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Trial record 1 of 1 for:    NCT01597193
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Safety Study of Enzalutamide (MDV3100) in Patients With Incurable Breast Cancer

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ClinicalTrials.gov Identifier: NCT01597193
Recruitment Status : Completed
First Posted : May 11, 2012
Results First Posted : May 8, 2019
Last Update Posted : May 8, 2019
Sponsor:
Collaborators:
Astellas Pharma Inc
Medivation LLC, a wholly owned subsidiary of Pfizer Inc.
Information provided by (Responsible Party):
Pfizer

Study Type Interventional
Study Design Allocation: Non-Randomized;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Breast Cancer
Interventions Drug: enzalutamide
Drug: anastrozole
Drug: exemestane
Drug: fulvestrant
Enrollment 101
Recruitment Details  
Pre-assignment Details 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
Hide 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
Reason Not Completed
Disease progression             7             8             0             0             0             0             0
Period Title: Stage 2: Dose Expansion (1067 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
Reason Not Completed
Adverse Event             0             0             0             1             2             3             0
Disease progression             0             0             14             18             14             18             11
Other             0             0             0             0             0             1             0
Withdrawal by Subject             0             0             0             1             0             1             0
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
Hide 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 Number of Baseline Participants 7 8 14 20 16 23 11 99
Hide Baseline Analysis Population Description
Safety analysis population included all enrolled participants who received at least 1 dose of Enzalutamide.
Age, Customized  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 7 participants 8 participants 14 participants 20 participants 16 participants 23 participants 11 participants 99 participants
Less than (<) 65 years
6
  85.7%
5
  62.5%
11
  78.6%
12
  60.0%
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
  25.0%
2
  12.5%
12
  52.2%
4
  36.4%
29
  29.3%
Greater than or equal to (>=) 75 years
0
   0.0%
0
   0.0%
1
   7.1%
3
  15.0%
1
   6.3%
1
   4.3%
1
   9.1%
7
   7.1%
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 7 participants 8 participants 14 participants 20 participants 16 participants 23 participants 11 participants 99 participants
Female
7
 100.0%
8
 100.0%
14
 100.0%
20
 100.0%
16
 100.0%
23
 100.0%
11
 100.0%
99
 100.0%
Male
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
1.Primary Outcome
Title Dose-Escalation Phase: Percentage of Participants With Dose-limiting Toxicity (DLTs)
Hide 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
Hide Outcome Measure Data
Hide 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
Hide 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.
Overall Number of Participants Analyzed 6 7
Measure Type: Number
Unit of Measure: percentage of participants
16.7 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)
Hide 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)
Hide Outcome Measure Data
Hide 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
Hide 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.
Overall Number of Participants Analyzed 7 8 14 20 16 23 11
Measure Type: Number
Unit of Measure: percentage of participants
57.1 12.5 21.4 30.0 37.5 39.1 36.4
3.Primary Outcome
Title Percentage of Participants With Treatment-Emergent Serious Adverse Events (SAEs)
Hide 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)
Hide Outcome Measure Data
Hide 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
Hide 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.
Overall Number of Participants Analyzed 7 8 14 20 16 23 11
Measure Type: Number
Unit of Measure: percentage of participants
28.6 12.5 14.3 5.0 31.3 13.0 18.2
4.Primary Outcome
Title Percentage of Participants Who Discontinued the Study Drug Due to Adverse Events or Serious Adverse Events
Hide 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)
Hide Outcome Measure Data
Hide 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
Hide 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.
Overall Number of Participants Analyzed 7 8 14 20 16 23 11
Measure Type: Number
Unit of Measure: percentage of participants
0.0 0.0 7.1 5.0 12.5 13.0 0.0
5.Primary Outcome
Title Percentage of Participants Who Require Dose Reductions Due to Adverse Events
Hide 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)
Hide Outcome Measure Data
Hide 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
Hide 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.
Overall Number of Participants Analyzed 7 8 14 20 16 23 11
Measure Type: Number
Unit of Measure: percentage of participants
0.0 0.0 0.0 20.0 12.5 8.7 18.2
6.Primary Outcome
Title Percentage of Participants With Potentially Clinically Significant Change From Baseline in Vital Signs
Hide 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)
Hide Outcome Measure Data
Hide 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
Hide 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.
Overall Number of Participants Analyzed 7 8 14 20 16 23 11
Measure Type: Number
Unit of Measure: percentage of participants
Blood pressure 1 0 1 0 1 2 1
Heart rate 0 2 1 0 0 0 0
7.Primary Outcome
Title Dose-Escalation Phase: Maximum Plasma Concentration (Cmax) of Enzalutamide and Its Metabolites After Single Dose
Hide 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
Hide Outcome Measure Data
Hide 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
Hide 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.
Overall Number of Participants Analyzed 7 8
Mean (Standard Deviation)
Unit of Measure: micrograms per milliliter
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
Hide 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
Hide Outcome Measure Data
Hide 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
Hide 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.
Overall Number of Participants Analyzed 7 8
Median (Full Range)
Unit of Measure: hours
Enzalutamide
0.500
(0.500 to 2.00)
1.00
(0.350 to 4.00)
M1
24.1
(5.55 to 25.1)
23.1
(4.00 to 23.9)
M2
23.9
(21.1 to 25.1)
23.7
(20.8 to 24.5)
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
Hide 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
Hide Outcome Measure Data
Hide 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
Hide 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.
Overall Number of Participants Analyzed 7 8
Mean (Standard Deviation)
Unit of Measure: micrograms*hour per milliliter
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
Hide Description [Not Specified]
Time Frame pre-dose, 0.5, 1, 2, 4, 6, 24, 48 and 72 hours post dose on Day 1
Hide Outcome Measure Data
Hide 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
Hide 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.
Overall Number of Participants Analyzed 7 8
Mean (Standard Deviation)
Unit of Measure: 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
Hide 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
Hide Outcome Measure Data
Hide 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
Hide 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.
Overall Number of Participants Analyzed 7 8
Mean (Standard Deviation)
Unit of Measure: 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
Hide 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
Hide Outcome Measure Data
Hide 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
Hide 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.
Overall Number of Participants Analyzed 7 8
Mean (Standard Deviation)
Unit of Measure: hours
280  (170) 198  (105)
13.Primary Outcome
Title Dose Escalation Phase: Apparent Oral Clearance (CL/F) of Enzalutamide After Single Dosing
Hide 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
Hide Outcome Measure Data
Hide 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
Hide 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.
Overall Number of Participants Analyzed 7 8
Mean (Standard Deviation)
Unit of Measure: 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
Hide 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
Hide Outcome Measure Data
Hide 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
Hide 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.
Overall Number of Participants Analyzed 7 8
Mean (Standard Deviation)
Unit of Measure: 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
Hide 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
Hide Outcome Measure Data
Hide 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
Hide 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.
Overall Number of Participants Analyzed 3 6
Mean (Standard Deviation)
Unit of Measure: micrograms per milliliter
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
Hide 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
Hide Outcome Measure Data
Hide 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
Hide 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.
