Hormone Refractory Prostate Cancer, Prostate Cancer
Conditions
Keywords
Prostate, Cancer, Hormone, Refractory, Castration
Brief summary
This is a multi-center open-label dose-escalation study of a novel compound (MDV3100) to treat patients with castration-resistant (hormone-refractory) prostate cancer. Additional patients will be enrolled in expanded cohorts at doses determined to be tolerable. Patients who tolerate the drug and do not progress will be allowed to continue to look for PSA response.
Detailed description
This is a Phase 1, open-label, uncontrolled, dose-escalation study with dose-expansion at doses determined to be tolerated. Patients who tolerate the drug and do not progress will be allowed to continue treatment. The study endpoints are safety and tolerability and pharmacokinetics. PSA values will also be collected to look for PSA response.
Interventions
DRUGMDV3100
MDV3100 daily until progression or dose-limiting toxicity
Sponsors
Astellas Pharma Inc
Medivation LLC, a wholly owned subsidiary of Pfizer Inc.
Pfizer
Study design
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
MALE
Healthy volunteers
No
Inclusion criteria
1. Histologically or cytologically confirmed adenocarcinoma of the prostate; 2. Ongoing androgen deprivation therapy with a gonadotropin releasing hormone (GnRH) analogue or inhibitor, or orchiectomy (i.e., surgical or medical castration); 3. Progressive disease after medical or surgical castration,
Exclusion criteria
1\. Metastases in the brain or active epidural disease. (Note: patients with treated epidural disease are allowed);
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Maximum Tolerated Dose (MTD) of MDV3100: Multiple Dose Period | Baseline up to first 35 days of the study treatment in multiple dose period | Tolerability was defined as if less than (\<) 4/12 in participants with no prior exposure to MDV3100 (chemo-naive) and \< 4/12 prior chemotherapy participants experienced a DLT within the first 35 days of the multiple dose period. For doses higher than 360 mg/day, tolerability was defined if \<8/24 participants previously treated with chemotherapy experience a DLT within the first 35 days of the multiple dose period. MTD was defined as a dose below the intolerable dose. |
| Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (SAEs) | Baseline up to 30 days after last dose of study treatment (approximately maximum of 129 months) | An adverse events (AE) was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. An SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. A treatment emergent AE was defined as an event that emerged during the treatment period that was absent before treatment, or worsened during the treatment period relative to the pretreatment state. AEs included both SAEs and non-SAEs. |
| Percentage of Participants With at Least 1 Dose-limiting Toxicity (DLT): Multiple Dose Period | Baseline up to first 35 days of the study treatment in multiple dose period | DLT was defined as a national cancer institute's common toxicity criteria for adverse events (NCI-CTCAE) version 3.0 grade 3 or greater toxicity regardless of perceived causality that is not improved by the use of adequate/maximal medical intervention. Grade 3 alopecia, fever without neutropenia, nausea, vomiting, fatigue, and self-limited or medically controllable adverse events were not considered as DLTs. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Area Under the Plasma Concentration Versus Time Curve From Time Zero to Infinity (AUC[0-inf]) of MDV3100: Single Dose Period | Pre-dose, 0.5, 1, 2, 4, 6, 24, 48, 72, 96, 120 hours post dose on Day 1 of Single Dose Period | — |
| Time to Reach Maximum Plasma Concentration (Tmax) of MDV3100: Single Dose Period | Pre-dose, 0.5, 1, 2, 4, 6, 24, 48, 72, 96, 120 hours post dose on Day 1 of Single Dose Period | — |
| Maximum Plasma Concentration (Cmax) of MDV3100: Single Dose Period | Pre-dose, 0.5, 1, 2, 4, 6, 24, 48, 72, 96, 120 hours post dose on Day 1 of Single Dose Period | — |
| Apparent Terminal Elimination Half-Life (T1/2) of MDV3100: Single Dose Period | Pre-dose, 0.5, 1, 2, 4, 6, 24, 48, 72, 96, 120 hours post dose on Day 1 of Single Dose Period | T 1/2 is the time measured for the plasma concentration of MDV3100 to decrease by one half. |
| Apparent Volume of Distribution (V/F) of MDV3100: Single Dose Period | Pre-dose, 0.5, 1, 2, 4, 6, 24, 48, 72, 96, 120 hours post dose on Day 1 of Single Dose Period | Volume of distribution is defined as the theoretical volume in which the total amount of MDV3100 would need to be uniformly distributed to produce the desired plasma concentration of MDV3100. Apparent volume of distribution after oral dose (V/F) is influenced by the fraction absorbed. |
| Area Under the Plasma Concentration Versus Time Curve From Time Zero to 24 Hours Post Dose (AUC[0-24]) of MDV3100: Multiple Dose Period | Pre-dose, 0.5, 1, 2, 24 hours post dose on Day 84 of Multiple Dose Period | — |
| Time to Reach Maximum Plasma Concentration (Tmax) of MDV3100: Multiple Dose Period | Pre-dose, 0.5, 1, 2, 24 hours post dose on Day 84 of Multiple Dose Period | — |
| Maximum Plasma Concentration (Cmax) of MDV3100: Multiple Dose Period | Pre-dose, 0.5, 1, 2, 24 hours post dose on Day 84 of Multiple Dose Period | — |
| Minimum Observed Plasma Concentration (Cmin) of MDV3100: Multiple Dose Period | Pre-dose on Day 1 of Multiple Dose Period | — |
| Apparent Total Plasma Clearance (CL/F) of MDV3100: Multiple Dose Period | Pre-dose, 0.5, 1, 2, 24 hours post dose on Day 84 of Multiple Dose Period | Clearance of a MDV3100 is a measure of the rate at which a MDV3100 is metabolized or eliminated by normal biological processes. Clearance obtained after oral dose (apparent oral clearance) is influenced by the fraction of the dose absorbed. |
