Advanced Prostate Cancer, Locally Advanced Prostate Cancer, Metastatic Prostate Cancer
Conditions
Brief summary
The main aim of this study is to assess the effectiveness and safety of the 6-month formulation of triptorelin pamoate in Chinese participants with locally advanced or metastatic cancer of the prostate. Participants will receive 1 injection of triptorelin pamoate 6-month formulation.
Interventions
DRUGTriptorelin pamoate (embonate) salt
Triptorelin pamoate 22.5 mg (6-month formulation), i.m. injection, single dose on Day 1.
Sponsors
Ipsen
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
MALE
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
: * Participant is capable of giving signed informed consent * Participant must be over 18 years of age, at the time of signing the informed consent. * Has a histologically or cytologically confirmed adenocarcinoma, locally advanced or metastatic prostate cancer. Or participant has PSA recurrence after curative treatment and be a candidate for androgen deprivation therapy (ADT). * Has serum testosterone level \>150 ng/dL (\> 5.2 nmol/L). * Has expected survival time ≥12 months according to the investigator's assessment. * Has Eastern Cooperative Oncology Group (ECOG) performance status score ≤1
Exclusion criteria
: * Risk of a serious complication in the case of tumour flare * Presence of another neoplastic lesion or brain metastases. * Previous history of QT prolongation or concomitant use of medicinal products known to prolong the QT interval or with a known risk of torsades de pointes. * Metastatic hormone-sensitive prostate cancer with high tumour burden. * Metastatic castration-resistant prostate cancer. * Previous surgical castration. * Previous hormone therapy (including abiraterone) for prostate cancer within 6 months prior to study start. * Previous cytotoxic chemotherapy treatment within 6 months prior to study screening. * Use of finasteride or dutasteride within 2 months prior to study screening. * Previous hypophysectomy or adrenalectomy * Any current use or use 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 antiandrogens. * Current use of systemic or inhaled corticosteroids (topical application permitted). * Any previous use of traditional Chinese medicine or herbal products within 1 month prior to study screening or planned use during the study of products, which are known to have cytotoxic effect or affect the metabolism and/or secretion of androgenic hormones * Participation in another study with an investigational drug or treatment within 3 months prior to study screening or within 5 drug half-lives of the investigational drug (whichever is the longer). * Severe kidney or liver impairment (creatinine \>2 x upper limit of normal (ULN), aspartate aminotransferase (AST) and alanine aminotransferase (ALT) \>3 x ULN). * Any concomitant disorder or resulting therapy that is likely to interfere with participant compliance, the i.m. administration of the drug or with the study in the opinion of the investigator. * Known hypersensitivity to triptorelin or any of its excipients, GnRH, other GnRH agonist/analogues. * Known active use of recreational drug or alcohol dependence in the opinion of the investigator.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants Who Achieved Castrate Levels of Serum Testosterone on Day 29 | Day 29 | Blood samples were collected to determine the serum testosterone concentrations using a validated, specific and sensitive liquid chromatography tandem mass spectrometry (LC-MS/MS) method. Achievement of testosterone castration was defined as serum testosterone level \<50 nanograms per deciliter (ng/dL) or 1.735 nanomoles/liter (nmol/L). Percentages are rounded off to the tenth decimal place. |
| Percentage of Participants Who Maintained the Castrate Levels From Week 8 to Week 24 | From Week 8 to Week 24 | Blood samples were collected to determine the serum testosterone concentrations using a validated, specific and sensitive LC-MS/MS method. Maintenance of castration was defined as serum testosterone level \<50 ng/dL or 1.735 nmol/L. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Time to Maximum Observed Plasma Concentration (Tmax) of Triptorelin Pamoate | Pre-dose, 1, 2, 3, 4, 6, 8, 12, 24, 48, 96 and 168 hours post-dose on Day 1, Days 15, 22, 29, 57, 85, 113, 141 and 169 | Blood samples were collected at specified timepoints for the assessment of tmax of triptorelin pamoate. The PK parameters were performed using non-compartmental analysis. |
