Endometriosis MedDRA version: 19.0 Level: PT Classification code 10014778 Term: Endometriosis System Organ Class: 10038604 - Reproductive system and breast disorders
Conditions
Interventions
Product Name: Zoreline 3.6 mg goserelin
Pharmaceutical Form: Implant in pre-filled syringe
INN or Proposed INN: GOSERELIN
CAS Number: 65807-02-5
Concentration unit: mg milligram(s)
Concentration type:
Sponsors
Novalon S.A
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Premenopausal women aged between 18 and 45 years inclusive; 2. Clinical diagnosis of endometriosis within the last 5 years and indicated for hormonal suppression therapy. Clinical diagnosis should be based on clinical symptoms of endometriosis (such as chronic pelvic pain, dyspareunia, cyclic intestinal pain [bloating/diarrhoea/constipation], uterine cramping in young females, severe dysmenorrhea, dyspareunia, ovulation pain, cyclical/menstrual symptoms with or without abnormal bleeding, infertility, chronic fatigue) confirmed by laparoscopy with or without histology and/or transvaginal/rectal ultrasound (bladder, ovarian or rectum locations) and/or enema studies (for deeply infiltrating endometriosis); 3. Good physical and mental health as judged by the investigator determined by medical history, physical examination, clinical laboratory and vital signs; 4. Willing to provide informed consent in writing; 5. Willing to use non-hormonal anti-conception method (male/female condom/copper intrauterine device [IUD]) from Screening (Visit 1; Day -28 to Day -4) till the end of treatment period (Visit 14; Day 85±2 days); 6. Willing and able to attend the scheduled study visits and to comply with the study procedures; 7. Body Mass Index (BMI) between 18 and 32 kg/m2 inclusive. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 142 F.1.3 Elderly (>=65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: 1. Previous or current hormonal treatment for endometriosis, including GnRH receptor agonists, GnRH receptor antagonists, within 6 months prior to the screening visit; 2. Alanine aminotransferase (ALT)/serum glutamic-pyruvic transaminase (SGPT) or aspartate transaminase (AST)/serum glutamic oxaloacetic transaminase (SGOT) =2 x upper limit of normal (ULN); 3. Moderate (stage 3B) or severe (stage 4 and 5) chronic kidney disease with an estimated glomerular filtration rate (eGFR), using the modification of diet in renal disease (MDRD) equation, <45 mL/min/1,73 m2; 4. Use of contraceptive treatments that interfere with oestradiol plasma level 1 week (or 5 half lives; whichever is longest) before IMP administration; 5. Has endometriosis surgery scheduled for between the Screening and Enrolment visit. (Endometriosis surgery allowed following Visit 14 [Day 85±2 days]); 6. Implanted progestin treatment should be released at least 1 month before study enrolment; 7. Has received an investigational drug within the last 28 days before the Screening visit (Visit 1) or longer if considered to possibly influencing the outcome of this study; 8. Has an unstable medical condition or chronic disease such as but not limited to neurological hepatic, renal, cardiovascular, gastrointestinal, pulmonary, or endocrine disease; 9. History or presence of any malignancy other than treated squamous cell/basal cell carcinoma of the skin within the last 5 years; 10. Evidence (including clinically significant abnormal bilirubin and/or albumin values) or history of chronic hepatic disease; 11. Have a repeatable prolongation of the QTc interval at screening (mean QTcB =450 ms); or personal or family history of long QT syndrome or significant risk factors of prolonged QT interval arrhythmias. (as determined by the investigator); 12. Patient for which a possible loss in bone mass which in the judgment of the investigator would affect the patient's health; 13. History of severe uncontrolled asthma, anaphylactic reactions, or severe urticarial and/or angioedema, and particularly, history of hypersensitivity towards any components of the IMP; 14. Other abnormal laboratory results which in the judgment of the investigator would affect the patient's health or the outcome of the study; 15. Pregnancy (or willingness to become pregnant during the study) or breast-feeding during study period; 16. Has an intellectual incapacity or inability to comprehend, precluding adequate understanding or co-operation.