| Apparent Total Plasma Clearance (CL/F) of MDV3100: Single Dose Period | Pre-dose, 0.5, 1, 2, 4, 6, 24, 48, 72, 96, 120 hours post dose on Day 1 of Single Dose Period | Clearance of a MDV3100 is a measure of the rate at which a MDV3100 is metabolized or eliminated by normal biological processes. Clearance obtained after oral dose (apparent oral clearance) is influenced by the fraction of the dose absorbed. |
| Area Under the Plasma Concentration Versus Time Curve From Time Zero to 24 Hours Post Dose (AUC[0-24]) of MDV3100: Single Dose Period | Pre-dose, 0.5, 1, 2, 4, 6, 24 hours post dose on Day 1 of Single Dose Period | — |
| Area Under the Plasma Concentration Versus Time Curve From Time Zero to the Last Measurable Concentration (AUC[0-t]) of MDV3100: Single Dose Period | Pre-dose, 0.5, 1, 2, 4, 6, 24, 48, 72, 96, 120 hours postdose on Day 1 of Single Dose Period | — |
Other
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With Prostate Specific Antigen (PSA) Response at Day 84: Multiple Dose Period | Baseline, Day 84 | Prostate-specific antigen is a glycoprotein considered as a biomarker for the response to therapy in men with prostate cancer. A 50 percent (%) decline in PSA from baseline to the PSA level at Day 84 was considered as a PSA response. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| MDV3100 (Enzalutamide) 30 mg/Day Participants received 30 mg of Enzalutamide on Day 1 and were followed for 6 days in single dose period and continued to receive the same dose in multiple dose period for 84 days. | 3 |
| MDV3100 (Enzalutamide) 60 mg /Day Participants received 60 mg of Enzalutamide on Day 1 and were followed for 6 days in single dose period and continued to receive the same dose in multiple dose period for 84 days. | 27 |
| MDV3100 (Enzalutamide) 150/160 mg/Day Participants who received 150 mg of Enzalutamide on Day 1 and were followed for 6 days in single dose period. This dose was then changed subsequently to 160 mg/day according to Protocol amendment. Participants continued to receive the same dose in multiple dose period for 84 days. | 28 |
| MDV3100 (Enzalutamide) 240 mg /Day Participants received 240 mg of Enzalutamide on Day 1 and were followed for 6 days in single dose period and continued to receive the same dose in multiple dose period for 84 days. | 29 |
| MDV3100 (Enzalutamide) 360 mg /Day Participants received 360 mg of Enzalutamide on Day 1 and were followed for 6 days in single dose period and continued to receive the same dose in multiple dose period for 84 days. | 28 |
| MDV3100 (Enzalutamide) 480 mg /Day Participants received 480 mg of Enzalutamide on Day 1 and were followed for 6 days in single dose period and continued to receive the same dose in multiple dose period for 84 days. | 22 |
| MDV3100 (Enzalutamide) 600 mg /Day Participants received 600 mg of Enzalutamide on Day 1 and were followed for 6 days in single dose period and continued to receive the same dose in multiple dose period for 84 days. | 3 |
| Total | 140 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Multiple Dose Period: 12 Weeks | Adverse Event | 1 | 8 |
| Multiple Dose Period: 12 Weeks | Clinical Disease Progression | 1 | 3 |
| Multiple Dose Period: 12 Weeks | Other | 1 | 1 |
| Multiple Dose Period: 12 Weeks | PSA Disease Progression | 3 | 6 |
| Multiple Dose Period: 12 Weeks | Radiologic Disease Progression | 8 | 11 |
| Multiple Dose Period: 12 Weeks | Withdrawal by Subject | 1 | 3 |
Baseline characteristics
| Characteristic | MDV3100 (Enzalutamide) 30 mg/Day | MDV3100 (Enzalutamide) 60 mg /Day | MDV3100 (Enzalutamide) 150/160 mg/Day | MDV3100 (Enzalutamide) 240 mg /Day | MDV3100 (Enzalutamide) 360 mg /Day | MDV3100 (Enzalutamide) 480 mg /Day | MDV3100 (Enzalutamide) 600 mg /Day | Total |
|---|---|---|---|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 2 Participants | 12 Participants | 18 Participants | 21 Participants | 18 Participants | 15 Participants | 0 Participants | 86 Participants |
| Age, Categorical Between 18 and 65 years | 1 Participants | 15 Participants | 10 Participants | 8 Participants | 10 Participants | 7 Participants | 3 Participants | 54 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 3 Participants | 0 Participants | 1 Participants | 1 Participants | 0 Participants | 0 Participants | 5 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 3 Participants | 24 Participants | 28 Participants | 27 Participants | 27 Participants | 22 Participants | 3 Participants | 134 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 1 Participants | 0 Participants | 1 Participants | 2 Participants | 0 Participants | 0 Participants | 4 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 3 Participants | 26 Participants | 28 Participants | 28 Participants | 25 Participants | 22 Participants | 3 Participants | 135 Participants |
| Sex: Female, Male Female | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Male | 3 Participants | 27 Participants | 28 Participants | 29 Participants | 28 Participants | 22 Participants | 3 Participants | 140 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk | EG006 affected / at risk | EG007 affected / at risk |
|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 3 / 3 | 27 / 27 | 27 / 28 | 29 / 29 | 28 / 28 | 21 / 22 | 3 / 3 | 17 / 18 |
| serious Total, serious adverse events | 0 / 3 | 6 / 27 | 14 / 28 | 8 / 29 | 6 / 28 | 1 / 22 | 1 / 3 | 10 / 18 |
Outcome results
Primary
Maximum Tolerated Dose (MTD) of MDV3100: Multiple Dose Period
Tolerability was defined as if less than (\<) 4/12 in participants with no prior exposure to MDV3100 (chemo-naive) and \< 4/12 prior chemotherapy participants experienced a DLT within the first 35 days of the multiple dose period. For doses higher than 360 mg/day, tolerability was defined if \<8/24 participants previously treated with chemotherapy experience a DLT within the first 35 days of the multiple dose period. MTD was defined as a dose below the intolerable dose.
