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A Pharmacokinetic/Pharmacodynamic (PK/PD) and Safety Evaluation of Oseltamivir [Tamiflu] in the Treatment of Infants 0 to <12 Months of Age With Confirmed Flu Infection

30 января 2017 г. обновлено: Hoffmann-La Roche

An Open Label, Prospective, Pharmacokinetic/Pharmacodynamic and Safety Evaluation of Oseltamivir (Tamiflu®) in the Treatment of Infants 0 to <12 Months of Age With Confirmed Influenza Infection

This study will assess the pharmacokinetics/pharmacodynamics and safety of oseltamivir [Tamiflu] therapy in infants less than 1 year of age with influenza diagnosed in the 96 hours prior to the first dose. Patients age 3-12 months will receive 3 mg/kg, 1-3 months will receive 2.5 mg/kg, and birth to 1 month will receive 2 mg/kg twice a day for a total of 10 doses. Patients positive for influenza virus on Day 6 will be eligible to receive continued study treatment for an additional 10 doses (5 days). The anticipated time on study treatment is 4 weeks, and the target sample size is 65-85 male and female infants.

Обзор исследования

Статус

Завершенный

Условия

Вмешательство/лечение

Тип исследования

Интервенционный

Регистрация (Действительный)

65

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

  • Бельгия
      • Bruxelles, Бельгия, 1200
        • Cliniques Universitaires St-Luc
  • Германия
      • Berlin, Германия, 13353
        • CAMPUS VIRCHOW-KLINIKUM CharitéCentrum 17 Klinik f.Pädiatrie Abt.Pneumologie u.Immunologie
      • Bochum, Германия, 44792
        • LWL-Klinik-Bochum
      • Worms, Германия, 67547
        • Onkologische Schwerpunktpraxis Dr. Med. O. Burkhard & B. Reimann
  • Испания
      • Madrid, Испания, 28905
        • Hospital Universitario de Getafe; Servicio de Pediatria
    • La Coruña
      • Santiago de Compostela, La Coruña, Испания, 15706
        • Complejo Hospitalario Universitario de Santiago (CHUS) ; Intermedios y Urgencias Pediatricas
  • Италия
    • Lombardia
      • Milan, Lombardia, Италия, 20122
        • Fondazione Ospedale Maggiore Policlinico
  • Польша
      • Bydgoszcz, Польша, 85-021
        • Vitamed
      • Bydgoszcz, Польша, 85-168
        • Samodzielny Publiczny Zakład Opieki; Wcześniaków I Intensywnej Terapii
      • Debica, Польша, 39-200
        • Zespol Opieki Zdrowotnej Debica; Oddzial Dzieciecy
      • Trzebnica, Польша, 55-100
        • St Hedwig Hospital In Trzebnica
  • Франция
      • Bron, Франция, 69677
        • Hôpital Femme Mère Enfant; Service de rhumatologie pédiatrique

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

Не старше 1 год (Ребенок)

Принимает здоровых добровольцев

Нет

Полы, имеющие право на обучение

Все

Описание

Inclusion Criteria:

  • infants </=12 months of age
  • laboratory confirmed diagnosis of influenza within 96 hours prior to first dose
  • influenza symptoms for </=96 hours prior to first dose

Exclusion Criteria:

  • preterm infants less than 40 weeks (corrected for gestational age)
  • weight less than 5th percentile for age (corrected for gestational age)
  • concurrent gastrointestinal conditions that preclude enteric absorption of the drug
  • bronchopulmonary dysplasia/chronic lung disease on assisted ventilation at time of enrollment
  • active or uncontrolled respiratory, cardiac, hepatic, CNS or renal disease at baseline
  • symptomatic inborn errors of metabolism

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: Нерандомизированный
  • Интервенционная модель: Параллельное назначение
  • Маскировка: Нет (открытая этикетка)

Оружие и интервенции

Группа участников / Армия
Вмешательство/лечение
Экспериментальный: Oseltamivir 3 mg
infants 3 to <12 months
Лекарство: Tamiflu
oral repeating dose
Экспериментальный: Oseltamivir 2.5 mg
infants 1 to <3 months of age
Лекарство: Tamiflu
oral repeating dose
Экспериментальный: Oseltamivir 2 mg
infants 0 to 30 days (post natal) of age
Лекарство: Tamiflu
oral repeating dose

Что измеряет исследование?

