Prostatic Adenoma
Conditions
Brief summary
The purpose of this study is to assess the safety and efficacy of teverelix TFA in the treatment of advanced prostate cancer
Detailed description
After being informed about the study and potential risks, all patients giving written informed consent will undergo an up to 7 day screening period to determine eligibility for study entry. On Day 0, patients who meet the eligibility requirements will be enrolled in an open-label manner and will receive a loading dose of teverelix TFA (one subcutaneous (SC) injection in the abdomen and one intramuscular (IM) injection in the buttock). Patients will then receive maintenance doses of teverelix TFA (one SC injection in the abdomen) at 4- or 6-weekly intervals up to week 24. The patients will return for a final assessment 4 weeks after their last maintenance dose injection. The initial dosing regimen to be tested (Group 1) is: Loading Dose = 120 mg teverelix TFA SC + 120 mg teverelix TFA IM Maintenance Dose = 120 mg teverelix TFA SC every 6 weeks If this dosing regimen is unsuccessful (more than 2 (of 20) patients fail treatment) then recruitment to Group 1 will end and enrollment in Group 2 will open. The dosing regimen that may be tested (Group 2) is: Loading Dose = 180 mg teverelix TFA SC + 180 mg teverelix TFA IM Maintenance Dose = 180 mg teverelix TFA SC every 6 weeks If this dosing regimen is unsuccessful (more than 6 (of 60) patients fail treatment) then recruitment to Group 2 will end and the study will be terminated.
Interventions
DRUGteverelix TFA 120 mg
Teverelix TFA 240 mg Day 0 and 120 mg every 6 weeks from week 6 to week 24
DRUGteverelix TFA 180 mg
Teverelix TFA 360 mg Day 0 and 180 mg every 6 weeks from week 6 to week 24
Sponsors
Antev Ltd.
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
Adaptive design - enrollment will open in Group 1 (6-weekly dosing regimen). Only if Group 1 dosing regimen is unsuccessful will enrollment open in Group 2 (4-weekly dosing regimen)
Eligibility
Sex/Gender
MALE
Age
18 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
* Is male, aged ≤80 years (≥18 years) at the beginning of the treatment period (Day 0) * Has histologically proven advanced adenocarcinoma of the prostate (metastatic or non metastatic hormone-sensitive non curative), suitable for ADT * Is treatment naïve for any of the following: a. GnRH analogues b. Androgen receptor antagonists, or c. Androgen synthesis inhibitors (e.g. abiraterone) * Agrees to practice contraception during the entire study treatment period and for 3 months after the last dose of IMP is administered: a. Either by using double barrier contraception, b. or, is truly sexually abstinent, when this is in line with the preferred and usual lifestyle of the participant * Has provided written (personally signed and dated) informed consent before completing any study-related procedure, which means any assessment or evaluation that would not have formed a part of his normal medical care
Exclusion criteria
* Has abnormal screening and/or baseline laboratory values that suggest a clinically significant underlying disease, or the following laboratory values: a. Liver function test (aspartate aminotransferase \[ASAT/SGOT\], alanine aminotransferase \[ALAT/SGPT\]), or total bilirubin exceeding twice the upper limit of the normal (ULN) range b. Creatinine twice the ULN range c. Uncontrolled diabetes (HbA1c \>7.5%) or previously undiagnosed diabetes mellitus with HbA1c \>6.5% * Has any contraindication to the use of teverelix TFA * Has life expectancy of less than 1 year * Has T levels \<2.0 ng/mL at screening * Has a medical history of bilateral orchidectomy * Using any of the following prohibited treatments: a. Within 25 weeks prior to screening: dutasteride b. Within 12 weeks prior to screening: finasteride c. Current use of any of the following: i. Anti-androgen therapy, including T replacement therapy and 5α-reductase inhibitor treatment etc. ii. GnRH analogues, androgen receptor antagonists iii. Androgen synthesis inhibitors (e.g. abiraterone) iv. Any other medication or herbal product that may affect hormone levels and might, therefore, confound interpretation of the study results (e.g. St. John's wort) * Has neurological disease, psychiatric disease, drug or alcohol abuse, which could interfere with the participant's proper compliance * Has a history of myocardial infarction, unstable symptomatic ischaemic heart disease, any ongoing cardiac arrhythmias of grade \>2 (chronic stable atrial fibrillation on stable anticoagulant therapy is allowed), thromboembolic events (e.g. deep vein thrombosis, pulmonary embolism, or symptomatic cerebrovascular events), or any other significant cardiac condition (e.g. pericardial effusion, restrictive cardiomyopathy) within 6 months before screening * Has congenital long QT syndrome or ECG abnormalities at screening of: a. Q-wave infarction, unless identified ≥6 months before screening b. Fridericia corrected QT interval (QTcF interval) \>480 msec. If QTcF is prolonged in a participant with a pacemaker, the participant may be enrolled in the study upon discussion with the project clinician c. If the QTcF interval is 450-480 msec, inclusive, in a participant with current use of medications with known effects on QT interval, the participant may be enrolled in the study following discussion with the Medical Lead * Has known or suspected severe renal impairment * Has a medical history of diagnosis of, or treatment for, another malignancy within 2 years before the first dose of IMP, or previous diagnosis of another malignancy with evidence of residual disease. Participants with nonmelanoma skin cancer or carcinoma in situ of any type are not excluded if they have undergone complete resection * Is currently using Class IA (e.g. quinidine, procainamide) or Class III (e.g. amiodarone, sotalol) antiarrhythmic medications * Has uncontrolled hypertension despite appropriate medical therapy (sitting BP of \>180 millimetres of mercury \[mmHg\] systolic and \>95 mmHg diastolic at 2 separate measurements taken no more than 60 minutes apart during the screening visit). Participants with isolated systolic BP measurements \>180 mmHg may be rescreened. Participants with isolated systolic BP measurements 141 to 180 mmHg or isolated diastolic BP measurements ≥95 mmHg, although eligible, should be referred for further management of hypertension if indicated * Has known, previously diagnosed human immunodeficiency virus (HIV) infection, active chronic hepatitis B or C, life-threatening illness unrelated to prostate cancer, or any serious medical condition that could, in the investigator's opinion, potentially interfere with participation in this study. Specific screening for chronic viral illness is at the discretion of the site and/or local Institutional Review Board (IRB) * Has been exposed to another investigational drug within the 3 months prior to screening * Has anticipated non-availability for study visits/procedures * Plans to undergo surgery during the study period * Known presence of hepatic metastases
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Testosterone (T) Levels (Castrate) at Week 4 | 4 weeks | Proportion of participants achieving castration level with serum T \<0.5 ng/mL at Day 28. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Testosterone (T) Levels (Castrate) at Week 6 | 6 weeks | Proportion of participants achieving castration level with serum T \<0.5 ng/mL at Day 42 |
| Testosterone (T) Levels (0.2 ng/mL) at Week 6 | 6 weeks | Proportion of participants achieving profound castration level (0.2 ng/mL) with serum T \<0.5 ng/mL at Day 42 |
| Testosterone Levels (Castrate) at Week 24 | 24 weeks | Proportion of participants achieving a T castration rate over 168 days of treatment period |
| Testosterone Levels (0.2 ng/mL) at Week 24 | 24 weeks | Proportion of participants achieving profound castration rate (\<0.2 ng/mL) over 168 days of treatment period |
| Time to Achieve Castrate Levels of Testosterone (T) | 4 weeks | Mean time to T levels falling below castration level (\<0.5 ng/mL) for the first time |
