Metastatic Castration-Resistant Prostate Cancer
Conditions
Keywords
Metastatic Castration-Resistant Prostate Cancer (mCRPC), Phase 1b/2a, Prostate Cancer, Pharmacokinetics (PK), ZEN003694, ZEN-3694, Metastatic Castrate-Resistant Prostate Cancer, BET inhibitor (BETi), Bromodomain, Pharmacodynamics (PD), Enzalutamide, XTANDI, MDV3100, Epigenetics
Brief summary
This is an open label, non-randomized, Phase 1b/2a, dose escalation and dose confirmation study of ZEN003694 in combination with enzalutamide in patients with mCRPC.
Interventions
DRUGZEN003694
DRUGEnzalutamide
Sponsors
Zenith Epigenetics
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
MALE
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Males age ≥ 18 years 2. Metastatic, castrate resistant, histologically confirmed prostate cancer; surgically castrated or continuous medical castration for ≥ 8 weeks prior to screening 3. Serum testosterone \< 50 ng/dL determined within 4 weeks of first administration of study drug 4. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 5. Adequate laboratory parameters \[absolute neutrophil (ANC), platelets, asparate aminotransferase (AST), alanine aminotransferase (ALT), total bilirubin, creatinine and coagulation parameters\] at screening 6. Dose Escalation Cohort DE-A: Prior progression on enzalutamide or apalutamide at any time by PCWG2 criteria and receiving a stable dose of enzalutamide at the start of study treatment. 7. Dose Escalation Cohort DE-B: Enzalutamide-naïve and apalutamide-naïve patients following prior progression on abiraterone by PCWG2 criteria and receiving a stable dose of enzalutamide at the start of study treatment. 8. Dose Confirmation Cohort A (DC-A) only: Currently receiving enzalutamide as most recent systemic therapy for mCRPC and have experienced PSA progression by PCWG2 criteria in the absence of radiographic and/or clinical progression. Patients may or may not have experienced prior progression on abiraterone. 9. Dose Confirmation Cohort B (DC-B) only: Enzalutamide-naïve patients following prior progression on abiraterone by PCWG2 criteria and within 12 weeks of discontinuing abiraterone.
Exclusion criteria
1. Any history of brain metastases or prior seizure or conditions predisposing to seizure activity 2. Have previously received an investigational BET inhibitor (including previous participation in this study or Study ZEN003694-001) 3. Have received prior systemic anti-cancer therapy (including abiraterone) or investigational therapy within 2 weeks or five half-lives, whichever is shorter, prior to the first administration of study drug 4. Failure to recover to Grade 1 or lower toxicity related to prior systemic therapy (excluding alopecia and neuropathy) prior to study entry 5. Radiation therapy within 2 weeks of the first administration of study drug 6. Have received prior chemotherapy in the metastatic castration-resistant setting (prior chemotherapy in the hormone-sensitive setting is allowed provided last dose was at least 6 months prior to study entry) 7. Have received prior investigational anti-androgen therapy, including ARN-509 8. Currently receiving medications known to be strong inhibitors of CYP2C8, strong inducers (except enzalutamide) or inhibitors of CYP3A4 and substrates of CYP3A4, CYP2C9 and CYP2C19 with a narrow therapeutic window. Strong inducers, inhibitors and substrates must be discontinued at least 7 days prior to the first administration of study drug. 9. Not a candidate for enzalutamide treatment, in the opinion of the Investigator
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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. | Cycle 1 (Day 1 thru Day 28) | 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. |
| For Dose Escalation and Dose Confirmation: Incidence of Treatment-emergent Adverse Events (TEAE) and Treatment-related Serious Adverse Events (SAE) | Cycle 1 Day 1 to 30 days post last dose | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Evaluate Overall Median Progression-free Survival by PCWG2 Criteria | Screening up to 35 months | 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. |
| Evaluate Median Radiographic Progression-Free Survival by PCWG2 Criteria | Screening up to 35 months | 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. |
| Evaluate Prostate-specific Antigen (PSA) Response Rate by PCWG2 Criteria | Screening up to 35 months | 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. |
| Measure the Pharmacokinetic (PK) Parameter: Cmax of ZEN003694 and ZEN003791 (Active Metabolite) Administered in Combination With Enzalutamide | 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 | Cmax is defined as the maximum or peak plasma concentration of drug. |
| Measure the Pharmacokinetic (PK) Parameter: AUC(0-24h) of ZEN003694 and ZEN003791 (Active Metabolite) Administered in Combination With Enzalutamide. | 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 | AUC(0-24h) is defined as the area under the curve (plasma concentration of drug over a 24-hour time period). |
| Evaluate Radiographic Response Rate (Overall Response Rate) by PCWG2 Criteria | Screening up to 35 months | 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. |
Countries
United States
Participant flow
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.
Participants by arm
| Arm | Count |
|---|---|
| DE-A - 48 mg ZEN003694 + Enzalutamide 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. | 2 |
| DE-A - 60 mg ZEN003694 + Enzalutamide 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. | 2 |
| DE-A - 72 mg ZEN003694 + Enzalutamide 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. | 3 |
| DE-A - 96 mg ZEN003694 + Enzalutamide 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. | 5 |
| DE-A - 120 mg ZEN003694 + Enzalutamide 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. | 4 |
| DE-A - 144 mg ZEN003694 + Enzalutamide 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. | 3 |
| DE-B - 36 mg ZEN003694 + Enzalutamide 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. | 4 |
| DE-B - 48 mg ZEN003694 + Enzalutamide 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. | 4 |
| DE-B - 60 mg ZEN003694 + Enzalutamide 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. | 4 |
| DE-B - 72 mg ZEN003694 + Enzalutamide 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. | 3 |
| DE-B - 96 mg ZEN003694 + Enzalutamide 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. | 1 |
| DC-A - 48 mg ZEN003694 + Enzalutamide 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. | 9 |
| DC-A - 96 mg ZEN003694 + Enzalutamide 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. | 17 |
| DC-B - 48 mg ZEN003694 + Enzalutamide 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. | 6 |
| DC-B - 96 mg ZEN003694 + Enzalutamide 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. | 8 |
| Total | 75 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 | FG006 | FG007 | FG008 | FG009 | FG010 | FG011 | FG012 | FG013 | FG014 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study | Adverse Event | 0 | 0 | 0 | 1 | 2 | 0 | 0 | 1 | 1 | 1 | 1 | 0 | 0 | 0 | 2 |
| Overall Study | Clinical progression | 1 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 1 | 0 | 0 | 2 | 4 | 1 | 1 |
| Overall Study | Physician Decision | 0 | 0 | 0 | 2 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Overall Study | PSA progression with clinical progression | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 1 | 0 |
| Overall Study | PSA progression with radiographic progression | 0 | 1 | 0 | 0 | 0 | 2 | 2 | 1 | 0 | 1 | 0 | 1 | 2 | 3 | 3 |
| Overall Study | Radiographic progression | 1 | 1 | 2 | 0 | 1 | 0 | 0 | 0 | 2 | 1 | 0 | 5 | 3 | 0 | 1 |
| Overall Study | Withdrawal by Subject | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 1 | 6 | 0 | 1 |
Baseline characteristics
