Prostate Cancer
Conditions
Brief summary
The purpose of this trial was to select a dose of degarelix (FE 200486). Three groups of patients were treated for six months on different doses. The patients had blood samples taken and measured for Testosterone in order to determine the most efficient dose to provide fast and sustained castration. The patients came to the clinic for 16 visits and dependent on the blood sample results they were invited to return for additional blood samples on a two weekly basis.
Detailed description
Degarelix was not FDA regulated at the time of the trial. After completion of the trial degarelix has been approved by the FDA and is thus an FDA regulated intervention.
Interventions
DRUGDegarelix
Given as a 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
* Signed informed consent before any trial related activity * Proven prostate cancer with a need for endocrine treatment * Testosterone level within the normal range for the age
Exclusion criteria
* Previous or current hormonal treatment of prostate cancer * Candidate for prostatectomy or radiotherapy * History of severe asthma, anaphylactic reactions or Quincke's Oedema * Hypersensitivity towards any component of FE200486 * Cancer disease within the last ten years except for prostate cancer and some skin cancers * Presenting with significant neurological, gastrointestinal, renal, hepatic, cardiovascular, psychological, pulmonary, metabolic, endocrine, haematological, dermatological or infectious disorder. In addition any other condition such as excessive alcohol or drug abuse that may interfere with trial participation or influence the conclusion of the trial as judged by the investigator * Mental incapacity or language barrier * Having received an investigational product within the last 12 weeks preceding the trial * Previous participation in this trial
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Number of Participants With Testosterone <0.5 Nanogram/Milliliter | Weeks 1,2,4,8,12,16,20,24 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants Not Meeting a Testosterone Withdrawal Criterion Between Weeks 4-24 | Weeks 4-24 | Participants with one testoterone value \> 1.0 nanogram/millliliter or two consecutive values between 0.5-1.0 nanogram/milliliter were withdrawn from the study due to insufficient response. |
| Number of Participants Who Met the Withdrawl Criteria for Prostate-specific Antigen | Six months | Participants who met at least one of the three criteria for inadequate response on prostate-specific antigen levels (PA). (1) \>=25 percent and/or 50 nanogram/milliliter compared to baseline (2) reduction of \<=50% compared to baseline at week 12 (3) increase of \>=10 nanogram/milliliter compared to nadir from week 4. |
| Number of Participants With Testosterone < 0.5 Nanogram/Milliliter at All Visits Between Weeks 4-24 | Weeks 4-24 | — |
| The Number of Participants With Abnormal Liver Function Tests | Six months | The number of participants who had abnormal \[defined as above upper limit of normal range (ULN)\] alanine aminotransferase (ALT), participants with ALT increases \> 3x ULN, and participants with ALT increases \> 3x ULN with concurrent increases in bilirubin \> 1.5 ULN. |
| Percentage Change in Vital Signs and Body Weight | Baseline and Six months | Percentage changes in vital signs (systolic and diastolic blood pressure and pulse) and body weight at the end of trial as compared to baseline. |
| Number of Participants With Normal Prostate-specific Antigen Levels During the Study | Weeks 12, 24 | The number of participants whose prostate-specific antigen levels at weeks 12 and 24 were \<= 4 nanogram/millliliter (normal level). |
Countries
United Kingdom
Participant flow
Pre-assignment details
One hundred and fifty-nine participants were screened. One hundred and twenty-nine participants were randomised, two of these participants withdrew before receiving any treatment.
