Prostate Cancer
Conditions
Keywords
Prostate Cancer, Androgen ablation therapy
Brief summary
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.
Interventions
DRUGDegarelix
One dose (2 x 2 mL) of degarelix 40 mg (10 mg/mL), subcutaneous injection.
Sponsors
Ferring Pharmaceuticals
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
MALE
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Time to Meet Insufficient Testosterone Response | 3 months | 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. |
| Number of Participants With Testostestone Serum Levels Below 0.5 ng/mL for at Least 28 Days | 28 days | The number of participants suppressed for at least 28 days was defined as the estimated survival probability at time=Day 28. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Time to 50% Reduction in Prostate-specific Antigen Levels | 3 months | 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. |
| Time to Testosterone Castration (Testosterone ≤0.5 ng/mL). | 1, 3, 7, 14, 21, 28, 42 days | 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. |
| Liver Function Tests | 3 months | 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. |
| Time to 90% Reduction in Prostate-specific Antigen Levels | 3 months | 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. |
| Number of Participants With Sufficient Testosterone Suppression for at Least 84 Days | 3 months | 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. |
Countries
United States
Participant flow
Recruitment details
The patients were followed until they met a pre-defined criterion for insufficient testosterone or prostate-specific antigen (PSA).
Participants by arm
| Arm | Count |
|---|---|
| Degarelix 40 mg Degarelix 40 mg (10 mg/mL) | 10 |
| Degarelix 80 mg Degarelix 80 mg (20 mg/mL) | 24 |
| Degarelix 120 mg Degarelix 120 mg (30 mg/mL) | 24 |
| Degarelix 160 mg Degarelix 160 mg (40 mg/mL) | 24 |
| Total | 82 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Overall Study | Hepatic abnormalities | 0 | 1 | 0 | 1 |
| Overall Study | Prostate-specific antigen increase >=25% | 0 | 1 | 1 | 2 |
| Overall Study | PSA increase >=10ng/mL | 0 | 1 | 1 | 0 |
| Overall Study | PSA reduction <=50% | 0 | 2 | 2 | 4 |
| Overall Study | Testosterone 0.5 - 1.0 ng/mL | 0 | 1 | 3 | 2 |
| Overall Study | Testosterone >1.0 ng/mL | 10 | 18 | 17 | 15 |
Baseline characteristics
| Characteristic | Total | Degarelix 40 mg | Degarelix 160 mg | Degarelix 120 mg | Degarelix 80 mg |
|---|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 74 Participants | 9 Participants | 20 Participants | 22 Participants | 23 Participants |
| Age, Categorical Between 18 and 65 years | 8 Participants | 1 Participants | 4 Participants | 2 Participants | 1 Participants |
| Age Continuous | 75.6 years STANDARD_DEVIATION 6.9 | 72.0 years STANDARD_DEVIATION 5.7 | 74.7 years STANDARD_DEVIATION 8.4 | 75.9 years STANDARD_DEVIATION 5.8 | 77.5 years STANDARD_DEVIATION 6.4 |
| Body mass index | 26.70 kilogram per square meter STANDARD_DEVIATION 5.72 | 26.70 kilogram per square meter STANDARD_DEVIATION 5.72 | 26.64 kilogram per square meter STANDARD_DEVIATION 3.38 | 27.22 kilogram per square meter STANDARD_DEVIATION 3.16 | 26.61 kilogram per square meter STANDARD_DEVIATION 3.55 |
| Gleason score 2-4 | 3 participants | 1 participants | 0 participants | 1 participants | 1 participants |
| Gleason score 5-6 | 42 participants | 3 participants | 13 participants | 12 participants | 14 participants |
| Gleason score 7-10 | 36 participants | 6 participants | 11 participants | 11 participants | 8 participants |
| Gleason score Unknown | 1 participants | 0 participants | 0 participants | 0 participants | 1 participants |
| Race/Ethnicity, Customized Black | 6 participants | 2 participants | 1 participants | 2 participants | 1 participants |
| Race/Ethnicity, Customized Caucasian | 63 participants | 5 participants | 20 participants | 15 participants | 23 participants |
| Race/Ethnicity, Customized Oriental/Asian | 0 participants | 0 participants | 0 participants | 0 participants | 0 participants |
| Race/Ethnicity, Customized Other | 13 participants | 3 participants | 3 participants | 7 participants | 0 participants |