| Time to Escape Castrate Levels of Testosterone (T) | Approximately 30 weeks | Mean time to (first) overstep of T castration level after achieving castration |
| Luteinizing Hormone (LH) Levels (Castrate) at Week 4 | 4 weeks | Proportion of participants achieving castration level for LH (LH \<1.1 U/L) at Day 28 |
| Luteinizing Hormone (LH) Levels (Castrate) at Week 24 | 24 weeks | Proportion of participants with effective LH castration rate over 168 days of treatment period |
| Time to Achieve Castrate Levels of Luteinizing Hormone (LH) | 4 weeks | Mean time to LH levels falling below castration level (LH \<1.1 U/L) for the first time |
| Time to Escape Castrate Levels of Luteinizing Hormone (LH) | 24 weeks | Mean time to (first) overstep of LH castration level after achieving castration |
| Change in Testosterone Levels Over Time (Change From Baseline at Day 168) | 24 weeks | The change in testosterone levels over time (Change from Baseline at Day 168) |
| Change in LH Levels Over Time | 24 weeks | The change in LH levels over time |
| Change in FSH Levels Over Time | 24 weeks | The change in FSH levels over time |
| Area Under the Concentration Time-curve From Time Zero up to the Last Quantifiable Concentration at Time Point t (AUC0-t) | 24 weeks | Area under the concentration time-curve from time zero up to the last quantifiable concentration at time point t (Ct), calculated using the linear up/log down trapezoidal rule. |
| Area Under the Concentration Time-curve From Time Zero up to the Concentration at Time Point t1 After Which the Concentrations Start to Rise Again Towards a Second Peak (AUC0-t1) | 24 weeks | Area under the concentration time-curve from time zero up to the concentration at time point t1 after which the concentrations start to rise again towards a second peak, calculated using the linear up/log down trapezoidal rule. t1 will be determined after review of the concentration-time profiles (immediate release component of total observed AUC). |
| Maximum Observed Plasma Teverelix Concentration After Administration (Cmax) | 24 weeks | The maximum observed plasma teverelix concentration after administration (Cmax) |
| Testosterone (T) Levels (0.2 ng/mL) at Week 4 | 4 weeks | Proportion of participants achieving castration level with serum T \<0.2 ng/mL at Day 28 |
| Maximum Observed Concentration After Administration From Time Point t1 up to Time Point t (Cmax,t1-t) | 24 weeks | The maximum observed concentration after administration from time point t1 up to time point t (Cmax,t1-t) |
| Time to Reach Cmax After Dosing (Tmax) | 24 weeks | The time to reach Cmax after dosing (tmax) |
| Time to Reach Cmax,0-t1 After Dosing (Tmax,0-t1) | 24 weeks | The time to reach Cmax,0-t1 after dosing (tmax,0-t1) |
| Time to Reach Cmax,t1-t After Dosing (Tmax,t1-t) | 24 weeks | The time to reach Cmax,t1-t after dosing (tmax,t1-t) |
| Apparent Terminal Elimination Rate Constant (Lambda-z) | 24 weeks | The apparent terminal elimination rate constant (lambda-z) |
| Apparent Terminal Plasma Half-life (t½) | 24 weeks | Apparent terminal plasma half-life, calculated as: ln 2 / lambda-z |
| Area Under the Concentration Time-curve From Time Zero up to Infinity (∞)(AUC0-∞) | 24 weeks | Area under the concentration time-curve from time zero up to infinity (∞),calculated using the linear up/log down trapezoidal rule. |
| Prostate Specific Antigen (PSA) Reduction (≥50 Percent) | 24 weeks | Number of participants with a PSA response of ≥50 percent reduction at the Day 168 visit |
| PSA Response Rate at Day 28 | 24 weeks | PSA response is defined as \>50% decline in PSA at Day 28. PSA response rate is the number of subjects with a PSA response. |
| PSA Response ≥50% at Day 168 | 24 weeks | The number of subjects with a PSA response ≥50% at Day 168 |
| Luteinizing Hormone (LH) Mean % Reduction at Day 168 | 24 weeks | Luteinizing Hormone (LH) - the mean % reduction at Day 168 |
| Testosterone (T) Mean % Reduction at Day 168 | 24 weeks | Testosterone (T) - the mean % reduction at Day 168 |
