A study in males with prostate cancer performed in several centers to assess the blood levels after injection of two subcutaneous implants containing 10.8 mg goserelin

• Register: EUCTR
• Last refreshed on: 5 March 2018
• Main ID: EUCTR2015-001756-30-BG
• Date of registration: 16/12/2015
• Prospective Registration: Yes
• Primary sponsor: Novalon S.A.
• Public title: A study in males with prostate cancer performed in several centers to assess the blood levels after injection of two subcutaneous implants containing 10.8 mg goserelin
• Scientific title: Open-label, multi-center, randomized parallel group study to assess the pharmacokinetic (PK) profile of Zoreline 10.8 mg goserelin subcutaneous implant (test product, Novalon S.A.) and of Zoladex® LA 10.8 mg goserelin subcutaneous implant (reference product, AstraZeneca UK Limited) in male patients with prostate cancer
• Date of first enrolment: 05/01/2016
• Target sample size: 58
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2015-001756-30
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes; Randomised: yes; Open: yes; Single blind: no; Double blind: no; Parallel group: yes; Cross over: no; Other: no; If controlled, specify comparator, Other Medicinial Product: yes; Placebo: no; Other: no; Number of treatment arms in the trial: 2
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): yes Therapeutic confirmatory - (Phase III): no Therapeutic use (Phase IV): no

Countries of recruitment

Bulgaria

Contacts

• Name: CMC Project Leader
• Affiliation: Novalon S.A.

• Name: CMC Project Leader
• Affiliation: Novalon S.A.

Key inclusion & exclusion criteria

Inclusion criteria:
1. Males Age 18 years (inclusive) or above
2. Histologically confirmed prostate adenocarcinoma and indicated for androgen deprivation therapy (ADT). Previous prostatectomy and/or prostate radiotherapy are allowed.
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 and able to attend the scheduled study visits and to comply with the study procedures
6. Testosterone level > 2.5 ng/mL at screening
7. PSA level =4ng/mL.
Exception: for patients who have had previous prostatectomy and/or prostate radiotherapy, all PSA levels are allowed.
8. Life expectancy > 1 year assessed at screening or within the last month
9. Body Mass Index between 18.5 and 35kg/m2 inclusive
10. ECOG score of =2 measured at screening
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 43
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 15

Exclusion criteria:
1. Previous or current hormonal treatment for prostate cancer (surgical castration or other hormonal manipulation, including GnRH receptor agonists, GnRH receptor antagonists, anti-androgens, estrogens, 5 alpha reductase inhibitors) within 6 months prior to the screening visit. All other prohibited medications that are listed in Appendix 3 should not have been administered within the last 3 months prior the study drug administration
2. Scheduled for prostatectomy or prostate radiotherapy during study period
3. Alanine aminotransferase (ALT) / serum glutamic-pyruvic transaminase (SGPT) or aspartate transaminase (AST) / serum glutamic oxaloacetic transaminase (SGOT) =2x upper limit of normal (ULN) or GGT =2.5 x upper limit of normal
4. Evidence (including clinically significant abnormal bilirubin and/or albumin values) or history for chronic hepatic disease
Moderate or severe chronic kidney disease with an estimated glomerular filtration rate (eGFR), using the modification of diet in renal disease (MDRD) equation, <60 mL/min/1,73m2
6. Has received an investigational drug within the last 28 days before the Screening visit or 5 times the half-life of the drug whichever is longer if considered by the investigator to possibly influencing the outcome of this trial
7. History or presence of any malignancy other than prostate cancer and treated squamous cell /basal cell carcinoma of the skin within the last five years
8. Have an unstable medical condition or chronic disease (including history of neurological [including cognitive], cardiovascular, gastrointestinal, pulmonary, or endocrine disease), that could confound interpretation of the study at investigator discretion
9. History of severe uncontrolled asthma, anaphylactic reactions, or severe urticarial and/or angioedema, and particularly, history of hypersensitivity towards any components of the study drug
10. Other abnormal laboratory results which in the judgment of the investigator would affect the patient's health or the outcome of the trial
11. Has an intellectual incapacity or language barrier precluding adequate understanding or co-operation
12. Have a prolonged QTc interval defined as mean QTcB > 450 ms at Screening. If the mean value of QTcB interval from the three measurements is above 450 ms, another triplicate ECG could be recorded once on the same day
13. Have a family history for prolonged QT interval including a history of arrhythmia, sudden unexplained death at a young age (before 40 years) in a first-degree relative, or a personal history of syncope
14. Evidence or history for significant active cardiac disease (e.g., congestive heart failure, mitral valve regurgitation, endocarditis, coronary artery heart disease), or symptoms of angina pectoris or transient ischaemic attacks


Age minimum:
Age maximum:
Gender:
Female: no
Male: yes

Health Condition(s) or Problem(s) studied

Therapeutic area: Diseases [C] - Cancer [C04]

prostate cancer
MedDRA version: 18.1 Level: PT Classification code 10060862 Term: Prostate cancer System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Intervention(s)

Product Name: Zoreline 10.8 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: equal
Concentration number: 10.8-

Trade Name: Zoladex® LA
Pharmaceutical Form: Implant in pre-filled syringe
INN or Proposed INN: GOSERELIN
CAS Number: 65807-02-5
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 10.8-

Primary Outcome(s)

Main Objective: To characterize the goserelin plasma concentration profile based on primary pharmacokinetic endpoints from Day 1 to 85 (1 treatment cycle, Day 85 represents the end of treatment), after injection with Zoreline 10.8 mg or Zoladex® LA 10.8 mg subcutaneous implant in male patients with prostate cancer

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 time-point within all patients in both groups (AUC0-tcom)

Secondary Objective: - To characterize additional PK parameters (plasma concentration at the end of the treatment period [CDay85], time to reach Cmax [tmax]).
- To characterize the testosterone plasma concentration (PD) profile including initial flare between Day 1 and Day 28 and time to achieve castrate level (=50 ng/dl) after injection with Zoreline 10.8 mg or Zoladex® LA 10.8 mg subcutaneous implant
- To assess general safety and acceptability of the drug in both groups

Exploratory:
• To assess the performance of a novel syringe used to inject Zoreline 10.8 mg subcutaneous implant

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 Outcome(s)

Secondary end point(s): Pharmacokinetics (PK):
- Time until the maximum goserelin plasma concentration is reached (t max)
- Goserelin plasma concentration at the end of the treatment period (CDay85)

Pharmacodynamics (PD):
- Maximum measured testosterone plasma concentration in both groups (Cmax)
- Area under the testosterone plasma concentration curve from administration to the last measurable concentration at time t in both groups (AUC0-t)
- Testosterone plasma concentrations to characterize initial flare between Day 1 and Day 28 and time to achieve castrate level (=50 ng/dl), in both groups
Safety:
- Occurrence of serious and non-serious adverse events, ECG, vital signs, physical examination and safety laboratory parameters

Exploratory variables:
- Performance score related to the use of the syringe through a questionnaire for the investigators.

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 and exploratory endpoints are described in section 20.1. of the protocol - Study visit schedule .

Secondary ID(s)

No0002-C201

Source(s) of Monetary Support

Novalon S.A.