Prostate Cancer
Conditions
Keywords
bone turnover, hormone-naïve, prostate specific antigen, Prostate Cancer
Brief summary
To evaluate the effect of enzalutamide on prostate specific antigen (PSA) level in men with prostate cancer.
Interventions
DRUGEnzalutamide
Oral
Sponsors
Medivation, Inc.
Astellas Pharma Inc
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
MALE
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Histologically confirmed prostate cancer (all stages) for whom androgen deprivation therapy is indicated (except when indicated in a neoadjuvant/adjuvant therapy) * Asymptomatic from prostate cancer * Non-castrate level of testosterone (≥ 8 nmol/L (230 ng/dL)) at screening * PSA ≥ 2 ng/mL at screening
Exclusion criteria
Has previously or is currently receiving: * Hormonal therapy with intent to treat prostate cancer * Systemic glucocorticoids * Chemotherapy with the intent to treat prostate cancer * Opiate analgesics for pain from prostate cancer * Radiation therapy for treatment of the primary tumor or metastases * Has history of known or suspected brain or skull metastases or leptomeningeal disease * Has history of seizure including febrile seizure or any condition that may predispose to seizure or history of loss of consciousness or transient ischemic attack * Clinically significant cardiovascular disease
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With a Prostate-Specific Antigen (PSA) Response at Week 25 | Baseline and Week 25 | A PSA response was defined as a decline from Baseline in PSA level of 80% or greater. Blood samples for PSA were collected and analyzed at a central laboratory. Participants with an unknown or missing response or who discontinued prior to week 25 for any reason were treated as non-responders. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Adverse Events | From first dose of study drug up to 30 days after last dose of study drug; median duration of treatment of 1666.0 days (range of 52-2052) | Each adverse event (AE) was assessed by the investigator for causal relationship to the study drug; those deemed possibly or probably related to study drug are reported as drug regimen related AEs (DRRAEs). A serious adverse event (SAE) was defined as any untoward medical occurrence that at any dose: * Resulted in death * Was life-threatening * Resulted in persistent or significant disability/incapacity * Resulted in congenital anomaly or birth defect * Required inpatient hospitalization or led to prolongation of hospitalization * Other medically important events. |
| Percent Change From Baseline in PSA | Baseline and Weeks 25, 49, 97, 169 and Week 265 (End of Study) | — |
| Percent Change From Baseline in Sex Hormone-Binding Globulin (SHBG) | Baseline and Weeks 25 and 49 | — |
| Percent Change From Baseline in Androstenedione | Baseline and Weeks 25 and 49 | — |
| Percent Change From Baseline in Dehydroepiandrosterone (DHEA) | Baseline and Weeks 25 and 49 | — |
| Percent Change From Baseline in Dihydrotestosterone (DHT) | Baseline and Week 25 and 49 | — |
| Percent Change From Baseline in Estradiol | Baseline and Weeks 25 and 49 | — |
| Percent Change From Baseline in Follicle-Stimulating Hormone (FSH) | Baseline and Weeks 25 and 49 | — |
| Percent Change From Baseline in Luteinizing Hormone (LH) | Baseline and Weeks 25 and 49 | — |
| Percent Change From Baseline in Prolactin | Baseline and Weeks 25 and 49 | — |
| Percent Change From Baseline in Total Testosterone | Baseline and Weeks 25 and 49 | — |
| Percent Change From Baseline in Free Testosterone | Baseline and Weeks 25 and 49 | — |
| Plasma Concentration of Enzalutamide at Pre-dose (Ctrough) | Pre-dose at Weeks 2, 3, 4, 5, 9, 13, 21 and 25 | — |
| Plasma Concentration of Enzalutamide Metabolite M2 at Pre-dose (Ctrough) | Pre-dose at Weeks 2, 3, 4, 5, 9, 13, 21 and 25 | — |
| Percentage of Participants With a PSA Response at Weeks 49, 97 and 169 | Baseline and Weeks 49, 97 and 169 | A PSA response was defined as a decline from baseline in PSA level of 80% or greater. Blood samples for PSA were collected and analyzed at a central laboratory. Participants with an unknown or missing response or who discontinued prior to week 49, week 97 or week 169 for any reason were treated as non-responders. |
