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The Efficacy and Safety of Degarelix One Month Dosing Regimens in Prostate Cancer

Sponsor
Ferring Pharmaceuticals (Industry)
Overall Status
Completed
CT.gov ID
NCT00295750
Collaborator
(none)
620
Enrollment
35
Locations
3
Arms
19.9
Duration (Months)
17.7
Patients Per Site
0.9
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The study was a three-arm, active-control, multi-centre, parallel group study.

Condition or Disease Intervention/Treatment Phase
Phase 3

Study Design

Study Type:
Interventional
Actual Enrollment :
620 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
An Open-label, Multi-Centre, Randomized, Parallel-group Study, Investigating the Efficacy and Safety of Degarelix One Month Dosing Regimens; 160 mg (40 mg/ml) and 80 mg (20mg/ml), in Comparison to LUPRON DEPOT® 7.5 mg in Patients With Prostate Cancer Requiring Androgen Ablation Therapy
Study Start Date :
Feb 1, 2006
Actual Primary Completion Date :
Oct 1, 2007
Actual Study Completion Date :
Oct 1, 2007

Arms and Interventions

Arm Intervention/Treatment
Experimental: degarelix 240/160 mg

Initial dose of 240 mg SC (by injection under the skin) on day 0. Maintenance dose of 160 mg SC (by injection under the skin) given every 28 days.

Drug: Degarelix
Initial dose of 240 mg SC (by injection under the skin) on day 0. Maintenance dose of 160 mg SC (by injection under the skin) given every 28 days for 364 days.
Other Names:
  • FE200486

    		•
    Experimental: degarelix 240/80 mg

    Initial dose of 240 mg SC (by injection under the skin) on day 0. Maintenance dose of 80 mg SC (by injection under the skin) given every 28 days.

    Drug: Degarelix
    Initial dose of 240 mg SC (by injection under the skin) on day 0. Maintenance dose of 80 mg SC (by injection under the skin) given every 28 days for 364 days.
    Other Names:
  • FE 200486

    		•
    Active Comparator: Leuprolide 7.5 mg

    Leuprolide (Lupron Depot) 7.5 mg IM (in the muscle) every 28 days starting at day 0.

    Drug: Leuprolide 7.5 mg
    Leuprolide (Lupron Depot) 7.5mg IM (in the muscle every 28 days starting at day 0.
    Other Names:
  • Lupron

    		•

    Outcome Measures

    Primary Outcome Measures

    1. Percentage of Patients With Testosterone <=0.5ng/mL From Day 28 Through Day 364 [12 months]

      Kaplan-Maier estimates of the cumulative probabilities of testosterone <=0.5 ng/mL from Day 28 to Day 364. The degarelix response rate estimation determined whether the lower bound of the 95% confidence interval for the cumulative probability of testosterone <=0.5 ng/mL from Day 28 to Day 364 was no lower than 90%.

    Secondary Outcome Measures

    1. Percentage of Patients With Testosterone Surge During the First Two Weeks of Treatment [2 weeks]

      A patient was defined as having a testosterone surge if the testosterone level exceeded baseline by >=15% on any two days during the first two weeks of treatment (i.e. two of Study Days 1, 3, 7 and 14).

    2. Percentage of Patients With Testosterone Level <=0.5 ng/mL at Day 3 [3 days]

      This outcome measure presents the testosterone levels 3 days after the initial dose of trial medication.

    3. Frequency and Size of Testosterone Changes at Day 255 and/or Day 259 Compared to the Testosterone Level at Day 252 [Day 252, Day 255, and Day 259]

      Testosterone increases on Day 255 and/or on Day 259 (highest value of Day 255 and Day 259 was used) were compared with Day 252 values. Patients were categorised with shifts of <=-0.25, >-0.25-0, >0-0.25, >0.25-0.5 and >0.5 ng/mL from mean testosterone levels on Day 252.

    4. Percentage Change in Prostate-specific Antigen From Baseline to Day 14 and Day 28 [Days 14 and 28]

      Percentage change from Baseline to Day 14 and Day 28 in prostate-specific antigen, which is a clinically important biological marker for treatment effect and prostate cancer progression.

    5. Participants Grouped by Time to Prostate-specific Antigen Failure [12 months]

      The time to prostate specific antigen failure was defined as the days from first dosing (scheduled dosing days) where an increase in serum prostate specific antigen of ≥50% from nadir and a least 5 ng/mL measured on two consecutive occasions at least two weeks apart was noted.

    6. Participants With Markedly Abnormal Change in Laboratory Variables (>=20 Percent of Patients) [Baseline to Day 364]

      Criteria for lab values changes from baseline to the end of the study considered markedly abnormal were set for each lab test. If 20% of patients reached that value, the results were reported.

    7. The Mean Value of QTc Interval as Measured by Electrocardiogram [12 months]

      The QTc interval results are calculated with Fridericia's correction. QTc intervals are a standard evaluation of an electrocardiogram and help measure the risk of developing ventricular arrhythmias.

    8. Participants With Markedly Abnormal Change in Vital Signs and Body Weight [12 months]

      Vital signs and body weight included incidence of markedly abnormal changes from baseline to the end of the study in blood pressure (systolic and diastolic), pulse, and body weight at the end of trial as compared to baseline. The table presents the number of patients in each group with normal baseline and markedly abnormal value post-baseline.

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    Male
    Accepts Healthy Volunteers:
    No
    Main Inclusion Criteria:

    • Patients, aged 18 years or over, with histologically proven prostate cancer of all stages in whom endocrine treatment is indicated.

    • Baseline testosterone >1.5 ng/mL.

    • Life expectancy of at least 12 months.