| Follicle Stimulating Hormone (FSH) Mean % Reduction at Day 168 | 24 weeks | Follicle Stimulating Hormone (FSH) - the mean % reduction at Day 168 |
| Treatment-emergent Adverse Events (AEs) | 24 weeks | Number of participants with treatment-emergent AEs |
| ECG QTcF Interval Prolongation >450 Msec at Day 28 | 24 weeks | ECG QTcF Interval prolongation \>450 msec at Day 28 study visit |
| Injection Site Reactions (ISRs) | 24 weeks | Number of participants with ISRs at each visit during the 168 days treatment period |
| Maximum Observed Concentration After Administration From Zero up to Time Point t1 (Cmax,0-t1) | 24 weeks | The maximum observed concentration after administration from zero up to time point t1 (Cmax,0-t1) |
Countries
Lithuania
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Teverelix TFA 120 mg 6-weekly Participants receive teverelix TFA loading dose on Day 0 (120 mg SC + 120 mg IM) and teverelix TFA maintenance doses of 120 mg SC at week 6 and 6-weekly thereafter up to week 24
teverelix TFA 120 mg: Teverelix TFA 240 mg Day 0 and 120 mg every 6 weeks from week 6 to week 24 | 9 |
| Teverelix TFA 180 mg 6-weekly Participants receive teverelix TFA loading dose on Day 0 (180 mg SC + 180 mg IM) and teverelix TFA maintenance doses of 180 mg SC at week 6 and 6-weekly thereafter up to week 24
teverelix TFA 180 mg: Teverelix TFA 360 mg Day 0 and 180 mg every 6 weeks from week 6 to week 24 | 41 |
| Total | 50 |
Baseline characteristics
| Characteristic | Teverelix TFA 120 mg 6-weekly | Teverelix TFA 180 mg 6-weekly | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 7 Participants | 32 Participants | 39 Participants |
| Age, Categorical Between 18 and 65 years | 2 Participants | 9 Participants | 11 Participants |
| Age, Continuous | 69.0 years STANDARD_DEVIATION 5.12 | 69.0 years STANDARD_DEVIATION 7.33 | 69.0 years STANDARD_DEVIATION 6.94 |
| Race/Ethnicity, Customized American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Asian | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Black or African American | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized White | 9 Participants | 41 Participants | 50 Participants |
| Region of Enrollment Lithuania | 9 Participants | 41 Participants | 50 Participants |
| Sex: Female, Male Female | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Male | 9 Participants | 41 Participants | 50 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 9 | 1 / 41 |
| other Total, other adverse events | 8 / 9 | 38 / 41 |
| serious Total, serious adverse events | 1 / 9 | 1 / 41 |
Outcome results
Primary
Testosterone (T) Levels (Castrate) at Week 4
Proportion of participants achieving castration level with serum T \<0.5 ng/mL at Day 28.
Time frame: 4 weeks
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Teverelix TFA 120 mg 6-weekly | Testosterone (T) Levels (Castrate) at Week 4 | 5 Participants |
| Teverelix TFA 180 mg 6-weekly | Testosterone (T) Levels (Castrate) at Week 4 | 39 Participants |
Secondary
Apparent Terminal Elimination Rate Constant (Lambda-z)
The apparent terminal elimination rate constant (lambda-z)
Time frame: 24 weeks
Population: Per Protocol
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Teverelix TFA 120 mg 6-weekly | Apparent Terminal Elimination Rate Constant (Lambda-z) | 0 L/h |
| Teverelix TFA 180 mg 6-weekly | Apparent Terminal Elimination Rate Constant (Lambda-z) | 0 L/h |
Secondary
Apparent Terminal Plasma Half-life (t½)
Apparent terminal plasma half-life, calculated as: ln 2 / lambda-z
Time frame: 24 weeks
Population: Per Protocol
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Teverelix TFA 120 mg 6-weekly | Apparent Terminal Plasma Half-life (t½) | 1380.3 hours |
| Teverelix TFA 180 mg 6-weekly | Apparent Terminal Plasma Half-life (t½) | 1103.1 hours |
Secondary
Area Under the Concentration Time-curve From Time Zero up to Infinity (∞)(AUC0-∞)
Area under the concentration time-curve from time zero up to infinity (∞),calculated using the linear up/log down trapezoidal rule.