| Maximum Observed Plasma Concentration (Cmax) of Triptorelin Pamoate | Pre-dose, 1, 2, 3, 4, 6, 8, 12, 24, 48, 96 and 168 hours post-dose on Day 1, Days 15, 22, 29, 57, 85, 113, 141 and 169 | Blood samples were collected at specified timepoints for the assessment of Cmax of triptorelin pamoate. The PK parameters were performed using non-compartmental analysis. |
| Area Under the Plasma Concentration Time Curve From Time 0 to the Visit on Day 169 (AUC0-169) of Triptorelin Pamoate | Pre-dose, 1, 2, 3, 4, 6, 8, 12, 24, 48, 96 and 168 hours post-dose on Day 1, Days 15, 22, 29, 57, 85, 113, 141 and 169 | Blood samples were collected at specified timepoints for the assessment of AUC0-169 of triptorelin pamoate. The PK parameters were performed using non-compartmental analysis. |
| Area Under the Plasma Concentration Time Curve From Time 0 to the Last Quantifiable Concentration (AUClast) of Triptorelin Pamoate | Pre-dose, 1, 2, 3, 4, 6, 8, 12, 24, 48, 96 and 168 hours post-dose on Day 1, Days 15, 22, 29, 57, 85, 113, 141 and 169 | Blood samples were collected at specified timepoints for the assessment of AUClast of triptorelin pamoate. The PK parameters were performed using non-compartmental analysis. |
| Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Treatment-Emergent Serious Adverse Events (TESAEs) and Treatment-Emergent Adverse Events of Local Tolerance | From the first dose of study intervention (Day 1) up to end of study visit (Week 24), approximately 169 days | An AE was any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. An SAE was any untoward medical occurrence that, at any dose, resulted in death, was life-threatening, required inpatient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity, was a congenital abnormality/birth defect, or any other medically important event. TEAEs were AEs with start date on or after the date of study intervention administration and up to 24 weeks after date of first dose of treatment. Local tolerance was assessed 2 hours (+/-15 minutes) after the single injection of 6-month formulation triptorelin by examination of injection site for signs including but not limited to tenderness, erythema, swelling, hematoma, rash, pain, itching and induration. |
| Maximum Observed Plasma Concentration of Testosterone | Pre-dose on Day 1 and Days 2, 3, 5, 8, 15, 22, 29, 57, 85, 113, 141 and 169 | Blood samples were collected at specified timepoints for the assessment of Cmax of testosterone. The PD parameters were performed using non-compartmental analysis. |
| Time to Castration of Testosterone | Pre-dose on Day 1 and Days 2, 3, 5, 8, 15, 22, 29, 57, 85, 113, 141 and 169 | Blood samples were collected at specified timepoints for the assessment of tcast of testosterone. tcast was defined as time to reach serum testosterone level \<50 ng/dL or 1.735 nmol/L. The PD parameters were performed using non-compartmental analysis. |
| Plasma Concentrations of Triptorelin Pamoate | Pre-dose on Day 1 and post-dose at Weeks 4, 8, 12, 16, 20 and 24 | Blood samples were collected at specified timepoints for the assessment of plasma concentration of triptorelin pamoate. |
| Serum Concentrations of Testosterone | Pre-dose on Day 1 and post-dose at Weeks 4, 8, 12, 16, 20 and 24 | Blood samples were collected at specified timepoints for the assessment of serum concentration of testosterone. |
| Time to Maximum Observed Plasma Concentration of Testosterone | Pre-dose on Day 1 and Days 2, 3, 5, 8, 15, 22, 29, 57, 85, 113, 141 and 169 | Blood samples were collected at specified timepoints for the assessment of tmax of testosterone. The PD parameters were performed using non-compartmental analysis. |
| Percent Change From Baseline in Prostate Specific Antigen (PSA) at Weeks 12 and 24 | Baseline (Day 1), Weeks 12 and 24 | Blood samples were collected for the measurement of plasma PSA concentrations. Percent change in PSA was defined as the absolute value of difference between the PSA values at Week 12 and Week 24 and the baseline value divided by the baseline value. Baseline was defined as the last non-missing measurement taken prior to first study intervention administration. |
Countries
China
Participant flow
Recruitment details
This Phase IIIb, open-label, single arm study was conducted at 27 investigational sites in participants with locally advanced or metastatic prostate cancer.
Pre-assignment details
The study consisted of a 4-week screening period, single dose study intervention administration on Day 1 and an end of study on Day 169. A subset of participants had a more extensive sampling during the study to evaluate pharmacokinetics (PK) and pharmacodynamics (PD). A total of 195 participants were enrolled in the study.
