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Safety Study of Enzalutamide (MDV3100) in Patients With Incurable Breast Cancer

Sponsor
Pfizer (Industry)
Overall Status
Completed
CT.gov ID
NCT01597193
Collaborator
Astellas Pharma Inc (Industry), Medivation LLC, a wholly owned subsidiary of Pfizer Inc. (Industry)
101
Enrollment
17
Locations
5
Arms
68.8
Actual Duration (Months)
5.9
Patients Per Site
0.1
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The purpose of this study is to determine the safety, tolerability and pharmacokinetics of enzalutamide alone and in combination with anastrozole, or exemestane, or fulvestrant in patients with incurable breast cancer.

Condition or Disease Intervention/Treatment Phase
Phase 1

Study Design

Study Type:
Interventional
Actual Enrollment :
101 participants
Allocation:
Non-Randomized
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
A PHASE 1 OPEN-LABEL, DOSE ESCALATION STUDY EVALUATING THE SAFETY, TOLERABILITY, AND PHARMACOKINETICS OF ENZALUTAMIDE (FORMERLY MDV3100) IN PATIENTS WITH INCURABLE BREAST CANCER
Actual Study Start Date :
Apr 30, 2012
Actual Primary Completion Date :
Dec 15, 2015
Actual Study Completion Date :
Jan 22, 2018

Arms and Interventions

Arm Intervention/Treatment
Experimental: enzalutamide (80-mg with increase to 160 mg)

enzalutamide be provided as two or four 40-mg capsules by mouth daily

Drug: enzalutamide
80 mg (2 capsules) or 160 mg (4 capsules) taken orally daily.
Other Names:
  • MDV3100, Xtandi

    		•
    Experimental: enzalutamide and anastrozole

    enzalutamide (160 mg) administered as four 40-mg capsules by mouth once daily in combination with anastrozole (1 mg) administered as one 1-mg tablet by mouth once daily.

    Drug: anastrozole
    1 mg/day
    Other Names:
  • Arimidex

    • Drug: enzalutamide
    160 mg (4 capsules) taken orally daily.
    Other Names:
  • MDV3100
  • Xtandi

    		•
    Experimental: enzalutamide and exemestane 25 mg

    enzalutamide (160 mg) administered as four 40-mg capsules by mouth once daily in combination with exemestane administered as one 25-mg tablet daily

    Drug: exemestane
    The exemestane dose is 25mg daily.
    Other Names:
  • Aromasin

    • Drug: enzalutamide
    160 mg (4 capsules) taken orally daily.
    Other Names:
  • MDV3100
  • Xtandi

    		•
    Experimental: enzalutamide and exemestane 50 mg

    enzalutamide (160 mg) administered as four 40-mg capsules by mouth once daily in combination with exemestane administered as two 25-mg tablets daily

    Drug: enzalutamide
    160 mg (4 capsules) taken orally daily.
    Other Names:
  • MDV3100
  • Xtandi

    • Drug: exemestane
    The exemestane dose is 50 mg daily.
    Other Names:
  • Aromasin

    		•
    Experimental: enzalutamide and fulvestrant

    enzalutamide (160 mg) administered as four 40-mg capsules by mouth once daily in combination with fulvestrant (500 mg) administered as two 250-mg intramuscular injections every 28 days

    Drug: fulvestrant
    500 mg every 28 days
    Other Names:
  • Faslodex

    • Drug: enzalutamide
    160 mg (4 capsules) taken orally daily.
    Other Names:
  • MDV3100
  • Xtandi

    		•

    Outcome Measures

    Primary Outcome Measures

    1. Dose-Escalation Phase: Percentage of Participants With Dose-limiting Toxicity (DLTs) [Baseline up to Day 35]

      DLTs were defined as any of following events related to the study drug: Any adverse event (AE) consistent with a seizure of any grade; Grade greater than equal to (>=) 3 fatigue, diarrhea, nausea, or vomiting that did not improve to Grade 1 within 14 days of initiating standard of care therapy; any Grade >=3 hematologic toxicity with the following modifications: 1) Grade >=3 platelet count associated with bleeding, 2) Grade >=3 absolute neutrophil count that persists for 7 or more days or that was associated with fevers (febrile neutropenia); Grade >=3 any other non-hematological toxicity that was determined to be related to study drug.

    2. Percentage of Participants With Adverse Events of Grade 3 or Higher Severity by National Cancer Institute Common Toxicity Criteria For Adverse Events (NCI CTCAE) (Version 4.03) [Day 1 up to 30 days after the last dose of study drug or before initiation of a new systemic antitumor treatment, whichever occurred first (up to 3.5 years)]

      An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. AE was assessed according to severity grading based on NCI CTCAE Version 4.03 and defined as Grade 3 AEs = severe or medically significant events but not immediately life-threatening, hospitalization or prolongation of hospitalization indicated, disabling, limiting self-care activities of daily living; Grade 4 AEs = life-threatening, urgent intervention indicated; Grade 5 AEs = death related to adverse event.

    3. Percentage of Participants With Treatment-Emergent Serious Adverse Events (SAEs) [Day 1 up to 30 days after the last dose of study drug or before initiation of a new systemic antitumor treatment, whichever occurred first (up to 3.5 years)]

      An AE was any untoward medical occurrence in a participant who received study treatment without regard to possibility of causal relationship. 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 or incapacity, congenital anomaly. Treatment-emergent are events between first dose of study drug and up to 30 days after last dose of study drug that were absent before treatment or that worsened relative to pretreatment state. AEs included both serious and non-serious adverse events.

    4. Percentage of Participants Who Discontinued the Study Drug Due to Adverse Events or Serious Adverse Events [Day 1 up to 30 days after the last dose of study drug or before initiation of a new systemic antitumor treatment, whichever occurred first (up to 3.5 years)]

      An AE was any untoward medical occurrence in a participant who received study treatment without regard to possibility of causal relationship. 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 or incapacity, congenital anomaly.

    5. Percentage of Participants Who Require Dose Reductions Due to Adverse Events [Day 1 up to 30 days after the last dose of study drug or before initiation of a new systemic antitumor treatment, whichever occurred first (up to 3.5 years)]

      An AE was any untoward medical occurrence in a participant who received study treatment without regard to possibility of causal relationship. 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 or incapacity, congenital anomaly.

    6. Percentage of Participants With Potentially Clinically Significant Change From Baseline in Vital Signs [Day 1 up to 30 days after the last dose of study drug or before initiation of a new systemic antitumor treatment, whichever occurred first (up to 3.5 years)]

      Absolute systolic blood pressure (SBP) greater than (>) 180 millimeter of mercury (mm Hg) and an increase of >40 mm Hg from baseline; absolute SBP less than (<) 90 mm Hg and an decrease of >30 mm Hg from baseline. Absolute diastolic blood pressure (DBP) >105 mm Hg and an increase of >30 mm Hg from baseline; absolute DBP <50 mm Hg and an increase of >20 mm Hg from baseline. Absolute heart rate >120 beats per minute (bpm) and an increase of >30 bpm from baseline; absolute heart rate <50 bpm and decrease of >20 bpm from baseline. Participants with any of these abnormalities were reported for this outcome in each arm.

    7. Dose-Escalation Phase: Maximum Plasma Concentration (Cmax) of Enzalutamide and Its Metabolites After Single Dose [pre-dose, 0.5, 1, 2, 4, 6, 24, 48, 72 and 96 hours post dose on Day 1]

      Carboxylic Acid (M1) and N-desmethyl (M2) are two metabolites of Enzalutamide.

    8. Dose-Escalation Phase: Time to Reach Maximum Plasma Concentration (Tmax) of Enzalutamide and Its Metabolites After Single Dosing [pre-dose, 0.5, 1, 2, 4, 6, 24, 48, 72 and 96 hours post dose on Day 1]

      Carboxylic Acid (M1) and N-desmethyl (M2) are two metabolites of Enzalutamide.

    9. Dose-Escalation Phase: Area Under the Plasma Concentration-time Curve From Time Zero to 24 Hours (AUC24h) of Enzalutamide and Its Metabolites After Single Dose [pre-dose, 0.5, 1, 2, 4, 6 and 24 hours post dose on Day 1]

      Carboxylic Acid (M1) and N-desmethyl (M2) are two metabolites of Enzalutamide.

    10. Dose-Escalation Phase: Area Under the Plasma Concentration-time Curve From Time Zero to 72 Hours (AUC72h) of Enzalutamide After Single Dosing [pre-dose, 0.5, 1, 2, 4, 6, 24, 48 and 72 hours post dose on Day 1]

    11. Dose-Escalation Phase: Area Under the Plasma Concentration-Time Profile From Time Zero Extrapolated to Infinite Time (AUCinf) of Enzalutamide After Single Dosing [pre-dose, 0.5, 1, 2, 4, 6, 24, 48, 72 and 96 hours post dose on Day 1]

      AUCinf = Area under the plasma concentration versus time curve (AUC) from time zero (pre-dose) to extrapolated infinite time (0 - inf).

    12. Dose-Escalation Phase: Terminal Elimination Half-Life (t1/2) of Enzalutamide After Single Dosing [pre-dose, 0.5, 1, 2, 4, 6, 24, 48, 72 and 96 hours post dose on Day 1]

      Terminal elimination half-life is the time measured for the plasma concentration of Enzalutamide to decrease by one-half of its initial concentration.

    13. Dose Escalation Phase: Apparent Oral Clearance (CL/F) of Enzalutamide After Single Dosing [pre-dose, 0.5, 1, 2, 4, 6, 24, 48, 72 and 96 hours post dose on Day 1]

      Apparent oral clearance of a drug is a measure of the rate at which a drug is metabolized or eliminated by normal biological processes. It was obtained after oral dose (apparent oral clearance) is influenced by the fraction of the dose absorbed.

    14. Dose Escalation Phase: Apparent Volume of Distribution (Vz/F) of Enzalutamide After Single Dosing [pre-dose, 0.5, 1, 2, 4, 6, 24, 48, 72 and 96 hours post dose on Day 1]

      Volume of distribution is defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired plasma concentration of a drug. Apparent volume of distribution after oral dose (Vz/F) is influenced by the fraction absorbed.

    15. Dose-Escalation Phase: Maximum Plasma Concentration (Cmax) of Enzalutamide and Its Metabolites After Multiple Dosing [pre-dose, 0.5, 1, 2, 4, 6, and 24 hours post-dose on Day 50]

      Carboxylic Acid (M1) and N-desmethyl (M2) are two metabolites of Enzalutamide.

    16. Dose-Escalation Phase: Time to Reach Maximum Plasma Concentration (Tmax) of Enzalutamide and Its Metabolites After Multiple Dosing [pre-dose, 0.5, 1, 2, 4, 6, and 24 hours post-dose on Day 50]

      Carboxylic Acid (M1) and N-desmethyl (M2) are two metabolites of Enzalutamide.

    17. Dose-Escalation Phase: Area Under the Curve From Time Zero to End of Dosing Interval (AUCtau) of Enzalutamide and Its Metabolites After Multiple Dosing [pre-dose, 0.5, 1, 2, 4, 6, and 24 hours post-dose on Day 50]

      Area under the plasma concentration versus time-curve from time zero to end of dosing interval (AUCtau), where dosing interval was 24 hours. Carboxylic Acid (M1) and N-desmethyl (M2) are two metabolites of Enzalutamide.

    18. Dose-Escalation Phase: Apparent Oral Clearance (CL/F) of Enzalutamide After Multiple Dosing [pre-dose, 0.5, 1, 2, 4, 6, and 24 hours post-dose on Day 50]

      Apparent oral clearance of a drug is a measure of the rate at which a drug is metabolized or eliminated by normal biological processes. It was obtained after oral dose (apparent oral clearance) is influenced by the fraction of the dose absorbed.

    19. Dose-Escalation Phase: Peak-to-Trough Ratio of Enzalutamide and Its Metabolites After Multiple Dosing [pre-dose, 0.5, 1, 2, 4, 6, and 24 hours post-dose on Day 50]

      Peak-to-trough ratio was calculated by dividing Cmax with Cmin of Enzalutamide and its Metabolites. Carboxylic Acid (M1) and N-desmethyl (M2) are two metabolites of Enzalutamide. Cmax was maximum plasma concentration during the dosing interval and Cmin was minimum observed plasma concentration during the dosing interval.

    20. Dose-Escalation Phase: Accumulation Ratio of AUC24 of Enzalutamide and Its Metabolites After Multiple Dosing [pre-dose, 0.5, 1, 2, 4, 6, and 24 hours post-dose on Day 1 and 50]

      Accumulation Ratio was defined as the ratio of AUC24 of Day 50 to AUC24 of Day 1, where AUC24 was area under the plasma concentration-time curve from time zero to 24 hours post-dose. Carboxylic Acid (M1) and N-desmethyl (M2) are two metabolites of Enzalutamide.

    Secondary Outcome Measures

    1. Dose-Expansion Phase: Trough Plasma Concentration for Enzalutamide [pre-dose on Day 57]

    Eligibility Criteria

    Criteria

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

    • Histologically confirmed breast cancer with accompanying pathology report;

    • Submit unstained representative tumor specimen, either as a paraffin block (preferred) or ≥ 10 unstained slides

    • Received at least 2 lines of systemic therapy in the advanced setting (for enzalutamide alone arm only);

    • Eastern Cooperative Oncology Group performance (ECOG) status of 0 or 1;

    • Estimated life expectancy of at least 3 months

    Exclusion Criteria:

    • Severe concurrent disease, infection, or comorbidity that, in the judgment of the Investigator, would make the patient inappropriate for enrollment;

    • Pregnant or lactating;

    • Known or suspected brain metastasis or leptomeningeal disease;

    • History of another malignancy within the previous 5 years other than curatively treated in situ carcinomas;

    • For patients who are enrolled to receive enzalutamide plus anastrozole or exemestane or fulvestrant must not have received tamoxifen or any medication known to be a potent CYP3A4 inducer or inhibitor.

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 ATTN-Research Pharmacist Aurora Colorado United States 80045
    2 University of Colorado Cancer Center Aurora Colorado United States 80045
    3 University of Colorado Hospital, Anschutz Outpatient Pavilion Aurora Colorado United States 80045
    4 Connecticut Multispecialty Group Enfield Connecticut United States 06082
    5 Florida Cancer Specialists Sarasota Florida United States 34232
    6 Karmanos Cancer Institute Detroit Michigan United States 48201
    7 The West Clinic, PC Corinth Mississippi United States 38834
    8 The West Clinic Southaven Mississippi United States 38671
    9 Memorial Sloan Kettering Cancer Center New York New York United States 10022
    10 Memorial Sloan Kettering Cancer Center - IDS Pharmacy New York New York United States 10065
    11 Memorial Sloan Kettering Cancer Center - OPD Pharmacy New York New York United States 10065
    12 Memorial Sloan Kettering Cancer Center New York New York United States 10065
    13 The West Clinic Germantown Tennessee United States 38138
    14 The West Clinic Memphis Tennessee United States 38104
    15 The West Clinic Memphis Tennessee United States 38120
    16 Tennessee Oncology, PLLC. Nashville Tennessee United States 37203
    17 The Sarah Cannon Research Institute Nashville Tennessee United States 37203

    Sponsors and Collaborators

    • Pfizer
    • Astellas Pharma Inc
    • Medivation LLC, a wholly owned subsidiary of Pfizer Inc.