| Characteristic | Total | 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 | DE-A - 48 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | 70 years | 63 years | 74 years | 63 years | 67.5 years | 72 years | 73.5 years | 63.5 years | 74.5 years | 71 years | 62 years | 69.5 years | 66 years | 70 years | 67 years | 72 years |
| ECOG performance status 0 | 45 Participants | 1 Participants | 2 Participants | 4 Participants | 3 Participants | 3 Participants | 1 Participants | 3 Participants | 1 Participants | 1 Participants | 1 Participants | 1 Participants | 6 Participants | 10 Participants | 4 Participants | 4 Participants |
| ECOG performance status 1 | 30 Participants | 1 Participants | 1 Participants | 1 Participants | 1 Participants | 0 Participants | 3 Participants | 1 Participants | 3 Participants | 2 Participants | 0 Participants | 1 Participants | 3 Participants | 7 Participants | 2 Participants | 4 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 7 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 1 Participants | 1 Participants | 1 Participants | 0 Participants | 2 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 68 Participants | 2 Participants | 3 Participants | 4 Participants | 4 Participants | 3 Participants | 4 Participants | 4 Participants | 4 Participants | 2 Participants | 1 Participants | 1 Participants | 8 Participants | 16 Participants | 6 Participants | 6 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Mean Body Mass Index | 28.54 kg/m^2 STANDARD_DEVIATION 4.895 | 38.54 kg/m^2 STANDARD_DEVIATION 0.882 | 27.18 kg/m^2 STANDARD_DEVIATION 5.505 | 29.01 kg/m^2 STANDARD_DEVIATION 5.201 | 33.99 kg/m^2 STANDARD_DEVIATION 6.138 | 32.58 kg/m^2 STANDARD_DEVIATION 6.447 | 25.91 kg/m^2 STANDARD_DEVIATION 1.557 | 29.74 kg/m^2 STANDARD_DEVIATION 6.805 | 30.25 kg/m^2 STANDARD_DEVIATION 6.699 | 27.54 kg/m^2 STANDARD_DEVIATION 0.825 | 34.87 kg/m^2 | 25.26 kg/m^2 STANDARD_DEVIATION 1.854 | 28.1 kg/m^2 STANDARD_DEVIATION 3.763 | 26.05 kg/m^2 STANDARD_DEVIATION 4.183 | 28.13 kg/m^2 STANDARD_DEVIATION 2.523 | 28.34 kg/m^2 STANDARD_DEVIATION 3.67 |
| Mean PSA | 84.364 ng/mL STANDARD_DEVIATION 156.2876 | 96.855 ng/mL STANDARD_DEVIATION 132.7452 | 10.383 ng/mL STANDARD_DEVIATION 7.845 | 8.996 ng/mL STANDARD_DEVIATION 7.0365 | 90.718 ng/mL STANDARD_DEVIATION 87.184 | 6.280 ng/mL STANDARD_DEVIATION 4.7483 | 149.423 ng/mL STANDARD_DEVIATION 157.4893 | 34.766 ng/mL STANDARD_DEVIATION 10.52727 | 53.404 ng/mL STANDARD_DEVIATION 21.9723 | 24.433 ng/mL STANDARD_DEVIATION 5.2254 | 12.720 ng/mL | 37.295 ng/mL STANDARD_DEVIATION 17.9534 | 38.358 ng/mL STANDARD_DEVIATION 41.2016 | 167.043 ng/mL STANDARD_DEVIATION 274.6941 | 112.449 ng/mL STANDARD_DEVIATION 185.2442 | 88.141 ng/mL STANDARD_DEVIATION 78.42 |
| Median Body Mass Index | 27.69 kg/m^2 | 38.54 kg/m^2 | 27.8 kg/m^2 | 29.24 kg/m^2 | 32.83 kg/m^2 | 29.49 kg/m^2 | 25.98 kg/m^2 | 29.02 kg/m^2 | 29.62 kg/m^2 | 27.53 kg/m^2 | 34.87 kg/m^2 | 25.26 kg/m^2 | 27.09 kg/m^2 | 25.81 kg/m^2 | 27.66 kg/m^2 | 29.38 kg/m^2 |
| Median PSA | 28.700 ng/mL | 96.855 ng/mL | 8.090 ng/mL | 10.449 ng/mL | 90.850 ng/mL | 5.500 ng/mL | 130.866 ng/mL | 29.881 ng/mL | 53.697 ng/mL | 23.722 ng/mL | 12.720 ng/mL | 37.295 ng/mL | 25.600 ng/mL | 29.750 ng/mL | 52.043 ng/mL | 87.518 ng/mL |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 4 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 4 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 4 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 2 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 4 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 1 Participants | 2 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 63 Participants | 2 Participants | 3 Participants | 4 Participants | 4 Participants | 3 Participants | 4 Participants | 3 Participants | 4 Participants | 2 Participants | 1 Participants | 1 Participants | 7 Participants | 11 Participants | 6 Participants | 8 Participants |
| Sex: Female, Male Female | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Male | 75 Participants | 2 Participants | 3 Participants | 5 Participants | 4 Participants | 3 Participants | 4 Participants | 4 Participants | 4 Participants | 3 Participants | 1 Participants | 2 Participants | 9 Participants | 17 Participants | 6 Participants | 8 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk | EG006 affected / at risk |
|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 4 | 0 / 21 | 0 / 6 | 0 / 6 | 0 / 31 | 0 / 4 | 0 / 3 |
| other Total, other adverse events | 3 / 4 | 19 / 21 | 5 / 6 | 6 / 6 | 31 / 31 | 4 / 4 | 3 / 3 |
| serious Total, serious adverse events | 1 / 4 | 3 / 21 | 1 / 6 | 2 / 6 | 6 / 31 | 1 / 4 | 3 / 3 |
Outcome results
Primary
For Dose Escalation and Dose Confirmation: Incidence of Treatment-emergent Adverse Events (TEAE) and Treatment-related Serious Adverse Events (SAE)
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
Population: All participants
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| DE A+B - 36 mg ZEN003694 + Enzalutamide | For Dose Escalation and Dose Confirmation: Incidence of Treatment-emergent Adverse Events (TEAE) and Treatment-related Serious Adverse Events (SAE) | Rash maculopapular | 0 Participants |
| DE A+B - 36 mg ZEN003694 + Enzalutamide | For Dose Escalation and Dose Confirmation: Incidence of Treatment-emergent Adverse Events (TEAE) and Treatment-related Serious Adverse Events (SAE) | Dizziness | 0 Participants |
| DE A+B - 36 mg ZEN003694 + Enzalutamide | For Dose Escalation and Dose Confirmation: Incidence of Treatment-emergent Adverse Events (TEAE) and Treatment-related Serious Adverse Events (SAE) | Nasal congestion | 0 Participants |
| DE A+B - 36 mg ZEN003694 + Enzalutamide | For Dose Escalation and Dose Confirmation: Incidence of Treatment-emergent Adverse Events (TEAE) and Treatment-related Serious Adverse Events (SAE) | Decreased appetite | 0 Participants |
| DE A+B - 36 mg ZEN003694 + Enzalutamide | For Dose Escalation and Dose Confirmation: Incidence of Treatment-emergent Adverse Events (TEAE) and Treatment-related Serious Adverse Events (SAE) | Photosensitivity | 0 Participants |
| DE A+B - 36 mg ZEN003694 + Enzalutamide | For Dose Escalation and Dose Confirmation: Incidence of Treatment-emergent Adverse Events (TEAE) and Treatment-related Serious Adverse Events (SAE) | Diarrhea | 0 Participants |
| DE A+B - 36 mg ZEN003694 + Enzalutamide | For Dose Escalation and Dose Confirmation: Incidence of Treatment-emergent Adverse Events (TEAE) and Treatment-related Serious Adverse Events (SAE) | Visual symptoms | 3 Participants |
| DE A+B - 36 mg ZEN003694 + Enzalutamide | For Dose Escalation and Dose Confirmation: Incidence of Treatment-emergent Adverse Events (TEAE) and Treatment-related Serious Adverse Events (SAE) | Photopsia | 0 Participants |
| DE A+B - 36 mg ZEN003694 + Enzalutamide | For Dose Escalation and Dose Confirmation: Incidence of Treatment-emergent Adverse Events (TEAE) and Treatment-related Serious Adverse Events (SAE) | Blood creatinine increased | 0 Participants |
| DE A+B - 36 mg ZEN003694 + Enzalutamide | For Dose Escalation and Dose Confirmation: Incidence of Treatment-emergent Adverse Events (TEAE) and Treatment-related Serious Adverse Events (SAE) | Fatigue | 1 Participants |
| DE A+B - 36 mg ZEN003694 + Enzalutamide | For Dose Escalation and Dose Confirmation: Incidence of Treatment-emergent Adverse Events (TEAE) and Treatment-related Serious Adverse Events (SAE) | Weight loss and abnormal weight loss | 1 Participants |
| DE A+B - 36 mg ZEN003694 + Enzalutamide | For Dose Escalation and Dose Confirmation: Incidence of Treatment-emergent Adverse Events (TEAE) and Treatment-related Serious Adverse Events (SAE) | Thrombocytopenia | 0 Participants |
| DE A+B - 36 mg ZEN003694 + Enzalutamide | For Dose Escalation and Dose Confirmation: Incidence of Treatment-emergent Adverse Events (TEAE) and Treatment-related Serious Adverse Events (SAE) | Nausea | 0 Participants |
| DE A+B - 36 mg ZEN003694 + Enzalutamide | For Dose Escalation and Dose Confirmation: Incidence of Treatment-emergent Adverse Events (TEAE) and Treatment-related Serious Adverse Events (SAE) | Rash | 0 Participants |
