Prostate Cancer
Conditions
Keywords
Lupron Depot, prostate cancer, leuprolide acetate
Brief summary
To assess the efficacy and safety of 2 new formulations of leuprolide acetate 45 mg 6-month depot, Formulation A or Formulation B, for the treatment of patients with prostate cancer. A formulation will be deemed successful if the percentage of subjects with suppression of testosterone to \<= 50 ng/dL from Week 4 to Week 48 is not less than 87%, (the lower bound of the 2-sided 90% confidence interval), a protocol-specified criterion.
Detailed description
A total of 300 male subjects were planned to be enrolled. Subjects were to receive a total of 2 intramuscular (IM) injections of the same formulation, either Formulation A or Formulation B, administered 24 weeks apart. The first 150 subjects were to receive Formulation A for both injections and the next 150 subjects were to receive Formulation B for both injections. The sponsor was to conduct an ongoing review of the primary endpoint data (suppression of testosterone \<= 50 ng/dL) and planned to stop enrollment of Formulation A or Formulation B, or not to administer the second injection of Formulation A or Formulation B, if 15 or more subjects did not achieve testosterone suppression by Week 4 or failed to maintain testosterone suppression during the treatment period. All analyses and summaries were to be conducted separately for subjects who received Formulation A or Formulation B. This study was to be conducted at approximately 60-80 investigative sites. Subjects participated in the trial for approximately 14 months. This trial was to include a Screening Period (up to 4 weeks), a 12-month Treatment Period (two 6-month treatment cycles), and a Follow-Up Period (30 days).
Interventions
DRUGLeuprolide acetate - Formulation A
Leuprolide acetate was administered as 2 intramuscular (IM) injections of Formulation A, 45 mg 6 month depot, 24 weeks apart.
DRUGLeuprolide acetate - Formulation B
Leuprolide acetate was administered as 2 intramuscular (IM) injections of Formulation B, 45 mg 6 month depot, 24 weeks apart.
Sponsors
Abbott
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
MALE
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Voluntarily sign an IRB-approved informed consent form and any required privacy statement/authorization form. * Pre-trial serum testosterone level \>150 ng/dL. * Histologically-confirmed prostatic adenocarcinoma in Jewett Clinical Stage A2, B, C or D and TNM\* classification cT1b-4, N: any, M: any. \*Tumor/Nodes/Metastases * Subjects with a rising PSA following radical prostatectomy defined as an increase of 0.2 ng/mL from the previous test on two consecutive testings or rising PSA following prostate irradiation using Phoenix Definition of a rise of greater than or equal to 2.0 ng/mL above the nadir. * Prostate cancer and general clinical status is sufficient to warrant at least 48 weeks of continuous androgen deprivation treatment, without concomitant antiandrogen treatment. * Eastern Cooperative Oncology Group (ECOG) Performance status grades 0,1,or 2 at the time of pre-trial screening. * Life expectancy of at least 18 months. * Subjects with serum creatinine ≤1.9 mg/dL, bilirubin ≤2.0 mg/dL (unless Gilbert's syndrome with normal AST, ALT); AST and ALT ≤2.5 times the upper limit of normal.
Exclusion criteria
* Requires additional treatment including radical prostatectomy, radiotherapy or cryotherapy of local disease. * Historical, clinical, or radiographic evidence of central nervous system metastases, including spinal cord metastasis. * Clinical evidence of urinary tract obstruction. * History of bilateral orchiectomy, adrenalectomy, or hypophysectomy. * History of clinical hypogonadism. * Current malignancy or history of malignancy except for prostate cancer or basal or squamous cell carcinoma of the skin. * Clinical or laboratory evidence of any severe underlying disease state (excluding prostate cancer) that would place subjects in additional jeopardy by participating in this trial. * Hypersensitivity to leuprolide, polylactic acid, or any excipient of the drug. * Incomplete recovery from the effects of any major surgery. * History of receiving of the following prostate cancer therapies within 8 weeks prior to the Screening Visit: chemotherapy, immunotherapy, antiandrogen, radiation therapy, cryotherapy, strontium, or biological response modifiers. * History of prostatic surgery within 4 weeks prior to the Screening Visit. * Received hormonal therapy, including GnRH analogs (less than or equal to 6 month depot administration), estrogen, Megace and phytotherapy, within 32 weeks prior to the Screening Visit and during the trial. * Alternative medical therapies which have an estrogenic, androgenic, or antiandrogenic effect (including phyto-estrogens and phyto-androgens) within 12 weeks prior to the Screening Visit and during the trial. * Requires the chronic use of systemic corticosteroids and anticonvulsants that may affect bone loss such as carbamazepine, phenobarbital, phenytoin, valproic acid or primidone. * May require antiandrogen, immuno-, or surgical therapy for prostate cancer during the trial. * History of alcoholism or consumes \>14 alcoholic beverages per week or illicit drug abuse within 12 months prior to screening. * Received therapy with a GnRH analog (1 year implant) within 60 weeks prior to the Screening Visit. * Received therapy with finasteride or ketoconazole within 1 week prior to the Screening Visit; dutasteride within 25 weeks prior to the Screening Visit.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Subjects With Suppression of Serum Testosterone (<=50 ng/dL) From Week 4 to Week 48 for Formulation A: Intent-to-treat (ITT) Population for the Primary Endpoint. | Week 4 to Week 48 | The percentage of subjects with testosterone suppression (\<= 50 ng/dL) from Week 4 to Week 48 was calculated by the Kaplan-Meier method for right-censored observations. Subjects who failed testosterone suppression were considered failures on the first day of a testosterone measurement (\>50 ng/dL). Subjects who prematurely discontinued without escaping and those who were successfully suppressed through Week 48 were censored at their last measured testosterone value (Day 337 to Day 340 at Week 48). The 90% 2-sided confidence interval was calculated from Kaplan-Meier estimates. |