| Serum prostate-specific antigen levels | 9.35 nanogram per milliliter | 9.30 nanogram per milliliter | 6.40 nanogram per milliliter | 9.10 nanogram per milliliter | 13.40 nanogram per milliliter |
| Serum testosterone levels | 3.93 nanogram per milliliter | 3.98 nanogram per milliliter | 3.89 nanogram per milliliter | 3.96 nanogram per milliliter | 4.10 nanogram per milliliter |
| Sex: Female, Male Female | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Male | 82 Participants | 10 Participants | 24 Participants | 24 Participants | 24 Participants |
| Stage of prostate cancer Localized | 38 participants | 5 participants | 10 participants | 12 participants | 11 participants |
| Stage of prostate cancer Locally advanced | 16 participants | 0 participants | 5 participants | 5 participants | 6 participants |
| Stage of prostate cancer Metastatic | 10 participants | 2 participants | 2 participants | 2 participants | 4 participants |
| Stage of prostate cancer Not classifiable | 18 participants | 3 participants | 7 participants | 5 participants | 3 participants |
| Time since prostate cancer diagnosis | 1181 days STANDARD_DEVIATION 1494 | 851 days STANDARD_DEVIATION 1077 | 1095 days STANDARD_DEVIATION 1385 | 1609 days STANDARD_DEVIATION 1836 | 954 days STANDARD_DEVIATION 1328 |
| Weight | 81.01 kilogram STANDARD_DEVIATION 12.61 | 78.97 kilogram STANDARD_DEVIATION 11.73 | 81.40 kilogram STANDARD_DEVIATION 14.36 | 80.77 kilogram STANDARD_DEVIATION 12.83 | 81.73 kilogram STANDARD_DEVIATION 11.5 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 6 / — | 18 / — | 20 / — | 13 / — |
| serious Total, serious adverse events | 0 / — | 1 / — | 1 / — | 0 / — |
Outcome results
Primary
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.
Time frame: 28 days
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Degarelix 40 mg | Number of Participants With Testostestone Serum Levels Below 0.5 ng/mL for at Least 28 Days | 1 participants |
| Degarelix 80 mg | Number of Participants With Testostestone Serum Levels Below 0.5 ng/mL for at Least 28 Days | 17 participants |
| Degarelix 120 mg | Number of Participants With Testostestone Serum Levels Below 0.5 ng/mL for at Least 28 Days | 19 participants |
| Degarelix 160 mg | Number of Participants With Testostestone Serum Levels Below 0.5 ng/mL for at Least 28 Days | 13 participants |
p-value: 0.181Cochran-Armitage Trend Test.
Comparison: Kaplan Meier-estimates of the percentage of participants with testostestone serum levels below 0.5 ng/mL for at least 28 days.95% CI: [0.3, 44.5]
Comparison: Kaplan Meier-estimates of the percentage of participants with testostestone serum levels below 0.5 ng/mL for at least 28 days.95% CI: [48.9, 87.4]
Comparison: Kaplan Meier-estimates of the percentage of participants with testostestone serum levels below 0.5 ng/mL for at least 28 days.95% CI: [57.8, 92.9]
Comparison: Kaplan Meier-estimates of the percentage of participants with testostestone serum levels below 0.5 ng/mL for at least 28 days.95% CI: [32.8, 74.4]
Primary
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.
Time frame: 3 months
Population: Patients who withdrew without meeting the insufficient testosterone (T) suppression criteria were censored as of the time for last available T measurement prior to discontinuation. For the 40 mg group the 95% confidence interval around the time estimate was non-estimable and no statistical analysis is presented (the estimate was 14 days).
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Degarelix 40 mg | Time to Meet Insufficient Testosterone Response | 14 days |
| Degarelix 80 mg | Time to Meet Insufficient Testosterone Response | 77 days |
| Degarelix 120 mg | Time to Meet Insufficient Testosterone Response | 98 days |
| Degarelix 160 mg | Time to Meet Insufficient Testosterone Response | 28 days |
p-value: <0.001Log Rank
Comparison: Kaplan-Meier estimates of the time to meet insufficient testosterone (T) response.95% CI: [35, 112]
Comparison: Kaplan-Meier estimates of the time to meet insufficient testosterone (T) response95% CI: [70, 126]
Comparison: Kaplan-Meier estimates of the time to meet insufficient testosterone (T) response95% CI: [14, 98]
Secondary
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.