Overall Number of Participants Analyzed 3 6
Median (Full Range)
Unit of Measure: hours
Enzalutamide
0.500
(0.00 to 5.50)
1.00
(0.570 to 4.00)
M1
5.70
(0.500 to 24.0)
2.29
(0.00 to 24.0)
M2
24.0
(0.570 to 24.0)
0.58
(0.00 to 24.0)
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
Hide 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
Hide Outcome Measure Data
Hide 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
Hide 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.
Overall Number of Participants Analyzed 3 6
Mean (Standard Deviation)
Unit of Measure: milligram*hour per milliliter
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
Hide 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
Hide Outcome Measure Data
Hide 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
Hide 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.
Overall Number of Participants Analyzed 3 6
Mean (Standard Deviation)
Unit of Measure: 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
Hide 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
Hide Outcome Measure Data
Hide 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
Hide 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.
Overall Number of Participants Analyzed 3 6
Mean (Standard Deviation)
Unit of Measure: ratio
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
Hide 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
Hide Outcome Measure Data
Hide 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
Hide 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.
Overall Number of Participants Analyzed 3 6
Mean (Standard Deviation)
Unit of Measure: ratio
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
Hide Description [Not Specified]
Time Frame pre-dose on Day 57
Hide Outcome Measure Data
Hide 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
Hide 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.
Overall Number of Participants Analyzed 3 9 5 12 7
Mean (Standard Deviation)
Unit of Measure: micrograms per milliliter
13.40  (2.51) 14.33  (3.99) 13.52  (2.62) 12.41  (3.76) 11.62  (4.69)
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
Hide 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 (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   0/7 (0.00%)   0/8 (0.00%)   1/14 (7.14%)   0/20 (0.00%)   0/16 (0.00%)   0/23 (0.00%)   0/11 (0.00%) 
Hide 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 (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   2/7 (28.57%)   1/8 (12.50%)   2/14 (14.29%)   1/20 (5.00%)   5/16 (31.25%)   3/23 (13.04%)   2/11 (18.18%) 
Blood and lymphatic system disorders               
Anaemia * 1  0/7 (0.00%)  1/8 (12.50%)  0/14 (0.00%)  0/20 (0.00%)  0/16 (0.00%)  0/23 (0.00%)  0/11 (0.00%) 
Iron Deficiency Anaemia * 1  0/7 (0.00%)  0/8 (0.00%)  0/14 (0.00%)  0/20 (0.00%)  0/16 (0.00%)  0/23 (0.00%)  1/11 (9.09%) 
Cardiac disorders               
Pericardial Effusion * 1  0/7 (0.00%)  0/8 (0.00%)  0/14 (0.00%)  0/20 (0.00%)  1/16 (6.25%)  0/23 (0.00%)  0/11 (0.00%) 
Endocrine disorders               
Adrenal Insufficiency * 1  1/7 (14.29%)  0/8 (0.00%)  0/14 (0.00%)  0/20 (0.00%)  0/16 (0.00%)  0/23 (0.00%)  0/11 (0.00%) 
Gastrointestinal disorders               
Abdominal Pain * 1  0/7 (0.00%)  0/8 (0.00%)  1/14 (7.14%)  0/20 (0.00%)  0/16 (0.00%)  0/23 (0.00%)  0/11 (0.00%) 
Gastritis Erosive * 1  0/7 (0.00%)  0/8 (0.00%)  0/14 (0.00%)  0/20 (0.00%)  0/16 (0.00%)  0/23 (0.00%)  1/11 (9.09%) 
Infections and infestations               
Urosepsis * 1  0/7 (0.00%)  0/8 (0.00%)  1/14 (7.14%)  0/20 (0.00%)  0/16 (0.00%)  0/23 (0.00%)  0/11 (0.00%) 
Pneumonia * 1  0/7 (0.00%)  0/8 (0.00%)  0/14 (0.00%)  0/20 (0.00%)  0/16 (0.00%)  2/23 (8.70%)  0/11 (0.00%) 
Urinary Tract Infection * 1  0/7 (0.00%)  0/8 (0.00%)  0/14 (0.00%)  0/20 (0.00%)  0/16 (0.00%)  0/23 (0.00%)  1/11 (9.09%) 
Enterocolitis infectious * 1  0/7 (0.00%)  0/8 (0.00%)  0/14 (0.00%)  0/20 (0.00%)  1/16 (6.25%)  0/23 (0.00%)  0/11 (0.00%) 
Injury, poisoning and procedural complications               
In-Stent Coronary Artery Restenosis * 1  0/7 (0.00%)  0/8 (0.00%)  1/14 (7.14%)  0/20 (0.00%)  0/16 (0.00%)  0/23 (0.00%)  0/11 (0.00%) 