| Adjusted Percentage of Subjects With Suppression of Serum Testosterone (<=50 ng/dL) From Week 4 to Week 48 for Formulation A: ITT Population for the Primary Endpoint Adjusted | Week 4 to Week 48 | The adjusted percentage of subjects with testosterone suppression (\<= 50 ng/dL) from Week 4 to Week 48 was calculated by the Kaplan-Meier method for right-censored observations. The primary efficacy analysis was adjusted to censor subjects who received an anti-androgen at the last testosterone measurement before use of the anti-androgen. One additional subject was censored because of a laboratory error, at the last measurement before the error. The adjusted 90% 2-sided confidence interval was calculated from Kaplan-Meier estimates. |
| Percentage of Subjects With Suppression of Serum Testosterone (<=50 ng/dL) From Week 4 to Week 48 for Formulation B: ITT Population for the Primary Endpoint Preplanned | Week 4 to Week 48 | The percentage of subjects with testosterone suppression (\<= 50 ng/dL) from Week 4 to Week 48 was calculated by the Kaplan-Meier method for right-censored observations. Subjects who failed testosterone suppression were considered failures on the first day of a testosterone measurement (\>50 ng/dL). Subjects who prematurely discontinued without escaping and those who were successfully suppressed through Week 48 were censored at their last measured testosterone value (Day 337 to Day 340 at Week 48). The 90% 2-sided confidence interval was calculated from Kaplan-Meier estimates. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Mean (+/- Standard Error) Acute-on-chronic Changes in Testosterone From Pre-injection Levels for Formulation B: ITT Population | Week 24 before the second injection until 2 weeks after Week 24 (2 h, 4 h, 8 h, 1 d, 2 d, 3-10 d, and 11-17 d postdose) | The acute-on-chronic effect is an agonistic stimulation of serum testosterone after the second depot injection of Formulation B. The mean +/- standard error changes were measured to assess this effect from just before to 2 weeks after the second injection. |
| Mean (+/- Standard Error) Acute-on-chronic Changes in Luteinizing Hormone From Pre-injection Levels for Formulation A: ITT Population | Week 24 before the second injection until 2 weeks after Week 24 (2 h, 4 h, 8 h, 1 d, 2 d, 3-10 d, and 11-17 d postdose) | The acute-on-chronic effect is an agonistic stimulation of luteinizing hormone after the second depot injection of Formulation A. The mean +/- standard error changes were measured to assess this effect from just before to 2 weeks after the second injection. |
| Mean Testosterone Concentration (+/- Standard Error) at Each Visit for Formulation A: ITT Population | Baseline, Days 2 and 8, Weeks 2, 4, 8, 14, 20, 24, 26, 30, 34, 40, 46, 48, and Final Visit | Baseline was the last measurement before the first dose of Formulation A. The mean +/- standard error was calculated at each visit. The final visit occurred at Week 48 unless the subject prematurely discontinued the study. |
| Mean (+/- Standard Error) Prostate Specific Antigen (PSA) at Baseline, Visits Throughout the Study, and at Final Visit for Formulation A: ITT Population | Baseline, Day 8, Week 14, Week 24, Week 30, Week 40, Week 48, and the Final Visit | PSA levels were measured at baseline and each treatment visit for Formulation A. The mean (+/- standard error) was calculated at each visit. The final visit occurred at Week 48 unless the subject prematurely discontinued the study. |
| Mean (+/- Standard Error) Prostate Specific Antigen (PSA) at Baseline, Visits Throughout the Study, and at Final Visit for Formulation B: ITT Population | Baseline, Day 8, Week 14, Week 24, Week 30, Week 40, Week 48, and the Final Visit | PSA levels were measured at baseline and each treatment visit for Formulation B. The mean (+/- standard error) was calculated at each visit. The final visit occurred at Week 48 unless the subject prematurely discontinued the study. |
| Mean (+/- Standard Error) Acute-on-chronic Changes in Luteinizing Hormone From Pre-injection Levels for Formulation B: ITT Population | Week 24 before the second injection until 2 weeks after Week 24 (2 h, 4 h, 8 h, 1 d, 2 d, 3-10 d, and 11-17 d postdose) | The acute-on-chronic effect is an agonistic stimulation of luteinizing hormone after the second depot injection of Formulation B. The mean +/- standard error changes were measured to assess this effect from just before to 2 weeks after the second injection. |
| Mean Testosterone Concentration (+/- Standard Error) at Each Visit for Formulation B: ITT Population | Baseline, Days 2 and 8, Weeks 2, 4, 8, 14, 20, 24, 26, 30, 34, 40, 46, 48, and Final Visit | Baseline was the last measurement before the first dose of Formulation B. The mean +/- standard error was calculated at each visit. The final visit occurred at Week 48 unless the subject prematurely discontinued the study. |
| Mean (+/- Standard Error) Acute-on-chronic Changes in Testosterone From Pre-injection Levels for Formulation A: ITT Population | Week 24 before the second injection until 2 weeks after Week 24 (2 hours [h], 4 h, 8 h, 1 day [d], 2 d, 3-10 d, and 11-17 d postdose) | The acute-on-chronic effect is an agonistic stimulation of serum testosterone after the second depot injection of Formulation A. The mean +/- standard error changes were measured to assess this effect from just before to 2 weeks after the second injection. |
Countries
United States
Participant flow
Recruitment details
The enrollment of subjects with Formulation A occurred sequentially before the enrollment of subjects with Formulation B.