    Investigators

    • Study Director: Pfizer Pfizer CT.gov Call Center, Pfizer

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    Pfizer
    ClinicalTrials.gov Identifier:
    NCT01597193
    Other Study ID Numbers:
    • MDV3100-08
    • C3431006
    First Posted:
    May 11, 2012
    Last Update Posted:
    May 8, 2019
    Last Verified:
    May 1, 2019
    Individual Participant Data (IPD) Sharing Statement:
    No
    Plan to Share IPD:
    No
    Keywords provided by Pfizer
    enzalutamide
    MDV3100
    breast cancer
    Additional relevant MeSH terms:
    Breast Neoplasms
    Fulvestrant
    Anastrozole
    Exemestane

    Study Results

    Participant Flow

    Recruitment Details
    Pre-assignment Detail Stage 1: Included participants with incurable breast cancer. Stage 2: Included participants with hormone receptor-positive incurable breast cancer.
    Arm/Group Title Dose Escalation: Enzalutamide 80 mg Dose Escalation: Enzalutamide 160 mg Dose Expansion: Enzalutamide 160 mg Dose Expansion: Enzalutamide 160 mg + Anastrozole 1 mg Dose Expansion: Enzalutamide 160 mg + Exemestane 25 mg Dose Expansion: Enzalutamide 160 mg + Exemestane 50 mg Dose Expansion: Enzalutamide 160 mg + Fulvestrant 500 mg
    Arm/Group Description Participants received enzalutamide 80 milligram (mg) (two 40 mg) capsules, orally, once daily until documented disease progression, initiation of a new antitumor treatment, an intolerable adverse event (including any seizure), noncompliance, withdrawal of consent, discontinuation by sponsor, or investigator. Participants were followed-up until 30 days after last dose of study drug or before initiation of a new antitumor or investigational therapy, whichever occurred first. Participants received enzalutamide 160 mg (four 40 mg) capsules, orally, once daily until documented disease progression, initiation of a new antitumor treatment, an intolerable adverse event (including any seizure), noncompliance, withdrawal of consent, discontinuation by sponsor, or investigator. Participants were followed-up until 30 days after last dose of study drug or before initiation of a new antitumor or investigational therapy, whichever occurred first. Participants received enzalutamide 160 mg (four 40 mg) capsules, orally, once daily until documented disease progression, initiation of a new antitumor treatment, an intolerable adverse event (including any seizure), noncompliance, withdrawal of consent, discontinuation by the sponsor, or investigator. Participants were followed-up until 30 days after last dose of study drug or before initiation of a new antitumor or investigational therapy, whichever occurred first. Participants received enzalutamide 160 mg (four 40 mg) capsule in combination with the anastrozole 1 mg tablet, orally, once daily until documented disease progression, initiation of a new antitumor treatment, an intolerable adverse event (including any seizure), noncompliance, withdrawal of consent, discontinuation by sponsor, or investigator. Participants were followed-up until 30 days after last dose of study drug or before initiation of a new antitumor or investigational therapy, whichever occurred first. Participants received enzalutamide 160 mg (four 40 mg) capsule in combination with the exemestane 25 mg tablet, orally, once daily until documented disease progression, initiation of a new antitumor treatment, an intolerable adverse event (including any seizure), noncompliance, withdrawal of consent, discontinuation by sponsor, or investigator. Participants were followed-up until 30 days after last dose of study drug or before initiation of a new antitumor or investigational therapy, whichever occurred first. Participants received enzalutamide 160 mg (four 40 mg) capsule in combination with the exemestane 50 mg tablet, orally, once daily until documented disease progression, initiation of a new antitumor treatment, an intolerable adverse event (including any seizure), noncompliance, withdrawal of consent, discontinuation by sponsor, or investigator. Participants were followed-up until 30 days after last dose of study drug or before initiation of a new antitumor or investigational therapy, whichever occurred first. Participants received enzalutamide 160 mg (four 40 mg) capsule once daily in combination with the fulvestrant 500 mg intramuscular injection, once every 28 days until documented disease progression, initiation of a new antitumor treatment, an intolerable adverse event (including any seizure), noncompliance, withdrawal of consent, discontinuation by the sponsor, or investigator. Participants were followed-up until 30 days after last dose of study drug or before initiation of a new antitumor or investigational therapy, whichever occurred first.
    Period Title: Stage 1: Dose Escalation (141 Days)
    STARTED 7 8 0 0 0 0 0
    COMPLETED 0 0 0 0 0 0 0
    NOT COMPLETED 7 8 0 0 0 0 0
    Period Title: Stage 1: Dose Escalation (141 Days)
    STARTED 0 0 14 20 16 23 11
    COMPLETED 0 0 0 0 0 0 0
    NOT COMPLETED 0 0 14 20 16 23 11

    Baseline Characteristics

    Arm/Group Title Dose Escalation: Enzalutamide 80 mg Dose Escalation: Enzalutamide 160 mg Dose Expansion: Enzalutamide 160 mg Dose Expansion: Enzalutamide 160 mg + Anastrozole 1 mg Dose Expansion: Enzalutamide 160 mg + Exemestane 25 mg Dose Expansion: Enzalutamide 160 mg + Exemestane 50 mg Dose Expansion: Enzalutamide 160 mg + Fulvestrant 500 mg Total
    Arm/Group Description Participants received enzalutamide 80 mg (two 40 mg) capsules, orally, once daily until documented disease progression, initiation of a new antitumor treatment, an intolerable adverse event (including any seizure), noncompliance, withdrawal of consent, discontinuation by sponsor, or investigator. Participants were followed-up until 30 days after last dose of study drug or before initiation of a new antitumor or investigational therapy, whichever occurred first. Participants received enzalutamide 160 mg (four 40 mg) capsules, orally, once daily until documented disease progression, initiation of a new antitumor treatment, an intolerable adverse event (including any seizure), noncompliance, withdrawal of consent, discontinuation by sponsor, or investigator. Participants were followed-up until 30 days after last dose of study drug or before initiation of a new antitumor or investigational therapy, whichever occurred first. Participants received enzalutamide 160 mg (four 40 mg) capsules, orally, once daily until documented disease progression, initiation of a new antitumor treatment, an intolerable adverse event (including any seizure), noncompliance, withdrawal of consent, discontinuation by the sponsor, or investigator. Participants were followed-up until 30 days after last dose of study drug or before initiation of a new antitumor or investigational therapy, whichever occurred first. Participants received enzalutamide 160 mg (four 40 mg) capsule in combination with the anastrozole 1 mg tablet, orally, once daily until documented disease progression, initiation of a new antitumor treatment, an intolerable adverse event (including any seizure), noncompliance, withdrawal of consent, discontinuation by sponsor, or investigator. Participants were followed-up until 30 days after last dose of study drug or before initiation of a new antitumor or investigational therapy, whichever occurred first. Participants received enzalutamide 160 mg (four 40 mg) capsule in combination with the exemestane 25 mg tablet, orally, once daily until documented disease progression, initiation of a new antitumor treatment, an intolerable adverse event (including any seizure), noncompliance, withdrawal of consent, discontinuation by sponsor, or investigator. Participants were followed-up until 30 days after last dose of study drug or before initiation of a new antitumor or investigational therapy, whichever occurred first. Participants received enzalutamide 160 mg (four 40 mg) capsule in combination with the exemestane 50 mg tablet, orally, once daily until documented disease progression, initiation of a new antitumor treatment, an intolerable adverse event (including any seizure), noncompliance, withdrawal of consent, discontinuation by sponsor, or investigator. Participants were followed-up until 30 days after last dose of study drug or before initiation of a new antitumor or investigational therapy, whichever occurred first. Participants received enzalutamide 160 mg (four 40 mg) capsule once daily in combination with the fulvestrant 500 mg intramuscular injection, once every 28 days until documented disease progression, initiation of a new antitumor treatment, an intolerable adverse event (including any seizure), noncompliance, withdrawal of consent, discontinuation by the sponsor, or investigator. Participants were followed-up until 30 days after last dose of study drug or before initiation of a new antitumor or investigational therapy, whichever occurred first. Total of all reporting groups
    Overall Participants 7 8 14 20 16 23 11 99
    Age, Customized (Count of Participants)
    Less than (<) 65 years
    6
    85.7%
    5
    62.5%
    11
    78.6%
    12
    60%
    13
    81.3%
    10
    43.5%
    6
    54.5%
    63
    63.6%
    Between 65 to 74 years
    1
    14.3%
    3
    37.5%
    2
    14.3%
    5
    25%
    2
    12.5%
    12
    52.2%
    4
    36.4%
    29
    29.3%
    Greater than or equal to (>=) 75 years
    0
    0%
    0
    0%
    1
    7.1%
    3
    15%
    1
    6.3%
    1
    4.3%
    1
    9.1%
    7
    7.1%
    Sex: Female, Male (Count of Participants)
    Female
    7
    100%
    8
    100%
    14
    100%
    20
    100%
    16
    100%
    23
    100%
    11
    100%
    99
    100%
    Male
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%

    Outcome Measures

    1. Primary Outcome
    Title Dose-Escalation Phase: Percentage of Participants With Dose-limiting Toxicity (DLTs)
    Description DLTs were defined as any of following events related to the study drug: Any adverse event (AE) consistent with a seizure of any grade; Grade greater than equal to (>=) 3 fatigue, diarrhea, nausea, or vomiting that did not improve to Grade 1 within 14 days of initiating standard of care therapy; any Grade >=3 hematologic toxicity with the following modifications: 1) Grade >=3 platelet count associated with bleeding, 2) Grade >=3 absolute neutrophil count that persists for 7 or more days or that was associated with fevers (febrile neutropenia); Grade >=3 any other non-hematological toxicity that was determined to be related to study drug.
    Time Frame Baseline up to Day 35

    Outcome Measure Data

    Analysis Population Description
    Safety analysis population included all enrolled participants who received at least 1 dose of Enzalutamide. Here, number of participants analyzed signifies those participants who were evaluable for this outcome measure.
    Arm/Group Title Dose Escalation: Enzalutamide 80 mg Dose Escalation: Enzalutamide 160 mg
    Arm/Group Description Participants received enzalutamide 80 mg (two 40 mg) capsules, orally, once daily until documented disease progression, initiation of a new antitumor treatment, an intolerable adverse event (including any seizure), noncompliance, withdrawal of consent, discontinuation by sponsor, or investigator. Participants were followed-up until 30 days after last dose of study drug or before initiation of a new antitumor or investigational therapy, whichever occurred first. Participants received enzalutamide 160 mg (four 40 mg) capsules, orally, once daily until documented disease progression, initiation of a new antitumor treatment, an intolerable adverse event (including any seizure), noncompliance, withdrawal of consent, discontinuation by sponsor, or investigator. Participants were followed-up until 30 days after last dose of study drug or before initiation of a new antitumor or investigational therapy, whichever occurred first.
    Measure Participants 6 7
    Number [percentage of participants]
    16.7
    238.6%
    0.0
    0%
    2. Primary Outcome
    Title Percentage of Participants With Adverse Events of Grade 3 or Higher Severity by National Cancer Institute Common Toxicity Criteria For Adverse Events (NCI CTCAE) (Version 4.03)
    Description An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. AE was assessed according to severity grading based on NCI CTCAE Version 4.03 and defined as Grade 3 AEs = severe or medically significant events but not immediately life-threatening, hospitalization or prolongation of hospitalization indicated, disabling, limiting self-care activities of daily living; Grade 4 AEs = life-threatening, urgent intervention indicated; Grade 5 AEs = death related to adverse event.
    Time Frame Day 1 up to 30 days after the last dose of study drug or before initiation of a new systemic antitumor treatment, whichever occurred first (up to 3.5 years)

    Outcome Measure Data

    Analysis Population Description
    Safety analysis population included all enrolled participants who received at least 1 dose of Enzalutamide.
    Arm/Group Title Dose Escalation: Enzalutamide 80 mg Dose Escalation: Enzalutamide 160 mg Dose Expansion: Enzalutamide 160 mg Dose Expansion: Enzalutamide 160 mg + Anastrozole 1 mg Dose Expansion: Enzalutamide 160 mg + Exemestane 25 mg Dose Expansion: Enzalutamide 160 mg + Exemestane 50 mg Dose Expansion: Enzalutamide 160 mg + Fulvestrant 500 mg
    Arm/Group Description Participants received enzalutamide 80 mg (two 40 mg) capsules, orally, once daily until documented disease progression, initiation of a new antitumor treatment, an intolerable adverse event (including any seizure), noncompliance, withdrawal of consent, discontinuation by sponsor, or investigator. Participants were followed-up until 30 days after last dose of study drug or before initiation of a new antitumor or investigational therapy, whichever occurred first. Participants received enzalutamide 160 mg (four 40 mg) capsules, orally, once daily until documented disease progression, initiation of a new antitumor treatment, an intolerable adverse event (including any seizure), noncompliance, withdrawal of consent, discontinuation by sponsor, or investigator. Participants were followed-up until 30 days after last dose of study drug or before initiation of a new antitumor or investigational therapy, whichever occurred first. Participants received enzalutamide 160 mg (four 40 mg) capsules, orally, once daily until documented disease progression, initiation of a new antitumor treatment, an intolerable adverse event (including any seizure), noncompliance, withdrawal of consent, discontinuation by the sponsor, or investigator. Participants were followed-up until 30 days after last dose of study drug or before initiation of a new antitumor or investigational therapy, whichever occurred first. Participants received enzalutamide 160 mg (four 40 mg) capsule in combination with the anastrozole 1 mg tablet, orally, once daily until documented disease progression, initiation of a new antitumor treatment, an intolerable adverse event (including any seizure), noncompliance, withdrawal of consent, discontinuation by sponsor, or investigator. Participants were followed-up until 30 days after last dose of study drug or before initiation of a new antitumor or investigational therapy, whichever occurred first. Participants received enzalutamide 160 mg (four 40 mg) capsule in combination with the exemestane 25 mg tablet, orally, once daily until documented disease progression, initiation of a new antitumor treatment, an intolerable adverse event (including any seizure), noncompliance, withdrawal of consent, discontinuation by sponsor, or investigator. Participants were followed-up until 30 days after last dose of study drug or before initiation of a new antitumor or investigational therapy, whichever occurred first. Participants received enzalutamide 160 mg (four 40 mg) capsule in combination with the exemestane 50 mg tablet, orally, once daily until documented disease progression, initiation of a new antitumor treatment, an intolerable adverse event (including any seizure), noncompliance, withdrawal of consent, discontinuation by sponsor, or investigator. Participants were followed-up until 30 days after last dose of study drug or before initiation of a new antitumor or investigational therapy, whichever occurred first. Participants received enzalutamide 160 mg (four 40 mg) capsule once daily in combination with the fulvestrant 500 mg intramuscular injection, once every 28 days until documented disease progression, initiation of a new antitumor treatment, an intolerable adverse event (including any seizure), noncompliance, withdrawal of consent, discontinuation by the sponsor, or investigator. Participants were followed-up until 30 days after last dose of study drug or before initiation of a new antitumor or investigational therapy, whichever occurred first.
    Measure Participants 7 8 14 20 16 23 11
    Number [percentage of participants]
    57.1
    815.7%
    12.5
    156.3%
    21.4
    152.9%
    30.0
    150%
    37.5
    234.4%
    39.1
    170%
    36.4
    330.9%
    3. Primary Outcome
    Title Percentage of Participants With Treatment-Emergent Serious Adverse Events (SAEs)
    Description An AE was any untoward medical occurrence in a participant who received study treatment without regard to possibility of causal relationship. 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 or incapacity, congenital anomaly. Treatment-emergent are events between first dose of study drug and up to 30 days after last dose of study drug that were absent before treatment or that worsened relative to pretreatment state. AEs included both serious and non-serious adverse events.
    Time Frame Day 1 up to 30 days after the last dose of study drug or before initiation of a new systemic antitumor treatment, whichever occurred first (up to 3.5 years)

