Эта страница была переведена автоматически, точность перевода не гарантируется. Пожалуйста, обратитесь к английской версии для исходного текста.

Подкожный имплантат-биоабсорбируемый гестриноновый гранулят для лечения тазовой боли при эндометриозе (GLADE)

5 ноября 2026 г. обновлено: Science Valley Research Institute

Фаза II, рандомизированное, плацебо-контролируемое, двойное слепое, многоцентровое исследование по изучению безопасности и исследовательской эффективности подкожного имплантата-биорассасывающегося гестринона в виде гранул при тазовой боли, вторичной по отношению к лечению эндометриоза

Pelvic pain is considered a symptom of multifactorial origin among which Endometriosis is the main gynecological cause affecting 5-10% of worldwide women in their reproductive years, negatively impacting their quality of life and work efficiency. Treatment of endometriosis-associated pelvic pain is challenging and there are surgical and/or hormonal treatments available with variable endpoints. Gestrinone is a synthetic derivative of 19-nortestosterone with anti-estrogen, anti-progestin, androgenic, and weak estrogen-like action. Previous studies show that the oral treatment with Gestrinone induced an improvement in symptoms associated with endometriosis but with adverse events such as androgenization and uterine bleeding. Parenteral administration of Gestrinone could be effective to treat pain symptoms secondary to endometriosis and minimize these adverse events. This study evaluates the safety and tolerability of subdermal implant-bioabsorbable gestrinone pellet use in women with pelvic pain secondary to endometriosis after 6 months of Gestrinone pellet insertion versus placebo pellet. PK profile of the gestrinone pellet will be monitored.

Обзор исследования

Статус

Завершенный

Условия

Вмешательство/лечение

Подробное описание

This is a Phase 2, exploratory, multicenter, randomized, double-blind, placebo-controlled study followed by an optional open-label pharmacokinetic extension.

This study aimed to assess the safety and tolerability profile of a subdermal 85-mg gestrinone bioabsorbable implant compared with a matched placebo bioabsorbable implant, in women with endometriosis-associated pelvic pain. The pharmacokinetics of the gestrinone implant will be monitored. Exploratory efficacy analyses will be descriptively reported for participant satisfaction, change in pelvic pain intensity, use of rescue pain medication, and quality of life.

One hundred patients will be randomized in a 1: 1 ratio. Initially, all the patients will undergo insertion of an intrauterine system of levonorgestrel release (Kyleena) as a contraceptive method. On the same day, after randomization, the subdermal implantation of the gestrinone (85 mg) or placebo pellet will be performed. Visits will occur after 3 and 6 months of the pellet insertion. Primary endpoint is a combination of serious adverse events (SAEs) accumulated within 6 months of pellet insertion and collected through spontaneous reporting and/or clinical findings.

Тип исследования

Интервенционный

Регистрация (Действительный)

100

Фаза

  • Фаза 2

Контакты и местонахождение

В этом разделе приведены контактные данные лиц, проводящих исследование, и информация о том, где проводится это исследование.

Места учебы

  • Бразилия
    • São Paulo
      • São Paulo, São Paulo, Бразилия
        • Science Valley Research Institute

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

От 18 лет до 50 лет (Взрослый)

Принимает здоровых добровольцев

Нет

Полы, имеющие право на обучение

Женский

Описание

Inclusion Criteria

  1. Willingness to provide informed consent
  2. Woman aged between 18 and 50 years
  3. Body weight between 50 ± 5 kg and 90 ± 5 kg
  4. Having pelvic pain secondary to endometriosis, independent of pain intensity
  5. Endometriosis documented by biopsies (histopathological examination)
  6. Last endometriosis surgery at least 3 months before randomization
  7. Not planning to become pregnant within 12 months after the screening visit or be surgically sterilized
  8. Absence of changes in the breast (BI-RADS1 and BIRADS-2 classification) documented by an imaging report (mammogram for women aged > 40 years or bilateral breast ultrasound for women aged < 40 years) performed less than 12 months before randomization
  9. Agreement not to use other hormones (estrogens, androgens and progestins) in any pharmaceutical form during the study