| DE A+B - 36 mg ZEN003694 + Enzalutamide | For Dose Escalation and Dose Confirmation: Incidence of Treatment-emergent Adverse Events (TEAE) and Treatment-related Serious Adverse Events (SAE) | Vomiting | 0 Participants |
| DE A+B - 36 mg ZEN003694 + Enzalutamide | For Dose Escalation and Dose Confirmation: Incidence of Treatment-emergent Adverse Events (TEAE) and Treatment-related Serious Adverse Events (SAE) | Dyspepsia | 0 Participants |
| DE A+B - 36 mg ZEN003694 + Enzalutamide | For Dose Escalation and Dose Confirmation: Incidence of Treatment-emergent Adverse Events (TEAE) and Treatment-related Serious Adverse Events (SAE) | Constipation | 0 Participants |
| DE A+B - 36 mg ZEN003694 + Enzalutamide | For Dose Escalation and Dose Confirmation: Incidence of Treatment-emergent Adverse Events (TEAE) and Treatment-related Serious Adverse Events (SAE) | Taste disorder | 0 Participants |
| DE A+B - 36 mg ZEN003694 + Enzalutamide | For Dose Escalation and Dose Confirmation: Incidence of Treatment-emergent Adverse Events (TEAE) and Treatment-related Serious Adverse Events (SAE) | Dysgeusia | 0 Participants |
| DE A+B - 36 mg ZEN003694 + Enzalutamide | For Dose Escalation and Dose Confirmation: Incidence of Treatment-emergent Adverse Events (TEAE) and Treatment-related Serious Adverse Events (SAE) | Vision blurred | 0 Participants |
| DE A+B - 48 mg ZEN003694 + Enzalutamide | For Dose Escalation and Dose Confirmation: Incidence of Treatment-emergent Adverse Events (TEAE) and Treatment-related Serious Adverse Events (SAE) | Blood creatinine increased | 0 Participants |
| DE A+B - 48 mg ZEN003694 + Enzalutamide | For Dose Escalation and Dose Confirmation: Incidence of Treatment-emergent Adverse Events (TEAE) and Treatment-related Serious Adverse Events (SAE) | Photosensitivity | 2 Participants |
| DE A+B - 48 mg ZEN003694 + Enzalutamide | For Dose Escalation and Dose Confirmation: Incidence of Treatment-emergent Adverse Events (TEAE) and Treatment-related Serious Adverse Events (SAE) | Rash | 0 Participants |
| DE A+B - 48 mg ZEN003694 + Enzalutamide | For Dose Escalation and Dose Confirmation: Incidence of Treatment-emergent Adverse Events (TEAE) and Treatment-related Serious Adverse Events (SAE) | Constipation | 1 Participants |
| DE A+B - 48 mg ZEN003694 + Enzalutamide | For Dose Escalation and Dose Confirmation: Incidence of Treatment-emergent Adverse Events (TEAE) and Treatment-related Serious Adverse Events (SAE) | Weight loss and abnormal weight loss | 0 Participants |
| DE A+B - 48 mg ZEN003694 + Enzalutamide | For Dose Escalation and Dose Confirmation: Incidence of Treatment-emergent Adverse Events (TEAE) and Treatment-related Serious Adverse Events (SAE) | Visual symptoms | 12 Participants |
| DE A+B - 48 mg ZEN003694 + Enzalutamide | For Dose Escalation and Dose Confirmation: Incidence of Treatment-emergent Adverse Events (TEAE) and Treatment-related Serious Adverse Events (SAE) | Decreased appetite | 2 Participants |
| DE A+B - 48 mg ZEN003694 + Enzalutamide | For Dose Escalation and Dose Confirmation: Incidence of Treatment-emergent Adverse Events (TEAE) and Treatment-related Serious Adverse Events (SAE) | Diarrhea | 0 Participants |
| DE A+B - 48 mg ZEN003694 + Enzalutamide | For Dose Escalation and Dose Confirmation: Incidence of Treatment-emergent Adverse Events (TEAE) and Treatment-related Serious Adverse Events (SAE) | Vision blurred | 0 Participants |
| DE A+B - 48 mg ZEN003694 + Enzalutamide | For Dose Escalation and Dose Confirmation: Incidence of Treatment-emergent Adverse Events (TEAE) and Treatment-related Serious Adverse Events (SAE) | Dizziness | 0 Participants |
| DE A+B - 48 mg ZEN003694 + Enzalutamide | For Dose Escalation and Dose Confirmation: Incidence of Treatment-emergent Adverse Events (TEAE) and Treatment-related Serious Adverse Events (SAE) | Dysgeusia | 2 Participants |
| DE A+B - 48 mg ZEN003694 + Enzalutamide | For Dose Escalation and Dose Confirmation: Incidence of Treatment-emergent Adverse Events (TEAE) and Treatment-related Serious Adverse Events (SAE) | Thrombocytopenia | 1 Participants |
| DE A+B - 48 mg ZEN003694 + Enzalutamide | For Dose Escalation and Dose Confirmation: Incidence of Treatment-emergent Adverse Events (TEAE) and Treatment-related Serious Adverse Events (SAE) | Dyspepsia | 1 Participants |
| DE A+B - 48 mg ZEN003694 + Enzalutamide | For Dose Escalation and Dose Confirmation: Incidence of Treatment-emergent Adverse Events (TEAE) and Treatment-related Serious Adverse Events (SAE) | Vomiting | 1 Participants |
| DE A+B - 48 mg ZEN003694 + Enzalutamide | For Dose Escalation and Dose Confirmation: Incidence of Treatment-emergent Adverse Events (TEAE) and Treatment-related Serious Adverse Events (SAE) | Fatigue | 8 Participants |
| DE A+B - 48 mg ZEN003694 + Enzalutamide | For Dose Escalation and Dose Confirmation: Incidence of Treatment-emergent Adverse Events (TEAE) and Treatment-related Serious Adverse Events (SAE) | Taste disorder | 0 Participants |
| DE A+B - 48 mg ZEN003694 + Enzalutamide | For Dose Escalation and Dose Confirmation: Incidence of Treatment-emergent Adverse Events (TEAE) and Treatment-related Serious Adverse Events (SAE) | Nasal congestion | 0 Participants |
| DE A+B - 48 mg ZEN003694 + Enzalutamide | For Dose Escalation and Dose Confirmation: Incidence of Treatment-emergent Adverse Events (TEAE) and Treatment-related Serious Adverse Events (SAE) | Photopsia | 1 Participants |
| DE A+B - 48 mg ZEN003694 + Enzalutamide | For Dose Escalation and Dose Confirmation: Incidence of Treatment-emergent Adverse Events (TEAE) and Treatment-related Serious Adverse Events (SAE) | Nausea | 7 Participants |
| DE A+B - 48 mg ZEN003694 + Enzalutamide | For Dose Escalation and Dose Confirmation: Incidence of Treatment-emergent Adverse Events (TEAE) and Treatment-related Serious Adverse Events (SAE) | Rash maculopapular | 3 Participants |
| DE A+B - 60 mg ZEN003694 + Enzalutamide | For Dose Escalation and Dose Confirmation: Incidence of Treatment-emergent Adverse Events (TEAE) and Treatment-related Serious Adverse Events (SAE) | Dizziness | 0 Participants |
| DE A+B - 60 mg ZEN003694 + Enzalutamide | For Dose Escalation and Dose Confirmation: Incidence of Treatment-emergent Adverse Events (TEAE) and Treatment-related Serious Adverse Events (SAE) | Constipation | 0 Participants |
| DE A+B - 60 mg ZEN003694 + Enzalutamide | For Dose Escalation and Dose Confirmation: Incidence of Treatment-emergent Adverse Events (TEAE) and Treatment-related Serious Adverse Events (SAE) | Dysgeusia | 0 Participants |
| DE A+B - 60 mg ZEN003694 + Enzalutamide | For Dose Escalation and Dose Confirmation: Incidence of Treatment-emergent Adverse Events (TEAE) and Treatment-related Serious Adverse Events (SAE) | Vomiting | 0 Participants |
| DE A+B - 60 mg ZEN003694 + Enzalutamide | For Dose Escalation and Dose Confirmation: Incidence of Treatment-emergent Adverse Events (TEAE) and Treatment-related Serious Adverse Events (SAE) | Thrombocytopenia | 1 Participants |
| DE A+B - 60 mg ZEN003694 + Enzalutamide | For Dose Escalation and Dose Confirmation: Incidence of Treatment-emergent Adverse Events (TEAE) and Treatment-related Serious Adverse Events (SAE) | Dyspepsia | 0 Participants |
| DE A+B - 60 mg ZEN003694 + Enzalutamide | For Dose Escalation and Dose Confirmation: Incidence of Treatment-emergent Adverse Events (TEAE) and Treatment-related Serious Adverse Events (SAE) | Photopsia | 0 Participants |
| DE A+B - 60 mg ZEN003694 + Enzalutamide | For Dose Escalation and Dose Confirmation: Incidence of Treatment-emergent Adverse Events (TEAE) and Treatment-related Serious Adverse Events (SAE) | Rash | 0 Participants |
| DE A+B - 60 mg ZEN003694 + Enzalutamide | For Dose Escalation and Dose Confirmation: Incidence of Treatment-emergent Adverse Events (TEAE) and Treatment-related Serious Adverse Events (SAE) | Nausea | 2 Participants |