Participants by arm
| Arm | Count |
|---|---|
| Triptorelin Pamoate Participants received a single dose of triptorelin pamoate 22.5 mg IM injection on Day 1. | 195 |
| Total | 195 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Physician Decision | 1 |
| Overall Study | Withdrawal by Subject | 6 |
Baseline characteristics
| Characteristic | Triptorelin Pamoate |
|---|---|
| Age, Continuous | 70.8 years STANDARD_DEVIATION 8.3 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 195 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race/Ethnicity, Customized Asian | 195 Participants |
| Sex: Female, Male Female | 0 Participants |
| Sex: Female, Male Male | 195 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 195 |
| other Total, other adverse events | 90 / 195 |
| serious Total, serious adverse events | 8 / 195 |
Outcome results
Primary
Percentage of Participants Who Achieved Castrate Levels of Serum Testosterone on Day 29
Blood samples were collected to determine the serum testosterone concentrations using a validated, specific and sensitive liquid chromatography tandem mass spectrometry (LC-MS/MS) method. Achievement of testosterone castration was defined as serum testosterone level \<50 nanograms per deciliter (ng/dL) or 1.735 nanomoles/liter (nmol/L). Percentages are rounded off to the tenth decimal place.
Time frame: Day 29
Population: The full analysis set (FAS) included all treated participants who completed the study or were a treatment failure.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Triptorelin Pamoate | Percentage of Participants Who Achieved Castrate Levels of Serum Testosterone on Day 29 | 99.5 percentage of participants |
Primary
Percentage of Participants Who Maintained the Castrate Levels From Week 8 to Week 24
Blood samples were collected to determine the serum testosterone concentrations using a validated, specific and sensitive LC-MS/MS method. Maintenance of castration was defined as serum testosterone level \<50 ng/dL or 1.735 nmol/L.
Time frame: From Week 8 to Week 24
Population: The FAS included all treated participants who completed the study or were a treatment failure.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Triptorelin Pamoate | Percentage of Participants Who Maintained the Castrate Levels From Week 8 to Week 24 | 100 percentage of participants |
Secondary
Area Under the Plasma Concentration Time Curve From Time 0 to the Last Quantifiable Concentration (AUClast) of Triptorelin Pamoate
Blood samples were collected at specified timepoints for the assessment of AUClast of triptorelin pamoate. The PK parameters were performed using non-compartmental analysis.
Time frame: Pre-dose, 1, 2, 3, 4, 6, 8, 12, 24, 48, 96 and 168 hours post-dose on Day 1, Days 15, 22, 29, 57, 85, 113, 141 and 169
Population: The rich PK analysis set included all participants in the rich PK/PD subset who received 1 dose of study intervention, had no major protocol deviations affecting the PK variables, and who had a sufficient number of plasma concentrations to estimate the main PK parameters (Cmax, tmax and AUC).
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Triptorelin Pamoate | Area Under the Plasma Concentration Time Curve From Time 0 to the Last Quantifiable Concentration (AUClast) of Triptorelin Pamoate | 46.3 ng*day/mL | Standard Deviation 22.1 |
Secondary
Area Under the Plasma Concentration Time Curve From Time 0 to the Visit on Day 169 (AUC0-169) of Triptorelin Pamoate
Blood samples were collected at specified timepoints for the assessment of AUC0-169 of triptorelin pamoate. The PK parameters were performed using non-compartmental analysis.
Time frame: Pre-dose, 1, 2, 3, 4, 6, 8, 12, 24, 48, 96 and 168 hours post-dose on Day 1, Days 15, 22, 29, 57, 85, 113, 141 and 169
Population: The rich PK analysis set included all participants in the rich PK/PD subset who received 1 dose of study intervention, had no major protocol deviations affecting the PK variables, and who had a sufficient number of plasma concentrations to estimate the main PK parameters (Cmax, tmax and AUC). Only those participants with data collected at specified timepoints are reported.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Triptorelin Pamoate | Area Under the Plasma Concentration Time Curve From Time 0 to the Visit on Day 169 (AUC0-169) of Triptorelin Pamoate | 51.7 ng*day/mL | Standard Deviation 22.9 |
Secondary
Maximum Observed Plasma Concentration (Cmax) of Triptorelin Pamoate
Blood samples were collected at specified timepoints for the assessment of Cmax of triptorelin pamoate. The PK parameters were performed using non-compartmental analysis.
Time frame: Pre-dose, 1, 2, 3, 4, 6, 8, 12, 24, 48, 96 and 168 hours post-dose on Day 1, Days 15, 22, 29, 57, 85, 113, 141 and 169
Population: The rich PK analysis set included all participants in the rich PK/PD subset who received 1 dose of study intervention, had no major protocol deviations affecting the PK variables, and who had a sufficient number of plasma concentrations to estimate the main PK parameters (Cmax, tmax and AUC).