Time frame: Baseline up to first 35 days of the study treatment in multiple dose period
Population: Safety population included all enrolled participants who received at least 1 dose of study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| MDV3100 (Enzalutamide) 30 mg/Day | Maximum Tolerated Dose (MTD) of MDV3100: Multiple Dose Period | 240 milligrams per day |
Primary
Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (SAEs)
An adverse events (AE) was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. An SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. A treatment emergent AE was defined as an event that emerged during the treatment period that was absent before treatment, or worsened during the treatment period relative to the pretreatment state. AEs included both SAEs and non-SAEs.
Time frame: Baseline up to 30 days after last dose of study treatment (approximately maximum of 129 months)
Population: Safety population included all enrolled participants who received at least 1 dose of study drug.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| MDV3100 (Enzalutamide) 30 mg/Day | Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (SAEs) | 0 Participants |
| MDV3100 (Enzalutamide) 60 mg /Day | Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (SAEs) | 6 Participants |
| MDV3100 (Enzalutamide) 150/160 mg/Day | Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (SAEs) | 14 Participants |
| MDV3100 (Enzalutamide) 240 mg /Day | Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (SAEs) | 8 Participants |
| MDV3100 (Enzalutamide) 360 mg /Day | Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (SAEs) | 6 Participants |
| MDV3100 (Enzalutamide) 480 mg /Day | Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (SAEs) | 1 Participants |
| MDV3100 (Enzalutamide) 600 mg /Day | Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (SAEs) | 1 Participants |
| MDV3100 (Enzalutamide) 160 mg /Day: Long Term Dosing Period | Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (SAEs) | 10 Participants |
Primary
Percentage of Participants With at Least 1 Dose-limiting Toxicity (DLT): Multiple Dose Period
DLT was defined as a national cancer institute's common toxicity criteria for adverse events (NCI-CTCAE) version 3.0 grade 3 or greater toxicity regardless of perceived causality that is not improved by the use of adequate/maximal medical intervention. Grade 3 alopecia, fever without neutropenia, nausea, vomiting, fatigue, and self-limited or medically controllable adverse events were not considered as DLTs.
Time frame: Baseline up to first 35 days of the study treatment in multiple dose period
Population: Safety population included all enrolled participants who received at least 1 dose of study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| MDV3100 (Enzalutamide) 30 mg/Day | Percentage of Participants With at Least 1 Dose-limiting Toxicity (DLT): Multiple Dose Period | 0 percentage of participants |
| MDV3100 (Enzalutamide) 60 mg /Day | Percentage of Participants With at Least 1 Dose-limiting Toxicity (DLT): Multiple Dose Period | 0 percentage of participants |
| MDV3100 (Enzalutamide) 150/160 mg/Day | Percentage of Participants With at Least 1 Dose-limiting Toxicity (DLT): Multiple Dose Period | 0 percentage of participants |
| MDV3100 (Enzalutamide) 240 mg /Day | Percentage of Participants With at Least 1 Dose-limiting Toxicity (DLT): Multiple Dose Period | 0 percentage of participants |
| MDV3100 (Enzalutamide) 360 mg /Day | Percentage of Participants With at Least 1 Dose-limiting Toxicity (DLT): Multiple Dose Period | 1 percentage of participants |
| MDV3100 (Enzalutamide) 480 mg /Day | Percentage of Participants With at Least 1 Dose-limiting Toxicity (DLT): Multiple Dose Period | 1 percentage of participants |
| MDV3100 (Enzalutamide) 600 mg /Day | Percentage of Participants With at Least 1 Dose-limiting Toxicity (DLT): Multiple Dose Period | 2 percentage of participants |
Secondary
Apparent Terminal Elimination Half-Life (T1/2) of MDV3100: Single Dose Period
T 1/2 is the time measured for the plasma concentration of MDV3100 to decrease by one half.