Time frame: 24 weeks
Population: Per Protocol
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Teverelix TFA 120 mg 6-weekly | Area Under the Concentration Time-curve From Time Zero up to Infinity (∞)(AUC0-∞) | 24888 h*ng/mL |
| Teverelix TFA 180 mg 6-weekly | Area Under the Concentration Time-curve From Time Zero up to Infinity (∞)(AUC0-∞) | 35794 h*ng/mL |
Secondary
Area Under the Concentration Time-curve From Time Zero up to the Concentration at Time Point t1 After Which the Concentrations Start to Rise Again Towards a Second Peak (AUC0-t1)
Area under the concentration time-curve from time zero up to the concentration at time point t1 after which the concentrations start to rise again towards a second peak, calculated using the linear up/log down trapezoidal rule. t1 will be determined after review of the concentration-time profiles (immediate release component of total observed AUC).
Time frame: 24 weeks
Population: Per Protocol
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Teverelix TFA 120 mg 6-weekly | Area Under the Concentration Time-curve From Time Zero up to the Concentration at Time Point t1 After Which the Concentrations Start to Rise Again Towards a Second Peak (AUC0-t1) | 1324.3 h*ng/mL |
| Teverelix TFA 180 mg 6-weekly | Area Under the Concentration Time-curve From Time Zero up to the Concentration at Time Point t1 After Which the Concentrations Start to Rise Again Towards a Second Peak (AUC0-t1) | 1759.3 h*ng/mL |
Secondary
Area Under the Concentration Time-curve From Time Zero up to the Last Quantifiable Concentration at Time Point t (AUC0-t)
Area under the concentration time-curve from time zero up to the last quantifiable concentration at time point t (Ct), calculated using the linear up/log down trapezoidal rule.
Time frame: 24 weeks
Population: Per Protocol
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Teverelix TFA 120 mg 6-weekly | Area Under the Concentration Time-curve From Time Zero up to the Last Quantifiable Concentration at Time Point t (AUC0-t) | 16007 h*ng/mL |
| Teverelix TFA 180 mg 6-weekly | Area Under the Concentration Time-curve From Time Zero up to the Last Quantifiable Concentration at Time Point t (AUC0-t) | 27511 h*ng/mL |
Secondary
Change in FSH Levels Over Time
The change in FSH levels over time
Time frame: 24 weeks
Population: Per Protocol
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Teverelix TFA 120 mg 6-weekly | Change in FSH Levels Over Time | -71.8909 IU/L | Standard Deviation 12.83868 |
| Teverelix TFA 180 mg 6-weekly | Change in FSH Levels Over Time | -82.3272 IU/L | Standard Deviation 12.6762 |
Secondary
Change in LH Levels Over Time
The change in LH levels over time
Time frame: 24 weeks
Population: Per Protocol
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Teverelix TFA 120 mg 6-weekly | Change in LH Levels Over Time | -69.8825 IU/L | Standard Deviation 22.99177 |
| Teverelix TFA 180 mg 6-weekly | Change in LH Levels Over Time | -83.3425 IU/L | Standard Deviation 26.87486 |
Secondary
Change in Testosterone Levels Over Time (Change From Baseline at Day 168)
The change in testosterone levels over time (Change from Baseline at Day 168)
Time frame: 24 weeks
Population: Per Protocol
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Teverelix TFA 120 mg 6-weekly | Change in Testosterone Levels Over Time (Change From Baseline at Day 168) | -16.68 nmol/L | Standard Deviation 5.43 |
| Teverelix TFA 180 mg 6-weekly | Change in Testosterone Levels Over Time (Change From Baseline at Day 168) | -20.26 nmol/L | Standard Deviation 7.37 |
Secondary
ECG QTcF Interval Prolongation >450 Msec at Day 28
ECG QTcF Interval prolongation \>450 msec at Day 28 study visit
Time frame: 24 weeks
Population: Safety Population
