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
Overview
- Phase
- Phase 2
- Intervention
- Gestrinone
- Conditions
- Deep Endometriosis
- Sponsor
- Science Valley Research Institute
- Enrollment
- 100
- Locations
- 1
- Primary Endpoint
- 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
- Status
- Completed
- Last Updated
- 3 months ago
Overview
Brief Summary
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.
Detailed Description
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 serious adverse events (SAEs) accumulated within 6 months of pellet insertion and collected through spontaneous reporting and/or clinical findings.
Investigators
Eligibility Criteria
Inclusion Criteria
- •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
- •Deep infiltrative 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
Exclusion Criteria
- •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
Arms & Interventions
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
Intervention: Gestrinone
Placebo
Subdermal implant-bioabsorbable placebo pellet (cholesterol) All patients will undergo insertion of an intrauterine system of levonorgestrel release (Kyleena®) as a contraceptive method
Intervention: Placebo
Outcomes
Primary Outcomes
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
Time Frame: From randomization to the end of study on Day 180
Proportion of patients who do NOT have 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.
Secondary Outcomes
- 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)