E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
The aim of the proposed study is to assess the activity on inflammation biomarkers of L.S.E.S.r (PERMIXON® 160mg hard capsule) and Tamsulosine LP in the treatment of BPH. The potential links between serum and urinary markers of inflammation and BPH clinical symptoms at baseline and on treatment will be explored. |
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E.1.1.1 | Medical condition in easily understood language |
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E.1.1.2 | Therapeutic area | Diseases [C] - Male diseases of the urinary and reproductive systems [C12] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 14.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10004447 |
E.1.2 | Term | Benign prostatic hypertrophy |
E.1.2 | System Organ Class | 10038604 - Reproductive system and breast disorders |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
• Main objective :
To evaluate the effect of L.S.E.S.r. 160 mg b.i.d. and Tamsulosine LP 0.4 mg o.a.d. at D30 and D90 on biomarkers of inflammation in patients suffering from BPH :
- Urine inflammation markers on the first urine flow :
- Gene (mRNA) expression profile of inflammation in BPH
- Protein expression profile of inflammation in BPH of the main expressed genes
- Serum inflammation markers :
- CRP and Sedimentation Rate
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E.2.2 | Secondary objectives of the trial |
-To assess the efficacy of L.S.E.S.r. 160 mg b.i.d. and Tamsulosine LP 0.4 mg o.a.d. through the assessment of I-PSS.
-To assess the efficacy of L.S.E.S.r. 160 mg b.i.d. and Tamsulosine LP 0.4 mg o.a.d. through the assessment of QoL.
- To assess the effect of L.S.E.S.r. 160 mg b.i.d. and Tamsulosine LP 0.4 mg o.a.d. on sexual function (MSF-4).
-To assess the efficacy of L.S.E.S.r. 160 mg b.i.d. and Tamsulosine LP 0.4 mg o.a.d. through the assessment of Qmax.
-To assess the efficacy of L.S.E.S.r. 160 mg b.i.d. and Tamsulosine LP 0.4 mg
o.a.d. through the assessment of post-void residual urine volume.
-To evaluate the effect of L.S.E.S.r. 160 mg b.i.d. and Tamsulosine LP 0.4 mg o.a.d. on prostate volume.
- To perform an exploratory analysis of the link between inflammation biomarkers and BPH clinical symptoms at baseline and on treatment.
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
- Male patient
- Between 45 and 85 years old.
- Patient with bothersome lower urinary tract symptoms such as pollakiuria
(daytime or night time), urgency, sensation of incomplete voiding, delayed
urination or weak stream, existing for over 12 months
- I-PSS ≥ 10 at selection visit and ≥ 12 at randomisation visit (visit 2)
- Stable patient’s disease at randomisation defined as an absolute difference of 2
or less on I-PSS between selection and randomisation visits (visit 1 and visit 2)
- I-PSS QoL score ≥ 3 evaluated at selection and randomisation visits,
- 5 mL/s ≤ maximum urinary flow rate < 15 mL/s for a voided volume ≥ 150 mL
and ≤ 500 mL evaluated at randomisation visit (2 measurements if necessary)
- Prostatic volume ≥30 cm³ determined by transrectal ultrasound at
randomisation visit (visit 2)
- Serum total PSA at randomisation visit (visit 2) :
a) ≤ 4 ng/mL
or
b) ≤ 10 ng/mL and
PSA (free) / PSA (total) ≥ 25% or negative prostate biopsy within the past 6
months prior to selection visit.
Ethical /legal considerations:
- Patient able to understand and sign the informed consent and understand and
fill in self-questionnaires
- Having signed his written informed consent
- Affiliated to a social security system, or is a beneficiary (if applicable in the
national regulation). |
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E.4 | Principal exclusion criteria |
- Post-void residual urine volume > 200 mL (by suprapubic ultrasound) at randomisation visit (visit 2).
- Urological history :
Urethral stricture disease and/or bladder neck disease
Active (at selection and randomisation visits) or recent (< 3 months) or
recurrent urinary tract infection
Urinary retention with indwelling catheter or intermittent catheterisation
History of unprompted acute urinary retention in the past
Indication of BPH surgery
Stone in bladder or urethra
Acute or chronic (documented) prostatitis
Prostate cancer treated or untreated
Bladder cancer
Interstitial cystitis (documented by symptoms and/or biopsy)
Active upper tract stone disease causing symptoms
- Patient with history of surgery of the prostate, bladder neck or pelvic region
- Any local and/or systemic inflammation disorders at selection and randomisation visit
- Any neurologic or psychiatric disease/disorder interfering with detrusor or sphincter muscle
- Insulin-dependent diabetes mellitus and non-controlled non insulin-dependent diabetes mellitus
- Chronic renal insufficiency, with serum creatinine ≥ 30 % above the upper normal range at randomisation visit (visit 2)
- History of severe hepatic failure
- Orthostatic hypotension defined as a decrease of at least 20 mmHg in SBP or 10 mmHg in DBP between supine and 2-minute standing positions at selection (visit 1) and randomisation visit (visit 2)
- Patient with any severe underlying disease considered as life threatening in the short or medium term
- Known hypersensitivity to one of the constituents of the study drugs
- Concomitant medication with at selection visit (visit 1) and randomisation visit (visit 2) :
Anti-androgens (must be discontinued at least 6 months prior to selection)
LH-RH analogues (must be discontinued at least 6 months prior to selection)
5 alpha-reductase inhibitors (must be discontinued at least 3 months prior to selection)
Plants extracts used for treatment of LUTS (must be discontinued at least 3 months prior to selection)
Alpha blockers and alpha/beta blockers (must be discontinued at least 1 month prior to selection)
ACE inhibitors, calcium antagonists, beta blockers or diuretics (except if stable dose and initiated more than 6 weeks prior to selection)
NSAIDs by systemic route (except aspirin up to 325 mg/day for cardiovascular prophylaxis)
Corticosteroids by systemic route.
Antibiotics by systemic route
Sympathomimetics, antihistamines, antidepressants (anticholinergic), atropine, antispasmodic drugs, antiparkinsonism drugs, pseudoephedrine,
chlorpheniramine, spironolactone, mepartricine
- Patient with a history of drug or alcohol abuse |
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E.5 End points |
E.5.1 | Primary end point(s) |
Inflammation biomarkers assay in patients suffering from BPH :
- Urine inflammation markers (mRNA and proteins) on the first urine flow after digital rectal examination (DRE) at D1, D30 and D90
- Serum inflammation markers at D1, D30 and D90 :
- CRP and Sedimentation Rate (at 1 hour & 2 hours)
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
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E.5.2 | Secondary end point(s) |
Secondary efficacy criteria :
-Assessment of I-PSS at selection, D1, D30 and D90.
-Assessment of QoL at selection, D1, D30 and D90.
-Assessment of sexual function (MSF-4) at D1, D30 and D90.
-Assessment of Qmax at D1, D30 and D90, by uroflowmetry
- Assessment of post-void residual urine volume at D1, D30 and D90, by supra-pubic ultrasound
- Assessment of prostate volume at D1, D30 and D90, by transrectal ultrasound
Safety criteria
-Adverse events
-Physical examination at selection visit and at each visit including body temperature and weight and height (at selection visit only)
-Vital signs at selection visit and at each visit |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | Yes |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | Yes |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | Yes |
E.8.1.7.1 | Other trial design description |
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E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | Yes |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 2 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 3 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 35 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 0 |
E.8.9.1 | In the Member State concerned months | 9 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 0 |
E.8.9.2 | In all countries concerned by the trial months | 14 |
E.8.9.2 | In all countries concerned by the trial days | 0 |