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Triptorelin Pamoate | Maximum Observed Plasma Concentration (Cmax) of Triptorelin Pamoate | 44.5 ng/milliliter (mL) | Standard Deviation 17.5 |
Secondary
Maximum Observed Plasma Concentration of Testosterone
Blood samples were collected at specified timepoints for the assessment of Cmax of testosterone. The PD parameters were performed using non-compartmental analysis.
Time frame: Pre-dose on Day 1 and Days 2, 3, 5, 8, 15, 22, 29, 57, 85, 113, 141 and 169
Population: The rich PD analysis set included all participants in the rich PK/PD subset who had a sufficient number of PD (testosterone) measurements to estimate the main PD parameters (Cmax, tmax and tcast).
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Triptorelin Pamoate | Maximum Observed Plasma Concentration of Testosterone | 21.9 nmol/L | Standard Deviation 6.55 |
Secondary
Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Treatment-Emergent Serious Adverse Events (TESAEs) and Treatment-Emergent Adverse Events of Local Tolerance
An AE was any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. An SAE was any untoward medical occurrence that, at any dose, resulted in death, was life-threatening, required inpatient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity, was a congenital abnormality/birth defect, or any other medically important event. TEAEs were AEs with start date on or after the date of study intervention administration and up to 24 weeks after date of first dose of treatment. Local tolerance was assessed 2 hours (+/-15 minutes) after the single injection of 6-month formulation triptorelin by examination of injection site for signs including but not limited to tenderness, erythema, swelling, hematoma, rash, pain, itching and induration.
Time frame: From the first dose of study intervention (Day 1) up to end of study visit (Week 24), approximately 169 days
Population: The safety set included all participants who received the single dose of study intervention.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Triptorelin Pamoate | Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Treatment-Emergent Serious Adverse Events (TESAEs) and Treatment-Emergent Adverse Events of Local Tolerance | Any TEAEs | 160 Participants |
| Triptorelin Pamoate | Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Treatment-Emergent Serious Adverse Events (TESAEs) and Treatment-Emergent Adverse Events of Local Tolerance | Any TESAEs | 8 Participants |
| Triptorelin Pamoate | Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Treatment-Emergent Serious Adverse Events (TESAEs) and Treatment-Emergent Adverse Events of Local Tolerance | TEAEs of Local Tolerance | 7 Participants |
Secondary
Percent Change From Baseline in Prostate Specific Antigen (PSA) at Weeks 12 and 24
Blood samples were collected for the measurement of plasma PSA concentrations. Percent change in PSA was defined as the absolute value of difference between the PSA values at Week 12 and Week 24 and the baseline value divided by the baseline value. Baseline was defined as the last non-missing measurement taken prior to first study intervention administration.
Time frame: Baseline (Day 1), Weeks 12 and 24
Population: The FAS included all treated participants who completed the study or were a treatment failure. Only participants with data collected at specified timepoints are reported.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Triptorelin Pamoate | Percent Change From Baseline in Prostate Specific Antigen (PSA) at Weeks 12 and 24 | Week 12 | -90.6815 percent change | Standard Deviation 10.8057 |
| Triptorelin Pamoate | Percent Change From Baseline in Prostate Specific Antigen (PSA) at Weeks 12 and 24 | Week 24 | -92.1673 percent change | Standard Deviation 12.2853 |
Secondary
Plasma Concentrations of Triptorelin Pamoate
Blood samples were collected at specified timepoints for the assessment of plasma concentration of triptorelin pamoate.