| Percentage of Participants With a 90% or Greater Reduction From Baseline in PSA Level | Baseline and Weeks 25, 49, 97 and 169 | Participants with unknown or missing PSA results at week 25 or who discontinued prior to week 25 were considered non-responders at week 25. Participants with unknown or missing PSA results at week 49, week 97 or week 169 were considered non-responders. |
| Percentage of Participants With PSA ≤ 4 ng/ml | Weeks 25, 49, 97 and 169 | Participants with unknown or missing PSA results at week 25 or who discontinued prior to Week 25 were considered non-responders at Week 25. Participants with unknown or missing PSA results at week 49, 97 and 169 were considered non-responders. |
| Percentage of Participants With PSA ≤ 0.1 ng/ml | Weeks 25, 49, 97 and 169 | Participants with unknown or missing PSA results at week 25 or who discontinued prior to week 25 were considered non-responders at week 25. Participants with unknown or missing PSA results at week 49, 97 or 169 were considered non-responders. |
| Maximum Decline From Baseline in PSA | Baseline to Week 25 and from Baseline up to the EOS date of 27 Apr 2017; median duration of treatment of 1666.0 days (range of 52-2052) | The maximum decline from Baseline in PSA was calculated as the largest reduction from Baseline in PSA level that occurred at any point after treatment start up to week 25 and up to and including the assessment made at the safety follow-up visit, divided by the PSA Baseline value and multiplied by 100, i.e., the maximum percent change from baseline. |
| Time to PSA Response | From first dose until the EOS date of 27-Apr-2017; median duration of treatment of 1666.0 days (range of 52-2052) | Time to PSA response (PSA decline ≥ 80% from Baseline) is defined as the time interval from the first study drug dose to the first date a decline from Baseline in PSA level of 80% or greater was recorded. Time to response was estimated using the Kaplan-Meier method. |
| Time to PSA Decline ≥ 90% | From first dose until the EOS date of 27-Apr-2017; median duration of treatment of 1666.0 days (range of 52-2052) | Time to PSA decline ≥ 90% is defined as the time interval from the first study drug dose to the first date a decline from Baseline in PSA level of 90% or greater was recorded. Time to PSA decline ≥ 90% was estimated using the Kaplan-Meier method. |
| Time to PSA ≤ 4 ng/ml | From first dose until the EOS date of 27-Apr-2017; median duration of treatment of 1666.0 days (range of 52-2052) | Time to PSA ≤ 4 ng/ml is defined as the time interval from the first study drug dose to the first date a decline in PSA to a result of 4 ng/ml or below was recorded. Time to PSA ≤ 4 ng/ml was estimated using the Kaplan-Meier method. |
| Time to PSA ≤ 0.1 ng/ml | From first dose until the EOS date of 27-Apr-2017; median duration of treatment of 1666.0 days (range of 52-2052) | Time to PSA ≤ 0.1 ng/ml is defined as the time interval from the first study drug dose to the first date a decline in PSA to a result of 0.1 ng/ml or below was recorded. Time to PSA ≤ 0.1 ng/ml was estimated using the Kaplan-Meier method. |
| Time to PSA Progression | From first dose until the EOS date of 27-Apr-2017; median duration of treatment of 1666.0 days (range of 52-2052) | Time to PSA progression is defined as the time interval from the first study drug dose to the first date of PSA progression. PSA progression is defined as a ≥ 25% increase in PSA with an absolute increase of ≥ 2 ng/mL above the nadir unless the PSA next measurement(s), if available, does not confirm the PSA progression. |
| PSA Doubling Time | From Baseline to Week 25 | PSA doubling time was to be calculated from the slope estimated from a linear regression of the natural log of PSA fitted on time, if the slope was positive. Since the slope was negative for all participants, PSA doubling time could not be calculated. |
Countries
Belgium, Czechia, Denmark, Germany
Participant flow
Recruitment details
This was a multinational, phase 2, open-label, single-arm, efficacy and safety study of oral enzalutamide in participants with prostate cancer who had noncastrate levels of testosterone at study entry.
