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A Study of ZEN003694 in Combination With Enzalutamide in Patients With Metastatic Castration-Resistant Prostate Cancer

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02711956
Recruitment Status : Completed
First Posted : March 17, 2016
Results First Posted : August 10, 2021
Last Update Posted : November 30, 2021
Sponsor:
Information provided by (Responsible Party):
Zenith Epigenetics

Study Type Interventional
Study Design Allocation: N/A;   Intervention Model: Single Group Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Metastatic Castration-Resistant Prostate Cancer
Interventions Drug: ZEN003694
Drug: Enzalutamide
Enrollment 75
Recruitment Details The study was conducted at seven investigational sites in the United States between December 2016 and November 2019
Pre-assignment Details 75 participants were enrolled and treated in the study.
Arm/Group Title DE-A - 48 mg ZEN003694 + Enzalutamide DE-A - 60 mg ZEN003694 + Enzalutamide DE-A - 72 mg ZEN003694 + Enzalutamide DE-A - 96 mg ZEN003694 + Enzalutamide DE-A - 120 mg ZEN003694 + Enzalutamide DE-A - 144 mg ZEN003694 + Enzalutamide DE-B - 36 mg ZEN003694 + Enzalutamide DE-B - 48 mg ZEN003694 + Enzalutamide DE-B 60 mg ZEN003694 + Enzalutamide DE-B - 72 mg ZEN003694 + Enzalutamide DE-B 96 mg ZEN003694 + Enzalutamide DC-A 48 mg ZEN003694 + Enzalutamide DC-A 96 mg ZEN003694 + Enzalutamide DC-B 48 mg ZEN003694 + Enzalutamide DC-B 96 mg ZEN003694 + Enzalutamide
Hide Arm/Group Description Dose Escalation - Cohort A - Enzalutamide (160 mg) PO QD 14 days lead-in followed by the combination of ZEN003694 (48 mg) PO QD and enzalutamide (160 mg) PO QD in 28-day cycles. Dose Escalation - Cohort A - Enzalutamide (160 mg) PO QD 14 days lead-in followed by the combination of ZEN003694 (60 mg) PO QD and enzalutamide (160 mg) PO QD in 28-day cycles. Dose Escalation - Cohort A - Enzalutamide (160 mg) PO QD 14 days lead-in followed by the combination of ZEN003694 (72 mg) PO QD and enzalutamide (160 mg) PO QD in 28-day cycles. Dose Escalation - Cohort A - Enzalutamide (160 mg) PO QD 14 days lead-in followed by the combination of ZEN003694 (96 mg) PO QD and enzalutamide (160 mg) PO QD in 28-day cycles. Dose Escalation - Cohort A - Enzalutamide (160 mg) PO QD 14 days lead-in followed by the combination of ZEN003694 (120 mg) PO QD and enzalutamide (160 mg) PO QD in 28-day cycles. Dose Escalation - Cohort A - Enzalutamide (160 mg) PO QD 14 days lead-in followed by the combination of ZEN003694 (144 mg) PO QD and enzalutamide (160 mg) PO QD in 28-day cycles. Dose Escalation - Cohort B - Enzalutamide (160 mg) PO QD 14 days lead-in followed by the combination of ZEN003694 (36 mg) PO QD and enzalutamide (160 mg) PO QD in 28-day cycles. Dose Escalation - Cohort B - Enzalutamide (160 mg) PO QD 14 days lead-in followed by the combination of ZEN003694 (48 mg) PO QD and enzalutamide (160 mg) PO QD in 28-day cycles. Dose Escalation - Cohort B - Enzalutamide (160 mg) PO QD 14 days lead-in followed by the combination of ZEN003694 (60 mg) PO QD and enzalutamide (160 mg) PO QD in 28-day cycles. Dose Escalation - Cohort B - Enzalutamide (160 mg) PO QD 14 days lead-in followed by the combination of ZEN003694 (72 mg) PO QD and enzalutamide (160 mg) PO QD in 28-day cycles. Dose Escalation - Cohort B - Enzalutamide (160 mg) PO QD 14 days lead-in followed by the combination of ZEN003694 (96 mg) PO QD and enzalutamide (160 mg) PO QD in 28-day cycles. Dose Confirmation - Cohort A - Enzalutamide (160 mg) PO QD 14 days lead-in followed by the combination of ZEN003694 (48 mg) PO QD and enzalutamide (160 mg) PO QD in 28-day cycles. Dose Confirmation - Cohort A - Enzalutamide (160 mg) PO QD 14 days lead-in followed by the combination of ZEN003694 (96 mg) PO QD and enzalutamide (160 mg) PO QD in 28-day cycles Dose Confirmation - Cohort B - Enzalutamide (160 mg) PO QD 14 days lead-in followed by the combination of ZEN003694 (48 mg) PO QD and enzalutamide (160 mg) PO QD in 28-day cycles Dose Confirmation - Cohort B - Enzalutamide (160 mg) PO QD 14 days lead-in followed by the combination of ZEN003694 (96 mg) PO QD and enzalutamide (160 mg) PO QD in 28-day cycles
Period Title: Overall Study
Started 2 2 3 5 4 3 4 4 4 3 1 9 17 6 8
Completed 0 0 1 2 0 1 0 2 0 0 0 0 1 1 0
Not Completed 2 2 2 3 4 2 4 2 4 3 1 9 16 5 8
Reason Not Completed
Adverse Event             0             0             0             1             2             0             0             1             1             1             1             0             0             0             2
Physician Decision             0             0             0             2             0             0             0             0             0             0             0             0             0             0             0
Withdrawal by Subject             0             0             0             0             0             0             1             0             0             0             0             1             6             0             1
Clinical progression             1             0             0             0             0             0             1             0             1             0             0             2             4             1             1
Radiographic progression             1             1             2             0             1             0             0             0             2             1             0             5             3             0             1
PSA progression with clinical progression             0             0             0             0             1             0             0             0             0             0             0             0             1             1             0
PSA progression with radiographic progression             0             1             0             0             0             2             2             1             0             1             0             1             2             3             3
