Prostate Cancer
Conditions
Brief summary
The purpose of this study is to evaluate the serum testosterone levels in patients with Metastatic Castration-Resistant Prostate Cancer on SoluMatrix™ Abiraterone Acetate as Compared to Abiraterone Acetate
Detailed description
This was a 12-week, open-label study of abiraterone acetate in at least 50 patients with metastatic castration-resistant prostate cancer.
Interventions
Zytiga® 1,000 mg (4 x 250 mg qd) tablets plus one 5 mg prednisone tablet to be taken bid, spaced approximately 12 hours apart
DRUGSoluMatrix™ (Abiraterone Acetate)
SoluMatrix™ 500 mg (4 x 125 mg qd) tablets plus one 4 mg methylprednisolone tablet bid, spaced approximately 12 hours apart
Sponsors
Sun Pharmaceutical Industries Limited
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
MALE
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Written informed consent obtained prior to any study-related procedure being performed 2. Male subjects at least 18 years of age or older at time of consent 3. Pathologically confirmed adenocarcinoma of the prostate 4. Ongoing therapy with a GnRH agonist or antagonist AND serum testosterone level \<50 ng/dL at screening 5. Metastatic disease documented by computed tomography (CT)/ magnetic resonance imaging (MRI) or bone scan. Imaging obtained within 42 days prior to the start of study medication will be accepted. 6. Meeting disease progression according to the recommendations of the prostate cancer working group 2 by one of the following criteria: * Two rises of PSA (taken a minimum of 1 week apart) from a baseline measurement of at least 2 ng/mL, * Imaging progression (CT/MRI) by RECIST criteria * Nuclear scan progression by new lesion. 7. Discontinuation of flutamide or nilutamide, and other anti-androgens at least 4 weeks prior to the start of study medication; discontinuation of bicalutamide at least 6 weeks prior to start of study medication. 8. Discontinuation of Radiotherapy \> 4 weeks prior to start of study medication. 9. ECOG performance status of 0-1 at screening 10. Screening blood counts of the following: * Absolute neutrophil count \> 1500/µL * Platelets \> 100,000/µL * Hemoglobin \> 9 g/dL 11. Screening chemistry values of the following: * ALT and AST \< 2.5 x ULN * Total bilirubin \< 1.5 x ULN * Creatinine\< 1.5 x ULN * Albumin \> 3.0 g/dL 12. Potassium \> 3.5 mmol/L 13. Life expectancy of at least 6 months at screening 14. Subject is willing and able to comply with all protocol requirements assessments 15. Agrees to protocol-defined use of effective contraception.
Exclusion criteria
1. History of impaired pituitary or adrenal gland function 2. Prior therapy with abiraterone acetate, orteronel, ketoconazole or any other CYP17 inhibitor 3. Prior therapy with enzalutamide 4. Prior use of experimental androgen receptor antagonist 5. Previous exposure to Ra-223:Xofigo 6. Previous chemotherapy 7. Initiation of bisphosphonate or denosumab therapy within 30 days prior to the start of study medication. Patients who are on a stable dose of these medications for at least 30 days at the time of starting study drug are eligible. 8. Therapy with estrogen within 30 days prior to the start of study medication 9. Use of systemic glucocorticoids equivalent to \> 10 mg of prednisone daily; patients who have discontinued or have reduced dose to \< 10 mg prednisone within 14 days prior to the start of study medication will be eligible 10. Prior use of any herbal products that may decrease PSA levels (eg., saw palmetto) within 30 days of start of study medication 11. Known metastases to the brain or CNS involvement 12. History of other malignancy within the previous 2 years 13. Major surgery within 30 days prior to the start of study medication 14. Blood transfusion within 30 days of screening 15. Serious, persistent infection within 14 days of the start of study medication 16. Persistent pain that requires the use of a narcotic analgesic 17. Known gastrointestinal disease or condition that may impair absorption 18. Treatment with any investigational drug within 4 weeks prior to Day -1 of the study. 19. Known history of human immunodeficiency virus (HIV) or seropositive test for hepatitis C virus or hepatitis B virus 20. Have poorly controlled diabetes. 21. Uncontrolled hypertension 22. History of New York Heart Association (NYHA) class III or IV heart failure 23. Serious concurrent illness, including psychiatric illness, that would interfere with study participation 24. Inability to swallow tablets whole 25. Known hypersensitivity to any excipients in study medications 26. Moderate to severe hepatic impairment (Child-Pugh Classes B and C)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Testosterone Levels | Average of Day 9 and 10 | Blood Sample tested for Serum Testosterone Levels |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percent of Subjects With PSA-50 Response | Day 28, Day 56, and Day 84 | Proportion of patients with complete suppression of PSA-50 were reported by treatment and compared for between-group differences. These were assessed only at the said Outcome Measure Time Frame. No additional time points to the said endpoint. |