Pre-assignment details
Eighty-two participants were assessed for participation in the study, 15 were excluded and 67 were enrolled. Participants who continued to receive clinical benefit as assessed by the investigator and did not meet any treatment discontinuation criteria were eligible to transition to an open-label extension study 9785-CL-0123 (NCT02960022).
Participants by arm
| Arm | Count |
|---|---|
| Enzalutamide Participants received oral enzalutamide at 160 mg once daily for 24 weeks. Participants who had clinical benefit at week 25 could continue to receive enzalutamide until disease progression, objective or clinical, or occurrence of an unacceptable toxicity, at the discretion of the investigator. | 67 |
| Total | 67 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Death | 5 |
| Overall Study | Other-Miscellaneous Reason | 2 |
| Overall Study | Other-Transitioned to 9785-CL-0123 | 29 |
| Overall Study | Withdrawal by Subject | 4 |
Baseline characteristics
| Characteristic | Enzalutamide |
|---|---|
| Age, Continuous | 73.0 Years |
| Body Mass Index (BMI) | 26.17 kg/m² |
| Clinical Lymph Node Stage (N) at Initial Diagnosis N0: No regional lymph node metastasis | 22 Participants |
| Clinical Lymph Node Stage (N) at Initial Diagnosis N1: Metastasis in regional lymph node(s) | 6 Participants |
| Clinical Lymph Node Stage (N) at Initial Diagnosis NX: Regional lymph nodes were not assessed | 24 Participants |
| Clinical Lymph Node Stage (N) at Initial Diagnosis Unknown | 15 Participants |
| Clinical Tumor Stage (T) at Initial Diagnosis T0: No evidence of primary tumor | 1 Participants |
| Clinical Tumor Stage (T) at Initial Diagnosis T1: Tumor neither palpable or visible by imaging | 9 Participants |
| Clinical Tumor Stage (T) at Initial Diagnosis T2: Tumor confined within the prostate | 31 Participants |
| Clinical Tumor Stage (T) at Initial Diagnosis T3: Tumor extends through the prostatic capsule | 18 Participants |
| Clinical Tumor Stage (T) at Initial Diagnosis T4: Tumor is fixed or invades adjacent structures | 1 Participants |
| Clinical Tumor Stage (T) at Initial Diagnosis TX: Primary tumor cannot be assessed | 1 Participants |
| Clinical Tumor Stage (T) at Initial Diagnosis Unknown | 6 Participants |
| Distant Metastasis (M) at Initial Diagnosis M0: No distant metastasis | 35 Participants |
| Distant Metastasis (M) at Initial Diagnosis M1: Distant metastasis | 10 Participants |
| Distant Metastasis (M) at Initial Diagnosis MX: Distant metastasis could not be assessed | 11 Participants |
| Distant Metastasis (M) at Initial Diagnosis Unknown | 11 Participants |
| Duration of Prostate Cancer | 1.0 years |
| Number of Metastatic Lesions by Bone Scan | 1 Lesions |
| Participants With Metastases at Study Entry | 26 Participants |
| Previous Interventions Other Surgeries/Procedures | 4 Participants |
| Previous Interventions Pelvic Lymph Node Dissection | 6 Participants |
| Previous Interventions Prostatectomy | 24 Participants |
| Previous Interventions Radiotherapy | 16 Participants |
| Previous Interventions Transurethral Resection of the Prostate | 4 Participants |
| Previous Interventions Watchful Waiting | 14 Participants |
| Prostate Specific Antigen (PSA) | 18.2 ng/mL INTER_QUARTILE_RANGE 102.99 |
| Sex: Female, Male Female | 0 Participants |
| Sex: Female, Male Male | 67 Participants |
| Total Gleason Score at Initial Diagnosis 10 | 3 Participants |
| Total Gleason Score at Initial Diagnosis 4 | 1 Participants |
| Total Gleason Score at Initial Diagnosis 5 | 5 Participants |
| Total Gleason Score at Initial Diagnosis 6 | 10 Participants |
| Total Gleason Score at Initial Diagnosis 7 | 34 Participants |
| Total Gleason Score at Initial Diagnosis 8 | 7 Participants |
| Total Gleason Score at Initial Diagnosis 9 | 6 Participants |
| Total Gleason Score at Initial Diagnosis Unknown | 1 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 5 / 67 |
| other Total, other adverse events | 66 / 67 |
| serious Total, serious adverse events | 24 / 67 |
Outcome results
Primary
Percentage of Participants With a Prostate-Specific Antigen (PSA) Response at Week 25
A PSA response was defined as a decline from Baseline in PSA level of 80% or greater. Blood samples for PSA were collected and analyzed at a central laboratory. Participants with an unknown or missing response or who discontinued prior to week 25 for any reason were treated as non-responders.