Pre-assignment details
Formulation A and Formulation B treatment groups were enrolled sequentially. All analyses and summaries were conducted separately for both treatment groups.
Participants by arm
| Arm | Count |
|---|---|
| Leuprolide Acetate - Formulation A Leuprolide acetate 45 mg, 6-month depot administered as 2 intramuscular (IM) injections of Formulation A, 24 weeks apart. Injections were administered on Day 1 and Day 169. The first 150 subjects were to receive Formulation A and then the next 150 subjects were to receive Formulation B in a sequential manner. | 151 |
| Leuprolide Acetate - Formulation B Leuprolide acetate 45 mg, 6-month depot administered as 2 intramuscular injections of Formulation B, 24 weeks apart. Injections were administered on Day 1 and Day 169. The first 150 subjects were to receive Formulation A and then the next 150 subjects were to receive Formulation B in a sequential manner. | 159 |
| Total | 310 |
Baseline characteristics
| Characteristic | Leuprolide Acetate - Formulation A | Leuprolide Acetate - Formulation B | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 133 Participants | 126 Participants | 259 Participants |
| Age, Categorical Between 18 and 65 years | 18 Participants | 33 Participants | 51 Participants |
| Region of Enrollment United States | 151 participants | 159 participants | 310 participants |
| Sex: Female, Male Female | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Male | 151 Participants | 159 Participants | 310 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 133 / 151 | 127 / 159 |
| serious Total, serious adverse events | 31 / 151 | 41 / 159 |
Outcome results
Primary
Adjusted Percentage of Subjects With Suppression of Serum Testosterone (<=50 ng/dL) From Week 4 to Week 48 for Formulation A: ITT Population for the Primary Endpoint Adjusted
The adjusted percentage of subjects with testosterone suppression (\<= 50 ng/dL) from Week 4 to Week 48 was calculated by the Kaplan-Meier method for right-censored observations. The primary efficacy analysis was adjusted to censor subjects who received an anti-androgen at the last testosterone measurement before use of the anti-androgen. One additional subject was censored because of a laboratory error, at the last measurement before the error. The adjusted 90% 2-sided confidence interval was calculated from Kaplan-Meier estimates.
Time frame: Week 4 to Week 48
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Leuprolide Acetate - Formulation A | Adjusted Percentage of Subjects With Suppression of Serum Testosterone (<=50 ng/dL) From Week 4 to Week 48 for Formulation A: ITT Population for the Primary Endpoint Adjusted | 93.4 Percent Suppressed |
Primary
Percentage of Subjects With Suppression of Serum Testosterone (<=50 ng/dL) From Week 4 to Week 48 for Formulation A: Intent-to-treat (ITT) Population for the Primary Endpoint.
The percentage of subjects with testosterone suppression (\<= 50 ng/dL) from Week 4 to Week 48 was calculated by the Kaplan-Meier method for right-censored observations. Subjects who failed testosterone suppression were considered failures on the first day of a testosterone measurement (\>50 ng/dL). Subjects who prematurely discontinued without escaping and those who were successfully suppressed through Week 48 were censored at their last measured testosterone value (Day 337 to Day 340 at Week 48). The 90% 2-sided confidence interval was calculated from Kaplan-Meier estimates.
Time frame: Week 4 to Week 48
Population: The ITT population for the primary endpoint was the same as the ITT population for the secondary endpoints and also excluded subjects whose final testosterone values were measured before Day 19 without suppression (\>50 ng/dL) or whose testosterone levels remained suppressed through Week 48 but testosterone levels were not measured at Week 4.
| Arm | Measure | Value (NUMBER) | Dispersion |
|---|---|---|---|
| Leuprolide Acetate - Formulation A | Percentage of Subjects With Suppression of Serum Testosterone (<=50 ng/dL) From Week 4 to Week 48 for Formulation A: Intent-to-treat (ITT) Population for the Primary Endpoint. | 93.6 Percent Suppressed | 90% Confidence Interval 2.05 |
Primary
Percentage of Subjects With Suppression of Serum Testosterone (<=50 ng/dL) From Week 4 to Week 48 for Formulation B: ITT Population for the Primary Endpoint Preplanned
The percentage of subjects with testosterone suppression (\<= 50 ng/dL) from Week 4 to Week 48 was calculated by the Kaplan-Meier method for right-censored observations. Subjects who failed testosterone suppression were considered failures on the first day of a testosterone measurement (\>50 ng/dL). Subjects who prematurely discontinued without escaping and those who were successfully suppressed through Week 48 were censored at their last measured testosterone value (Day 337 to Day 340 at Week 48). The 90% 2-sided confidence interval was calculated from Kaplan-Meier estimates.