| Serum Testosterone Levels | Day 28, Day 56, and Day 84 | These were assessed only at the said Outcome Measure Time Frame. No additional time points to the said endpoint. |
| Steady State Trough Concentration of Arbiraterone | Day 09, Day 28, Day 56, and Day 84 | These were assessed only at the said Outcome Measure Time Frame. No additional time points to the said endpoint. |
| PSA Levels | Day 28, Day 56, and Day 84 | All patients randomized to one of the two treatment groups, round about level of PSA. These were assessed only at the said Outcome Measure Time Frame. No additional time points to the said endpoint |
| AUC (0-24 hr) | 60 to 30 minutes prior to dosing and over 24 Hours post-dose | Blood samples for pre-dose PK profiling were to be collected approximately 45 minutes before dosing, i.e., within 60 to 30 minutes prior to dosing. Post-dose blood samples were to be collected throughout the day at the times (15 mins, 30 mins, 1 hr, 1.5 hr, 2.0 hr 3 hr, 4 hr, 6 hr, 8 hr, 9 hr, 24 hr). |
| AUC (0-t) | 60 to 30 minutes prior to dosing and over 24 Hours post-dose | Blood samples for pre-dose PK profiling were to be collected approximately 45 minutes before dosing, i.e., within 60 to 30 minutes prior to dosing. Post-dose blood samples were to be collected throughout the day at the times (15 mins, 30 mins, 1 hr, 1.5 hr, 2.0 hr 3 hr, 4 hr, 6 hr, 8 hr, 9 hr, 24 hr). |
| Cmax | 60 to 30 minutes prior to dosing and over 24 Hours post-dose | Blood samples for pre-dose PK profiling were to be collected approximately 45 minutes before dosing, i.e., within 60 to 30 minutes prior to dosing. Post-dose blood samples were to be collected throughout the day at the times (15 mins, 30 mins, 1 hr, 1.5 hr, 2.0 hr 3 hr, 4 hr, 6 hr, 8 hr, 9 hr, 24 hr). |
| AUC (0-inf) | 60 to 30 minutes prior to dosing and over 24 Hours post-dose | Steady state systemic exposure parameters |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Zytiga® (Abiraterone Acetate) Zytiga® 1,000 mg (4 x 250 mg qd) tablets | 29 |
| SoluMatrix™ (Abiraterone Acetate) SoluMatrix™ 500 mg (4 x 125 mg qd) tablets | 24 |
| Total | 53 |
Baseline characteristics
| Characteristic | SoluMatrix™ (Abiraterone Acetate) | Total | Zytiga® (Abiraterone Acetate) |
|---|---|---|---|
| Age, Continuous | 77 years STANDARD_DEVIATION 8.9 | 75.1 years STANDARD_DEVIATION 9.3 | 73.5 years STANDARD_DEVIATION 9.4 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 4 Participants | 6 Participants | 2 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 20 Participants | 47 Participants | 27 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 3 Participants | 11 Participants | 8 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) White | 20 Participants | 40 Participants | 20 Participants |
| Region of Enrollment United States | 24 participants | 53 participants | 29 participants |
| Sex: Female, Male Female | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Male | 24 Participants | 53 Participants | 29 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 2 / 29 | 0 / 24 |
| other Total, other adverse events | 22 / 29 | 16 / 24 |
| serious Total, serious adverse events | 2 / 29 | 5 / 24 |
Outcome results
Primary
Testosterone Levels
Blood Sample tested for Serum Testosterone Levels
Time frame: Average of Day 9 and 10
Population: Analysis of serum T levels in the ITT population
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Zytiga® (Abiraterone Acetate) | Testosterone Levels | 1.02 ng/dL | Standard Error 0.03 |
| SoluMatrix™ (Abiraterone Acetate) | Testosterone Levels | 1.05 ng/dL | Standard Error 0.04 |
p-value: 0.487990% CI: [0.964, 1.077]ANOVA
Secondary
AUC (0-24 hr)
Blood samples for pre-dose PK profiling were to be collected approximately 45 minutes before dosing, i.e., within 60 to 30 minutes prior to dosing. Post-dose blood samples were to be collected throughout the day at the times (15 mins, 30 mins, 1 hr, 1.5 hr, 2.0 hr 3 hr, 4 hr, 6 hr, 8 hr, 9 hr, 24 hr).