Humerus Fracture * 1  0/7 (0.00%)  0/8 (0.00%)  0/14 (0.00%)  0/20 (0.00%)  0/16 (0.00%)  1/23 (4.35%)  0/11 (0.00%) 
Metabolism and nutrition disorders               
Dehydration * 1  0/7 (0.00%)  0/8 (0.00%)  0/14 (0.00%)  0/20 (0.00%)  0/16 (0.00%)  0/23 (0.00%)  1/11 (9.09%) 
Hypercalcaemia * 1  0/7 (0.00%)  0/8 (0.00%)  0/14 (0.00%)  0/20 (0.00%)  1/16 (6.25%)  0/23 (0.00%)  0/11 (0.00%) 
Musculoskeletal and connective tissue disorders               
Pathological Fracture * 1  0/7 (0.00%)  0/8 (0.00%)  0/14 (0.00%)  0/20 (0.00%)  1/16 (6.25%)  0/23 (0.00%)  0/11 (0.00%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)               
Tumour Pain * 1  0/7 (0.00%)  0/8 (0.00%)  0/14 (0.00%)  0/20 (0.00%)  1/16 (6.25%)  0/23 (0.00%)  0/11 (0.00%) 
Renal and urinary disorders               
Hydronephrosis * 1  1/7 (14.29%)  0/8 (0.00%)  0/14 (0.00%)  0/20 (0.00%)  0/16 (0.00%)  0/23 (0.00%)  0/11 (0.00%) 
Obstructive Uropathy * 1  0/7 (0.00%)  0/8 (0.00%)  1/14 (7.14%)  0/20 (0.00%)  0/16 (0.00%)  0/23 (0.00%)  0/11 (0.00%) 
Renal Failure Acute * 1  0/7 (0.00%)  0/8 (0.00%)  0/14 (0.00%)  0/20 (0.00%)  1/16 (6.25%)  0/23 (0.00%)  0/11 (0.00%) 
Ureteric Obstruction * 1  0/7 (0.00%)  0/8 (0.00%)  0/14 (0.00%)  0/20 (0.00%)  1/16 (6.25%)  0/23 (0.00%)  0/11 (0.00%) 
Respiratory, thoracic and mediastinal disorders               
Pleural Effusion * 1  0/7 (0.00%)  0/8 (0.00%)  0/14 (0.00%)  1/20 (5.00%)  0/16 (0.00%)  0/23 (0.00%)  0/11 (0.00%) 
1
Term from vocabulary, MedDRA 15.0
*
Indicates events were collected by non-systematic assessment
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
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 (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   7/7 (100.00%)   8/8 (100.00%)   14/14 (100.00%)   20/20 (100.00%)   15/16 (93.75%)   21/23 (91.30%)   11/11 (100.00%) 
Blood and lymphatic system disorders               
Anaemia * 1  2/7 (28.57%)  2/8 (25.00%)  1/14 (7.14%)  1/20 (5.00%)  5/16 (31.25%)  0/23 (0.00%)  1/11 (9.09%) 
Thrombocytopenia * 1  0/7 (0.00%)  1/8 (12.50%)  1/14 (7.14%)  2/20 (10.00%)  0/16 (0.00%)  1/23 (4.35%)  1/11 (9.09%) 
Iron Deficiency Anaemia * 1  0/7 (0.00%)  0/8 (0.00%)  0/14 (0.00%)  0/20 (0.00%)  0/16 (0.00%)  0/23 (0.00%)  1/11 (9.09%) 
Lymph Node Pain * 1  0/7 (0.00%)  0/8 (0.00%)  0/14 (0.00%)  0/20 (0.00%)  1/16 (6.25%)  0/23 (0.00%)  0/11 (0.00%) 
Neutropenia * 1  0/7 (0.00%)  0/8 (0.00%)  0/14 (0.00%)  1/20 (5.00%)  2/16 (12.50%)  0/23 (0.00%)  1/11 (9.09%) 
Haemolytic anaemia * 1  0/7 (0.00%)  0/8 (0.00%)  0/14 (0.00%)  0/20 (0.00%)  1/16 (6.25%)  0/23 (0.00%)  0/11 (0.00%) 
Cardiac disorders               
Palpitations * 1  1/7 (14.29%)  1/8 (12.50%)  0/14 (0.00%)  0/20 (0.00%)  0/16 (0.00%)  0/23 (0.00%)  0/11 (0.00%) 
Angina Pectoris * 1  0/7 (0.00%)  0/8 (0.00%)  1/14 (7.14%)  0/20 (0.00%)  0/16 (0.00%)  0/23 (0.00%)  0/11 (0.00%) 
Tachycardia * 1  1/7 (14.29%)  0/8 (0.00%)  0/14 (0.00%)  0/20 (0.00%)  0/16 (0.00%)  0/23 (0.00%)  1/11 (9.09%) 
Cardiac Tamponade * 1  0/7 (0.00%)  0/8 (0.00%)  0/14 (0.00%)  0/20 (0.00%)  1/16 (6.25%)  0/23 (0.00%)  0/11 (0.00%) 
Eye disorders               
Dry Eye * 1  0/7 (0.00%)  2/8 (25.00%)  0/14 (0.00%)  1/20 (5.00%)  0/16 (0.00%)  0/23 (0.00%)  0/11 (0.00%) 
Conjunctivitis * 1  1/7 (14.29%)  0/8 (0.00%)  0/14 (0.00%)  0/20 (0.00%)  0/16 (0.00%)  0/23 (0.00%)  1/11 (9.09%) 
Eye Movement Disorder * 1  0/7 (0.00%)  0/8 (0.00%)  1/14 (7.14%)  0/20 (0.00%)  0/16 (0.00%)  0/23 (0.00%)  0/11 (0.00%) 
Eyelid Oedema * 1  0/7 (0.00%)  0/8 (0.00%)  1/14 (7.14%)  0/20 (0.00%)  0/16 (0.00%)  0/23 (0.00%)  0/11 (0.00%) 
Lacrimation Increased * 1  0/7 (0.00%)  1/8 (12.50%)  0/14 (0.00%)  0/20 (0.00%)  0/16 (0.00%)  0/23 (0.00%)  0/11 (0.00%) 
Abnormal Sensation In Eye * 1  0/7 (0.00%)  0/8 (0.00%)  0/14 (0.00%)  0/20 (0.00%)  0/16 (0.00%)  0/23 (0.00%)  1/11 (9.09%) 
Vision Blurred * 1  0/7 (0.00%)  0/8 (0.00%)  0/14 (0.00%)  0/20 (0.00%)  0/16 (0.00%)  0/23 (0.00%)  1/11 (9.09%) 
Visual Acuity Reduced * 1  0/7 (0.00%)  0/8 (0.00%)  0/14 (0.00%)  0/20 (0.00%)  1/16 (6.25%)  0/23 (0.00%)  0/11 (0.00%) 
Gastrointestinal disorders               
Vomiting * 1  1/7 (14.29%)  0/8 (0.00%)  5/14 (35.71%)  3/20 (15.00%)  2/16 (12.50%)  7/23 (30.43%)  3/11 (27.27%) 
