Prostate Cancer
Conditions
Keywords
prostate cancer, leuprolide
Brief summary
The purpose of this study is to assess the pharmacokinetics, pharmacodynamics, efficacy and safety of CAM2032 versus Eligard, in patients with prostate cancer. All patients will receive leuprolide acetate administered subcutaneously once monthly during 3 months.
Interventions
DRUGleuprolide acetate FluidCrystal® injection depot
DRUGleuprolide acetate
Sponsors
Camurus AB
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
MALE
Age
40 Years to 85 Years
Healthy volunteers
No
Inclusion criteria
* Men ≥40 and ≤85 years of age * Histological or cytological proven adenocarcinoma of the prostate requiring hormone therapy * Life expectancy over 12 months * World Health Organisation/ The Eastern Cooperative Oncology Group (WHO/ECOG) performance status of 0, 1 or 2 * Adequate and stable renal function * Adequate and stable hepatic function
Exclusion criteria
* Evidence of brain metastasis, spinal cord compression, or urinary tract obstruction * Serum Testosterone levels below 150 ng/dL at Screening visit * Medical or radiological prostate cancer treatments within 2 months prior to the Screening visit * Surgical treatment of prostate cancer within 2 weeks prior to the Screening visit * Prior orchiectomy, hypophysectomy, or adrenalectomy * Prior use of LHRH agonists within 12 months prior to the Screening visit and during the study
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Observed Maximum Serum Leuprolide Concentration (Cmax) for Dose 1 and Dose 3 | 84 days | Blood samples for analysis of serum leuprolide concentrations were collected at pre-determined time points throughout the trial (with full PK profiles after Dose 1 and Dose 3). The PK parameter, Cmax was derived for Doses 1 and 3 of the investigational medicinal product (IMP). |
| Apparent Terminal Half-life (t½) for Dose 1 and Dose 3 | Days 0-28 and Days 56-84 | Blood samples for analysis of serum leuprolide concentrations were collected at pre-determined time points throughout the trial (with full PK profiles after Dose 1 and Dose 3). The PK parameter, t1/2 was derived for Doses 1 and 3 of the IMP. |
| Area Under the Serum Concentration-time Curve (AUC) Over the Dosing Interval (AUCtau) for Dose 1 and Dose 3 | Days 0-28 and Days 56-84 (0-672 hours after Doses 1 and 3) | Blood samples for analysis of serum leuprolide concentrations were collected at pre-determined time points throughout the trial (with full PK profiles after Dose 1 and Dose 3). The PK parameter, AUCtau was derived for Doses 1 and 3 of the IMP. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Time (Days) to Testosterone Recovery After Dose 3 | Days 56-126 | The pharmacodynamic (PD) effects of leuprolide were assessed by measuring serum testosterone during the trial. Time to testosterone recovery after last dose of the IMP. Blood samples for analyses of serum testosterone concentrations were collected at Screening and on Days 0 to 126. |
| Profiles of Testesterone Concentration (ng/dL) Following Injections of the Investigational Medicinal Product (IMP) | Days 0-126 | The PD effects of leuprolide were assessed by measuring serum testosterone concentrations during the trial. The following PD variable was analyzed: The profiles of testosterone concentration (ng/dL) following injections of the IMP. Blood samples for analyses of serum testosterone concentrations were collected at Screening and on Days 0 to 126. |
| Mean Prostate Specific Antigen (PSA) Concentration | Days 0-126 | The PD effects of leuprolide were assessed by measuring serum PSA concentrations during the trial. The following PD variable was analyzed: PSA (ng/mL) response to IMP. Blood samples for analyses of plasma PSA concentrations were collected at Screening and on Days 0 to 126. |
Countries
Finland, Hungary
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| CAM2032 3.75 mg Single subcutaneous buttock injections of CAM2032 (leuprolide acetate FluidCrystal® injection depot) 3.75 mg on Days 0, 28 and 56. | 19 |
| CAM2032 7.5 mg Single subcutaneous buttock injections of CAM2032 (leuprolide acetate FluidCrystal® injection depot) 7.5 mg on Days 0, 28 and 56. | 15 |
| Eligard 7.5 mg Single subcutaneous buttock injections of Eligard® 7.5 mg on Days 0, 28 and 56. | 17 |
| Total | 51 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Need for radiotherapy | 1 | 0 | 0 |
Baseline characteristics
| Characteristic | CAM2032 3.75 mg | CAM2032 7.5 mg | Eligard 7.5 mg | Total |
|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 13 Participants | 14 Participants | 15 Participants | 42 Participants |
| Age, Categorical Between 18 and 65 years | 6 Participants | 1 Participants | 2 Participants | 9 Participants |
| Age, Continuous | 69.7 years STANDARD_DEVIATION 9.5 | 71.9 years STANDARD_DEVIATION 6.3 | 70.9 years STANDARD_DEVIATION 7 | 70.8 years STANDARD_DEVIATION 7.8 |
| Region of Enrollment Finland | 13 participants | 10 participants | 8 participants | 31 participants |
| Region of Enrollment Hungary | 6 participants | 5 participants | 9 participants | 20 participants |
| Sex: Female, Male Female | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Male | 19 Participants | 15 Participants | 17 Participants | 51 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 14 / 19 | 12 / 15 | 10 / 17 |
| serious Total, serious adverse events | 0 / 19 | 1 / 15 | 0 / 17 |
Outcome results
Primary
Apparent Terminal Half-life (t½) for Dose 1 and Dose 3
Blood samples for analysis of serum leuprolide concentrations were collected at pre-determined time points throughout the trial (with full PK profiles after Dose 1 and Dose 3). The PK parameter, t1/2 was derived for Doses 1 and 3 of the IMP.