| DE A+B - 60 mg ZEN003694 + Enzalutamide | For Dose Escalation and Dose Confirmation: Incidence of Treatment-emergent Adverse Events (TEAE) and Treatment-related Serious Adverse Events (SAE) | Fatigue | 1 Participants |
| DE A+B - 60 mg ZEN003694 + Enzalutamide | For Dose Escalation and Dose Confirmation: Incidence of Treatment-emergent Adverse Events (TEAE) and Treatment-related Serious Adverse Events (SAE) | Photosensitivity | 0 Participants |
| DE A+B - 60 mg ZEN003694 + Enzalutamide | For Dose Escalation and Dose Confirmation: Incidence of Treatment-emergent Adverse Events (TEAE) and Treatment-related Serious Adverse Events (SAE) | Taste disorder | 1 Participants |
| DE A+B - 60 mg ZEN003694 + Enzalutamide | For Dose Escalation and Dose Confirmation: Incidence of Treatment-emergent Adverse Events (TEAE) and Treatment-related Serious Adverse Events (SAE) | Blood creatinine increased | 2 Participants |
| DE A+B - 60 mg ZEN003694 + Enzalutamide | For Dose Escalation and Dose Confirmation: Incidence of Treatment-emergent Adverse Events (TEAE) and Treatment-related Serious Adverse Events (SAE) | Weight loss and abnormal weight loss | 0 Participants |
| DE A+B - 60 mg ZEN003694 + Enzalutamide | For Dose Escalation and Dose Confirmation: Incidence of Treatment-emergent Adverse Events (TEAE) and Treatment-related Serious Adverse Events (SAE) | Decreased appetite | 2 Participants |
| DE A+B - 60 mg ZEN003694 + Enzalutamide | For Dose Escalation and Dose Confirmation: Incidence of Treatment-emergent Adverse Events (TEAE) and Treatment-related Serious Adverse Events (SAE) | Nasal congestion | 0 Participants |
| DE A+B - 60 mg ZEN003694 + Enzalutamide | For Dose Escalation and Dose Confirmation: Incidence of Treatment-emergent Adverse Events (TEAE) and Treatment-related Serious Adverse Events (SAE) | Diarrhea | 0 Participants |
| DE A+B - 60 mg ZEN003694 + Enzalutamide | For Dose Escalation and Dose Confirmation: Incidence of Treatment-emergent Adverse Events (TEAE) and Treatment-related Serious Adverse Events (SAE) | Vision blurred | 0 Participants |
| DE A+B - 60 mg ZEN003694 + Enzalutamide | For Dose Escalation and Dose Confirmation: Incidence of Treatment-emergent Adverse Events (TEAE) and Treatment-related Serious Adverse Events (SAE) | Visual symptoms | 4 Participants |
| DE A+B - 60 mg ZEN003694 + Enzalutamide | For Dose Escalation and Dose Confirmation: Incidence of Treatment-emergent Adverse Events (TEAE) and Treatment-related Serious Adverse Events (SAE) | Rash maculopapular | 0 Participants |
| DE A+B - 72 mg ZEN003694 + Enzalutamide | For Dose Escalation and Dose Confirmation: Incidence of Treatment-emergent Adverse Events (TEAE) and Treatment-related Serious Adverse Events (SAE) | Vision blurred | 0 Participants |
| DE A+B - 72 mg ZEN003694 + Enzalutamide | For Dose Escalation and Dose Confirmation: Incidence of Treatment-emergent Adverse Events (TEAE) and Treatment-related Serious Adverse Events (SAE) | Vomiting | 0 Participants |
| DE A+B - 72 mg ZEN003694 + Enzalutamide | For Dose Escalation and Dose Confirmation: Incidence of Treatment-emergent Adverse Events (TEAE) and Treatment-related Serious Adverse Events (SAE) | Constipation | 0 Participants |
| DE A+B - 72 mg ZEN003694 + Enzalutamide | For Dose Escalation and Dose Confirmation: Incidence of Treatment-emergent Adverse Events (TEAE) and Treatment-related Serious Adverse Events (SAE) | Thrombocytopenia | 2 Participants |
| DE A+B - 72 mg ZEN003694 + Enzalutamide | For Dose Escalation and Dose Confirmation: Incidence of Treatment-emergent Adverse Events (TEAE) and Treatment-related Serious Adverse Events (SAE) | Fatigue | 2 Participants |
| DE A+B - 72 mg ZEN003694 + Enzalutamide | For Dose Escalation and Dose Confirmation: Incidence of Treatment-emergent Adverse Events (TEAE) and Treatment-related Serious Adverse Events (SAE) | Blood creatinine increased | 0 Participants |
| DE A+B - 72 mg ZEN003694 + Enzalutamide | For Dose Escalation and Dose Confirmation: Incidence of Treatment-emergent Adverse Events (TEAE) and Treatment-related Serious Adverse Events (SAE) | Weight loss and abnormal weight loss | 1 Participants |
| DE A+B - 72 mg ZEN003694 + Enzalutamide | For Dose Escalation and Dose Confirmation: Incidence of Treatment-emergent Adverse Events (TEAE) and Treatment-related Serious Adverse Events (SAE) | Dysgeusia | 0 Participants |
| DE A+B - 72 mg ZEN003694 + Enzalutamide | For Dose Escalation and Dose Confirmation: Incidence of Treatment-emergent Adverse Events (TEAE) and Treatment-related Serious Adverse Events (SAE) | Dizziness | 1 Participants |
| DE A+B - 72 mg ZEN003694 + Enzalutamide | For Dose Escalation and Dose Confirmation: Incidence of Treatment-emergent Adverse Events (TEAE) and Treatment-related Serious Adverse Events (SAE) | Nausea | 3 Participants |
| DE A+B - 72 mg ZEN003694 + Enzalutamide | For Dose Escalation and Dose Confirmation: Incidence of Treatment-emergent Adverse Events (TEAE) and Treatment-related Serious Adverse Events (SAE) | Rash maculopapular | 0 Participants |
| DE A+B - 72 mg ZEN003694 + Enzalutamide | For Dose Escalation and Dose Confirmation: Incidence of Treatment-emergent Adverse Events (TEAE) and Treatment-related Serious Adverse Events (SAE) | Visual symptoms | 6 Participants |
| DE A+B - 72 mg ZEN003694 + Enzalutamide | For Dose Escalation and Dose Confirmation: Incidence of Treatment-emergent Adverse Events (TEAE) and Treatment-related Serious Adverse Events (SAE) | Photopsia | 0 Participants |
| DE A+B - 72 mg ZEN003694 + Enzalutamide | For Dose Escalation and Dose Confirmation: Incidence of Treatment-emergent Adverse Events (TEAE) and Treatment-related Serious Adverse Events (SAE) | Rash | 0 Participants |
| DE A+B - 72 mg ZEN003694 + Enzalutamide | For Dose Escalation and Dose Confirmation: Incidence of Treatment-emergent Adverse Events (TEAE) and Treatment-related Serious Adverse Events (SAE) | Dyspepsia | 0 Participants |
| DE A+B - 72 mg ZEN003694 + Enzalutamide | For Dose Escalation and Dose Confirmation: Incidence of Treatment-emergent Adverse Events (TEAE) and Treatment-related Serious Adverse Events (SAE) | Nasal congestion | 0 Participants |
| DE A+B - 72 mg ZEN003694 + Enzalutamide | For Dose Escalation and Dose Confirmation: Incidence of Treatment-emergent Adverse Events (TEAE) and Treatment-related Serious Adverse Events (SAE) | Diarrhea | 1 Participants |
| DE A+B - 72 mg ZEN003694 + Enzalutamide | For Dose Escalation and Dose Confirmation: Incidence of Treatment-emergent Adverse Events (TEAE) and Treatment-related Serious Adverse Events (SAE) | Taste disorder | 1 Participants |
| DE A+B - 72 mg ZEN003694 + Enzalutamide | For Dose Escalation and Dose Confirmation: Incidence of Treatment-emergent Adverse Events (TEAE) and Treatment-related Serious Adverse Events (SAE) | Photosensitivity | 0 Participants |
| DE A+B - 72 mg ZEN003694 + Enzalutamide | For Dose Escalation and Dose Confirmation: Incidence of Treatment-emergent Adverse Events (TEAE) and Treatment-related Serious Adverse Events (SAE) | Decreased appetite | 1 Participants |
| DE A+B - 96 mg ZEN003694 + Enzalutamide | For Dose Escalation and Dose Confirmation: Incidence of Treatment-emergent Adverse Events (TEAE) and Treatment-related Serious Adverse Events (SAE) | Vomiting | 3 Participants |
| DE A+B - 96 mg ZEN003694 + Enzalutamide | For Dose Escalation and Dose Confirmation: Incidence of Treatment-emergent Adverse Events (TEAE) and Treatment-related Serious Adverse Events (SAE) | Weight loss and abnormal weight loss | 3 Participants |
| DE A+B - 96 mg ZEN003694 + Enzalutamide | For Dose Escalation and Dose Confirmation: Incidence of Treatment-emergent Adverse Events (TEAE) and Treatment-related Serious Adverse Events (SAE) | Blood creatinine increased | 3 Participants |
| DE A+B - 96 mg ZEN003694 + Enzalutamide | For Dose Escalation and Dose Confirmation: Incidence of Treatment-emergent Adverse Events (TEAE) and Treatment-related Serious Adverse Events (SAE) | Constipation | 3 Participants |