    Outcome Measure Data

    Analysis Population Description
    Safety analysis population included all enrolled participants who received at least 1 dose of Enzalutamide.
    Arm/Group Title Dose Escalation: Enzalutamide 80 mg Dose Escalation: Enzalutamide 160 mg Dose Expansion: Enzalutamide 160 mg Dose Expansion: Enzalutamide 160 mg + Anastrozole 1 mg Dose Expansion: Enzalutamide 160 mg + Exemestane 25 mg Dose Expansion: Enzalutamide 160 mg + Exemestane 50 mg Dose Expansion: Enzalutamide 160 mg + Fulvestrant 500 mg
    Arm/Group Description Participants received enzalutamide 80 mg (two 40 mg) capsules, orally, once daily until documented disease progression, initiation of a new antitumor treatment, an intolerable adverse event (including any seizure), noncompliance, withdrawal of consent, discontinuation by sponsor, or investigator. Participants were followed-up until 30 days after last dose of study drug or before initiation of a new antitumor or investigational therapy, whichever occurred first. Participants received enzalutamide 160 mg (four 40 mg) capsules, orally, once daily until documented disease progression, initiation of a new antitumor treatment, an intolerable adverse event (including any seizure), noncompliance, withdrawal of consent, discontinuation by sponsor, or investigator. Participants were followed-up until 30 days after last dose of study drug or before initiation of a new antitumor or investigational therapy, whichever occurred first. Participants received enzalutamide 160 mg (four 40 mg) capsules, orally, once daily until documented disease progression, initiation of a new antitumor treatment, an intolerable adverse event (including any seizure), noncompliance, withdrawal of consent, discontinuation by the sponsor, or investigator. Participants were followed-up until 30 days after last dose of study drug or before initiation of a new antitumor or investigational therapy, whichever occurred first. Participants received enzalutamide 160 mg (four 40 mg) capsule in combination with the anastrozole 1 mg tablet, orally, once daily until documented disease progression, initiation of a new antitumor treatment, an intolerable adverse event (including any seizure), noncompliance, withdrawal of consent, discontinuation by sponsor, or investigator. Participants were followed-up until 30 days after last dose of study drug or before initiation of a new antitumor or investigational therapy, whichever occurred first. Participants received enzalutamide 160 mg (four 40 mg) capsule in combination with the exemestane 25 mg tablet, orally, once daily until documented disease progression, initiation of a new antitumor treatment, an intolerable adverse event (including any seizure), noncompliance, withdrawal of consent, discontinuation by sponsor, or investigator. Participants were followed-up until 30 days after last dose of study drug or before initiation of a new antitumor or investigational therapy, whichever occurred first. Participants received enzalutamide 160 mg (four 40 mg) capsule in combination with the exemestane 50 mg tablet, orally, once daily until documented disease progression, initiation of a new antitumor treatment, an intolerable adverse event (including any seizure), noncompliance, withdrawal of consent, discontinuation by sponsor, or investigator. Participants were followed-up until 30 days after last dose of study drug or before initiation of a new antitumor or investigational therapy, whichever occurred first. Participants received enzalutamide 160 mg (four 40 mg) capsule once daily in combination with the fulvestrant 500 mg intramuscular injection, once every 28 days until documented disease progression, initiation of a new antitumor treatment, an intolerable adverse event (including any seizure), noncompliance, withdrawal of consent, discontinuation by the sponsor, or investigator. Participants were followed-up until 30 days after last dose of study drug or before initiation of a new antitumor or investigational therapy, whichever occurred first.
    Measure Participants 7 8 14 20 16 23 11
    Number [percentage of participants]
    28.6
    408.6%
    12.5
    156.3%
    14.3
    102.1%
    5.0
    25%
    31.3
    195.6%
    13.0
    56.5%
    18.2
    165.5%
    4. Primary Outcome
    Title Percentage of Participants Who Discontinued the Study Drug Due to Adverse Events or Serious Adverse Events
    Description An AE was any untoward medical occurrence in a participant who received study treatment without regard to possibility of causal relationship. 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 or incapacity, congenital anomaly.
    Time Frame Day 1 up to 30 days after the last dose of study drug or before initiation of a new systemic antitumor treatment, whichever occurred first (up to 3.5 years)

    Outcome Measure Data

    Analysis Population Description
    Safety analysis population included all enrolled participants who received at least 1 dose of Enzalutamide.
    Arm/Group Title Dose Escalation: Enzalutamide 80 mg Dose Escalation: Enzalutamide 160 mg Dose Expansion: Enzalutamide 160 mg Dose Expansion: Enzalutamide 160 mg + Anastrozole 1 mg Dose Expansion: Enzalutamide 160 mg + Exemestane 25 mg Dose Expansion: Enzalutamide 160 mg + Exemestane 50 mg Dose Expansion: Enzalutamide 160 mg + Fulvestrant 500 mg
    Arm/Group Description Participants received enzalutamide 80 mg (two 40 mg) capsules, orally, once daily until documented disease progression, initiation of a new antitumor treatment, an intolerable adverse event (including any seizure), noncompliance, withdrawal of consent, discontinuation by sponsor, or investigator. Participants were followed-up until 30 days after last dose of study drug or before initiation of a new antitumor or investigational therapy, whichever occurred first. Participants received enzalutamide 160 mg (four 40 mg) capsules, orally, once daily until documented disease progression, initiation of a new antitumor treatment, an intolerable adverse event (including any seizure), noncompliance, withdrawal of consent, discontinuation by sponsor, or investigator. Participants were followed-up until 30 days after last dose of study drug or before initiation of a new antitumor or investigational therapy, whichever occurred first. Participants received enzalutamide 160 mg (four 40 mg) capsules, orally, once daily until documented disease progression, initiation of a new antitumor treatment, an intolerable adverse event (including any seizure), noncompliance, withdrawal of consent, discontinuation by the sponsor, or investigator. Participants were followed-up until 30 days after last dose of study drug or before initiation of a new antitumor or investigational therapy, whichever occurred first. Participants received enzalutamide 160 mg (four 40 mg) capsule in combination with the anastrozole 1 mg tablet, orally, once daily until documented disease progression, initiation of a new antitumor treatment, an intolerable adverse event (including any seizure), noncompliance, withdrawal of consent, discontinuation by sponsor, or investigator. Participants were followed-up until 30 days after last dose of study drug or before initiation of a new antitumor or investigational therapy, whichever occurred first. Participants received enzalutamide 160 mg (four 40 mg) capsule in combination with the exemestane 25 mg tablet, orally, once daily until documented disease progression, initiation of a new antitumor treatment, an intolerable adverse event (including any seizure), noncompliance, withdrawal of consent, discontinuation by sponsor, or investigator. Participants were followed-up until 30 days after last dose of study drug or before initiation of a new antitumor or investigational therapy, whichever occurred first. Participants received enzalutamide 160 mg (four 40 mg) capsule in combination with the exemestane 50 mg tablet, orally, once daily until documented disease progression, initiation of a new antitumor treatment, an intolerable adverse event (including any seizure), noncompliance, withdrawal of consent, discontinuation by sponsor, or investigator. Participants were followed-up until 30 days after last dose of study drug or before initiation of a new antitumor or investigational therapy, whichever occurred first. Participants received enzalutamide 160 mg (four 40 mg) capsule once daily in combination with the fulvestrant 500 mg intramuscular injection, once every 28 days until documented disease progression, initiation of a new antitumor treatment, an intolerable adverse event (including any seizure), noncompliance, withdrawal of consent, discontinuation by the sponsor, or investigator. Participants were followed-up until 30 days after last dose of study drug or before initiation of a new antitumor or investigational therapy, whichever occurred first.
    Measure Participants 7 8 14 20 16 23 11
    Number [percentage of participants]
    0.0
    0%
    0.0
    0%
    7.1
    50.7%
    5.0
    25%
    12.5
    78.1%
    13.0
    56.5%
    0.0
    0%
    5. Primary Outcome
    Title Percentage of Participants Who Require Dose Reductions Due to Adverse Events
    Description An AE was any untoward medical occurrence in a participant who received study treatment without regard to possibility of causal relationship. 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 or incapacity, congenital anomaly.
    Time Frame Day 1 up to 30 days after the last dose of study drug or before initiation of a new systemic antitumor treatment, whichever occurred first (up to 3.5 years)

    Outcome Measure Data

    Analysis Population Description
    Safety analysis population included all enrolled participants who received at least 1 dose of Enzalutamide.
    Arm/Group Title Dose Escalation: Enzalutamide 80 mg Dose Escalation: Enzalutamide 160 mg Dose Expansion: Enzalutamide 160 mg Dose Expansion: Enzalutamide 160 mg + Anastrozole 1 mg Dose Expansion: Enzalutamide 160 mg + Exemestane 25 mg Dose Expansion: Enzalutamide 160 mg + Exemestane 50 mg Dose Expansion: Enzalutamide 160 mg + Fulvestrant 500 mg
    Arm/Group Description Participants received enzalutamide 80 mg (two 40 mg) capsules, orally, once daily until documented disease progression, initiation of a new antitumor treatment, an intolerable adverse event (including any seizure), noncompliance, withdrawal of consent, discontinuation by sponsor, or investigator. Participants were followed-up until 30 days after last dose of study drug or before initiation of a new antitumor or investigational therapy, whichever occurred first. Participants received enzalutamide 160 mg (four 40 mg) capsules, orally, once daily until documented disease progression, initiation of a new antitumor treatment, an intolerable adverse event (including any seizure), noncompliance, withdrawal of consent, discontinuation by sponsor, or investigator. Participants were followed-up until 30 days after last dose of study drug or before initiation of a new antitumor or investigational therapy, whichever occurred first. Participants received enzalutamide 160 mg (four 40 mg) capsules, orally, once daily until documented disease progression, initiation of a new antitumor treatment, an intolerable adverse event (including any seizure), noncompliance, withdrawal of consent, discontinuation by the sponsor, or investigator. Participants were followed-up until 30 days after last dose of study drug or before initiation of a new antitumor or investigational therapy, whichever occurred first. Participants received enzalutamide 160 mg (four 40 mg) capsule in combination with the anastrozole 1 mg tablet, orally, once daily until documented disease progression, initiation of a new antitumor treatment, an intolerable adverse event (including any seizure), noncompliance, withdrawal of consent, discontinuation by sponsor, or investigator. Participants were followed-up until 30 days after last dose of study drug or before initiation of a new antitumor or investigational therapy, whichever occurred first. Participants received enzalutamide 160 mg (four 40 mg) capsule in combination with the exemestane 25 mg tablet, orally, once daily until documented disease progression, initiation of a new antitumor treatment, an intolerable adverse event (including any seizure), noncompliance, withdrawal of consent, discontinuation by sponsor, or investigator. Participants were followed-up until 30 days after last dose of study drug or before initiation of a new antitumor or investigational therapy, whichever occurred first. Participants received enzalutamide 160 mg (four 40 mg) capsule in combination with the exemestane 50 mg tablet, orally, once daily until documented disease progression, initiation of a new antitumor treatment, an intolerable adverse event (including any seizure), noncompliance, withdrawal of consent, discontinuation by sponsor, or investigator. Participants were followed-up until 30 days after last dose of study drug or before initiation of a new antitumor or investigational therapy, whichever occurred first. Participants received enzalutamide 160 mg (four 40 mg) capsule once daily in combination with the fulvestrant 500 mg intramuscular injection, once every 28 days until documented disease progression, initiation of a new antitumor treatment, an intolerable adverse event (including any seizure), noncompliance, withdrawal of consent, discontinuation by the sponsor, or investigator. Participants were followed-up until 30 days after last dose of study drug or before initiation of a new antitumor or investigational therapy, whichever occurred first.
    Measure Participants 7 8 14 20 16 23 11
    Number [percentage of participants]
    0.0
    0%
    0.0
    0%
    0.0
    0%
    20.0
    100%
    12.5
    78.1%
    8.7
    37.8%
    18.2
    165.5%
    6. Primary Outcome
    Title Percentage of Participants With Potentially Clinically Significant Change From Baseline in Vital Signs
    Description Absolute systolic blood pressure (SBP) greater than (>) 180 millimeter of mercury (mm Hg) and an increase of >40 mm Hg from baseline; absolute SBP less than (<) 90 mm Hg and an decrease of >30 mm Hg from baseline. Absolute diastolic blood pressure (DBP) >105 mm Hg and an increase of >30 mm Hg from baseline; absolute DBP <50 mm Hg and an increase of >20 mm Hg from baseline. Absolute heart rate >120 beats per minute (bpm) and an increase of >30 bpm from baseline; absolute heart rate <50 bpm and decrease of >20 bpm from baseline. Participants with any of these abnormalities were reported for this outcome in each arm.
    Time Frame Day 1 up to 30 days after the last dose of study drug or before initiation of a new systemic antitumor treatment, whichever occurred first (up to 3.5 years)

