Study Investigating the Pharmacokinetics, Pharmacodynamics and Safety of FE200486

Study Overview
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Brief Summary
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Population pharmacokinetic and pharmacodynamic data from Study FE200486 CS06 and FE200486 CS02 provided further knowledge of the optimal dose regimens for FE200486 (degarelix). Both studies were to guide dose selection for phase III. In addition, safety and tolerance data were generated.

Official Title
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An Open-Label, Multi-Center, Ascending, Single Dose Study Investigating the Pharmacokinetics, Pharmacodynamics and Safety of FE200486

Conditions
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Prostate Cancer

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


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Each patient must meet the following inclusion criteria before entry into the study: Has given written consent before any study related activity is performed (A study related activity is defined as any procedure that would not have been performed during the normal management of the patient.) Is a male patient with histologically proven adenocarcinoma of the prostate (all stages) in whom endocrine treatment is indicated, except for neoadjuvant hormonal therapy. For patients, prostate-specific antigen (PSA) increases on two consecutive determinations at least 2 weeks apart prior to Visit 1 must be documented. Is at least 18 years. Has an ECOG score of 2. Has a baseline testosterone level within the age specific normal range as measured by the central laboratory. Has a PSA value of 2 ng/mL as measured by the central laboratory. Has a life expectancy of at least 6 months. Exclusion Criteria: Any patient meeting one or more of the following exclusion criteria will not be entered into the study: Previous or present hormonal management of prostate cancer (surgical castration or other hormonal manipulation, e.g. GnRH agonists, GnRH antagonists, antiandrogens, estrogens, PC-Spec) except for neoadjuvant hormonal therapy of < 6 months duration and completed > 6 months prior to Visit 1. Requires hormonal therapy for neoadjuvant purposes. Is recently (within the last 12 weeks preceding Visit 1) or presently treated with any other drug modifying the testosterone level or function. Is considered to be a candidate for curative therapy, i.e., radical prostatectomy or radiotherapy within 6 months after Visit 1. Has a history of severe asthma requiring daily treatment with inhalation steroids, angioedema or anaphylactic reactions. Has hypersensitivity towards any component of the investigational product. Has had a cancer disease within the last 10 years except for prostate cancer, and surgically removed basocellular or squamous cell carcinoma of the skin. Has a clinically significant neurologic, gastrointestinal, renal, hepatic, cardiovascular, psychological, pulmonary, metabolic, endocrine, hematological, dermatological or infectious disorder or any other condition, including excessive alcohol or drug abuse, which may interfere with trial participation, or which may affect the conclusion of the study, as judged by the investigator. Any clinically significant laboratory abnormalities which, in the judgment of the investigator, would interfere with the patient's participation in this study or evaluation of study results (liver transaminases must be within normal limits). Has a mental incapacity or language barrier precluding adequate understanding or co-operation. Has received an investigational drug within the last 12 weeks preceding Visit 1. Has previously participated in this study.

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 |
| --- | --- |
| Experimental: Degarelix 40 mg<br>Degarelix 40 mg (10 mg/mL) | Drug: Degarelix<br>* One dose (2 x 2 mL) of degarelix 40 mg (10 mg/mL), subcutaneous injection.<br>* Other names: FE200486;|
| Experimental: Degarelix 80 mg<br>Degarelix 80 mg (20 mg/mL) | Drug: Degarelix<br>* One dose (2 x 2 mL) of degarelix 80 mg (20 mg/mL), subcutaneous injection.<br>* Other names: FE200486;|
| Experimental: Degarelix 120 mg<br>Degarelix 120 mg (30 mg/mL) | Drug: Degarelix<br>* One dose (2 x 2 mL) of degarelix 120 mg (30 mg/mL), subcutaneous injection.<br>* Other names: FE200486;|
| Experimental: Degarelix 160 mg<br>Degarelix 160 mg (40 mg/mL) | Drug: Degarelix<br>* One dose (2 x 2 mL) of degarelix 160 mg (40 mg/mL), subcutaneous injection.<br>* Other names: FE200486;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to Meet Insufficient Testosterone Response | Figures in the table are Kaplan-Meier estimates of the time to meeting insufficient testosterone response. Insufficient testosterone response was defined as testosterone >1.0 ng/mL at one visit or testosterone 0.5-1.0 at two consecutive visits. | 3 months | 
| Number of Participants With Testostestone Serum Levels Below 0.5 ng/mL for at Least 28 Days | The number of participants suppressed for at least 28 days was defined as the estimated survival probability at time=Day 28. | 28 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to Testosterone Castration (Testosterone ≤0.5 ng/mL). | Time to testosterone castration was calculated as the number of days from dosing to the first scheduled visit when testosterone was less than 0.5 ng/mL. The figures in the table present the number of participants who were castrated after 1, 3, 7, 14, 21, 28, and 42 days. | 1, 3, 7, 14, 21, 28, 42 days | 
| Number of Participants With Sufficient Testosterone Suppression for at Least 84 Days | Sufficient testosterone suppression was defined as not meeting an insufficient testosterone response criterion. Insufficient testosterone response was defined as testosterone >1.0 ng/mL at one visit or testosterone 0.5-1.0 at two consecutive visits. | 3 months | 
| Time to 50% Reduction in Prostate-specific Antigen Levels | The time to 50% prostate-specific antigen (PSA) reduction from baseline was defined as the median number of days from dosing to the first visit where a 50% reduction in PSA level was reached. | 3 months | 
| Time to 90% Reduction in Prostate-specific Antigen Levels | The time to 90% prostate-specific antigen (PSA) reduction from baseline was defined as the median number of days from dosing to the first visit where a 90% reduction in PSA level was reached. | 3 months | 
| Liver Function Tests | The number of participants who had abnormal (defined as above upper limit of normal range (ULN)) alanine aminotransferase (ALT) levels, aspartate aminotransferas levels, and bilirubin levels plus the number of participants who had ALT increases >3x ULN and ALT increases >3x ULN with concurrently increased bilirubin >1.5 ULN. | 3 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Prostate Cancer, Androgen ablation therapy