Time frame: Pre-dose, 0.5, 1, 2, 4, 6, 24, 48, 72, 96, 120 hours post dose on Day 1 of Single Dose Period
Population: PK evaluable population: all participants who received study drug and had sufficient PK samples for calculation of at least 1 MDV3100 PK parameter. Here, Overall Number of Participants Analyzed signifies participants who were evaluable for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| MDV3100 (Enzalutamide) 30 mg/Day | Apparent Terminal Elimination Half-Life (T1/2) of MDV3100: Single Dose Period | 164.9 hours | Standard Deviation 69.8 |
| MDV3100 (Enzalutamide) 60 mg /Day | Apparent Terminal Elimination Half-Life (T1/2) of MDV3100: Single Dose Period | 100.5 hours | Standard Deviation 30.9 |
| MDV3100 (Enzalutamide) 150/160 mg/Day | Apparent Terminal Elimination Half-Life (T1/2) of MDV3100: Single Dose Period | 143.7 hours | Standard Deviation 34.8 |
| MDV3100 (Enzalutamide) 240 mg /Day | Apparent Terminal Elimination Half-Life (T1/2) of MDV3100: Single Dose Period | 138.9 hours | Standard Deviation 22.6 |
| MDV3100 (Enzalutamide) 360 mg /Day | Apparent Terminal Elimination Half-Life (T1/2) of MDV3100: Single Dose Period | 149.1 hours | Standard Deviation 26.1 |
| MDV3100 (Enzalutamide) 480 mg /Day | Apparent Terminal Elimination Half-Life (T1/2) of MDV3100: Single Dose Period | 144.0 hours | Standard Deviation 68.4 |
| MDV3100 (Enzalutamide) 600 mg /Day | Apparent Terminal Elimination Half-Life (T1/2) of MDV3100: Single Dose Period | 130.4 hours | Standard Deviation 37.7 |
Secondary
Apparent Total Plasma Clearance (CL/F) of MDV3100: Multiple Dose Period
Clearance of a MDV3100 is a measure of the rate at which a MDV3100 is metabolized or eliminated by normal biological processes. Clearance obtained after oral dose (apparent oral clearance) is influenced by the fraction of the dose absorbed.
Time frame: Pre-dose, 0.5, 1, 2, 24 hours post dose on Day 84 of Multiple Dose Period
Population: PK evaluable population: all participants who received study drug and had sufficient PK samples for calculation of at least 1 MDV3100 PK parameter. Here, Overall Number of Participants Analyzed signifies participants who were evaluable for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| MDV3100 (Enzalutamide) 30 mg/Day | Apparent Total Plasma Clearance (CL/F) of MDV3100: Multiple Dose Period | 0.507 liters per hour | Standard Deviation 0.111 |
| MDV3100 (Enzalutamide) 60 mg /Day | Apparent Total Plasma Clearance (CL/F) of MDV3100: Multiple Dose Period | 0.580 liters per hour | Standard Deviation 0.245 |
| MDV3100 (Enzalutamide) 150/160 mg/Day | Apparent Total Plasma Clearance (CL/F) of MDV3100: Multiple Dose Period | 0.530 liters per hour | Standard Deviation 0.149 |
| MDV3100 (Enzalutamide) 240 mg /Day | Apparent Total Plasma Clearance (CL/F) of MDV3100: Multiple Dose Period | 0.628 liters per hour | Standard Deviation 0.179 |
| MDV3100 (Enzalutamide) 360 mg /Day | Apparent Total Plasma Clearance (CL/F) of MDV3100: Multiple Dose Period | 0.755 liters per hour | Standard Deviation 0.176 |
| MDV3100 (Enzalutamide) 480 mg /Day | Apparent Total Plasma Clearance (CL/F) of MDV3100: Multiple Dose Period | 1.037 liters per hour | — |
Secondary
Apparent Total Plasma Clearance (CL/F) of MDV3100: Single Dose Period
Clearance of a MDV3100 is a measure of the rate at which a MDV3100 is metabolized or eliminated by normal biological processes. Clearance obtained after oral dose (apparent oral clearance) is influenced by the fraction of the dose absorbed.
Time frame: Pre-dose, 0.5, 1, 2, 4, 6, 24, 48, 72, 96, 120 hours post dose on Day 1 of Single Dose Period
Population: PK evaluable population: all participants who received study drug and had sufficient PK samples for calculation of at least 1 MDV3100 PK parameter. Here, Overall Number of Participants Analyzed signifies participants who were evaluable for this outcome measure.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| MDV3100 (Enzalutamide) 30 mg/Day | Apparent Total Plasma Clearance (CL/F) of MDV3100: Single Dose Period | 0.585 liters per hour | Geometric Coefficient of Variation 39.81 |
| MDV3100 (Enzalutamide) 60 mg /Day | Apparent Total Plasma Clearance (CL/F) of MDV3100: Single Dose Period | 0.647 liters per hour | Geometric Coefficient of Variation 18.988 |
| MDV3100 (Enzalutamide) 150/160 mg/Day | Apparent Total Plasma Clearance (CL/F) of MDV3100: Single Dose Period | 0.453 liters per hour | Geometric Coefficient of Variation 14.583 |
| MDV3100 (Enzalutamide) 240 mg /Day | Apparent Total Plasma Clearance (CL/F) of MDV3100: Single Dose Period | 0.523 liters per hour | Geometric Coefficient of Variation 32.679 |
| MDV3100 (Enzalutamide) 360 mg /Day | Apparent Total Plasma Clearance (CL/F) of MDV3100: Single Dose Period | 0.509 liters per hour | Geometric Coefficient of Variation 17.711 |
| MDV3100 (Enzalutamide) 480 mg /Day | Apparent Total Plasma Clearance (CL/F) of MDV3100: Single Dose Period | 0.504 liters per hour | Geometric Coefficient of Variation 42.437 |
| MDV3100 (Enzalutamide) 600 mg /Day | Apparent Total Plasma Clearance (CL/F) of MDV3100: Single Dose Period | 0.694 liters per hour | Geometric Coefficient of Variation 34.625 |
Secondary
Apparent Volume of Distribution (V/F) of MDV3100: Single Dose Period
Volume of distribution is defined as the theoretical volume in which the total amount of MDV3100 would need to be uniformly distributed to produce the desired plasma concentration of MDV3100. Apparent volume of distribution after oral dose (V/F) is influenced by the fraction absorbed.