Diarrhoea * 1  3/7 (42.86%)  1/8 (12.50%)  2/14 (14.29%)  6/20 (30.00%)  4/16 (25.00%)  3/23 (13.04%)  4/11 (36.36%) 
Constipation * 1  0/7 (0.00%)  2/8 (25.00%)  2/14 (14.29%)  3/20 (15.00%)  3/16 (18.75%)  3/23 (13.04%)  3/11 (27.27%) 
Gastrooesophageal Reflux Disease * 1  0/7 (0.00%)  0/8 (0.00%)  4/14 (28.57%)  0/20 (0.00%)  2/16 (12.50%)  2/23 (8.70%)  0/11 (0.00%) 
Abdominal Discomfort * 1  1/7 (14.29%)  0/8 (0.00%)  1/14 (7.14%)  1/20 (5.00%)  0/16 (0.00%)  0/23 (0.00%)  0/11 (0.00%) 
Abdominal Pain Upper * 1  0/7 (0.00%)  0/8 (0.00%)  3/14 (21.43%)  1/20 (5.00%)  0/16 (0.00%)  2/23 (8.70%)  0/11 (0.00%) 
Abdominal Pain * 1  0/7 (0.00%)  0/8 (0.00%)  2/14 (14.29%)  1/20 (5.00%)  1/16 (6.25%)  0/23 (0.00%)  2/11 (18.18%) 
Haematemesis * 1  0/7 (0.00%)  0/8 (0.00%)  1/14 (7.14%)  0/20 (0.00%)  0/16 (0.00%)  0/23 (0.00%)  0/11 (0.00%) 
Abdominal Distension * 1  0/7 (0.00%)  0/8 (0.00%)  1/14 (7.14%)  1/20 (5.00%)  0/16 (0.00%)  1/23 (4.35%)  1/11 (9.09%) 
Dry Mouth * 1  0/7 (0.00%)  1/8 (12.50%)  0/14 (0.00%)  1/20 (5.00%)  0/16 (0.00%)  1/23 (4.35%)  0/11 (0.00%) 
Epigastric Discomfort * 1  0/7 (0.00%)  0/8 (0.00%)  1/14 (7.14%)  0/20 (0.00%)  0/16 (0.00%)  0/23 (0.00%)  0/11 (0.00%) 
Eructation * 1  1/7 (14.29%)  0/8 (0.00%)  0/14 (0.00%)  0/20 (0.00%)  0/16 (0.00%)  0/23 (0.00%)  0/11 (0.00%) 
Flatulence * 1  0/7 (0.00%)  0/8 (0.00%)  1/14 (7.14%)  0/20 (0.00%)  0/16 (0.00%)  0/23 (0.00%)  0/11 (0.00%) 
Stomatitis * 1  0/7 (0.00%)  0/8 (0.00%)  1/14 (7.14%)  0/20 (0.00%)  0/16 (0.00%)  0/23 (0.00%)  0/11 (0.00%) 
Abdominal Pain Lower * 1  0/7 (0.00%)  0/8 (0.00%)  0/14 (0.00%)  1/20 (5.00%)  0/16 (0.00%)  0/23 (0.00%)  1/11 (9.09%) 
Dyspepsia * 1  0/7 (0.00%)  0/8 (0.00%)  0/14 (0.00%)  1/20 (5.00%)  0/16 (0.00%)  1/23 (4.35%)  1/11 (9.09%) 
Frequent Bowel Movements * 1  0/7 (0.00%)  0/8 (0.00%)  0/14 (0.00%)  0/20 (0.00%)  0/16 (0.00%)  0/23 (0.00%)  1/11 (9.09%) 
Gastritis * 1  0/7 (0.00%)  0/8 (0.00%)  0/14 (0.00%)  0/20 (0.00%)  0/16 (0.00%)  0/23 (0.00%)  1/11 (9.09%) 
Nausea * 1  1/7 (14.29%)  3/8 (37.50%)  8/14 (57.14%)  9/20 (45.00%)  7/16 (43.75%)  12/23 (52.17%)  8/11 (72.73%) 
Faecal incontinence * 1  0/7 (0.00%)  0/8 (0.00%)  0/14 (0.00%)  0/20 (0.00%)  1/16 (6.25%)  0/23 (0.00%)  0/11 (0.00%) 
Dysphagia * 1  0/7 (0.00%)  0/8 (0.00%)  1/14 (7.14%)  0/20 (0.00%)  0/16 (0.00%)  1/23 (4.35%)  0/11 (0.00%) 
General disorders               
Fatigue * 1  0/7 (0.00%)  2/8 (25.00%)  8/14 (57.14%)  12/20 (60.00%)  8/16 (50.00%)  12/23 (52.17%)  8/11 (72.73%) 
Chills * 1  0/7 (0.00%)  1/8 (12.50%)  1/14 (7.14%)  2/20 (10.00%)  0/16 (0.00%)  0/23 (0.00%)  0/11 (0.00%) 
Oedema Peripheral * 1  0/7 (0.00%)  0/8 (0.00%)  2/14 (14.29%)  1/20 (5.00%)  1/16 (6.25%)  1/23 (4.35%)  1/11 (9.09%) 
Pyrexia * 1  0/7 (0.00%)  1/8 (12.50%)  1/14 (7.14%)  1/20 (5.00%)  0/16 (0.00%)  2/23 (8.70%)  1/11 (9.09%) 
Asthenia * 1  0/7 (0.00%)  0/8 (0.00%)  1/14 (7.14%)  5/20 (25.00%)  0/16 (0.00%)  1/23 (4.35%)  0/11 (0.00%) 
Axillary Pain * 1  0/7 (0.00%)  1/8 (12.50%)  0/14 (0.00%)  0/20 (0.00%)  0/16 (0.00%)  0/23 (0.00%)  0/11 (0.00%) 
Chest Discomfort * 1  1/7 (14.29%)  0/8 (0.00%)  0/14 (0.00%)  0/20 (0.00%)  0/16 (0.00%)  0/23 (0.00%)  0/11 (0.00%) 
Early Satiety * 1  1/7 (14.29%)  0/8 (0.00%)  0/14 (0.00%)  1/20 (5.00%)  0/16 (0.00%)  0/23 (0.00%)  0/11 (0.00%) 
Gait Disturbance * 1  0/7 (0.00%)  0/8 (0.00%)  1/14 (7.14%)  0/20 (0.00%)  0/16 (0.00%)  0/23 (0.00%)  0/11 (0.00%) 
Influenza Like Illness * 1  0/7 (0.00%)  1/8 (12.50%)  0/14 (0.00%)  1/20 (5.00%)  0/16 (0.00%)  1/23 (4.35%)  0/11 (0.00%) 
Irritability * 1  0/7 (0.00%)  0/8 (0.00%)  1/14 (7.14%)  1/20 (5.00%)  0/16 (0.00%)  0/23 (0.00%)  0/11 (0.00%) 
Spinal Pain * 1  1/7 (14.29%)  0/8 (0.00%)  0/14 (0.00%)  0/20 (0.00%)  0/16 (0.00%)  0/23 (0.00%)  0/11 (0.00%) 
Suprapubic Pain * 1  0/7 (0.00%)  0/8 (0.00%)  1/14 (7.14%)  0/20 (0.00%)  0/16 (0.00%)  0/23 (0.00%)  0/11 (0.00%) 
Local Swelling * 1  0/7 (0.00%)  0/8 (0.00%)  0/14 (0.00%)  0/20 (0.00%)  1/16 (6.25%)  0/23 (0.00%)  0/11 (0.00%) 
Hepatobiliary disorders               
Hepatomegaly * 1  1/7 (14.29%)  0/8 (0.00%)  0/14 (0.00%)  0/20 (0.00%)  0/16 (0.00%)  0/23 (0.00%)  0/11 (0.00%) 
