Prostate Cancer
Conditions
Brief summary
The purpose of this study is to demonstrate the pharmacodynamic equivalence of triptorelin pamoate (Pamorelin® LA 11.25 mg), applied either IM or SC, in terms of the area under the curve \[AUC1-85day\] for serum testosterone in patients with advanced prostate cancer.
Interventions
DRUGTriptorelin Pamoate (Pamorelin® LA 11.25 mg)
Pamorelin® LA 11.25 mg administered as standard IM injection (= reference group) at Day 1 and Day 85. Triptorelin Pamoate (Pamorelin® LA 11.25 mg) applied subcutaneously (s.c.) at Day 1 and Day 85.
Sponsors
Ipsen
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
* Histologically or cytologically proven prostate cancer, locally advanced or metastatic, or rising PSA (prostate-specific antigen) after failed local therapy, and the patient scheduled to receive androgen deprivation therapy * Serum testosterone levels ≥ 125 ng/dl (1.25 ng/ml, 1.25 microg/l, 4.3 nmol/l) measured by any laboratory or on site within the previous 6 months or at study start * Karnofsky performance index \> 70 * Expected survival ≥ 9 months
Exclusion criteria
* Prior hormonal treatment for prostate cancer including gonadotropin-releasing hormone (GnRH) agonists or antagonists within the last 12 months preceding the study or concomitant treatment with one or more of these substance(s) * Any current use or within 6 months prior to treatment start of medications which are known to affect the metabolism and/or secretion of androgenic hormones: ketoconazole, aminoglutethimide, oestrogens and progesterone * Patient at risk of spinal cord compression or ureter obstruction * Prior hypophysectomy or adrenalectomy
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Area Under the Curve of Testosterone Serum Concentration Between D1 and D85 (AUC1-85d). | 1, 3, 5, 8, 15, 22, 29, 57, 85 days post-dose | Area under the curve (AUC) calculated from serum testosterone concentration taken at intervals between the first administration (Day 1) of the study drug and Day 85 after dosing. From the curve describing serum testosterone concentration levels (ng/mL) over time, the AUC was calculated using numerical integration methods. This value was log-transformed to more closely meet the assumption of the statistical method. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Area Under the Curve of Testosterone Serum Concentration Between D85 and D169 (AUC85-169d) | 85, 87, 113, 141 and 169 days post-dose | Area under the curve calculated from serum testosterone concentration taken at intervals between Day 85 and Day 169 after dosing. From the curve describing serum testosterone concentration levels (ng/mL) over time, the AUC was calculated using numerical integration methods. This value was log-transformed to more closely meet the assumption of the statistical method. |
| Maximum Concentration of Serum Testosterone [Cmax] - Raw Data | 1, 3, 5, 8, 15, 22, 29, 57, 85, 87, 113, 141 and 169 days post-dose | Cmax was assessed as the maximum testosterone serum concentration between the first administration of the study drug and Day 169. |
| Area Under the Curve of Testosterone Serum Concentration Between D1 and D169 (AUC1-169d) | 1, 3, 5, 8, 15, 22, 29, 57, 85, 87, 113, 141 and 169 days post-dose | Area under the curve calculated from serum testosterone concentration taken at intervals between the first administration (Day 1) of the study drug and Day 169 after dosing. From the curve describing serum testosterone concentration levels (ng/mL) over time, the AUC was calculated using numerical integration methods. This value was log-transformed to more closely meet the assumption of the statistical method. |
| Time to Castration [Tcast] - Testosterone Level Less Than or Equal to 0.5 ng/mL | 12 weeks | tcast is the number of days between day of first administration of the study drug and the day the testosterone level reaches the limit of castration defined as testosterone level less than or equal to 0.5 ng/mL for the first time. Analysis of tcast was based on the Kaplan-Meier estimator. |
| Time to Castration [Tcast] - Testosterone Level Less Than 0.5 ng/mL | 12 weeks | tcast is the number of days between day of first administration of the study drug and the day the testosterone level reaches the limit of castration defined as testosterone level less than 0.5 ng/mL for the first time. Analysis of tcast was based on the Kaplan-Meier estimator. |
| Maximum Concentration of Serum Testosterone [Cmax] - Log-transformed Data | 1, 3, 5, 8, 15, 22, 29, 57, 85, 87, 113, 141 and 169 days post-dose | Cmax was assessed as the maximum testosterone serum concentration between the first administration of the study drug and Day 169. |
Countries
Germany
Participant flow
Recruitment details
Patients diagnosed with advanced prostate cancer (locally advanced or metastatic, histologically proven) recruited at 23 investigational sites in Germany.
Pre-assignment details
109 patients screened and 6 of these did not fulfil randomisation criteria therefore 103 patients were randomised to either group of treatment with triptorelin pamoate 3-month formulation applied intramuscularly or subcutaneously.