Arm/Group Title DE-A - 48 mg ZEN003694 + Enzalutamide DE-A - 60 mg ZEN003694 + Enzalutamide DE-A - 72 mg ZEN003694 + Enzalutamide DE-A - 96 mg ZEN003694 + Enzalutamide DE-A - 120 mg ZEN003694 + Enzalutamide DE-A - 144 mg ZEN003694 + Enzalutamide DE-B - 36 mg ZEN003694 + Enzalutamide DE-B - 48 mg ZEN003694 + Enzalutamide DE-B - 60 mg ZEN003694 + Enzalutamide DE-B - 72 mg ZEN003694 + Enzalutamide DE-B - 96 mg ZEN003694 + Enzalutamide DC-A - 48 mg ZEN003694 + Enzalutamide DC-A - 96 mg ZEN003694 + Enzalutamide DC-B - 48 mg ZEN003694 + Enzalutamide DC-B - 96 mg ZEN003694 + Enzalutamide Total
Hide Arm/Group Description Dose Escalation - Cohort A - Enzalutamide (160 mg) PO QD 14 days lead-in followed by the combination of ZEN003694 (48 mg) PO QD and enzalutamide (160 mg) PO QD in 28-day cycles. Dose Escalation - Cohort A - Enzalutamide (160 mg) PO QD 14 days lead-in followed by the combination of ZEN003694 (60 mg) PO QD and enzalutamide (160 mg) PO QD in 28-day cycles. Dose Escalation - Cohort A - Enzalutamide (160 mg) PO QD 14 days lead-in followed by the combination of ZEN003694 (72 mg) PO QD and enzalutamide (160 mg) PO QD in 28-day cycles. Dose Escalation - Cohort A - Enzalutamide (160 mg) PO QD 14 days lead-in followed by the combination of ZEN003694 (96 mg) PO QD and enzalutamide (160 mg) PO QD in 28-day cycles. Dose Escalation - Cohort A - Enzalutamide (160 mg) PO QD 14 days lead-in followed by the combination of ZEN003694 (120 mg) PO QD and enzalutamide (160 mg) PO QD in 28-day cycles. Dose Escalation - Cohort A - Enzalutamide (160 mg) PO QD 14 days lead-in followed by the combination of ZEN003694 (144 mg) PO QD and enzalutamide (160 mg) PO QD in 28-day cycles. Dose Escalation - Cohort B - Enzalutamide (160 mg) PO QD 14 days lead-in followed by the combination of ZEN003694 (36 mg) PO QD and enzalutamide (160 mg) PO QD in 28-day cycles. Dose Escalation - Cohort B - Enzalutamide (160 mg) PO QD 14 days lead-in followed by the combination of ZEN003694 (48 mg) PO QD and enzalutamide (160 mg) PO QD in 28-day cycles. Dose Escalation - Cohort B - Enzalutamide (160 mg) PO QD 14 days lead-in followed by the combination of ZEN003694 (60 mg) PO QD and enzalutamide (160 mg) PO QD in 28-day cycles. Dose Escalation - Cohort B - Enzalutamide (160 mg) PO QD 14 days lead-in followed by the combination of ZEN003694 (72 mg) PO QD and enzalutamide (160 mg) PO QD in 28-day cycles. Dose Escalation - Cohort B - Enzalutamide (160 mg) PO QD 14 days lead-in followed by the combination of ZEN003694 (96 mg) PO QD and enzalutamide (160 mg) PO QD in 28-day cycles. Dose Confirmation - Cohort A - Enzalutamide (160 mg) PO QD 14 days lead-in followed by the combination of ZEN003694 (48 mg) PO QD and enzalutamide (160 mg) PO QD in 28-day cycles. Dose Confirmation - Cohort A - Enzalutamide (160 mg) PO QD 14 days lead-in followed by the combination of ZEN003694 (96 mg) PO QD and enzalutamide (160 mg) PO QD in 28-day cycles. Dose Confirmation - Cohort B - Enzalutamide (160 mg) PO QD 14 days lead-in followed by the combination of ZEN003694 (48 mg) PO QD and enzalutamide (160 mg) PO QD in 28-day cycles. Dose Confirmation - Cohort B - Enzalutamide (160 mg) PO QD 14 days lead-in followed by the combination of ZEN003694 (96 mg) PO QD and enzalutamide (160 mg) PO QD in 28-day cycles. Total of all reporting groups
Overall Number of Baseline Participants 2 2 3 5 4 3 4 4 4 3 1 9 17 6 8 75
Hide Baseline Analysis Population Description
All treated safety population consisted of all treated participants.
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 2 participants 2 participants 3 participants 5 participants 4 participants 3 participants 4 participants 4 participants 4 participants 3 participants 1 participants 9 participants 17 participants 6 participants 8 participants 75 participants
69.5  (0.71) 63.0  (1.41) 69.0  (18.03) 62.6  (10.26) 66.5  (5.80) 73.0  (3.61) 73.8  (3.50) 65.5  (11.33) 75.0  (13.49) 67.0  (12.49) 62 67.9  (9.20) 71.2  (7.59) 68.2  (6.71) 71.3  (7.98) 69.2  (8.68)
Age, Continuous  
Median (Full Range)
Unit of measure:  Years
Number Analyzed 2 participants 2 participants 3 participants 5 participants 4 participants 3 participants 4 participants 4 participants 4 participants 3 participants 1 participants 9 participants 17 participants 6 participants 8 participants 75 participants
69.5
(69 to 70)
63
(62 to 64)
74
(49 to 84)
63
(47 to 74)
67.5
(59 to 72)
72
(70 to 77)
73.5
(70 to 78)
63.5
(54 to 81)
74.5
(62 to 89)
71
(53 to 77)
62
66
(52 to 82)
70
(59 to 83)
67
(61 to 77)
72
(57 to 84)
70
(47 to 89)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 2 participants 2 participants 3 participants 5 participants 4 participants 3 participants 4 participants 4 participants 4 participants 3 participants 1 participants 9 participants 17 participants 6 participants 8 participants 75 participants
Female
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Male
2
 100.0%
2
 100.0%
3
 100.0%
5
 100.0%
4
 100.0%
3
 100.0%
4
 100.0%
4
 100.0%
4
 100.0%
3
 100.0%
1
 100.0%
9
 100.0%
17
 100.0%
6
 100.0%
8
 100.0%
75
 100.0%
Ethnicity (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 2 participants 2 participants 3 participants 5 participants 4 participants 3 participants 4 participants 4 participants 4 participants 3 participants 1 participants 9 participants 17 participants 6 participants 8 participants 75 participants
Hispanic or Latino
1
  50.0%
0
   0.0%
0
   0.0%
1
  20.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
1
  33.3%
0
   0.0%
1
  11.1%
1
   5.9%
0
   0.0%
2
  25.0%
7
   9.3%
Not Hispanic or Latino
1
  50.0%
2
 100.0%
3
 100.0%
4
  80.0%
4
 100.0%
3
 100.0%
4
 100.0%
4
 100.0%
4
 100.0%
2
  66.7%
1
 100.0%
8
  88.9%
16
  94.1%
6
 100.0%
6
  75.0%
68
  90.7%
Unknown or Not Reported
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 2 participants 2 participants 3 participants 5 participants 4 participants 3 participants 4 participants 4 participants 4 participants 3 participants 1 participants 9 participants 17 participants 6 participants 8 participants 75 participants
American Indian or Alaska Native
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Asian
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
4
  23.5%
0
   0.0%
0
   0.0%
4
   5.3%
Native Hawaiian or Other Pacific Islander