Первичные показатели результатов

Мера результата
Мера Описание
Временное ограничение
Steady-state Area Under the Plasma Concentration Versus Time Curve From Time Zero to 12 Hours of Oseltamivir and Oseltamivir Carboxylate
Временное ограничение: 15 minutes pre-dose; 1 hour +/- 15 minutes, 2-3, 5-7, 10-12 hours post-dose on Day 3 if two doses taken on Day 1 or 15 minutes pre-dose; 1 hour +/- 15 minutes, 2-3, 5-7, 10-12 hours post-dose on Day 4 if one dose taken on Day 1
Oseltamivir carboxylate is active metabolite of oseltamivir. AUC0-12 was estimated for oseltamivir and oseltamivir carboxylate by linear trapezoidal rule
15 minutes pre-dose; 1 hour +/- 15 minutes, 2-3, 5-7, 10-12 hours post-dose on Day 3 if two doses taken on Day 1 or 15 minutes pre-dose; 1 hour +/- 15 minutes, 2-3, 5-7, 10-12 hours post-dose on Day 4 if one dose taken on Day 1
Steady-state Maximum Observed Plasma Concentration of Oseltamivir and Oseltamivir Carboxylate
Временное ограничение: 15 minutes pre-dose; 1 hour +/- 15 minutes, 2-3, 5-7, 10-12 hours post-dose on Day 3 if two doses taken on Day 1 or 15 minutes pre-dose; 1 hour +/- 15 minutes, 2-3, 5-7, 10-12 hours post-dose on Day 4 if one dose taken on Day 1
Oseltamivir carboxylate is an active metabolite of oseltamivir. Cmax was estimated for both oseltamivir and Oseltamivir carboxylate by non-compartmental analysis.
15 minutes pre-dose; 1 hour +/- 15 minutes, 2-3, 5-7, 10-12 hours post-dose on Day 3 if two doses taken on Day 1 or 15 minutes pre-dose; 1 hour +/- 15 minutes, 2-3, 5-7, 10-12 hours post-dose on Day 4 if one dose taken on Day 1
Steady-state Minimum Observed Plasma Concentration of Oseltamivir and Oseltamivir Carboxylate
Временное ограничение: 15 minutes pre-dose; 1 hour +/- 15 minutes, 2-3, 5-7, 10-12 hours post-dose on Day 3 if two doses taken on Day 1 or 15 minutes pre-dose; 1 hour +/- 15 minutes, 2-3, 5-7, 10-12 hours post-dose on Day 4 if one dose taken on Day 1
Oseltamivir carboxylate is active metabolite of oseltamivir. Cmin was estimated for both oseltamivir and oseltamivir carboxylate by non-compartmental analysis
15 minutes pre-dose; 1 hour +/- 15 minutes, 2-3, 5-7, 10-12 hours post-dose on Day 3 if two doses taken on Day 1 or 15 minutes pre-dose; 1 hour +/- 15 minutes, 2-3, 5-7, 10-12 hours post-dose on Day 4 if one dose taken on Day 1