Time frame: Baseline and Week 25
Population: The analysis population was safety analysis set (SAF), which consisted of participants who received at least one dose of study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Enzalutamide | Percentage of Participants With a Prostate-Specific Antigen (PSA) Response at Week 25 | 92.5 Percentage of Participants |
Secondary
Maximum Decline From Baseline in PSA
The maximum decline from Baseline in PSA was calculated as the largest reduction from Baseline in PSA level that occurred at any point after treatment start up to week 25 and up to and including the assessment made at the safety follow-up visit, divided by the PSA Baseline value and multiplied by 100, i.e., the maximum percent change from baseline.
Time frame: Baseline to Week 25 and from Baseline up to the EOS date of 27 Apr 2017; median duration of treatment of 1666.0 days (range of 52-2052)
Population: Safety Analysis Set with available data at each time point
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Enzalutamide | Maximum Decline From Baseline in PSA | Maximum Decline by Week 25 | -98.32 Percent Change | Standard Deviation 2.88 |
| Enzalutamide | Maximum Decline From Baseline in PSA | Maximum Decline by EOS | -99.10 Percent Change | Standard Deviation 2.659 |
Secondary
Number of Participants With Adverse Events
Each adverse event (AE) was assessed by the investigator for causal relationship to the study drug; those deemed possibly or probably related to study drug are reported as drug regimen related AEs (DRRAEs). A serious adverse event (SAE) was defined as any untoward medical occurrence that at any dose: * Resulted in death * Was life-threatening * Resulted in persistent or significant disability/incapacity * Resulted in congenital anomaly or birth defect * Required inpatient hospitalization or led to prolongation of hospitalization * Other medically important events.
Time frame: From first dose of study drug up to 30 days after last dose of study drug; median duration of treatment of 1666.0 days (range of 52-2052)
Population: Safety Analysis Set
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Enzalutamide | Number of Participants With Adverse Events | Any Adverse Events | 67 Participants |
| Enzalutamide | Number of Participants With Adverse Events | Drug Regimen Related Adverse Events | 65 Participants |
| Enzalutamide | Number of Participants With Adverse Events | Deaths | 5 Participants |
| Enzalutamide | Number of Participants With Adverse Events | Serious Adverse Events | 24 Participants |
| Enzalutamide | Number of Participants With Adverse Events | Drug Regimen Related Serious Adverse Events | 5 Participants |
| Enzalutamide | Number of Participants With Adverse Events | AEs Leading to Discontinuation of Study Drug | 14 Participants |
| Enzalutamide | Number of Participants With Adverse Events | DRRAEs Leading to Discontinuation of Study Drug | 7 Participants |
Secondary
Percentage of Participants With a 90% or Greater Reduction From Baseline in PSA Level
Participants with unknown or missing PSA results at week 25 or who discontinued prior to week 25 were considered non-responders at week 25. Participants with unknown or missing PSA results at week 49, week 97 or week 169 were considered non-responders.