Time frame: 60 to 30 minutes prior to dosing and over 24 Hours post-dose
Population: Overall, 14 subjects were analyzed in the PK population, amongst which, 8 were in the Zytiga group and 5 were in the SoluMatrix group.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Zytiga® (Abiraterone Acetate) | AUC (0-24 hr) | 870.859 ng*hr/mL | Standard Error 221.709 |
| SoluMatrix™ (Abiraterone Acetate) | AUC (0-24 hr) | 626.066 ng*hr/mL | Standard Error 280.443 |
Secondary
AUC (0-inf)
Steady state systemic exposure parameters
Time frame: 60 to 30 minutes prior to dosing and over 24 Hours post-dose
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Zytiga® (Abiraterone Acetate) | AUC (0-inf) | 1020.218 ng*hr/mL | Standard Error 154.549 |
| SoluMatrix™ (Abiraterone Acetate) | AUC (0-inf) | 326.458 ng*hr/mL | Standard Error 218.565 |
Secondary
AUC (0-t)
Blood samples for pre-dose PK profiling were to be collected approximately 45 minutes before dosing, i.e., within 60 to 30 minutes prior to dosing. Post-dose blood samples were to be collected throughout the day at the times (15 mins, 30 mins, 1 hr, 1.5 hr, 2.0 hr 3 hr, 4 hr, 6 hr, 8 hr, 9 hr, 24 hr).
Time frame: 60 to 30 minutes prior to dosing and over 24 Hours post-dose
Population: Overall, 14 subjects were analyzed in the PK population, amongst which, 8 were in the Zytiga group and 5 were in the SoluMatrix group.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Zytiga® (Abiraterone Acetate) | AUC (0-t) | 870.859 ng*hr/mL | Standard Error 221.709 |
| SoluMatrix™ (Abiraterone Acetate) | AUC (0-t) | 626.066 ng*hr/mL | Standard Error 280.443 |
Secondary
Cmax
Blood samples for pre-dose PK profiling were to be collected approximately 45 minutes before dosing, i.e., within 60 to 30 minutes prior to dosing. Post-dose blood samples were to be collected throughout the day at the times (15 mins, 30 mins, 1 hr, 1.5 hr, 2.0 hr 3 hr, 4 hr, 6 hr, 8 hr, 9 hr, 24 hr).
Time frame: 60 to 30 minutes prior to dosing and over 24 Hours post-dose
Population: Overall, 14 subjects were analyzed in the PK population, amongst which, 8 were in the Zytiga group and 5 were in the SoluMatrix group.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Zytiga® (Abiraterone Acetate) | Cmax | 268.261 ng/mL | Standard Error 69.967 |
| SoluMatrix™ (Abiraterone Acetate) | Cmax | 111.316 ng/mL | Standard Error 88.503 |
p-value: 0.1917ANOVA
Secondary
Percent of Subjects With PSA-50 Response
Proportion of patients with complete suppression of PSA-50 were reported by treatment and compared for between-group differences. These were assessed only at the said Outcome Measure Time Frame. No additional time points to the said endpoint.