Immune system disorders               
Drug Hypersensitivity * 1  0/7 (0.00%)  0/8 (0.00%)  0/14 (0.00%)  0/20 (0.00%)  0/16 (0.00%)  0/23 (0.00%)  1/11 (9.09%) 
Infections and infestations               
Breast Cellulitis * 1  1/7 (14.29%)  0/8 (0.00%)  0/14 (0.00%)  0/20 (0.00%)  0/16 (0.00%)  0/23 (0.00%)  0/11 (0.00%) 
Cellulitis * 1  0/7 (0.00%)  1/8 (12.50%)  0/14 (0.00%)  0/20 (0.00%)  1/16 (6.25%)  1/23 (4.35%)  0/11 (0.00%) 
Cystitis * 1  0/7 (0.00%)  0/8 (0.00%)  1/14 (7.14%)  0/20 (0.00%)  0/16 (0.00%)  0/23 (0.00%)  0/11 (0.00%) 
Ear Infection * 1  0/7 (0.00%)  1/8 (12.50%)  0/14 (0.00%)  0/20 (0.00%)  0/16 (0.00%)  0/23 (0.00%)  0/11 (0.00%) 
Infected Cyst * 1  0/7 (0.00%)  0/8 (0.00%)  1/14 (7.14%)  0/20 (0.00%)  0/16 (0.00%)  0/23 (0.00%)  0/11 (0.00%) 
Pneumonia * 1  0/7 (0.00%)  0/8 (0.00%)  1/14 (7.14%)  0/20 (0.00%)  0/16 (0.00%)  0/23 (0.00%)  0/11 (0.00%) 
Pneumonia Bacterial * 1  0/7 (0.00%)  0/8 (0.00%)  1/14 (7.14%)  0/20 (0.00%)  0/16 (0.00%)  0/23 (0.00%)  0/11 (0.00%) 
Sinusitis * 1  0/7 (0.00%)  1/8 (12.50%)  0/14 (0.00%)  0/20 (0.00%)  1/16 (6.25%)  0/23 (0.00%)  1/11 (9.09%) 
Skin Infection * 1  0/7 (0.00%)  0/8 (0.00%)  1/14 (7.14%)  0/20 (0.00%)  0/16 (0.00%)  1/23 (4.35%)  0/11 (0.00%) 
Upper Respiratory Tract Infection * 1  0/7 (0.00%)  0/8 (0.00%)  1/14 (7.14%)  0/20 (0.00%)  0/16 (0.00%)  0/23 (0.00%)  1/11 (9.09%) 
Urinary Tract Infection * 1  0/7 (0.00%)  0/8 (0.00%)  1/14 (7.14%)  0/20 (0.00%)  1/16 (6.25%)  2/23 (8.70%)  1/11 (9.09%) 
Viral Upper Respiratory Tract * 1  1/7 (14.29%)  0/8 (0.00%)  0/14 (0.00%)  0/20 (0.00%)  0/16 (0.00%)  0/23 (0.00%)  0/11 (0.00%) 
Acute Sinusitis * 1  0/7 (0.00%)  0/8 (0.00%)  0/14 (0.00%)  0/20 (0.00%)  0/16 (0.00%)  0/23 (0.00%)  1/11 (9.09%) 
Folliculitis * 1  0/7 (0.00%)  0/8 (0.00%)  0/14 (0.00%)  0/20 (0.00%)  0/16 (0.00%)  0/23 (0.00%)  1/11 (9.09%) 
Herpes Zoster * 1  0/7 (0.00%)  0/8 (0.00%)  0/14 (0.00%)  0/20 (0.00%)  1/16 (6.25%)  1/23 (4.35%)  0/11 (0.00%) 
Nasopharyngitis * 1  0/7 (0.00%)  0/8 (0.00%)  0/14 (0.00%)  0/20 (0.00%)  1/16 (6.25%)  0/23 (0.00%)  0/11 (0.00%) 
Device Related Infection * 1  0/7 (0.00%)  0/8 (0.00%)  1/14 (7.14%)  0/20 (0.00%)  0/16 (0.00%)  0/23 (0.00%)  0/11 (0.00%) 
Injury, poisoning and procedural complications               
Contusion * 1  0/7 (0.00%)  1/8 (12.50%)  0/14 (0.00%)  0/20 (0.00%)  0/16 (0.00%)  1/23 (4.35%)  0/11 (0.00%) 
Open Wound * 1  0/7 (0.00%)  0/8 (0.00%)  1/14 (7.14%)  0/20 (0.00%)  0/16 (0.00%)  0/23 (0.00%)  0/11 (0.00%) 
Concussion * 1  0/7 (0.00%)  0/8 (0.00%)  0/14 (0.00%)  0/20 (0.00%)  0/16 (0.00%)  0/23 (0.00%)  1/11 (9.09%) 
Fall * 1  0/7 (0.00%)  0/8 (0.00%)  0/14 (0.00%)  0/20 (0.00%)  0/16 (0.00%)  2/23 (8.70%)  2/11 (18.18%) 
Investigations               
Aspartate Aminotransferase Increased * 1  4/7 (57.14%)  1/8 (12.50%)  0/14 (0.00%)  2/20 (10.00%)  1/16 (6.25%)  0/23 (0.00%)  0/11 (0.00%) 
Alanine Aminotransferase Increased * 1  2/7 (28.57%)  0/8 (0.00%)  0/14 (0.00%)  1/20 (5.00%)  2/16 (12.50%)  0/23 (0.00%)  0/11 (0.00%) 
Blood Alkaline Phosphatase Increased * 1  1/7 (14.29%)  2/8 (25.00%)  0/14 (0.00%)  0/20 (0.00%)  2/16 (12.50%)  1/23 (4.35%)  1/11 (9.09%) 
International Normalised Ratio Increased * 1  2/7 (28.57%)  0/8 (0.00%)  0/14 (0.00%)  0/20 (0.00%)  1/16 (6.25%)  0/23 (0.00%)  0/11 (0.00%) 
Weight Decreased * 1  0/7 (0.00%)  2/8 (25.00%)  0/14 (0.00%)  3/20 (15.00%)  4/16 (25.00%)  1/23 (4.35%)  3/11 (27.27%) 
Blood Lactate Dehydrogenase Increased * 1  1/7 (14.29%)  0/8 (0.00%)  0/14 (0.00%)  0/20 (0.00%)  0/16 (0.00%)  0/23 (0.00%)  0/11 (0.00%) 
Lymphocyte Count Decreased * 1  1/7 (14.29%)  0/8 (0.00%)  0/14 (0.00%)  0/20 (0.00%)  0/16 (0.00%)  0/23 (0.00%)  0/11 (0.00%) 
White Blood Cell Count Decreased * 1  0/7 (0.00%)  1/8 (12.50%)  0/14 (0.00%)  2/20 (10.00%)  3/16 (18.75%)  1/23 (4.35%)  0/11 (0.00%) 
Activated Partial Thromboplastin Time Prolonged * 1  0/7 (0.00%)  0/8 (0.00%)  0/14 (0.00%)  0/20 (0.00%)  1/16 (6.25%)  0/23 (0.00%)  1/11 (9.09%) 
Blood Bilirubin Increased * 1  0/7 (0.00%)  0/8 (0.00%)  0/14 (0.00%)  1/20 (5.00%)  1/16 (6.25%)  1/23 (4.35%)  0/11 (0.00%) 