Time frame: Baseline and Weeks 25, 49, 97 and 169
Population: Safety Analysis Set; Week 49, 97 and 169 analyses include participants who were on study at each time point
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Enzalutamide | Percentage of Participants With a 90% or Greater Reduction From Baseline in PSA Level | Week 25 | 91.0 Percentage of Participants |
| Enzalutamide | Percentage of Participants With a 90% or Greater Reduction From Baseline in PSA Level | Week 49 | 98.1 Percentage of Participants |
| Enzalutamide | Percentage of Participants With a 90% or Greater Reduction From Baseline in PSA Level | Week 97 | 100.0 Percentage of Participants |
| Enzalutamide | Percentage of Participants With a 90% or Greater Reduction From Baseline in PSA Level | Week 169 | 88.1 Percentage of Participants |
Secondary
Percentage of Participants With a PSA Response at Weeks 49, 97 and 169
A PSA response was defined as a decline from baseline in PSA level of 80% or greater. Blood samples for PSA were collected and analyzed at a central laboratory. Participants with an unknown or missing response or who discontinued prior to week 49, week 97 or week 169 for any reason were treated as non-responders.
Time frame: Baseline and Weeks 49, 97 and 169
Population: Safety Analysis Set
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Enzalutamide | Percentage of Participants With a PSA Response at Weeks 49, 97 and 169 | Week 49 | 80.6 Percentage of Participants |
| Enzalutamide | Percentage of Participants With a PSA Response at Weeks 49, 97 and 169 | Week 97 | 67.2 Percentage of Participants |
| Enzalutamide | Percentage of Participants With a PSA Response at Weeks 49, 97 and 169 | Week 169 | 56.7 Percentage of Participants |
Secondary
Percentage of Participants With PSA ≤ 0.1 ng/ml
Participants with unknown or missing PSA results at week 25 or who discontinued prior to week 25 were considered non-responders at week 25. Participants with unknown or missing PSA results at week 49, 97 or 169 were considered non-responders.
Time frame: Weeks 25, 49, 97 and 169
Population: Safety Analysis Set; Week 49, 97 and 169 analyses include participants who were on study at each time point
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Enzalutamide | Percentage of Participants With PSA ≤ 0.1 ng/ml | Week 25 | 44.8 Percentage of Participants |
| Enzalutamide | Percentage of Participants With PSA ≤ 0.1 ng/ml | Week 49 | 63.0 Percentage of Participants |
| Enzalutamide | Percentage of Participants With PSA ≤ 0.1 ng/ml | Week 97 | 73.3 Percentage of Participants |
| Enzalutamide | Percentage of Participants With PSA ≤ 0.1 ng/ml | Week 169 | 61.9 Percentage of Participants |
Secondary
Percentage of Participants With PSA ≤ 4 ng/ml
Participants with unknown or missing PSA results at week 25 or who discontinued prior to Week 25 were considered non-responders at Week 25. Participants with unknown or missing PSA results at week 49, 97 and 169 were considered non-responders.
Time frame: Weeks 25, 49, 97 and 169
Population: Safety Analysis Set; Week 49, 97 and 169 analyses include participants who were on study at each time point
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Enzalutamide | Percentage of Participants With PSA ≤ 4 ng/ml | Week 49 | 94.4 Percentage of Participants |
| Enzalutamide | Percentage of Participants With PSA ≤ 4 ng/ml | Week 97 | 100.0 Percentage of Participants |
| Enzalutamide | Percentage of Participants With PSA ≤ 4 ng/ml | Week 169 | 95.2 Percentage of Participants |
| Enzalutamide | Percentage of Participants With PSA ≤ 4 ng/ml | Week 25 | 92.5 Percentage of Participants |
Secondary
Percent Change From Baseline in Androstenedione
Time frame: Baseline and Weeks 25 and 49
Population: Safety Analysis Set with available data at each time point