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Urology Centers of Alabama Homewood Alabama United States 35209
    2 Alaska Clinical Research Center, LLC Anchorage Alaska United States 99508
    3 Advanced Urology Medical Center Anaheim California United States 92801
    4 Pacific Clinical Center Beverly Hills California United States 90210
    5 Simi-San Faernando Valley Urology Associates Granada Hills California United States 91344
    6 South Orange County Medical Research Center Laguna Woods, California United States 92653
    7 Western Clinical Research Torrance California United States 90505
    8 Urology Associate PC Denver Colorado United States 80210
    9 University of Colorado Denver Colorado United States 80262
    10 South Florida Medical Research Aventura Florida United States 33180
    11 Florida Foundation for Healthcare Research Ocala Florida United States 34474
    12 Regional Urology Shreveport Louisiana United States 71106
    13 Lawrenceville Urology Lawrenceville New Jersey United States 08648
    14 Jay A. Motola, MD, FACS Carmel New York United States 10512
    15 Northeast Urology Research Concord North Carolina United States 28025
    16 The Urology Center Greensboro North Carolina United States 27401
    17 State College Urologic Association State College Pennsylvania United States 16801
    18 Univeristy Urological Research Institute Providence Rhode Island United States 02904
    19 University Urological Research Institute Providence Rhode Island United States 02904
    20 Grand Strand Urology Myrtle Beach South Carolina United States 29572
    21 Urology San Antonio Research San Antonio Texas United States 78229
    22 Urology of Virginia Research Norfolk Virginia United States 23502
    23 Office of Jeffrey Frankel Seattle Washington United States 98166
    24 Bruce W. Palmer Urology Inc, 125-70 Exhibition Street Kentville Nova Scotia Canada B4N 4KB
    25 Nemocnice Jindrichuv Hradec a.s., U Nemocnice 380/III Jindrichuv Hradec Czech Republic 37738
    26 Urologische Klinik, Universitatsklinikum Mannheim, Theodor-Kutzer-Ufer 1-3 Mannheim Germany 68167
    27 Szeged M.J.V.O. Korhaza, Urologiai Osztaly, Kalvaria sugarut 57 Szeged Hungary H-6725
    28 Hospital General "Dr Santiago Ramon y Cajal", ISSSTE Predio Canoas S/N Durango, DGO Mexico 34079
    29 Atrium MC, Henri Dunantstraat 5 Heerlen Netherlands 6419 PC
    30 Cristo Redentor Hospital La Hacienda Puerto Rico 00784
    31 San Juan VA Medical Center San Juan Puerto Rico 00921
    32 Provita Center, 2 Primaverii Street Constanta Romania 900635
    33 Andros Urology Clinic, Ulitsa Lenina 36A St Petersburg Russian Federation 197136
    34 Kiev City Clinical Hospital #3, Petr Ivaschenko 26, Petra Zaporogtsa str. Kiev Ukraine 2125
    35 Derriford Hospital, Derriford Road Plymouth United Kingdom PL6 8DH

    Sponsors and Collaborators

    • Ferring Pharmaceuticals

    Investigators

    • Study Director: Clinical Development Support, Ferring Pharmaceuticals

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    Ferring Pharmaceuticals
    ClinicalTrials.gov Identifier:
    NCT00295750
    Other Study ID Numbers:
    • FE200486 CS21
    First Posted:
    Feb 24, 2006
    Last Update Posted:
    Dec 19, 2012
    Last Verified:
    Dec 1, 2012
    Keywords provided by Ferring Pharmaceuticals
    Prostate Cancer
    Additional relevant MeSH terms:
    Prostatic Neoplasms
    Leuprolide

    Study Results

    Participant Flow

    Recruitment Details
    Pre-assignment Detail
    Arm/Group Title Degarelix 240/160 mg Degarelix 240/80 mg Leuprolide 7.5 mg
    Arm/Group Description Initial dose of 240 mg SC (by injection under the skin) on day 0. Maintenance dose of 160 mg SC (by injection under the skin) given every 28 days. Initial dose of 240 mg SC (by injection under the skin) on day 0. Maintenance dose of 80 mg SC (by injection under the skin) given every 28 days. Lupron Depot 7.5 mg IM (in the muscle) every 28 days starting at day 0.
    Period Title: Overall Study
    STARTED 206 210 204
    Intent-to-treat (ITT) Population 202 207 201
    COMPLETED 163 169 172
    NOT COMPLETED 43 41 32