    Outcome Measure Data

    Analysis Population Description
    Safety analysis population included all enrolled participants who received at least 1 dose of Enzalutamide.
    Arm/Group Title Dose Escalation: Enzalutamide 80 mg Dose Escalation: Enzalutamide 160 mg Dose Expansion: Enzalutamide 160 mg Dose Expansion: Enzalutamide 160 mg + Anastrozole 1 mg Dose Expansion: Enzalutamide 160 mg + Exemestane 25 mg Dose Expansion: Enzalutamide 160 mg + Exemestane 50 mg Dose Expansion: Enzalutamide 160 mg + Fulvestrant 500 mg
    Arm/Group Description Participants received enzalutamide 80 mg (two 40 mg) capsules, orally, once daily until documented disease progression, initiation of a new antitumor treatment, an intolerable adverse event (including any seizure), noncompliance, withdrawal of consent, discontinuation by sponsor, or investigator. Participants were followed-up until 30 days after last dose of study drug or before initiation of a new antitumor or investigational therapy, whichever occurred first. Participants received enzalutamide 160 mg (four 40 mg) capsules, orally, once daily until documented disease progression, initiation of a new antitumor treatment, an intolerable adverse event (including any seizure), noncompliance, withdrawal of consent, discontinuation by sponsor, or investigator. Participants were followed-up until 30 days after last dose of study drug or before initiation of a new antitumor or investigational therapy, whichever occurred first. Participants received enzalutamide 160 mg (four 40 mg) capsules, orally, once daily until documented disease progression, initiation of a new antitumor treatment, an intolerable adverse event (including any seizure), noncompliance, withdrawal of consent, discontinuation by the sponsor, or investigator. Participants were followed-up until 30 days after last dose of study drug or before initiation of a new antitumor or investigational therapy, whichever occurred first. Participants received enzalutamide 160 mg (four 40 mg) capsule in combination with the anastrozole 1 mg tablet, orally, once daily until documented disease progression, initiation of a new antitumor treatment, an intolerable adverse event (including any seizure), noncompliance, withdrawal of consent, discontinuation by sponsor, or investigator. Participants were followed-up until 30 days after last dose of study drug or before initiation of a new antitumor or investigational therapy, whichever occurred first. Participants received enzalutamide 160 mg (four 40 mg) capsule in combination with the exemestane 25 mg tablet, orally, once daily until documented disease progression, initiation of a new antitumor treatment, an intolerable adverse event (including any seizure), noncompliance, withdrawal of consent, discontinuation by sponsor, or investigator. Participants were followed-up until 30 days after last dose of study drug or before initiation of a new antitumor or investigational therapy, whichever occurred first. Participants received enzalutamide 160 mg (four 40 mg) capsule in combination with the exemestane 50 mg tablet, orally, once daily until documented disease progression, initiation of a new antitumor treatment, an intolerable adverse event (including any seizure), noncompliance, withdrawal of consent, discontinuation by sponsor, or investigator. Participants were followed-up until 30 days after last dose of study drug or before initiation of a new antitumor or investigational therapy, whichever occurred first. Participants received enzalutamide 160 mg (four 40 mg) capsule once daily in combination with the fulvestrant 500 mg intramuscular injection, once every 28 days until documented disease progression, initiation of a new antitumor treatment, an intolerable adverse event (including any seizure), noncompliance, withdrawal of consent, discontinuation by the sponsor, or investigator. Participants were followed-up until 30 days after last dose of study drug or before initiation of a new antitumor or investigational therapy, whichever occurred first.
    Measure Participants 7 8 14 20 16 23 11
    Blood pressure
    1
    14.3%
    0
    0%
    1
    7.1%
    0
    0%
    1
    6.3%
    2
    8.7%
    1
    9.1%
    Heart rate
    0
    0%
    2
    25%
    1
    7.1%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    7. Primary Outcome
    Title Dose-Escalation Phase: Maximum Plasma Concentration (Cmax) of Enzalutamide and Its Metabolites After Single Dose
    Description Carboxylic Acid (M1) and N-desmethyl (M2) are two metabolites of Enzalutamide.
    Time Frame pre-dose, 0.5, 1, 2, 4, 6, 24, 48, 72 and 96 hours post dose on Day 1

    Outcome Measure Data

    Analysis Population Description
    Pharmacokinetic (PK) analysis population included all participants who had at least 1 dose of Enzalutamide and had sufficient PK data to calculate at least 1 of the PK parameters of interest in at least 1 treatment period.
    Arm/Group Title Dose Escalation: Enzalutamide 80 mg Dose Escalation: Enzalutamide 160 mg
    Arm/Group Description Participants received enzalutamide 80 mg (two 40 mg) capsules, orally, once daily until documented disease progression, initiation of a new antitumor treatment, an intolerable adverse event (including any seizure), noncompliance, withdrawal of consent, discontinuation by sponsor, or investigator. Participants were followed-up until 30 days after last dose of study drug or before initiation of a new antitumor or investigational therapy, whichever occurred first. Participants received enzalutamide 160 mg (four 40 mg) capsules, orally, once daily until documented disease progression, initiation of a new antitumor treatment, an intolerable adverse event (including any seizure), noncompliance, withdrawal of consent, discontinuation by sponsor, or investigator. Participants were followed-up until 30 days after last dose of study drug or before initiation of a new antitumor or investigational therapy, whichever occurred first.
    Measure Participants 7 8
    Enzalutamide
    1.90
    (0.757)
    4.01
    (2.09)
    M1
    0.0375
    (0.0286)
    0.0707
    (0.0379)
    M2
    0.0879
    (0.0718)
    0.184
    (0.0689)
    8. Primary Outcome
    Title Dose-Escalation Phase: Time to Reach Maximum Plasma Concentration (Tmax) of Enzalutamide and Its Metabolites After Single Dosing
    Description Carboxylic Acid (M1) and N-desmethyl (M2) are two metabolites of Enzalutamide.
    Time Frame pre-dose, 0.5, 1, 2, 4, 6, 24, 48, 72 and 96 hours post dose on Day 1

    Outcome Measure Data

    Analysis Population Description
    PK analysis population included all participants who had at least 1 dose of Enzalutamide and had sufficient PK data to calculate at least 1 of the PK parameters of interest in at least 1 treatment period.
    Arm/Group Title Dose Escalation: Enzalutamide 80 mg Dose Escalation: Enzalutamide 160 mg
    Arm/Group Description Participants received enzalutamide 80 mg (two 40 mg) capsules, orally, once daily until documented disease progression, initiation of a new antitumor treatment, an intolerable adverse event (including any seizure), noncompliance, withdrawal of consent, discontinuation by sponsor, or investigator. Participants were followed-up until 30 days after last dose of study drug or before initiation of a new antitumor or investigational therapy, whichever occurred first. Participants received enzalutamide 160 mg (four 40 mg) capsules, orally, once daily until documented disease progression, initiation of a new antitumor treatment, an intolerable adverse event (including any seizure), noncompliance, withdrawal of consent, discontinuation by sponsor, or investigator. Participants were followed-up until 30 days after last dose of study drug or before initiation of a new antitumor or investigational therapy, whichever occurred first.
    Measure Participants 7 8
    Enzalutamide
    0.500
    1.00
    M1
    24.1
    23.1
    M2
    23.9
    23.7
    9. Primary Outcome
    Title Dose-Escalation Phase: Area Under the Plasma Concentration-time Curve From Time Zero to 24 Hours (AUC24h) of Enzalutamide and Its Metabolites After Single Dose
    Description Carboxylic Acid (M1) and N-desmethyl (M2) are two metabolites of Enzalutamide.
    Time Frame pre-dose, 0.5, 1, 2, 4, 6 and 24 hours post dose on Day 1

    Outcome Measure Data

    Analysis Population Description
    PK analysis population included all participants who had at least 1 dose of Enzalutamide and had sufficient PK data to calculate at least 1 of the PK parameters of interest in at least 1 treatment period.
    Arm/Group Title Dose Escalation: Enzalutamide 80 mg Dose Escalation: Enzalutamide 160 mg
    Arm/Group Description Participants received enzalutamide 80 mg (two 40 mg) capsules, orally, once daily until documented disease progression, initiation of a new antitumor treatment, an intolerable adverse event (including any seizure), noncompliance, withdrawal of consent, discontinuation by sponsor, or investigator. Participants were followed-up until 30 days after last dose of study drug or before initiation of a new antitumor or investigational therapy, whichever occurred first. Participants received enzalutamide 160 mg (four 40 mg) capsules, orally, once daily until documented disease progression, initiation of a new antitumor treatment, an intolerable adverse event (including any seizure), noncompliance, withdrawal of consent, discontinuation by sponsor, or investigator. Participants were followed-up until 30 days after last dose of study drug or before initiation of a new antitumor or investigational therapy, whichever occurred first.
    Measure Participants 7 8
    Enzalutamide
    17.3
    (8.32)
    41.6
    (8.19)
    M1
    0.632
    (0.385)
    1.20
    (0.648)
    M2
    1.13
    (0.916)
    2.76
    (1.00)
    10. Primary Outcome
    Title Dose-Escalation Phase: Area Under the Plasma Concentration-time Curve From Time Zero to 72 Hours (AUC72h) of Enzalutamide After Single Dosing
    Description
    Time Frame pre-dose, 0.5, 1, 2, 4, 6, 24, 48 and 72 hours post dose on Day 1

    Outcome Measure Data

    Analysis Population Description
    PK analysis population included all participants who had at least 1 dose of Enzalutamide and had sufficient PK data to calculate at least 1 of the PK parameters of interest in at least 1 treatment period.
    Arm/Group Title Dose Escalation: Enzalutamide 80 mg Dose Escalation: Enzalutamide 160 mg
    Arm/Group Description Participants received enzalutamide 80 mg (two 40 mg) capsules, orally, once daily until documented disease progression, initiation of a new antitumor treatment, an intolerable adverse event (including any seizure), noncompliance, withdrawal of consent, discontinuation by sponsor, or investigator. Participants were followed-up until 30 days after last dose of study drug or before initiation of a new antitumor or investigational therapy, whichever occurred first. Participants received enzalutamide 160 mg (four 40 mg) capsules, orally, once daily until documented disease progression, initiation of a new antitumor treatment, an intolerable adverse event (including any seizure), noncompliance, withdrawal of consent, discontinuation by sponsor, or investigator. Participants were followed-up until 30 days after last dose of study drug or before initiation of a new antitumor or investigational therapy, whichever occurred first.
    Measure Participants 7 8
    Mean (Standard Deviation) [micrograms*hour per milliliter]
    43.0
    (21.4)
    107
    (15.6)
    11. Primary Outcome
    Title Dose-Escalation Phase: Area Under the Plasma Concentration-Time Profile From Time Zero Extrapolated to Infinite Time (AUCinf) of Enzalutamide After Single Dosing
    Description AUCinf = Area under the plasma concentration versus time curve (AUC) from time zero (pre-dose) to extrapolated infinite time (0 - inf).
    Time Frame pre-dose, 0.5, 1, 2, 4, 6, 24, 48, 72 and 96 hours post dose on Day 1

    Outcome Measure Data

    Analysis Population Description
    PK analysis population included all participants who had at least 1 dose of Enzalutamide and had sufficient PK data to calculate at least 1 of the PK parameters of interest in at least 1 treatment period.
    Arm/Group Title Dose Escalation: Enzalutamide 80 mg Dose Escalation: Enzalutamide 160 mg
    Arm/Group Description Participants received enzalutamide 80 mg (two 40 mg) capsules, orally, once daily until documented disease progression, initiation of a new antitumor treatment, an intolerable adverse event (including any seizure), noncompliance, withdrawal of consent, discontinuation by sponsor, or investigator. Participants were followed-up until 30 days after last dose of study drug or before initiation of a new antitumor or investigational therapy, whichever occurred first. Participants received enzalutamide 160 mg (four 40 mg) capsules, orally, once daily until documented disease progression, initiation of a new antitumor treatment, an intolerable adverse event (including any seizure), noncompliance, withdrawal of consent, discontinuation by sponsor, or investigator. Participants were followed-up until 30 days after last dose of study drug or before initiation of a new antitumor or investigational therapy, whichever occurred first.
    Measure Participants 7 8
    Mean (Standard Deviation) [micrograms*hour per milliliter]
    208
    (66.0)
    478
    (232)
    12. Primary Outcome
    Title Dose-Escalation Phase: Terminal Elimination Half-Life (t1/2) of Enzalutamide After Single Dosing
    Description Terminal elimination half-life is the time measured for the plasma concentration of Enzalutamide to decrease by one-half of its initial concentration.
    Time Frame pre-dose, 0.5, 1, 2, 4, 6, 24, 48, 72 and 96 hours post dose on Day 1

    Outcome Measure Data

    Analysis Population Description
    PK analysis population included all participants who had at least 1 dose of Enzalutamide and had sufficient PK data to calculate at least 1 of the PK parameters of interest in at least 1 treatment period.
    Arm/Group Title Dose Escalation: Enzalutamide 80 mg Dose Escalation: Enzalutamide 160 mg
    Arm/Group Description Participants received enzalutamide 80 mg (two 40 mg) capsules, orally, once daily until documented disease progression, initiation of a new antitumor treatment, an intolerable adverse event (including any seizure), noncompliance, withdrawal of consent, discontinuation by sponsor, or investigator. Participants were followed-up until 30 days after last dose of study drug or before initiation of a new antitumor or investigational therapy, whichever occurred first. Participants received enzalutamide 160 mg (four 40 mg) capsules, orally, once daily until documented disease progression, initiation of a new antitumor treatment, an intolerable adverse event (including any seizure), noncompliance, withdrawal of consent, discontinuation by sponsor, or investigator. Participants were followed-up until 30 days after last dose of study drug or before initiation of a new antitumor or investigational therapy, whichever occurred first.
    Measure Participants 7 8
    Mean (Standard Deviation) [hours]
    280
    (170)
    198
    (105)
    13. Primary Outcome
    Title Dose Escalation Phase: Apparent Oral Clearance (CL/F) of Enzalutamide After Single Dosing
    Description Apparent oral clearance of a drug is a measure of the rate at which a drug is metabolized or eliminated by normal biological processes. It was 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 and 96 hours post dose on Day 1

    Outcome Measure Data

    Analysis Population Description
    PK analysis population included all participants who had at least 1 dose of Enzalutamide and had sufficient PK data to calculate at least 1 of the PK parameters of interest in at least 1 treatment period.
    Arm/Group Title Dose Escalation: Enzalutamide 80 mg Dose Escalation: Enzalutamide 160 mg
    Arm/Group Description Participants received enzalutamide 80 mg (two 40 mg) capsules, orally, once daily until documented disease progression, initiation of a new antitumor treatment, an intolerable adverse event (including any seizure), noncompliance, withdrawal of consent, discontinuation by sponsor, or investigator. Participants were followed-up until 30 days after last dose of study drug or before initiation of a new antitumor or investigational therapy, whichever occurred first. Participants received enzalutamide 160 mg (four 40 mg) capsules, orally, once daily until documented disease progression, initiation of a new antitumor treatment, an intolerable adverse event (including any seizure), noncompliance, withdrawal of consent, discontinuation by sponsor, or investigator. Participants were followed-up until 30 days after last dose of study drug or before initiation of a new antitumor or investigational therapy, whichever occurred first.
    Measure Participants 7 8
    Mean (Standard Deviation) [liter per hour]
    0.426
    (0.160)
    0.382
    (0.115)
    14. Primary Outcome
    Title Dose Escalation Phase: Apparent Volume of Distribution (Vz/F) of Enzalutamide After Single Dosing
    Description Volume of distribution is defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired plasma concentration of a drug. Apparent volume of distribution after oral dose (Vz/F) is influenced by the fraction absorbed.
    Time Frame pre-dose, 0.5, 1, 2, 4, 6, 24, 48, 72 and 96 hours post dose on Day 1