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Enzalutamide | Percent Change From Baseline in Androstenedione | Week 25 | 51.06 Percent Change | Standard Deviation 59.367 |
| Enzalutamide | Percent Change From Baseline in Androstenedione | Week 49 | 49.94 Percent Change | Standard Deviation 55.449 |
Secondary
Percent Change From Baseline in Dehydroepiandrosterone (DHEA)
Time frame: Baseline and Weeks 25 and 49
Population: Safety Analysis Set with available data at each time point
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Enzalutamide | Percent Change From Baseline in Dehydroepiandrosterone (DHEA) | Week 25 | 9.59 Percent Change | Standard Deviation 58.247 |
| Enzalutamide | Percent Change From Baseline in Dehydroepiandrosterone (DHEA) | Week 49 | 10.54 Percent Change | Standard Deviation 54.864 |
Secondary
Percent Change From Baseline in Dihydrotestosterone (DHT)
Time frame: Baseline and Week 25 and 49
Population: Safety Analysis Set with available data at each time point
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Enzalutamide | Percent Change From Baseline in Dihydrotestosterone (DHT) | Week 25 | 51.72 Percent Change | Standard Deviation 57.511 |
| Enzalutamide | Percent Change From Baseline in Dihydrotestosterone (DHT) | Week 49 | 74.35 Percent Change | Standard Deviation 101.451 |
Secondary
Percent Change From Baseline in Estradiol
Time frame: Baseline and Weeks 25 and 49
Population: Safety Analysis Set with available data at each time point
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Enzalutamide | Percent Change From Baseline in Estradiol | Week 25 | 71.69 Percent Change | Standard Deviation 73.15 |
| Enzalutamide | Percent Change From Baseline in Estradiol | Week 49 | 81.00 Percent Change | Standard Deviation 82.811 |
Secondary
Percent Change From Baseline in Follicle-Stimulating Hormone (FSH)
Time frame: Baseline and Weeks 25 and 49
Population: Safety Analysis Set with available data at each time point
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Enzalutamide | Percent Change From Baseline in Follicle-Stimulating Hormone (FSH) | Week 25 | 46.99 Percent Change | Standard Deviation 46.389 |
| Enzalutamide | Percent Change From Baseline in Follicle-Stimulating Hormone (FSH) | Week 49 | 62.18 Percent Change | Standard Deviation 78.371 |
Secondary
Percent Change From Baseline in Free Testosterone
Time frame: Baseline and Weeks 25 and 49
Population: Safety Analysis Set with available data at each time point
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Enzalutamide | Percent Change From Baseline in Free Testosterone | Week 25 | 46.39 Percent Change | Standard Deviation 59.551 |
| Enzalutamide | Percent Change From Baseline in Free Testosterone | Week 49 | 43.74 Percent Change | Standard Deviation 55.721 |
Secondary
Percent Change From Baseline in Luteinizing Hormone (LH)
Time frame: Baseline and Weeks 25 and 49
Population: Safety Analysis Set with available data at each time point
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Enzalutamide | Percent Change From Baseline in Luteinizing Hormone (LH) | Week 25 | 184.66 Percent Change | Standard Deviation 120.683 |
| Enzalutamide | Percent Change From Baseline in Luteinizing Hormone (LH) | Week 49 | 215.18 Percent Change | Standard Deviation 163.732 |
Secondary
Percent Change From Baseline in Prolactin
Time frame: Baseline and Weeks 25 and 49
Population: Safety Analysis Set with available data at each time point
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Enzalutamide | Percent Change From Baseline in Prolactin | Week 25 | 16.79 Percent Change | Standard Deviation 45.497 |
| Enzalutamide | Percent Change From Baseline in Prolactin | Week 49 | 9.64 Percent Change | Standard Deviation 30.003 |
Secondary
Percent Change From Baseline in PSA
Time frame: Baseline and Weeks 25, 49, 97, 169 and Week 265 (End of Study)
