A Phase II, Randomized, Placebo-controlled, Double-blind, Multicenter Study to Investigate the Safety and Exploratory Efficacy of a Subdermal Implant-bioabsorbable Gestrinone Pellet for Pelvic Pain Secondary to Endometriosis Treatment
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 100
- 试验地点
- 2
- 主要终点
- 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
研究概览
简要总结
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.
详细描述
This is a multicenter, prospective, randomized, double-blind and placebo-controlled study to evaluate the safety and tolerability of of subdermal implant-bioabsorbable gestrinone pellet use in women with pelvic pain secondary to endometriosis. The exploratory aim is to compare the use of a gestrinone pellet with a placebo pellet in the results of participant satisfaction, change in pelvic pain intensity, use of rescue pain medication, quality of life, sexual function, and work activity. PK profile of the gestrinone pellet will be monitored. 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 treatment-related serious adverse events (SAEs) accumulated within 6 months of pellet insertion and collected through spontaneous reporting and/or clinical findings.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 50 Years（Adult）
- 性别
- Female
- 接受健康志愿者
- 否
入选标准
- •Willingness to provide informed consent
- •Woman aged between 18 and 50 years
- •Body weight between 50 ± 5 kg and 90 ± 5 kg
- •Pelvic pain secondary to endometriosis surgically treated with refractory symptoms, independent of pain intensity
- •Endometriosis documented by biopsies (histopathological examination)
- •Last endometriosis surgery at least 3 months before randomization
- •Not planning to become pregnant within 12 months after the screening visit or be surgically sterilized
- •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
- •Agreement not to use other hormones (estrogens, androgens and progestins) in any pharmaceutical form during the study
排除标准
- •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
- •Suspected or confirmed diagnosis of immunodeficiency based on medical history and/or physical or laboratory examination
- •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
- •Personal history of thromboembolic events
- •Use anticoagulant medication
- •Contraindication to the use of hormonal contraceptives
- •Suspected or confirmed pregnancy
- •Breastfeeding
- •Current or recurrent pelvic inflammatory disease or other conditions that increase the risk of pelvic infections
- •Postpartum endometritis or septic miscarriage in the last 3 months
- •Abnormal uterine bleeding of unknown etiology
- •Congenital or acquired uterine anomalies, including fibroids (leiomyomas or fibromas) that cause distortion of the uterine cavity
- •Uterine or cervical malignancy
- •Suspected or confirmed diagnosis of estrogen-dependent neoplasm, including breast cancer
- •Cervicitis or vaginitis, including bacterial vaginosis or another uncontrolled lower urinary tract infection
- •Cervical dysplasia
- •Active liver disease or dysfunction
- •Benign or malignant liver tumors
- •Allergy or intolerance to levonorgestrel, gestrinone or any other ingredient or component of the Kyleena® formulation or hormonal pellets
- •Previously inserted intrauterine device or levonorgestrel-releasing intrauterine system that has not been removed
- •History of recent trophoblastic disease and continued high HCG levels
- •Bacterial endocarditis
- •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
- •Diagnosis of polycystic ovary syndrome
- •Participation in another pharmacotherapeutic or investigational medical device study within 30 days prior to the start of study treatment
- •Tobacco Use
- •Use of testosterone-derived hormones and analogues in the last month
研究组 & 干预措施
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
干预措施: Gestrinone (Drug)
Placebo
Subdermal implant-bioabsorbable placebo pellet (cholesterol) All patients will undergo insertion of an intrauterine system of levonorgestrel release (Kyleena®) as a contraceptive method
干预措施: Placebo (Drug)
结局指标
主要结局
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
时间窗: From randomization to the end of study on Day 180
Proportion of patients who dhave SAEs: 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. The treatment-related SAEs were considered for the primary safety outcome.
次要结局
- Uterine Bleeding Pattern(daily for 3 months after pellet insertion of the gestrinone or placebo pellet)
- Hematological disorders(pre-insertion of the pellet (baseline) and 3 months after pellet insertion of the gestrinone or placebo pellet)
- Renal adverse events(pre-insertion of the pellet (baseline) and 3 months after pellet insertion of the gestrinone or placebo pellet)
- Androgenization(pre-insertion assessment of the pellet (baseline), 3 and 6 months after insertion of the gestrinone or placebo pellet)
- Plasma concentration of steroid hormones(pre-insertion of the pellet (baseline) and 3 months after pellet insertion of the gestrinone or placebo pellet)
- Hepatic adverse events(pre-insertion of the pellet (baseline) and 3 months after pellet insertion of the gestrinone or placebo pellet)
- Lipid profile(pre-insertion of the pellet (baseline) and 3 months after pellet insertion of the gestrinone or placebo pellet)