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To assess the ability of Zoreline 3.6 mg SC implant to induce by Visit 7 (Day 29±1 day) of Cycle 1 at the latest and maintain up to Visit 14 (end of treatment; Day 85±2 days) oestradiol plasma suppression (=30 pg/mL) in women with confirmed endometriosis;Secondary Objective: •To assess general safety and acceptability of the drug and syringe combination in line with standard of care. •To characterize the goserelin plasma concentration profile (maximum plasma concentration [Cmax], time to reach Cmax [Tmax], minimum plasma concentration [Cmin], area under the plasma concentration-time curve [AUC]) from Visit 2 (Day 1) to Visit 7, from Visit 7 to Visit 12, and from Visit 12 to Visit 14, i.e. during three consecutive treatment cycles, and during follow-up period until Visit 15. The area under the curve will be extrapolated to infinity (AUC0-8) and terminal (apparent elimination) half-life (t½) will be determined if possible. •To characterize the (Cmax, AUC) from Visit 2 (Day 1) to Visit 15 including initial flare between Visit 2 (Day 1) and Visit 7, time to achieve menopause level, acute or chronic phenomenon (surge at re-injection between Visit 8 (Day 30) and Visit 9 (Day 32) and potential escape (surge) from Visit 10 (Day 36±1 day) to Visit 14. ;Primary end point(s): The primary objective will be considered as achieved if the lower limit of the 2-sided 95% CI on the responder rate is =90%.;Timepoint(s) of evaluation of this end point: A responder is defined as a subject who reached plasma oestradiol levels below the menopause level (=30 pg/mL) by Visit 7 (Day 29±1 day) at the latest and maintained plasma oestradiol levels below the menopause level (=30 pg/mL) until Visit 14 (end of treatment; Day 85±2 days), except for : •Oestradiol level during the acute-on-chronic period from Visit 8 (Day 30) to Visit 9 (Day 32); •Oestradiol escape following the onset of suppression from Visit 10 (Day 36±1 day) to Visit 13 (Day 71±2 days) not confirmed at the next s | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Pharmacodynamics (PD): ? Plasma concentrations of oestradiol from Visit 2 (Day 1) to Visit 15 (as soon as possible after return of the patient’s menses or at the latest at Day 141±3 days) including initial flare between Visit 2 (Day 1) and Visit 7 (Day 29±1 day), time to achieve menopause level, acute or chronic phenomenon (surge(s) at re-injection) between Visit 8 (Day 30) and Visit 9 (Day 32) and potential escape (surge) from Visit 10 (Day 36±1 day) to Visit 14 (end of treatment; Day 85±2 days). Pharmacokinetics (PK): ? Plasma concentrations of goserelin. Safety: ? Occurrence of serious and non-serious adverse events (AEs).;Timepoint(s) of evaluation of this end point: Blood samples will be drawn at Visits 2 (Day 1), Visit 3 (Day 2), Visit 4 (Day 4), Visit 5 (Day 8±1 day), Visit 6 (Day 15±2 days), Visit 7 (Day 29±1 day), Visit 8 (Day 30), Visit 9 (Day 32), Visit 10 (Day 36±1 day), Visit 11 (Day 43±2 days), Visit 12 (Day 57±1 day), Visit 13 (Day 71±2 days), Visit 14 (Day 85±2 days) and Visit 15 (as soon as possible after return of the patient’s menses or at the latest at Day 141±3 days) for oestradiol, LH, FSH and goserelin levels. Blood samples for biochemistry and haematology testing and a urine sample for urinalysis will be collected at Visit 1 (Screening; Day -28 to Day -4) and Visit 15 (as soon as possible after return of the patient’s menses or at the latest at Day 141±3 days) for safety purposes. | — |
Countries
Hungary
Contacts
Public ContactGeert Winnen
Novalon S.A
Outcome results
None listed