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Black or African American
0
   0.0%
0
   0.0%
0
   0.0%
1
  20.0%
0
   0.0%
0
   0.0%
0
   0.0%
1
  25.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
2
  11.8%
0
   0.0%
0
   0.0%
4
   5.3%
White
1
  50.0%
2
 100.0%
3
 100.0%
4
  80.0%
4
 100.0%
3
 100.0%
4
 100.0%
3
  75.0%
4
 100.0%
2
  66.7%
1
 100.0%
7
  77.8%
11
  64.7%
6
 100.0%
8
 100.0%
63
  84.0%
More than one race
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Unknown or Not Reported
1
  50.0%
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
  33.3%
0
   0.0%
2
  22.2%
0
   0.0%
0
   0.0%
0
   0.0%
4
   5.3%
Mean Body Mass Index   [1] 
Mean (Standard Deviation)
Unit of measure:  Kg/m^2
Number Analyzed 2 participants 2 participants 3 participants 5 participants 4 participants 3 participants 4 participants 4 participants 4 participants 3 participants 1 participants 8 participants 17 participants 6 participants 8 participants 74 participants
25.26  (1.854) 38.54  (0.882) 27.18  (5.505) 29.01  (5.201) 33.99  (6.138) 32.58  (6.447) 25.91  (1.557) 29.74  (6.805) 30.25  (6.699) 27.54  (0.825) 34.87 28.1  (3.763) 26.05  (4.183) 28.13  (2.523) 28.34  (3.670) 28.54  (4.895)
[1]
Measure Analysis Population Description: BMI not available for one participant in DC-A 48 mg
Median Body Mass Index   [1] 
Median (Full Range)
Unit of measure:  Kg/m^2
Number Analyzed 2 participants 2 participants 3 participants 5 participants 4 participants 3 participants 4 participants 4 participants 4 participants 3 participants 1 participants 8 participants 17 participants 6 participants 8 participants 74 participants
25.26
(24.0 to 26.6)
38.54
(37.9 to 39.2)
27.8
(21.4 to 32.3)
29.24
(22.3 to 36.7)
32.83
(28.0 to 42.3)
29.49
(28.2 to 40.0)
25.98
(24.2 to 27.5)
29.02
(22.3 to 38.6)
29.62
(22.8 to 38.9)
27.53
(26.7 to 28.4)
34.87
27.09
(24.2 to 36.4)
25.81
(21.2 to 39.2)
27.66
(25.2 to 32.5)
29.38
(23.8 to 32.7)
27.69
(21.2 to 42.3)
[1]
Measure Analysis Population Description: BMI not available for one participant in DC-A 48 mg
Mean PSA  
Mean (Standard Deviation)
Unit of measure:  ng/mL
Number Analyzed 2 participants 2 participants 3 participants 5 participants 4 participants 3 participants 4 participants 4 participants 4 participants 3 participants 1 participants 9 participants 17 participants 6 participants 8 participants 75 participants
37.295  (17.9534) 96.855  (132.7452) 10.383  (7.8450) 8.996  (7.0365) 90.718  (87.1840) 6.280  (4.7483) 149.423  (157.4893) 34.766  (10.52727) 53.404  (21.9723) 24.433  (5.2254) 12.720 38.358  (41.2016) 167.043  (274.6941) 112.449  (185.2442) 88.141  (78.4200) 84.364  (156.2876)
Median PSA  
Median (Full Range)
Unit of measure:  ng/mL
Number Analyzed 2 participants 2 participants 3 participants 5 participants 4 participants 3 participants 4 participants 4 participants 4 participants 3 participants 1 participants 9 participants 17 participants 6 participants 8 participants 75 participants
37.295
(24.6 to 49.99)
96.855
(2.99 to 190.72)
8.090
(3.94 to 19.12)
10.449
(1.12 to 18.77)
90.850
(6.21 to 174.96)
5.500
(1.97 to 11.37)
130.866
(5.42 to 330.54)
29.881
(28.70 to 50.60)
53.697
(30.58 to 75.65)
23.722
(19.60 to 29.98)
12.720
25.600
(0.09 to 116.44)
29.750
(1.18 to 1079.06)
52.043
(1.16 to 486.60)
87.518
(1.48 to 184.24)
28.700
(0.09 to 1079.06)
ECOG performance status   [1] 
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 2 participants 2 participants 3 participants 5 participants 4 participants 3 participants 4 participants 4 participants 4 participants 3 participants 1 participants 9 participants 17 participants 6 participants 8 participants 75 participants
0
1
  50.0%
1
  50.0%
2
  66.7%
4
  80.0%
3
  75.0%
3
 100.0%
1
  25.0%
3
  75.0%
1
  25.0%
1
  33.3%
1
 100.0%
6
  66.7%
10
  58.8%
4
  66.7%
4
  50.0%
45
  60.0%
1
1
  50.0%
1
  50.0%
1
  33.3%
1
  20.0%
1
  25.0%
0
   0.0%
3
  75.0%
1
  25.0%
3
  75.0%
2
  66.7%
0
   0.0%
3
  33.3%
7
  41.2%
2
  33.3%
4
  50.0%
30
  40.0%
[1]
Measure Description:

Classified on a 6-point (0 to 5) rating scale.

0 - Fully active, able to carry on all pre-disease performance without restriction; 1 - Restricted in physically strenuous activity but ambulatory and able to carry out work of light or sedentary nature; 2 - Ambulatory and capable of all self-care but unable to carry out any work activities. Up and about more than 50% of waking hours; 3 - Capable of only limited self-care, confined to bed or chair more than 50% of waking hours; 4 - Completely disabled. Cannot carry on any self-care. Totally confined to bed or chair; 5 - Dead
1.Primary Outcome
Title For Dose Escalation: Incidence of Dose-limiting Toxicities (DLT) to Determine the Maximum Tolerated Dose (MTD) and Recommended Phase 2 Dose (RP2D) of ZEN003694 in Combination With Enzalutamide.
Hide Description Determination of DLT was made during the first 28 days of treatment in the dose escalation phase. A DLT is defined as a clinically significant AE or laboratory abnormality that is considered possibly, probably, or definitely related to study drug. The MTD reflects the highest dose of ZEN003694 in combination with enzalutamide that did not cause a DLT in more than 1 of 6 patients. The RP2D is the recommended dose of ZEN003694 in combination with enzalutamide as determined in the dose confirmation phase of the study.
Time Frame Cycle 1 (Day 1 thru Day 28)
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Hide Analysis Population Description
Participants in dose escalation
Arm/Group Title DE A+B - 36 mg ZEN003694 + Enzalutamide DE A+B - 48 mg ZEN003694 + Enzalutamide DE A+B - 60 mg ZEN003694 + Enzalutamide DE A+B - 72 mg ZEN003694 + Enzalutamide DE A+B - 96 mg ZEN003694 + Enzalutamide DE A+B - 120 mg ZEN003694 + Enzalutamide DE A+B - 144 mg ZEN003694 + Enzalutamide
Hide Arm/Group Description:
Dose Escalation - Cohorts A + B - Enzalutamide (160 mg) PO QD 14 days lead-in followed by the combination of ZEN003694 (36 mg) PO QD and enzalutamide (160 mg) PO QD in 28-day cycles.
Dose Escalation - Cohorts A + B - Enzalutamide (160 mg) PO QD 14 days lead-in followed by the combination of ZEN003694 (48 mg) PO QD and enzalutamide (160 mg) PO QD in 28-day cycles.
