A Randomized, Double-Blind, Placebo Controlled Study to Evaluate the Effect of Tadalafil Once Daily for 8 Weeks on Prostatic Blood Flow and Perfusion Parameters in Men with Signs and Symptoms of Benign Prostatic Hyperplasia - LVIR

• Register: EUCTR
• Last refreshed on: 16 October 2012
• Main ID: EUCTR2010-020220-22-AT
• Date of registration: 23/08/2010
• Prospective Registration: Yes
• Primary sponsor: Eli Lilly and Company
• Public title: A Randomized, Double-Blind, Placebo Controlled Study to Evaluate the Effect of Tadalafil Once Daily for 8 Weeks on Prostatic Blood Flow and Perfusion Parameters in Men with Signs and Symptoms of Benign Prostatic Hyperplasia - LVIR
• Scientific title: A Randomized, Double-Blind, Placebo Controlled Study to Evaluate the Effect of Tadalafil Once Daily for 8 Weeks on Prostatic Blood Flow and Perfusion Parameters in Men with Signs and Symptoms of Benign Prostatic Hyperplasia - LVIR
• Date of first enrolment: 03/02/2011
• Target sample size: 106
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2010-020220-22
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: no Single blind: no Double blind: yes Parallel group: yes Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: no Placebo: yes Other: no

Countries of recruitment

Austria, Belgium, Italy

Key inclusion & exclusion criteria

Inclusion criteria:
Subjects are eligible to be included in the study only if they meet all of the following criteria:
[1] Present with benign prostatic hyperplasia (BPH; also referred to as BPH-LUTS [lower urinary tract symptoms]) based on the disease diagnostic criteria at screening.
[2] Are men 45 years of age or older at screening.
[3] Provide signed informed consent at screening.
[4] Agree not to use any other approved or experimental pharmacologic BPH, overactive bladder (OAB), or erectile dysfunction (ED) treatments, including alpha blockers, 5-alpha reductase inhibitors (5-ARIs), antimuscarinics, phosphodiesterase type 5 (PDE5) inhibitors, or herbal preparations at any time during the study.
[5] Have not taken the following treatments within the indicated duration:
• Finasteride therapy for at least 3 months prior to the TRUS assessment period.
• Dutasteride therapy for at least 6 months prior to the TRUS assessment period.
• All other BPH therapy (including herbal preparations and vitamin preparations containing saw palmetto) for at least 4 weeks prior to the TRUS assessment period.
• Overactive bladder therapy for at least 4 weeks prior to the TRUS assessment period.
• ED therapy for at least 4 weeks prior to the TRUS assessment period.
• Any other experimental or off-label BPH therapy, such as injectable therapies with a protracted effect, for at least 6 months prior to the TRUS assessment period.
[6] Have LUTS with a total IPSS =13 under 1 of the following conditions:
• At screening if the subject does not require wash-out of therapy for BPH-LUTS.
• At the start of the TRUS assessment period if the subject requires wash-out (4 weeks) of BPH-LUTS therapy.
[7] Have bladder outlet obstruction as defined by a urinary peak flow rate (Qmax) of =4 to =15 mL/second (from a prevoid total bladder volume [assessed by ultrasound] of =150 to =550 mL and a minimum voided volume of 125 mL) under 1 of the following conditions:
• At screening if the subject does not require wash-out of therapy for BPH-LUTS.
• At the start of the TRUS assessment period if the subject requires wash-out (4 weeks) of BPH-LUTS therapy.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range