Participants by arm
| Arm | Count |
|---|---|
| Triptorelin Pamoate (Pamorelin® LA 11.25 mg) SC. Subcutaneous (SC) application of triptorelin pamoate (Pamorelin LA 11.25 mg)administered on Day 1 and Day 85. | 52 |
| Triptorelin Pamoate (Pamorelin® LA 11.25 mg) IM. Intramuscular (IM) application of triptorelin pamoate (Pamorelin LA 11.25 mg) administered on Day 1 and Day 85. | 51 |
| Total | 103 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 1 | 1 |
| Overall Study | Death | 1 | 0 |
| Overall Study | Lack of Efficacy | 3 | 3 |
| Overall Study | Protocol Violation | 1 | 1 |
| Overall Study | Withdrawal by Subject | 0 | 1 |
Baseline characteristics
| Characteristic | Triptorelin Pamoate (Pamorelin® LA 11.25 mg) SC. | Triptorelin Pamoate (Pamorelin® LA 11.25 mg) IM. | Total |
|---|---|---|---|
| Age, Continuous | 73.4 years STANDARD_DEVIATION 6.7 | 73.3 years STANDARD_DEVIATION 7 | 73.3 years STANDARD_DEVIATION 6.8 |
| Age, Customized 50 to < 60 years | 2 participants | 2 participants | 4 participants |
| Age, Customized 60 to < 70 years | 10 participants | 11 participants | 21 participants |
| Age, Customized 70 to < 80 years | 30 participants | 31 participants | 61 participants |
| Age, Customized 80 to < 90 years | 10 participants | 7 participants | 17 participants |
| Karnofsky index (%) 100% | 21 participants | 27 participants | 48 participants |
| Karnofsky index (%) 80% | 13 participants | 12 participants | 25 participants |
| Karnofsky index (%) 90% | 18 participants | 12 participants | 30 participants |
| Prostate specific antigen (PSA) level | 47.1 ng/mL STANDARD_DEVIATION 174.9 | 97.2 ng/mL STANDARD_DEVIATION 368 | 71.7 ng/mL STANDARD_DEVIATION 286 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 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 | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 52 Participants | 51 Participants | 103 Participants |
| Sex: Female, Male Female | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Male | 52 Participants | 51 Participants | 103 Participants |
| Testosterone serum level | 3.23 ng/mL STANDARD_DEVIATION 1.28 | 3.12 ng/mL STANDARD_DEVIATION 1.36 | 3.18 ng/mL STANDARD_DEVIATION 1.31 |
| Tumour-related pain | 0.25 cm STANDARD_DEVIATION 0.58 | 0.37 cm STANDARD_DEVIATION 0.99 | 0.31 cm STANDARD_DEVIATION 0.81 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 32 / 52 | 25 / 51 |
| serious Total, serious adverse events | 11 / 52 | 7 / 51 |
Outcome results
Primary
Area Under the Curve of Testosterone Serum Concentration Between D1 and D85 (AUC1-85d).
Area under the curve (AUC) calculated from serum testosterone concentration taken at intervals between the first administration (Day 1) of the study drug and Day 85 after dosing. From the curve describing serum testosterone concentration levels (ng/mL) over time, the AUC was calculated using numerical integration methods. This value was log-transformed to more closely meet the assumption of the statistical method.
Time frame: 1, 3, 5, 8, 15, 22, 29, 57, 85 days post-dose
Population: Analysed from ITT population.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Triptorelin Pamoate (Pamorelin® LA 11.25 mg) SC. | Area Under the Curve of Testosterone Serum Concentration Between D1 and D85 (AUC1-85d). | 4.24 log(ng*day/mL) | Standard Deviation 0.4 |
| Triptorelin Pamoate (Pamorelin® LA 11.25 mg) IM. | Area Under the Curve of Testosterone Serum Concentration Between D1 and D85 (AUC1-85d). | 4.23 log(ng*day/mL) | Standard Deviation 0.5 |
90% CI: [0.88, 1.08]ANCOVA
Secondary
Area Under the Curve of Testosterone Serum Concentration Between D1 and D169 (AUC1-169d)
Area under the curve calculated from serum testosterone concentration taken at intervals between the first administration (Day 1) of the study drug and Day 169 after dosing. From the curve describing serum testosterone concentration levels (ng/mL) over time, the AUC was calculated using numerical integration methods. This value was log-transformed to more closely meet the assumption of the statistical method.
Time frame: 1, 3, 5, 8, 15, 22, 29, 57, 85, 87, 113, 141 and 169 days post-dose
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Triptorelin Pamoate (Pamorelin® LA 11.25 mg) SC. | Area Under the Curve of Testosterone Serum Concentration Between D1 and D169 (AUC1-169d) | 4.49 log(ng*day/mL) | Standard Deviation 0.42 |
| Triptorelin Pamoate (Pamorelin® LA 11.25 mg) IM. | Area Under the Curve of Testosterone Serum Concentration Between D1 and D169 (AUC1-169d) | 4.52 log(ng*day/mL) | Standard Deviation 0.56 |
90% CI: [0.82, 1.06]ANCOVA
Secondary
Area Under the Curve of Testosterone Serum Concentration Between D85 and D169 (AUC85-169d)
Area under the curve calculated from serum testosterone concentration taken at intervals between Day 85 and Day 169 after dosing. From the curve describing serum testosterone concentration levels (ng/mL) over time, the AUC was calculated using numerical integration methods. This value was log-transformed to more closely meet the assumption of the statistical method.
