A Phase 3, Randomized, Double-Blind, Placebo-Controlled, Parallel-Design, Global Multicenter Study to Evaluate the Efficacy and Safety of Tadalafil Once Daily Dosing for 12 Weeks in Men with Signs and Symptoms of Benign Prostatic Hyperplasia - ND

• Register: EUCTR
• Last refreshed on: 19 March 2012
• Main ID: EUCTR2009-010739-42-IT
• Date of registration: 01/10/2009
• Prospective Registration: Yes
• Primary sponsor: ELI LILLY
• Public title: A Phase 3, Randomized, Double-Blind, Placebo-Controlled, Parallel-Design, Global Multicenter Study to Evaluate the Efficacy and Safety of Tadalafil Once Daily Dosing for 12 Weeks in Men with Signs and Symptoms of Benign Prostatic Hyperplasia - ND
• Scientific title: A Phase 3, Randomized, Double-Blind, Placebo-Controlled, Parallel-Design, Global Multicenter Study to Evaluate the Efficacy and Safety of Tadalafil Once Daily Dosing for 12 Weeks in Men with Signs and Symptoms of Benign Prostatic Hyperplasia - ND
• Date of first enrolment: 17/11/2009
• Target sample size: 453
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2009-010739-42
• 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: yes Placebo: yes Other: no

Countries of recruitment

Austria, Belgium, France, Germany, Greece, Italy, Netherlands

Key inclusion & exclusion criteria

Inclusion criteria:
[1] Present with BPH (also referred to as BPH-LUTS) based on the
disease diagnostic criteria (Section 8.1.1) at Visit 1.
[2] Are men 45 years of age or older at Visit 1.
[3] Provide signed informed consent at Visit 1.
[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:
[a] Finasteride therapy for at least 3 months prior to Visit 2.
[b] Dutasteride therapy for at least 6 months prior to Visit 2.
[c] Other BPH therapy (including herbal preparations) for at least
4 weeks prior to Visit 2.
[d] OAB therapy for at least 4 weeks prior to Visit 2.
[e] ED therapy for at least 4 weeks prior to Visit 2.
[f] Other experimental or off-label BPH therapy, such as injectable
therapies with a protracted effect, for at least 1/2 year prior to
Visit 2.
[6] Have LUTS with a Total IPSS ≥13 at Visit 2.
[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) at Visit 2 (see Protocol Attachment LVID.3).
[8] Demonstrate compliance with study drug administration requirements
during the placebo lead-in period by administering ≥70% of prescribed
doses, confirmed by documentation that the subject returned ≤30% of
prescribed doses at Visit 3
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:
[9] Prostate-specific antigen (PSA) >10.0 ng/mL at Visit 1.
[10] PSA ≥4.0 to ≤10.0 ng/mL at Visit 1 if prostate malignancy has not
been ruled out to the satisfaction of an urologist.
[11] Bladder PVR ≥300 mL by ultrasound determination at Visit 1.
[12] History of any of the following pelvic conditions:
[a] Pelvic surgery or any other pelvic procedure, including radical
prostatectomy, pelvic surgery for removal of malignancy, or
bowel resection.
[b] Pelvic radiotherapy.
[c] Any pelvic surgical procedure of the urinary tract, including
minimally invasive BPH-LUTS therapies and penile implant
surgery.
[d] Lower urinary tract malignancy or trauma.
[13] Lower urinary tract instrumentation (including prostate biopsy) within
30 days of Visit 1.
[14] History of urinary retention or lower urinary tract (bladder) stones
within 6 months of Visit 1.
[15] History of urethral obstruction due to stricture, valves, sclerosis, or
tumor.
[16] Clinical evidence of any of the following bladder conditions:
[a] Mullerian duct cysts.
[b] Atonic, decompensated, or hypocontractile bladder.
[c] Detrusor-sphincter dyssynergia (contraction of the detrusor
without sphincter relaxation).
[d] Intravesical obstruction (for example, intravesical median lobe of
the prostate).
[e] Interstitial cystitis
[17] Clinical evidence of any of the following urinary tract conditions at
Visit 1:
[a] Urinary tract infection.
[b] Urinary tract inflammation (including prostatitis).
Urinary tract infection/inflammation is defined as a positive result for
leukocyte esterase from a urine dipstick or >5 white blood cells
(WBCs) per high-powered field on urinalysis from a centrifuged,
clean-catch, midstream urine specimen.
[c] Current antibiotic therapy for urinary tract infection.
[d] Clinically significant microscopic hematuria as determined by a
urologist.
[18] Clinical evidence of prostate cancer.
[19] Current neurologic disease or condition associated with neurogenic
bladder (for example, Parkinsons disease, multiple sclerosis).
[20] History of significant renal insufficiency, defined as receiving renal
dialysis or having an estimated creatinine clearance <30 mL/minute at
Visit 1 as calculated by the central laboratory using the Cockroft-Gault
formula:
(140 &#8722; age [years]) ? weight [kg] / (72 ? serum creatinine [mg/dL])
[21] Clinical evidence of severe hepatic impairment at Visit 1.
[22] History of any of the following cardiac conditions:
[a] Angina requiring treatment with long-acting nitrates.
[b] Angina requiring treatment with short-acting nitrates within
90 days of Visit 1.
[c] Unstable angina as defined in Protocol Attachment LVID.4
(Braunwald 1989) within 90 days of Visit 1.
[d] Positive cardiac stress test without documented evidence of
subsequent, effective cardiac intervention.
[23] History of any of the following coronary conditions within 90 days of
Visit 1:
[a] Myocardial infarction.
[b] Coronary artery bypass graft surgery.
[c] Percutaneous coronary intervention (for example, angioplasty or
stent placement).
[24] Any evidence of heart disease (New York Heart Association [NYHA]
&#8805; Class III as defined in Protocol Attachment LVID.5 within 6 months
of Visit 1.
[25] Systolic blood pressure >160 or <90 mm Hg or diastolic blood
pressure >100 or <50 mm Hg at Visit 1 (if stress is suspected, retest
under basal conditions), or malignant hypertension.
[26] Scheduled or planned surgery (or any procedure requiring general,
spinal, or

