endometriosis MedDRA version: 20.0 Level: PT Classification code 10014778 Term: Endometriosis System Organ Class: 10038604 - Reproductive system and breast disorders
Conditions
Interventions
Product Name: Zoreline 3.6 mg implant
Pharmaceutical Form: Implant in pre-filled syringe
INN or Proposed INN: GOSERELIN
CAS Number: 65807-02-5
Concentration unit: mg milligram(s)
Concentration type: e
Sponsors
Novalon S.A.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Women aged between 18 and 45 years (inclusive), who are not menopausal. 2. Clinical diagnosis of endometriosis, within the last 5 years indicated for treatment with hormone therapy as judged by the investigator. Note: As per clinical guidelines: Clinical diagnosis is 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 give informed consent in writing. 5. Willing to use non-hormonal anti-conception from screening visit till the end of treatment (Day 29 of Period 2). 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 68 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 usage of GnRH receptor agonists or GnRH receptor antagonists within 6 months prior to the screening visit. 2. Use of treatments that interfere with estradiol plasma level within one week (or 5 half-lives, whichever is longer) before drug administration. 3. Endometriosis surgery scheduled in the period between screening and end of study. 4. Alanine aminotransferase (ALT)/ serum glutamic-pyruvic transaminase (SGPT) or aspartate transaminase (AST) / serum glutamic oxaloacetic transaminase (SGOT) levels = 2x upper limit of normal (ULN) or GGT = 2.5 x upper limit of normal. 5. Evidence (including clinically significant abnormal bilirubin and/or albumin values) or history for chronic hepatic disease. Gilbert’s disease however is allowed. 6. Moderate or severe chronic kidney disease with an estimated glomerular filtration rate (eGFR), calculated by using the modification of diet in renal disease (MDRD) equation, 450 ms at Screening or on Day 1 of Period 1 as measured by triplicate ECG. Note: If the mean value of the QTcF interval from the three measurements is above 450 ms, another triplicate ECG should be recorded once. 14. Family history for prolonged QT interval including history of arrhythmia, sudden unexplained death at a young age (before 40 years) in a first-degree relative. 15. Patients with unstable angina pectoris or stable angina pectoris classified higher than Canadian Cardiovascular Society Class II, or a myocardial infarction, or stroke within 6 months before Visit 1 ( Screening visit ). 16. History of hospitalization within 12 months before Visit 1 (Screening visit) caused by heart failure or a diagnosis of heart failure higher than New York Heart Association Class II. 17. Patient with decompensated diabetes mellitus. 18. Other abnormal laboratory results, which according to the investigator would affect the patient's health or the outcome of the trial. 19. Pregnancy (or willingness to become pregnant during the study) or breast-feeding. 20. Intellectual incapacity or inability to comprehend, precluding adequate understanding or co-operation. 21. Any contraindications for goserelin administration.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To characterize the goserelin plasma concentration profile based on primary pharmacokinetic endpoints from Day 1 to 29 of Period 1 and Day 1 (coinciding with Day 29 of Period 1) to Day 17 of Period 2 (2 treatment cycles whereas Day 29 of Period 2 represents the end of treatment), after 2 consecutive injections with Zoreline 3.6 mg or Zoladex® 3.6 mg subcutaneous implant in female subjects with confirmed endometriosis.;Secondary Objective: -To characterize additional PK parameters: gosereline plasma concentration at the end of the first treatment cycle[CDay29 of Period 1] and 17 days post-second implant injection [CDay17 of Period 2]; time to reach Cmax [tmax]. -To assess the general safety and acceptability of the drug in both groups. ;Primary end point(s): - Maximum measured goserelin plasma concentration in both groups (Cmax). - Area under the goserelin plasma concentration curve from administration to the last measurable concentration at time t in both groups (AUC0-t). - Area under the goserelin plasma concentration curve from administration to the last common measurable concentration time-point within all patients in both groups (AUC0-tcom).;Timepoint(s) of evaluation of this end point: The timepoints of evaluation of these endpoints are described in table 8.1-1 of the protocol. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Pharmacokinetics (PK): - Time to reach the maximum goserelin plasma concentration (t max). - Goserelin plasma concentration at the end of the first dosing interval (CDay29 of Period 1) and 17 days after second implant injection (CDay17 of Period 2). Pharmacodynamics (PD): - Maximum measured estradiol plasma concentration in both groups (Cmax). - Area under the estradiol plasma concentration curve from administration to the last measurable concentration at time t in both groups (AUC0-t). Safety: - Occurrence of serious and non-serious adverse events including clinically significant abnormalities in ECGs, vital signs, physical examination, and safety laboratory parameters.;Timepoint(s) of evaluation of this end point: The timepoints of evaluation of the PK and PD endpoints are described in table 8.1-1 of the protocol. The timepoints of evaluation of safety are described in table 5.3-1 of the protocol. | — |
Countries
Bulgaria
Contacts
Public ContactClinical Project Leader
Novalon S.A.
Outcome results
None listed