Time frame: Week 4 to Week 48
Population: The ITT population for the primary endpoint was the same as the ITT population for the secondary endpoints and also excluded subjects whose final testosterone values were measured before Day 19 without suppression (\>50 ng/dL) or whose testosterone levels remained suppressed through Week 48 but testosterone levels were not measured at Week 4.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Leuprolide Acetate - Formulation A | Percentage of Subjects With Suppression of Serum Testosterone (<=50 ng/dL) From Week 4 to Week 48 for Formulation B: ITT Population for the Primary Endpoint Preplanned | 86.9 Percent suppressed |
Secondary
Mean (+/- Standard Error) Acute-on-chronic Changes in Luteinizing Hormone From Pre-injection Levels for Formulation A: ITT Population
The acute-on-chronic effect is an agonistic stimulation of luteinizing hormone after the second depot injection of Formulation A. The mean +/- standard error changes were measured to assess this effect from just before to 2 weeks after the second injection.
Time frame: Week 24 before the second injection until 2 weeks after Week 24 (2 h, 4 h, 8 h, 1 d, 2 d, 3-10 d, and 11-17 d postdose)
Population: The ITT population included subjects who received at least 1 dose of study drug, who had at least 1 postbaseline measurement, and who did not use prohibited medications during the first 32 days after the initiation of study drug treatment that either lowered testosterone levels or blocked its action.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Leuprolide Acetate - Formulation A | Mean (+/- Standard Error) Acute-on-chronic Changes in Luteinizing Hormone From Pre-injection Levels for Formulation A: ITT Population | Testosterone concentration at 2 hours postdose | 0.2 ng/dL | Standard Error 0.03 |
| Leuprolide Acetate - Formulation A | Mean (+/- Standard Error) Acute-on-chronic Changes in Luteinizing Hormone From Pre-injection Levels for Formulation A: ITT Population | Testosterone concentration at 4 hours postdose | 0.2 ng/dL | Standard Error 0.03 |
| Leuprolide Acetate - Formulation A | Mean (+/- Standard Error) Acute-on-chronic Changes in Luteinizing Hormone From Pre-injection Levels for Formulation A: ITT Population | Testosterone concentration at 8 hours postdose | 0.2 ng/dL | Standard Error 0.02 |
| Leuprolide Acetate - Formulation A | Mean (+/- Standard Error) Acute-on-chronic Changes in Luteinizing Hormone From Pre-injection Levels for Formulation A: ITT Population | Testosterone concentration at Day 1 postdose | 0.2 ng/dL | Standard Error 0.02 |
| Leuprolide Acetate - Formulation A | Mean (+/- Standard Error) Acute-on-chronic Changes in Luteinizing Hormone From Pre-injection Levels for Formulation A: ITT Population | Testosterone concentration at Day 2 postdose | 0.1 ng/dL | Standard Error 0.01 |
| Leuprolide Acetate - Formulation A | Mean (+/- Standard Error) Acute-on-chronic Changes in Luteinizing Hormone From Pre-injection Levels for Formulation A: ITT Population | Testosterone concentration at Days 3-10 postdose | 0.1 ng/dL | Standard Error 0.01 |
| Leuprolide Acetate - Formulation A | Mean (+/- Standard Error) Acute-on-chronic Changes in Luteinizing Hormone From Pre-injection Levels for Formulation A: ITT Population | Testosterone concentration at Days 11-17 postdose | 0.1 ng/dL | Standard Error 0.02 |
Secondary
Mean (+/- Standard Error) Acute-on-chronic Changes in Luteinizing Hormone From Pre-injection Levels for Formulation B: ITT Population
The acute-on-chronic effect is an agonistic stimulation of luteinizing hormone after the second depot injection of Formulation B. The mean +/- standard error changes were measured to assess this effect from just before to 2 weeks after the second injection.