Neutrophil Count Decreased * 1  0/7 (0.00%)  0/8 (0.00%)  0/14 (0.00%)  0/20 (0.00%)  0/16 (0.00%)  1/23 (4.35%)  1/11 (9.09%) 
Platelet Count Decreased * 1  0/7 (0.00%)  0/8 (0.00%)  0/14 (0.00%)  0/20 (0.00%)  2/16 (12.50%)  1/23 (4.35%)  0/11 (0.00%) 
Metabolism and nutrition disorders               
Hyperglycaemia * 1  1/7 (14.29%)  3/8 (37.50%)  0/14 (0.00%)  1/20 (5.00%)  3/16 (18.75%)  2/23 (8.70%)  1/11 (9.09%) 
Decreased Appetite * 1  1/7 (14.29%)  1/8 (12.50%)  1/14 (7.14%)  10/20 (50.00%)  5/16 (31.25%)  4/23 (17.39%)  2/11 (18.18%) 
Hyperkalaemia * 1  0/7 (0.00%)  0/8 (0.00%)  2/14 (14.29%)  0/20 (0.00%)  1/16 (6.25%)  0/23 (0.00%)  1/11 (9.09%) 
Hypokalaemia * 1  1/7 (14.29%)  0/8 (0.00%)  1/14 (7.14%)  0/20 (0.00%)  1/16 (6.25%)  1/23 (4.35%)  1/11 (9.09%) 
Hypernatraemia * 1  0/7 (0.00%)  1/8 (12.50%)  0/14 (0.00%)  2/20 (10.00%)  2/16 (12.50%)  0/23 (0.00%)  0/11 (0.00%) 
Hypoalbuminaemia * 1  0/7 (0.00%)  0/8 (0.00%)  1/14 (7.14%)  0/20 (0.00%)  2/16 (12.50%)  0/23 (0.00%)  0/11 (0.00%) 
Hypocalcaemia * 1  0/7 (0.00%)  0/8 (0.00%)  1/14 (7.14%)  0/20 (0.00%)  2/16 (12.50%)  0/23 (0.00%)  0/11 (0.00%) 
Hypomagnesaemia * 1  0/7 (0.00%)  0/8 (0.00%)  1/14 (7.14%)  0/20 (0.00%)  1/16 (6.25%)  0/23 (0.00%)  0/11 (0.00%) 
Hypophosphataemia * 1  0/7 (0.00%)  1/8 (12.50%)  0/14 (0.00%)  0/20 (0.00%)  1/16 (6.25%)  0/23 (0.00%)  1/11 (9.09%) 
Increased Appetite * 1  0/7 (0.00%)  0/8 (0.00%)  1/14 (7.14%)  0/20 (0.00%)  0/16 (0.00%)  0/23 (0.00%)  0/11 (0.00%) 
Iron Deficiency * 1  0/7 (0.00%)  0/8 (0.00%)  1/14 (7.14%)  0/20 (0.00%)  0/16 (0.00%)  0/23 (0.00%)  0/11 (0.00%) 
Dehydration * 1  0/7 (0.00%)  0/8 (0.00%)  0/14 (0.00%)  1/20 (5.00%)  1/16 (6.25%)  2/23 (8.70%)  0/11 (0.00%) 
Hypercalcaemia * 1  0/7 (0.00%)  0/8 (0.00%)  0/14 (0.00%)  0/20 (0.00%)  1/16 (6.25%)  1/23 (4.35%)  0/11 (0.00%) 
Hypoglycaemia * 1  0/7 (0.00%)  0/8 (0.00%)  0/14 (0.00%)  1/20 (5.00%)  0/16 (0.00%)  0/23 (0.00%)  1/11 (9.09%) 
Hyponatraemia * 1  0/7 (0.00%)  0/8 (0.00%)  0/14 (0.00%)  2/20 (10.00%)  0/16 (0.00%)  0/23 (0.00%)  1/11 (9.09%) 
Musculoskeletal and connective tissue disorders               
Musculoskeletal Pain * 1  1/7 (14.29%)  3/8 (37.50%)  1/14 (7.14%)  2/20 (10.00%)  2/16 (12.50%)  6/23 (26.09%)  3/11 (27.27%) 
Back Pain * 1  0/7 (0.00%)  1/8 (12.50%)  5/14 (35.71%)  3/20 (15.00%)  2/16 (12.50%)  5/23 (21.74%)  6/11 (54.55%) 
Groin Pain * 1  0/7 (0.00%)  1/8 (12.50%)  2/14 (14.29%)  0/20 (0.00%)  0/16 (0.00%)  0/23 (0.00%)  0/11 (0.00%) 
Arthralgia * 1  1/7 (14.29%)  0/8 (0.00%)  1/14 (7.14%)  3/20 (15.00%)  1/16 (6.25%)  4/23 (17.39%)  0/11 (0.00%) 
Bone Pain * 1  0/7 (0.00%)  2/8 (25.00%)  0/14 (0.00%)  0/20 (0.00%)  0/16 (0.00%)  0/23 (0.00%)  0/11 (0.00%) 
Joint Stiffness * 1  1/7 (14.29%)  1/8 (12.50%)  0/14 (0.00%)  2/20 (10.00%)  1/16 (6.25%)  1/23 (4.35%)  0/11 (0.00%) 
Musculoskeletal Chest Pain * 1  1/7 (14.29%)  1/8 (12.50%)  0/14 (0.00%)  0/20 (0.00%)  0/16 (0.00%)  3/23 (13.04%)  0/11 (0.00%) 
Neck Pain * 1  0/7 (0.00%)  1/8 (12.50%)  1/14 (7.14%)  0/20 (0.00%)  0/16 (0.00%)  1/23 (4.35%)  1/11 (9.09%) 
Pain In Extremity * 1  0/7 (0.00%)  0/8 (0.00%)  1/14 (7.14%)  2/20 (10.00%)  2/16 (12.50%)  1/23 (4.35%)  2/11 (18.18%) 
Muscle Spasms * 1  0/7 (0.00%)  1/8 (12.50%)  0/14 (0.00%)  2/20 (10.00%)  2/16 (12.50%)  1/23 (4.35%)  0/11 (0.00%) 
Pain In Jaw * 1  0/7 (0.00%)  1/8 (12.50%)  0/14 (0.00%)  0/20 (0.00%)  0/16 (0.00%)  1/23 (4.35%)  0/11 (0.00%) 
Arthritis * 1  0/7 (0.00%)  0/8 (0.00%)  0/14 (0.00%)  0/20 (0.00%)  1/16 (6.25%)  1/23 (4.35%)  0/11 (0.00%) 
Flank Pain * 1  0/7 (0.00%)  0/8 (0.00%)  0/14 (0.00%)  1/20 (5.00%)  1/16 (6.25%)  0/23 (0.00%)  0/11 (0.00%) 
Myalgia * 1  0/7 (0.00%)  0/8 (0.00%)  0/14 (0.00%)  2/20 (10.00%)  0/16 (0.00%)  2/23 (8.70%)  2/11 (18.18%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)               
Malignant Pleural Effusion * 1  1/7 (14.29%)  0/8 (0.00%)  1/14 (7.14%)  0/20 (0.00%)  0/16 (0.00%)  0/23 (0.00%)  0/11 (0.00%) 
Skin Papilloma * 1  1/7 (14.29%)  0/8 (0.00%)  0/14 (0.00%)  0/20 (0.00%)  0/16 (0.00%)  0/23 (0.00%)  0/11 (0.00%) 
Tumour Associated Fever * 1  0/7 (0.00%)  1/8 (12.50%)  0/14 (0.00%)  0/20 (0.00%)  0/16 (0.00%)  0/23 (0.00%)  0/11 (0.00%) 