Time frame: Days 0-28 and Days 56-84
Population: The Per-Protocol Set (PPS) consisted of all randomized participants in the safety population who had a complete PK profile. In the CAM2032 3.75 mg group 15 of the 19 randomized participants were included in the PPS.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| CAM2032 3.75 mg | Apparent Terminal Half-life (t½) for Dose 1 and Dose 3 | Dose 1 | 205 hour | Standard Deviation 113 |
| CAM2032 3.75 mg | Apparent Terminal Half-life (t½) for Dose 1 and Dose 3 | Dose 3 | 299 hour | Standard Deviation 277 |
| CAM2032 7.5 mg | Apparent Terminal Half-life (t½) for Dose 1 and Dose 3 | Dose 1 | 231 hour | Standard Deviation 142 |
| CAM2032 7.5 mg | Apparent Terminal Half-life (t½) for Dose 1 and Dose 3 | Dose 3 | 434 hour | Standard Deviation 867 |
| Eligard 7.5 mg | Apparent Terminal Half-life (t½) for Dose 1 and Dose 3 | Dose 1 | 743 hour | Standard Deviation 1677 |
| Eligard 7.5 mg | Apparent Terminal Half-life (t½) for Dose 1 and Dose 3 | Dose 3 | 378 hour | Standard Deviation 570 |
Primary
Area Under the Serum Concentration-time Curve (AUC) Over the Dosing Interval (AUCtau) for Dose 1 and Dose 3
Blood samples for analysis of serum leuprolide concentrations were collected at pre-determined time points throughout the trial (with full PK profiles after Dose 1 and Dose 3). The PK parameter, AUCtau was derived for Doses 1 and 3 of the IMP.
Time frame: Days 0-28 and Days 56-84 (0-672 hours after Doses 1 and 3)
Population: The Per-Protocol Set (PPS) consisted of all randomized participants in the safety population who had a complete PK profile. In the CAM2032 3.75 mg group 15 of the 19 randomized participants were included in the PPS.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| CAM2032 3.75 mg | Area Under the Serum Concentration-time Curve (AUC) Over the Dosing Interval (AUCtau) for Dose 1 and Dose 3 | Dose 1 | 329 h*ng/mL | Geometric Coefficient of Variation 37.6 |
| CAM2032 3.75 mg | Area Under the Serum Concentration-time Curve (AUC) Over the Dosing Interval (AUCtau) for Dose 1 and Dose 3 | Dose 3 | 343 h*ng/mL | Geometric Coefficient of Variation 24.7 |
| CAM2032 7.5 mg | Area Under the Serum Concentration-time Curve (AUC) Over the Dosing Interval (AUCtau) for Dose 1 and Dose 3 | Dose 1 | 622 h*ng/mL | Geometric Coefficient of Variation 45.2 |
| CAM2032 7.5 mg | Area Under the Serum Concentration-time Curve (AUC) Over the Dosing Interval (AUCtau) for Dose 1 and Dose 3 | Dose 3 | 757 h*ng/mL | Geometric Coefficient of Variation 53.4 |
| Eligard 7.5 mg | Area Under the Serum Concentration-time Curve (AUC) Over the Dosing Interval (AUCtau) for Dose 1 and Dose 3 | Dose 1 | 397 h*ng/mL | Geometric Coefficient of Variation 45.3 |
| Eligard 7.5 mg | Area Under the Serum Concentration-time Curve (AUC) Over the Dosing Interval (AUCtau) for Dose 1 and Dose 3 | Dose 3 | 460 h*ng/mL | Geometric Coefficient of Variation 62.2 |
Primary
Observed Maximum Serum Leuprolide Concentration (Cmax) for Dose 1 and Dose 3
Blood samples for analysis of serum leuprolide concentrations were collected at pre-determined time points throughout the trial (with full PK profiles after Dose 1 and Dose 3). The PK parameter, Cmax was derived for Doses 1 and 3 of the investigational medicinal product (IMP).