    Baseline Characteristics

    Arm/Group Title Degarelix 240/160 mg Degarelix 240/80 mg Leuprolide 7.5 mg Total
    Arm/Group Description Initial dose of 240 mg SC (by injection under the skin) on day 0. Maintenance dose of 160 mg SC (by injection under the skin) given every 28 days. Initial dose of 240 mg SC (by injection under the skin) on day 0. Maintenance dose of 80 mg SC (by injection under the skin) given every 28 days. Lupron Depot 7.5 mg IM (in the muscle) every 28 days starting at day 0. Total of all reporting groups
    Overall Participants 202 207 201 610
    Age (Count of Participants)
    <=18 years
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Between 18 and 65 years
    37
    18.3%
    43
    20.8%
    38
    18.9%
    118
    19.3%
    >=65 years
    165
    81.7%
    164
    79.2%
    163
    81.1%
    492
    80.7%
    Age (years) [Median (Full Range) ]
    Median (Full Range) [years]
    72
    (8.47)
    72
    (8.12)
    74
    (8.77)
    73
    (8.45)
    Sex: Female, Male (Count of Participants)
    Female
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Male
    202
    100%
    207
    100%
    201
    100%
    610
    100%
    Race (NIH/OMB) (Count of Participants)
    American Indian or Alaska Native
    22
    10.9%
    18
    8.7%
    19
    9.5%
    59
    9.7%
    Asian
    1
    0.5%
    1
    0.5%
    0
    0%
    2
    0.3%
    Native Hawaiian or Other Pacific Islander
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Black or African American
    11
    5.4%
    17
    8.2%
    10
    5%
    38
    6.2%
    White
    168
    83.2%
    171
    82.6%
    172
    85.6%
    511
    83.8%
    More than one race
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Unknown or Not Reported
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Region of Enrollment (participants) [Number]
    North America
    84
    41.6%
    87
    42%
    86
    42.8%
    257
    42.1%
    Europe
    118
    58.4%
    120
    58%
    115
    57.2%
    353
    57.9%
    Curative Intent (participants) [Number]
    Yes
    24
    11.9%
    30
    14.5%
    24
    11.9%
    78
    12.8%
    No
    178
    88.1%
    177
    85.5%
    177
    88.1%
    532
    87.2%
    Gleason Score (participants) [Number]
    2-4
    21
    10.4%
    20
    9.7%
    24
    11.9%
    65
    10.7%
    5-6
    67
    33.2%
    68
    32.9%
    63
    31.3%
    198
    32.5%
    7
    56
    27.7%
    63
    30.4%
    62
    30.8%
    181
    29.7%
    8-10
    56
    27.7%
    56
    27.1%
    51
    25.4%
    163
    26.7%
    Stage of Prostate Cancer (participants) [Number]
    Localized
    59
    29.2%
    69
    33.3%
    63
    31.3%
    191
    31.3%
    Locally advanced
    62
    30.7%
    64
    30.9%
    52
    25.9%
    178
    29.2%
    Metastatic
    41
    20.3%
    37
    17.9%
    47
    23.4%
    125
    20.5%
    Not classifiable
    40
    19.8%
    37
    17.9%
    39
    19.4%
    116
    19%
    Body Mass Index (kilogram per square meter) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [kilogram per square meter]
    26.6
    (3.70)
    26.7
    (4.21)
    26.9
    (3.86)
    26.8
    (3.93)
    Serum Prostate-specific Antigen Levels (nanogram per milliliter) [Median (Inter-Quartile Range) ]
    Median (Inter-Quartile Range) [nanogram per milliliter]
    19.9
    19.8
    19.0
    19.0
    Serum Testosterone Levels (nanogram per milliliter) [Median (Inter-Quartile Range) ]
    Median (Inter-Quartile Range) [nanogram per milliliter]
    3.78
    4.11
    3.84
    3.93
    Time Since Prostate Cancer Diagnosis (days) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [days]
    485
    (1109)
    491
    (994)
    497
    (1088)
    491
    (1063)
    Weight (kilogram) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [kilogram]
    78.7
    (13.0)
    79.8
    (14.9)
    79.4
    (12.2)
    79.3
    (13.4)

    Outcome Measures

    1. Primary Outcome
    Title Percentage of Patients With Testosterone <=0.5ng/mL From Day 28 Through Day 364
    Description Kaplan-Maier estimates of the cumulative probabilities of testosterone <=0.5 ng/mL from Day 28 to Day 364. The degarelix response rate estimation determined whether the lower bound of the 95% confidence interval for the cumulative probability of testosterone <=0.5 ng/mL from Day 28 to Day 364 was no lower than 90%.
    Time Frame 12 months

    Outcome Measure Data

    Analysis Population Description
    Intent-to-treat (ITT) population.
    Arm/Group Title Degarelix 240/160 mg Degarelix 240/80 mg Leuprolide 7.5 mg
    Arm/Group Description Initial dose of 240 mg SC (by injection under the skin) on day 0. Maintenance dose of 160 mg SC (by injection under the skin) given every 28 days. Initial dose of 240 mg SC (by injection under the skin) on day 0. Maintenance dose of 80 mg SC (by injection under the skin) given every 28 days. Lupron Depot 7.5 mg IM (in the muscle) every 28 days starting at day 0.
    Measure Participants 202 207 201
    Mean (95% Confidence Interval) [percentage of patients]
    98.3
    97.2
    96.4
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Degarelix 240/160 mg, Leuprolide 7.5 mg
    Comments A non-inferiority assessment determined whether degarelix was non-inferior to leuprolide with respect to the cumulative probability of testosterone <=0.5 ng/mL from Day 28 to Day 364.
    Type of Statistical Test Non-Inferiority or Equivalence
    Comments The non-inferiority limit was -10 percentage points.
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Difference in cumulative probability
    Estimated Value 1.9
    Confidence Interval () 97.5%
    -1.8 to 5.7
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Degarelix 240/80 mg, Leuprolide 7.5 mg
    Comments A non-inferiority assessment determined whether degarelix was non-inferior to leuprolide with respect to the cumulative probability of testosterone <=0.5 ng/mL from Day 28 to Day 364.
    Type of Statistical Test Non-Inferiority or Equivalence
    Comments The non-inferiority limit was -10 percentage points.
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Difference in cumulative probability
    Estimated Value 0.9
    Confidence Interval () 97.5%
    -3.2 to 5.0
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    2. Secondary Outcome
    Title Percentage of Patients With Testosterone Surge During the First Two Weeks of Treatment
    Description A patient was defined as having a testosterone surge if the testosterone level exceeded baseline by >=15% on any two days during the first two weeks of treatment (i.e. two of Study Days 1, 3, 7 and 14).
    Time Frame 2 weeks