Time frame: Pre-dose, 0.5, 1, 2, 4, 6, 24, 48, 72, 96, 120 hours post dose on Day 1 of Single Dose Period
Population: PK evaluable population: all participants who received study drug and had sufficient PK samples for calculation of at least 1 MDV3100 PK parameter. Here, Overall Number of Participants Analyzed signifies participants who were evaluable for this outcome measure.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| MDV3100 (Enzalutamide) 30 mg/Day | Apparent Volume of Distribution (V/F) of MDV3100: Single Dose Period | 131.7 liters | Geometric Coefficient of Variation 15.6 |
| MDV3100 (Enzalutamide) 60 mg /Day | Apparent Volume of Distribution (V/F) of MDV3100: Single Dose Period | 90.5 liters | Geometric Coefficient of Variation 16 |
| MDV3100 (Enzalutamide) 150/160 mg/Day | Apparent Volume of Distribution (V/F) of MDV3100: Single Dose Period | 91.89 liters | Geometric Coefficient of Variation 13.31 |
| MDV3100 (Enzalutamide) 240 mg /Day | Apparent Volume of Distribution (V/F) of MDV3100: Single Dose Period | 103.8 liters | Geometric Coefficient of Variation 48.5 |
| MDV3100 (Enzalutamide) 360 mg /Day | Apparent Volume of Distribution (V/F) of MDV3100: Single Dose Period | 108.2 liters | Geometric Coefficient of Variation 15.8 |
| MDV3100 (Enzalutamide) 480 mg /Day | Apparent Volume of Distribution (V/F) of MDV3100: Single Dose Period | 97.4 liters | Geometric Coefficient of Variation 30.7 |
| MDV3100 (Enzalutamide) 600 mg /Day | Apparent Volume of Distribution (V/F) of MDV3100: Single Dose Period | 126.4 liters | Geometric Coefficient of Variation 8.8 |
Secondary
Area Under the Plasma Concentration Versus Time Curve From Time Zero to 24 Hours Post Dose (AUC[0-24]) of MDV3100: Multiple Dose Period
Time frame: Pre-dose, 0.5, 1, 2, 24 hours post dose on Day 84 of Multiple Dose Period
Population: PK evaluable population: all participants who received study drug and had sufficient PK samples for calculation of at least 1 MDV3100 PK parameter. Here, Overall Number of Participants Analyzed signifies participants who were evaluable for this outcome measure.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| MDV3100 (Enzalutamide) 30 mg/Day | Area Under the Plasma Concentration Versus Time Curve From Time Zero to 24 Hours Post Dose (AUC[0-24]) of MDV3100: Multiple Dose Period | 60.0 microgram*hour per milliliter | Geometric Coefficient of Variation 21 |
| MDV3100 (Enzalutamide) 60 mg /Day | Area Under the Plasma Concentration Versus Time Curve From Time Zero to 24 Hours Post Dose (AUC[0-24]) of MDV3100: Multiple Dose Period | 109.8 microgram*hour per milliliter | Geometric Coefficient of Variation 34.4 |
| MDV3100 (Enzalutamide) 150/160 mg/Day | Area Under the Plasma Concentration Versus Time Curve From Time Zero to 24 Hours Post Dose (AUC[0-24]) of MDV3100: Multiple Dose Period | 291.7 microgram*hour per milliliter | Geometric Coefficient of Variation 24.9 |
| MDV3100 (Enzalutamide) 240 mg /Day | Area Under the Plasma Concentration Versus Time Curve From Time Zero to 24 Hours Post Dose (AUC[0-24]) of MDV3100: Multiple Dose Period | 395.7 microgram*hour per milliliter | Geometric Coefficient of Variation 27.4 |
| MDV3100 (Enzalutamide) 360 mg /Day | Area Under the Plasma Concentration Versus Time Curve From Time Zero to 24 Hours Post Dose (AUC[0-24]) of MDV3100: Multiple Dose Period | 488.9 microgram*hour per milliliter | Geometric Coefficient of Variation 23.9 |
| MDV3100 (Enzalutamide) 480 mg /Day | Area Under the Plasma Concentration Versus Time Curve From Time Zero to 24 Hours Post Dose (AUC[0-24]) of MDV3100: Multiple Dose Period | 463.1 microgram*hour per milliliter | — |
Secondary
Area Under the Plasma Concentration Versus Time Curve From Time Zero to 24 Hours Post Dose (AUC[0-24]) of MDV3100: Single Dose Period
Time frame: Pre-dose, 0.5, 1, 2, 4, 6, 24 hours post dose on Day 1 of Single Dose Period
Population: Pharmacokinetic (PK) evaluable population: all participants who received study drug and had sufficient PK samples for calculation of at least 1 MDV3100 PK parameter. Here, Overall Number of Participants Analyzed signifies participants who were evaluable for this outcome measure.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| MDV3100 (Enzalutamide) 30 mg/Day | Area Under the Plasma Concentration Versus Time Curve From Time Zero to 24 Hours Post Dose (AUC[0-24]) of MDV3100: Single Dose Period | 5.43 microgram*hour per milliliter | Geometric Coefficient of Variation 11.8 |
| MDV3100 (Enzalutamide) 60 mg /Day | Area Under the Plasma Concentration Versus Time Curve From Time Zero to 24 Hours Post Dose (AUC[0-24]) of MDV3100: Single Dose Period | 15.64 microgram*hour per milliliter | Geometric Coefficient of Variation 3.5 |
| MDV3100 (Enzalutamide) 150/160 mg/Day | Area Under the Plasma Concentration Versus Time Curve From Time Zero to 24 Hours Post Dose (AUC[0-24]) of MDV3100: Single Dose Period | 38.21 microgram*hour per milliliter | Geometric Coefficient of Variation 23.64 |