Time frame: 3 months
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Degarelix 40 mg | Liver Function Tests | ALAT >3x upper limit of normal (ULN) | 0 participants |
| Degarelix 40 mg | Liver Function Tests | Abnormal aspartate aminotransferase | 1 participants |
| Degarelix 40 mg | Liver Function Tests | ALAT >3x ULN, bilirubin >1.5x ULN | 0 participants |
| Degarelix 40 mg | Liver Function Tests | Abnormal bilirubin | 2 participants |
| Degarelix 40 mg | Liver Function Tests | Abnormal alanine aminotransferase (ALAT) | 0 participants |
| Degarelix 80 mg | Liver Function Tests | Abnormal bilirubin | 0 participants |
| Degarelix 80 mg | Liver Function Tests | ALAT >3x upper limit of normal (ULN) | 1 participants |
| Degarelix 80 mg | Liver Function Tests | ALAT >3x ULN, bilirubin >1.5x ULN | 0 participants |
| Degarelix 80 mg | Liver Function Tests | Abnormal aspartate aminotransferase | 11 participants |
| Degarelix 80 mg | Liver Function Tests | Abnormal alanine aminotransferase (ALAT) | 3 participants |
| Degarelix 120 mg | Liver Function Tests | Abnormal bilirubin | 2 participants |
| Degarelix 120 mg | Liver Function Tests | Abnormal alanine aminotransferase (ALAT) | 3 participants |
| Degarelix 120 mg | Liver Function Tests | Abnormal aspartate aminotransferase | 13 participants |
| Degarelix 120 mg | Liver Function Tests | ALAT >3x upper limit of normal (ULN) | 0 participants |
| Degarelix 120 mg | Liver Function Tests | ALAT >3x ULN, bilirubin >1.5x ULN | 0 participants |
| Degarelix 160 mg | Liver Function Tests | ALAT >3x upper limit of normal (ULN) | 0 participants |
| Degarelix 160 mg | Liver Function Tests | Abnormal aspartate aminotransferase | 9 participants |
| Degarelix 160 mg | Liver Function Tests | Abnormal alanine aminotransferase (ALAT) | 6 participants |
| Degarelix 160 mg | Liver Function Tests | Abnormal bilirubin | 2 participants |
| Degarelix 160 mg | Liver Function Tests | ALAT >3x ULN, bilirubin >1.5x ULN | 0 participants |
Secondary
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.
Time frame: 3 months
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Degarelix 40 mg | Number of Participants With Sufficient Testosterone Suppression for at Least 84 Days | 0 participants |
| Degarelix 80 mg | Number of Participants With Sufficient Testosterone Suppression for at Least 84 Days | 9 participants |
| Degarelix 120 mg | Number of Participants With Sufficient Testosterone Suppression for at Least 84 Days | 14 participants |
| Degarelix 160 mg | Number of Participants With Sufficient Testosterone Suppression for at Least 84 Days | 7 participants |
Comparison: Kaplan-Meier estimates of the percentage of participants with sufficient testosterone suppression.95% CI: [0, 0]
Comparison: Kaplan-Meier estimates of the percentage of participants with sufficient testosterone suppression.95% CI: [22, 63.4]
Comparison: Kaplan-Meier estimates of the percentage of participants with sufficient testosterone suppression.95% CI: [41.8, 81.3]
Comparison: Kaplan-Meier estimates of the percentage of participants with sufficient testosterone suppression.95% CI: [15.8, 55.5]
Secondary
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.
Time frame: 3 months
Population: Participants who did not achieve the actual level of reduction were censored as of the time from dosing for the last available observation. In the 40 mg group only two participants reached a 50% reduction in PSA and the Kaplan-Meier estimate could not be calculated (ie no statistical analysis is presented for this group).
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Degarelix 40 mg | Time to 50% Reduction in Prostate-specific Antigen Levels | 10.5 days |
| Degarelix 80 mg | Time to 50% Reduction in Prostate-specific Antigen Levels | 14 days |
| Degarelix 120 mg | Time to 50% Reduction in Prostate-specific Antigen Levels | 14 days |
| Degarelix 160 mg | Time to 50% Reduction in Prostate-specific Antigen Levels | 14 days |
p-value: 0.046Log Rank
Comparison: Kaplan-Meier estimates of the time (days) to 50% reduction in PSA95% CI: [14, 28]
Comparison: Kaplan-Meier estimates of the time (days) to 50% reduction in PSA95% CI: [14, 28]
Comparison: Kaplan-Meier estimates of the time (days) to 50% reduction in PSA95% CI: [14, 41]
Secondary
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.
Time frame: 3 months
Population: Participants who did not achieve the actual level of reduction were censored as of the time from dosing for the last available observation. In the 40 mg group only one participant reached a 90% reduction in PSA and the Kaplan-Meier estimate could not be calculated (ie no statistical analysis is presented for this group).
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Degarelix 40 mg | Time to 90% Reduction in Prostate-specific Antigen Levels | 28 days |
| Degarelix 80 mg | Time to 90% Reduction in Prostate-specific Antigen Levels | 35 days |
| Degarelix 120 mg | Time to 90% Reduction in Prostate-specific Antigen Levels | 35 days |
| Degarelix 160 mg | Time to 90% Reduction in Prostate-specific Antigen Levels | 31.5 days |
p-value: 0.926Log Rank
Comparison: Kaplan-Meier estimates of the time (days) to 90% reduction in PSA.95% CI: [35, 56]
Comparison: Kaplan-Meier estimates of the time (days) to 90% reduction in PSA.95% CI: [35, 84]
Comparison: Kaplan-Meier estimates of the time (days) to 90% reduction in PSA.95% CI: [35, 100]
Secondary
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.