Вторичные показатели результатов

Мера результата
Мера Описание
Временное ограничение
Time to the Maximum Observed Plasma Concentration of Oseltamivir and Oseltamivir Carboxylate
Временное ограничение: 15 minutes pre-dose; 1 hour +/- 15 minutes, 2-3, 5-7, 10-12 hours post-dose on Day 3 if two doses taken on Day 1 or 15 minutes pre-dose; 1 hour +/- 15 minutes, 2-3, 5-7, 10-12 hours post-dose on Day 4 if one dose taken on Day 1
Oseltamivir carboxylate is an active metabolite of oseltamivir.Tmax was estimated using non-compartmental methods
15 minutes pre-dose; 1 hour +/- 15 minutes, 2-3, 5-7, 10-12 hours post-dose on Day 3 if two doses taken on Day 1 or 15 minutes pre-dose; 1 hour +/- 15 minutes, 2-3, 5-7, 10-12 hours post-dose on Day 4 if one dose taken on Day 1
Apparent Elimination Half Life of Oseltamivir and Oseltamivir Carboxylate
Временное ограничение: 15 minutes pre-dose; 1 hour +/- 15 minutes, 2-3, 5-7, 10-12 hours post-dose on Day 3 if two doses taken on Day 1 or 15 minutes pre-dose; 1 hour +/-15 minutes, 2-3, 5-7, 10-12 hours post-dose on Day 4 if one dose taken on Day 1
Elimination half-life is defined as the time required for elimination of a drug to half its plasma concentration and was computed using non-compartmental method
15 minutes pre-dose; 1 hour +/- 15 minutes, 2-3, 5-7, 10-12 hours post-dose on Day 3 if two doses taken on Day 1 or 15 minutes pre-dose; 1 hour +/-15 minutes, 2-3, 5-7, 10-12 hours post-dose on Day 4 if one dose taken on Day 1
Apparent First-order Elimination Rate Constant of Oseltamivir and Oseltamivir Carboxylate
Временное ограничение: 15 minutes pre-dose; 1 hour +/- 15 minutes, 2-3, 5-7, 10-12 hours post-dose on Day 3 if two doses taken on Day 1 or 15 minutes pre-dose; 1 hour +/- 15 minutes, 2-3, 5-7, 10-12 hours post-dose on Day 4 if one dose taken on Day 1
Oseltamivir carboxylate is active metabolite of oseltamivir.The apparent first-order elimination rate constant (Lambda Z) was determined by linear regression analysis of terminal data points. A minimum of 3 data points were used for lambda Z estimation. By reporting tool convention, if n<3, no summary statistics were calculated
15 minutes pre-dose; 1 hour +/- 15 minutes, 2-3, 5-7, 10-12 hours post-dose on Day 3 if two doses taken on Day 1 or 15 minutes pre-dose; 1 hour +/- 15 minutes, 2-3, 5-7, 10-12 hours post-dose on Day 4 if one dose taken on Day 1
Total Plasma Clearance as a Function of Bioavailability and Apparent Plasma Clearance of the Metabolite as a Function of Bioavailability (CLm/F) of Oseltamivir and Oseltamivir Carboxylate
Временное ограничение: 15 minutes pre-dose; 1 hour +/- 15 minutes, 2-3, 5-7, 10-12 hours post-dose on Day 3 if two doses taken on Day 1 or 15 minutes pre-dose; 1 hour +/- 15 minutes, 2-3, 5-7, 10-12 hours post-dose on Day 4 if one dose taken on Day 1
Oseltamivir carboxylate is active metabolite of oseltamivir. CL/F was calculated as dose/AUCinf, where AUCinf represents the area under the concentration-time curve of the analyte in plasma over the time interval from zero extrapolated to infinity
15 minutes pre-dose; 1 hour +/- 15 minutes, 2-3, 5-7, 10-12 hours post-dose on Day 3 if two doses taken on Day 1 or 15 minutes pre-dose; 1 hour +/- 15 minutes, 2-3, 5-7, 10-12 hours post-dose on Day 4 if one dose taken on Day 1
The Volume of Distribution as a Function of Bioavailability of Oseltamivir and Oseltamivir Carboxylate
Временное ограничение: 15 minutes pre-dose; 1 hour +/- 15 minutes, 2-3, 5-7, 10-12 hours post-dose on Day 3 if two doses taken on Day 1 or 15 minutes pre-dose; 1 hour +/- 15 minutes, 2-3, 5-7, 10-12 hours post-dose on Day 4 if one dose taken on Day 1
Oseltamivir carboxylate is active metabolite of oseltamivir. V/F is defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired blood concentration of a drug.
15 minutes pre-dose; 1 hour +/- 15 minutes, 2-3, 5-7, 10-12 hours post-dose on Day 3 if two doses taken on Day 1 or 15 minutes pre-dose; 1 hour +/- 15 minutes, 2-3, 5-7, 10-12 hours post-dose on Day 4 if one dose taken on Day 1
Clast of Oseltamivir and Oseltamivir Carboxylate
Временное ограничение: 15 minutes pre-dose; 1 hour +/- 15 minutes, 2-3, 5-7, 10-12 hours post-dose on Day 3 if two doses taken on Day 1 or 15 minutes pre-dose; 1 hour +/- 15 minutes, 2-3, 5-7, 10-12 hours post-dose on Day 4 if one dose taken on Day 1
The last measurable plasma concentration of oseltamivir and oseltamivir carboxylate was the last quantifiable concentration of oseltamivir or oseltamivir carboxylate, respectively.
15 minutes pre-dose; 1 hour +/- 15 minutes, 2-3, 5-7, 10-12 hours post-dose on Day 3 if two doses taken on Day 1 or 15 minutes pre-dose; 1 hour +/- 15 minutes, 2-3, 5-7, 10-12 hours post-dose on Day 4 if one dose taken on Day 1
Time of the Last Measurable Plasma Concentration for Oseltamivir and Oseltamivir Carboxylate
Временное ограничение: 15 minutes pre-dose; 1 hour +/- 15 minutes, 2-3, 5-7, 10-12 hours post-dose on Day 3 if two doses taken on Day 1 or 15 minutes pre-dose; 1 hour +/- 15 minutes, 2-3, 5-7, 10-12 hours post-dose on Day 4 if one dose taken on Day 1