Tumour Haemorrhage * 1  0/7 (0.00%)  0/8 (0.00%)  1/14 (7.14%)  0/20 (0.00%)  0/16 (0.00%)  0/23 (0.00%)  0/11 (0.00%) 
Metastases To Ovary * 1  0/7 (0.00%)  0/8 (0.00%)  0/14 (0.00%)  0/20 (0.00%)  0/16 (0.00%)  0/23 (0.00%)  1/11 (9.09%) 
Nervous system disorders               
Dizziness * 1  2/7 (28.57%)  1/8 (12.50%)  3/14 (21.43%)  2/20 (10.00%)  3/16 (18.75%)  2/23 (8.70%)  3/11 (27.27%) 
Headache * 1  1/7 (14.29%)  1/8 (12.50%)  3/14 (21.43%)  3/20 (15.00%)  1/16 (6.25%)  2/23 (8.70%)  4/11 (36.36%) 
Neuropathy Peripheral * 1  1/7 (14.29%)  2/8 (25.00%)  0/14 (0.00%)  2/20 (10.00%)  1/16 (6.25%)  0/23 (0.00%)  0/11 (0.00%) 
Cognitive Disorder * 1  0/7 (0.00%)  0/8 (0.00%)  2/14 (14.29%)  1/20 (5.00%)  3/16 (18.75%)  0/23 (0.00%)  4/11 (36.36%) 
Memory Impairment * 1  0/7 (0.00%)  0/8 (0.00%)  2/14 (14.29%)  2/20 (10.00%)  0/16 (0.00%)  2/23 (8.70%)  1/11 (9.09%) 
Restless Legs Syndrome * 1  1/7 (14.29%)  1/8 (12.50%)  0/14 (0.00%)  2/20 (10.00%)  0/16 (0.00%)  1/23 (4.35%)  2/11 (18.18%) 
Disturbance In Attention * 1  0/7 (0.00%)  0/8 (0.00%)  1/14 (7.14%)  1/20 (5.00%)  0/16 (0.00%)  0/23 (0.00%)  0/11 (0.00%) 
Hypoaesthesia * 1  0/7 (0.00%)  0/8 (0.00%)  1/14 (7.14%)  0/20 (0.00%)  1/16 (6.25%)  0/23 (0.00%)  0/11 (0.00%) 
Sciatica * 1  1/7 (14.29%)  0/8 (0.00%)  0/14 (0.00%)  0/20 (0.00%)  0/16 (0.00%)  0/23 (0.00%)  0/11 (0.00%) 
Amnesia * 1  0/7 (0.00%)  0/8 (0.00%)  0/14 (0.00%)  0/20 (0.00%)  0/16 (0.00%)  1/23 (4.35%)  1/11 (9.09%) 
Aphasia * 1  0/7 (0.00%)  0/8 (0.00%)  0/14 (0.00%)  0/20 (0.00%)  1/16 (6.25%)  0/23 (0.00%)  0/11 (0.00%) 
Ataxia * 1  0/7 (0.00%)  0/8 (0.00%)  0/14 (0.00%)  0/20 (0.00%)  1/16 (6.25%)  1/23 (4.35%)  1/11 (9.09%) 
Dysgeusia * 1  0/7 (0.00%)  0/8 (0.00%)  0/14 (0.00%)  4/20 (20.00%)  1/16 (6.25%)  0/23 (0.00%)  2/11 (18.18%) 
Peripheral Sensory Neuropathy * 1  0/7 (0.00%)  0/8 (0.00%)  0/14 (0.00%)  0/20 (0.00%)  1/16 (6.25%)  0/23 (0.00%)  0/11 (0.00%) 
Sinus Headache * 1  0/7 (0.00%)  0/8 (0.00%)  0/14 (0.00%)  0/20 (0.00%)  1/16 (6.25%)  0/23 (0.00%)  0/11 (0.00%) 
Somnolence * 1  0/7 (0.00%)  0/8 (0.00%)  0/14 (0.00%)  0/20 (0.00%)  0/16 (0.00%)  0/23 (0.00%)  1/11 (9.09%) 
Dysaesthesia * 1  0/7 (0.00%)  0/8 (0.00%)  0/14 (0.00%)  0/20 (0.00%)  0/16 (0.00%)  0/23 (0.00%)  1/11 (9.09%) 
Psychiatric disorders               
Anxiety * 1  0/7 (0.00%)  3/8 (37.50%)  1/14 (7.14%)  3/20 (15.00%)  2/16 (12.50%)  1/23 (4.35%)  2/11 (18.18%) 
Insomnia * 1  0/7 (0.00%)  2/8 (25.00%)  1/14 (7.14%)  5/20 (25.00%)  2/16 (12.50%)  2/23 (8.70%)  1/11 (9.09%) 
Depression * 1  1/7 (14.29%)  0/8 (0.00%)  0/14 (0.00%)  0/20 (0.00%)  1/16 (6.25%)  2/23 (8.70%)  2/11 (18.18%) 
Agitation * 1  0/7 (0.00%)  0/8 (0.00%)  0/14 (0.00%)  1/20 (5.00%)  0/16 (0.00%)  0/23 (0.00%)  3/11 (27.27%) 
Confusional State * 1  0/7 (0.00%)  0/8 (0.00%)  0/14 (0.00%)  2/20 (10.00%)  1/16 (6.25%)  0/23 (0.00%)  0/11 (0.00%) 
Hallucination, Visual * 1  0/7 (0.00%)  0/8 (0.00%)  0/14 (0.00%)  0/20 (0.00%)  1/16 (6.25%)  0/23 (0.00%)  0/11 (0.00%) 
Restlessness * 1  0/7 (0.00%)  0/8 (0.00%)  0/14 (0.00%)  0/20 (0.00%)  0/16 (0.00%)  0/23 (0.00%)  1/11 (9.09%) 
Renal and urinary disorders               
Hydronephrosis * 1  0/7 (0.00%)  0/8 (0.00%)  1/14 (7.14%)  0/20 (0.00%)  1/16 (6.25%)  1/23 (4.35%)  0/11 (0.00%) 
Micturition Urgency * 1  0/7 (0.00%)  0/8 (0.00%)  1/14 (7.14%)  0/20 (0.00%)  0/16 (0.00%)  0/23 (0.00%)  0/11 (0.00%) 
Renal Failure Acute * 1  0/7 (0.00%)  0/8 (0.00%)  1/14 (7.14%)  0/20 (0.00%)  0/16 (0.00%)  0/23 (0.00%)  1/11 (9.09%) 
Urinary Incontinence * 1  0/7 (0.00%)  0/8 (0.00%)  1/14 (7.14%)  0/20 (0.00%)  0/16 (0.00%)  0/23 (0.00%)  0/11 (0.00%) 
Reproductive system and breast disorders               
Breast Pain * 1  0/7 (0.00%)  0/8 (0.00%)  1/14 (7.14%)  0/20 (0.00%)  0/16 (0.00%)  1/23 (4.35%)  0/11 (0.00%) 
Vulvovaginal Dryness * 1  0/7 (0.00%)  0/8 (0.00%)  1/14 (7.14%)  1/20 (5.00%)  0/16 (0.00%)  1/23 (4.35%)  0/11 (0.00%) 
Ovarian Cyst * 1  0/7 (0.00%)  0/8 (0.00%)  0/14 (0.00%)  0/20 (0.00%)  0/16 (0.00%)  0/23 (0.00%)  1/11 (9.09%) 
Respiratory, thoracic and mediastinal disorders               
Cough * 1  0/7 (0.00%)  4/8 (50.00%)  2/14 (14.29%)  3/20 (15.00%)  3/16 (18.75%)  4/23 (17.39%)  1/11 (9.09%) 