Dose Escalation - Cohorts A+B - Enzalutamide (160 mg) PO QD 14 days lead-in followed by the combination of ZEN003694 (60 mg) PO QD and enzalutamide (160 mg) PO QD in 28-day cycles.
Dose Escalation - Cohorts A + B - Enzalutamide (160 mg) PO QD 14 days lead-in followed by the combination of ZEN003694 (72 mg) PO QD and enzalutamide (160 mg) PO QD in 28-day cycles.
Dose Escalation - Cohorts A + B - Enzalutamide (160 mg) PO QD 14 days lead-in followed by the combination of ZEN003694 (96 mg) PO QD and enzalutamide (160 mg) PO QD in 28-day cycles.
Dose Escalation Cohorts A + B - Enzalutamide (160 mg) PO QD 14 days lead-in followed by the combination of ZEN003694 (120 mg) PO QD and enzalutamide (160 mg) PO QD in 28-day cycles.
Dose Escalation - Cohorts A + B - Enzalutamide (160 mg) PO QD 14 days lead-in followed by the combination of ZEN003694 (144 mg) PO QD and enzalutamide (160 mg) PO QD in 28-day cycles.
Overall Number of Participants Analyzed 4 6 6 6 6 4 3
Measure Type: Count of Participants
Unit of Measure: Participants
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
1
  16.7%
0
   0.0%
0
   0.0%
2.Primary Outcome
Title For Dose Escalation and Dose Confirmation: Incidence of Treatment-emergent Adverse Events (TEAE) and Treatment-related Serious Adverse Events (SAE)
Hide Description Treatment-emergent adverse events (TEAEs) were defined as any adverse events (AEs) that begin or worsen on or after the start of study drug through 30 days after the last dose of study drug. The severity of AEs was graded based on the National Cancer Institute's Common Terminology for Adverse Events (V4.03). A serious adverse event (SAE) was any AE that was: fatal; life-threatening; required in-patient hospitalization or prolonged an existing hospitalization; disabling or incapacitating; a congenital anomaly or birth defect; or any other important medical event.
Time Frame Cycle 1 Day 1 to 30 days post last dose
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Hide Analysis Population Description
All participants
Arm/Group Title DE - 36 mg ZEN003694 + Enzalutamide DE/DC - 48 mg ZEN003694 + Enzalutamide DE - 60 mg ZEN003694 + Enzalutamide DE - 72 mg ZEN003694 + Enzalutamide DE/DC - 96 mg ZEN003694 + Enzalutamide DE - 120 mg ZEN003694 + Enzalutamide DE - 144 mg ZEN003694 + Enzalutamide
Hide Arm/Group Description:
Dose Escalation - Enzalutamide (160 mg) PO QD 14 days lead-in followed by the combination of ZEN003694 (36 mg) PO QD and enzalutamide (160 mg) PO QD in 28-day cycles.
Dose Escalation + Dose Confirmation - Enzalutamide (160 mg) PO QD 14 days lead-in followed by the combination of ZEN003694 (48 mg) PO QD and enzalutamide (160 mg) PO QD in 28-day cycles.
Dose Escalation - Enzalutamide (160 mg) PO QD 14 days lead-in followed by the combination of ZEN003694 (60 mg) PO QD and enzalutamide (160 mg) PO QD in 28-day cycles.
Dose Escalation - Enzalutamide (160 mg) PO QD 14 days lead-in followed by the combination of ZEN003694 (72 mg) PO QD and enzalutamide (160 mg) PO QD in 28-day cycles.
Dose Escalation + Dose Confirmation - Enzalutamide (160 mg) PO QD 14 days lead-in followed by the combination of ZEN003694 (96 mg) PO QD and enzalutamide (160 mg) PO QD in 28-day cycles.
Dose Escalation - Enzalutamide (160 mg) PO QD 14 days lead-in followed by the combination of ZEN003694 (120 mg) PO QD and enzalutamide (160 mg) PO QD in 28-day cycles.
Dose Escalation - Enzalutamide (160 mg) PO QD 14 days lead-in followed by the combination of ZEN003694 (144 mg) PO QD and enzalutamide (160 mg) PO QD in 28-day cycles.
Overall Number of Participants Analyzed 4 21 6 6 31 4 3
Measure Type: Count of Participants
Unit of Measure: Participants
Blood creatinine increased
0
   0.0%
0
   0.0%
2
  33.3%
0
   0.0%
3
   9.7%
0
   0.0%
0
   0.0%
Constipation
0
   0.0%
1
   4.8%
0
   0.0%
0
   0.0%
3
   9.7%
0
   0.0%
0
   0.0%
Decreased appetite
0
   0.0%
2
   9.5%
2
  33.3%
1
  16.7%
10
  32.3%
3
  75.0%
2
  66.7%
Diarrhea
0
   0.0%
0
   0.0%
0
   0.0%
1
  16.7%
5
  16.1%
0
   0.0%
0
   0.0%
Dizziness
0
   0.0%
0
   0.0%
0
   0.0%
1
  16.7%
3
   9.7%
0
   0.0%
0
   0.0%
Dysgeusia
0
   0.0%
2
   9.5%
0
   0.0%
0
   0.0%
10
  32.3%
1
  25.0%
3
 100.0%
Dyspepsia
0
   0.0%
1
   4.8%
0
   0.0%
0
   0.0%
2
   6.5%
0
   0.0%
0
   0.0%
Fatigue
1
  25.0%
8
  38.1%
1
  16.7%
2
  33.3%
13
  41.9%
3
  75.0%
1
  33.3%
Nasal congestion
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
3
   9.7%
0
   0.0%
0
   0.0%
Nausea
0
   0.0%
7
  33.3%
2
  33.3%
3
  50.0%
17
  54.8%
3
  75.0%
2
  66.7%
Photopsia
0
   0.0%
1
   4.8%
0
   0.0%
0
   0.0%
3
   9.7%
0
   0.0%
0
   0.0%
Photosensitivity
0
   0.0%
2
   9.5%
0
   0.0%
0
   0.0%
3
   9.7%
0
   0.0%
0
   0.0%
Rash
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
3
   9.7%
0
   0.0%
0
   0.0%
Rash maculopapular
0
   0.0%
3
  14.3%
0
   0.0%
0
   0.0%
1
   3.2%
0
   0.0%
1
  33.3%
Taste disorder
0
   0.0%
0
   0.0%
1
  16.7%
1
  16.7%
3
   9.7%
0
   0.0%
0
   0.0%
Thrombocytopenia
0
   0.0%
1
   4.8%
1
  16.7%
2
  33.3%
6
  19.4%
0
   0.0%
1
  33.3%
Vision blurred
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
2
   6.5%
1
  25.0%
0
   0.0%
Visual symptoms
3
  75.0%
12
  57.1%
4
  66.7%
6
 100.0%
17
  54.8%
4
 100.0%
2
  66.7%
Vomiting
0
   0.0%
1
   4.8%
0
   0.0%
0
   0.0%
3
   9.7%
1
  25.0%
0
   0.0%
Weight loss and abnormal weight loss
1
  25.0%
0
   0.0%
0
   0.0%
1
  16.7%
3
   9.7%
1
  25.0%
2
  66.7%
3.Secondary Outcome
Title Evaluate Prostate-specific Antigen (PSA) Response Rate by PCWG2 Criteria
Hide Description The PSA response rate will be evaluated using PCWG2 criteria and defined as the proportion of patients with a PSA decline of at least 50%. Any change from baseline is confirmed by a second measurement at least 3 weeks later. PSA Response Rate will be evaluated using PCWG2 criteria and defined as following: Percentage change from baseline in PSA to 12 weeks post ZEN003694 dose. Only evaluate for patients with at least 12 weeks of treatment, the PSA assessment at 12 weeks (84 days +/-3 days) will be used; Maximum percent decrease in PSA from baseline that occurs at any point after treatment. Evaluable for all patients with post-baseline PSA. Arms will be combined to analyze efficacy in Cohort A and Cohort B.