| DE A+B - 96 mg ZEN003694 + Enzalutamide | For Dose Escalation and Dose Confirmation: Incidence of Treatment-emergent Adverse Events (TEAE) and Treatment-related Serious Adverse Events (SAE) | Decreased appetite | 10 Participants |
| DE A+B - 96 mg ZEN003694 + Enzalutamide | For Dose Escalation and Dose Confirmation: Incidence of Treatment-emergent Adverse Events (TEAE) and Treatment-related Serious Adverse Events (SAE) | Diarrhea | 5 Participants |
| DE A+B - 96 mg ZEN003694 + Enzalutamide | For Dose Escalation and Dose Confirmation: Incidence of Treatment-emergent Adverse Events (TEAE) and Treatment-related Serious Adverse Events (SAE) | Dizziness | 3 Participants |
| DE A+B - 96 mg ZEN003694 + Enzalutamide | For Dose Escalation and Dose Confirmation: Incidence of Treatment-emergent Adverse Events (TEAE) and Treatment-related Serious Adverse Events (SAE) | Dysgeusia | 10 Participants |
| DE A+B - 96 mg ZEN003694 + Enzalutamide | For Dose Escalation and Dose Confirmation: Incidence of Treatment-emergent Adverse Events (TEAE) and Treatment-related Serious Adverse Events (SAE) | Dyspepsia | 2 Participants |
| DE A+B - 96 mg ZEN003694 + Enzalutamide | For Dose Escalation and Dose Confirmation: Incidence of Treatment-emergent Adverse Events (TEAE) and Treatment-related Serious Adverse Events (SAE) | Fatigue | 13 Participants |
| DE A+B - 96 mg ZEN003694 + Enzalutamide | For Dose Escalation and Dose Confirmation: Incidence of Treatment-emergent Adverse Events (TEAE) and Treatment-related Serious Adverse Events (SAE) | Nasal congestion | 3 Participants |
| DE A+B - 96 mg ZEN003694 + Enzalutamide | For Dose Escalation and Dose Confirmation: Incidence of Treatment-emergent Adverse Events (TEAE) and Treatment-related Serious Adverse Events (SAE) | Nausea | 17 Participants |
| DE A+B - 96 mg ZEN003694 + Enzalutamide | For Dose Escalation and Dose Confirmation: Incidence of Treatment-emergent Adverse Events (TEAE) and Treatment-related Serious Adverse Events (SAE) | Photopsia | 3 Participants |
| DE A+B - 96 mg ZEN003694 + Enzalutamide | For Dose Escalation and Dose Confirmation: Incidence of Treatment-emergent Adverse Events (TEAE) and Treatment-related Serious Adverse Events (SAE) | Photosensitivity | 3 Participants |
| DE A+B - 96 mg ZEN003694 + Enzalutamide | For Dose Escalation and Dose Confirmation: Incidence of Treatment-emergent Adverse Events (TEAE) and Treatment-related Serious Adverse Events (SAE) | Rash | 3 Participants |
| DE A+B - 96 mg ZEN003694 + Enzalutamide | For Dose Escalation and Dose Confirmation: Incidence of Treatment-emergent Adverse Events (TEAE) and Treatment-related Serious Adverse Events (SAE) | Rash maculopapular | 1 Participants |
| DE A+B - 96 mg ZEN003694 + Enzalutamide | For Dose Escalation and Dose Confirmation: Incidence of Treatment-emergent Adverse Events (TEAE) and Treatment-related Serious Adverse Events (SAE) | Taste disorder | 3 Participants |
| DE A+B - 96 mg ZEN003694 + Enzalutamide | For Dose Escalation and Dose Confirmation: Incidence of Treatment-emergent Adverse Events (TEAE) and Treatment-related Serious Adverse Events (SAE) | Thrombocytopenia | 6 Participants |
| DE A+B - 96 mg ZEN003694 + Enzalutamide | For Dose Escalation and Dose Confirmation: Incidence of Treatment-emergent Adverse Events (TEAE) and Treatment-related Serious Adverse Events (SAE) | Vision blurred | 2 Participants |
| DE A+B - 96 mg ZEN003694 + Enzalutamide | For Dose Escalation and Dose Confirmation: Incidence of Treatment-emergent Adverse Events (TEAE) and Treatment-related Serious Adverse Events (SAE) | Visual symptoms | 17 Participants |
| DE A+B - 120 mg ZEN003694 + Enzalutamide | For Dose Escalation and Dose Confirmation: Incidence of Treatment-emergent Adverse Events (TEAE) and Treatment-related Serious Adverse Events (SAE) | Rash maculopapular | 0 Participants |
| DE A+B - 120 mg ZEN003694 + Enzalutamide | For Dose Escalation and Dose Confirmation: Incidence of Treatment-emergent Adverse Events (TEAE) and Treatment-related Serious Adverse Events (SAE) | Dizziness | 0 Participants |
| DE A+B - 120 mg ZEN003694 + Enzalutamide | For Dose Escalation and Dose Confirmation: Incidence of Treatment-emergent Adverse Events (TEAE) and Treatment-related Serious Adverse Events (SAE) | Nausea | 3 Participants |
| DE A+B - 120 mg ZEN003694 + Enzalutamide | For Dose Escalation and Dose Confirmation: Incidence of Treatment-emergent Adverse Events (TEAE) and Treatment-related Serious Adverse Events (SAE) | Diarrhea | 0 Participants |
| DE A+B - 120 mg ZEN003694 + Enzalutamide | For Dose Escalation and Dose Confirmation: Incidence of Treatment-emergent Adverse Events (TEAE) and Treatment-related Serious Adverse Events (SAE) | Taste disorder | 0 Participants |
| DE A+B - 120 mg ZEN003694 + Enzalutamide | For Dose Escalation and Dose Confirmation: Incidence of Treatment-emergent Adverse Events (TEAE) and Treatment-related Serious Adverse Events (SAE) | Nasal congestion | 0 Participants |
| DE A+B - 120 mg ZEN003694 + Enzalutamide | For Dose Escalation and Dose Confirmation: Incidence of Treatment-emergent Adverse Events (TEAE) and Treatment-related Serious Adverse Events (SAE) | Vision blurred | 1 Participants |
| DE A+B - 120 mg ZEN003694 + Enzalutamide | For Dose Escalation and Dose Confirmation: Incidence of Treatment-emergent Adverse Events (TEAE) and Treatment-related Serious Adverse Events (SAE) | Dyspepsia | 0 Participants |
| DE A+B - 120 mg ZEN003694 + Enzalutamide | For Dose Escalation and Dose Confirmation: Incidence of Treatment-emergent Adverse Events (TEAE) and Treatment-related Serious Adverse Events (SAE) | Decreased appetite | 3 Participants |
| DE A+B - 120 mg ZEN003694 + Enzalutamide | For Dose Escalation and Dose Confirmation: Incidence of Treatment-emergent Adverse Events (TEAE) and Treatment-related Serious Adverse Events (SAE) | Blood creatinine increased | 0 Participants |
| DE A+B - 120 mg ZEN003694 + Enzalutamide | For Dose Escalation and Dose Confirmation: Incidence of Treatment-emergent Adverse Events (TEAE) and Treatment-related Serious Adverse Events (SAE) | Constipation | 0 Participants |
| DE A+B - 120 mg ZEN003694 + Enzalutamide | For Dose Escalation and Dose Confirmation: Incidence of Treatment-emergent Adverse Events (TEAE) and Treatment-related Serious Adverse Events (SAE) | Dysgeusia | 1 Participants |
| DE A+B - 120 mg ZEN003694 + Enzalutamide | For Dose Escalation and Dose Confirmation: Incidence of Treatment-emergent Adverse Events (TEAE) and Treatment-related Serious Adverse Events (SAE) | Vomiting | 1 Participants |
| DE A+B - 120 mg ZEN003694 + Enzalutamide | For Dose Escalation and Dose Confirmation: Incidence of Treatment-emergent Adverse Events (TEAE) and Treatment-related Serious Adverse Events (SAE) | Visual symptoms | 4 Participants |
| DE A+B - 120 mg ZEN003694 + Enzalutamide | For Dose Escalation and Dose Confirmation: Incidence of Treatment-emergent Adverse Events (TEAE) and Treatment-related Serious Adverse Events (SAE) | Fatigue | 3 Participants |
| DE A+B - 120 mg ZEN003694 + Enzalutamide | For Dose Escalation and Dose Confirmation: Incidence of Treatment-emergent Adverse Events (TEAE) and Treatment-related Serious Adverse Events (SAE) | Photosensitivity | 0 Participants |
| DE A+B - 120 mg ZEN003694 + Enzalutamide | For Dose Escalation and Dose Confirmation: Incidence of Treatment-emergent Adverse Events (TEAE) and Treatment-related Serious Adverse Events (SAE) | Weight loss and abnormal weight loss | 1 Participants |
| DE A+B - 120 mg ZEN003694 + Enzalutamide | For Dose Escalation and Dose Confirmation: Incidence of Treatment-emergent Adverse Events (TEAE) and Treatment-related Serious Adverse Events (SAE) | Thrombocytopenia | 0 Participants |
| DE A+B - 120 mg ZEN003694 + Enzalutamide | For Dose Escalation and Dose Confirmation: Incidence of Treatment-emergent Adverse Events (TEAE) and Treatment-related Serious Adverse Events (SAE) | Rash | 0 Participants |