Time frame: 84 days
Population: The Per-Protocol Set (PPS) consisted of all randomized participants in the safety population who had a complete PK profile. In the CAM2032 3.75 mg group 15 of the 19 randomized participants were included in the PPS.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| CAM2032 3.75 mg | Observed Maximum Serum Leuprolide Concentration (Cmax) for Dose 1 and Dose 3 | Dose 1 | 6.14 ng/mL | Geometric Coefficient of Variation 41.1 |
| CAM2032 3.75 mg | Observed Maximum Serum Leuprolide Concentration (Cmax) for Dose 1 and Dose 3 | Dose 3 | 5.36 ng/mL | Geometric Coefficient of Variation 33.3 |
| CAM2032 7.5 mg | Observed Maximum Serum Leuprolide Concentration (Cmax) for Dose 1 and Dose 3 | Dose 1 | 9.66 ng/mL | Geometric Coefficient of Variation 31.5 |
| CAM2032 7.5 mg | Observed Maximum Serum Leuprolide Concentration (Cmax) for Dose 1 and Dose 3 | Dose 3 | 11.3 ng/mL | Geometric Coefficient of Variation 36.8 |
| Eligard 7.5 mg | Observed Maximum Serum Leuprolide Concentration (Cmax) for Dose 1 and Dose 3 | Dose 1 | 13.6 ng/mL | Geometric Coefficient of Variation 54.7 |
| Eligard 7.5 mg | Observed Maximum Serum Leuprolide Concentration (Cmax) for Dose 1 and Dose 3 | Dose 3 | 12.1 ng/mL | Geometric Coefficient of Variation 47.3 |
Secondary
Mean Prostate Specific Antigen (PSA) Concentration
The PD effects of leuprolide were assessed by measuring serum PSA concentrations during the trial. The following PD variable was analyzed: PSA (ng/mL) response to IMP. Blood samples for analyses of plasma PSA concentrations were collected at Screening and on Days 0 to 126.
Time frame: Days 0-126
Population: The Per-Protocol Set (PPS) consisted of all randomized participants in the safety population who had a complete PK profile. In the CAM2032 3.75 mg group 15 of the 19 randomized participants were included in the PPS.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| CAM2032 3.75 mg | Mean Prostate Specific Antigen (PSA) Concentration | Day 84 | 2.3 ng/mL |
| CAM2032 3.75 mg | Mean Prostate Specific Antigen (PSA) Concentration | Day 56 (predose) | 3.6 ng/mL |
| CAM2032 3.75 mg | Mean Prostate Specific Antigen (PSA) Concentration | Day 0 (predose) | 14.9 ng/mL |
| CAM2032 3.75 mg | Mean Prostate Specific Antigen (PSA) Concentration | Day 28 (predose) | 9 ng/mL |
| CAM2032 3.75 mg | Mean Prostate Specific Antigen (PSA) Concentration | Day 126 | 4.7 ng/mL |
| CAM2032 7.5 mg | Mean Prostate Specific Antigen (PSA) Concentration | Day 56 (predose) | 5.8 ng/mL |
| CAM2032 7.5 mg | Mean Prostate Specific Antigen (PSA) Concentration | Day 0 (predose) | 18.8 ng/mL |
| CAM2032 7.5 mg | Mean Prostate Specific Antigen (PSA) Concentration | Day 28 (predose) | 8.3 ng/mL |
| CAM2032 7.5 mg | Mean Prostate Specific Antigen (PSA) Concentration | Day 84 | 2.6 ng/mL |
| CAM2032 7.5 mg | Mean Prostate Specific Antigen (PSA) Concentration | Day 126 | 3.1 ng/mL |
| Eligard 7.5 mg | Mean Prostate Specific Antigen (PSA) Concentration | Day 126 | 1.6 ng/mL |
| Eligard 7.5 mg | Mean Prostate Specific Antigen (PSA) Concentration | Day 84 | 1.6 ng/mL |
| Eligard 7.5 mg | Mean Prostate Specific Antigen (PSA) Concentration | Day 0 (predose) | 14.6 ng/mL |
| Eligard 7.5 mg | Mean Prostate Specific Antigen (PSA) Concentration | Day 56 (predose) | 2.1 ng/mL |
| Eligard 7.5 mg | Mean Prostate Specific Antigen (PSA) Concentration | Day 28 (predose) | 4.6 ng/mL |
Secondary
Profiles of Testesterone Concentration (ng/dL) Following Injections of the Investigational Medicinal Product (IMP)
The PD effects of leuprolide were assessed by measuring serum testosterone concentrations during the trial. The following PD variable was analyzed: The profiles of testosterone concentration (ng/dL) following injections of the IMP. Blood samples for analyses of serum testosterone concentrations were collected at Screening and on Days 0 to 126.
