Benign Prostatic Hypertrophy
Conditions
Keywords
Cetrorelix
Brief summary
Benign Prostatic Hypertrophy (BPH) is a common and bothersome condition of aging men. It is characterized by an enlargement of the prostate occurring in human male over the age of 50 which increases in prevalence with age, and among those aged 50 to 80, about 40% report moderate or severe urinary symptoms of prostatism. The aim of treatment is to improve patients' quality of life which primarily depends on the severity of the symptoms of BPH. Current treatments of BPH have a benefit / risk ratio which leaves room for improvement. For this study, study medication (Cetrorelix pamoate or placebo) is administered by injection in the buttocks (Intramuscular). All patients completing the double-blind portion (Week 0 to 52) are eligible to receive the active drug during the open-label part of the study (Week 52 to 90).
Detailed description
The objectives of the study are to develop a safe and tolerable intermittent dosage regimen of cetrorelix pamoate that provides prolonged improvement in BPH-related signs and symptoms. Patients will enter a 4-week run-in no-treatment observation period to confirm severity and stability of voiding symptoms based on the International Prostate Symptom Score (IPSS). Patients will then be allocated to study drug in a double-blind, randomized, double-dummy, placebo-controlled fashion. Patients will be administered an IM injection of study drug at Week 0, 2, 26 and 28 and will be followed up to Week 52. Then, in an open label fashion, patients will be administered an IM injection of study drug at Week 52, 54, 78 and 80 and will be followed up to Week 90.
Interventions
DRUGCetrorelix 78 mg + 78 mg
DRUGCetrorelix 78 mg + 52 mg
DRUGPlacebo
Sponsors
AEterna Zentaris
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
MALE
Age
50 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Benign Prostatic Hyperplasia, based on medical history * Voiding symptoms
Exclusion criteria
* Urgent need for prostate surgery or prior surgical treatment of the prostate or bladder * Major organ dysfunction * Eczema (atopic dermatitis) treated during the last 6 months * Current or recent treatment with sexual hormone drugs or 5 α reductase inhibitors or botulinum toxin type a (Botox) within the last 6 months prior randomization or with α blockers or saw palmetto within the last 6 weeks prior to randomization * Urologic disorders including neurogenic bladder dysfunction due to diabetes mellitus or documented neurologic disorder, urethral stricture disease or history of pelvic radiation therapy * History of acute obstructive, infectious, or neurological disorders of the genitourinary tract within the last 3 months
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| International Prostate Symptoms Score (IPSS) | Baseline and 52 weeks | The International Prostate Symptoms Score (IPSS) score of benign prostata hyperplasia (BPH) symptoms is calculated based on a patient questionnaire assessing 7 items (incomplete voiding, frequency, intermittency, urgency, weak stream, hesitancy, nocturia) on a scale from 0 (best) to 5 (worst); total range: 0 points (best) to 35 points (worst) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Time Course of Quality of Life | Quality of life assessment in the following weeks: 4,12,26,30,38,46,52 | The time course of quality of life: assessed by the following disease specific quality of life:If you were to spend the rest of your life with the urinary conditions just the way it is now, how would you feel about that? The rating scale is comprising a range of values from 0 to 6, with = delighted, 1 = pleased, 2 = mostly satisfied, 3 = mixed, 4 = mostly dissatisfied, 5 = unhappy, 6 = terrible. |
Countries
Bulgaria, Canada, Germany, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Cetrorelix 78+78 78+78 means 78 mg combining Week 0 (52 mg) and Week 2 (26 mg) + 78 mg combining Week 26 (52 mg) and Week 28 (26 mg) | 219 |
| Cetrorelix 78+52 78+52 means 78 mg combining Week 0 (52 mg) and Week 2 (26 mg) + 52 mg combining Week 26 (52 mg) and Week 28 (0 mg) | 230 |
| Placebo Placebo on Week 0, 2 26 and 28 | 218 |
| Total | 667 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Adverse Event | 11 | 18 | 9 |
| Overall Study | Lack of Efficacy | 1 | 2 | 2 |
| Overall Study | Other | 16 | 13 | 14 |
| Overall Study | Protocol Violation | 1 | 2 | 1 |
| Overall Study | Withdrawal by Subject | 17 | 18 | 21 |
Baseline characteristics
| Characteristic | Cetrorelix 78+78 | Cetrorelix 78+52 | Placebo | Total |
|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 110 Participants | 104 Participants | 107 Participants | 321 Participants |
| Age, Categorical Between 18 and 65 years | 109 Participants | 126 Participants | 111 Participants | 346 Participants |