Exclusion criteria:
[8] Prostate specific antigen (PSA) >10.0 ng/mL at screening
[9] PSA =4.0 to =10.0 ng/mL at screening if prostate malignancy has not been ruled out to the satisfaction of a urologist
[10] Bladder postvoid residual volume = 300 mL by ultrasound determination at screening
[11] History of any of the following pelvic conditions:
• Pelvic surgery or any other pelvic procedure
• Pelvic radiotherapy
• Any pelvic surgical procedure of the urinary tract
• Lower urinary tract malignancy or trauma
[12] Lower urinary tract instrumentation within 30 days of screening
[13] History of urinary retention or lower urinary tract stones within 6 months of screening
[14] History of urethral obstruction due to stricture, valves, sclerosis, or tumor
[15] Clinical evidence or medical history of any of the following bladder conditions:
• Mullerian duct cysts
• Atonic, decompensated or hypocontractile bladder
• Detrusor-sphincter dyssynergia
• Intravesical obstruction
• Interstitial cystitis
[16] Clinical evidence of any of the following urinary tract conditions at screening:
• Urinary tract infection
• Urinary tract inflammation
• Current antibiotic therapy for urinary tract infection
• Clinically significant microscopic hematuria
[17] Clinical evidence of prostate cancer
[18] History of prostate saturation biopsy
[19] Any condition which may preclude or negatively influence tolerance to TRUS
[20] Clinical evidence on TRUS of any of the following prostate conditions at the start of the TRUS assessment period or other findings related to prostate anatomy on screening TRUS that may interfere with measurement of ultrasound blood flow parameters
• Prominent median or midline lobe
• Multiple prostatic cystic changes or multiple calcifications
• Scarring from previous prostate biopsies
[21] Current neurologic disease or condition associated with neurogenic bladder
[22] History of significant renal insufficiency
[23] Clinical evidence of severe hepatic impairment at screening
[24] History of any of the following cardiac conditions:
• Angina requiring treatment with long-acting nitrates
• Angina requiring treatment with short-acting nitrates within 90 days of screening
• Unstable angina within 90 days of screening
• Positive cardiac stress test without documented evidence of subsequent, effective cardiac intervention
[25] History of any of the following coronary conditions within 90 days of screening:
• Myocardial infarction
• Coronary artery bypass graft surgery
• Percutaneous coronary intervention
[26] Any evidence of moderate to severe cardiac disease within 6 months of screening
[27] Systolic blood pressure >160 or <90 mm Hg or diastolic blood pressure >100 or <50 mm Hg at screening (if stress is suspected, retest under basal conditions) or malignant hypertension
[28] Scheduled or planned surgery during the course of the study
[29] History of drug, alcohol, or substance abuse within 6 months of screening
[30] Any condition that would interfere with subject ability to provide informed consent or comply with study instructions, would place subject at increased risk, or might confound the interpretation of the study results
[31] Current treatment with nitrates (as outlined in Exclusion Criterion 24), androgens, antiandrogens, estrogens, luteinizing hormone-releasing hormone agonists/antagonists, anabolic steroids, or non-prescription products containing estrogenic or androgenic supplements
[32] Current systemic treatment with any of the following:
• Pote

Age minimum:
Age maximum:
Gender:
Female: no
Male: yes

Health Condition(s) or Problem(s) studied

Benign Prostatic Hyperplasia (BPH)
MedDRA version: 12.1 Level: LLT Classification code 10004446 Term: Benign prostatic hyperplasia

Intervention(s)

Trade Name: CIALIS 5 mg film-coated tablets
Product Name: Tadalafil
Product Code: LY450190
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: TADALAFIL
CAS Number: 171596-29-5
Current Sponsor code: LY450190
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 5-
Pharmaceutical form of the placebo: Film-coated tablet
Route of administration of the placebo: Oral use

Primary Outcome(s)

Primary end point(s): The primary endpoint, and basis for comparison between treatment groups, will be the change from baseline in prostatic transitional zone resistive index (RI) from baseline to Week 8.

Secondary Objective: The secondary objectives of the study are as follows:
•To evaluate the effect of tadalafil 5 mg once daily for 8 weeks versus placebo on other regional blood flow and perfusion parameters in the prostate as measured by: Color Doppler ultrasound pixel intensity (color pixel intensity, CPI) in the prostate transition zone and arterial RI and CPI in prostate peripheral zone
• To evaluate the effect of tadalafil 5 mg once daily for 8 weeks versus placebo on blood flow and perfusion parameters in the bladder neck as measured by arterial RI and CPI
• To evaluate the effect of tadalafil 5 mg once daily for 4 weeks versus placebo on all of the above blood flow and perfusion parameters in the prostate and bladder neck

Main Objective: The primary objective of Study LVIR is to evaluate the effect of tadalafil 5 mg once daily for 8 weeks compared with placebo on improving prostatic blood perfusion in men with signs and symptoms of BPH, also referred to as BPH-LUTS (lower urinary tract symptoms), as measured by arterial resistive index (RI) in the prostate transition zone.

Secondary ID(s)

H6D-MC-LVIR

2010-020220-22-BE