| MDV3100 (Enzalutamide) 240 mg /Day | Area Under the Plasma Concentration Versus Time Curve From Time Zero to 24 Hours Post Dose (AUC[0-24]) of MDV3100: Single Dose Period | 58.39 microgram*hour per milliliter | Geometric Coefficient of Variation 47.64 |
| MDV3100 (Enzalutamide) 360 mg /Day | Area Under the Plasma Concentration Versus Time Curve From Time Zero to 24 Hours Post Dose (AUC[0-24]) of MDV3100: Single Dose Period | 79.26 microgram*hour per milliliter | Geometric Coefficient of Variation 19.29 |
Secondary
Area Under the Plasma Concentration Versus Time Curve From Time Zero to Infinity (AUC[0-inf]) of MDV3100: Single Dose Period
Time frame: Pre-dose, 0.5, 1, 2, 4, 6, 24, 48, 72, 96, 120 hours post dose on Day 1 of Single Dose Period
Population: PK evaluable population: all participants who received study drug and had sufficient PK samples for calculation of at least 1 MDV3100 PK parameter. Here, Overall Number of Participants Analyzed signifies participants who were evaluable for this outcome measure.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| MDV3100 (Enzalutamide) 30 mg/Day | Area Under the Plasma Concentration Versus Time Curve From Time Zero to Infinity (AUC[0-inf]) of MDV3100: Single Dose Period | 51.3 microgram*hour per milliliter | Geometric Coefficient of Variation 39.8 |
| MDV3100 (Enzalutamide) 60 mg /Day | Area Under the Plasma Concentration Versus Time Curve From Time Zero to Infinity (AUC[0-inf]) of MDV3100: Single Dose Period | 92.7 microgram*hour per milliliter | Geometric Coefficient of Variation 19 |
| MDV3100 (Enzalutamide) 150/160 mg/Day | Area Under the Plasma Concentration Versus Time Curve From Time Zero to Infinity (AUC[0-inf]) of MDV3100: Single Dose Period | 331.5 microgram*hour per milliliter | Geometric Coefficient of Variation 14.6 |
| MDV3100 (Enzalutamide) 240 mg /Day | Area Under the Plasma Concentration Versus Time Curve From Time Zero to Infinity (AUC[0-inf]) of MDV3100: Single Dose Period | 459.2 microgram*hour per milliliter | Geometric Coefficient of Variation 32.7 |
| MDV3100 (Enzalutamide) 360 mg /Day | Area Under the Plasma Concentration Versus Time Curve From Time Zero to Infinity (AUC[0-inf]) of MDV3100: Single Dose Period | 706.7 microgram*hour per milliliter | Geometric Coefficient of Variation 17.7 |
| MDV3100 (Enzalutamide) 480 mg /Day | Area Under the Plasma Concentration Versus Time Curve From Time Zero to Infinity (AUC[0-inf]) of MDV3100: Single Dose Period | 952.7 microgram*hour per milliliter | Geometric Coefficient of Variation 42.4 |
| MDV3100 (Enzalutamide) 600 mg /Day | Area Under the Plasma Concentration Versus Time Curve From Time Zero to Infinity (AUC[0-inf]) of MDV3100: Single Dose Period | 865.0 microgram*hour per milliliter | Geometric Coefficient of Variation 34.6 |
Secondary
Area Under the Plasma Concentration Versus Time Curve From Time Zero to the Last Measurable Concentration (AUC[0-t]) of MDV3100: Single Dose Period
Time frame: Pre-dose, 0.5, 1, 2, 4, 6, 24, 48, 72, 96, 120 hours postdose on Day 1 of Single Dose Period
Population: PK evaluable population: all participants who received study drug and had sufficient PK samples for calculation of at least 1 MDV3100 PK parameter. Here, Overall Number of Participants Analyzed signifies participants who were evaluable for this outcome measure.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| MDV3100 (Enzalutamide) 30 mg/Day | Area Under the Plasma Concentration Versus Time Curve From Time Zero to the Last Measurable Concentration (AUC[0-t]) of MDV3100: Single Dose Period | 21.2 microgram*hour per milliliter | Geometric Coefficient of Variation 14.2 |
| MDV3100 (Enzalutamide) 60 mg /Day | Area Under the Plasma Concentration Versus Time Curve From Time Zero to the Last Measurable Concentration (AUC[0-t]) of MDV3100: Single Dose Period | 53.1 microgram*hour per milliliter | Geometric Coefficient of Variation 4.1 |
| MDV3100 (Enzalutamide) 150/160 mg/Day | Area Under the Plasma Concentration Versus Time Curve From Time Zero to the Last Measurable Concentration (AUC[0-t]) of MDV3100: Single Dose Period | 145.3 microgram*hour per milliliter | Geometric Coefficient of Variation 10 |
| MDV3100 (Enzalutamide) 240 mg /Day | Area Under the Plasma Concentration Versus Time Curve From Time Zero to the Last Measurable Concentration (AUC[0-t]) of MDV3100: Single Dose Period | 208.5 microgram*hour per milliliter | Geometric Coefficient of Variation 44 |
| MDV3100 (Enzalutamide) 360 mg /Day | Area Under the Plasma Concentration Versus Time Curve From Time Zero to the Last Measurable Concentration (AUC[0-t]) of MDV3100: Single Dose Period | 320.2 microgram*hour per milliliter | Geometric Coefficient of Variation 12.9 |