Time frame: Day 28, Day 56, and Day 84
Population: ITT population:The intention-to-treat (ITT) population is defined as all subjects who are randomized to one of the two treatment groups. The ITT population is the primary population for PD evaluation. The ITT population will be identified and finalized before the database is locked.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Zytiga® (Abiraterone Acetate) | Percent of Subjects With PSA-50 Response | Day 28 | 70.4 percentage of Participants |
| Zytiga® (Abiraterone Acetate) | Percent of Subjects With PSA-50 Response | Day 56 | 65.4 percentage of Participants |
| Zytiga® (Abiraterone Acetate) | Percent of Subjects With PSA-50 Response | Day 84 | 72.0 percentage of Participants |
| SoluMatrix™ (Abiraterone Acetate) | Percent of Subjects With PSA-50 Response | Day 28 | 66.7 percentage of Participants |
| SoluMatrix™ (Abiraterone Acetate) | Percent of Subjects With PSA-50 Response | Day 56 | 63.6 percentage of Participants |
| SoluMatrix™ (Abiraterone Acetate) | Percent of Subjects With PSA-50 Response | Day 84 | 68.4 percentage of Participants |
p-value: 1Fisher Exact
Secondary
PSA Levels
All patients randomized to one of the two treatment groups, round about level of PSA. These were assessed only at the said Outcome Measure Time Frame. No additional time points to the said endpoint
Time frame: Day 28, Day 56, and Day 84
Population: ITT population:The intention-to-treat (ITT) population is defined as all subjects who are randomized to one of the two treatment groups. The ITT population is the primary population for PD evaluation. The ITT population will be identified and finalized before the database is locked.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Zytiga® (Abiraterone Acetate) | PSA Levels | Day 28 | 37.5 ng/mL | Standard Error 11.33 |
| Zytiga® (Abiraterone Acetate) | PSA Levels | Day 56 | 40.84 ng/mL | Standard Error 12.58 |
| Zytiga® (Abiraterone Acetate) | PSA Levels | Day 84 | 33.88 ng/mL | Standard Error 13.43 |
| SoluMatrix™ (Abiraterone Acetate) | PSA Levels | Day 28 | 22.37 ng/mL | Standard Error 12.02 |
| SoluMatrix™ (Abiraterone Acetate) | PSA Levels | Day 56 | 25.29 ng/mL | Standard Error 13.68 |
| SoluMatrix™ (Abiraterone Acetate) | PSA Levels | Day 84 | 26.46 ng/mL | Standard Error 15.41 |
p-value: 0.364290% CI: [0.0451, 2.192]ANOVA
p-value: 0.406990% CI: [0.338, 1.939]ANOVA
p-value: 0.718690% CI: [0.412, 2.617]ANOVA
Secondary
Serum Testosterone Levels
These were assessed only at the said Outcome Measure Time Frame. No additional time points to the said endpoint.
Time frame: Day 28, Day 56, and Day 84
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Zytiga® (Abiraterone Acetate) | Serum Testosterone Levels | Day 28 | 1.01 ng/dL | Standard Error 0.01 |
| Zytiga® (Abiraterone Acetate) | Serum Testosterone Levels | Day 56 | 1.01 ng/dL | Standard Error 1.03 |
| Zytiga® (Abiraterone Acetate) | Serum Testosterone Levels | Day 84 | 1 ng/dL | Standard Error 0 |
| SoluMatrix™ (Abiraterone Acetate) | Serum Testosterone Levels | Day 28 | 1.01 ng/dL | Standard Error 0.01 |
| SoluMatrix™ (Abiraterone Acetate) | Serum Testosterone Levels | Day 56 | 2.56 ng/dL | Standard Error 1.07 |
| SoluMatrix™ (Abiraterone Acetate) | Serum Testosterone Levels | Day 84 | 1 ng/dL | Standard Error 0 |
p-value: 0.921190% CI: [0.98, 1.018]ANOVA
p-value: 0.303790% CI: [0.9, 1.515]ANOVA
90% CI: [1, 1]ANOVA
Secondary
Steady State Trough Concentration of Arbiraterone
These were assessed only at the said Outcome Measure Time Frame. No additional time points to the said endpoint.
Time frame: Day 09, Day 28, Day 56, and Day 84
Population: Safety Population
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Zytiga® (Abiraterone Acetate) | Steady State Trough Concentration of Arbiraterone | Day 09 | 20.938 ng/dL | Standard Error 7.044 |
| Zytiga® (Abiraterone Acetate) | Steady State Trough Concentration of Arbiraterone | Day 28 | 56.721 ng/dL | Standard Error 23.104 |
| Zytiga® (Abiraterone Acetate) | Steady State Trough Concentration of Arbiraterone | Day 56 | 29.978 ng/dL | Standard Error 8.117 |
| Zytiga® (Abiraterone Acetate) | Steady State Trough Concentration of Arbiraterone | Day 84 | 18.263 ng/dL | Standard Error 3.087 |
| SoluMatrix™ (Abiraterone Acetate) | Steady State Trough Concentration of Arbiraterone | Day 84 | 13.819 ng/dL | Standard Error 3.381 |
| SoluMatrix™ (Abiraterone Acetate) | Steady State Trough Concentration of Arbiraterone | Day 09 | 27.259 ng/dL | Standard Error 7.772 |
| SoluMatrix™ (Abiraterone Acetate) | Steady State Trough Concentration of Arbiraterone | Day 56 | 18.707 ng/dL | Standard Error 9.175 |
| SoluMatrix™ (Abiraterone Acetate) | Steady State Trough Concentration of Arbiraterone | Day 28 | 18.662 ng/dL | Standard Error 24.18 |
p-value: 0.5495ANOVA
p-value: 0.2616ANOVA
p-value: 0.3632ANOVA
p-value: 0.3393ANOVA