Time frame: 85, 87, 113, 141 and 169 days post-dose
Population: 95 patients (IM: 47 patients, SC: 48 patients) received a second injection of the study drug.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Triptorelin Pamoate (Pamorelin® LA 11.25 mg) SC. | Area Under the Curve of Testosterone Serum Concentration Between D85 and D169 (AUC85-169d) | 2.80 log(ng*day/mL) | Standard Deviation 0.45 |
| Triptorelin Pamoate (Pamorelin® LA 11.25 mg) IM. | Area Under the Curve of Testosterone Serum Concentration Between D85 and D169 (AUC85-169d) | 2.88 log(ng*day/mL) | Standard Deviation 0.38 |
90% CI: [0.81, 1.02]ANCOVA
Secondary
Maximum Concentration of Serum Testosterone [Cmax] - Log-transformed Data
Cmax was assessed as the maximum testosterone serum concentration between the first administration of the study drug and Day 169.
Time frame: 1, 3, 5, 8, 15, 22, 29, 57, 85, 87, 113, 141 and 169 days post-dose
Population: Analysed for intent-to-treat (ITT) population comprised of 103 patients (IM: 51 and SC: 52 patients).
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Triptorelin Pamoate (Pamorelin® LA 11.25 mg) SC. | Maximum Concentration of Serum Testosterone [Cmax] - Log-transformed Data | 1.67 log(ng/mL) | Standard Deviation 0.42 |
| Triptorelin Pamoate (Pamorelin® LA 11.25 mg) IM. | Maximum Concentration of Serum Testosterone [Cmax] - Log-transformed Data | 1.62 log(ng/mL) | Standard Deviation 0.42 |
p-value: 0.8595% CI: [-0.09, 0.11]ANCOVA
Secondary
Maximum Concentration of Serum Testosterone [Cmax] - Raw Data
Cmax was assessed as the maximum testosterone serum concentration between the first administration of the study drug and Day 169.
Time frame: 1, 3, 5, 8, 15, 22, 29, 57, 85, 87, 113, 141 and 169 days post-dose
Population: Analysed for intent-to-treat (ITT) population comprised of 103 patients (IM: 51 and SC: 52 patients).
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Triptorelin Pamoate (Pamorelin® LA 11.25 mg) SC. | Maximum Concentration of Serum Testosterone [Cmax] - Raw Data | 5.74 ng/mL | Standard Deviation 2.33 |
| Triptorelin Pamoate (Pamorelin® LA 11.25 mg) IM. | Maximum Concentration of Serum Testosterone [Cmax] - Raw Data | 5.50 ng/mL | Standard Deviation 2.35 |
Secondary
Time to Castration [Tcast] - Testosterone Level Less Than 0.5 ng/mL
tcast is the number of days between day of first administration of the study drug and the day the testosterone level reaches the limit of castration defined as testosterone level less than 0.5 ng/mL for the first time. Analysis of tcast was based on the Kaplan-Meier estimator.
Time frame: 12 weeks
Population: Analysed for intent-to-treat (ITT) population comprised of 103 patients (IM: 51 and SC: 52 patients).
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Triptorelin Pamoate (Pamorelin® LA 11.25 mg) SC. | Time to Castration [Tcast] - Testosterone Level Less Than 0.5 ng/mL | 22.0 days |
| Triptorelin Pamoate (Pamorelin® LA 11.25 mg) IM. | Time to Castration [Tcast] - Testosterone Level Less Than 0.5 ng/mL | 22.0 days |
p-value: 0.84Log Rank
Secondary
Time to Castration [Tcast] - Testosterone Level Less Than or Equal to 0.5 ng/mL
tcast is the number of days between day of first administration of the study drug and the day the testosterone level reaches the limit of castration defined as testosterone level less than or equal to 0.5 ng/mL for the first time. Analysis of tcast was based on the Kaplan-Meier estimator.
Time frame: 12 weeks
Population: Analysed for intent-to-treat (ITT) population comprised of 103 patients (IM: 51 and SC: 52 patients).
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Triptorelin Pamoate (Pamorelin® LA 11.25 mg) SC. | Time to Castration [Tcast] - Testosterone Level Less Than or Equal to 0.5 ng/mL | 22.0 days |
| Triptorelin Pamoate (Pamorelin® LA 11.25 mg) IM. | Time to Castration [Tcast] - Testosterone Level Less Than or Equal to 0.5 ng/mL | 22.0 days |
p-value: 0.98Log Rank