Time frame: Week 24 before the second injection until 2 weeks after Week 24 (2 h, 4 h, 8 h, 1 d, 2 d, 3-10 d, and 11-17 d postdose)
Population: The ITT population included subjects who received at least 1 dose of study drug, who had at least 1 postbaseline measurement, and who did not use prohibited medications during the first 32 days after the initiation of study drug treatment that either lowered testosterone levels or blocked its action.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Leuprolide Acetate - Formulation A | Mean (+/- Standard Error) Acute-on-chronic Changes in Luteinizing Hormone From Pre-injection Levels for Formulation B: ITT Population | Testosterone concentration at 2 hours postdose | 0.4 ng/dL | Standard Error 0.07 |
| Leuprolide Acetate - Formulation A | Mean (+/- Standard Error) Acute-on-chronic Changes in Luteinizing Hormone From Pre-injection Levels for Formulation B: ITT Population | Testosterone concentration at 4 hours postdose | 0.5 ng/dL | Standard Error 0.12 |
| Leuprolide Acetate - Formulation A | Mean (+/- Standard Error) Acute-on-chronic Changes in Luteinizing Hormone From Pre-injection Levels for Formulation B: ITT Population | Testosterone concentration at 8 hours postdose | 0.4 ng/dL | Standard Error 0.11 |
| Leuprolide Acetate - Formulation A | Mean (+/- Standard Error) Acute-on-chronic Changes in Luteinizing Hormone From Pre-injection Levels for Formulation B: ITT Population | Testosterone concentration at Day 1 postdose | 0.4 ng/dL | Standard Error 0.08 |
| Leuprolide Acetate - Formulation A | Mean (+/- Standard Error) Acute-on-chronic Changes in Luteinizing Hormone From Pre-injection Levels for Formulation B: ITT Population | Testosterone concentration at Day 2 postdose | 0.2 ng/dL | Standard Error 0.04 |
| Leuprolide Acetate - Formulation A | Mean (+/- Standard Error) Acute-on-chronic Changes in Luteinizing Hormone From Pre-injection Levels for Formulation B: ITT Population | Testosterone concentration at Days 3-10 postdose | 0.1 ng/dL | Standard Error 0.02 |
| Leuprolide Acetate - Formulation A | Mean (+/- Standard Error) Acute-on-chronic Changes in Luteinizing Hormone From Pre-injection Levels for Formulation B: ITT Population | Testosterone concentration at Days 11-17 postdose | -0.1 ng/dL | Standard Error 0.04 |
Secondary
Mean (+/- Standard Error) Acute-on-chronic Changes in Testosterone From Pre-injection Levels for Formulation A: ITT Population
The acute-on-chronic effect is an agonistic stimulation of serum testosterone after the second depot injection of Formulation A. The mean +/- standard error changes were measured to assess this effect from just before to 2 weeks after the second injection.
Time frame: Week 24 before the second injection until 2 weeks after Week 24 (2 hours [h], 4 h, 8 h, 1 day [d], 2 d, 3-10 d, and 11-17 d postdose)
Population: The ITT population included subjects who received at least 1 dose of study drug, who had at least 1 postbaseline measurement, and who did not use prohibited medications during the first 32 days after the initiation of study drug treatment that either lowered testosterone levels or blocked its action.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Leuprolide Acetate - Formulation A | Mean (+/- Standard Error) Acute-on-chronic Changes in Testosterone From Pre-injection Levels for Formulation A: ITT Population | Testosterone concentration at 2 hours postdose | -1.9 ng/dL | Standard Error 0.85 |
| Leuprolide Acetate - Formulation A | Mean (+/- Standard Error) Acute-on-chronic Changes in Testosterone From Pre-injection Levels for Formulation A: ITT Population | Testosterone concentration at 4 hours postdose | -1.2 ng/dL | Standard Error 0.93 |
| Leuprolide Acetate - Formulation A | Mean (+/- Standard Error) Acute-on-chronic Changes in Testosterone From Pre-injection Levels for Formulation A: ITT Population | Testosterone concentration at 8 hours postdose | -1.3 ng/dL | Standard Error 1.02 |
| Leuprolide Acetate - Formulation A | Mean (+/- Standard Error) Acute-on-chronic Changes in Testosterone From Pre-injection Levels for Formulation A: ITT Population | Testosterone concentration at Day 1 postdose | -0.1 ng/dL | Standard Error 0.95 |
| Leuprolide Acetate - Formulation A | Mean (+/- Standard Error) Acute-on-chronic Changes in Testosterone From Pre-injection Levels for Formulation A: ITT Population | Testosterone concentration at Day 2 postdose | -0.1 ng/dL | Standard Error 0.92 |
| Leuprolide Acetate - Formulation A | Mean (+/- Standard Error) Acute-on-chronic Changes in Testosterone From Pre-injection Levels for Formulation A: ITT Population | Testosterone concentration at Days 3-10 postdose | -1.0 ng/dL | Standard Error 0.89 |
| Leuprolide Acetate - Formulation A | Mean (+/- Standard Error) Acute-on-chronic Changes in Testosterone From Pre-injection Levels for Formulation A: ITT Population | Testosterone concentration at Days 11-17 postdose | -2.1 ng/dL | Standard Error 0.87 |
Secondary
Mean (+/- Standard Error) Acute-on-chronic Changes in Testosterone From Pre-injection Levels for Formulation B: ITT Population
The acute-on-chronic effect is an agonistic stimulation of serum testosterone after the second depot injection of Formulation B. The mean +/- standard error changes were measured to assess this effect from just before to 2 weeks after the second injection.