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Teverelix TFA 120 mg 6-weekly | ECG QTcF Interval Prolongation >450 Msec at Day 28 | 1 Participants |
| Teverelix TFA 180 mg 6-weekly | ECG QTcF Interval Prolongation >450 Msec at Day 28 | 3 Participants |
Secondary
Follicle Stimulating Hormone (FSH) Mean % Reduction at Day 168
Follicle Stimulating Hormone (FSH) - the mean % reduction at Day 168
Time frame: 24 weeks
Population: Per Protocol
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Teverelix TFA 120 mg 6-weekly | Follicle Stimulating Hormone (FSH) Mean % Reduction at Day 168 | -71.89 % of baseline | Standard Deviation 12.84 |
| Teverelix TFA 180 mg 6-weekly | Follicle Stimulating Hormone (FSH) Mean % Reduction at Day 168 | -82.33 % of baseline | Standard Deviation 12.68 |
Secondary
Injection Site Reactions (ISRs)
Number of participants with ISRs at each visit during the 168 days treatment period
Time frame: 24 weeks
Population: Safety Population
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Teverelix TFA 120 mg 6-weekly | Injection Site Reactions (ISRs) | 5 Participants |
| Teverelix TFA 180 mg 6-weekly | Injection Site Reactions (ISRs) | 26 Participants |
Secondary
Luteinizing Hormone (LH) Levels (Castrate) at Week 24
Proportion of participants with effective LH castration rate over 168 days of treatment period
Time frame: 24 weeks
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Teverelix TFA 120 mg 6-weekly | Luteinizing Hormone (LH) Levels (Castrate) at Week 24 | 2 Participants |
| Teverelix TFA 180 mg 6-weekly | Luteinizing Hormone (LH) Levels (Castrate) at Week 24 | 22 Participants |
Secondary
Luteinizing Hormone (LH) Levels (Castrate) at Week 4
Proportion of participants achieving castration level for LH (LH \<1.1 U/L) at Day 28
Time frame: 4 weeks
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Teverelix TFA 120 mg 6-weekly | Luteinizing Hormone (LH) Levels (Castrate) at Week 4 | 5 Participants |
| Teverelix TFA 180 mg 6-weekly | Luteinizing Hormone (LH) Levels (Castrate) at Week 4 | 38 Participants |
Secondary
Luteinizing Hormone (LH) Mean % Reduction at Day 168
Luteinizing Hormone (LH) - the mean % reduction at Day 168
Time frame: 24 weeks
Population: Per Protocol
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Teverelix TFA 120 mg 6-weekly | Luteinizing Hormone (LH) Mean % Reduction at Day 168 | -69.88 % of baseline value | Standard Deviation 22.99 |
| Teverelix TFA 180 mg 6-weekly | Luteinizing Hormone (LH) Mean % Reduction at Day 168 | -83.34 % of baseline value | Standard Deviation 26.87 |
Secondary
Maximum Observed Concentration After Administration From Time Point t1 up to Time Point t (Cmax,t1-t)
The maximum observed concentration after administration from time point t1 up to time point t (Cmax,t1-t)
Time frame: 24 weeks
Population: Per Protocol
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Teverelix TFA 120 mg 6-weekly | Maximum Observed Concentration After Administration From Time Point t1 up to Time Point t (Cmax,t1-t) | 16.9 ng/mL |
| Teverelix TFA 180 mg 6-weekly | Maximum Observed Concentration After Administration From Time Point t1 up to Time Point t (Cmax,t1-t) | 20.4 ng/mL |
Secondary
Maximum Observed Concentration After Administration From Zero up to Time Point t1 (Cmax,0-t1)
The maximum observed concentration after administration from zero up to time point t1 (Cmax,0-t1)
Time frame: 24 weeks
Population: Per Protocol
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Teverelix TFA 120 mg 6-weekly | Maximum Observed Concentration After Administration From Zero up to Time Point t1 (Cmax,0-t1) | 38.22 ng/mL |
| Teverelix TFA 180 mg 6-weekly | Maximum Observed Concentration After Administration From Zero up to Time Point t1 (Cmax,0-t1) | 53.1 ng/mL |
Secondary