    Outcome Measure Data

    Analysis Population Description
    PK analysis population included all participants who had at least 1 dose of Enzalutamide and had sufficient PK data to calculate at least 1 of the PK parameters of interest in at least 1 treatment period.
    Arm/Group Title Dose Escalation: Enzalutamide 80 mg Dose Escalation: Enzalutamide 160 mg
    Arm/Group Description Participants received enzalutamide 80 mg (two 40 mg) capsules, orally, once daily until documented disease progression, initiation of a new antitumor treatment, an intolerable adverse event (including any seizure), noncompliance, withdrawal of consent, discontinuation by sponsor, or investigator. Participants were followed-up until 30 days after last dose of study drug or before initiation of a new antitumor or investigational therapy, whichever occurred first. Participants received enzalutamide 160 mg (four 40 mg) capsules, orally, once daily until documented disease progression, initiation of a new antitumor treatment, an intolerable adverse event (including any seizure), noncompliance, withdrawal of consent, discontinuation by sponsor, or investigator. Participants were followed-up until 30 days after last dose of study drug or before initiation of a new antitumor or investigational therapy, whichever occurred first.
    Measure Participants 7 8
    Mean (Standard Deviation) [liter]
    151
    (73.6)
    94.5
    (13.7)
    15. Primary Outcome
    Title Dose-Escalation Phase: Maximum Plasma Concentration (Cmax) of Enzalutamide and Its Metabolites After Multiple Dosing
    Description Carboxylic Acid (M1) and N-desmethyl (M2) are two metabolites of Enzalutamide.
    Time Frame pre-dose, 0.5, 1, 2, 4, 6, and 24 hours post-dose on Day 50

    Outcome Measure Data

    Analysis Population Description
    PK analysis population included all participants who had at least 1 dose of Enzalutamide and had sufficient PK data to calculate at least 1 of the PK parameters of interest in at least 1 treatment period. Here, number of participants analyzed signifies those participants who were evaluable for this outcome measure.
    Arm/Group Title Dose Escalation: Enzalutamide 80 mg Dose Escalation: Enzalutamide 160 mg
    Arm/Group Description Participants received enzalutamide 80 mg (two 40 mg) capsules, orally, once daily until documented disease progression, initiation of a new antitumor treatment, an intolerable adverse event (including any seizure), noncompliance, withdrawal of consent, discontinuation by sponsor, or investigator. Participants were followed-up until 30 days after last dose of study drug or before initiation of a new antitumor or investigational therapy, whichever occurred first. Participants received enzalutamide 160 mg (four 40 mg) capsules, orally, once daily until documented disease progression, initiation of a new antitumor treatment, an intolerable adverse event (including any seizure), noncompliance, withdrawal of consent, discontinuation by sponsor, or investigator. Participants were followed-up until 30 days after last dose of study drug or before initiation of a new antitumor or investigational therapy, whichever occurred first.
    Measure Participants 3 6
    Enzalutamide
    11.6
    (1.95)
    15.3
    (2.62)
    M1
    1.77
    (0.521)
    6.24
    (2.28)
    M2
    6.42
    (0.132)
    14.1
    (3.66)
    16. Primary Outcome
    Title Dose-Escalation Phase: Time to Reach Maximum Plasma Concentration (Tmax) of Enzalutamide and Its Metabolites After Multiple Dosing
    Description Carboxylic Acid (M1) and N-desmethyl (M2) are two metabolites of Enzalutamide.
    Time Frame pre-dose, 0.5, 1, 2, 4, 6, and 24 hours post-dose on Day 50

    Outcome Measure Data

    Analysis Population Description
    PK analysis population included all participants who had at least 1 dose of Enzalutamide and had sufficient PK data to calculate at least 1 of the PK parameters of interest in at least 1 treatment period. Here, number of participants analyzed signifies those participants who were evaluable for this outcome measure.
    Arm/Group Title Dose Escalation: Enzalutamide 80 mg Dose Escalation: Enzalutamide 160 mg
    Arm/Group Description Participants received enzalutamide 80 mg (two 40 mg) capsules, orally, once daily until documented disease progression, initiation of a new antitumor treatment, an intolerable adverse event (including any seizure), noncompliance, withdrawal of consent, discontinuation by sponsor, or investigator. Participants were followed-up until 30 days after last dose of study drug or before initiation of a new antitumor or investigational therapy, whichever occurred first. Participants received enzalutamide 160 mg (four 40 mg) capsules, orally, once daily until documented disease progression, initiation of a new antitumor treatment, an intolerable adverse event (including any seizure), noncompliance, withdrawal of consent, discontinuation by sponsor, or investigator. Participants were followed-up until 30 days after last dose of study drug or before initiation of a new antitumor or investigational therapy, whichever occurred first.
    Measure Participants 3 6
    Enzalutamide
    0.500
    1.00
    M1
    5.70
    2.29
    M2
    24.0
    0.58
    17. Primary Outcome
    Title Dose-Escalation Phase: Area Under the Curve From Time Zero to End of Dosing Interval (AUCtau) of Enzalutamide and Its Metabolites After Multiple Dosing
    Description Area under the plasma concentration versus time-curve from time zero to end of dosing interval (AUCtau), where dosing interval was 24 hours. Carboxylic Acid (M1) and N-desmethyl (M2) are two metabolites of Enzalutamide.
    Time Frame pre-dose, 0.5, 1, 2, 4, 6, and 24 hours post-dose on Day 50

    Outcome Measure Data

    Analysis Population Description
    PK analysis population included all participants who had at least 1 dose of Enzalutamide and had sufficient PK data to calculate at least 1 of the PK parameters of interest in at least 1 treatment period. Here, number of participants analyzed signifies those participants who were evaluable for this outcome measure.
    Arm/Group Title Dose Escalation: Enzalutamide 80 mg Dose Escalation: Enzalutamide 160 mg
    Arm/Group Description Participants received enzalutamide 80 mg (two 40 mg) capsules, orally, once daily until documented disease progression, initiation of a new antitumor treatment, an intolerable adverse event (including any seizure), noncompliance, withdrawal of consent, discontinuation by sponsor, or investigator. Participants were followed-up until 30 days after last dose of study drug or before initiation of a new antitumor or investigational therapy, whichever occurred first. Participants received enzalutamide 160 mg (four 40 mg) capsules, orally, once daily until documented disease progression, initiation of a new antitumor treatment, an intolerable adverse event (including any seizure), noncompliance, withdrawal of consent, discontinuation by sponsor, or investigator. Participants were followed-up until 30 days after last dose of study drug or before initiation of a new antitumor or investigational therapy, whichever occurred first.
    Measure Participants 3 6
    Enzalutamide
    207
    (24.3)
    325
    (61.6)
    M1
    33.0
    (13.0)
    120
    (56.0)
    M2
    140
    (6.08)
    317
    (89.4)
    18. Primary Outcome
    Title Dose-Escalation Phase: Apparent Oral Clearance (CL/F) of Enzalutamide After Multiple Dosing
    Description Apparent oral clearance of a drug is a measure of the rate at which a drug is metabolized or eliminated by normal biological processes. It was 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, and 24 hours post-dose on Day 50

    Outcome Measure Data

    Analysis Population Description
    PK analysis population included all participants who had at least 1 dose of Enzalutamide and had sufficient PK data to calculate at least 1 of the PK parameters of interest in at least 1 treatment period. Here, number of participants analyzed signifies those participants who were evaluable for this outcome measure.
    Arm/Group Title Dose Escalation: Enzalutamide 80 mg Dose Escalation: Enzalutamide 160 mg
    Arm/Group Description Participants received enzalutamide 80 mg (two 40 mg) capsules, orally, once daily until documented disease progression, initiation of a new antitumor treatment, an intolerable adverse event (including any seizure), noncompliance, withdrawal of consent, discontinuation by sponsor, or investigator. Participants were followed-up until 30 days after last dose of study drug or before initiation of a new antitumor or investigational therapy, whichever occurred first. Participants received enzalutamide 160 mg (four 40 mg) capsules, orally, once daily until documented disease progression, initiation of a new antitumor treatment, an intolerable adverse event (including any seizure), noncompliance, withdrawal of consent, discontinuation by sponsor, or investigator. Participants were followed-up until 30 days after last dose of study drug or before initiation of a new antitumor or investigational therapy, whichever occurred first.
    Measure Participants 3 6
    Mean (Standard Deviation) [liter per hour]
    0.390
    (0.0491)
    0.507
    (0.0906)
    19. Primary Outcome
    Title Dose-Escalation Phase: Peak-to-Trough Ratio of Enzalutamide and Its Metabolites After Multiple Dosing
    Description Peak-to-trough ratio was calculated by dividing Cmax with Cmin of Enzalutamide and its Metabolites. Carboxylic Acid (M1) and N-desmethyl (M2) are two metabolites of Enzalutamide. Cmax was maximum plasma concentration during the dosing interval and Cmin was minimum observed plasma concentration during the dosing interval.
    Time Frame pre-dose, 0.5, 1, 2, 4, 6, and 24 hours post-dose on Day 50

    Outcome Measure Data

    Analysis Population Description
    PK analysis population included all participants who had at least 1 dose of Enzalutamide and had sufficient PK data to calculate at least 1 of the PK parameters of interest in at least 1 treatment period. Here, number of participants analyzed signifies those participants who were evaluable for this outcome measure.
    Arm/Group Title Dose Escalation: Enzalutamide 80 mg Dose Escalation: Enzalutamide 160 mg
    Arm/Group Description Participants received enzalutamide 80 mg (two 40 mg) capsules, orally, once daily until documented disease progression, initiation of a new antitumor treatment, an intolerable adverse event (including any seizure), noncompliance, withdrawal of consent, discontinuation by sponsor, or investigator. Participants were followed-up until 30 days after last dose of study drug or before initiation of a new antitumor or investigational therapy, whichever occurred first. Participants received enzalutamide 160 mg (four 40 mg) capsules, orally, once daily until documented disease progression, initiation of a new antitumor treatment, an intolerable adverse event (including any seizure), noncompliance, withdrawal of consent, discontinuation by sponsor, or investigator. Participants were followed-up until 30 days after last dose of study drug or before initiation of a new antitumor or investigational therapy, whichever occurred first.
    Measure Participants 3 6
    Enzalutamide
    1.39
    (0.400)
    1.14
    (0.174)
    M1
    1.32
    (0.407)
    1.42
    (0.388)
    M2
    0.999
    (0.0012)
    1.00
    (0.0420)
    20. Primary Outcome
    Title Dose-Escalation Phase: Accumulation Ratio of AUC24 of Enzalutamide and Its Metabolites After Multiple Dosing
    Description Accumulation Ratio was defined as the ratio of AUC24 of Day 50 to AUC24 of Day 1, where AUC24 was area under the plasma concentration-time curve from time zero to 24 hours post-dose. Carboxylic Acid (M1) and N-desmethyl (M2) are two metabolites of Enzalutamide.
    Time Frame pre-dose, 0.5, 1, 2, 4, 6, and 24 hours post-dose on Day 1 and 50

    Outcome Measure Data

    Analysis Population Description
    PK analysis population included all participants who had at least 1 dose of Enzalutamide and had sufficient PK data to calculate at least 1 of the PK parameters of interest in at least 1 treatment period. Here, number of participants analyzed signifies those participants who were evaluable for this outcome measure.
    Arm/Group Title Dose Escalation: Enzalutamide 80 mg Dose Escalation: Enzalutamide 160 mg
    Arm/Group Description Participants received enzalutamide 80 mg (two 40 mg) capsules, orally, once daily until documented disease progression, initiation of a new antitumor treatment, an intolerable adverse event (including any seizure), noncompliance, withdrawal of consent, discontinuation by sponsor, or investigator. Participants were followed-up until 30 days after last dose of study drug or before initiation of a new antitumor or investigational therapy, whichever occurred first. Participants received enzalutamide 160 mg (four 40 mg) capsules, orally, once daily until documented disease progression, initiation of a new antitumor treatment, an intolerable adverse event (including any seizure), noncompliance, withdrawal of consent, discontinuation by sponsor, or investigator. Participants were followed-up until 30 days after last dose of study drug or before initiation of a new antitumor or investigational therapy, whichever occurred first.
    Measure Participants 3 6
    Enzalutamide
    17.9
    (2.69)
    9.39
    (3.75)
    M1
    47.6
    (21.4)
    68.0
    (35.8)
    M2
    157
    (48.2)
    77.8
    (35.7)
    21. Secondary Outcome
    Title Dose-Expansion Phase: Trough Plasma Concentration for Enzalutamide
    Description
    Time Frame pre-dose on Day 57

    Outcome Measure Data

    Analysis Population Description
    PK analysis population included all participants who had at least 1 dose of Enzalutamide and had sufficient PK data to calculate at least 1 of the PK parameters of interest in at least 1 treatment period.
    Arm/Group Title Dose Expansion: Enzalutamide 160 mg Dose Expansion: Enzalutamide 160 mg + Anastrozole 1 mg Dose Expansion: Enzalutamide 160 mg + Exemestane 25 mg Dose Expansion: Enzalutamide 160 mg + Exemestane 50 mg Dose Expansion: Enzalutamide 160 mg + Fulvestrant 500 mg
    Arm/Group Description Participants received enzalutamide 160 mg (four 40 mg) capsules, orally, once daily until documented disease progression, initiation of a new antitumor treatment, an intolerable adverse event (including any seizure), noncompliance, withdrawal of consent, discontinuation by the sponsor, or investigator. Participants were followed-up until 30 days after last dose of study drug or before initiation of a new antitumor or investigational therapy, whichever occurred first. Participants received enzalutamide 160 mg (four 40 mg) capsule in combination with the exemestane 25 mg tablet, orally, once daily until documented disease progression, initiation of a new antitumor treatment, an intolerable adverse event (including any seizure), noncompliance, withdrawal of consent, discontinuation by sponsor, or investigator. Participants were followed-up until 30 days after last dose of study drug or before initiation of a new antitumor or investigational therapy, whichever occurred first. Participants received enzalutamide 160 mg (four 40 mg) capsule in combination with the exemestane 25 mg tablet, orally, once daily until documented disease progression, initiation of a new antitumor treatment, an intolerable adverse event (including any seizure), noncompliance, withdrawal of consent, discontinuation by sponsor, or investigator. Participants were followed-up until 30 days after last dose of study drug or before initiation of a new antitumor or investigational therapy, whichever occurred first. Participants received enzalutamide 160 mg (four 40 mg) capsule in combination with the exemestane 50 mg tablet, orally, once daily until documented disease progression, initiation of a new antitumor treatment, an intolerable adverse event (including any seizure), noncompliance, withdrawal of consent, discontinuation by sponsor, or investigator. Participants were followed-up until 30 days after last dose of study drug or before initiation of a new antitumor or investigational therapy, whichever occurred first. Participants received enzalutamide 160 mg (four 40 mg) capsule once daily in combination with the fulvestrant 500 mg intramuscular injection, once every 28 days until documented disease progression, initiation of a new antitumor treatment, an intolerable adverse event (including any seizure), noncompliance, withdrawal of consent, discontinuation by the sponsor, or investigator. Participants were followed-up until 30 days after last dose of study drug or before initiation of a new antitumor or investigational therapy, whichever occurred first.
    Measure Participants 3 9 5 12 7
    Mean (Standard Deviation) [micrograms per milliliter]
    13.40
    (2.51)
    14.33
    (3.99)
    13.52
    (2.62)
    12.41
    (3.76)
    11.62
    (4.69)