| DE A+B - 120 mg ZEN003694 + Enzalutamide | For Dose Escalation and Dose Confirmation: Incidence of Treatment-emergent Adverse Events (TEAE) and Treatment-related Serious Adverse Events (SAE) | Photopsia | 0 Participants |
| DE A+B - 144 mg ZEN003694 + Enzalutamide | For Dose Escalation and Dose Confirmation: Incidence of Treatment-emergent Adverse Events (TEAE) and Treatment-related Serious Adverse Events (SAE) | Rash | 0 Participants |
| DE A+B - 144 mg ZEN003694 + Enzalutamide | For Dose Escalation and Dose Confirmation: Incidence of Treatment-emergent Adverse Events (TEAE) and Treatment-related Serious Adverse Events (SAE) | Nausea | 2 Participants |
| DE A+B - 144 mg ZEN003694 + Enzalutamide | For Dose Escalation and Dose Confirmation: Incidence of Treatment-emergent Adverse Events (TEAE) and Treatment-related Serious Adverse Events (SAE) | Nasal congestion | 0 Participants |
| DE A+B - 144 mg ZEN003694 + Enzalutamide | For Dose Escalation and Dose Confirmation: Incidence of Treatment-emergent Adverse Events (TEAE) and Treatment-related Serious Adverse Events (SAE) | Rash maculopapular | 1 Participants |
| DE A+B - 144 mg ZEN003694 + Enzalutamide | For Dose Escalation and Dose Confirmation: Incidence of Treatment-emergent Adverse Events (TEAE) and Treatment-related Serious Adverse Events (SAE) | Fatigue | 1 Participants |
| DE A+B - 144 mg ZEN003694 + Enzalutamide | For Dose Escalation and Dose Confirmation: Incidence of Treatment-emergent Adverse Events (TEAE) and Treatment-related Serious Adverse Events (SAE) | Dyspepsia | 0 Participants |
| DE A+B - 144 mg ZEN003694 + Enzalutamide | For Dose Escalation and Dose Confirmation: Incidence of Treatment-emergent Adverse Events (TEAE) and Treatment-related Serious Adverse Events (SAE) | Weight loss and abnormal weight loss | 2 Participants |
| DE A+B - 144 mg ZEN003694 + Enzalutamide | For Dose Escalation and Dose Confirmation: Incidence of Treatment-emergent Adverse Events (TEAE) and Treatment-related Serious Adverse Events (SAE) | Taste disorder | 0 Participants |
| DE A+B - 144 mg ZEN003694 + Enzalutamide | For Dose Escalation and Dose Confirmation: Incidence of Treatment-emergent Adverse Events (TEAE) and Treatment-related Serious Adverse Events (SAE) | Dysgeusia | 3 Participants |
| DE A+B - 144 mg ZEN003694 + Enzalutamide | For Dose Escalation and Dose Confirmation: Incidence of Treatment-emergent Adverse Events (TEAE) and Treatment-related Serious Adverse Events (SAE) | Dizziness | 0 Participants |
| DE A+B - 144 mg ZEN003694 + Enzalutamide | For Dose Escalation and Dose Confirmation: Incidence of Treatment-emergent Adverse Events (TEAE) and Treatment-related Serious Adverse Events (SAE) | Thrombocytopenia | 1 Participants |
| DE A+B - 144 mg ZEN003694 + Enzalutamide | For Dose Escalation and Dose Confirmation: Incidence of Treatment-emergent Adverse Events (TEAE) and Treatment-related Serious Adverse Events (SAE) | Diarrhea | 0 Participants |
| DE A+B - 144 mg ZEN003694 + Enzalutamide | For Dose Escalation and Dose Confirmation: Incidence of Treatment-emergent Adverse Events (TEAE) and Treatment-related Serious Adverse Events (SAE) | Decreased appetite | 2 Participants |
| DE A+B - 144 mg ZEN003694 + Enzalutamide | For Dose Escalation and Dose Confirmation: Incidence of Treatment-emergent Adverse Events (TEAE) and Treatment-related Serious Adverse Events (SAE) | Vomiting | 0 Participants |
| DE A+B - 144 mg ZEN003694 + Enzalutamide | For Dose Escalation and Dose Confirmation: Incidence of Treatment-emergent Adverse Events (TEAE) and Treatment-related Serious Adverse Events (SAE) | Vision blurred | 0 Participants |
| DE A+B - 144 mg ZEN003694 + Enzalutamide | For Dose Escalation and Dose Confirmation: Incidence of Treatment-emergent Adverse Events (TEAE) and Treatment-related Serious Adverse Events (SAE) | Constipation | 0 Participants |
| DE A+B - 144 mg ZEN003694 + Enzalutamide | For Dose Escalation and Dose Confirmation: Incidence of Treatment-emergent Adverse Events (TEAE) and Treatment-related Serious Adverse Events (SAE) | Blood creatinine increased | 0 Participants |
| DE A+B - 144 mg ZEN003694 + Enzalutamide | For Dose Escalation and Dose Confirmation: Incidence of Treatment-emergent Adverse Events (TEAE) and Treatment-related Serious Adverse Events (SAE) | Photosensitivity | 0 Participants |
| DE A+B - 144 mg ZEN003694 + Enzalutamide | For Dose Escalation and Dose Confirmation: Incidence of Treatment-emergent Adverse Events (TEAE) and Treatment-related Serious Adverse Events (SAE) | Photopsia | 0 Participants |
| DE A+B - 144 mg ZEN003694 + Enzalutamide | For Dose Escalation and Dose Confirmation: Incidence of Treatment-emergent Adverse Events (TEAE) and Treatment-related Serious Adverse Events (SAE) | Visual symptoms | 2 Participants |
Primary
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.
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)
Population: Participants in dose escalation
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| DE A+B - 36 mg ZEN003694 + Enzalutamide | 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. | 0 Participants |
| DE A+B - 48 mg ZEN003694 + Enzalutamide | 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. | 0 Participants |
| DE A+B - 60 mg ZEN003694 + Enzalutamide | 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. | 0 Participants |
| DE A+B - 72 mg ZEN003694 + Enzalutamide | 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. | 0 Participants |
| DE A+B - 96 mg ZEN003694 + Enzalutamide | 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. | 1 Participants |
| DE A+B - 120 mg ZEN003694 + Enzalutamide | 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. | 0 Participants |
| DE A+B - 144 mg ZEN003694 + Enzalutamide | 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. | 0 Participants |
Secondary
Evaluate Median Radiographic Progression-Free Survival by PCWG2 Criteria
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
Population: 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 | Measure | Value (MEDIAN) |
|---|---|---|
| DE A+B - 36 mg ZEN003694 + Enzalutamide | Evaluate Median Radiographic Progression-Free Survival by PCWG2 Criteria | 10.2 months |
| DE A+B - 48 mg ZEN003694 + Enzalutamide | Evaluate Median Radiographic Progression-Free Survival by PCWG2 Criteria | 8.8 months |
Secondary
Evaluate Overall Median Progression-free Survival by PCWG2 Criteria
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
Population: 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 | Measure | Value (MEDIAN) |
|---|---|---|
| DE A+B - 36 mg ZEN003694 + Enzalutamide | Evaluate Overall Median Progression-free Survival by PCWG2 Criteria | 4.7 months |
| DE A+B - 48 mg ZEN003694 + Enzalutamide | Evaluate Overall Median Progression-free Survival by PCWG2 Criteria | 6.2 months |
Secondary
Evaluate Prostate-specific Antigen (PSA) Response Rate by PCWG2 Criteria
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
Population: 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 | Measure | Value (NUMBER) |
|---|---|---|
| DE A+B - 36 mg ZEN003694 + Enzalutamide | Evaluate Prostate-specific Antigen (PSA) Response Rate by PCWG2 Criteria | 4.4 percentage of participants |
| DE A+B - 48 mg ZEN003694 + Enzalutamide | Evaluate Prostate-specific Antigen (PSA) Response Rate by PCWG2 Criteria | 23.3 percentage of participants |
Secondary
Evaluate Radiographic Response Rate (Overall Response Rate) by PCWG2 Criteria
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
Population: 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 | Measure | Value (NUMBER) |
|---|---|---|
| DE A+B - 36 mg ZEN003694 + Enzalutamide | Evaluate Radiographic Response Rate (Overall Response Rate) by PCWG2 Criteria | 2.6 percentage of participants |
| DE A+B - 48 mg ZEN003694 + Enzalutamide | Evaluate Radiographic Response Rate (Overall Response Rate) by PCWG2 Criteria | 3.8 percentage of participants |
Secondary
Measure the Pharmacokinetic (PK) Parameter: AUC(0-24h) of ZEN003694 and ZEN003791 (Active Metabolite) Administered in Combination With Enzalutamide.
