SV, Fanget MC, MacLauchlin C, Clausen VA, Li J, Cloutier D, Shen L, Robbie GJ, Mogalian E. Clinical and Preclinical Single-Dose Pharmacokinetics of VIR-2218, an RNAi Therapeutic Targeting HBV Infection. Drugs R D. 2021 Dec;21(4):455-465. doi: 10.1007/s40268-021-00369-w. Epub 2021 Nov 6.
- Zhou X, Lee TI, Zhu M, Ma P. Prediction of Belimumab Pharmacokinetics in Chinese Pediatric Patients with Systemic Lupus Erythematosus. Drugs R D. 2021 Dec;21(4):407-417. doi: 10.1007/s40268-021-00363-2. Epub 2021 Oct 9.
- Brunner HI, Abud-Mendoza C, Mori M, Pilkington CA, Syed R, Takei S, Viola DO, Furie RA, Navarra S, Zhang F, Bass DL, Eriksson G, Hammer AE, Ji BN, Okily M, Roth DA, Quasny H, Ruperto N. Efficacy and safety of belimumab in paediatric and adult patients with systemic lupus erythematosus: an across-study comparison. RMD Open. 2021 Sep;7(3):e001747. doi: 10.1136/rmdopen-2021-001747.
- Zhang F, Bae SC, Bass D, Chu M, Egginton S, Gordon D, Roth DA, Zheng J, Tanaka Y. A pivotal phase III, randomised, placebo-controlled study of belimumab in patients with systemic lupus erythematosus located in China, Japan and South Korea. Ann Rheum Dis. 2018 Mar;77(3):355-363. doi: 10.1136/annrheumdis-2017-211631. Epub 2018 Jan 2.
- Zhang F, Zheng J, Li Y, Wang G, Wang M, Su Y, Gu J, Li X, Bass D, Chu M, Curtis P, DeRose K, Kurrasch R, Lowe J, Meizlik P, Roth DA. Phase 3, long-term, open-label extension period of safety and efficacy of belimumab in patients with systemic lupus erythematosus in China, for up to 6 years. RMD Open. 2022 Apr;8(1):e001669. doi: 10.1136/rmdopen-2021-001669.
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 (Действительный)
23 мая 2011 г.
Первичное завершение (Действительный)
15 сентября 2015 г.
Завершение исследования (Действительный)
21 сентября 2018 г.
Даты регистрации исследования
Первый отправленный
28 апреля 2011 г.
Впервые представлено, что соответствует критериям контроля качества
28 апреля 2011 г.
Первый опубликованный (Оценивать)
2 мая 2011 г.
Обновления учебных записей
Последнее опубликованное обновление (Действительный)
4 октября 2019 г.
Последнее отправленное обновление, отвечающее критериям контроля качества
20 сентября 2019 г.
Последняя проверка
1 сентября 2019 г.
Дополнительная информация
Термины, связанные с этим исследованием
Ключевые слова
Дополнительные соответствующие термины MeSH
Другие идентификационные номера исследования
- 113750
Информация о лекарствах и устройствах, исследовательские документы
Изучает лекарственный продукт, регулируемый FDA США.
Нет
Изучает продукт устройства, регулируемый Управлением по санитарному надзору за качеством пищевых продуктов и медикаментов США.
Нет
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. .