    Adverse Events

    Time Frame Day 1 up to 30 days after the last dose of study drug or before initiation of a new systemic antitumor treatment, whichever occurred first (up to 3.5 years)
    Adverse Event Reporting Description Same event may appear as both an AE and SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.
    Arm/Group Title Dose Escalation: Enzalutamide 80 mg Dose Escalation: Enzalutamide 160 mg Dose Expansion: Enzalutamide 160 mg Dose Expansion: Enzalutamide 160 mg + Anastrozole 1 mg Dose Expansion: Enzalutamide 160 mg + Exemestane 25 mg Dose Expansion: Enzalutamide 160 mg + Exemestane 50 mg Dose Expansion: Enzalutamide 160 mg + Fulvestrant 500 mg
    Arm/Group Description Participants received enzalutamide 80 mg (two 40 mg) capsules, orally, once daily until documented disease progression, initiation of a new antitumor treatment, an intolerable adverse event (including any seizure), noncompliance, withdrawal of consent, discontinuation by sponsor, or investigator. Participants were followed-up until 30 days after last dose of study drug or before initiation of a new antitumor or investigational therapy, whichever occurred first. Participants received enzalutamide 160 mg (four 40 mg) capsules, orally, once daily until documented disease progression, initiation of a new antitumor treatment, an intolerable adverse event (including any seizure), noncompliance, withdrawal of consent, discontinuation by sponsor, or investigator. Participants were followed-up until 30 days after last dose of study drug or before initiation of a new antitumor or investigational therapy, whichever occurred first. Participants received enzalutamide 160 mg (four 40 mg) capsules, orally, once daily until documented disease progression, initiation of a new antitumor treatment, an intolerable adverse event (including any seizure), noncompliance, withdrawal of consent, discontinuation by the sponsor, or investigator. Participants were followed-up until 30 days after last dose of study drug or before initiation of a new antitumor or investigational therapy, whichever occurred first. Participants received enzalutamide 160 mg (four 40 mg) capsule in combination with the anastrozole 1 mg tablet, orally, once daily until documented disease progression, initiation of a new antitumor treatment, an intolerable adverse event (including any seizure), noncompliance, withdrawal of consent, discontinuation by sponsor, or investigator. Participants were followed-up until 30 days after last dose of study drug or before initiation of a new antitumor or investigational therapy, whichever occurred first. Participants received enzalutamide 160 mg (four 40 mg) capsule in combination with the exemestane 25 mg tablet, orally, once daily until documented disease progression, initiation of a new antitumor treatment, an intolerable adverse event (including any seizure), noncompliance, withdrawal of consent, discontinuation by sponsor, or investigator. Participants were followed-up until 30 days after last dose of study drug or before initiation of a new antitumor or investigational therapy, whichever occurred first. Participants received enzalutamide 160 mg (four 40 mg) capsule in combination with the exemestane 50 mg tablet, orally, once daily until documented disease progression, initiation of a new antitumor treatment, an intolerable adverse event (including any seizure), noncompliance, withdrawal of consent, discontinuation by sponsor, or investigator. Participants were followed-up until 30 days after last dose of study drug or before initiation of a new antitumor or investigational therapy, whichever occurred first. Participants received enzalutamide 160 mg (four 40 mg) capsule once daily in combination with the fulvestrant 500 mg intramuscular injection, once every 28 days until documented disease progression, initiation of a new antitumor treatment, an intolerable adverse event (including any seizure), noncompliance, withdrawal of consent, discontinuation by the sponsor, or investigator. Participants were followed-up until 30 days after last dose of study drug or before initiation of a new antitumor or investigational therapy, whichever occurred first.
    All Cause Mortality
    Dose Escalation: Enzalutamide 80 mg Dose Escalation: Enzalutamide 160 mg Dose Expansion: Enzalutamide 160 mg Dose Expansion: Enzalutamide 160 mg + Anastrozole 1 mg Dose Expansion: Enzalutamide 160 mg + Exemestane 25 mg Dose Expansion: Enzalutamide 160 mg + Exemestane 50 mg Dose Expansion: Enzalutamide 160 mg + Fulvestrant 500 mg
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 0/7 (0%) 0/8 (0%) 1/14 (7.1%) 0/20 (0%) 0/16 (0%) 0/23 (0%) 0/11 (0%)
    Serious Adverse Events
    Dose Escalation: Enzalutamide 80 mg Dose Escalation: Enzalutamide 160 mg Dose Expansion: Enzalutamide 160 mg Dose Expansion: Enzalutamide 160 mg + Anastrozole 1 mg Dose Expansion: Enzalutamide 160 mg + Exemestane 25 mg Dose Expansion: Enzalutamide 160 mg + Exemestane 50 mg Dose Expansion: Enzalutamide 160 mg + Fulvestrant 500 mg
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 2/7 (28.6%) 1/8 (12.5%) 2/14 (14.3%) 1/20 (5%) 5/16 (31.3%) 3/23 (13%) 2/11 (18.2%)
    Blood and lymphatic system disorders
    Anaemia 0/7 (0%) 1/8 (12.5%) 0/14 (0%) 0/20 (0%) 0/16 (0%) 0/23 (0%) 0/11 (0%)
    Iron Deficiency Anaemia 0/7 (0%) 0/8 (0%) 0/14 (0%) 0/20 (0%) 0/16 (0%) 0/23 (0%) 1/11 (9.1%)
    Cardiac disorders
    Pericardial Effusion 0/7 (0%) 0/8 (0%) 0/14 (0%) 0/20 (0%) 1/16 (6.3%) 0/23 (0%) 0/11 (0%)
    Endocrine disorders
    Adrenal Insufficiency 1/7 (14.3%) 0/8 (0%) 0/14 (0%) 0/20 (0%) 0/16 (0%) 0/23 (0%) 0/11 (0%)
    Gastrointestinal disorders
    Abdominal Pain 0/7 (0%) 0/8 (0%) 1/14 (7.1%) 0/20 (0%) 0/16 (0%) 0/23 (0%) 0/11 (0%)
    Gastritis Erosive 0/7 (0%) 0/8 (0%) 0/14 (0%) 0/20 (0%) 0/16 (0%) 0/23 (0%) 1/11 (9.1%)
    Infections and infestations
    Urosepsis 0/7 (0%) 0/8 (0%) 1/14 (7.1%) 0/20 (0%) 0/16 (0%) 0/23 (0%) 0/11 (0%)
    Pneumonia 0/7 (0%) 0/8 (0%) 0/14 (0%) 0/20 (0%) 0/16 (0%) 2/23 (8.7%) 0/11 (0%)
    Urinary Tract Infection 0/7 (0%) 0/8 (0%) 0/14 (0%) 0/20 (0%) 0/16 (0%) 0/23 (0%) 1/11 (9.1%)
    Enterocolitis infectious 0/7 (0%) 0/8 (0%) 0/14 (0%) 0/20 (0%) 1/16 (6.3%) 0/23 (0%) 0/11 (0%)
    Injury, poisoning and procedural complications
    In-Stent Coronary Artery Restenosis 0/7 (0%) 0/8 (0%) 1/14 (7.1%) 0/20 (0%) 0/16 (0%) 0/23 (0%) 0/11 (0%)
    Humerus Fracture 0/7 (0%) 0/8 (0%) 0/14 (0%) 0/20 (0%) 0/16 (0%) 1/23 (4.3%) 0/11 (0%)
    Metabolism and nutrition disorders
    Dehydration 0/7 (0%) 0/8 (0%) 0/14 (0%) 0/20 (0%) 0/16 (0%) 0/23 (0%) 1/11 (9.1%)
    Hypercalcaemia 0/7 (0%) 0/8 (0%) 0/14 (0%) 0/20 (0%) 1/16 (6.3%) 0/23 (0%) 0/11 (0%)
    Musculoskeletal and connective tissue disorders
    Pathological Fracture 0/7 (0%) 0/8 (0%) 0/14 (0%) 0/20 (0%) 1/16 (6.3%) 0/23 (0%) 0/11 (0%)
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Tumour Pain 0/7 (0%) 0/8 (0%) 0/14 (0%) 0/20 (0%) 1/16 (6.3%) 0/23 (0%) 0/11 (0%)
    Renal and urinary disorders
    Hydronephrosis 1/7 (14.3%) 0/8 (0%) 0/14 (0%) 0/20 (0%) 0/16 (0%) 0/23 (0%) 0/11 (0%)
    Obstructive Uropathy 0/7 (0%) 0/8 (0%) 1/14 (7.1%) 0/20 (0%) 0/16 (0%) 0/23 (0%) 0/11 (0%)
    Renal Failure Acute 0/7 (0%) 0/8 (0%) 0/14 (0%) 0/20 (0%) 1/16 (6.3%) 0/23 (0%) 0/11 (0%)
    Ureteric Obstruction 0/7 (0%) 0/8 (0%) 0/14 (0%) 0/20 (0%) 1/16 (6.3%) 0/23 (0%) 0/11 (0%)
    Respiratory, thoracic and mediastinal disorders
    Pleural Effusion 0/7 (0%) 0/8 (0%) 0/14 (0%) 1/20 (5%) 0/16 (0%) 0/23 (0%) 0/11 (0%)
    Other (Not Including Serious) Adverse Events
    Dose Escalation: Enzalutamide 80 mg Dose Escalation: Enzalutamide 160 mg Dose Expansion: Enzalutamide 160 mg Dose Expansion: Enzalutamide 160 mg + Anastrozole 1 mg Dose Expansion: Enzalutamide 160 mg + Exemestane 25 mg Dose Expansion: Enzalutamide 160 mg + Exemestane 50 mg Dose Expansion: Enzalutamide 160 mg + Fulvestrant 500 mg
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 7/7 (100%) 8/8 (100%) 14/14 (100%) 20/20 (100%) 15/16 (93.8%) 21/23 (91.3%) 11/11 (100%)
    Blood and lymphatic system disorders
    Anaemia 2/7 (28.6%) 2/8 (25%) 1/14 (7.1%) 1/20 (5%) 5/16 (31.3%) 0/23 (0%) 1/11 (9.1%)
    Thrombocytopenia 0/7 (0%) 1/8 (12.5%) 1/14 (7.1%) 2/20 (10%) 0/16 (0%) 1/23 (4.3%) 1/11 (9.1%)
    Iron Deficiency Anaemia 0/7 (0%) 0/8 (0%) 0/14 (0%) 0/20 (0%) 0/16 (0%) 0/23 (0%) 1/11 (9.1%)
    Lymph Node Pain 0/7 (0%) 0/8 (0%) 0/14 (0%) 0/20 (0%) 1/16 (6.3%) 0/23 (0%) 0/11 (0%)
    Neutropenia 0/7 (0%) 0/8 (0%) 0/14 (0%) 1/20 (5%) 2/16 (12.5%) 0/23 (0%) 1/11 (9.1%)
    Haemolytic anaemia 0/7 (0%) 0/8 (0%) 0/14 (0%) 0/20 (0%) 1/16 (6.3%) 0/23 (0%) 0/11 (0%)
    Cardiac disorders
    Palpitations 1/7 (14.3%) 1/8 (12.5%) 0/14 (0%) 0/20 (0%) 0/16 (0%) 0/23 (0%) 0/11 (0%)
    Angina Pectoris 0/7 (0%) 0/8 (0%) 1/14 (7.1%) 0/20 (0%) 0/16 (0%) 0/23 (0%) 0/11 (0%)
    Tachycardia 1/7 (14.3%) 0/8 (0%) 0/14 (0%) 0/20 (0%) 0/16 (0%) 0/23 (0%) 1/11 (9.1%)