Time frame: Days 0-126
Population: The Per-Protocol Set (PPS) consisted of all randomized participants in the safety population who had a complete PK profile. In the CAM2032 3.75 mg group 15 of the 19 randomized participants were included in the PPS.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| CAM2032 3.75 mg | Profiles of Testesterone Concentration (ng/dL) Following Injections of the Investigational Medicinal Product (IMP) | Day 84 | 14.8 ng/dL |
| CAM2032 3.75 mg | Profiles of Testesterone Concentration (ng/dL) Following Injections of the Investigational Medicinal Product (IMP) | Day 56 (predose) | 14.6 ng/dL |
| CAM2032 3.75 mg | Profiles of Testesterone Concentration (ng/dL) Following Injections of the Investigational Medicinal Product (IMP) | Day 0 (predose) | 443 ng/dL |
| CAM2032 3.75 mg | Profiles of Testesterone Concentration (ng/dL) Following Injections of the Investigational Medicinal Product (IMP) | Day 28 (predose) | 20.9 ng/dL |
| CAM2032 3.75 mg | Profiles of Testesterone Concentration (ng/dL) Following Injections of the Investigational Medicinal Product (IMP) | Day 126 | 423 ng/dL |
| CAM2032 7.5 mg | Profiles of Testesterone Concentration (ng/dL) Following Injections of the Investigational Medicinal Product (IMP) | Day 56 (predose) | 13.8 ng/dL |
| CAM2032 7.5 mg | Profiles of Testesterone Concentration (ng/dL) Following Injections of the Investigational Medicinal Product (IMP) | Day 0 (predose) | 321 ng/dL |
| CAM2032 7.5 mg | Profiles of Testesterone Concentration (ng/dL) Following Injections of the Investigational Medicinal Product (IMP) | Day 28 (predose) | 24.5 ng/dL |
| CAM2032 7.5 mg | Profiles of Testesterone Concentration (ng/dL) Following Injections of the Investigational Medicinal Product (IMP) | Day 84 | 10.6 ng/dL |
| CAM2032 7.5 mg | Profiles of Testesterone Concentration (ng/dL) Following Injections of the Investigational Medicinal Product (IMP) | Day 126 | 278 ng/dL |
| Eligard 7.5 mg | Profiles of Testesterone Concentration (ng/dL) Following Injections of the Investigational Medicinal Product (IMP) | Day 126 | 85.8 ng/dL |
| Eligard 7.5 mg | Profiles of Testesterone Concentration (ng/dL) Following Injections of the Investigational Medicinal Product (IMP) | Day 84 | 12.4 ng/dL |
| Eligard 7.5 mg | Profiles of Testesterone Concentration (ng/dL) Following Injections of the Investigational Medicinal Product (IMP) | Day 0 (predose) | 350 ng/dL |
| Eligard 7.5 mg | Profiles of Testesterone Concentration (ng/dL) Following Injections of the Investigational Medicinal Product (IMP) | Day 56 (predose) | 12 ng/dL |
| Eligard 7.5 mg | Profiles of Testesterone Concentration (ng/dL) Following Injections of the Investigational Medicinal Product (IMP) | Day 28 (predose) | 18.1 ng/dL |
Secondary
Time (Days) to Testosterone Recovery After Dose 3
The pharmacodynamic (PD) effects of leuprolide were assessed by measuring serum testosterone during the trial. Time to testosterone recovery after last dose of the IMP. Blood samples for analyses of serum testosterone concentrations were collected at Screening and on Days 0 to 126.
Time frame: Days 56-126
Population: The Per-Protocol Set (PPS) consisted of all randomized participants in the safety population who had a complete PK profile. In the CAM2032 3.75 mg group 15 of the 19 randomized participants were included in the PPS.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| CAM2032 3.75 mg | Time (Days) to Testosterone Recovery After Dose 3 | 46.2 days | Standard Deviation 13.6 |
| CAM2032 7.5 mg | Time (Days) to Testosterone Recovery After Dose 3 | 52.3 days | Standard Deviation 20.6 |
| Eligard 7.5 mg | Time (Days) to Testosterone Recovery After Dose 3 | 65 days | Standard Deviation 5.7 |