| Age, Continuous | 63.86 years STANDARD_DEVIATION 8.27 | 64.04 years STANDARD_DEVIATION 7.54 | 64.20 years STANDARD_DEVIATION 7.76 | 64.03 years STANDARD_DEVIATION 7.84 |
| Region of Enrollment Bulgaria | 11 participants | 12 participants | 12 participants | 35 participants |
| Region of Enrollment Canada | 38 participants | 42 participants | 39 participants | 119 participants |
| Region of Enrollment Germany | 28 participants | 28 participants | 27 participants | 83 participants |
| Region of Enrollment United States | 142 participants | 148 participants | 140 participants | 430 participants |
| Sex: Female, Male Female | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Male | 219 Participants | 230 Participants | 218 Participants | 667 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 177 / 219 | 179 / 230 | 169 / 218 |
| serious Total, serious adverse events | 11 / 219 | 16 / 230 | 21 / 218 |
Outcome results
Primary
International Prostate Symptoms Score (IPSS)
The International Prostate Symptoms Score (IPSS) score of benign prostata hyperplasia (BPH) symptoms is calculated based on a patient questionnaire assessing 7 items (incomplete voiding, frequency, intermittency, urgency, weak stream, hesitancy, nocturia) on a scale from 0 (best) to 5 (worst); total range: 0 points (best) to 35 points (worst)
Time frame: Baseline and 52 weeks
Population: The Intent-to-treat (ITT) population included all participants for whom at least one post-baseline efficacy assessment was available; imputation per Last Observation Carried Forward (LOCF)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Cetrorelix 78+78 | International Prostate Symptoms Score (IPSS) | -4.0 Units on a scale | Standard Deviation 6.61 |
| Cetrorelix 78+52 | International Prostate Symptoms Score (IPSS) | -3.7 Units on a scale | Standard Deviation 5.9 |
| Placebo | International Prostate Symptoms Score (IPSS) | -3.8 Units on a scale | Standard Deviation 6.22 |
p-value: 0.742495% CI: [-1.38, 0.98]ANOVA
p-value: 0.92695% CI: [-1.1, 1.21]ANOVA
p-value: 0.669995% CI: [-1.41, 0.91]ANOVA
Secondary
Time Course of Quality of Life
The time course of quality of life: assessed by the following disease specific quality of life:If you were to spend the rest of your life with the urinary conditions just the way it is now, how would you feel about that? The rating scale is comprising a range of values from 0 to 6, with = delighted, 1 = pleased, 2 = mostly satisfied, 3 = mixed, 4 = mostly dissatisfied, 5 = unhappy, 6 = terrible.
Time frame: Quality of life assessment in the following weeks: 4,12,26,30,38,46,52
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Cetrorelix 78+78 | Time Course of Quality of Life | Week 38 | -0.62 score on a scale | Standard Deviation 1.2 |
| Cetrorelix 78+78 | Time Course of Quality of Life | Week 26 | -0.48 score on a scale | Standard Deviation 1.18 |
| Cetrorelix 78+78 | Time Course of Quality of Life | Week 30 | -0.64 score on a scale | Standard Deviation 1.2 |
| Cetrorelix 78+78 | Time Course of Quality of Life | Week 12 | -0.52 score on a scale | Standard Deviation 1.21 |
| Cetrorelix 78+78 | Time Course of Quality of Life | Week 46 | -0.71 score on a scale | Standard Deviation 1.28 |
| Cetrorelix 78+78 | Time Course of Quality of Life | Week 4 | -0.33 score on a scale | Standard Deviation 1.16 |
| Cetrorelix 78+78 | Time Course of Quality of Life | Week 52 | -0.55 score on a scale | Standard Deviation 1.25 |
| Cetrorelix 78+52 | Time Course of Quality of Life | Week 30 | -0.71 score on a scale | Standard Deviation 1.4 |
| Cetrorelix 78+52 | Time Course of Quality of Life | Week 12 | -0.67 score on a scale | Standard Deviation 1.25 |
| Cetrorelix 78+52 | Time Course of Quality of Life | Week 4 | -0.42 score on a scale | Standard Deviation 1.09 |
| Cetrorelix 78+52 | Time Course of Quality of Life | Week 26 | -0.70 score on a scale | Standard Deviation 1.41 |
| Cetrorelix 78+52 | Time Course of Quality of Life | Week 38 | -0.77 score on a scale | Standard Deviation 1.38 |
| Cetrorelix 78+52 | Time Course of Quality of Life | Week 46 | -0.67 score on a scale | Standard Deviation 1.41 |
| Cetrorelix 78+52 | Time Course of Quality of Life | Week 52 | -0.62 score on a scale | Standard Deviation 1.39 |
| Placebo | Time Course of Quality of Life | Week 38 | -0.59 score on a scale | Standard Deviation 1.22 |
| Placebo | Time Course of Quality of Life | Week 26 | -0.46 score on a scale | Standard Deviation 1.07 |
| Placebo | Time Course of Quality of Life | Week 52 | -0.60 score on a scale | Standard Deviation 1.11 |
| Placebo | Time Course of Quality of Life | Week 46 | -0.58 score on a scale | Standard Deviation 1.2 |
| Placebo | Time Course of Quality of Life | Week 30 | -0.58 score on a scale | Standard Deviation 1.24 |
| Placebo | Time Course of Quality of Life | Week 4 | -0.35 score on a scale | Standard Deviation 1 |
| Placebo | Time Course of Quality of Life | Week 12 | -0.47 score on a scale | Standard Deviation 1.05 |