Time frame: Pre-dose on Day 1 and post-dose at Weeks 4, 8, 12, 16, 20 and 24
Population: The population PK analysis set included all participants who received 1 dose of triptorelin and who had at least 1 triptorelin plasma concentration and no major protocol deviations affecting PK variables. Only participants with data collected at specified timepoints are reported.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Triptorelin Pamoate | Plasma Concentrations of Triptorelin Pamoate | Day 1 | NA ng/mL | — |
| Triptorelin Pamoate | Plasma Concentrations of Triptorelin Pamoate | Week 4 | 0.0743 ng/mL | Standard Deviation 0.0342 |
| Triptorelin Pamoate | Plasma Concentrations of Triptorelin Pamoate | Week 8 | 0.1236 ng/mL | Standard Deviation 0.0536 |
| Triptorelin Pamoate | Plasma Concentrations of Triptorelin Pamoate | Week 12 | 0.0602 ng/mL | Standard Deviation 0.0551 |
| Triptorelin Pamoate | Plasma Concentrations of Triptorelin Pamoate | Week 16 | 0.1555 ng/mL | Standard Deviation 0.0974 |
| Triptorelin Pamoate | Plasma Concentrations of Triptorelin Pamoate | Week 20 | 0.0607 ng/mL | Standard Deviation 0.0401 |
| Triptorelin Pamoate | Plasma Concentrations of Triptorelin Pamoate | Week 24 | 0.0249 ng/mL | Standard Deviation 0.0225 |
Secondary
Serum Concentrations of Testosterone
Blood samples were collected at specified timepoints for the assessment of serum concentration of testosterone.
Time frame: Pre-dose on Day 1 and post-dose at Weeks 4, 8, 12, 16, 20 and 24
Population: The FAS included all treated participants who completed the study or were a treatment failure. Only participants with data collected at specified timepoints are reported.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Triptorelin Pamoate | Serum Concentrations of Testosterone | Day 1 | 17.0506 nmol/L | Standard Deviation 7.0323 |
| Triptorelin Pamoate | Serum Concentrations of Testosterone | Week 4 | 0.5602 nmol/L | Standard Deviation 0.2749 |
| Triptorelin Pamoate | Serum Concentrations of Testosterone | Week 8 | 0.3294 nmol/L | Standard Deviation 0.1513 |
| Triptorelin Pamoate | Serum Concentrations of Testosterone | Week 12 | 0.3281 nmol/L | Standard Deviation 0.1416 |
| Triptorelin Pamoate | Serum Concentrations of Testosterone | Week 16 | 0.3334 nmol/L | Standard Deviation 0.1539 |
| Triptorelin Pamoate | Serum Concentrations of Testosterone | Week 20 | 0.3404 nmol/L | Standard Deviation 0.158 |
| Triptorelin Pamoate | Serum Concentrations of Testosterone | Week 24 | 0.3828 nmol/L | Standard Deviation 0.1899 |
Secondary
Time to Castration of Testosterone
Blood samples were collected at specified timepoints for the assessment of tcast of testosterone. tcast was defined as time to reach serum testosterone level \<50 ng/dL or 1.735 nmol/L. The PD parameters were performed using non-compartmental analysis.
Time frame: Pre-dose on Day 1 and Days 2, 3, 5, 8, 15, 22, 29, 57, 85, 113, 141 and 169
Population: The rich PD analysis set included all participants in the rich PK/PD subset who had a sufficient number of PD (testosterone) measurements to estimate the main PD parameters (Cmax, tmax and tcast).
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Triptorelin Pamoate | Time to Castration of Testosterone | 19.3 day |
Secondary
Time to Maximum Observed Plasma Concentration of Testosterone
Blood samples were collected at specified timepoints for the assessment of tmax of testosterone. The PD parameters were performed using non-compartmental analysis.
Time frame: Pre-dose on Day 1 and Days 2, 3, 5, 8, 15, 22, 29, 57, 85, 113, 141 and 169
Population: The rich PD analysis set included all participants in the rich PK/PD subset who had a sufficient number of PD (testosterone) measurements to estimate the main PD parameters (Cmax, tmax and time to castration \[tcast\]).
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Triptorelin Pamoate | Time to Maximum Observed Plasma Concentration of Testosterone | 2.00 day |
Secondary
Time to Maximum Observed Plasma Concentration (Tmax) of Triptorelin Pamoate
Blood samples were collected at specified timepoints for the assessment of tmax of triptorelin pamoate. The PK parameters were performed using non-compartmental analysis.
Time frame: Pre-dose, 1, 2, 3, 4, 6, 8, 12, 24, 48, 96 and 168 hours post-dose on Day 1, Days 15, 22, 29, 57, 85, 113, 141 and 169
Population: The rich PK analysis set included all participants in the rich PK/PD subset who received 1 dose of study intervention, had no major protocol deviations affecting the PK variables, and who had a sufficient number of plasma concentrations to estimate the main PK parameters (maximum observed plasma drug concentration \[Cmax\], tmax and area under the plasma concentration time curve \[AUC\]).
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Triptorelin Pamoate | Time to Maximum Observed Plasma Concentration (Tmax) of Triptorelin Pamoate | 2.95 hour |