Time frame: Week 24 before the second injection until 2 weeks after Week 24 (2 h, 4 h, 8 h, 1 d, 2 d, 3-10 d, and 11-17 d postdose)
Population: The ITT population included subjects who received at least 1 dose of study drug, who had at least 1 postbaseline measurement, and who did not use prohibited medications during the first 32 days after the initiation of study drug treatment that either lowered testosterone levels or blocked its action.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Leuprolide Acetate - Formulation A | Mean (+/- Standard Error) Acute-on-chronic Changes in Testosterone From Pre-injection Levels for Formulation B: ITT Population | Testosterone concentration at 2 hours postdose | -0.7 ng/dL | Standard Error 0.66 |
| Leuprolide Acetate - Formulation A | Mean (+/- Standard Error) Acute-on-chronic Changes in Testosterone From Pre-injection Levels for Formulation B: ITT Population | Testosterone concentration at 4 hours postdose | 1.6 ng/dL | Standard Error 1.13 |
| Leuprolide Acetate - Formulation A | Mean (+/- Standard Error) Acute-on-chronic Changes in Testosterone From Pre-injection Levels for Formulation B: ITT Population | Testosterone concentration at 8 hours postdose | 3.6 ng/dL | Standard Error 1.35 |
| Leuprolide Acetate - Formulation A | Mean (+/- Standard Error) Acute-on-chronic Changes in Testosterone From Pre-injection Levels for Formulation B: ITT Population | Testosterone concentration at Day 1 postdose | 8.0 ng/dL | Standard Error 1.8 |
| Leuprolide Acetate - Formulation A | Mean (+/- Standard Error) Acute-on-chronic Changes in Testosterone From Pre-injection Levels for Formulation B: ITT Population | Testosterone concentration at Day 2 postdose | 7.8 ng/dL | Standard Error 1.81 |
| Leuprolide Acetate - Formulation A | Mean (+/- Standard Error) Acute-on-chronic Changes in Testosterone From Pre-injection Levels for Formulation B: ITT Population | Testosterone concentration at Days 3-10 postdose | 4.5 ng/dL | Standard Error 1.07 |
| Leuprolide Acetate - Formulation A | Mean (+/- Standard Error) Acute-on-chronic Changes in Testosterone From Pre-injection Levels for Formulation B: ITT Population | Testosterone concentration at Day 11-17 postdose | -4.2 ng/dL | Standard Error 1.43 |
Secondary
Mean (+/- Standard Error) Prostate Specific Antigen (PSA) at Baseline, Visits Throughout the Study, and at Final Visit for Formulation A: ITT Population
PSA levels were measured at baseline and each treatment visit for Formulation A. The mean (+/- standard error) was calculated at each visit. The final visit occurred at Week 48 unless the subject prematurely discontinued the study.
Time frame: Baseline, Day 8, Week 14, Week 24, Week 30, Week 40, Week 48, and the Final Visit
Population: The ITT population included subjects who received at least 1 dose of study drug, who had at least 1 postbaseline measurement, and who did not use prohibited medications during the first 32 days after the initiation of study drug treatment that either lowered testosterone levels or blocked its action.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Leuprolide Acetate - Formulation A | Mean (+/- Standard Error) Prostate Specific Antigen (PSA) at Baseline, Visits Throughout the Study, and at Final Visit for Formulation A: ITT Population | PSA concentration at baseline | 35.0 ng/mL | Standard Error 11.21 |
| Leuprolide Acetate - Formulation A | Mean (+/- Standard Error) Prostate Specific Antigen (PSA) at Baseline, Visits Throughout the Study, and at Final Visit for Formulation A: ITT Population | PSA Concentration at Day 8 | 40.4 ng/mL | Standard Error 12.9 |
| Leuprolide Acetate - Formulation A | Mean (+/- Standard Error) Prostate Specific Antigen (PSA) at Baseline, Visits Throughout the Study, and at Final Visit for Formulation A: ITT Population | PSA Concentration at Week 14 | 2.4 ng/mL | Standard Error 0.62 |
| Leuprolide Acetate - Formulation A | Mean (+/- Standard Error) Prostate Specific Antigen (PSA) at Baseline, Visits Throughout the Study, and at Final Visit for Formulation A: ITT Population | PSA Concentration at Week 24 | 2.9 ng/mL | Standard Error 1.09 |
| Leuprolide Acetate - Formulation A | Mean (+/- Standard Error) Prostate Specific Antigen (PSA) at Baseline, Visits Throughout the Study, and at Final Visit for Formulation A: ITT Population | PSA Concentration at Week 30 | 1.6 ng/mL | Standard Error 0.46 |
| Leuprolide Acetate - Formulation A | Mean (+/- Standard Error) Prostate Specific Antigen (PSA) at Baseline, Visits Throughout the Study, and at Final Visit for Formulation A: ITT Population | PSA Concentration at Week 40 | 2.2 ng/mL | Standard Error 0.82 |
| Leuprolide Acetate - Formulation A | Mean (+/- Standard Error) Prostate Specific Antigen (PSA) at Baseline, Visits Throughout the Study, and at Final Visit for Formulation A: ITT Population | PSA Concentration at Week 48/Final Visit | 3.7 ng/mL | Standard Error 1.51 |
Secondary
Mean (+/- Standard Error) Prostate Specific Antigen (PSA) at Baseline, Visits Throughout the Study, and at Final Visit for Formulation B: ITT Population
PSA levels were measured at baseline and each treatment visit for Formulation B. The mean (+/- standard error) was calculated at each visit. The final visit occurred at Week 48 unless the subject prematurely discontinued the study.
