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COMPARISON OF A NEW FORMULATION OF GOSERELIN (Pepti 3.6 mg) to Zoladex® 3.6 mg

Phase 1
Completed
Conditions
Dysfunctional Uterine Bleeding
Interventions
Drug: Pepti 3.6 mg
Registration Number
NCT04428684
Lead Sponsor
Peptigroupe Inc.
Brief Summary

The comparator drug (Zoladex 3.6 mg) is approved for use as a thinning agent for the endometrium prior to endometrial ablation. The dosing recommendation is one or two depots with each depot given four weeks apart. When two depots are administered, surgery should be performed within two to four weeks following administration of the second depot.

Detailed Description

The primary objective of the study is to demonstrate non-inferiority of a generic formulation of goserelin 3.6 mg as compared to Zoladex ® 3.6 mg on endometrial thinning prior to surgery. The study is an open label, multicenter, prospective, parallel group randomized study.

Blind for Sponsor, ultrasound assessment, testing labs and statistician, the study will be performed in premenopausal women with dysfunctional uterine bleeding (DUB) eligible for endometrial ablation. Patients will be randomized in a 1 to 1 ratio to receive either the Peptigroupe test product (Pepti 3.6 mg) or Zoladex® 3.6 mg for a treatment of 8 weeks (two injections).

Ultrasonic measurement of endometrial thickness will be performed on screening and on days 0 (pre-injection), 28 (pre-injection) and 42 (pre surgical procedure).

The pharmacodynamics profile will be tabulated at the end of the study on the basis of the following data:

1. Estradiol

2. LH and FSH as additional information on hormone response

Goserelin safety profile will be assessed throughout the study on the basis of the following assessments:

1. Treatment-emergent AEs

2. Physical examinations

3. Vital signs

4. 12-Lead ECG

5. Laboratory parameters (i.e., biochemistry, haematology, and urinalysis)

Recruitment & Eligibility

Status
COMPLETED
Sex
Female
Target Recruitment
80
Inclusion Criteria
  1. Be pre-Menopausal females with regular menstrual cycles and > 30 years of age 2. Premenopausal at enrollment as determined by FSH measurement ≤ 60 IU/mL. 3. Endometrial thickness at pre-treatment less than 20 mm. 4. Diagnosis of Dysfunctional Uterine Bleeding and requiring endometrial ablation 5. Tumour negative cytology and histology 6. Appropriate sized uterus with no anatomic pathologies 7. Patient is not pregnant and does not wish to become pregnant in the future 8. Patient is willing to use a non-hormonal contraception method during the study, nor an intra-uterine device 9. Patient has no endocrine disorders, is not receiving hormonal therapies or non-steroidal anti-inflammatory medication. (prophylactic antibiotics can be administered according to the usual practice of the investigator) 10. Have the ability to understand the requirements of the study and is willing to provide written informed consent 11. Agree to abide by the study restrictions and return for the required assessments 12. Only patients which can be discontinued safely from contra-indicated medications discussed below in section 7.4 can be included in the study.
Exclusion Criteria
  1. Be pregnant or have desire to conceive

  2. Have abnormal endometrial cytology as confirmed by histology

  3. Have active endometritis

  4. Have active pelvic inflammatory disease

  5. Have active sexually transmitted disease (STD), at the time of ablation. Note: Treatment of STD documented in the chart serves as sufficient evidence of infection resolution. Patient may be considered for study enrollment.

  6. Presence of bacteremia, sepsis, or other active systemic infection

  7. Have active infection of the genitals, vagina, cervix, uterus or urinary tract at the time of inclusion

  8. Known/suspected gynecological malignancy within the past 5 years

  9. Known clotting defects or bleeding disorders

  10. Untreated/unevaluated cervical dysplasia

  11. Known/suspected abdominal/pelvic cancer

  12. Atypical Hyperplasia

  13. Prior uterine surgery (except low segment cesarean section) that interrupts the integrity of the uterine wall (e.g., myomectomy or classical cesarean section

  14. Currently on medications that could thin the myometrial muscle, such as long-term steroid use (except inhaler or nasal therapy for asthma)

  15. Currently on anticoagulants

  16. Have a known hypersensitivity to gonadotropin releasing hormone (GnRH), GnRH agonists, any LHRH agonists (e.g., leuprolide (Lupron®), goserelin ( Zoladex®) etc.) or to the PLGA polymers contained in the study formulation

  17. Have a severe liver disease (e.g., cirrhosis, chronic active hepatitis or chronic persistent hepatitis) or has persistent ALT, AST ˃ 2 X ULN, serum creatinine ˃ 2 X ULN, serum bilirubin ˃ 2 X ULN

  18. Have received an investigational drug or participated in a clinical trial within the last 30 days

  19. Have clinically serious and/or unstable concurrent infection, medical illnesses or conditions that are uncontrolled or whose control, in the opinion of the Investigator, may be jeopardized by participation in this study or by the complications of this therapy

  20. Patients with BMI ˂ 18

  21. Anticoagulated patients with INR ≥ 2

  22. Patients with a history of QT prolongation, congenital long QT syndrome, electrolyte abnormalities, CHF, or concurrent administration with QT prolonging drugs or QTc ˃450 msec.

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
Pepti 3.6 treatmentPepti 3.6 mgPatients treated with goserelin depot 3.6 mg. One injection on Day 0 and a second injection on Day 28
Zoladex 3.6 mg treatmentPepti 3.6 mgPatients treated with goserelin depot 3.6 mg. One injection on Day 0 and a second injection on Day 28
Primary Outcome Measures
NameTimeMethod
Non-inferiority in terms of activity of test drug versus comparator1 year

Non-inferiority of test drug compared to comparator in terms of reduction of the endometrial thickness prior to surgical ablation

Secondary Outcome Measures
NameTimeMethod

Trial Locations

Locations (5)

Central Military Hospital

🇺🇦

Kyiv, Ukraine

LLC Medical Center

🇺🇦

Kyiv, Ukraine

Maternity Hospital no 3

🇺🇦

Kyiv, Ukraine

Center for Innovative Medical Technologies of the National Academy of Sciences

🇺🇦

Kyiv, Ukraine

City Clinical Hospital

🇺🇦

Kyiv, Ukraine

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