    Outcome Measure Data

    Analysis Population Description
    ITT population. If one or more of the testosterone values on Days 1, 3, 7 or 14 was missing, the last observation was carried forward.
    Arm/Group Title Degarelix 240/160 mg Degarelix 240/80 mg Leuprolide 7.5 mg
    Arm/Group Description Initial dose of 240 mg SC (by injection under the skin) on day 0. Maintenance dose of 160 mg SC (by injection under the skin) given every 28 days. Initial dose of 240 mg SC (by injection under the skin) on day 0. Maintenance dose of 80 mg SC (by injection under the skin) given every 28 days. Lupron Depot 7.5 mg IM (in the muscle) every 28 days starting at day 0.
    Measure Participants 202 207 201
    Mean (95% Confidence Interval) [percentage of patients]
    0.5
    0.0
    80.1
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Degarelix 240/160 mg, Leuprolide 7.5 mg
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <0.0001
    Comments
    Method Fisher Exact
    Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Degarelix 240/80 mg, Leuprolide 7.5 mg
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <0.0001
    Comments
    Method Fisher Exact
    Comments
    3. Secondary Outcome
    Title Percentage of Patients With Testosterone Level <=0.5 ng/mL at Day 3
    Description This outcome measure presents the testosterone levels 3 days after the initial dose of trial medication.
    Time Frame 3 days

    Outcome Measure Data

    Analysis Population Description
    ITT population.
    Arm/Group Title Degarelix 240/160 mg Degarelix 240/80 mg Leuprolide 7.5 mg
    Arm/Group Description Initial dose of 240 mg SC (by injection under the skin) on day 0. Maintenance dose of 160 mg SC (by injection under the skin) given every 28 days. Initial dose of 240 mg SC (by injection under the skin) on day 0. Maintenance dose of 80 mg SC (by injection under the skin) given every 28 days. Lupron Depot 7.5 mg IM (in the muscle) every 28 days starting at day 0.
    Measure Participants 202 207 201
    Mean (95% Confidence Interval) [percentage of patients]
    95.5
    96.1
    0
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Degarelix 240/160 mg, Leuprolide 7.5 mg
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <0.0001
    Comments
    Method Fisher Exact
    Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Degarelix 240/80 mg, Leuprolide 7.5 mg
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <0.0001
    Comments
    Method Fisher Exact
    Comments
    4. Secondary Outcome
    Title Frequency and Size of Testosterone Changes at Day 255 and/or Day 259 Compared to the Testosterone Level at Day 252
    Description Testosterone increases on Day 255 and/or on Day 259 (highest value of Day 255 and Day 259 was used) were compared with Day 252 values. Patients were categorised with shifts of <=-0.25, >-0.25-0, >0-0.25, >0.25-0.5 and >0.5 ng/mL from mean testosterone levels on Day 252.
    Time Frame Day 252, Day 255, and Day 259

    Outcome Measure Data

    Analysis Population Description
    ITT population who had blood samples drawn on Day 252, Day 255, and Day 259.
    Arm/Group Title Degarelix 240/160 mg Degarelix 240/80 mg Leuprolide 7.5 mg
    Arm/Group Description Initial dose of 240 mg SC (by injection under the skin) on day 0. Maintenance dose of 160 mg SC (by injection under the skin) given every 28 days. Initial dose of 240 mg SC (by injection under the skin) on day 0. Maintenance dose of 80 mg SC (by injection under the skin) given every 28 days. Lupron Depot 7.5 mg IM (in the muscle) every 28 days starting at day 0.
    Measure Participants 176 178 179
    <=-0.25 ng/mL
    1
    0.5%
    3
    1.4%
    0
    0%
    >-0.25-0 ng/mL
    84
    41.6%
    85
    41.1%
    49
    24.4%
    >0-0.25 ng/mL
    91
    45%
    90
    43.5%
    122
    60.7%
    >0.25-0.5 ng/mL
    0
    0%
    0
    0%
    5
    2.5%
    >0.5 ng/mL
    0
    0%
    0
    0%
    3
    1.5%
    5. Secondary Outcome
    Title Percentage Change in Prostate-specific Antigen From Baseline to Day 14 and Day 28
    Description Percentage change from Baseline to Day 14 and Day 28 in prostate-specific antigen, which is a clinically important biological marker for treatment effect and prostate cancer progression.
    Time Frame Days 14 and 28

    Outcome Measure Data

    Analysis Population Description
    ITT population.
    Arm/Group Title Degarelix 240/160 mg Degarelix 240/80 mg Leuprolide 7.5 mg
    Arm/Group Description Initial dose of 240 mg SC (by injection under the skin) on day 0. Maintenance dose of 160 mg SC (by injection under the skin) given every 28 days. Initial dose of 240 mg SC (by injection under the skin) on day 0. Maintenance dose of 80 mg SC (by injection under the skin) given every 28 days. Lupron Depot 7.5 mg IM (in the muscle) every 28 days starting at day 0.
    Measure Participants 202 207 201
    Day 14
    -64.6
    -63.4
    -17.9
    Day 28
    -82.3
    -84.9
    -66.7
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Degarelix 240/160 mg, Leuprolide 7.5 mg
    Comments Percentage change from baseline to Day 14
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <0.0001
    Comments
    Method Wilcoxon (Mann-Whitney)
    Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Degarelix 240/80 mg, Leuprolide 7.5 mg
    Comments Percentage change from baseline to Day 14
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <0.0001
    Comments
    Method Wilcoxon (Mann-Whitney)
    Comments
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection Degarelix 240/160 mg, Leuprolide 7.5 mg
    Comments Percentage change from baseline to Day 28
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <0.0001
    Comments
    Method Wilcoxon (Mann-Whitney)
    Comments
    Statistical Analysis 4
    Statistical Analysis Overview Comparison Group Selection Degarelix 240/80 mg, Leuprolide 7.5 mg
    Comments Percentage change from baseline to Day 28
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <0.0001
    Comments
    Method Wilcoxon (Mann-Whitney)
    Comments
    6. Secondary Outcome
    Title Participants Grouped by Time to Prostate-specific Antigen Failure
    Description The time to prostate specific antigen failure was defined as the days from first dosing (scheduled dosing days) where an increase in serum prostate specific antigen of ≥50% from nadir and a least 5 ng/mL measured on two consecutive occasions at least two weeks apart was noted.
    Time Frame 12 months