Time frame: Baseline, Day 8, Week 14, Week 24, Week 30, Week 40, Week 48, and the Final Visit
Population: The ITT population included subjects who received at least 1 dose of study drug, who had at least 1 postbaseline measurement, and who did not use prohibited medications during the first 32 days after the initiation of study drug treatment that either lowered testosterone levels or blocked its action.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Leuprolide Acetate - Formulation A | Mean (+/- Standard Error) Prostate Specific Antigen (PSA) at Baseline, Visits Throughout the Study, and at Final Visit for Formulation B: ITT Population | PSA concentration at baseline | 20.5 ng/mL | Standard Error 3.88 |
| Leuprolide Acetate - Formulation A | Mean (+/- Standard Error) Prostate Specific Antigen (PSA) at Baseline, Visits Throughout the Study, and at Final Visit for Formulation B: ITT Population | PSA Concentration at Day 8 | 23.1 ng/mL | Standard Error 4.03 |
| Leuprolide Acetate - Formulation A | Mean (+/- Standard Error) Prostate Specific Antigen (PSA) at Baseline, Visits Throughout the Study, and at Final Visit for Formulation B: ITT Population | PSA Concentration at Week 14 | 2.4 ng/mL | Standard Error 0.51 |
| Leuprolide Acetate - Formulation A | Mean (+/- Standard Error) Prostate Specific Antigen (PSA) at Baseline, Visits Throughout the Study, and at Final Visit for Formulation B: ITT Population | PSA Concentration at Week 24 | 2.5 ng/mL | Standard Error 0.65 |
| Leuprolide Acetate - Formulation A | Mean (+/- Standard Error) Prostate Specific Antigen (PSA) at Baseline, Visits Throughout the Study, and at Final Visit for Formulation B: ITT Population | PSA Concentration at Week 30 | 2.7 ng/mL | Standard Error 0.86 |
| Leuprolide Acetate - Formulation A | Mean (+/- Standard Error) Prostate Specific Antigen (PSA) at Baseline, Visits Throughout the Study, and at Final Visit for Formulation B: ITT Population | PSA Concentration at Week 40 | 2.5 ng/mL | Standard Error 0.85 |
| Leuprolide Acetate - Formulation A | Mean (+/- Standard Error) Prostate Specific Antigen (PSA) at Baseline, Visits Throughout the Study, and at Final Visit for Formulation B: ITT Population | PSA Concentration at Week 48/Final Visit | 6.2 ng/mL | Standard Error 2.75 |
Secondary
Mean Testosterone Concentration (+/- Standard Error) at Each Visit for Formulation A: ITT Population
Baseline was the last measurement before the first dose of Formulation A. The mean +/- standard error was calculated at each visit. The final visit occurred at Week 48 unless the subject prematurely discontinued the study.
Time frame: Baseline, Days 2 and 8, Weeks 2, 4, 8, 14, 20, 24, 26, 30, 34, 40, 46, 48, and Final Visit
Population: The ITT population included subjects who received at least 1 dose of study drug, who had at least 1 postbaseline measurement, and who did not use prohibited medications during the first 32 days after the initiation of study drug treatment that either lowered testosterone levels or blocked its action.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Leuprolide Acetate - Formulation A | Mean Testosterone Concentration (+/- Standard Error) at Each Visit for Formulation A: ITT Population | Testosterone concentration at baseline | 432.9 ng/dL | Standard Error 14.35 |
| Leuprolide Acetate - Formulation A | Mean Testosterone Concentration (+/- Standard Error) at Each Visit for Formulation A: ITT Population | Testosterone concentration at Day 2 | 613.1 ng/dL | Standard Error 21.53 |
| Leuprolide Acetate - Formulation A | Mean Testosterone Concentration (+/- Standard Error) at Each Visit for Formulation A: ITT Population | Testosterone concentration at Day 8 | 468.2 ng/dL | Standard Error 16.55 |
| Leuprolide Acetate - Formulation A | Mean Testosterone Concentration (+/- Standard Error) at Each Visit for Formulation A: ITT Population | Testosterone concentration at Week 2 | 127.1 ng/dL | Standard Error 7.36 |
| Leuprolide Acetate - Formulation A | Mean Testosterone Concentration (+/- Standard Error) at Each Visit for Formulation A: ITT Population | Testosterone concentration at Week 4 | 16.0 ng/dL | Standard Error 0.7 |
| Leuprolide Acetate - Formulation A | Mean Testosterone Concentration (+/- Standard Error) at Each Visit for Formulation A: ITT Population | Testosterone concentration at Week 8 | 9.6 ng/dL | Standard Error 0.46 |
| Leuprolide Acetate - Formulation A | Mean Testosterone Concentration (+/- Standard Error) at Each Visit for Formulation A: ITT Population | Testosterone concentration at Week 14 | 9.2 ng/dL | Standard Error 0.46 |
| Leuprolide Acetate - Formulation A | Mean Testosterone Concentration (+/- Standard Error) at Each Visit for Formulation A: ITT Population | Testosterone concentration at Week 20 | 8.5 ng/dL | Standard Error 0.46 |
| Leuprolide Acetate - Formulation A | Mean Testosterone Concentration (+/- Standard Error) at Each Visit for Formulation A: ITT Population | Testosterone concentration at Week 24 | 14.3 ng/dL | Standard Error 1.25 |
| Leuprolide Acetate - Formulation A | Mean Testosterone Concentration (+/- Standard Error) at Each Visit for Formulation A: ITT Population | Testosterone concentration at Week 26 | 9.0 ng/dL | Standard Error 0.47 |
| Leuprolide Acetate - Formulation A | Mean Testosterone Concentration (+/- Standard Error) at Each Visit for Formulation A: ITT Population | Testosterone concentration at Week 30 | 9.9 ng/dL | Standard Error 1.67 |
| Leuprolide Acetate - Formulation A | Mean Testosterone Concentration (+/- Standard Error) at Each Visit for Formulation A: ITT Population | Testosterone concentration at Week 34 | 13.0 ng/dL | Standard Error 4.14 |
| Leuprolide Acetate - Formulation A | Mean Testosterone Concentration (+/- Standard Error) at Each Visit for Formulation A: ITT Population | Testosterone concentration at Week 40 | 8.8 ng/dL | Standard Error 0.41 |
| Leuprolide Acetate - Formulation A | Mean Testosterone Concentration (+/- Standard Error) at Each Visit for Formulation A: ITT Population | Testosterone concentration at Week 46 | 8.8 ng/dL | Standard Error 0.46 |
| Leuprolide Acetate - Formulation A | Mean Testosterone Concentration (+/- Standard Error) at Each Visit for Formulation A: ITT Population | Testosterone concentration at Week 48/Final Visit | 13.3 ng/dL | Standard Error 3.67 |
Secondary
Mean Testosterone Concentration (+/- Standard Error) at Each Visit for Formulation B: ITT Population
Baseline was the last measurement before the first dose of Formulation B. The mean +/- standard error was calculated at each visit. The final visit occurred at Week 48 unless the subject prematurely discontinued the study.