Participants by arm
| Arm | Count |
|---|---|
| Degarelix 80/80 + 40 Loading doses of Degarelix 80 mg on Days 0 and 3. Maintenance doses of 40 mg given on days 28, 56, 84, 112 and 140. | 43 |
| Degarelix 40/40 + 40 Loading doses of Degarelix 40 mg on Days 0 and 3. Maintenance doses of 40 mg given on days 28, 56, 84, 112 and 140. | 46 |
| Degarelix 80 + 20 Loading dose of Degarelix 80 mg on Day 0. Maintenance doses of 20 mg given on days 28, 56, 84, 112 and 140. | 40 |
| Total | 129 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Adverse Event | 0 | 5 | 3 |
| Overall Study | Bad prostate-specific antigen response | 3 | 2 | 0 |
| Overall Study | Insufficient testosterone response | 5 | 8 | 10 |
| Overall Study | Mistakenly withdrawn | 0 | 1 | 0 |
| Overall Study | Other | 1 | 0 | 0 |
| Overall Study | Protocol Violation | 1 | 0 | 1 |
| Overall Study | Withdrawal by Subject | 1 | 0 | 0 |
Baseline characteristics
| Characteristic | Degarelix 40/40 + 40 | Total | Degarelix 80/80 + 40 | Degarelix 80 + 20 |
|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 41 Participants | 111 Participants | 37 Participants | 33 Participants |
| Age, Categorical Between 18 and 65 years | 5 Participants | 18 Participants | 6 Participants | 7 Participants |
| Age, Continuous | 73.7 years STANDARD_DEVIATION 7.2 | 72.7 years STANDARD_DEVIATION 7 | 72.4 years STANDARD_DEVIATION 6.6 | 71.8 years STANDARD_DEVIATION 7.1 |
| Body Mass Index | 26.6 kilogram per square meter | 26.1 kilogram per square meter | 26.2 kilogram per square meter | 25.2 kilogram per square meter |
| Days Since Diagnosis of Prostate Cancer | 153.8 days STANDARD_DEVIATION 518.1 | 99.9 days STANDARD_DEVIATION 377.2 | 52.7 days STANDARD_DEVIATION 116 | 88.8 days STANDARD_DEVIATION 370 |
| Participant Counts by Gleason Score 2-4 | 4 participants | 9 participants | 3 participants | 2 participants |
| Participant Counts by Gleason Score 5-6 | 7 participants | 29 participants | 11 participants | 11 participants |
| Participant Counts by Gleason Score 7-10 | 34 participants | 88 participants | 28 participants | 26 participants |
| Participant Counts by Gleason Score unknown | 1 participants | 3 participants | 1 participants | 1 participants |
| Race/Ethnicity, Customized Afro-carribean | 0 participants | 1 participants | 0 participants | 1 participants |
| Race/Ethnicity, Customized Black | 3 participants | 5 participants | 1 participants | 1 participants |
| Race/Ethnicity, Customized Indian | 0 participants | 1 participants | 0 participants | 1 participants |
| Race/Ethnicity, Customized Oriental / Asian | 0 participants | 0 participants | 0 participants | 0 participants |
| Race/Ethnicity, Customized White | 43 participants | 122 participants | 42 participants | 37 participants |
| Region of Enrollment United Kingdom | 46 participants | 129 participants | 43 participants | 40 participants |
| Serum Prostate-Specific Antigen level | 64.6 nanogram/milliliter | 61.1 nanogram/milliliter | 50.3 nanogram/milliliter | 82.9 nanogram/milliliter |
| Serum Testosterone level | 4.1 nanogram/milliliter | 4.0 nanogram/milliliter | 3.7 nanogram/milliliter | 4.8 nanogram/milliliter |
| Sex: Female, Male Female | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Male | 46 Participants | 129 Participants | 43 Participants | 40 Participants |
| Stage of Prostate Cancer Localized | 9 participants | 22 participants | 8 participants | 5 participants |
| Stage of Prostate Cancer Locally advanced | 21 participants | 60 participants | 21 participants | 18 participants |
| Stage of Prostate Cancer Metastatic | 14 participants | 42 participants | 11 participants | 17 participants |
| Stage of Prostate Cancer Not classifiable | 2 participants | 5 participants | 3 participants | 0 participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 38 / — | 38 / — | 32 / — |
