None listed
Conditions
Interventions
Pepti 10.8mg Type of group
This randomized, two-treatment, single blind parallel multicenter study is designed to compare the pharmacokinetic profiles of a new depot formulation of goserelin, Pepti 10.8mg in ambulatory patients with advanced carcinoma of the prostate, in comparison with that of Zoladex 10.8mg.
A 12 week (84 days) parallel study in 110 patients (55 with one injection of Pepti 10.8 mg and 55 with one injection of Zoladex 10.8 mg).
During a screening phase, all patients will come to the clinic for a Sc
This randomized, two-treatment, single blind parallel multicenter study is designed to compare the pharmacokinetic profiles of a new depot formulation of goserelin, Pepti 10.8mg in ambulatory patients with advanced carcinoma of the prostate, in comparison with that of Zoladex 10.8mg.
A 12 week (84 days) parallel study in 110 patients (55 with one injection of Pepti 10.8 mg and 55 with one injection of Zoladex 10.8 mg).
During a screening phase, all patients will come
Sponsors
PEPTIGROUPE Inc,
Eligibility
Inclusion criteria
Inclusion criteria: 1 Be a male ≥ 18 years of age 2 Be an ambulatory patient with advanced carcinoma of the prostate, as verified by an available previous biopsy 3 Have a life expectancy ≥ 1 year 4 Have a testosterone level ˃ 5 nmol/L or ˃ 1.5 ng/mL at screening 5 Have the ability to understand the requirements of the study and is willing to provide written informed consent 6 Agree to abide by the study restrictions and return for the required assessments
Exclusion criteria
Exclusion criteria: 1. Have brain metastases 2. Have vertebral metastases with evidence of spinal cord compression 3. Have renal impairment due to ureteric obstruction or a recent history of obstructive uropathy 4. Have excruciating, severe bone pain due to extensive bone metastases. Concomitant therapy with either flutamide or bicalutamide is permitted during the first month of the study, in the case where bone metastases are present or suspected 5. Have undergone orchiectomy, adrenalectomy or hypophysectomy 6. Have undergone prostatic surgical procedures (e.g., radical prostatectomy, transurethral resection of the prostate) within the last month 7. Have undergone localized external beam radiotherapy, brachytherapy, thermotherapy, cryotherapy within the last 4 weeks 8. Have undergone systemic chemotherapy, immunotherapy (e.g., antibody therapies, tumor-vaccines) or biological response modifiers (e.g., cytokines) within the last 3 months 9. Have been treated with 5-alpha-reductase inhibitors (e.g., finasteride (Proscar®, Propecia® ) dutasteride (Avodart®)) within the last 3 months 10. Have been previously treated with luteinizing hormone releasing hormone agonists (LHRHa) (e.g., leuprolide (Lupron®), goserelin (Zoladex) etc.) in the past 6 months. 11. Have an ongoing treatment with androgen receptor (AR) blockers (e.g megestrol (Megace®) cyproterone (Androcur®). (For the mitigation of the initial testosterone flare, Bicalutamide (Casodex®) treatment is permitted, but must be initiated prior to study and terminated at the latest 30 days after the patient has received goserelin depot injection). 12. 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 13. Have a severe liver disease (e.g., cirrhosis, chronic active hepatitis or chronic persistent hepatitis) or have persistent ALT, AST ˃ 2 X ULN, serum creatinine ˃ 2 X ULN, serum bilirubin ˃ 2 X ULN 14. Have received an investigational drug or participated in a clinical trial within the last 30 days 15. Have a 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 16. Have a BMI450 msec.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Outcome name:Goserelin pharmacokinetic profile will be assessed at the end of the study. Blood sampling for the determination of goserelin pharmacokinetic profile will be performed according to the Sampling Schedule mentioned efecto aleatorio. Se calculara el intervalo deabove in section 5.1. Methods are described in the Laboratory Manual. The pharmacokinetic endpoints are defined as follows:  AUC 0-t: Area under the curve from time 0 to the final sample on day 84  Cmax Maximum serum concentration Bioequivalence will be based on the test to reference ratio and 90% confidence interval for both AUC0-t and Cmax lying between 80-125%. Patients included in the PK analysis population will be used to assess bioequivalence. Descriptive statistics (n, arithmetic mean, standard-deviation, geometric mean, coefficient of variation) will be presented per formulation and visit (timepoint) for concentration levels and per formulation for PK parameters. Bioequivalence will be evaluated through analysis of variance (ANOVA) of the natural log (ln) of the maximal concentration (Cmax) and of Area Under Curve from time zero to day 84 (AUC0-t). For each of the dependent variables ln (Cmax) and ln (AUC0-t) the ANOVA shall include formulation as fixed effect and country as random effect. 90% confidence interval will be calculated on the Test to Reference ratio of the geometric means (estimated from the ANOVA). Measure:Bioequivalence Timepoints:From Day 0 to day 84 | — |
Secondary
| Measure | Time frame |
|---|---|
| Outcome name:It is expected that testosterone levels will increase during the first days of treatment. Nevertheless, serum T levels should remain below castration level after Day 21 and throughout the study. The main PD endpoint will be the testosterone response rate defined as the percentage of patients under castration level (1.75 nmol/L) from Day 35 to Day 84. A patient will be considered under castration level if no time points are above the castration level from Day 35 to Day 84 inclusively. The supportive PD endpoints are: • Testosterone levels and % of patients under the castration levels at each time point, especially on Day 35 and 84 • LH and FSH levels to gather additional information on hormone response • PSA levels to gather information on the evolution of the tumor, although the study is a bioequivalence study, and is not designed to assess and compare tumor response. Pharmacodynamic analysis will be conducted using the mITT and PP populations. For the analyses using mITT, imputation of missing observations will be performed. Details will be presented in the statistical analysis plan. For the analyses using PP, the observed case principle will be used (i.e. no imputation of missing observations will be done).Testosterone concentration levels and % of patients under the castration level (1.75 nmol./L) will be presented descriptively per formulation and visit. Moreover, non-inferiority of Pepti 10.8 mg to Zoladex 10.8 mg based on the testosterone response rate will be evaluated in the PP and mITT populations. Based on the standard method used for binary outcomes (success/failure), if the lower 97.5% confidence limit (calculated using Yates’ continuity correction) for the difference between the proportion of patients considered as having achieved castration levels throughout Day 35 to Day 84 is ≥ -0.020, then non-inferiority of Pepti 10.8 mg to Zoladex 10.8 mg will be considered to have been demonstrated. Measure:Pharm | — |
Countries
Canada, Chile, Colombia, Peru, Serbia, Ukraine
Contacts
Public ContactRomina Trigo
RESOLUTION LATIN AMERICA PERU S.A.
Outcome results
None listed