    Outcome Measure Data

    Analysis Population Description
    ITT population. Missing values were not imputed for this endpoint. Number in table represents the number of patients with prostate-specific antigen failure.
    Arm/Group Title Degarelix 240/160 mg Degarelix 240/80 mg Leuprolide 7.5 mg
    Arm/Group Description Initial dose of 240 mg SC (by injection under the skin) on day 0. Maintenance dose of 160 mg SC (by injection under the skin) given every 28 days. Initial dose of 240 mg SC (by injection under the skin) on day 0. Maintenance dose of 80 mg SC (by injection under the skin) given every 28 days. Lupron Depot 7.5 mg IM (in the muscle) every 28 days starting at day 0.
    Measure Participants 202 207 201
    Day 0-28 (patients at risk=193, 201, 194)
    1
    0.5%
    0
    0%
    1
    0.5%
    Day 0-56 (patients at risk=192, 197, 192)
    1
    0.5%
    0
    0%
    1
    0.5%
    Day 0-84 (patients at risk=190, 193, 190)
    1
    0.5%
    0
    0%
    1
    0.5%
    Day 0-112 (patients at risk=190, 189, 188)
    1
    0.5%
    1
    0.5%
    3
    1.5%
    Day 0-140 (patients at risk=187, 187, 182)
    2
    1%
    2
    1%
    7
    3.5%
    Day 0-168 (patients at risk=179, 185, 180)
    7
    3.5%
    4
    1.9%
    9
    4.5%
    Day 0-196 (patients at risk=173, 181, 175)
    11
    5.4%
    4
    1.9%
    11
    5.5%
    Day 0-224 (patients at risk=168, 175, 173)
    14
    6.9%
    7
    3.4%
    12
    6%
    Day 0-252 (patients at risk=165, 169, 168)
    16
    7.9%
    9
    4.3%
    14
    7%
    Day 0-280 (patients at risk=157, 165, 163)
    20
    9.9%
    11
    5.3%
    18
    9%
    Day 0-308 (patients at risk=153, 161, 156)
    23
    11.4%
    12
    5.8%
    21
    10.4%
    Day 0-336 (patients at risk=149, 156, 150)
    26
    12.9%
    15
    7.2%
    24
    11.9%
    Day 0-364 (patients at risk=149, 155, 148)
    26
    12.9%
    16
    7.7%
    26
    12.9%
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Degarelix 240/160 mg
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Cumulative probability
    Estimated Value 85.8
    Confidence Interval () 95%
    79.8 to 90.1
    Parameter Dispersion Type:
    Value:
    Estimation Comments 95% confidence interval for the cumulative probability of completing the study without prostate specific antigen failure from Day 0 to Day 364.
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Degarelix 240/80 mg
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Cumulative probability
    Estimated Value 91.1
    Confidence Interval () 95%
    85.9 to 94.5
    Parameter Dispersion Type:
    Value:
    Estimation Comments 95% confidence interval for the cumulative probability of completing the study without prostate specific antigen failure from Day 0 to Day 364.
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection Leuprolide 7.5 mg
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Cumulative probability
    Estimated Value 85.9
    Confidence Interval () 95%
    79.9 to 90.2
    Parameter Dispersion Type:
    Value:
    Estimation Comments 95% confidence interval for the cumulative probability of completing the study without prostate specific antigen failure from Day 0 to Day 364.
    7. Secondary Outcome
    Title Participants With Markedly Abnormal Change in Laboratory Variables (>=20 Percent of Patients)
    Description Criteria for lab values changes from baseline to the end of the study considered markedly abnormal were set for each lab test. If 20% of patients reached that value, the results were reported.
    Time Frame Baseline to Day 364

    Outcome Measure Data

    Analysis Population Description
    ITT population
    Arm/Group Title Degarelix 240/160 mg Degarelix 240/80 mg Leuprolide 7.5 mg
    Arm/Group Description Initial dose of 240 mg SC (by injection under the skin) on day 0. Maintenance dose of 160 mg SC (by injection under the skin) given every 28 days. Initial dose of 240 mg SC (by injection under the skin) on day 0. Maintenance dose of 80 mg SC (by injection under the skin) given every 28 days. Lupron Depot 7.5 mg IM (in the muscle) every 28 days starting at day 0.
    Measure Participants 202 207 201
    Haematocrit (<=0.37 ratio)
    73
    36.1%
    80
    38.6%
    73
    36.3%
    Haemoglobin (<=115 g/L)
    32
    15.8%
    45
    21.7%
    38
    18.9%
    Serum Urea Nitrogen (>=10.7 mmol/L)
    48
    23.8%
    41
    19.8%
    50
    24.9%
    Urine Protein (>=2 units from baseline)
    65
    32.2%
    64
    30.9%
    63
    31.3%
    Urine Bacteria (0 at baseline and >0 on treatment)
    96
    47.5%
    105
    50.7%
    107
    53.2%
    8. Secondary Outcome
    Title The Mean Value of QTc Interval as Measured by Electrocardiogram
    Description The QTc interval results are calculated with Fridericia's correction. QTc intervals are a standard evaluation of an electrocardiogram and help measure the risk of developing ventricular arrhythmias.
    Time Frame 12 months