Oseltamivir carboxylate is an active metabolite of oseltamivir.
15 minutes pre-dose; 1 hour +/- 15 minutes, 2-3, 5-7, 10-12 hours post-dose on Day 3 if two doses taken on Day 1 or 15 minutes pre-dose; 1 hour +/- 15 minutes, 2-3, 5-7, 10-12 hours post-dose on Day 4 if one dose taken on Day 1
Number of Participants With Change From Baseline in Neurological Assessment Scores
Временное ограничение: Baseline (Day 1); Day 3 for who received two does on Day 1 or Day 4 for who received one dose on Day 1; Day 6, Day 11, Day 18, Day 30
Neurological assessment was performed to assess the mental state of the participants through two scales: Infant face scale and Glasgow coma scale. Each scale consists of 3 subscales: eye opening (ranging 1 to 4), verbal response (ranging 1 to 5), and motor responses (ranging 1 to 6). The final score is the sum of these ranges and is scored between 3 and 15. 3 being the worst, and 15 the best. Change from baseline is change of final score post-baseline minus the final score at baseline.
Baseline (Day 1); Day 3 for who received two does on Day 1 or Day 4 for who received one dose on Day 1; Day 6, Day 11, Day 18, Day 30
Median Time to Cessation of Viral Shedding in Participants With Positive Culture at Baseline
Временное ограничение: Days 1, 3 or 4, 6, 11, 18, and 30
Median time to cessation of viral shedding was calculated for all patients with positive by culture / by polymerase chain reaction (PCR) at baseline using all data points between the start of the treatment and the 1st time point of negative culture without subsequent positive culture results. These time-to event analyses were only performed for the viral titre.
Days 1, 3 or 4, 6, 11, 18, and 30
Number of Participants With Virus Shedding by Virus Type
Временное ограничение: Baseline (Day 1), Day3/4, Day 6, Day 11, Day 18+/-2 days, Day 30+/-2 days
The viral titer was measured by culture and reported in log10 (50% tissue culture infective dose [TCID50]). The viral load was analyzed by PCR and reported as log10 particles/mL. The number of patients positive for viral shedding by virus sub-type was measured on specified days from baseline to last visit on Day 30.
Baseline (Day 1), Day3/4, Day 6, Day 11, Day 18+/-2 days, Day 30+/-2 days
Time to Resolution of Fever in Participants With Fever at the Baseline
Временное ограничение: Days 1 to 11; Day 18; Day 30
This was performed for all participants who had fever at baseline. Fever is defined as body temperature >37.0 degree Celsius. Rectal temperature is converted by subtracting 1 degree Celsius. Time to Resolution of Fever was defined as the time from the initiation of treatment to first time the afebrile state was reached and maintained for at least 21.5 hours, where afebrile state was defined as axillary temperature ≤ 37 degree Celsius.
Days 1 to 11; Day 18; Day 30
Percentage of Participants With Decline of Body Temperature to the Afebrile State
Временное ограничение: Baseline (Day 1), Day3/4, Day 6, Day 11, Day 18+/-2 days, Day 30+/-2 days
This was performed for all participants who had fever at baseline Fever is defined as body temperature >37.0ºC. Rectal temperature is converted by subtracting 1 ºC. The rate of decline of body temperature was calculated as the slope of body temperature between the baseline temperature and the 1st temperature below 37°C. Participants with decline in body temperature were considered to have no fever; however, participants who did not show any decline in body temperature were considered to have persisting fever.
Baseline (Day 1), Day3/4, Day 6, Day 11, Day 18+/-2 days, Day 30+/-2 days
Number of Participants With Adverse Events, Serious Adverse Events and Secondary Illness
Временное ограничение: Up to 3 days after the last dose of oseltamivir (Approximately 14 days)
An Adverse Event (AEs) is defined as any untoward medical occurrence in a participant or clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered to be related to the medicinal product. An Serious Adverse Event (SAE) is any untoward medical occurrence that, at any dose, results in death, is life threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, or results in a congenital anomaly/birth defect. Secondary illnesses were influenza disease-related events, namely bronchitis, pneumonia, otitis media, and sinusitis that resolved without sequelae. Adverse events, serious adverse events, and secondary illness are reported for on-treatment period (from the first dose of oseltamivir upto 3 days after the last dose of oseltamivir [Approximately 14 days].
Up to 3 days after the last dose of oseltamivir (Approximately 14 days)
Number of Participants Showing Within-patient Variability in Vital Signs
Временное ограничение: Post baseline, Day 3, 4, 6, 11, 18+/- 2 days, 30+/-2 days
Systolic blood pressure, diastolic blood pressure, pulse rate, respiratory rate, and heart rate were examined for any consistent within-patient post-baseline changes.
Post baseline, Day 3, 4, 6, 11, 18+/- 2 days, 30+/-2 days