Population: Safety Analysis Set with available data at each time point
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Enzalutamide | Percent Change From Baseline in PSA | Week 25 | -97.82 Percent Change | Standard Deviation 5.744 |
| Enzalutamide | Percent Change From Baseline in PSA | Week 49 | -98.96 Percent Change | Standard Deviation 2.767 |
| Enzalutamide | Percent Change From Baseline in PSA | Week 97 | -99.44 Percent Change | Standard Deviation 1.114 |
| Enzalutamide | Percent Change From Baseline in PSA | Week 169 | -91.74 Percent Change | Standard Deviation 27.808 |
| Enzalutamide | Percent Change From Baseline in PSA | Week 265 (End of Study) | -0.70 Percent Change | Standard Deviation 368.253 |
Secondary
Percent Change From Baseline in Sex Hormone-Binding Globulin (SHBG)
Time frame: Baseline and Weeks 25 and 49
Population: Safety Analysis Set with available data at each time point
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Enzalutamide | Percent Change From Baseline in Sex Hormone-Binding Globulin (SHBG) | Week 25 | 100.60 Percent Change | Standard Deviation 49.362 |
| Enzalutamide | Percent Change From Baseline in Sex Hormone-Binding Globulin (SHBG) | Week 49 | 88.45 Percent Change | Standard Deviation 41.911 |
Secondary
Percent Change From Baseline in Total Testosterone
Time frame: Baseline and Weeks 25 and 49
Population: Safety Analysis Set with available data at each time point
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Enzalutamide | Percent Change From Baseline in Total Testosterone | Week 25 | 114.29 Percent Change | Standard Deviation 73.692 |
| Enzalutamide | Percent Change From Baseline in Total Testosterone | Week 49 | 101.73 Percent Change | Standard Deviation 76.07 |
Secondary
Plasma Concentration of Enzalutamide at Pre-dose (Ctrough)
Time frame: Pre-dose at Weeks 2, 3, 4, 5, 9, 13, 21 and 25
Population: Pharmacokinetic Analysis Set (PKAS) (participants who had taken at least 1 dose of study drug and who had at least 1 pharmacokinetic concentration value) with available data at each time point
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Enzalutamide | Plasma Concentration of Enzalutamide at Pre-dose (Ctrough) | Week 2 | 7.225 μg/mL | Standard Deviation 1.805 |
| Enzalutamide | Plasma Concentration of Enzalutamide at Pre-dose (Ctrough) | Week 3 | 10.559 μg/mL | Standard Deviation 2.1967 |
| Enzalutamide | Plasma Concentration of Enzalutamide at Pre-dose (Ctrough) | Week 4 | 11.838 μg/mL | Standard Deviation 2.4605 |
| Enzalutamide | Plasma Concentration of Enzalutamide at Pre-dose (Ctrough) | Week 5 | 12.161 μg/mL | Standard Deviation 2.8496 |
| Enzalutamide | Plasma Concentration of Enzalutamide at Pre-dose (Ctrough) | Week 9 | 11.606 μg/mL | Standard Deviation 3.0084 |
| Enzalutamide | Plasma Concentration of Enzalutamide at Pre-dose (Ctrough) | Week 13 | 11.868 μg/mL | Standard Deviation 2.976 |
| Enzalutamide | Plasma Concentration of Enzalutamide at Pre-dose (Ctrough) | Week 21 | 11.224 μg/mL | Standard Deviation 2.8899 |
| Enzalutamide | Plasma Concentration of Enzalutamide at Pre-dose (Ctrough) | Week 25 | 11.668 μg/mL | Standard Deviation 2.7624 |
Secondary
Plasma Concentration of Enzalutamide Metabolite M2 at Pre-dose (Ctrough)
Time frame: Pre-dose at Weeks 2, 3, 4, 5, 9, 13, 21 and 25
Population: Pharmacokinetic Analysis Set with available data at each time point
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Enzalutamide | Plasma Concentration of Enzalutamide Metabolite M2 at Pre-dose (Ctrough) | Week 25 | 12.146 μg/mL | Standard Deviation 2.5845 |
| Enzalutamide | Plasma Concentration of Enzalutamide Metabolite M2 at Pre-dose (Ctrough) | Week 2 | 2.527 μg/mL | Standard Deviation 1.044 |
| Enzalutamide | Plasma Concentration of Enzalutamide Metabolite M2 at Pre-dose (Ctrough) | Week 3 | 5.344 μg/mL | Standard Deviation 1.7079 |