    Outcome Measure Data

    Analysis Population Description
    ITT population. End of Study values obtained at day 364 (+-7 days) for patients who completed. Patients who withdrew early had variable timeframes for the end of study value.
    Arm/Group Title Degarelix 240/160 mg Degarelix 240/80 mg Leuprolide 7.5 mg
    Arm/Group Description Initial dose of 240 mg SC (by injection under the skin) on day 0. Maintenance dose of 160 mg SC (by injection under the skin) given every 28 days. Initial dose of 240 mg SC (by injection under the skin) on day 0. Maintenance dose of 80 mg SC (by injection under the skin) given every 28 days. Lupron Depot 7.5 mg IM (in the muscle) every 28 days starting at day 0.
    Measure Participants 202 207 201
    Baseline Day 0 (n=202, 207, 201)
    403
    (20.2)
    407
    (21.6)
    404
    (19.4)
    Day 3 (n=195, 204, 197)
    404
    (22.1)
    411
    (23.5)
    405
    (23.0)
    End of study 12 months (n=202, 207, 201)
    415
    (21.7)
    420
    (22.3)
    419
    (23.3)
    9. Secondary Outcome
    Title Participants With Markedly Abnormal Change in Vital Signs and Body Weight
    Description Vital signs and body weight included incidence of markedly abnormal changes from baseline to the end of the study in blood pressure (systolic and diastolic), pulse, and body weight at the end of trial as compared to baseline. The table presents the number of patients in each group with normal baseline and markedly abnormal value post-baseline.
    Time Frame 12 months

    Outcome Measure Data

    Analysis Population Description
    ITT population. The first value in the category represents the actual clinical reading and the second is the change from baseline for blood pressure (units: millimeters of mercury) and heart rate (units:beats per minute). The weight category includes patients whose percent weight change from baseline fit the stated ranges.
    Arm/Group Title Degarelix 240/160 mg Degarelix 240/80 mg Leuprolide 7.5 mg
    Arm/Group Description Initial dose of 240 mg SC (by injection under the skin) on day 0. Maintenance dose of 160 mg SC (by injection under the skin) given every 28 days. Initial dose of 240 mg SC (by injection under the skin) on day 0. Maintenance dose of 80 mg SC (by injection under the skin) given every 28 days. Lupron Depot 7.5 mg IM (in the muscle) every 28 days starting at day 0.
    Measure Participants 202 207 201
    Systolic blood pressure <=90 and decrease >=20
    12
    5.9%
    8
    3.9%
    6
    3%
    Systolic blood pressure >=180 and increase >=20
    20
    9.9%
    16
    7.7%
    23
    11.4%
    Diastolic blood pressure <=50 and decrease >=15
    12
    5.9%
    10
    4.8%
    9
    4.5%
    Diastolic blood pressure >=105 and increase >=15
    5
    2.5%
    13
    6.3%
    8
    4%
    Heart rate <=50 and decrease >=15
    8
    4%
    7
    3.4%
    9
    4.5%
    Heart rate >=120 and increase >=15
    1
    0.5%
    0
    0%
    1
    0.5%
    Body weight decrease of >=7 percent
    5
    2.5%
    6
    2.9%
    10
    5%
    Body weight increase of >=7 percent
    24
    11.9%
    15
    7.2%
    23
    11.4%