Соавторы и исследователи

Здесь вы найдете людей и организации, участвующие в этом исследовании.

Спонсор

Hoffmann-La Roche

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

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 января 2011 г.

Первичное завершение (Действительный)

1 апреля 2012 г.

Завершение исследования (Действительный)

1 апреля 2012 г.

Даты регистрации исследования

Первый отправленный

30 сентября 2009 г.

Впервые представлено, что соответствует критериям контроля качества

30 сентября 2009 г.

Первый опубликованный (Оценивать)

2 октября 2009 г.

Обновления учебных записей

Последнее опубликованное обновление (Действительный)

20 марта 2017 г.

Последнее отправленное обновление, отвечающее критериям контроля качества

30 января 2017 г.

Последняя проверка

1 января 2017 г.

Дополнительная информация

Термины, связанные с этим исследованием

Дополнительные соответствующие термины MeSH

Другие идентификационные номера исследования

  • WP22849
  • 2009-014365-12

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. .

Клинические исследования Грипп

  • QIAGEN Gaithersburg, Inc
    Завершенный
    Сбор и тестирование респираторных образцов
    Респираторно-синцитиальные вирусные инфекции | Грипп А | Риновирус | Грипп В | Расширенная панель QIAGEN ResPlex II | Инфекция, вызванная вирусом парагриппа человека 1 | Парагрипп Тип 2 | Парагрипп 3 типа | Парагрипп 4 типа | Метапневмовирус человека A/B | Вирус Коксаки/Эховирус | Аденовирусы типов B/C/E | Подтипы... и другие заболевания
    Соединенные Штаты

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