| MDV3100 (Enzalutamide) 480 mg /Day | Area Under the Plasma Concentration Versus Time Curve From Time Zero to the Last Measurable Concentration (AUC[0-t]) of MDV3100: Single Dose Period | 363.4 microgram*hour per milliliter | Geometric Coefficient of Variation 38.7 |
| MDV3100 (Enzalutamide) 600 mg /Day | Area Under the Plasma Concentration Versus Time Curve From Time Zero to the Last Measurable Concentration (AUC[0-t]) of MDV3100: Single Dose Period | 391.9 microgram*hour per milliliter | Geometric Coefficient of Variation 14 |
Secondary
Maximum Plasma Concentration (Cmax) of MDV3100: Multiple Dose Period
Time frame: Pre-dose, 0.5, 1, 2, 24 hours post dose on Day 84 of Multiple Dose Period
Population: PK evaluable population: all participants who received study drug and had sufficient PK samples for calculation of at least 1 MDV3100 PK parameter. Here, Overall Number of Participants Analyzed signifies participants who were evaluable for this outcome measure.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| MDV3100 (Enzalutamide) 30 mg/Day | Maximum Plasma Concentration (Cmax) of MDV3100: Multiple Dose Period | 2.76 microgram per milliliter | Geometric Coefficient of Variation 21.1 |
| MDV3100 (Enzalutamide) 60 mg /Day | Maximum Plasma Concentration (Cmax) of MDV3100: Multiple Dose Period | 5.49 microgram per milliliter | Geometric Coefficient of Variation 28.88 |
| MDV3100 (Enzalutamide) 150/160 mg/Day | Maximum Plasma Concentration (Cmax) of MDV3100: Multiple Dose Period | 14.07 microgram per milliliter | Geometric Coefficient of Variation 25.36 |
| MDV3100 (Enzalutamide) 240 mg /Day | Maximum Plasma Concentration (Cmax) of MDV3100: Multiple Dose Period | 18.91 microgram per milliliter | Geometric Coefficient of Variation 26.57 |
| MDV3100 (Enzalutamide) 360 mg /Day | Maximum Plasma Concentration (Cmax) of MDV3100: Multiple Dose Period | 24.57 microgram per milliliter | Geometric Coefficient of Variation 21 |
| MDV3100 (Enzalutamide) 480 mg /Day | Maximum Plasma Concentration (Cmax) of MDV3100: Multiple Dose Period | 27.90 microgram per milliliter | — |
Secondary
Maximum Plasma Concentration (Cmax) of MDV3100: Single Dose Period
Time frame: Pre-dose, 0.5, 1, 2, 4, 6, 24, 48, 72, 96, 120 hours post dose on Day 1 of Single Dose Period
Population: PK evaluable population: all participants who received study drug and had sufficient PK samples for calculation of at least 1 MDV3100 PK parameter.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| MDV3100 (Enzalutamide) 30 mg/Day | Maximum Plasma Concentration (Cmax) of MDV3100: Single Dose Period | 0.43 microgram per milliliter | Geometric Coefficient of Variation 15.97 |
| MDV3100 (Enzalutamide) 60 mg /Day | Maximum Plasma Concentration (Cmax) of MDV3100: Single Dose Period | 1.65 microgram per milliliter | Geometric Coefficient of Variation 28.77 |
| MDV3100 (Enzalutamide) 150/160 mg/Day | Maximum Plasma Concentration (Cmax) of MDV3100: Single Dose Period | 3.30 microgram per milliliter | Geometric Coefficient of Variation 22.85 |
| MDV3100 (Enzalutamide) 240 mg /Day | Maximum Plasma Concentration (Cmax) of MDV3100: Single Dose Period | 5.19 microgram per milliliter | Geometric Coefficient of Variation 18.64 |
| MDV3100 (Enzalutamide) 360 mg /Day | Maximum Plasma Concentration (Cmax) of MDV3100: Single Dose Period | 6.68 microgram per milliliter | Geometric Coefficient of Variation 39.61 |
| MDV3100 (Enzalutamide) 480 mg /Day | Maximum Plasma Concentration (Cmax) of MDV3100: Single Dose Period | 5.93 microgram per milliliter | Geometric Coefficient of Variation 66.03 |
| MDV3100 (Enzalutamide) 600 mg /Day | Maximum Plasma Concentration (Cmax) of MDV3100: Single Dose Period | 5.17 microgram per milliliter | Geometric Coefficient of Variation 19.51 |
Secondary
Minimum Observed Plasma Concentration (Cmin) of MDV3100: Multiple Dose Period
Time frame: Pre-dose on Day 1 of Multiple Dose Period
Population: PK evaluable population: all participants who received study drug and had sufficient PK samples for calculation of at least 1 MDV3100 PK parameter. Here, Overall Number of Participants Analyzed signifies participants who were evaluable for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| MDV3100 (Enzalutamide) 30 mg/Day | Minimum Observed Plasma Concentration (Cmin) of MDV3100: Multiple Dose Period | 0.10 microgram per milliliter | Standard Deviation 0.03 |
| MDV3100 (Enzalutamide) 60 mg /Day | Minimum Observed Plasma Concentration (Cmin) of MDV3100: Multiple Dose Period | 0.00 microgram per milliliter | Standard Deviation 0 |
| MDV3100 (Enzalutamide) 150/160 mg/Day | Minimum Observed Plasma Concentration (Cmin) of MDV3100: Multiple Dose Period | 0.04 microgram per milliliter | Standard Deviation 0.19 |
| MDV3100 (Enzalutamide) 240 mg /Day | Minimum Observed Plasma Concentration (Cmin) of MDV3100: Multiple Dose Period | 0.00 microgram per milliliter | Standard Deviation 0 |