    Adverse Events

    Time Frame
    Adverse Event Reporting Description
    Arm/Group Title Degarelix 240/160 mg Degarelix 240/80 mg Leuprolide 7.5 mg
    Arm/Group Description Initial dose of 240 mg SC (by injection under the skin) on day 0. Maintenance dose of 160 mg SC (by injection under the skin) given every 28 days. Initial dose of 240 mg SC (by injection under the skin) on day 0. Maintenance dose of 80 mg SC (by injection under the skin) given every 28 days. Lupron Depot 7.5 mg IM (in the muscle) every 28 days starting at day 0.
    All Cause Mortality
    Degarelix 240/160 mg Degarelix 240/80 mg Leuprolide 7.5 mg
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total / (NaN) / (NaN) / (NaN)
    Serious Adverse Events
    Degarelix 240/160 mg Degarelix 240/80 mg Leuprolide 7.5 mg
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 24/ (NaN) 21/ (NaN) 28/ (NaN)
    Blood and lymphatic system disorders
    Anaemia 2/202 (1%) 2 0/207 (0%) 0 3/201 (1.5%) 3
    Iron deficiency anaemia 1/202 (0.5%) 1 0/207 (0%) 0 0/201 (0%) 0
    Cardiac disorders
    Cardiac arrest 0/202 (0%) 0 2/207 (1%) 2 0/201 (0%) 0
    Acute coronary syndrome 1/202 (0.5%) 1 0/207 (0%) 0 1/201 (0.5%) 1
    Acute myocardial infarction 1/202 (0.5%) 1 0/207 (0%) 0 1/201 (0.5%) 1
    Angina unstable 1/202 (0.5%) 1 0/207 (0%) 0 1/201 (0.5%) 1
    Bradycardia 1/202 (0.5%) 1 0/207 (0%) 0 0/201 (0%) 0
    Cardiac failure 1/202 (0.5%) 1 0/207 (0%) 0 1/201 (0.5%) 1
    Cardiopulmonary failure 1/202 (0.5%) 1 0/207 (0%) 0 1/201 (0.5%) 1
    Coronary artery disease 0/202 (0%) 0 1/207 (0.5%) 1 1/201 (0.5%) 1
    Myocardial infarction 0/202 (0%) 0 1/207 (0.5%) 1 2/201 (1%) 2
    Cardiac disorder 0/202 (0%) 0 0/207 (0%) 0 1/201 (0.5%) 1
    Cardiac failure congestive 0/202 (0%) 0 0/207 (0%) 0 1/201 (0.5%) 1
    Cardiovascular disorder 0/202 (0%) 0 0/207 (0%) 0 1/201 (0.5%) 1
    Myocardial ischaemia 0/202 (0%) 0 0/207 (0%) 0 1/201 (0.5%) 1
    Myopericarditis 0/202 (0%) 0 0/207 (0%) 0 1/201 (0.5%) 1
    Eye disorders
    Cataract 0/202 (0%) 0 0/207 (0%) 0 1/201 (0.5%) 1
    Gastrointestinal disorders
    Inguinal hernia 1/202 (0.5%) 1 1/207 (0.5%) 1 0/201 (0%) 0
    Gastric haemorrhage 0/202 (0%) 0 1/207 (0.5%) 1 0/201 (0%) 0
    Gastric ulcer haemorrhage 1/202 (0.5%) 1 0/207 (0%) 0 0/201 (0%) 0
    Gastritis 0/202 (0%) 0 1/207 (0.5%) 1 0/201 (0%) 0
    Inguinal hernia, obstructive 0/202 (0%) 0 1/207 (0.5%) 1 0/201 (0%) 0
    Duodenal ulcer haemorrhage 0/202 (0%) 0 0/207 (0%) 0 1/201 (0.5%) 1
    Gastrointestinal haemorrhage 0/202 (0%) 0 0/207 (0%) 0 1/201 (0.5%) 1
    Large intestinal obstruction 0/202 (0%) 0 0/207 (0%) 0 1/201 (0.5%) 1
    Pancreatitis acute 0/202 (0%) 0 0/207 (0%) 0 1/201 (0.5%) 1
    Peritonitis 0/202 (0%) 0 0/207 (0%) 0 1/201 (0.5%) 1
    General disorders
    Non-cardiac chest pain 1/202 (0.5%) 1 0/207 (0%) 0 0/201 (0%) 0
    Pyrexia 0/202 (0%) 0 0/207 (0%) 0 1/201 (0.5%) 1
    Hepatobiliary disorders
    Cholecystitis acute 0/202 (0%) 0 1/207 (0.5%) 1 0/201 (0%) 0
    Hepatic failure 0/202 (0%) 0 0/207 (0%) 0 1/201 (0.5%) 1
    Hepatomegaly 0/202 (0%) 0 0/207 (0%) 0 1/201 (0.5%) 1
    Infections and infestations
    Bronchopneumonia 1/202 (0.5%) 1 1/207 (0.5%) 1 0/201 (0%) 0
    Ear infection 0/202 (0%) 0 1/207 (0.5%) 1 0/201 (0%) 0
    Gastroenteritis 0/202 (0%) 0 1/207 (0.5%) 1 0/201 (0%) 0
    Lobar pneumonia 1/202 (0.5%) 1 0/207 (0%) 0 0/201 (0%) 0
    Pneumonia 1/202 (0.5%) 1 0/207 (0%) 0 1/201 (0.5%) 1
    Post procedural cellulitis 1/202 (0.5%) 1 0/207 (0%) 0 0/201 (0%) 0
    Injury, poisoning and procedural complications
    Compression fracture 0/202 (0%) 0 1/207 (0.5%) 1 0/201 (0%) 0
    Overdose 1/202 (0.5%) 1 0/207 (0%) 0 0/201 (0%) 0
    Femoral neck fracture 0/202 (0%) 0 0/207 (0%) 0 1/201 (0.5%) 1
    Hip fracture 0/202 (0%) 0 0/207 (0%) 0 1/201 (0.5%) 1
    Spinal compression fracture 0/202 (0%) 0 0/207 (0%) 0 1/201 (0.5%) 1
    Investigations
    Prostate examination abnormal 1/202 (0.5%) 1 0/207 (0%) 0 1/201 (0.5%) 1
    Blood creatinine increased 0/202 (0%) 0 0/207 (0%) 0 1/201 (0.5%) 1
    Electrocardiogram (ECG) signs of myocardial ischaemia 0/202 (0%) 0 0/207 (0%) 0 1/201 (0.5%) 1
    Metabolism and nutrition disorders
    Dehydration 0/202 (0%) 0 1/207 (0.5%) 1 0/201 (0%) 0
    Diabetes mellitus 1/202 (0.5%) 1 0/207 (0%) 0 1/201 (0.5%) 1
    Musculoskeletal and connective tissue disorders
    Pathological fracture 0/202 (0%) 0 1/207 (0.5%) 1 0/201 (0%) 0
    Spinal column stenosis 0/202 (0%) 0 0/207 (0%) 0 1/201 (0.5%) 1
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Prostate cancer 1/202 (0.5%) 1 1/207 (0.5%) 1 1/201 (0.5%) 1
    Malignant lymphoma unclassifiable 1/202 (0.5%) 1 0/207 (0%) 0 0/201 (0%) 0
    Malignant melanoma 1/202 (0.5%) 1 0/207 (0%) 0 0/201 (0%) 0
    Metastases to bone 0/202 (0%) 0 1/207 (0.5%) 1 0/201 (0%) 0