    Cardiac Tamponade 0/7 (0%) 0/8 (0%) 0/14 (0%) 0/20 (0%) 1/16 (6.3%) 0/23 (0%) 0/11 (0%)
    Eye disorders
    Dry Eye 0/7 (0%) 2/8 (25%) 0/14 (0%) 1/20 (5%) 0/16 (0%) 0/23 (0%) 0/11 (0%)
    Conjunctivitis 1/7 (14.3%) 0/8 (0%) 0/14 (0%) 0/20 (0%) 0/16 (0%) 0/23 (0%) 1/11 (9.1%)
    Eye Movement Disorder 0/7 (0%) 0/8 (0%) 1/14 (7.1%) 0/20 (0%) 0/16 (0%) 0/23 (0%) 0/11 (0%)
    Eyelid Oedema 0/7 (0%) 0/8 (0%) 1/14 (7.1%) 0/20 (0%) 0/16 (0%) 0/23 (0%) 0/11 (0%)
    Lacrimation Increased 0/7 (0%) 1/8 (12.5%) 0/14 (0%) 0/20 (0%) 0/16 (0%) 0/23 (0%) 0/11 (0%)
    Abnormal Sensation In Eye 0/7 (0%) 0/8 (0%) 0/14 (0%) 0/20 (0%) 0/16 (0%) 0/23 (0%) 1/11 (9.1%)
    Vision Blurred 0/7 (0%) 0/8 (0%) 0/14 (0%) 0/20 (0%) 0/16 (0%) 0/23 (0%) 1/11 (9.1%)
    Visual Acuity Reduced 0/7 (0%) 0/8 (0%) 0/14 (0%) 0/20 (0%) 1/16 (6.3%) 0/23 (0%) 0/11 (0%)
    Gastrointestinal disorders
    Vomiting 1/7 (14.3%) 0/8 (0%) 5/14 (35.7%) 3/20 (15%) 2/16 (12.5%) 7/23 (30.4%) 3/11 (27.3%)
    Diarrhoea 3/7 (42.9%) 1/8 (12.5%) 2/14 (14.3%) 6/20 (30%) 4/16 (25%) 3/23 (13%) 4/11 (36.4%)
    Constipation 0/7 (0%) 2/8 (25%) 2/14 (14.3%) 3/20 (15%) 3/16 (18.8%) 3/23 (13%) 3/11 (27.3%)
    Gastrooesophageal Reflux Disease 0/7 (0%) 0/8 (0%) 4/14 (28.6%) 0/20 (0%) 2/16 (12.5%) 2/23 (8.7%) 0/11 (0%)
    Abdominal Discomfort 1/7 (14.3%) 0/8 (0%) 1/14 (7.1%) 1/20 (5%) 0/16 (0%) 0/23 (0%) 0/11 (0%)
    Abdominal Pain Upper 0/7 (0%) 0/8 (0%) 3/14 (21.4%) 1/20 (5%) 0/16 (0%) 2/23 (8.7%) 0/11 (0%)
    Abdominal Pain 0/7 (0%) 0/8 (0%) 2/14 (14.3%) 1/20 (5%) 1/16 (6.3%) 0/23 (0%) 2/11 (18.2%)
    Haematemesis 0/7 (0%) 0/8 (0%) 1/14 (7.1%) 0/20 (0%) 0/16 (0%) 0/23 (0%) 0/11 (0%)
    Abdominal Distension 0/7 (0%) 0/8 (0%) 1/14 (7.1%) 1/20 (5%) 0/16 (0%) 1/23 (4.3%) 1/11 (9.1%)
    Dry Mouth 0/7 (0%) 1/8 (12.5%) 0/14 (0%) 1/20 (5%) 0/16 (0%) 1/23 (4.3%) 0/11 (0%)
    Epigastric Discomfort 0/7 (0%) 0/8 (0%) 1/14 (7.1%) 0/20 (0%) 0/16 (0%) 0/23 (0%) 0/11 (0%)
    Eructation 1/7 (14.3%) 0/8 (0%) 0/14 (0%) 0/20 (0%) 0/16 (0%) 0/23 (0%) 0/11 (0%)
    Flatulence 0/7 (0%) 0/8 (0%) 1/14 (7.1%) 0/20 (0%) 0/16 (0%) 0/23 (0%) 0/11 (0%)
    Stomatitis 0/7 (0%) 0/8 (0%) 1/14 (7.1%) 0/20 (0%) 0/16 (0%) 0/23 (0%) 0/11 (0%)
    Abdominal Pain Lower 0/7 (0%) 0/8 (0%) 0/14 (0%) 1/20 (5%) 0/16 (0%) 0/23 (0%) 1/11 (9.1%)
    Dyspepsia 0/7 (0%) 0/8 (0%) 0/14 (0%) 1/20 (5%) 0/16 (0%) 1/23 (4.3%) 1/11 (9.1%)
    Frequent Bowel Movements 0/7 (0%) 0/8 (0%) 0/14 (0%) 0/20 (0%) 0/16 (0%) 0/23 (0%) 1/11 (9.1%)
    Gastritis 0/7 (0%) 0/8 (0%) 0/14 (0%) 0/20 (0%) 0/16 (0%) 0/23 (0%) 1/11 (9.1%)
    Nausea 1/7 (14.3%) 3/8 (37.5%) 8/14 (57.1%) 9/20 (45%) 7/16 (43.8%) 12/23 (52.2%) 8/11 (72.7%)
    Faecal incontinence 0/7 (0%) 0/8 (0%) 0/14 (0%) 0/20 (0%) 1/16 (6.3%) 0/23 (0%) 0/11 (0%)
    Dysphagia 0/7 (0%) 0/8 (0%) 1/14 (7.1%) 0/20 (0%) 0/16 (0%) 1/23 (4.3%) 0/11 (0%)
    General disorders
    Fatigue 0/7 (0%) 2/8 (25%) 8/14 (57.1%) 12/20 (60%) 8/16 (50%) 12/23 (52.2%) 8/11 (72.7%)
    Chills 0/7 (0%) 1/8 (12.5%) 1/14 (7.1%) 2/20 (10%) 0/16 (0%) 0/23 (0%) 0/11 (0%)
    Oedema Peripheral 0/7 (0%) 0/8 (0%) 2/14 (14.3%) 1/20 (5%) 1/16 (6.3%) 1/23 (4.3%) 1/11 (9.1%)
    Pyrexia 0/7 (0%) 1/8 (12.5%) 1/14 (7.1%) 1/20 (5%) 0/16 (0%) 2/23 (8.7%) 1/11 (9.1%)
    Asthenia 0/7 (0%) 0/8 (0%) 1/14 (7.1%) 5/20 (25%) 0/16 (0%) 1/23 (4.3%) 0/11 (0%)
    Axillary Pain 0/7 (0%) 1/8 (12.5%) 0/14 (0%) 0/20 (0%) 0/16 (0%) 0/23 (0%) 0/11 (0%)
    Chest Discomfort 1/7 (14.3%) 0/8 (0%) 0/14 (0%) 0/20 (0%) 0/16 (0%) 0/23 (0%) 0/11 (0%)
    Early Satiety 1/7 (14.3%) 0/8 (0%) 0/14 (0%) 1/20 (5%) 0/16 (0%) 0/23 (0%) 0/11 (0%)
    Gait Disturbance 0/7 (0%) 0/8 (0%) 1/14 (7.1%) 0/20 (0%) 0/16 (0%) 0/23 (0%) 0/11 (0%)
    Influenza Like Illness 0/7 (0%) 1/8 (12.5%) 0/14 (0%) 1/20 (5%) 0/16 (0%) 1/23 (4.3%) 0/11 (0%)
    Irritability 0/7 (0%) 0/8 (0%) 1/14 (7.1%) 1/20 (5%) 0/16 (0%) 0/23 (0%) 0/11 (0%)
    Spinal Pain 1/7 (14.3%) 0/8 (0%) 0/14 (0%) 0/20 (0%) 0/16 (0%) 0/23 (0%) 0/11 (0%)
    Suprapubic Pain 0/7 (0%) 0/8 (0%) 1/14 (7.1%) 0/20 (0%) 0/16 (0%) 0/23 (0%) 0/11 (0%)
    Local Swelling 0/7 (0%) 0/8 (0%) 0/14 (0%) 0/20 (0%) 1/16 (6.3%) 0/23 (0%) 0/11 (0%)
    Hepatobiliary disorders
    Hepatomegaly 1/7 (14.3%) 0/8 (0%) 0/14 (0%) 0/20 (0%) 0/16 (0%) 0/23 (0%) 0/11 (0%)
    Immune system disorders
    Drug Hypersensitivity 0/7 (0%) 0/8 (0%) 0/14 (0%) 0/20 (0%) 0/16 (0%) 0/23 (0%) 1/11 (9.1%)
    Infections and infestations
    Breast Cellulitis 1/7 (14.3%) 0/8 (0%) 0/14 (0%) 0/20 (0%) 0/16 (0%) 0/23 (0%) 0/11 (0%)
    Cellulitis 0/7 (0%) 1/8 (12.5%) 0/14 (0%) 0/20 (0%) 1/16 (6.3%) 1/23 (4.3%) 0/11 (0%)
    Cystitis 0/7 (0%) 0/8 (0%) 1/14 (7.1%) 0/20 (0%) 0/16 (0%) 0/23 (0%) 0/11 (0%)
    Ear Infection 0/7 (0%) 1/8 (12.5%) 0/14 (0%) 0/20 (0%) 0/16 (0%) 0/23 (0%) 0/11 (0%)
    Infected Cyst 0/7 (0%) 0/8 (0%) 1/14 (7.1%) 0/20 (0%) 0/16 (0%) 0/23 (0%) 0/11 (0%)
    Pneumonia 0/7 (0%) 0/8 (0%) 1/14 (7.1%) 0/20 (0%) 0/16 (0%) 0/23 (0%) 0/11 (0%)
    Pneumonia Bacterial 0/7 (0%) 0/8 (0%) 1/14 (7.1%) 0/20 (0%) 0/16 (0%) 0/23 (0%) 0/11 (0%)
    Sinusitis 0/7 (0%) 1/8 (12.5%) 0/14 (0%) 0/20 (0%) 1/16 (6.3%) 0/23 (0%) 1/11 (9.1%)
    Skin Infection 0/7 (0%) 0/8 (0%) 1/14 (7.1%) 0/20 (0%) 0/16 (0%) 1/23 (4.3%) 0/11 (0%)
    Upper Respiratory Tract Infection 0/7 (0%) 0/8 (0%) 1/14 (7.1%) 0/20 (0%) 0/16 (0%) 0/23 (0%) 1/11 (9.1%)
    Urinary Tract Infection 0/7 (0%) 0/8 (0%) 1/14 (7.1%) 0/20 (0%) 1/16 (6.3%) 2/23 (8.7%) 1/11 (9.1%)
    Viral Upper Respiratory Tract 1/7 (14.3%) 0/8 (0%) 0/14 (0%) 0/20 (0%) 0/16 (0%) 0/23 (0%) 0/11 (0%)
    Acute Sinusitis 0/7 (0%) 0/8 (0%) 0/14 (0%) 0/20 (0%) 0/16 (0%) 0/23 (0%) 1/11 (9.1%)
    Folliculitis 0/7 (0%) 0/8 (0%) 0/14 (0%) 0/20 (0%) 0/16 (0%) 0/23 (0%) 1/11 (9.1%)
    Herpes Zoster 0/7 (0%) 0/8 (0%) 0/14 (0%) 0/20 (0%) 1/16 (6.3%) 1/23 (4.3%) 0/11 (0%)
    Nasopharyngitis 0/7 (0%) 0/8 (0%) 0/14 (0%) 0/20 (0%) 1/16 (6.3%) 0/23 (0%) 0/11 (0%)
    Device Related Infection 0/7 (0%) 0/8 (0%) 1/14 (7.1%) 0/20 (0%) 0/16 (0%) 0/23 (0%) 0/11 (0%)
    Injury, poisoning and procedural complications
    Contusion 0/7 (0%) 1/8 (12.5%) 0/14 (0%) 0/20 (0%) 0/16 (0%) 1/23 (4.3%) 0/11 (0%)
    Open Wound 0/7 (0%) 0/8 (0%) 1/14 (7.1%) 0/20 (0%) 0/16 (0%) 0/23 (0%) 0/11 (0%)
    Concussion 0/7 (0%) 0/8 (0%) 0/14 (0%) 0/20 (0%) 0/16 (0%) 0/23 (0%) 1/11 (9.1%)
    Fall 0/7 (0%) 0/8 (0%) 0/14 (0%) 0/20 (0%) 0/16 (0%) 2/23 (8.7%) 2/11 (18.2%)
    Investigations
    Aspartate Aminotransferase Increased 4/7 (57.1%) 1/8 (12.5%) 0/14 (0%) 2/20 (10%) 1/16 (6.3%) 0/23 (0%) 0/11 (0%)
    Alanine Aminotransferase Increased 2/7 (28.6%) 0/8 (0%) 0/14 (0%) 1/20 (5%) 2/16 (12.5%) 0/23 (0%) 0/11 (0%)
    Blood Alkaline Phosphatase Increased 1/7 (14.3%) 2/8 (25%) 0/14 (0%) 0/20 (0%) 2/16 (12.5%) 1/23 (4.3%) 1/11 (9.1%)
    International Normalised Ratio Increased 2/7 (28.6%) 0/8 (0%) 0/14 (0%) 0/20 (0%) 1/16 (6.3%) 0/23 (0%) 0/11 (0%)
    Weight Decreased 0/7 (0%) 2/8 (25%) 0/14 (0%) 3/20 (15%) 4/16 (25%) 1/23 (4.3%) 3/11 (27.3%)
    Blood Lactate Dehydrogenase Increased 1/7 (14.3%) 0/8 (0%) 0/14 (0%) 0/20 (0%) 0/16 (0%) 0/23 (0%) 0/11 (0%)
    Lymphocyte Count Decreased 1/7 (14.3%) 0/8 (0%) 0/14 (0%) 0/20 (0%) 0/16 (0%) 0/23 (0%) 0/11 (0%)
    White Blood Cell Count Decreased 0/7 (0%) 1/8 (12.5%) 0/14 (0%) 2/20 (10%) 3/16 (18.8%) 1/23 (4.3%) 0/11 (0%)
    Activated Partial Thromboplastin Time Prolonged 0/7 (0%) 0/8 (0%) 0/14 (0%) 0/20 (0%) 1/16 (6.3%) 0/23 (0%) 1/11 (9.1%)
    Blood Bilirubin Increased 0/7 (0%) 0/8 (0%) 0/14 (0%) 1/20 (5%) 1/16 (6.3%) 1/23 (4.3%) 0/11 (0%)
    Neutrophil Count Decreased 0/7 (0%) 0/8 (0%) 0/14 (0%) 0/20 (0%) 0/16 (0%) 1/23 (4.3%) 1/11 (9.1%)
    Platelet Count Decreased 0/7 (0%) 0/8 (0%) 0/14 (0%) 0/20 (0%) 2/16 (12.5%) 1/23 (4.3%) 0/11 (0%)
    Metabolism and nutrition disorders
    Hyperglycaemia 1/7 (14.3%) 3/8 (37.5%) 0/14 (0%) 1/20 (5%) 3/16 (18.8%) 2/23 (8.7%) 1/11 (9.1%)
    Decreased Appetite 1/7 (14.3%) 1/8 (12.5%) 1/14 (7.1%) 10/20 (50%) 5/16 (31.3%) 4/23 (17.4%) 2/11 (18.2%)
    Hyperkalaemia 0/7 (0%) 0/8 (0%) 2/14 (14.3%) 0/20 (0%) 1/16 (6.3%) 0/23 (0%) 1/11 (9.1%)
    Hypokalaemia 1/7 (14.3%) 0/8 (0%) 1/14 (7.1%) 0/20 (0%) 1/16 (6.3%) 1/23 (4.3%) 1/11 (9.1%)
    Hypernatraemia 0/7 (0%) 1/8 (12.5%) 0/14 (0%) 2/20 (10%) 2/16 (12.5%) 0/23 (0%) 0/11 (0%)
    Hypoalbuminaemia 0/7 (0%) 0/8 (0%) 1/14 (7.1%) 0/20 (0%) 2/16 (12.5%) 0/23 (0%) 0/11 (0%)
    Hypocalcaemia 0/7 (0%) 0/8 (0%) 1/14 (7.1%) 0/20 (0%) 2/16 (12.5%) 0/23 (0%) 0/11 (0%)
    Hypomagnesaemia 0/7 (0%) 0/8 (0%) 1/14 (7.1%) 0/20 (0%) 1/16 (6.3%) 0/23 (0%) 0/11 (0%)
    Hypophosphataemia 0/7 (0%) 1/8 (12.5%) 0/14 (0%) 0/20 (0%) 1/16 (6.3%) 0/23 (0%) 1/11 (9.1%)
    Increased Appetite 0/7 (0%) 0/8 (0%) 1/14 (7.1%) 0/20 (0%) 0/16 (0%) 0/23 (0%) 0/11 (0%)
    Iron Deficiency 0/7 (0%) 0/8 (0%) 1/14 (7.1%) 0/20 (0%) 0/16 (0%) 0/23 (0%) 0/11 (0%)
    Dehydration 0/7 (0%) 0/8 (0%) 0/14 (0%) 1/20 (5%) 1/16 (6.3%) 2/23 (8.7%) 0/11 (0%)
