Equivalence of Intramuscular (IM) Versus Subcutaneous (SC) Applications of Long Acting Pamorelin 11.25 mg

Study Overview
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Brief Summary
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The purpose of this study is to demonstrate the pharmacodynamic equivalence of triptorelin pamoate (Pamorelin® LA 11.25 mg), applied either IM or SC, in terms of the area under the curve [AUC1-85day] for serum testosterone in patients with advanced prostate cancer.

Official Title
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A Phase II, Multicentre, Open, Prospective, Randomised, Parallel-Group, Pharmacodynamic Equivalence Study on Intramuscular Versus Subcutaneous Applications of Triptorelin Pamoate (Pamorelin® LA 11.25 mg) in Patients With Advanced Prostate Cancer

Conditions
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Prostate Cancer

Intervention / Treatment
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* Drug: Triptorelin Pamoate (Pamorelin® LA 11.25 mg)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histologically or cytologically proven prostate cancer, locally advanced or metastatic, or rising PSA (prostate-specific antigen) after failed local therapy, and the patient scheduled to receive androgen deprivation therapy Serum testosterone levels ≥ 125 ng/dl (1.25 ng/ml, 1.25 microg/l, 4.3 nmol/l) measured by any laboratory or on site within the previous 6 months or at study start Karnofsky performance index > 70 Expected survival ≥ 9 months Exclusion Criteria: Prior hormonal treatment for prostate cancer including gonadotropin-releasing hormone (GnRH) agonists or antagonists within the last 12 months preceding the study or concomitant treatment with one or more of these substance(s) Any current use or within 6 months prior to treatment start of medications which are known to affect the metabolism and/or secretion of androgenic hormones: ketoconazole, aminoglutethimide, oestrogens and progesterone Patient at risk of spinal cord compression or ureter obstruction Prior hypophysectomy or adrenalectomy

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: Triptorelin Pamoate (Pamorelin® LA 11.25 mg) IM.<br> | Drug: Triptorelin Pamoate (Pamorelin® LA 11.25 mg)<br>* Pamorelin® LA 11.25 mg administered as standard IM injection (= reference group) at Day 1 and Day 85. Triptorelin Pamoate (Pamorelin® LA 11.25 mg) applied subcutaneously (s.c.) at Day 1 and Day 85.<br>|
| Other: Triptorelin Pamoate (Pamorelin® LA 11.25 mg) SC.<br> | Drug: Triptorelin Pamoate (Pamorelin® LA 11.25 mg)<br>* Pamorelin® LA 11.25 mg administered as standard IM injection (= reference group) at Day 1 and Day 85. Triptorelin Pamoate (Pamorelin® LA 11.25 mg) applied subcutaneously (s.c.) at Day 1 and Day 85.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Area Under the Curve of Testosterone Serum Concentration Between D1 and D85 (AUC1-85d). | Area under the curve (AUC) calculated from serum testosterone concentration taken at intervals between the first administration (Day 1) of the study drug and Day 85 after dosing. From the curve describing serum testosterone concentration levels (ng/mL) over time, the AUC was calculated using numerical integration methods. This value was log-transformed to more closely meet the assumption of the statistical method. | 1, 3, 5, 8, 15, 22, 29, 57, 85 days post-dose | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Area Under the Curve of Testosterone Serum Concentration Between D1 and D169 (AUC1-169d) | Area under the curve calculated from serum testosterone concentration taken at intervals between the first administration (Day 1) of the study drug and Day 169 after dosing. From the curve describing serum testosterone concentration levels (ng/mL) over time, the AUC was calculated using numerical integration methods. This value was log-transformed to more closely meet the assumption of the statistical method. | 1, 3, 5, 8, 15, 22, 29, 57, 85, 87, 113, 141 and 169 days post-dose | 
| Area Under the Curve of Testosterone Serum Concentration Between D85 and D169 (AUC85-169d) | Area under the curve calculated from serum testosterone concentration taken at intervals between Day 85 and Day 169 after dosing. From the curve describing serum testosterone concentration levels (ng/mL) over time, the AUC was calculated using numerical integration methods. This value was log-transformed to more closely meet the assumption of the statistical method. | 85, 87, 113, 141 and 169 days post-dose | 
| Maximum Concentration of Serum Testosterone [Cmax] - Raw Data | Cmax was assessed as the maximum testosterone serum concentration between the first administration of the study drug and Day 169. | 1, 3, 5, 8, 15, 22, 29, 57, 85, 87, 113, 141 and 169 days post-dose | 
| Maximum Concentration of Serum Testosterone [Cmax] - Log-transformed Data | Cmax was assessed as the maximum testosterone serum concentration between the first administration of the study drug and Day 169. | 1, 3, 5, 8, 15, 22, 29, 57, 85, 87, 113, 141 and 169 days post-dose | 
| Time to Castration [Tcast] - Testosterone Level Less Than or Equal to 0.5 ng/mL | tcast is the number of days between day of first administration of the study drug and the day the testosterone level reaches the limit of castration defined as testosterone level less than or equal to 0.5 ng/mL for the first time. Analysis of tcast was based on the Kaplan-Meier estimator. | 12 weeks | 
| Time to Castration [Tcast] - Testosterone Level Less Than 0.5 ng/mL | tcast is the number of days between day of first administration of the study drug and the day the testosterone level reaches the limit of castration defined as testosterone level less than 0.5 ng/mL for the first time. Analysis of tcast was based on the Kaplan-Meier estimator. | 12 weeks |