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
Population: All Evaluable Participants
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| DE A+B - 36 mg ZEN003694 + Enzalutamide | Measure the Pharmacokinetic (PK) Parameter: AUC(0-24h) of ZEN003694 and ZEN003791 (Active Metabolite) Administered in Combination With Enzalutamide. | ZEN003694 AUC(0-24h) Study Day 1 | 1001 ng*h/mL | Standard Error 494 |
| DE A+B - 36 mg ZEN003694 + Enzalutamide | Measure the Pharmacokinetic (PK) Parameter: AUC(0-24h) of ZEN003694 and ZEN003791 (Active Metabolite) Administered in Combination With Enzalutamide. | ZEN003694 AUC(0-24h) Study Day 15; C24 (24h) inputed with Day 15 C0 (pre-dose) for AUC calculations | 867 ng*h/mL | Standard Error 651 |
| DE A+B - 36 mg ZEN003694 + Enzalutamide | Measure the Pharmacokinetic (PK) Parameter: AUC(0-24h) of ZEN003694 and ZEN003791 (Active Metabolite) Administered in Combination With Enzalutamide. | ZEN003791 AUC(0-24h) Study Day 1 | 1335 ng*h/mL | Standard Error 659 |
| DE A+B - 36 mg ZEN003694 + Enzalutamide | Measure the Pharmacokinetic (PK) Parameter: AUC(0-24h) of ZEN003694 and ZEN003791 (Active Metabolite) Administered in Combination With Enzalutamide. | ZEN003791 AUC(0-24h) Study Day 15; C24 (24h) imputed with Day 15 C0 (pre-dose) for AUC calculations. | 1234 ng*h/mL | Standard Error 606 |
| DE A+B - 48 mg ZEN003694 + Enzalutamide | Measure the Pharmacokinetic (PK) Parameter: AUC(0-24h) of ZEN003694 and ZEN003791 (Active Metabolite) Administered in Combination With Enzalutamide. | ZEN003791 AUC(0-24h) Study Day 15; C24 (24h) imputed with Day 15 C0 (pre-dose) for AUC calculations. | 2216 ng*h/mL | Standard Error 1187 |
| DE A+B - 48 mg ZEN003694 + Enzalutamide | Measure the Pharmacokinetic (PK) Parameter: AUC(0-24h) of ZEN003694 and ZEN003791 (Active Metabolite) Administered in Combination With Enzalutamide. | ZEN003791 AUC(0-24h) Study Day 1 | 1874 ng*h/mL | Standard Error 635 |
| DE A+B - 48 mg ZEN003694 + Enzalutamide | Measure the Pharmacokinetic (PK) Parameter: AUC(0-24h) of ZEN003694 and ZEN003791 (Active Metabolite) Administered in Combination With Enzalutamide. | ZEN003694 AUC(0-24h) Study Day 1 | 985 ng*h/mL | Standard Error 374 |
| DE A+B - 48 mg ZEN003694 + Enzalutamide | Measure the Pharmacokinetic (PK) Parameter: AUC(0-24h) of ZEN003694 and ZEN003791 (Active Metabolite) Administered in Combination With Enzalutamide. | ZEN003694 AUC(0-24h) Study Day 15; C24 (24h) inputed with Day 15 C0 (pre-dose) for AUC calculations | 1046 ng*h/mL | Standard Error 512 |
| DE A+B - 60 mg ZEN003694 + Enzalutamide | Measure the Pharmacokinetic (PK) Parameter: AUC(0-24h) of ZEN003694 and ZEN003791 (Active Metabolite) Administered in Combination With Enzalutamide. | ZEN003791 AUC(0-24h) Study Day 1 | 3344 ng*h/mL | Standard Error 1101 |
| DE A+B - 60 mg ZEN003694 + Enzalutamide | Measure the Pharmacokinetic (PK) Parameter: AUC(0-24h) of ZEN003694 and ZEN003791 (Active Metabolite) Administered in Combination With Enzalutamide. | ZEN003694 AUC(0-24h) Study Day 15; C24 (24h) inputed with Day 15 C0 (pre-dose) for AUC calculations | 1487 ng*h/mL | Standard Error 871 |
| DE A+B - 60 mg ZEN003694 + Enzalutamide | Measure the Pharmacokinetic (PK) Parameter: AUC(0-24h) of ZEN003694 and ZEN003791 (Active Metabolite) Administered in Combination With Enzalutamide. | ZEN003694 AUC(0-24h) Study Day 1 | 2243 ng*h/mL | Standard Error 848 |
| DE A+B - 60 mg ZEN003694 + Enzalutamide | Measure the Pharmacokinetic (PK) Parameter: AUC(0-24h) of ZEN003694 and ZEN003791 (Active Metabolite) Administered in Combination With Enzalutamide. | ZEN003791 AUC(0-24h) Study Day 15; C24 (24h) imputed with Day 15 C0 (pre-dose) for AUC calculations. | 2979 ng*h/mL | Standard Error 1583 |
| DE A+B - 72 mg ZEN003694 + Enzalutamide | Measure the Pharmacokinetic (PK) Parameter: AUC(0-24h) of ZEN003694 and ZEN003791 (Active Metabolite) Administered in Combination With Enzalutamide. | ZEN003694 AUC(0-24h) Study Day 1 | 1966 ng*h/mL | Standard Error 1067 |
| DE A+B - 72 mg ZEN003694 + Enzalutamide | Measure the Pharmacokinetic (PK) Parameter: AUC(0-24h) of ZEN003694 and ZEN003791 (Active Metabolite) Administered in Combination With Enzalutamide. | ZEN003694 AUC(0-24h) Study Day 15; C24 (24h) inputed with Day 15 C0 (pre-dose) for AUC calculations | 1453 ng*h/mL | Standard Error 967 |
| DE A+B - 72 mg ZEN003694 + Enzalutamide | Measure the Pharmacokinetic (PK) Parameter: AUC(0-24h) of ZEN003694 and ZEN003791 (Active Metabolite) Administered in Combination With Enzalutamide. | ZEN003791 AUC(0-24h) Study Day 1 | 3277 ng*h/mL | Standard Error 1708 |
| DE A+B - 72 mg ZEN003694 + Enzalutamide | Measure the Pharmacokinetic (PK) Parameter: AUC(0-24h) of ZEN003694 and ZEN003791 (Active Metabolite) Administered in Combination With Enzalutamide. | ZEN003791 AUC(0-24h) Study Day 15; C24 (24h) imputed with Day 15 C0 (pre-dose) for AUC calculations. | 2586 ng*h/mL | Standard Error 1265 |
| DE A+B - 96 mg ZEN003694 + Enzalutamide | Measure the Pharmacokinetic (PK) Parameter: AUC(0-24h) of ZEN003694 and ZEN003791 (Active Metabolite) Administered in Combination With Enzalutamide. | ZEN003694 AUC(0-24h) Study Day 1 | 2424 ng*h/mL | Standard Error 1450 |
| DE A+B - 96 mg ZEN003694 + Enzalutamide | Measure the Pharmacokinetic (PK) Parameter: AUC(0-24h) of ZEN003694 and ZEN003791 (Active Metabolite) Administered in Combination With Enzalutamide. | ZEN003791 AUC(0-24h) Study Day 15; C24 (24h) imputed with Day 15 C0 (pre-dose) for AUC calculations. | 4478 ng*h/mL | Standard Error 2449 |
| DE A+B - 96 mg ZEN003694 + Enzalutamide | Measure the Pharmacokinetic (PK) Parameter: AUC(0-24h) of ZEN003694 and ZEN003791 (Active Metabolite) Administered in Combination With Enzalutamide. | ZEN003694 AUC(0-24h) Study Day 15; C24 (24h) inputed with Day 15 C0 (pre-dose) for AUC calculations | 2138 ng*h/mL | Standard Error 946 |
| DE A+B - 96 mg ZEN003694 + Enzalutamide | Measure the Pharmacokinetic (PK) Parameter: AUC(0-24h) of ZEN003694 and ZEN003791 (Active Metabolite) Administered in Combination With Enzalutamide. | ZEN003791 AUC(0-24h) Study Day 1 | 4090 ng*h/mL | Standard Error 1562 |
| DE A+B - 120 mg ZEN003694 + Enzalutamide | Measure the Pharmacokinetic (PK) Parameter: AUC(0-24h) of ZEN003694 and ZEN003791 (Active Metabolite) Administered in Combination With Enzalutamide. | ZEN003694 AUC(0-24h) Study Day 15; C24 (24h) inputed with Day 15 C0 (pre-dose) for AUC calculations | 2109 ng*h/mL | Standard Error 578 |
| DE A+B - 120 mg ZEN003694 + Enzalutamide | Measure the Pharmacokinetic (PK) Parameter: AUC(0-24h) of ZEN003694 and ZEN003791 (Active Metabolite) Administered in Combination With Enzalutamide. | ZEN003694 AUC(0-24h) Study Day 1 | 2153 ng*h/mL | Standard Error 1529 |
| DE A+B - 120 mg ZEN003694 + Enzalutamide | Measure the Pharmacokinetic (PK) Parameter: AUC(0-24h) of ZEN003694 and ZEN003791 (Active Metabolite) Administered in Combination With Enzalutamide. | ZEN003791 AUC(0-24h) Study Day 1 | 3712 ng*h/mL | Standard Error 2660 |
| DE A+B - 120 mg ZEN003694 + Enzalutamide | Measure the Pharmacokinetic (PK) Parameter: AUC(0-24h) of ZEN003694 and ZEN003791 (Active Metabolite) Administered in Combination With Enzalutamide. | ZEN003791 AUC(0-24h) Study Day 15; C24 (24h) imputed with Day 15 C0 (pre-dose) for AUC calculations. | 5275 ng*h/mL | Standard Error 2369 |
| DE A+B - 144 mg ZEN003694 + Enzalutamide | Measure the Pharmacokinetic (PK) Parameter: AUC(0-24h) of ZEN003694 and ZEN003791 (Active Metabolite) Administered in Combination With Enzalutamide. | ZEN003791 AUC(0-24h) Study Day 1 | 3815 ng*h/mL | Standard Error 2774 |
| DE A+B - 144 mg ZEN003694 + Enzalutamide | Measure the Pharmacokinetic (PK) Parameter: AUC(0-24h) of ZEN003694 and ZEN003791 (Active Metabolite) Administered in Combination With Enzalutamide. | ZEN003694 AUC(0-24h) Study Day 1 | 2119 ng*h/mL | Standard Error 1547 |