Time Frame Screening up to 35 months
Hide Outcome Measure Data
Hide Analysis Population Description
Arms were combined to analyze efficacy based on Cohorts defined by protocol. Cohort A is defined as patients with prior progression on enzalutamide or apalutamide by PCWG2 criteria. Cohort B is defined as patients who were enzalutamide-naïve with prior progression on abiraterone by PCWG2 criteria.
Arm/Group Title DE/DC-A ZEN003694 + Enzalutamide DE/DC-B ZEN003694 + Enzalutamide
Hide Arm/Group Description:
Dose Escalation + Dose Confirmation - Cohort A - Enzalutamide (160 mg) PO QD 14 days lead-in followed by the combination of ZEN003694 (48 -144 mg) PO QD and enzalutamide (160 mg) PO QD in 28-day cycles.
Dose Escalation + Dose Confirmation - Cohort B - Enzalutamide (160 mg) PO QD 14 days lead-in followed by the combination of ZEN003694 (36 - 96 mg) PO QD and enzalutamide (160 mg) PO QD in 28-day cycles.
Overall Number of Participants Analyzed 45 30
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
4.4
(0.5 to 15.1)
23.3
(9.9 to 42.3)
4.Secondary Outcome
Title Evaluate Radiographic Response Rate (Overall Response Rate) by PCWG2 Criteria
Hide Description Tumor response will be evaluated using the PCWG2 criteria. Patients with measurable disease will be evaluated for clinical benefit as determined by tumor response using RECIST v1.1. Patients with non-measurable bone disease will be evaluated for progression based on the presence of any new lesions by bone scans. Radiographic tumor evaluation will be performed at screening and every 3 cycles or more frequently as determined by the investigator. Using the tumor response that is determined by the investigator, best overall response will be determined using RECIST v1.1. Best overall response is defined as the best response recorded from the start of treatment until disease progression or study exit. Arms will be combined to analyze efficacy in Cohort A and Cohort B.
Time Frame Screening up to 35 months
Hide Outcome Measure Data
Hide Analysis Population Description
Arms were combined to analyze efficacy based on Cohorts defined by protocol. Cohort A is defined as patients with prior progression on enzalutamide or apalutamide by PCWG2 criteria. Cohort B is defined as patients who were enzalutamide-naïve with prior progression on abiraterone by PCWG2 criteria.
Arm/Group Title DE/DC A ZEN003694 + Enzalutamide DE/DC B ZEN003694 + Enzalutamide
Hide Arm/Group Description:
Dose Escalation + Dose Confirmation - Cohort A - Enzalutamide/Apalutamide Progressors - Enzalutamide (160 mg) PO QD 14 days lead-in followed by the combination of ZEN003694 (36 mg - 144 mg) PO QD and enzalutamide (160 mg) PO QD in 28-day cycles.
Dose Escalation + Dose Confirmation - Cohort B - Abiraterone Progressors - Enzalutamide (160 mg) PO QD 14 days lead-in followed by the combination of ZEN003694 (36 mg - 144 mg) PO QD and enzalutamide (160 mg) PO QD in 28-day cycles.
Overall Number of Participants Analyzed 39 26
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
2.6
(0.1 to 13.5)
3.8
(0.1 to 19.6)
5.Secondary Outcome
Title Evaluate Overall Median Progression-free Survival by PCWG2 Criteria
Hide Description Overall progression free survival (PFS) is determined using the PCWG2 criteria. Overall PFS is measured from screening until the time that disease progression (radiographic progressive disease or clinical deterioration) or death is documented, whichever occurs first. Arms will be combined to analyze efficacy in Cohort A and Cohort B.
Time Frame Screening up to 35 months
Hide Outcome Measure Data
Hide Analysis Population Description
Arms were combined to analyze efficacy based on Cohorts defined by protocol. Cohort A is defined as patients with prior progression on enzalutamide or apalutamide by PCWG2 criteria. Cohort B is defined as patients who were enzalutamide-naïve with prior progression on abiraterone by PCWG2 criteria.
Arm/Group Title DE/DC A ZEN003694 + Enzalutamide DE/DC B ZEN003694 + Enzalutamide
Hide Arm/Group Description:
Dose Escalation + Dose Confirmation - Cohort A - Enzalutamide/Apalutamide Progressors - Enzalutamide (160 mg) PO QD 14 days lead-in followed by the combination of ZEN003694 (36 mg - 144 mg) PO QD and enzalutamide (160 mg) PO QD in 28-day cycles.
Dose Escalation + Dose Confirmation - Cohort B -Abiraterone Progressors - Enzalutamide (160 mg) PO QD 14 days lead-in followed by the combination of ZEN003694 (36 mg - 144 mg) PO QD and enzalutamide (160 mg) PO QD in 28-day cycles.
Overall Number of Participants Analyzed 45 30
Median (95% Confidence Interval)
Unit of Measure: months
4.7
(3.5 to 9.0)
6.2
(4.6 to 7.9)
6.Secondary Outcome
Title Evaluate Median Radiographic Progression-Free Survival by PCWG2 Criteria
Hide Description Radiographic progression-free survival (rPFS) is determined using the PCWG2 criteria to assess both soft-tissue and bone assessments. The rPFS is measured from screening until the time the first radiographic scan shows disease progression, or until the time of death, whichever occurs first. If radiographic disease progression is identified at the first on-treatment radiographic assessment at Cycle 3 Day 1 (8 weeks), radiographic progression must be confirmed by a second assessment 6 or more weeks later. Patients who do not progress radiographically or did not die prior to study exit are censored on the date of their last dose of ZEN003694. Arms will be combined to analyze efficacy in Cohort A and Cohort B.
Time Frame Screening up to 35 months
Hide Outcome Measure Data
Hide Analysis Population Description
Arms were combined to analyze efficacy based on Cohorts defined by protocol. Cohort A is defined as patients with prior progression on enzalutamide or apalutamide by PCWG2 criteria. Cohort B is defined as patients who were enzalutamide-naïve with prior progression on abiraterone by PCWG2 criteria.