| Enzalutamide | Plasma Concentration of Enzalutamide Metabolite M2 at Pre-dose (Ctrough) | Week 4 | 8.182 μg/mL | Standard Deviation 2.4366 |
| Enzalutamide | Plasma Concentration of Enzalutamide Metabolite M2 at Pre-dose (Ctrough) | Week 5 | 9.962 μg/mL | Standard Deviation 2.7584 |
| Enzalutamide | Plasma Concentration of Enzalutamide Metabolite M2 at Pre-dose (Ctrough) | Week 9 | 12.128 μg/mL | Standard Deviation 3.1262 |
| Enzalutamide | Plasma Concentration of Enzalutamide Metabolite M2 at Pre-dose (Ctrough) | Week 13 | 12.780 μg/mL | Standard Deviation 3.2564 |
| Enzalutamide | Plasma Concentration of Enzalutamide Metabolite M2 at Pre-dose (Ctrough) | Week 21 | 11.717 μg/mL | Standard Deviation 2.9502 |
Secondary
PSA Doubling Time
PSA doubling time was to be calculated from the slope estimated from a linear regression of the natural log of PSA fitted on time, if the slope was positive. Since the slope was negative for all participants, PSA doubling time could not be calculated.
Time frame: From Baseline to Week 25
Population: Safety Analysis Set with a positive PSA versus time slope
Secondary
Time to PSA ≤ 0.1 ng/ml
Time to PSA ≤ 0.1 ng/ml is defined as the time interval from the first study drug dose to the first date a decline in PSA to a result of 0.1 ng/ml or below was recorded. Time to PSA ≤ 0.1 ng/ml was estimated using the Kaplan-Meier method.
Time frame: From first dose until the EOS date of 27-Apr-2017; median duration of treatment of 1666.0 days (range of 52-2052)
Population: Safety Analysis Set
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Enzalutamide | Time to PSA ≤ 0.1 ng/ml | 168 Days |
Secondary
Time to PSA ≤ 4 ng/ml
Time to PSA ≤ 4 ng/ml is defined as the time interval from the first study drug dose to the first date a decline in PSA to a result of 4 ng/ml or below was recorded. Time to PSA ≤ 4 ng/ml was estimated using the Kaplan-Meier method.
Time frame: From first dose until the EOS date of 27-Apr-2017; median duration of treatment of 1666.0 days (range of 52-2052)
Population: Safety Analysis Set
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Enzalutamide | Time to PSA ≤ 4 ng/ml | 29 Days |
Secondary
Time to PSA Decline ≥ 90%
Time to PSA decline ≥ 90% is defined as the time interval from the first study drug dose to the first date a decline from Baseline in PSA level of 90% or greater was recorded. Time to PSA decline ≥ 90% was estimated using the Kaplan-Meier method.
Time frame: From first dose until the EOS date of 27-Apr-2017; median duration of treatment of 1666.0 days (range of 52-2052)
Population: Safety Analysis Set
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Enzalutamide | Time to PSA Decline ≥ 90% | 55 Days |
Secondary
Time to PSA Progression
Time to PSA progression is defined as the time interval from the first study drug dose to the first date of PSA progression. PSA progression is defined as a ≥ 25% increase in PSA with an absolute increase of ≥ 2 ng/mL above the nadir unless the PSA next measurement(s), if available, does not confirm the PSA progression.
Time frame: From first dose until the EOS date of 27-Apr-2017; median duration of treatment of 1666.0 days (range of 52-2052)
Population: Safety Analysis Set
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Enzalutamide | Time to PSA Progression | NA Days |
Secondary
Time to PSA Response
Time to PSA response (PSA decline ≥ 80% from Baseline) is defined as the time interval from the first study drug dose to the first date a decline from Baseline in PSA level of 80% or greater was recorded. Time to response was estimated using the Kaplan-Meier method.
Time frame: From first dose until the EOS date of 27-Apr-2017; median duration of treatment of 1666.0 days (range of 52-2052)
Population: Safety Analysis Set
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Enzalutamide | Time to PSA Response | 29 Days |