Subdermal Implant-bioabsorbable Gestrinone Pellet for Endometriosis Pelvic Pain Treatment

NCT05570786 | Completed Phase 2 DMC

• 1 other identifier: GLADE
• Study Type: interventional
• Target: 100
• Locations: 1 country
• Sites: 1

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.

Conditions

Deep Endometriosis; Pelvic Pain

Keywords

Hormone Pellet Therapy; Implantable Hormone Pellets; Endometriosis; Pelvic pain

Outcome Measures

Primary Outcomes (1)

• 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

  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.

  From randomization to the end of study on Day 180

Secondary Outcomes (7)

• 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

• Lipid profile

  pre-insertion of the pellet (baseline) and 3 months after pellet insertion of the gestrinone or placebo pellet

• 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

Other Outcomes (10)

• Overall participant satisfaction

  3 months after pellet insertion of the gestrinone or placebo pellet

• Pelvic pain intensity

  pre-insertion assessment of the pellet (baseline), 3 and 6 months after insertion of the gestrinone or placebo pellet

• Use of pain relief medication

  pre-insertion assessment of the pellet (baseline), 3 and 6 months after insertion of the gestrinone or placebo pellet

Study Arms (2)

Gestrinone

EXPERIMENTAL

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

Drug: Gestrinone

Placebo

PLACEBO COMPARATOR

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

Drug: Placebo

Interventions

Gestrinone DRUG

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

Gestrinone

Placebo DRUG

Subdermal implant-bioabsorbable placebo pellet (cholesterol)

Placebo

Eligibility Criteria

• Age: 18 Years - 50 Years
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Science Valley Research Institute: lead
• Biós Farmacêutica: collaborator

Study Sites (1)

Science Valley Research Institute

São Paulo, São Paulo, Brazil

Location

Related Publications (6)

• Becker CM, Bokor A, Heikinheimo O, Horne A, Jansen F, Kiesel L, King K, Kvaskoff M, Nap A, Petersen K, Saridogan E, Tomassetti C, van Hanegem N, Vulliemoz N, Vermeulen N; ESHRE Endometriosis Guideline Group. ESHRE guideline: endometriosis. Hum Reprod Open. 2022 Feb 26;2022(2):hoac009. doi: 10.1093/hropen/hoac009. eCollection 2022.

  PMID: 35350465 BACKGROUND

• Coutinho EM. Treatment of endometriosis with gestrinone (R-2323), a synthetic antiestrogen, antiprogesterone. Am J Obstet Gynecol. 1982 Dec 15;144(8):895-8. doi: 10.1016/0002-9378(82)90180-6.

  PMID: 6216812 BACKGROUND

• Venturini PL, Bertolini S, Brunenghi MC, Daga A, Fasce V, Marcenaro A, Cimato M, De Cecco L. Endocrine, metabolic, and clinical effects of gestrinone in women with endometriosis. Fertil Steril. 1989 Oct;52(4):589-95. doi: 10.1016/s0015-0282(16)60969-x.

  PMID: 2806598 BACKGROUND

• Gestrinone versus a gonadotropin-releasing hormone agonist for the treatment of pelvic pain associated with endometriosis: a multicenter, randomized, double-blind study. Gestrinone Italian Study Group. Fertil Steril. 1996 Dec;66(6):911-9. doi: 10.1016/s0015-0282(16)58682-8.

  PMID: 8941054 BACKGROUND

• Devogelaer JP, Nagant de Deuxchaisnes C, Donnez J. Endometriosis. Lancet. 1993 Jan 30;341(8840):312-3. doi: 10.1016/0140-6736(93)92673-h. No abstract available.

  PMID: 8093956 BACKGROUND

• Malavasi A, Ribeiro CM, Agati LB, Silva Filho A, Berger C, Schor E, Comin A, Bezerra Neto EJ, Oliveira TH, Caldas PR, Lopes F, Westphalen N, Vieira F, Socca EAR, Komar D, Ramacciotti E. Rationale and design of the GLADE study: a randomized, multicenter, double-blind, placebo-controlled trial evaluating the safety and efficacy of gestrinone subdermal bioabsorbable pellet in endometriosis-related pelvic pain. Ann Med. 2025 Dec;57(1):2527352. doi: 10.1080/07853890.2025.2527352. Epub 2025 Jul 11.

  PMID: 40641309 BACKGROUND

MeSH Terms

Conditions

Pelvic Pain; Endometriosis

Interventions

Gestrinone

Condition Hierarchy (Ancestors)

Pain; Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Diseases

Intervention Hierarchy (Ancestors)

Norgestrienone; Norpregnatrienes; Norpregnanes; Norsteroids; Steroids; Fused-Ring Compounds; Polycyclic Compounds

Study Officials

• Eduardo Ramacciotti, MD, PhD

  Science Valley Research Institute

  STUDY CHAIR

• André Luiz M Oliveira, MD, MHS

  Science Valley Research Institute

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 3, 2022
• First Posted: October 7, 2022
• Study Start: February 13, 2023
• Primary Completion: May 21, 2025
• Study Completion: October 31, 2025
• Last Updated: January 12, 2026

Record last verified: 2026-01

Locations

BR (1)