Time frame: 1, 3, 7, 14, 21, 28, 42 days
Population: Half participants in the 40 mg group were not castrated and the median was not calculated (no statistical anaylsis was made). Two participants out of 24 in the 80 mg, 1/24 in the 120 mg, and 3/24 in the 160 mg groups were not castrated. For the 160 mg group the 95% CI was non-estimable and no statistical anaylsis was made.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Degarelix 40 mg | Time to Testosterone Castration (Testosterone ≤0.5 ng/mL). | 3 days | 3 days |
| Degarelix 40 mg | Time to Testosterone Castration (Testosterone ≤0.5 ng/mL). | 42 days | 0 days |
| Degarelix 40 mg | Time to Testosterone Castration (Testosterone ≤0.5 ng/mL). | 1 day | 1 days |
| Degarelix 40 mg | Time to Testosterone Castration (Testosterone ≤0.5 ng/mL). | 7 days | 1 days |
| Degarelix 40 mg | Time to Testosterone Castration (Testosterone ≤0.5 ng/mL). | 28 days | 0 days |
| Degarelix 40 mg | Time to Testosterone Castration (Testosterone ≤0.5 ng/mL). | 14 days | 0 days |
| Degarelix 40 mg | Time to Testosterone Castration (Testosterone ≤0.5 ng/mL). | 21 days | 0 days |
| Degarelix 80 mg | Time to Testosterone Castration (Testosterone ≤0.5 ng/mL). | 28 days | 1 days |
| Degarelix 80 mg | Time to Testosterone Castration (Testosterone ≤0.5 ng/mL). | 21 days | 1 days |
| Degarelix 80 mg | Time to Testosterone Castration (Testosterone ≤0.5 ng/mL). | 42 days | 1 days |
| Degarelix 80 mg | Time to Testosterone Castration (Testosterone ≤0.5 ng/mL). | 3 days | 12 days |
| Degarelix 80 mg | Time to Testosterone Castration (Testosterone ≤0.5 ng/mL). | 7 days | 2 days |
| Degarelix 80 mg | Time to Testosterone Castration (Testosterone ≤0.5 ng/mL). | 14 days | 2 days |
| Degarelix 80 mg | Time to Testosterone Castration (Testosterone ≤0.5 ng/mL). | 1 day | 3 days |
| Degarelix 120 mg | Time to Testosterone Castration (Testosterone ≤0.5 ng/mL). | 3 days | 12 days |
| Degarelix 120 mg | Time to Testosterone Castration (Testosterone ≤0.5 ng/mL). | 42 days | 0 days |
| Degarelix 120 mg | Time to Testosterone Castration (Testosterone ≤0.5 ng/mL). | 1 day | 11 days |
| Degarelix 120 mg | Time to Testosterone Castration (Testosterone ≤0.5 ng/mL). | 14 days | 0 days |
| Degarelix 120 mg | Time to Testosterone Castration (Testosterone ≤0.5 ng/mL). | 21 days | 0 days |
| Degarelix 120 mg | Time to Testosterone Castration (Testosterone ≤0.5 ng/mL). | 28 days | 0 days |
| Degarelix 120 mg | Time to Testosterone Castration (Testosterone ≤0.5 ng/mL). | 7 days | 0 days |
| Degarelix 160 mg | Time to Testosterone Castration (Testosterone ≤0.5 ng/mL). | 42 days | 0 days |
| Degarelix 160 mg | Time to Testosterone Castration (Testosterone ≤0.5 ng/mL). | 1 day | 6 days |
| Degarelix 160 mg | Time to Testosterone Castration (Testosterone ≤0.5 ng/mL). | 3 days | 14 days |
| Degarelix 160 mg | Time to Testosterone Castration (Testosterone ≤0.5 ng/mL). | 7 days | 1 days |
| Degarelix 160 mg | Time to Testosterone Castration (Testosterone ≤0.5 ng/mL). | 14 days | 0 days |
| Degarelix 160 mg | Time to Testosterone Castration (Testosterone ≤0.5 ng/mL). | 21 days | 0 days |
| Degarelix 160 mg | Time to Testosterone Castration (Testosterone ≤0.5 ng/mL). | 28 days | 0 days |
p-value: 0.003Log Rank
Comparison: Kaplan-Meier estimates of the median time to testosterone castration.95% CI: [3, 7]
Comparison: Kaplan-Meier estimates of the time to testosterone castration.95% CI: [1, 3]