    Prostate cancer metastatic 1/202 (0.5%) 1 0/207 (0%) 0 0/201 (0%) 0
    Squamous cell carcinoma 1/202 (0.5%) 1 0/207 (0%) 0 0/201 (0%) 0
    Gallbladder cancer 0/202 (0%) 0 0/207 (0%) 0 1/201 (0.5%) 1
    Linitis plastica 0/202 (0%) 0 0/207 (0%) 0 1/201 (0.5%) 1
    Metastases to liver 0/202 (0%) 0 0/207 (0%) 0 1/201 (0.5%) 1
    Metastases to lung 0/202 (0%) 0 0/207 (0%) 0 1/201 (0.5%) 1
    Pleural mesothelioma malignant 0/202 (0%) 0 0/207 (0%) 0 1/201 (0.5%) 1
    Nervous system disorders
    Cerebral infarction 1/202 (0.5%) 1 0/207 (0%) 0 0/201 (0%) 0
    Cerebrovascular accident 1/202 (0.5%) 1 0/207 (0%) 0 0/201 (0%) 0
    Cerebrovascular insufficiency 0/202 (0%) 0 1/207 (0.5%) 1 0/201 (0%) 0
    Hyperkinesia 1/202 (0.5%) 1 0/207 (0%) 0 0/201 (0%) 0
    Syncope 1/202 (0.5%) 1 0/207 (0%) 0 0/201 (0%) 0
    Ruptured cerebral aneurysm 0/202 (0%) 0 0/207 (0%) 0 1/201 (0.5%) 1
    Renal and urinary disorders
    Haematuria 2/202 (1%) 2 1/207 (0.5%) 1 0/201 (0%) 0
    Calculus bladder 1/202 (0.5%) 1 1/207 (0.5%) 1 0/201 (0%) 0
    Calculus ureteric 0/202 (0%) 0 2/207 (1%) 2 1/201 (0.5%) 1
    Urinary retention 2/202 (1%) 2 0/207 (0%) 0 2/201 (1%) 2
    Bladder obstruction 1/202 (0.5%) 1 0/207 (0%) 0 0/201 (0%) 0
    Hydronephrosis 1/202 (0.5%) 2 0/207 (0%) 0 1/201 (0.5%) 1
    Renal failure acute 1/202 (0.5%) 1 0/207 (0%) 0 1/201 (0.5%) 1
    Renal failure chronic 1/202 (0.5%) 2 0/207 (0%) 0 0/201 (0%) 0
    Urethral obstruction 0/202 (0%) 0 1/207 (0.5%) 1 0/201 (0%) 0
    Renal failure 0/202 (0%) 0 0/207 (0%) 0 1/201 (0.5%) 1
    Urethral stenosis 0/202 (0%) 0 0/207 (0%) 0 1/201 (0.5%) 1
    Respiratory, thoracic and mediastinal disorders
    Chronic obstructive pulmonary disease 1/202 (0.5%) 1 0/207 (0%) 0 0/201 (0%) 0
    Respiratory failure 0/202 (0%) 0 1/207 (0.5%) 1 0/201 (0%) 0
    Asthma 0/202 (0%) 0 0/207 (0%) 0 1/201 (0.5%) 1
    Orthopnoea 0/202 (0%) 0 0/207 (0%) 0 1/201 (0.5%) 1
    Vascular disorders
    Hypertension 0/202 (0%) 0 1/207 (0.5%) 1 0/201 (0%) 0
    Hypotension 0/202 (0%) 0 1/207 (0.5%) 1 0/201 (0%) 0
    Orthostatic hypotension 1/202 (0.5%) 1 0/207 (0%) 0 1/201 (0.5%) 1
    Deep vein thrombosis 0/202 (0%) 0 0/207 (0%) 0 2/201 (1%) 3
    Other (Not Including Serious) Adverse Events
    Degarelix 240/160 mg Degarelix 240/80 mg Leuprolide 7.5 mg
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 165/ (NaN) 162/ (NaN) 153/ (NaN)
    Gastrointestinal disorders
    Nausea 11/202 (5.4%) 15 9/207 (4.3%) 10 8/201 (4%) 9
    Constipation 6/202 (3%) 6 11/207 (5.3%) 12 10/201 (5%) 11
    General disorders
    Injection site pain 61/202 (30.2%) 108 58/207 (28%) 114 1/201 (0.5%) 1
    Injection site erythema 48/202 (23.8%) 63 36/207 (17.4%) 56 0/201 (0%) 0
    Injection site swelling 14/202 (6.9%) 23 13/207 (6.3%) 17 0/201 (0%) 0
    Fatigue 13/202 (6.4%) 14 7/207 (3.4%) 11 13/201 (6.5%) 14
    Injection site induration 11/202 (5.4%) 14 8/207 (3.9%) 11 0/201 (0%) 0
    Injection site nodule 13/202 (6.4%) 24 6/207 (2.9%) 8 0/201 (0%) 0
    Chills 7/202 (3.5%) 9 11/207 (5.3%) 19 0/201 (0%) 0
    Infections and infestations
    Urinary tract infection 3/202 (1.5%) 3 10/207 (4.8%) 14 18/201 (9%) 25
    Investigations
    Weight increased 22/202 (10.9%) 22 18/207 (8.7%) 18 24/201 (11.9%) 24
    Alanine aminotransferase increased 17/202 (8.4%) 17 20/207 (9.7%) 22 11/201 (5.5%) 11
    Aspartate aminostransferase increased 10/202 (5%) 11 11/207 (5.3%) 12 6/201 (3%) 6
    Metabolism and nutrition disorders
    Hypercholesterolaemia 12/202 (5.9%) 12 7/207 (3.4%) 7 5/201 (2.5%) 5
    Musculoskeletal and connective tissue disorders
    Back pain 12/202 (5.9%) 13 12/207 (5.8%) 12 17/201 (8.5%) 19
    Arthralgia 6/202 (3%) 6 11/207 (5.3%) 12 18/201 (9%) 20
    Vascular disorders
    Hot flush 53/202 (26.2%) 59 53/207 (25.6%) 71 43/201 (21.4%) 50
    Hypertension 14/202 (6.9%) 16 11/207 (5.3%) 12 8/201 (4%) 8

    Limitations/Caveats

    [Not Specified]

    More Information

    Certain Agreements

    Principal Investigators are NOT employed by the organization sponsoring the study.

    The only disclosure restriction on the PI is that the sponsor can review the draft manuscript prior to publication and can request delay of publication where any contents are deemed patentable by the sponsor or confidential to the sponsor. Comments will be given within four weeks from receipt of the draft manuscript.

    Results Point of Contact

    Name/Title Ferring Pharmaceuticals
    Organization Clinical Development Support
    Phone
    Email DK0-Disclosure@ferring.com
    Responsible Party:
    Ferring Pharmaceuticals
    ClinicalTrials.gov Identifier:
    NCT00295750
    Other Study ID Numbers:
    • FE200486 CS21
    First Posted:
    Feb 24, 2006
    Last Update Posted:
    Dec 19, 2012
    Last Verified:
    Dec 1, 2012