| MDV3100 (Enzalutamide) 360 mg /Day | Minimum Observed Plasma Concentration (Cmin) of MDV3100: Multiple Dose Period | 0.00 microgram per milliliter | Standard Deviation 0 |
| MDV3100 (Enzalutamide) 480 mg /Day | Minimum Observed Plasma Concentration (Cmin) of MDV3100: Multiple Dose Period | 0.00 microgram per milliliter | Standard Deviation 0 |
| MDV3100 (Enzalutamide) 600 mg /Day | Minimum Observed Plasma Concentration (Cmin) of MDV3100: Multiple Dose Period | 1.89 microgram per milliliter | Standard Deviation 0.55 |
Secondary
Time to Reach Maximum Plasma Concentration (Tmax) of MDV3100: Multiple Dose Period
Time frame: Pre-dose, 0.5, 1, 2, 24 hours post dose on Day 84 of Multiple Dose Period
Population: PK evaluable population: all participants who received study drug and had sufficient PK samples for calculation of at least 1 MDV3100 PK parameter. Here, Overall Number of Participants Analyzed signifies participants who were evaluable for this outcome measure.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| MDV3100 (Enzalutamide) 30 mg/Day | Time to Reach Maximum Plasma Concentration (Tmax) of MDV3100: Multiple Dose Period | 2.07 hours |
| MDV3100 (Enzalutamide) 60 mg /Day | Time to Reach Maximum Plasma Concentration (Tmax) of MDV3100: Multiple Dose Period | 1.07 hours |
| MDV3100 (Enzalutamide) 150/160 mg/Day | Time to Reach Maximum Plasma Concentration (Tmax) of MDV3100: Multiple Dose Period | 1.00 hours |
| MDV3100 (Enzalutamide) 240 mg /Day | Time to Reach Maximum Plasma Concentration (Tmax) of MDV3100: Multiple Dose Period | 1.08 hours |
| MDV3100 (Enzalutamide) 360 mg /Day | Time to Reach Maximum Plasma Concentration (Tmax) of MDV3100: Multiple Dose Period | 1.57 hours |
| MDV3100 (Enzalutamide) 480 mg /Day | Time to Reach Maximum Plasma Concentration (Tmax) of MDV3100: Multiple Dose Period | 0.00 hours |
Secondary
Time to Reach Maximum Plasma Concentration (Tmax) of MDV3100: Single Dose Period
Time frame: Pre-dose, 0.5, 1, 2, 4, 6, 24, 48, 72, 96, 120 hours post dose on Day 1 of Single Dose Period
Population: PK evaluable population: all participants who received study drug and had sufficient PK samples for calculation of at least 1 MDV3100 PK parameter.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| MDV3100 (Enzalutamide) 30 mg/Day | Time to Reach Maximum Plasma Concentration (Tmax) of MDV3100: Single Dose Period | 1.98 hours |
| MDV3100 (Enzalutamide) 60 mg /Day | Time to Reach Maximum Plasma Concentration (Tmax) of MDV3100: Single Dose Period | 0.50 hours |
| MDV3100 (Enzalutamide) 150/160 mg/Day | Time to Reach Maximum Plasma Concentration (Tmax) of MDV3100: Single Dose Period | 0.53 hours |
| MDV3100 (Enzalutamide) 240 mg /Day | Time to Reach Maximum Plasma Concentration (Tmax) of MDV3100: Single Dose Period | 1.00 hours |
| MDV3100 (Enzalutamide) 360 mg /Day | Time to Reach Maximum Plasma Concentration (Tmax) of MDV3100: Single Dose Period | 1.03 hours |
| MDV3100 (Enzalutamide) 480 mg /Day | Time to Reach Maximum Plasma Concentration (Tmax) of MDV3100: Single Dose Period | 1.54 hours |
| MDV3100 (Enzalutamide) 600 mg /Day | Time to Reach Maximum Plasma Concentration (Tmax) of MDV3100: Single Dose Period | 1.03 hours |
Other Pre-specified
Percentage of Participants With Prostate Specific Antigen (PSA) Response at Day 84: Multiple Dose Period
Prostate-specific antigen is a glycoprotein considered as a biomarker for the response to therapy in men with prostate cancer. A 50 percent (%) decline in PSA from baseline to the PSA level at Day 84 was considered as a PSA response.
Time frame: Baseline, Day 84
Population: Analysis population included all enrolled participants who received at least 1 dose of study drug. Here, Overall Number of Participants Analyzed signifies those participants who were evaluable for this outcome measure.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| MDV3100 (Enzalutamide) 30 mg/Day | Percentage of Participants With Prostate Specific Antigen (PSA) Response at Day 84: Multiple Dose Period | 33.3 percentage of participants |
| MDV3100 (Enzalutamide) 60 mg /Day | Percentage of Participants With Prostate Specific Antigen (PSA) Response at Day 84: Multiple Dose Period | 50.0 percentage of participants |
| MDV3100 (Enzalutamide) 150/160 mg/Day | Percentage of Participants With Prostate Specific Antigen (PSA) Response at Day 84: Multiple Dose Period | 66.7 percentage of participants |
| MDV3100 (Enzalutamide) 240 mg /Day | Percentage of Participants With Prostate Specific Antigen (PSA) Response at Day 84: Multiple Dose Period | 75.0 percentage of participants |
| MDV3100 (Enzalutamide) 360 mg /Day | Percentage of Participants With Prostate Specific Antigen (PSA) Response at Day 84: Multiple Dose Period | 71.4 percentage of participants |
| MDV3100 (Enzalutamide) 480 mg /Day | Percentage of Participants With Prostate Specific Antigen (PSA) Response at Day 84: Multiple Dose Period | 45.5 percentage of participants |