Exclusion Criteria

  1. Chronic severe disorders, including metastatic malignancies, end-stage renal disease with or without dialysis, clinically unstable heart disease, or any other disorder that, in the opinion of the investigator, excludes the participant from the study
  2. Suspected or confirmed diagnosis of immunodeficiency based on medical history and/or physical or laboratory examination
  3. Other medical or psychiatric conditions, including recent laboratory abnormalities (within the last 12 months) that may increase risks to the study participant or, at the discretion of the investigator, make the participant inappropriate for the study
  4. Personal history of thromboembolic events
  5. Use anticoagulant medication
  6. Contraindication to the use of hormonal contraceptives
  7. Suspected or confirmed pregnancy
  8. Breastfeeding
  9. Current or recurrent pelvic inflammatory disease or other conditions that increase the risk of pelvic infections
  10. Postpartum endometritis or septic miscarriage in the last 3 months
  11. Abnormal uterine bleeding of unknown etiology
  12. Congenital or acquired uterine anomalies, including fibroids (leiomyomas or fibromas) that cause distortion of the uterine cavity
  13. Uterine or cervical malignancy
  14. Suspected or confirmed diagnosis of estrogen-dependent neoplasm, including breast cancer
  15. Cervicitis or vaginitis, including bacterial vaginosis or another uncontrolled lower urinary tract infection
  16. Cervical dysplasia
  17. Active liver disease or dysfunction
  18. Benign or malignant liver tumors
  19. Allergy or intolerance to levonorgestrel, gestrinone or any other ingredient or component of the Kyleena® formulation or hormonal pellets
  20. Previously inserted intrauterine device or levonorgestrel-releasing intrauterine system that has not been removed
  21. History of recent trophoblastic disease and continued high HCG levels
  22. Bacterial endocarditis
  23. Hyperandrogenism at the time of randomization, defined by: hirsutism: Ferriman-Gallwey score ≥ 8; clitoromegaly: defined by the Clitoral index ≥ 35 mm2, acne: defined by the IGA scale (Investigator's global assessment) grade 5 - severe inflammatory acne dominates the area and there is a large number of comedones, pustules, papules and cystic acne; alopecia with sequelae of scalp thinning
  24. Diagnosis of polycystic ovary syndrome
  25. Participation in another pharmacotherapeutic or investigational medical device study within 30 days prior to the start of study treatment
  26. Tobacco Use
  27. Use of testosterone-derived hormones and analogues in the last month

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
Экспериментальный: Gestrinone

Subdermal implant-bioabsorbable gestrinone pellet (85 mg) All patients will undergo insertion of an intrauterine system of levonorgestrel release (Kyleena®) as a contraceptive method
Лекарство: Gestrinone

The intradermal gestrinone/placebo pellet will be inserted on the same day as the levonorgestrel intrauterine hormonal device (Kyleena®)
Плацебо Компаратор: Placebo

Subdermal implant-bioabsorbable placebo pellet (cholesterol) All patients will undergo insertion of an intrauterine system of levonorgestrel release (Kyleena®) as a contraceptive method
Лекарство: Placebo

Subdermal implant-bioabsorbable placebo pellet (cholesterol)

Что измеряет исследование?

Первичные показатели результатов

Мера результата
Мера Описание
Временное ограничение
Combination of serious adverse events (SAEs) accumulated within 6 months of gestrinone or placebo pellet insertion and collected through spontaneous reporting and/or clinical findings
Временное ограничение: From randomization to the end of study on 6 months after insertion of the gestrinone or placebo pellet

The primary safety outcome will be the proportion of patients who present serious adverse events (SAEs) over 6 months after randomization, defined as a combination of death, conditions that threat or present risk to life, conditions needing hospitalization or prolonging the pre-existing hospitalization, conditions causing disability or permanent damage, conditions leading to a congenital anomaly and any other significant medical occurrence that, based on appropriate medical judgment, may harm the participant and/or require medical or surgical intervention to prevent any of the other aforementioned occurrences.

In this study, the occurrence of thromboembolic events (such as, for example, acute myocardial infarction, pulmonary embolism, deep vein thrombosis, ischemic stroke, and transient ischemic attack) was predefined as a significant medical event.
From randomization to the end of study on 6 months after insertion of the gestrinone or placebo pellet

Вторичные показатели результатов

Мера результата
Мера Описание
Временное ограничение
Androgenization
Временное ограничение: pre-insertion assessment of the pellet (baseline), 3 and 6 months after insertion of the gestrinone or placebo pellet

Number of participants who experience androgenization defined by: Hirsutism (Ferriman-Gallwey Score ≥ 8), Clitoromegaly (Clitoridian index ≥ 35 mm2), Acne (IGA scale grade 5 - severe inflammatory acne dominates the area and there are large numbers of comedones, pustules, papules, and cystic acne), Alopecia, oiliness of the skin, and deepening of the voice
pre-insertion assessment of the pellet (baseline), 3 and 6 months after insertion of the gestrinone or placebo pellet
Plasma concentration of steroid hormones
Временное ограничение: pre-insertion of the pellet (baseline) and 3 months after pellet insertion of the gestrinone or placebo pellet