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

Health Condition(s) or Problem(s) studied

Benign Prostatic Hyperplasia
MedDRA version: 12.0 Level: LLT Classification code 10004446 Term: Benign prostatic hyperplasia

Intervention(s)

Trade Name: CIALIS
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: Tadalafil
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

Pharmaceutical Form: Modified-release capsule, hard
INN or Proposed INN: Tamsulosin
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: .4-
Pharmaceutical form of the placebo: Modified-release capsule, hard
Route of administration of the placebo: Oral use

Primary Outcome(s)

Secondary Objective: The secondary objectives of the study are as follows:
To evaluate the efficacy of tamsulosin 0.4 mg QD for 12 weeks compared with placebo in
improving IPSS in men with BPH-LUTS.
To evaluate the efficacy of tadalafil 5 mg QD compared with placebo and tamsulosin 0.4 mg QD
compared with placebo for 12 weeks in the treatment of men with BPH-LUTS as assessed by the
following measures:
- BPH Impact Index (BII)
- IPSS storage (irritative) subscore
- IPSS voiding (obstructive) subscore
- IPSS nocturia subscore
- IPSS Quality of Life (QoL) Index
- Patient Global Impression of Improvement (PGI-I)
- Clinician Global Impression of Improvement (CGI-I)
- The Treatment Satisfaction Scale - Benign Prostatic Hyperplasia (TSS-BPH)
To evaluate the efficacy of tadalafil 5 mg QD compared with placebo and tamsulosin 0.4 mg QD
compared with placebo after 1 week of treatment in men with BPH-LUTS as assessed by the Modified
IPSS (mIPSS).

Main Objective: The primary objective of Study LVID is to evaluate the efficacy of tadalafil 5 mg once daily (QD) for
12 weeks compared with placebo in improving the International Prostate Symptom Score (IPSS) in men
with signs and symptoms of benign prostatic hyperplasia (BPH; also referred to as BPH-LUTS [lower
urinary tract symptoms]).

Primary end point(s): Tadalafil 5 mg QD resulted in a clinically and statistically significant improvement in IPSS (primary endpoint) compared with placebo
after 12 weeks.

Secondary ID(s)

2009-010739-42-DE

H6D-MC-LVID