Arm/Group Title DE/DC A ZEN003694 + Enzalutamide DE/DC B ZEN003694 + Enzalutamide
Hide Arm/Group Description:
Dose Escalation + Dose Confirmation - Cohort A - Enzalutamide/Apalutamide Progressors - Enzalutamide (160 mg) PO QD 14 days lead-in followed by the combination of ZEN003694 (36 mg -144 mg) PO QD and enzalutamide (160 mg) PO QD in 28-day cycles.
Dose Escalation + Dose Confirmation - Cohort B - Abiraterone Progressors - Enzalutamide (160 mg) PO QD 14 days lead-in followed by the combination of ZEN003694 (36 mg -144 mg) PO QD and enzalutamide (160 mg) PO QD in 28-day cycles.
Overall Number of Participants Analyzed 45 30
Median (95% Confidence Interval)
Unit of Measure: months
10.2
(4.8 to 13.1)
8.8
(6.1 to 11.5)
7.Secondary Outcome
Title Measure the Pharmacokinetic (PK) Parameter: AUC(0-24h) of ZEN003694 and ZEN003791 (Active Metabolite) Administered in Combination With Enzalutamide.
Hide Description AUC(0-24h) is defined as the area under the curve (plasma concentration of drug over a 24-hour time period).
Time Frame Cycle 1 Day 1: pre-dose, 0.25, 0.5, 1, 2, 4, 6 and 8 hours post-dose; Cycle 1 Day 2: pre-dose; Cycle 1 Day 15: pre-dose, 0.25, 0.5, 1, 2, 4, 6 and 8 hours post-dose
Hide Outcome Measure Data
Hide Analysis Population Description
All Evaluable Participants
Arm/Group Title DE A+B 36 mg ZEN003694 + Enzalutamide DE/DC A+B 48 mg ZEN003694 + Enzalutamide DE A+B 60 mg ZEN003694 + Enzalutamide DE A+B 72 mg ZEN003694 + Enzalutamide DE/DC A+B 96 mg ZEN003694 + Enzalutamide DE A+B 120 mg ZEN003694 + Enzalutamide DE A+B 144 mg ZEN003694 + Enzalutamide
Hide Arm/Group Description:
Dose Escalation - Cohorts A + B - Enzalutamide (160 mg) PO QD 14 days lead-in followed by the combination of ZEN003694 (36 mg) PO QD and enzalutamide (160 mg) PO QD in 28-day cycles.
Dose Escalation + Dose Confirmation - Cohorts A+B - Enzalutamide (160 mg) PO QD 14 days lead-in followed by the combination of ZEN003694 (48 mg) PO QD and enzalutamide (160 mg) PO QD in 28-day cycles.
Dose Escalation - Cohorts A + B - Enzalutamide (160 mg) PO QD 14 days lead-in followed by the combination of ZEN003694 (60 mg) PO QD and enzalutamide (160 mg) PO QD in 28-day cycles.
Dose Escalation - Cohorts A + B - Enzalutamide (160 mg) PO QD 14 days lead-in followed by the combination of ZEN003694 (72 mg) PO QD and enzalutamide (160 mg) PO QD in 28-day cycles.
Dose Escalation + Dose Confirmation - Cohorts A + B - Enzalutamide (160 mg) PO QD 14 days lead-in followed by the combination of ZEN003694 (96 mg) PO QD and enzalutamide (160 mg) PO QD in 28-day cycles.
Dose Escalation - Cohorts A + B - Enzalutamide (160 mg) PO QD 14 days lead-in followed by the combination of ZEN003694 (120 mg) PO QD and enzalutamide (160 mg) PO QD in 28-day cycles.
Dose Escalation - Cohorts A +B - Enzalutamide (160 mg) PO QD 14 days lead-in followed by the combination of ZEN003694 (144 mg) PO QD and enzalutamide (160 mg) PO QD in 28-day cycles.
Overall Number of Participants Analyzed 4 21 6 6 31 4 3
Geometric Mean (Standard Error)
Unit of Measure: ng*h/mL
ZEN003694 AUC(0-24h) Study Day 1 1001  (494) 985  (374) 2243  (848) 1966  (1067) 2424  (1450) 2153  (1529) 2119  (1547)
ZEN003694 AUC(0-24h) Study Day 15; C24 (24h) inputed with Day 15 C0 (pre-dose) for AUC calculations 867  (651) 1046  (512) 1487  (871) 1453  (967) 2138  (946) 2109  (578) 1641  (704)
ZEN003791 AUC(0-24h) Study Day 1 1335  (659) 1874  (635) 3344  (1101) 3277  (1708) 4090  (1562) 3712  (2660) 3815  (2774)
ZEN003791 AUC(0-24h) Study Day 15; C24 (24h) imputed with Day 15 C0 (pre-dose) for AUC calculations. 1234  (606) 2216  (1187) 2979  (1583) 2586  (1265) 4478  (2449) 5275  (2369) 3155  (1858)
8.Secondary Outcome
Title Measure the Pharmacokinetic (PK) Parameter: Cmax of ZEN003694 and ZEN003791 (Active Metabolite) Administered in Combination With Enzalutamide
Hide Description Cmax is defined as the maximum or peak plasma concentration of drug.
Time Frame Cycle 1 Day 1: pre-dose, 0.25, 0.5, 1, 2, 4, 6 and 8 hours post-dose; Cycle 1 Day 2: pre-dose; Cycle 1 Day 15: pre-dose, 0.25, 0.5, 1, 2, 4, 6 and 8 hours post-dose
Hide Outcome Measure Data
Hide Analysis Population Description
All Evaluable Participants
Arm/Group Title DE A+B - 36 mg ZEN003694 + Enzalutamide DE/DC A+B 48 mg ZEN003694 + Enzalutamide DE A+B 60 mg ZEN003694 + Enzalutamide PO QD DE A+B 72 mg ZEN003694 + Enzalutamide DE/DC A+B 96 mg ZEN003694 + Enzalutamide DE A+B 120 mg ZEN003694 + Enzalutamide PO QD DE A+B 144 mg ZEN003694 + Enzalutamide
Hide Arm/Group Description:
Dose Escalation - Cohorts A + B - Enzalutamide (160 mg) PO QD 14 days lead-in followed by the combination of ZEN003694 (36 mg) PO QD and enzalutamide (160 mg) PO QD in 28-day cycles.
Dose Escalation + Dose Confirmation - Cohorts A + B - Enzalutamide (160 mg) PO QD 14 days lead-in followed by the combination of ZEN003694 (48 mg) PO QD and enzalutamide (160 mg) PO QD in 28-day cycles.
Dose Escalation - Cohorts A + B - Enzalutamide (160 mg) PO QD 14 days lead-in followed by the combination of ZEN003694 (60 mg) PO QD and enzalutamide (160 mg) PO QD in 28-day cycles.
Dose Escalation - Cohorts A + B - Enzalutamide (160 mg) PO QD 14 days lead-in followed by the combination of ZEN003694 (72 mg) PO QD and enzalutamide (160 mg) PO QD in 28-day cycles.
