Intramuscular Injections of Degarelix Administered in 1-Month Dosing Regimens in Patients With Prostate Cancer

Study Overview
=================
Brief Summary
-----------------
Intramuscular Injections of Degarelix Administered in 1-Month Dosing Regimens in Patients with Prostate Cancer.

Official Title
-----------------
Open-label, Multi-centre, Parallel Group Dose-Escalation Trial Assessing the Pharmacokinetics, Pharmacodynamics, Efficacy and Safety of Intramuscular Injections of Degarelix Administered in 1-Month Dosing Regimens in Patients With Prostate Cancer

Conditions
-----------------
Prostate Cancer

Intervention / Treatment
-----------------
* Drug: Degarelix


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Has a histologically confirmed adenocarcinoma of the prostate, for which endocrine therapy is indicated Has a current tumour, nodule and metastasis (TNM) staging within 12 weeks prior to treatment start and, if clinically indicated a bone scan Has a PSA level meeting one of these criteria: For treatment-naïve patients: Screening PSA level should be ≥2 ng/mL. For patients with recurrence after radical prostatectomy: Patients should have a serum PSA increase of ≥0.2 ng/mL from the previous test on two consecutive measurements For patients with recurrence after radiotherapy or cryotherapy: Patients should have a serum PSA (two measurements) to be >2 ng/mL higher than a previously confirmed PSA nadir Has a screening serum testosterone level above the lower limit of normal range in an elderly male population, globally defined as >150 ng/dL Has an Eastern Cooperative Oncology Group score of ≤2 Has a life expectancy of at least one year Exclusion Criteria: Has had previous or is currently under hormonal management of prostate cancer Is considered to be a candidate for curative therapy i.e. radical prostatectomy or radiotherapy during the trial period Has a history of bilateral orchiectomy, adrenalectomy, or hypophysectomy Has a marked baseline prolongation of QT/QTcF interval (e.g. repeated demonstration of a QTcF interval >450 ms) Has a history of risk factors for Torsade de Pointes ventricular arrhythmias (e.g. heart failure, hypokalemia, or family history of Long QT Syndrome) Has a previous history or presence of another malignancy, other than prostate Currently receiving chronic treatment with intramuscular medication injected into the ventrogluteal or dorsogluteal muscle Has received an investigational drug within the last 28 days preceding the Screening Visit or longer if considered to possibly influence the outcome of the current trial

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
Male

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Degarelix - Cohort 1<br>(gonadotrophin-releasing hormone (GnRH) receptor blocker) | Drug: Degarelix<br> <br> |
| Experimental: Degarelix - Cohort 2<br>(gonadotrophin-releasing hormone (GnRH) receptor blocker) | Drug: Degarelix<br> <br> |
| Experimental: Degarelix - Cohort 3<br>(gonadotrophin-releasing hormone (GnRH) receptor blocker) | Drug: Degarelix<br> <br> |

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Plasma degarelix PK profile (blood sample analysis): measured by (Cmax, AUC, Tmax) |  | Day 0-28 and at Day 112-140 | 
| Trough plasma levels (blood sample analysis) | Actual levels prior to dosing | Day 28, 56, 84, 112, 140, 168 and 196 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of patients with testosterone ≤0.5 ng/mL |  | From baseline to Day 196 | 
| Serum levels of testosterone and PSA |  | From baseline to Day 196 | 
| Percentage change in PSA levels |  | From baseline to Day 196 | 
| Changes in patient-reported injection site pain (VAS scores over time) | Will compare starting dose to maintenance doses | At 5 minutes and at 60 minutes after each injection | 
| Proportion of patients without clinically significant pain (VAS score of ≤10 mm) |  | 60 minutes after each dosing injection | 
| Incidence and severity of investigator-evaluated injection site reactions |  | From baseline to Day 196 | 
| Cumulative probabilities of suppressing testosterone to castrate level (≤0.5 ng/mL) by visit |  | From Day 28 onwards (up to Day 196) | 
| Predictive one-year suppression rate and 95% CI: The cumulative probability of suppressing testosterone to castrate levels (≤0.5 ng/mL) |  | From Day 28 to Day 364 | 
| Incidence of adverse events (AEs) examined by frequency, severity, seriousness and discontinuation from study due to AEs |  | From baseline to Day 196 | 
| Clinically significant changes in laboratory values |  | From baseline to Day 196 | 
| Clinically significant changes in ECGs, vital signs, physical examinations, and body weight |  | From baseline to Day 196 |