Number of participants with clinically relevant laboratory values outside the reference range for plasma concentration of total testosterone, free testosterone, and SHBG
pre-insertion of the pellet (baseline) and 3 months after pellet insertion of the gestrinone or placebo pellet
Lipid profile
Временное ограничение: pre-insertion of the pellet (baseline) and 3 months after pellet insertion of the gestrinone or placebo pellet

Number of participants with clinically relevant laboratory values outside the reference range for serum levels of total cholesterol, HDL-C, VLDL-C, and triglycerides
pre-insertion of the pellet (baseline) and 3 months after pellet insertion of the gestrinone or placebo pellet
Hematological disorders
Временное ограничение: pre-insertion of the pellet (baseline) and 3 months after pellet insertion of the gestrinone or placebo pellet

Number of participants with decreased lymphocyte count < 500/mm3 (or < 0.5 × 109/l); decrease in neutrophil count < 500/mm3 (or < 0.5 × 109/l); decrease in platelet count < 30,000/mm3 (or < 30.0 × 109/l); and anemia with decreased Hb < 7.0 g/dl (or < 4.35 mmol/l)
pre-insertion of the pellet (baseline) and 3 months after pellet insertion of the gestrinone or placebo pellet
Hepatic adverse events
Временное ограничение: pre-insertion of the pellet (baseline) and 3 months after pellet insertion of the gestrinone or placebo pellet

Number of participants with increased ALT or AST > 3 times ULN or baseline, alterations in ALT levels suspected hepatocellular or cholestatic hepatotoxicity
pre-insertion of the pellet (baseline) and 3 months after pellet insertion of the gestrinone or placebo pellet
Renal adverse events
Временное ограничение: pre-insertion of the pellet (baseline) and 3 months after pellet insertion of the gestrinone or placebo pellet

Number of participants with increased serum creatinine ≥ 1.5 times ULN or baseline; clinically significant increase in serum urea
pre-insertion of the pellet (baseline) and 3 months after pellet insertion of the gestrinone or placebo pellet

Другие показатели результатов

Мера результата
Мера Описание
Временное ограничение
Overall participant satisfaction
Временное ограничение: 3 months after pellet insertion of the gestrinone or placebo pellet

Median of the participant satisfaction scale (ranging from 1 to 5, from very satisfied to very dissatisfied)
3 months after pellet insertion of the gestrinone or placebo pellet
Pelvic pain intensity
Временное ограничение: pre-insertion assessment of the pellet (baseline), 3 and 6 months after insertion of the gestrinone or placebo pellet

Median of pelvic pain and dysmenorrhea intensity assessed by the NPRS scale, from 0 to 10 points where 10 points indicates worst pain
pre-insertion assessment of the pellet (baseline), 3 and 6 months after insertion of the gestrinone or placebo pellet
Use of pain relief medication
Временное ограничение: pre-insertion assessment of the pellet (baseline), 3 and 6 months after insertion of the gestrinone or placebo pellet

Number of participants who used pain relief medication (analgesics and anti-inflammatories)
pre-insertion assessment of the pellet (baseline), 3 and 6 months after insertion of the gestrinone or placebo pellet
Patient-reported Quality of Life
Временное ограничение: pre-insertion assessment of the pellet (baseline), 3 and 6 months after insertion of the gestrinone or placebo pellet

Number of participants with changes in the 36-Item Short Form Health Survey (SF-36). SF-36 is a patient-reported outcome (PRO) measure evaluating a participant's health status. It comprises 36 items covering 8 domains: physical functioning, role physical, role emotional, bodily pain, vitality, social functioning, mental health, and general health. Items are answered on Likert scales of varying lengths. Items from 8 domains contribute to the PCS. The summary scores range from 0 to 100, with higher scores indicating better levels of function and/or better health
pre-insertion assessment of the pellet (baseline), 3 and 6 months after insertion of the gestrinone or placebo pellet
Endometriosis Health Profile
Временное ограничение: pre-insertion of the pellet (baseline) and 3 months after pellet insertion of the gestrinone or placebo pellet

Number of participants with changes in the Endometriosis Health Profile Questionnaire (EHP-30). The Endometriosis Health Profile Questionnaire is a Health Related Quality of Life (HRQoL) patient self-report PRO, used to measure the wide range of effects that endometriosis can have on women's lives: pain, control and powerlessness, social support, emotional well-being, and self-image, range from 0-100, higher values indicate worse health status
pre-insertion of the pellet (baseline) and 3 months after pellet insertion of the gestrinone or placebo pellet
Uterine Bleeding Pattern
Временное ограничение: daily for 3 months after pellet insertion of the gestrinone or placebo pellet