Dose Escalation + Dose Confirmation - Cohorts A + B - Enzalutamide (160 mg) PO QD 14 days lead-in followed by the combination of ZEN003694 (96 mg) PO QD and enzalutamide (160 mg) PO QD in 28-day cycles.
Dose Escalation - Cohorts A + B - Enzalutamide (160 mg) PO QD 14 days lead-in followed by the combination of ZEN003694 (120 mg) PO QD and enzalutamide (160 mg) PO QD in 28-day cycles.
Dose Escalation - Cohorts A + B - Enzalutamide (160 mg) PO QD 14 days lead-in followed by the combination of ZEN003694 (144 mg) PO QD and enzalutamide (160 mg) PO QD in 28-day cycles.
Overall Number of Participants Analyzed 4 21 6 6 31 4 3
Geometric Mean (Standard Error)
Unit of Measure: ng/mL
ZEN003694 Cmax Study Day 1 181  (83) 216  (103) 290  (102) 452  (279) 492  (277) 425  (306) 494  (424)
ZEN003694 Cmax Study Day 15 184  (128) 236  (119) 289  (204) 392  (278) 484  (189) 458  (305) 457  (330)
ZEN003791 Cmax Study Day 1 125  (83) 184  (62) 244  (79) 306  (196) 374  (143) 342  (202) 417  (362)
ZEN003791 Cmax Study Day 15 129  (72) 220  (101) 259  (176) 319  (208) 477  (194) 552  (332) 432  (362)
Time Frame For an event to be recorded as an AE, the onset must occur during or after the patient's first exposure to study drug and no later than 30 days after the last study drug dose. There is no limit on reporting SAEs considered reasonably related to ZEN003694.
Adverse Event Reporting Description Adverse events were collected in all participants
 
Arm/Group Title DE A+B 36 mg ZEN003694 + Enzalutamide DE/DC A+B 48 mg ZEN003694 + Enzalutamide DE A+B 60 mg ZEN003694 + Enzalutamide DE A+B 72 mg ZEN003694 + Enzalutamide DE/DC A+B 96 mg ZEN003694 + Enzalutamide DE A+B 120 mg ZEN003694 + Enzalutamide DE A+B 144 mg ZEN003694 + Enzalutamide
Hide Arm/Group Description Dose Escalation - Cohorts A + B - Enzalutamide (160 mg) PO QD 14 days lead-in followed by the combination of ZEN003694 (36 mg) PO QD and enzalutamide (160 mg) PO QD in 28-day cycles. Dose Escalation + Dose Confirmation - Cohorts A + B - Enzalutamide (160 mg) PO QD 14 days lead-in followed by the combination of ZEN003694 (48 mg) PO QD and enzalutamide (160 mg) PO QD in 28-day cycles. Dose Escalation - Cohorts A + B - Enzalutamide (160 mg) PO QD 14 days lead-in followed by the combination of ZEN003694 (60 mg) PO QD and enzalutamide (160 mg) PO QD in 28-day cycles. Dose Escalation - Cohorts A + B - Enzalutamide (160 mg) PO QD 14 days lead-in followed by the combination of ZEN003694 (72 mg) PO QD and enzalutamide (160 mg) PO QD in 28-day cycles. Dose Escalation + Dose Confirmation - Cohorts A + B - Enzalutamide (160 mg) PO QD 14 days lead-in followed by the combination of ZEN003694 (96 mg) PO QD and enzalutamide (160 mg) PO QD in 28-day cycles. Dose Escalation - Cohorts A + B - Enzalutamide (160 mg) PO QD 14 days lead-in followed by the combination of ZEN003694 (120 mg) PO QD and enzalutamide (160 mg) PO QD in 28-day cycles. Dose Escalation - Cohorts A + B - Enzalutamide (160 mg) PO QD 14 days lead-in followed by the combination of ZEN003694 (144 mg) PO QD and enzalutamide (160 mg) PO QD in 28-day cycles.
All-Cause Mortality
DE A+B 36 mg ZEN003694 + Enzalutamide DE/DC A+B 48 mg ZEN003694 + Enzalutamide DE A+B 60 mg ZEN003694 + Enzalutamide DE A+B 72 mg ZEN003694 + Enzalutamide DE/DC A+B 96 mg ZEN003694 + Enzalutamide DE A+B 120 mg ZEN003694 + Enzalutamide DE A+B 144 mg ZEN003694 + Enzalutamide
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   0/4 (0.00%)   0/21 (0.00%)   0/6 (0.00%)   0/6 (0.00%)   0/31 (0.00%)   0/4 (0.00%)   0/3 (0.00%) 
Hide Serious Adverse Events
DE A+B 36 mg ZEN003694 + Enzalutamide DE/DC A+B 48 mg ZEN003694 + Enzalutamide DE A+B 60 mg ZEN003694 + Enzalutamide DE A+B 72 mg ZEN003694 + Enzalutamide DE/DC A+B 96 mg ZEN003694 + Enzalutamide DE A+B 120 mg ZEN003694 + Enzalutamide DE A+B 144 mg ZEN003694 + Enzalutamide
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   1/4 (25.00%)   3/21 (14.29%)   1/6 (16.67%)   2/6 (33.33%)   6/31 (19.35%)   1/4 (25.00%)   3/3 (100.00%) 
Blood and lymphatic system disorders               
Disseminated intravascular coagulation † 1  0/4 (0.00%)  0/21 (0.00%)  1/6 (16.67%)  0/6 (0.00%)  0/31 (0.00%)  0/4 (0.00%)  0/3 (0.00%) 
Cardiac disorders               
Myocardial ischaemia † 1  0/4 (0.00%)  0/21 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  1/31 (3.23%)  0/4 (0.00%)  0/3 (0.00%) 
Eye disorders               
Vision blurred † 1  0/4 (0.00%)  0/21 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/31 (0.00%)  0/4 (0.00%)  1/3 (33.33%) 
Gastrointestinal disorders               
Nausea † 1  0/4 (0.00%)  0/21 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  1/31 (3.23%)  0/4 (0.00%)  0/3 (0.00%) 
Small intestinal obstruction † 1  0/4 (0.00%)  0/21 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/31 (0.00%)  0/4 (0.00%)  1/3 (33.33%) 
Infections and infestations               
Enterococcal bacteraemia † 1  1/4 (25.00%)  0/21 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/31 (0.00%)  0/4 (0.00%)  0/3 (0.00%) 
Intervertebral discitis † 1  0/4 (0.00%)  0/21 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  1/31 (3.23%)  0/4 (0.00%)  0/3 (0.00%) 