    Hypercalcaemia 0/7 (0%) 0/8 (0%) 0/14 (0%) 0/20 (0%) 1/16 (6.3%) 1/23 (4.3%) 0/11 (0%)
    Hypoglycaemia 0/7 (0%) 0/8 (0%) 0/14 (0%) 1/20 (5%) 0/16 (0%) 0/23 (0%) 1/11 (9.1%)
    Hyponatraemia 0/7 (0%) 0/8 (0%) 0/14 (0%) 2/20 (10%) 0/16 (0%) 0/23 (0%) 1/11 (9.1%)
    Musculoskeletal and connective tissue disorders
    Musculoskeletal Pain 1/7 (14.3%) 3/8 (37.5%) 1/14 (7.1%) 2/20 (10%) 2/16 (12.5%) 6/23 (26.1%) 3/11 (27.3%)
    Back Pain 0/7 (0%) 1/8 (12.5%) 5/14 (35.7%) 3/20 (15%) 2/16 (12.5%) 5/23 (21.7%) 6/11 (54.5%)
    Groin Pain 0/7 (0%) 1/8 (12.5%) 2/14 (14.3%) 0/20 (0%) 0/16 (0%) 0/23 (0%) 0/11 (0%)
    Arthralgia 1/7 (14.3%) 0/8 (0%) 1/14 (7.1%) 3/20 (15%) 1/16 (6.3%) 4/23 (17.4%) 0/11 (0%)
    Bone Pain 0/7 (0%) 2/8 (25%) 0/14 (0%) 0/20 (0%) 0/16 (0%) 0/23 (0%) 0/11 (0%)
    Joint Stiffness 1/7 (14.3%) 1/8 (12.5%) 0/14 (0%) 2/20 (10%) 1/16 (6.3%) 1/23 (4.3%) 0/11 (0%)
    Musculoskeletal Chest Pain 1/7 (14.3%) 1/8 (12.5%) 0/14 (0%) 0/20 (0%) 0/16 (0%) 3/23 (13%) 0/11 (0%)
    Neck Pain 0/7 (0%) 1/8 (12.5%) 1/14 (7.1%) 0/20 (0%) 0/16 (0%) 1/23 (4.3%) 1/11 (9.1%)
    Pain In Extremity 0/7 (0%) 0/8 (0%) 1/14 (7.1%) 2/20 (10%) 2/16 (12.5%) 1/23 (4.3%) 2/11 (18.2%)
    Muscle Spasms 0/7 (0%) 1/8 (12.5%) 0/14 (0%) 2/20 (10%) 2/16 (12.5%) 1/23 (4.3%) 0/11 (0%)
    Pain In Jaw 0/7 (0%) 1/8 (12.5%) 0/14 (0%) 0/20 (0%) 0/16 (0%) 1/23 (4.3%) 0/11 (0%)
    Arthritis 0/7 (0%) 0/8 (0%) 0/14 (0%) 0/20 (0%) 1/16 (6.3%) 1/23 (4.3%) 0/11 (0%)
    Flank Pain 0/7 (0%) 0/8 (0%) 0/14 (0%) 1/20 (5%) 1/16 (6.3%) 0/23 (0%) 0/11 (0%)
    Myalgia 0/7 (0%) 0/8 (0%) 0/14 (0%) 2/20 (10%) 0/16 (0%) 2/23 (8.7%) 2/11 (18.2%)
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Malignant Pleural Effusion 1/7 (14.3%) 0/8 (0%) 1/14 (7.1%) 0/20 (0%) 0/16 (0%) 0/23 (0%) 0/11 (0%)
    Skin Papilloma 1/7 (14.3%) 0/8 (0%) 0/14 (0%) 0/20 (0%) 0/16 (0%) 0/23 (0%) 0/11 (0%)
    Tumour Associated Fever 0/7 (0%) 1/8 (12.5%) 0/14 (0%) 0/20 (0%) 0/16 (0%) 0/23 (0%) 0/11 (0%)
    Tumour Haemorrhage 0/7 (0%) 0/8 (0%) 1/14 (7.1%) 0/20 (0%) 0/16 (0%) 0/23 (0%) 0/11 (0%)
    Metastases To Ovary 0/7 (0%) 0/8 (0%) 0/14 (0%) 0/20 (0%) 0/16 (0%) 0/23 (0%) 1/11 (9.1%)
    Nervous system disorders
    Dizziness 2/7 (28.6%) 1/8 (12.5%) 3/14 (21.4%) 2/20 (10%) 3/16 (18.8%) 2/23 (8.7%) 3/11 (27.3%)
    Headache 1/7 (14.3%) 1/8 (12.5%) 3/14 (21.4%) 3/20 (15%) 1/16 (6.3%) 2/23 (8.7%) 4/11 (36.4%)
    Neuropathy Peripheral 1/7 (14.3%) 2/8 (25%) 0/14 (0%) 2/20 (10%) 1/16 (6.3%) 0/23 (0%) 0/11 (0%)
    Cognitive Disorder 0/7 (0%) 0/8 (0%) 2/14 (14.3%) 1/20 (5%) 3/16 (18.8%) 0/23 (0%) 4/11 (36.4%)
    Memory Impairment 0/7 (0%) 0/8 (0%) 2/14 (14.3%) 2/20 (10%) 0/16 (0%) 2/23 (8.7%) 1/11 (9.1%)
    Restless Legs Syndrome 1/7 (14.3%) 1/8 (12.5%) 0/14 (0%) 2/20 (10%) 0/16 (0%) 1/23 (4.3%) 2/11 (18.2%)
    Disturbance In Attention 0/7 (0%) 0/8 (0%) 1/14 (7.1%) 1/20 (5%) 0/16 (0%) 0/23 (0%) 0/11 (0%)
    Hypoaesthesia 0/7 (0%) 0/8 (0%) 1/14 (7.1%) 0/20 (0%) 1/16 (6.3%) 0/23 (0%) 0/11 (0%)
    Sciatica 1/7 (14.3%) 0/8 (0%) 0/14 (0%) 0/20 (0%) 0/16 (0%) 0/23 (0%) 0/11 (0%)
    Amnesia 0/7 (0%) 0/8 (0%) 0/14 (0%) 0/20 (0%) 0/16 (0%) 1/23 (4.3%) 1/11 (9.1%)
    Aphasia 0/7 (0%) 0/8 (0%) 0/14 (0%) 0/20 (0%) 1/16 (6.3%) 0/23 (0%) 0/11 (0%)
    Ataxia 0/7 (0%) 0/8 (0%) 0/14 (0%) 0/20 (0%) 1/16 (6.3%) 1/23 (4.3%) 1/11 (9.1%)
    Dysgeusia 0/7 (0%) 0/8 (0%) 0/14 (0%) 4/20 (20%) 1/16 (6.3%) 0/23 (0%) 2/11 (18.2%)
    Peripheral Sensory Neuropathy 0/7 (0%) 0/8 (0%) 0/14 (0%) 0/20 (0%) 1/16 (6.3%) 0/23 (0%) 0/11 (0%)
    Sinus Headache 0/7 (0%) 0/8 (0%) 0/14 (0%) 0/20 (0%) 1/16 (6.3%) 0/23 (0%) 0/11 (0%)
    Somnolence 0/7 (0%) 0/8 (0%) 0/14 (0%) 0/20 (0%) 0/16 (0%) 0/23 (0%) 1/11 (9.1%)
    Dysaesthesia 0/7 (0%) 0/8 (0%) 0/14 (0%) 0/20 (0%) 0/16 (0%) 0/23 (0%) 1/11 (9.1%)
    Psychiatric disorders
    Anxiety 0/7 (0%) 3/8 (37.5%) 1/14 (7.1%) 3/20 (15%) 2/16 (12.5%) 1/23 (4.3%) 2/11 (18.2%)
    Insomnia 0/7 (0%) 2/8 (25%) 1/14 (7.1%) 5/20 (25%) 2/16 (12.5%) 2/23 (8.7%) 1/11 (9.1%)
    Depression 1/7 (14.3%) 0/8 (0%) 0/14 (0%) 0/20 (0%) 1/16 (6.3%) 2/23 (8.7%) 2/11 (18.2%)
    Agitation 0/7 (0%) 0/8 (0%) 0/14 (0%) 1/20 (5%) 0/16 (0%) 0/23 (0%) 3/11 (27.3%)
    Confusional State 0/7 (0%) 0/8 (0%) 0/14 (0%) 2/20 (10%) 1/16 (6.3%) 0/23 (0%) 0/11 (0%)
    Hallucination, Visual 0/7 (0%) 0/8 (0%) 0/14 (0%) 0/20 (0%) 1/16 (6.3%) 0/23 (0%) 0/11 (0%)
    Restlessness 0/7 (0%) 0/8 (0%) 0/14 (0%) 0/20 (0%) 0/16 (0%) 0/23 (0%) 1/11 (9.1%)
    Renal and urinary disorders
    Hydronephrosis 0/7 (0%) 0/8 (0%) 1/14 (7.1%) 0/20 (0%) 1/16 (6.3%) 1/23 (4.3%) 0/11 (0%)
    Micturition Urgency 0/7 (0%) 0/8 (0%) 1/14 (7.1%) 0/20 (0%) 0/16 (0%) 0/23 (0%) 0/11 (0%)
    Renal Failure Acute 0/7 (0%) 0/8 (0%) 1/14 (7.1%) 0/20 (0%) 0/16 (0%) 0/23 (0%) 1/11 (9.1%)
    Urinary Incontinence 0/7 (0%) 0/8 (0%) 1/14 (7.1%) 0/20 (0%) 0/16 (0%) 0/23 (0%) 0/11 (0%)
    Reproductive system and breast disorders
    Breast Pain 0/7 (0%) 0/8 (0%) 1/14 (7.1%) 0/20 (0%) 0/16 (0%) 1/23 (4.3%) 0/11 (0%)
    Vulvovaginal Dryness 0/7 (0%) 0/8 (0%) 1/14 (7.1%) 1/20 (5%) 0/16 (0%) 1/23 (4.3%) 0/11 (0%)
    Ovarian Cyst 0/7 (0%) 0/8 (0%) 0/14 (0%) 0/20 (0%) 0/16 (0%) 0/23 (0%) 1/11 (9.1%)
    Respiratory, thoracic and mediastinal disorders
    Cough 0/7 (0%) 4/8 (50%) 2/14 (14.3%) 3/20 (15%) 3/16 (18.8%) 4/23 (17.4%) 1/11 (9.1%)
    Dyspnoea 0/7 (0%) 1/8 (12.5%) 4/14 (28.6%) 2/20 (10%) 2/16 (12.5%) 2/23 (8.7%) 4/11 (36.4%)
    Nasal Congestion 0/7 (0%) 3/8 (37.5%) 0/14 (0%) 0/20 (0%) 0/16 (0%) 0/23 (0%) 0/11 (0%)
    Dysphonia 1/7 (14.3%) 0/8 (0%) 1/14 (7.1%) 0/20 (0%) 2/16 (12.5%) 0/23 (0%) 0/11 (0%)
    Epistaxis 1/7 (14.3%) 0/8 (0%) 0/14 (0%) 0/20 (0%) 0/16 (0%) 1/23 (4.3%) 0/11 (0%)
    Productive Cough 1/7 (14.3%) 1/8 (12.5%) 0/14 (0%) 0/20 (0%) 0/16 (0%) 0/23 (0%) 0/11 (0%)
    Dyspnoea Exertional 1/7 (14.3%) 0/8 (0%) 0/14 (0%) 1/20 (5%) 1/16 (6.3%) 1/23 (4.3%) 0/11 (0%)
    Haemoptysis 1/7 (14.3%) 0/8 (0%) 0/14 (0%) 0/20 (0%) 0/16 (0%) 0/23 (0%) 0/11 (0%)
    Pleural Effusion 0/7 (0%) 1/8 (12.5%) 0/14 (0%) 0/20 (0%) 0/16 (0%) 0/23 (0%) 1/11 (9.1%)
    Pleuritic Pain 0/7 (0%) 0/8 (0%) 1/14 (7.1%) 0/20 (0%) 0/16 (0%) 0/23 (0%) 0/11 (0%)
    Oropharyngeal Pain 0/7 (0%) 0/8 (0%) 0/14 (0%) 1/20 (5%) 0/16 (0%) 1/23 (4.3%) 1/11 (9.1%)
    Rhinorrhoea 0/7 (0%) 0/8 (0%) 0/14 (0%) 0/20 (0%) 1/16 (6.3%) 1/23 (4.3%) 0/11 (0%)
    Upper-Airway Cough Syndrome 0/7 (0%) 0/8 (0%) 0/14 (0%) 0/20 (0%) 0/16 (0%) 0/23 (0%) 1/11 (9.1%)
    Wheezing 0/7 (0%) 0/8 (0%) 0/14 (0%) 0/20 (0%) 0/16 (0%) 0/23 (0%) 1/11 (9.1%)
    Skin and subcutaneous tissue disorders
    Rash 0/7 (0%) 1/8 (12.5%) 2/14 (14.3%) 2/20 (10%) 1/16 (6.3%) 2/23 (8.7%) 1/11 (9.1%)
    Acne 1/7 (14.3%) 0/8 (0%) 1/14 (7.1%) 0/20 (0%) 0/16 (0%) 0/23 (0%) 0/11 (0%)
    Dry Skin 0/7 (0%) 1/8 (12.5%) 1/14 (7.1%) 2/20 (10%) 2/16 (12.5%) 0/23 (0%) 0/11 (0%)
    Alopecia 0/7 (0%) 0/8 (0%) 1/14 (7.1%) 1/20 (5%) 2/16 (12.5%) 0/23 (0%) 2/11 (18.2%)
    Blood Blister 1/7 (14.3%) 0/8 (0%) 0/14 (0%) 0/20 (0%) 0/16 (0%) 0/23 (0%) 0/11 (0%)
    Pruritus 1/7 (14.3%) 0/8 (0%) 0/14 (0%) 1/20 (5%) 0/16 (0%) 3/23 (13%) 0/11 (0%)
    Rash Generalised 0/7 (0%) 0/8 (0%) 1/14 (7.1%) 1/20 (5%) 0/16 (0%) 0/23 (0%) 0/11 (0%)
    Skin Hyperpigmentation 0/7 (0%) 0/8 (0%) 1/14 (7.1%) 0/20 (0%) 0/16 (0%) 0/23 (0%) 0/11 (0%)
    Night Sweats 0/7 (0%) 0/8 (0%) 0/14 (0%) 0/20 (0%) 0/16 (0%) 1/23 (4.3%) 2/11 (18.2%)
    Rash Maculo-Papular 0/7 (0%) 0/8 (0%) 0/14 (0%) 2/20 (10%) 0/16 (0%) 1/23 (4.3%) 0/11 (0%)
    Erythema 0/7 (0%) 0/8 (0%) 0/14 (0%) 0/20 (0%) 1/16 (6.3%) 0/23 (0%) 0/11 (0%)
    Vascular disorders
    Hypertension 1/7 (14.3%) 4/8 (50%) 1/14 (7.1%) 1/20 (5%) 0/16 (0%) 5/23 (21.7%) 2/11 (18.2%)
    Hot Flush 0/7 (0%) 0/8 (0%) 4/14 (28.6%) 5/20 (25%) 2/16 (12.5%) 4/23 (17.4%) 3/11 (27.3%)
    Lymphoedema 0/7 (0%) 0/8 (0%) 1/14 (7.1%) 0/20 (0%) 0/16 (0%) 1/23 (4.3%) 0/11 (0%)
    Hypotension 0/7 (0%) 0/8 (0%) 0/14 (0%) 0/20 (0%) 1/16 (6.3%) 0/23 (0%) 1/11 (9.1%)

    Limitations/Caveats

    Prioritization of outcome measures as primary and secondary was based on the study team's discretion.

    More Information

    Certain Agreements

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

    Pfizer has the right to review disclosures, requesting a delay of less than 60 days. Investigator will postpone single center publications until after disclosure of pooled data (all sites), less than 12 months from study completion/termination at all participating sites. Investigator may not disclose previously undisclosed confidential information other than study results.

    Results Point of Contact

    Name/Title Pfizer ClinicalTrials.gov Call Center
    Organization Pfizer, Inc.
    Phone 1-800-718-1021
    Email ClinicalTrials.gov_Inquiries@pfizer.com
    Responsible Party:
    Pfizer
    ClinicalTrials.gov Identifier:
    NCT01597193
    Other Study ID Numbers:
    • MDV3100-08
    • C3431006
    First Posted:
    May 11, 2012
    Last Update Posted:
    May 8, 2019
    Last Verified:
    May 1, 2019