| DE A+B - 144 mg ZEN003694 + Enzalutamide | Measure the Pharmacokinetic (PK) Parameter: AUC(0-24h) of ZEN003694 and ZEN003791 (Active Metabolite) Administered in Combination With Enzalutamide. | ZEN003694 AUC(0-24h) Study Day 15; C24 (24h) inputed with Day 15 C0 (pre-dose) for AUC calculations | 1641 ng*h/mL | Standard Error 704 |
| DE A+B - 144 mg ZEN003694 + Enzalutamide | Measure the Pharmacokinetic (PK) Parameter: AUC(0-24h) of ZEN003694 and ZEN003791 (Active Metabolite) Administered in Combination With Enzalutamide. | ZEN003791 AUC(0-24h) Study Day 15; C24 (24h) imputed with Day 15 C0 (pre-dose) for AUC calculations. | 3155 ng*h/mL | Standard Error 1858 |
Secondary
Measure the Pharmacokinetic (PK) Parameter: Cmax of ZEN003694 and ZEN003791 (Active Metabolite) Administered in Combination With Enzalutamide
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
Population: All Evaluable Participants
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| DE A+B - 36 mg ZEN003694 + Enzalutamide | Measure the Pharmacokinetic (PK) Parameter: Cmax of ZEN003694 and ZEN003791 (Active Metabolite) Administered in Combination With Enzalutamide | ZEN003694 Cmax Study Day 1 | 181 ng/mL | Standard Error 83 |
| DE A+B - 36 mg ZEN003694 + Enzalutamide | Measure the Pharmacokinetic (PK) Parameter: Cmax of ZEN003694 and ZEN003791 (Active Metabolite) Administered in Combination With Enzalutamide | ZEN003694 Cmax Study Day 15 | 184 ng/mL | Standard Error 128 |
| DE A+B - 36 mg ZEN003694 + Enzalutamide | Measure the Pharmacokinetic (PK) Parameter: Cmax of ZEN003694 and ZEN003791 (Active Metabolite) Administered in Combination With Enzalutamide | ZEN003791 Cmax Study Day 1 | 125 ng/mL | Standard Error 83 |
| DE A+B - 36 mg ZEN003694 + Enzalutamide | Measure the Pharmacokinetic (PK) Parameter: Cmax of ZEN003694 and ZEN003791 (Active Metabolite) Administered in Combination With Enzalutamide | ZEN003791 Cmax Study Day 15 | 129 ng/mL | Standard Error 72 |
| DE A+B - 48 mg ZEN003694 + Enzalutamide | Measure the Pharmacokinetic (PK) Parameter: Cmax of ZEN003694 and ZEN003791 (Active Metabolite) Administered in Combination With Enzalutamide | ZEN003791 Cmax Study Day 15 | 220 ng/mL | Standard Error 101 |
| DE A+B - 48 mg ZEN003694 + Enzalutamide | Measure the Pharmacokinetic (PK) Parameter: Cmax of ZEN003694 and ZEN003791 (Active Metabolite) Administered in Combination With Enzalutamide | ZEN003791 Cmax Study Day 1 | 184 ng/mL | Standard Error 62 |
| DE A+B - 48 mg ZEN003694 + Enzalutamide | Measure the Pharmacokinetic (PK) Parameter: Cmax of ZEN003694 and ZEN003791 (Active Metabolite) Administered in Combination With Enzalutamide | ZEN003694 Cmax Study Day 1 | 216 ng/mL | Standard Error 103 |
| DE A+B - 48 mg ZEN003694 + Enzalutamide | Measure the Pharmacokinetic (PK) Parameter: Cmax of ZEN003694 and ZEN003791 (Active Metabolite) Administered in Combination With Enzalutamide | ZEN003694 Cmax Study Day 15 | 236 ng/mL | Standard Error 119 |
| DE A+B - 60 mg ZEN003694 + Enzalutamide | Measure the Pharmacokinetic (PK) Parameter: Cmax of ZEN003694 and ZEN003791 (Active Metabolite) Administered in Combination With Enzalutamide | ZEN003791 Cmax Study Day 1 | 244 ng/mL | Standard Error 79 |
| DE A+B - 60 mg ZEN003694 + Enzalutamide | Measure the Pharmacokinetic (PK) Parameter: Cmax of ZEN003694 and ZEN003791 (Active Metabolite) Administered in Combination With Enzalutamide | ZEN003694 Cmax Study Day 15 | 289 ng/mL | Standard Error 204 |
| DE A+B - 60 mg ZEN003694 + Enzalutamide | Measure the Pharmacokinetic (PK) Parameter: Cmax of ZEN003694 and ZEN003791 (Active Metabolite) Administered in Combination With Enzalutamide | ZEN003694 Cmax Study Day 1 | 290 ng/mL | Standard Error 102 |
| DE A+B - 60 mg ZEN003694 + Enzalutamide | Measure the Pharmacokinetic (PK) Parameter: Cmax of ZEN003694 and ZEN003791 (Active Metabolite) Administered in Combination With Enzalutamide | ZEN003791 Cmax Study Day 15 | 259 ng/mL | Standard Error 176 |
| DE A+B - 72 mg ZEN003694 + Enzalutamide | Measure the Pharmacokinetic (PK) Parameter: Cmax of ZEN003694 and ZEN003791 (Active Metabolite) Administered in Combination With Enzalutamide | ZEN003694 Cmax Study Day 1 | 452 ng/mL | Standard Error 279 |
| DE A+B - 72 mg ZEN003694 + Enzalutamide | Measure the Pharmacokinetic (PK) Parameter: Cmax of ZEN003694 and ZEN003791 (Active Metabolite) Administered in Combination With Enzalutamide | ZEN003694 Cmax Study Day 15 | 392 ng/mL | Standard Error 278 |
| DE A+B - 72 mg ZEN003694 + Enzalutamide | Measure the Pharmacokinetic (PK) Parameter: Cmax of ZEN003694 and ZEN003791 (Active Metabolite) Administered in Combination With Enzalutamide | ZEN003791 Cmax Study Day 1 | 306 ng/mL | Standard Error 196 |
| DE A+B - 72 mg ZEN003694 + Enzalutamide | Measure the Pharmacokinetic (PK) Parameter: Cmax of ZEN003694 and ZEN003791 (Active Metabolite) Administered in Combination With Enzalutamide | ZEN003791 Cmax Study Day 15 | 319 ng/mL | Standard Error 208 |
| DE A+B - 96 mg ZEN003694 + Enzalutamide | Measure the Pharmacokinetic (PK) Parameter: Cmax of ZEN003694 and ZEN003791 (Active Metabolite) Administered in Combination With Enzalutamide | ZEN003694 Cmax Study Day 1 | 492 ng/mL | Standard Error 277 |
| DE A+B - 96 mg ZEN003694 + Enzalutamide | Measure the Pharmacokinetic (PK) Parameter: Cmax of ZEN003694 and ZEN003791 (Active Metabolite) Administered in Combination With Enzalutamide | ZEN003791 Cmax Study Day 15 | 477 ng/mL | Standard Error 194 |
| DE A+B - 96 mg ZEN003694 + Enzalutamide | Measure the Pharmacokinetic (PK) Parameter: Cmax of ZEN003694 and ZEN003791 (Active Metabolite) Administered in Combination With Enzalutamide | ZEN003694 Cmax Study Day 15 | 484 ng/mL | Standard Error 189 |
| DE A+B - 96 mg ZEN003694 + Enzalutamide | Measure the Pharmacokinetic (PK) Parameter: Cmax of ZEN003694 and ZEN003791 (Active Metabolite) Administered in Combination With Enzalutamide | ZEN003791 Cmax Study Day 1 | 374 ng/mL | Standard Error 143 |
| DE A+B - 120 mg ZEN003694 + Enzalutamide | Measure the Pharmacokinetic (PK) Parameter: Cmax of ZEN003694 and ZEN003791 (Active Metabolite) Administered in Combination With Enzalutamide | ZEN003694 Cmax Study Day 15 | 458 ng/mL | Standard Error 305 |
| DE A+B - 120 mg ZEN003694 + Enzalutamide | Measure the Pharmacokinetic (PK) Parameter: Cmax of ZEN003694 and ZEN003791 (Active Metabolite) Administered in Combination With Enzalutamide | ZEN003694 Cmax Study Day 1 | 425 ng/mL | Standard Error 306 |
| DE A+B - 120 mg ZEN003694 + Enzalutamide | Measure the Pharmacokinetic (PK) Parameter: Cmax of ZEN003694 and ZEN003791 (Active Metabolite) Administered in Combination With Enzalutamide | ZEN003791 Cmax Study Day 1 | 342 ng/mL | Standard Error 202 |
| DE A+B - 120 mg ZEN003694 + Enzalutamide | Measure the Pharmacokinetic (PK) Parameter: Cmax of ZEN003694 and ZEN003791 (Active Metabolite) Administered in Combination With Enzalutamide | ZEN003791 Cmax Study Day 15 | 552 ng/mL | Standard Error 332 |
| DE A+B - 144 mg ZEN003694 + Enzalutamide | Measure the Pharmacokinetic (PK) Parameter: Cmax of ZEN003694 and ZEN003791 (Active Metabolite) Administered in Combination With Enzalutamide | ZEN003791 Cmax Study Day 1 | 417 ng/mL | Standard Error 362 |
| DE A+B - 144 mg ZEN003694 + Enzalutamide | Measure the Pharmacokinetic (PK) Parameter: Cmax of ZEN003694 and ZEN003791 (Active Metabolite) Administered in Combination With Enzalutamide | ZEN003694 Cmax Study Day 1 | 494 ng/mL | Standard Error 424 |
| DE A+B - 144 mg ZEN003694 + Enzalutamide | Measure the Pharmacokinetic (PK) Parameter: Cmax of ZEN003694 and ZEN003791 (Active Metabolite) Administered in Combination With Enzalutamide | ZEN003694 Cmax Study Day 15 | 457 ng/mL | Standard Error 330 |
| DE A+B - 144 mg ZEN003694 + Enzalutamide | Measure the Pharmacokinetic (PK) Parameter: Cmax of ZEN003694 and ZEN003791 (Active Metabolite) Administered in Combination With Enzalutamide | ZEN003791 Cmax Study Day 15 | 432 ng/mL | Standard Error 362 |