| serious Total, serious adverse events | 3 / — | 8 / — | 6 / — |
Outcome results
Primary
Number of Participants With Testosterone <0.5 Nanogram/Milliliter
Time frame: Weeks 1,2,4,8,12,16,20,24
Population: Per protocol population
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Degarelix 80/80 + 40 | Number of Participants With Testosterone <0.5 Nanogram/Milliliter | Week 24 (n=31, 29, 25) | 28 participants |
| Degarelix 80/80 + 40 | Number of Participants With Testosterone <0.5 Nanogram/Milliliter | Week 8 (n=36, 36, 31) | 36 participants |
| Degarelix 80/80 + 40 | Number of Participants With Testosterone <0.5 Nanogram/Milliliter | Week 20 (n=33, 31, 28) | 31 participants |
| Degarelix 80/80 + 40 | Number of Participants With Testosterone <0.5 Nanogram/Milliliter | Week 1 (n=38, 44, 38) | 38 participants |
| Degarelix 80/80 + 40 | Number of Participants With Testosterone <0.5 Nanogram/Milliliter | Week 12 (n=34, 34, 31) | 34 participants |
| Degarelix 80/80 + 40 | Number of Participants With Testosterone <0.5 Nanogram/Milliliter | Week 4 (n=38, 36, 33) | 38 participants |
| Degarelix 80/80 + 40 | Number of Participants With Testosterone <0.5 Nanogram/Milliliter | Week 2 (n=38, 44, 38) | 38 participants |
| Degarelix 80/80 + 40 | Number of Participants With Testosterone <0.5 Nanogram/Milliliter | Week 16 (n=34, 32, 30) | 33 participants |
| Degarelix 40/40 + 40 | Number of Participants With Testosterone <0.5 Nanogram/Milliliter | Week 1 (n=38, 44, 38) | 32 participants |
| Degarelix 40/40 + 40 | Number of Participants With Testosterone <0.5 Nanogram/Milliliter | Week 2 (n=38, 44, 38) | 36 participants |
| Degarelix 40/40 + 40 | Number of Participants With Testosterone <0.5 Nanogram/Milliliter | Week 20 (n=33, 31, 28) | 30 participants |
| Degarelix 40/40 + 40 | Number of Participants With Testosterone <0.5 Nanogram/Milliliter | Week 24 (n=31, 29, 25) | 27 participants |
| Degarelix 40/40 + 40 | Number of Participants With Testosterone <0.5 Nanogram/Milliliter | Week 4 (n=38, 36, 33) | 35 participants |
| Degarelix 40/40 + 40 | Number of Participants With Testosterone <0.5 Nanogram/Milliliter | Week 16 (n=34, 32, 30) | 31 participants |
| Degarelix 40/40 + 40 | Number of Participants With Testosterone <0.5 Nanogram/Milliliter | Week 8 (n=36, 36, 31) | 36 participants |
| Degarelix 40/40 + 40 | Number of Participants With Testosterone <0.5 Nanogram/Milliliter | Week 12 (n=34, 34, 31) | 34 participants |
| Degarelix 80 + 20 | Number of Participants With Testosterone <0.5 Nanogram/Milliliter | Week 24 (n=31, 29, 25) | 22 participants |
| Degarelix 80 + 20 | Number of Participants With Testosterone <0.5 Nanogram/Milliliter | Week 1 (n=38, 44, 38) | 27 participants |
| Degarelix 80 + 20 | Number of Participants With Testosterone <0.5 Nanogram/Milliliter | Week 4 (n=38, 36, 33) | 31 participants |
| Degarelix 80 + 20 | Number of Participants With Testosterone <0.5 Nanogram/Milliliter | Week 8 (n=36, 36, 31) | 31 participants |
| Degarelix 80 + 20 | Number of Participants With Testosterone <0.5 Nanogram/Milliliter | Week 12 (n=34, 34, 31) | 30 participants |
| Degarelix 80 + 20 | Number of Participants With Testosterone <0.5 Nanogram/Milliliter | Week 16 (n=34, 32, 30) | 27 participants |
| Degarelix 80 + 20 | Number of Participants With Testosterone <0.5 Nanogram/Milliliter | Week 20 (n=33, 31, 28) | 25 participants |
| Degarelix 80 + 20 | Number of Participants With Testosterone <0.5 Nanogram/Milliliter | Week 2 (n=38, 44, 38) | 33 participants |
Secondary
Number of Participants Not Meeting a Testosterone Withdrawal Criterion Between Weeks 4-24
Participants with one testoterone value \> 1.0 nanogram/millliliter or two consecutive values between 0.5-1.0 nanogram/milliliter were withdrawn from the study due to insufficient response.