Time frame: Baseline, Days 2 and 8, Weeks 2, 4, 8, 14, 20, 24, 26, 30, 34, 40, 46, 48, and Final Visit
Population: The ITT population included subjects who received at least 1 dose of study drug, who had at least 1 postbaseline measurement, and who did not use prohibited medications during the first 32 days after the initiation of study drug treatment that either lowered testosterone levels or blocked its action.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Leuprolide Acetate - Formulation A | Mean Testosterone Concentration (+/- Standard Error) at Each Visit for Formulation B: ITT Population | Testosterone concentration at baseline | 414.0 ng/dL | Standard Error 14.15 |
| Leuprolide Acetate - Formulation A | Mean Testosterone Concentration (+/- Standard Error) at Each Visit for Formulation B: ITT Population | Testosterone concentration at Day 2 | 578.0 ng/dL | Standard Error 20.14 |
| Leuprolide Acetate - Formulation A | Mean Testosterone Concentration (+/- Standard Error) at Each Visit for Formulation B: ITT Population | Testosterone concentration at Day 8 | 466.9 ng/dL | Standard Error 17.7 |
| Leuprolide Acetate - Formulation A | Mean Testosterone Concentration (+/- Standard Error) at Each Visit for Formulation B: ITT Population | Testosterone concentration at Week 2 | 127.4 ng/dL | Standard Error 7.35 |
| Leuprolide Acetate - Formulation A | Mean Testosterone Concentration (+/- Standard Error) at Each Visit for Formulation B: ITT Population | Testosterone concentration at Week 4 | 15.3 ng/dL | Standard Error 0.71 |
| Leuprolide Acetate - Formulation A | Mean Testosterone Concentration (+/- Standard Error) at Each Visit for Formulation B: ITT Population | Testosterone concentration at Week 8 | 9.1 ng/dL | Standard Error 0.44 |
| Leuprolide Acetate - Formulation A | Mean Testosterone Concentration (+/- Standard Error) at Each Visit for Formulation B: ITT Population | Testosterone concentration at Week 14 | 8.9 ng/dL | Standard Error 0.42 |
| Leuprolide Acetate - Formulation A | Mean Testosterone Concentration (+/- Standard Error) at Each Visit for Formulation B: ITT Population | Testosterone concentration at Week 20 | 9.6 ng/dL | Standard Error 0.54 |
| Leuprolide Acetate - Formulation A | Mean Testosterone Concentration (+/- Standard Error) at Each Visit for Formulation B: ITT Population | Testosterone concentration at Week 24 | 28.0 ng/dL | Standard Error 3.97 |
| Leuprolide Acetate - Formulation A | Mean Testosterone Concentration (+/- Standard Error) at Each Visit for Formulation B: ITT Population | Testosterone concentration at Week 26 | 15.6 ng/dL | Standard Error 2.63 |
| Leuprolide Acetate - Formulation A | Mean Testosterone Concentration (+/- Standard Error) at Each Visit for Formulation B: ITT Population | Testosterone concentration at Week 30 | 9.4 ng/dL | Standard Error 0.6 |
| Leuprolide Acetate - Formulation A | Mean Testosterone Concentration (+/- Standard Error) at Each Visit for Formulation B: ITT Population | Testosterone concentration at Week 34 | 9.7 ng/dL | Standard Error 0.53 |
| Leuprolide Acetate - Formulation A | Mean Testosterone Concentration (+/- Standard Error) at Each Visit for Formulation B: ITT Population | Testosterone concentration at Week 40 | 9.5 ng/dL | Standard Error 0.52 |
| Leuprolide Acetate - Formulation A | Mean Testosterone Concentration (+/- Standard Error) at Each Visit for Formulation B: ITT Population | Testosterone concentration at Week 46 | 9.4 ng/dL | Standard Error 0.64 |
| Leuprolide Acetate - Formulation A | Mean Testosterone Concentration (+/- Standard Error) at Each Visit for Formulation B: ITT Population | Testosterone concentration at Week 48/Final Visit | 13.8 ng/dL | Standard Error 1.87 |