Maximum Observed Plasma Teverelix Concentration After Administration (Cmax)
The maximum observed plasma teverelix concentration after administration (Cmax)
Time frame: 24 weeks
Population: Per Protocol
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Teverelix TFA 120 mg 6-weekly | Maximum Observed Plasma Teverelix Concentration After Administration (Cmax) | 38.22 ng/mL |
| Teverelix TFA 180 mg 6-weekly | Maximum Observed Plasma Teverelix Concentration After Administration (Cmax) | 53.1 ng/mL |
Secondary
Prostate Specific Antigen (PSA) Reduction (≥50 Percent)
Number of participants with a PSA response of ≥50 percent reduction at the Day 168 visit
Time frame: 24 weeks
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Teverelix TFA 120 mg 6-weekly | Prostate Specific Antigen (PSA) Reduction (≥50 Percent) | 5 Participants |
| Teverelix TFA 180 mg 6-weekly | Prostate Specific Antigen (PSA) Reduction (≥50 Percent) | 30 Participants |
Secondary
PSA Response ≥50% at Day 168
The number of subjects with a PSA response ≥50% at Day 168
Time frame: 24 weeks
Population: Per Protocol
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Teverelix TFA 120 mg 6-weekly | PSA Response ≥50% at Day 168 | 5 Participants |
| Teverelix TFA 180 mg 6-weekly | PSA Response ≥50% at Day 168 | 30 Participants |
Secondary
PSA Response Rate at Day 28
PSA response is defined as \>50% decline in PSA at Day 28. PSA response rate is the number of subjects with a PSA response.
Time frame: 24 weeks
Population: Per Protocol
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Teverelix TFA 120 mg 6-weekly | PSA Response Rate at Day 28 | 6 Participants |
| Teverelix TFA 180 mg 6-weekly | PSA Response Rate at Day 28 | 35 Participants |
Secondary
Testosterone Levels (0.2 ng/mL) at Week 24
Proportion of participants achieving profound castration rate (\<0.2 ng/mL) over 168 days of treatment period
Time frame: 24 weeks
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Teverelix TFA 120 mg 6-weekly | Testosterone Levels (0.2 ng/mL) at Week 24 | 0 Participants |
| Teverelix TFA 180 mg 6-weekly | Testosterone Levels (0.2 ng/mL) at Week 24 | 17 Participants |
Secondary
Testosterone Levels (Castrate) at Week 24
Proportion of participants achieving a T castration rate over 168 days of treatment period
Time frame: 24 weeks
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Teverelix TFA 120 mg 6-weekly | Testosterone Levels (Castrate) at Week 24 | 3 Participants |
| Teverelix TFA 180 mg 6-weekly | Testosterone Levels (Castrate) at Week 24 | 27 Participants |
Secondary
Testosterone (T) Levels (0.2 ng/mL) at Week 4
Proportion of participants achieving castration level with serum T \<0.2 ng/mL at Day 28
Time frame: 4 weeks
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Teverelix TFA 120 mg 6-weekly | Testosterone (T) Levels (0.2 ng/mL) at Week 4 | 2 Participants |
| Teverelix TFA 180 mg 6-weekly | Testosterone (T) Levels (0.2 ng/mL) at Week 4 | 32 Participants |
Secondary
Testosterone (T) Levels (0.2 ng/mL) at Week 6
Proportion of participants achieving profound castration level (0.2 ng/mL) with serum T \<0.5 ng/mL at Day 42
Time frame: 6 weeks
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Teverelix TFA 120 mg 6-weekly | Testosterone (T) Levels (0.2 ng/mL) at Week 6 | 1 Participants |
| Teverelix TFA 180 mg 6-weekly | Testosterone (T) Levels (0.2 ng/mL) at Week 6 | 26 Participants |
Secondary
Testosterone (T) Levels (Castrate) at Week 6
Proportion of participants achieving castration level with serum T \<0.5 ng/mL at Day 42
Time frame: 6 weeks
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Teverelix TFA 120 mg 6-weekly | Testosterone (T) Levels (Castrate) at Week 6 | 4 Participants |
| Teverelix TFA 180 mg 6-weekly | Testosterone (T) Levels (Castrate) at Week 6 | 33 Participants |