Time frame: Weeks 4-24
Population: Per protocol population
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Degarelix 80/80 + 40 | Number of Participants Not Meeting a Testosterone Withdrawal Criterion Between Weeks 4-24 | 29 participants |
| Degarelix 40/40 + 40 | Number of Participants Not Meeting a Testosterone Withdrawal Criterion Between Weeks 4-24 | 29 participants |
| Degarelix 80 + 20 | Number of Participants Not Meeting a Testosterone Withdrawal Criterion Between Weeks 4-24 | 25 participants |
Secondary
Number of Participants Who Met the Withdrawl Criteria for Prostate-specific Antigen
Participants who met at least one of the three criteria for inadequate response on prostate-specific antigen levels (PA). (1) \>=25 percent and/or 50 nanogram/milliliter compared to baseline (2) reduction of \<=50% compared to baseline at week 12 (3) increase of \>=10 nanogram/milliliter compared to nadir from week 4.
Time frame: Six months
Population: per protocol population
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Degarelix 80/80 + 40 | Number of Participants Who Met the Withdrawl Criteria for Prostate-specific Antigen | <=50% compared to baseline | 0 participants |
| Degarelix 80/80 + 40 | Number of Participants Who Met the Withdrawl Criteria for Prostate-specific Antigen | >=25% and/or 50 ng/mL compared to baseline | 0 participants |
| Degarelix 80/80 + 40 | Number of Participants Who Met the Withdrawl Criteria for Prostate-specific Antigen | >=10 ng/mL compared to nadir | 1 participants |
| Degarelix 40/40 + 40 | Number of Participants Who Met the Withdrawl Criteria for Prostate-specific Antigen | <=50% compared to baseline | 0 participants |
| Degarelix 40/40 + 40 | Number of Participants Who Met the Withdrawl Criteria for Prostate-specific Antigen | >=25% and/or 50 ng/mL compared to baseline | 0 participants |
| Degarelix 40/40 + 40 | Number of Participants Who Met the Withdrawl Criteria for Prostate-specific Antigen | >=10 ng/mL compared to nadir | 6 participants |
| Degarelix 80 + 20 | Number of Participants Who Met the Withdrawl Criteria for Prostate-specific Antigen | >=25% and/or 50 ng/mL compared to baseline | 0 participants |
| Degarelix 80 + 20 | Number of Participants Who Met the Withdrawl Criteria for Prostate-specific Antigen | >=10 ng/mL compared to nadir | 1 participants |
| Degarelix 80 + 20 | Number of Participants Who Met the Withdrawl Criteria for Prostate-specific Antigen | <=50% compared to baseline | 0 participants |
Secondary
Number of Participants With Normal Prostate-specific Antigen Levels During the Study
The number of participants whose prostate-specific antigen levels at weeks 12 and 24 were \<= 4 nanogram/millliliter (normal level).
Time frame: Weeks 12, 24
Population: Per Protocol Population
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Degarelix 80/80 + 40 | Number of Participants With Normal Prostate-specific Antigen Levels During the Study | Week 12 (n=34, 34, 31) | 18 participants |
| Degarelix 80/80 + 40 | Number of Participants With Normal Prostate-specific Antigen Levels During the Study | Week 24 (n=31, 29, 25) | 18 participants |
| Degarelix 40/40 + 40 | Number of Participants With Normal Prostate-specific Antigen Levels During the Study | Week 12 (n=34, 34, 31) | 18 participants |
| Degarelix 40/40 + 40 | Number of Participants With Normal Prostate-specific Antigen Levels During the Study | Week 24 (n=31, 29, 25) | 18 participants |
| Degarelix 80 + 20 | Number of Participants With Normal Prostate-specific Antigen Levels During the Study | Week 12 (n=34, 34, 31) | 16 participants |
| Degarelix 80 + 20 | Number of Participants With Normal Prostate-specific Antigen Levels During the Study | Week 24 (n=31, 29, 25) | 17 participants |
Secondary
Number of Participants With Testosterone < 0.5 Nanogram/Milliliter at All Visits Between Weeks 4-24
Time frame: Weeks 4-24
Population: Per protocol population
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Degarelix 80/80 + 40 | Number of Participants With Testosterone < 0.5 Nanogram/Milliliter at All Visits Between Weeks 4-24 | 28 participants |
| Degarelix 40/40 + 40 | Number of Participants With Testosterone < 0.5 Nanogram/Milliliter at All Visits Between Weeks 4-24 | 27 participants |
| Degarelix 80 + 20 | Number of Participants With Testosterone < 0.5 Nanogram/Milliliter at All Visits Between Weeks 4-24 | 20 participants |
Secondary
Percentage Change in Vital Signs and Body Weight
Percentage changes in vital signs (systolic and diastolic blood pressure and pulse) and body weight at the end of trial as compared to baseline.