Dyspnoea * 1  0/7 (0.00%)  1/8 (12.50%)  4/14 (28.57%)  2/20 (10.00%)  2/16 (12.50%)  2/23 (8.70%)  4/11 (36.36%) 
Nasal Congestion * 1  0/7 (0.00%)  3/8 (37.50%)  0/14 (0.00%)  0/20 (0.00%)  0/16 (0.00%)  0/23 (0.00%)  0/11 (0.00%) 
Dysphonia * 1  1/7 (14.29%)  0/8 (0.00%)  1/14 (7.14%)  0/20 (0.00%)  2/16 (12.50%)  0/23 (0.00%)  0/11 (0.00%) 
Epistaxis * 1  1/7 (14.29%)  0/8 (0.00%)  0/14 (0.00%)  0/20 (0.00%)  0/16 (0.00%)  1/23 (4.35%)  0/11 (0.00%) 
Productive Cough * 1  1/7 (14.29%)  1/8 (12.50%)  0/14 (0.00%)  0/20 (0.00%)  0/16 (0.00%)  0/23 (0.00%)  0/11 (0.00%) 
Dyspnoea Exertional * 1  1/7 (14.29%)  0/8 (0.00%)  0/14 (0.00%)  1/20 (5.00%)  1/16 (6.25%)  1/23 (4.35%)  0/11 (0.00%) 
Haemoptysis * 1  1/7 (14.29%)  0/8 (0.00%)  0/14 (0.00%)  0/20 (0.00%)  0/16 (0.00%)  0/23 (0.00%)  0/11 (0.00%) 
Pleural Effusion * 1  0/7 (0.00%)  1/8 (12.50%)  0/14 (0.00%)  0/20 (0.00%)  0/16 (0.00%)  0/23 (0.00%)  1/11 (9.09%) 
Pleuritic Pain * 1  0/7 (0.00%)  0/8 (0.00%)  1/14 (7.14%)  0/20 (0.00%)  0/16 (0.00%)  0/23 (0.00%)  0/11 (0.00%) 
Oropharyngeal Pain * 1  0/7 (0.00%)  0/8 (0.00%)  0/14 (0.00%)  1/20 (5.00%)  0/16 (0.00%)  1/23 (4.35%)  1/11 (9.09%) 
Rhinorrhoea * 1  0/7 (0.00%)  0/8 (0.00%)  0/14 (0.00%)  0/20 (0.00%)  1/16 (6.25%)  1/23 (4.35%)  0/11 (0.00%) 
Upper-Airway Cough Syndrome * 1  0/7 (0.00%)  0/8 (0.00%)  0/14 (0.00%)  0/20 (0.00%)  0/16 (0.00%)  0/23 (0.00%)  1/11 (9.09%) 
Wheezing * 1  0/7 (0.00%)  0/8 (0.00%)  0/14 (0.00%)  0/20 (0.00%)  0/16 (0.00%)  0/23 (0.00%)  1/11 (9.09%) 
Skin and subcutaneous tissue disorders               
Rash * 1  0/7 (0.00%)  1/8 (12.50%)  2/14 (14.29%)  2/20 (10.00%)  1/16 (6.25%)  2/23 (8.70%)  1/11 (9.09%) 
Acne * 1  1/7 (14.29%)  0/8 (0.00%)  1/14 (7.14%)  0/20 (0.00%)  0/16 (0.00%)  0/23 (0.00%)  0/11 (0.00%) 
Dry Skin * 1  0/7 (0.00%)  1/8 (12.50%)  1/14 (7.14%)  2/20 (10.00%)  2/16 (12.50%)  0/23 (0.00%)  0/11 (0.00%) 
Alopecia * 1  0/7 (0.00%)  0/8 (0.00%)  1/14 (7.14%)  1/20 (5.00%)  2/16 (12.50%)  0/23 (0.00%)  2/11 (18.18%) 
Blood Blister * 1  1/7 (14.29%)  0/8 (0.00%)  0/14 (0.00%)  0/20 (0.00%)  0/16 (0.00%)  0/23 (0.00%)  0/11 (0.00%) 
Pruritus * 1  1/7 (14.29%)  0/8 (0.00%)  0/14 (0.00%)  1/20 (5.00%)  0/16 (0.00%)  3/23 (13.04%)  0/11 (0.00%) 
Rash Generalised * 1  0/7 (0.00%)  0/8 (0.00%)  1/14 (7.14%)  1/20 (5.00%)  0/16 (0.00%)  0/23 (0.00%)  0/11 (0.00%) 
Skin Hyperpigmentation * 1  0/7 (0.00%)  0/8 (0.00%)  1/14 (7.14%)  0/20 (0.00%)  0/16 (0.00%)  0/23 (0.00%)  0/11 (0.00%) 
Night Sweats * 1  0/7 (0.00%)  0/8 (0.00%)  0/14 (0.00%)  0/20 (0.00%)  0/16 (0.00%)  1/23 (4.35%)  2/11 (18.18%) 
Rash Maculo-Papular * 1  0/7 (0.00%)  0/8 (0.00%)  0/14 (0.00%)  2/20 (10.00%)  0/16 (0.00%)  1/23 (4.35%)  0/11 (0.00%) 
Erythema * 1  0/7 (0.00%)  0/8 (0.00%)  0/14 (0.00%)  0/20 (0.00%)  1/16 (6.25%)  0/23 (0.00%)  0/11 (0.00%) 
Vascular disorders               
Hypertension * 1  1/7 (14.29%)  4/8 (50.00%)  1/14 (7.14%)  1/20 (5.00%)  0/16 (0.00%)  5/23 (21.74%)  2/11 (18.18%) 
Hot Flush * 1  0/7 (0.00%)  0/8 (0.00%)  4/14 (28.57%)  5/20 (25.00%)  2/16 (12.50%)  4/23 (17.39%)  3/11 (27.27%) 
Lymphoedema * 1  0/7 (0.00%)  0/8 (0.00%)  1/14 (7.14%)  0/20 (0.00%)  0/16 (0.00%)  1/23 (4.35%)  0/11 (0.00%) 
Hypotension * 1  0/7 (0.00%)  0/8 (0.00%)  0/14 (0.00%)  0/20 (0.00%)  1/16 (6.25%)  0/23 (0.00%)  1/11 (9.09%) 
1
Term from vocabulary, MedDRA 15.0
*
Indicates events were collected by non-systematic assessment
Prioritization of outcome measures as primary and secondary was based on the study team’s discretion.
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
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
Layout table for Results Point of Contact information
Name/Title: Pfizer ClinicalTrials.gov Call Center
Organization: Pfizer, Inc.
Phone: 1-800-718-1021
EMail: ClinicalTrials.gov_Inquiries@pfizer.com
Layout table for additonal information
Responsible Party: Pfizer
ClinicalTrials.gov Identifier: NCT01597193    
Other Study ID Numbers: MDV3100-08
C3431006 ( Other Identifier: Alias Study Number )
First Submitted: May 9, 2012
First Posted: May 11, 2012
Results First Submitted: June 4, 2018
Results First Posted: May 8, 2019
Last Update Posted: May 8, 2019