Leptospirosis † 1  0/4 (0.00%)  0/21 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/31 (0.00%)  0/4 (0.00%)  1/3 (33.33%) 
Proteus infection † 1  0/4 (0.00%)  1/21 (4.76%)  0/6 (0.00%)  0/6 (0.00%)  0/31 (0.00%)  0/4 (0.00%)  0/3 (0.00%) 
Pyelonephritis † 1  0/4 (0.00%)  1/21 (4.76%)  0/6 (0.00%)  0/6 (0.00%)  0/31 (0.00%)  0/4 (0.00%)  0/3 (0.00%) 
Urinary tract infection † 1  0/4 (0.00%)  1/21 (4.76%)  0/6 (0.00%)  0/6 (0.00%)  0/31 (0.00%)  0/4 (0.00%)  0/3 (0.00%) 
Injury, poisoning and procedural complications               
Hip fracture † 1  0/4 (0.00%)  1/21 (4.76%)  0/6 (0.00%)  0/6 (0.00%)  0/31 (0.00%)  0/4 (0.00%)  0/3 (0.00%) 
Musculoskeletal and connective tissue disorders               
Back pain † 1  0/4 (0.00%)  1/21 (4.76%)  0/6 (0.00%)  0/6 (0.00%)  0/31 (0.00%)  0/4 (0.00%)  0/3 (0.00%) 
Musculoskeletal pain † 1  0/4 (0.00%)  0/21 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  1/31 (3.23%)  0/4 (0.00%)  0/3 (0.00%) 
Pathological fracture † 1  1/4 (25.00%)  0/21 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/31 (0.00%)  0/4 (0.00%)  0/3 (0.00%) 
Nervous system disorders               
Spinal cord compression † 1  0/4 (0.00%)  0/21 (0.00%)  0/6 (0.00%)  1/6 (16.67%)  1/31 (3.23%)  0/4 (0.00%)  0/3 (0.00%) 
Transient ischaemic attack † 1  0/4 (0.00%)  0/21 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/31 (0.00%)  1/4 (25.00%)  0/3 (0.00%) 
Renal and urinary disorders               
Haematuria † 1  1/4 (25.00%)  0/21 (0.00%)  0/6 (0.00%)  1/6 (16.67%)  0/31 (0.00%)  0/4 (0.00%)  0/3 (0.00%) 
Acute kidney injury † 1  0/4 (0.00%)  0/21 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  1/31 (3.23%)  0/4 (0.00%)  0/3 (0.00%) 
1
Term from vocabulary, MedDRA (19.0)
†
Indicates events were collected by systematic assessment
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
DE A+B 36 mg ZEN003694 + Enzalutamide DE/DC A+B 48 mg ZEN003694 + Enzalutamide DE A+B 60 mg ZEN003694 + Enzalutamide DE A+B 72 mg ZEN003694 + Enzalutamide DE/DC A+B 96 mg ZEN003694 + Enzalutamide DE A+B 120 mg ZEN003694 + Enzalutamide DE A+B 144 mg ZEN003694 + Enzalutamide
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   3/4 (75.00%)   19/21 (90.48%)   5/6 (83.33%)   6/6 (100.00%)   31/31 (100.00%)   4/4 (100.00%)   3/3 (100.00%) 
Blood and lymphatic system disorders               
Thrombocytopenia † 1  0/4 (0.00%)  1/21 (4.76%)  1/6 (16.67%)  2/6 (33.33%)  6/31 (19.35%)  0/4 (0.00%)  1/3 (33.33%) 
Eye disorders               
Visual impairment † 1  3/4 (75.00%)  12/21 (57.14%)  4/6 (66.67%)  6/6 (100.00%)  18/31 (58.06%)  4/4 (100.00%)  2/3 (66.67%) 
Photosensitivity reaction † 1  0/4 (0.00%)  2/21 (9.52%)  0/6 (0.00%)  0/6 (0.00%)  3/31 (9.68%)  0/4 (0.00%)  0/3 (0.00%) 
Photopsia † 1  0/4 (0.00%)  1/21 (4.76%)  0/6 (0.00%)  0/6 (0.00%)  3/31 (9.68%)  0/4 (0.00%)  0/3 (0.00%) 
Gastrointestinal disorders               
Nausea † 1  0/4 (0.00%)  7/21 (33.33%)  2/6 (33.33%)  3/6 (50.00%)  16/31 (51.61%)  3/4 (75.00%)  2/3 (66.67%) 
Diarrhea † 1  0/4 (0.00%)  0/21 (0.00%)  0/6 (0.00%)  1/6 (16.67%)  5/31 (16.13%)  0/4 (0.00%)  0/3 (0.00%) 
Vomiting † 1  0/4 (0.00%)  1/21 (4.76%)  0/6 (0.00%)  0/6 (0.00%)  3/31 (9.68%)  1/4 (25.00%)  0/3 (0.00%) 
Constipation † 1  0/4 (0.00%)  1/21 (4.76%)  0/6 (0.00%)  0/6 (0.00%)  3/31 (9.68%)  0/4 (0.00%)  0/3 (0.00%) 
General disorders               
Fatigue † 1  1/4 (25.00%)  9/21 (42.86%)  1/6 (16.67%)  2/6 (33.33%)  13/31 (41.94%)  3/4 (75.00%)  1/3 (33.33%) 
Investigations               
Weight decreased † 1  1/4 (25.00%)  0/21 (0.00%)  0/6 (0.00%)  1/6 (16.67%)  3/31 (9.68%)  1/4 (25.00%)  2/3 (66.67%) 
Blood creatinine increased † 1  0/4 (0.00%)  0/21 (0.00%)  2/6 (33.33%)  0/6 (0.00%)  3/31 (9.68%)  0/4 (0.00%)  0/3 (0.00%) 
Metabolism and nutrition disorders               
Decreased appetite † 1  0/4 (0.00%)  2/21 (9.52%)  2/6 (33.33%)  1/6 (16.67%)  10/31 (32.26%)  3/4 (75.00%)  2/3 (66.67%) 
Nervous system disorders               
Dysgeusia † 1  0/4 (0.00%)  2/21 (9.52%)  0/6 (0.00%)  0/6 (0.00%)  10/31 (32.26%)  1/4 (25.00%)  3/3 (100.00%) 
Dizziness † 1  0/4 (0.00%)  0/21 (0.00%)  0/6 (0.00%)  1/6 (16.67%)  3/31 (9.68%)  0/4 (0.00%)  0/3 (0.00%) 
Taste disorder † 1  0/4 (0.00%)  0/21 (0.00%)  1/6 (16.67%)  1/6 (16.67%)  3/31 (9.68%)  0/4 (0.00%)  0/3 (0.00%) 
Skin and subcutaneous tissue disorders               
Rash maculopapular † 1  0/4 (0.00%)  2/21 (9.52%)  0/6 (0.00%)  0/6 (0.00%)  1/31 (3.23%)  0/4 (0.00%)  1/3 (33.33%) 
1
Term from vocabulary, MedDRA (19.0)
†
Indicates events were collected by systematic assessment
[Not Specified]
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.
Results Point of Contact
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Name/Title: Zenith Study Team
Organization: Zenith Epigenetics Ltd
Phone: (415) 470-5600
EMail: ZEN003694-002@zenithepigenetics.com
Layout table for additonal information
Responsible Party: Zenith Epigenetics
ClinicalTrials.gov Identifier: NCT02711956    
Other Study ID Numbers: ZEN003694-002
First Submitted: March 14, 2016
First Posted: March 17, 2016
Results First Submitted: June 18, 2021
Results First Posted: August 10, 2021
Last Update Posted: November 30, 2021