Time frame: Baseline and Six months
Population: Safety population.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Degarelix 80/80 + 40 | Percentage Change in Vital Signs and Body Weight | Diastolic blood pressure | 0.0 percentage |
| Degarelix 80/80 + 40 | Percentage Change in Vital Signs and Body Weight | Systolic blood pressure | -3.7 percentage |
| Degarelix 80/80 + 40 | Percentage Change in Vital Signs and Body Weight | Pulse | -3.1 percentage |
| Degarelix 80/80 + 40 | Percentage Change in Vital Signs and Body Weight | Weight | 2.8 percentage |
| Degarelix 40/40 + 40 | Percentage Change in Vital Signs and Body Weight | Weight | 2.6 percentage |
| Degarelix 40/40 + 40 | Percentage Change in Vital Signs and Body Weight | Diastolic blood pressure | -0.6 percentage |
| Degarelix 40/40 + 40 | Percentage Change in Vital Signs and Body Weight | Pulse | 0.0 percentage |
| Degarelix 40/40 + 40 | Percentage Change in Vital Signs and Body Weight | Systolic blood pressure | -2.4 percentage |
| Degarelix 80 + 20 | Percentage Change in Vital Signs and Body Weight | Weight | 3.5 percentage |
| Degarelix 80 + 20 | Percentage Change in Vital Signs and Body Weight | Systolic blood pressure | 0.0 percentage |
| Degarelix 80 + 20 | Percentage Change in Vital Signs and Body Weight | Pulse | -1.5 percentage |
| Degarelix 80 + 20 | Percentage Change in Vital Signs and Body Weight | Diastolic blood pressure | 0.0 percentage |
Secondary
The Number of Participants With Abnormal Liver Function Tests
The number of participants who had abnormal \[defined as above upper limit of normal range (ULN)\] alanine aminotransferase (ALT), participants with ALT increases \> 3x ULN, and participants with ALT increases \> 3x ULN with concurrent increases in bilirubin \> 1.5 ULN.
Time frame: Six months
Population: Randomized (Safety) population
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Degarelix 80/80 + 40 | The Number of Participants With Abnormal Liver Function Tests | ALT levels >3x upper limit | 0 participants |
| Degarelix 80/80 + 40 | The Number of Participants With Abnormal Liver Function Tests | Alanine aminotransferase (ALT) above upper limit | 13 participants |
| Degarelix 80/80 + 40 | The Number of Participants With Abnormal Liver Function Tests | ALT levels >3x and bilirubin >1.5x upper limit | 0 participants |
| Degarelix 40/40 + 40 | The Number of Participants With Abnormal Liver Function Tests | ALT levels >3x upper limit | 1 participants |
| Degarelix 40/40 + 40 | The Number of Participants With Abnormal Liver Function Tests | Alanine aminotransferase (ALT) above upper limit | 14 participants |
| Degarelix 40/40 + 40 | The Number of Participants With Abnormal Liver Function Tests | ALT levels >3x and bilirubin >1.5x upper limit | 0 participants |
| Degarelix 80 + 20 | The Number of Participants With Abnormal Liver Function Tests | Alanine aminotransferase (ALT) above upper limit | 12 participants |
| Degarelix 80 + 20 | The Number of Participants With Abnormal Liver Function Tests | ALT levels >3x and bilirubin >1.5x upper limit | 1 participants |
| Degarelix 80 + 20 | The Number of Participants With Abnormal Liver Function Tests | ALT levels >3x upper limit | 1 participants |