Secondary
Testosterone (T) Mean % Reduction at Day 168
Testosterone (T) - the mean % reduction at Day 168
Time frame: 24 weeks
Population: Per Protocol
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Teverelix TFA 120 mg 6-weekly | Testosterone (T) Mean % Reduction at Day 168 | -91.1 % of baseline | Standard Deviation 7.02 |
| Teverelix TFA 180 mg 6-weekly | Testosterone (T) Mean % Reduction at Day 168 | -95.9 % of baseline | Standard Deviation 4.57 |
Secondary
Time to Achieve Castrate Levels of Luteinizing Hormone (LH)
Mean time to LH levels falling below castration level (LH \<1.1 U/L) for the first time
Time frame: 4 weeks
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Teverelix TFA 120 mg 6-weekly | Time to Achieve Castrate Levels of Luteinizing Hormone (LH) | 1.0 days |
| Teverelix TFA 180 mg 6-weekly | Time to Achieve Castrate Levels of Luteinizing Hormone (LH) | 1.0 days |
Secondary
Time to Achieve Castrate Levels of Testosterone (T)
Mean time to T levels falling below castration level (\<0.5 ng/mL) for the first time
Time frame: 4 weeks
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Teverelix TFA 120 mg 6-weekly | Time to Achieve Castrate Levels of Testosterone (T) | 2.0 days |
| Teverelix TFA 180 mg 6-weekly | Time to Achieve Castrate Levels of Testosterone (T) | 2.0 days |
Secondary
Time to Escape Castrate Levels of Luteinizing Hormone (LH)
Mean time to (first) overstep of LH castration level after achieving castration
Time frame: 24 weeks
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Teverelix TFA 120 mg 6-weekly | Time to Escape Castrate Levels of Luteinizing Hormone (LH) | 4.5 days |
| Teverelix TFA 180 mg 6-weekly | Time to Escape Castrate Levels of Luteinizing Hormone (LH) | 8.5 days |
Secondary
Time to Escape Castrate Levels of Testosterone (T)
Mean time to (first) overstep of T castration level after achieving castration
Time frame: Approximately 30 weeks
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Teverelix TFA 120 mg 6-weekly | Time to Escape Castrate Levels of Testosterone (T) | 2.5 days |
| Teverelix TFA 180 mg 6-weekly | Time to Escape Castrate Levels of Testosterone (T) | 215.0 days |
Secondary
Time to Reach Cmax,0-t1 After Dosing (Tmax,0-t1)
The time to reach Cmax,0-t1 after dosing (tmax,0-t1)
Time frame: 24 weeks
Population: Per Protocol
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Teverelix TFA 120 mg 6-weekly | Time to Reach Cmax,0-t1 After Dosing (Tmax,0-t1) | 1.8 hours |
| Teverelix TFA 180 mg 6-weekly | Time to Reach Cmax,0-t1 After Dosing (Tmax,0-t1) | 1.5 hours |
Secondary
Time to Reach Cmax After Dosing (Tmax)
The time to reach Cmax after dosing (tmax)
Time frame: 24 weeks
Population: Per Protocol
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Teverelix TFA 120 mg 6-weekly | Time to Reach Cmax After Dosing (Tmax) | 1.8 hours |
| Teverelix TFA 180 mg 6-weekly | Time to Reach Cmax After Dosing (Tmax) | 1.5 hours |
Secondary
Time to Reach Cmax,t1-t After Dosing (Tmax,t1-t)
The time to reach Cmax,t1-t after dosing (tmax,t1-t)
Time frame: 24 weeks
Population: Per Protocol
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Teverelix TFA 120 mg 6-weekly | Time to Reach Cmax,t1-t After Dosing (Tmax,t1-t) | 96.0 hours |
| Teverelix TFA 180 mg 6-weekly | Time to Reach Cmax,t1-t After Dosing (Tmax,t1-t) | 167 hours |
Secondary
Treatment-emergent Adverse Events (AEs)
Number of participants with treatment-emergent AEs
Time frame: 24 weeks
Population: Safety Population
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Teverelix TFA 120 mg 6-weekly | Treatment-emergent Adverse Events (AEs) | 8 Participants |
| Teverelix TFA 180 mg 6-weekly | Treatment-emergent Adverse Events (AEs) | 38 Participants |