Changes in uterine bleeding pattern (spotting/bleeding)
daily for 3 months after pellet insertion of the gestrinone or placebo pellet
Serum total gestrinone concentration
Временное ограничение: pre-insertion of the pellet (baseline) and 24 hours; 7 days, 14 days , 21 days , 28 days , 56 days, 84 days, 112 days, 140 days and 168 days post-insertion

Multiple blood sample will be collected before pellet implantation and 24 hours; 7 days, 14 days , 21 days, 28 days, 56 days, 84 days, 112 days, 140 days and 168 days and will be determined by liquid chromatography (LC-MS/MS)
pre-insertion of the pellet (baseline) and 24 hours; 7 days, 14 days , 21 days , 28 days , 56 days, 84 days, 112 days, 140 days and 168 days post-insertion
Area under the curve (AUC(0 ∞))
Временное ограничение: pre-insertion of the pellet (baseline) and 24 hours; 7 days, 14 days , 21 days , 28 days , 56 days, 84 days, 112 days, 140 days and 168 days post-insertion

Multiple blood sample will be collected before pellet implantation and 24 hours; 7 days, 14 days , 21 days, 28 days, 56 days, 84 days, 112 days, 140 days and 168 days and will be determined by liquid chromatography (LC-MS/MS)
pre-insertion of the pellet (baseline) and 24 hours; 7 days, 14 days , 21 days , 28 days , 56 days, 84 days, 112 days, 140 days and 168 days post-insertion
Maximum concentration (Cmax)
Временное ограничение: pre-insertion of the pellet (baseline) and 24 hours; 7 days, 14 days , 21 days , 28 days , 56 days, 84 days, 112 days, 140 days and 168 days post-insertion

Multiple blood sample will be collected before pellet implantation and 24 hours; 7 days, 14 days , 21 days, 28 days, 56 days, 84 days, 112 days, 140 days and 168 days and will be determined by liquid chromatography (LC-MS/MS)
pre-insertion of the pellet (baseline) and 24 hours; 7 days, 14 days , 21 days , 28 days , 56 days, 84 days, 112 days, 140 days and 168 days post-insertion
Time to reach maximum concentration (tmax)
Временное ограничение: pre-insertion of the pellet (baseline) and 24 hours; 7 days, 14 days , 21 days , 28 days , 56 days, 84 days, 112 days, 140 days and 168 days post-insertion

Multiple blood sample will be collected before pellet implantation and 24 hours; 7 days, 14 days , 21 days, 28 days, 56 days, 84 days, 112 days, 140 days and 168 days and will be determined by liquid chromatography (LC-MS/MS)
pre-insertion of the pellet (baseline) and 24 hours; 7 days, 14 days , 21 days , 28 days , 56 days, 84 days, 112 days, 140 days and 168 days post-insertion
Half Life (t1/2)
Временное ограничение: pre-insertion of the pellet (baseline) and 24 hours; 7 days, 14 days , 21 days , 28 days , 56 days, 84 days, 112 days, 140 days and 168 days post-insertion

Multiple blood sample will be collected before pellet implantation and 24 hours; 7 days, 14 days , 21 days, 28 days, 56 days, 84 days, 112 days, 140 days and 168 days and will be determined by liquid chromatography (LC-MS/MS)
pre-insertion of the pellet (baseline) and 24 hours; 7 days, 14 days , 21 days , 28 days , 56 days, 84 days, 112 days, 140 days and 168 days post-insertion

Соавторы и исследователи

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

Спонсор

Science Valley Research Institute

Соавторы

Biós Farmacêutica

Следователи

  • Учебный стул: Eduardo Ramacciotti, MD, PhD, Science Valley Research Institute
  • Главный следователь: André Luiz M Oliveira, MD, MHS, Science Valley Research Institute

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 (Действительный)

13 февраля 2023 г.

Первичное завершение (Действительный)

21 мая 2025 г.

Завершение исследования (Действительный)

31 октября 2025 г.

Даты регистрации исследования

Первый отправленный

3 октября 2022 г.

Впервые представлено, что соответствует критериям контроля качества

3 октября 2022 г.

Первый опубликованный (Действительный)

7 октября 2022 г.

Обновления учебных записей

Последнее опубликованное обновление (Действительный)

10 ноября 2026 г.

Последнее отправленное обновление, отвечающее критериям контроля качества

5 ноября 2026 г.

Последняя проверка

1 ноября 2026 г.

Дополнительная информация

Термины, связанные с этим исследованием

Ключевые слова

Дополнительные соответствующие термины MeSH

Другие идентификационные номера исследования

  • GLADE

Планирование данных отдельных участников (IPD)

Планируете делиться данными об отдельных участниках (IPD)?

НЕ РЕШЕНО

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. .

Подписаться