Efficacy, Safety and Dose-response of Udenafil in Patients With Benign Prostatic Hyperplasia and Erectile Dysfunction

Phase 2

Withdrawn

• Conditions: Erectile Dysfunction; Benign Prostatic Hyperplasia
• Interventions: Drug: Placebo; Drug: Udenafil

• Registration Number: NCT01967251
• Lead Sponsor: Takeda

Brief Summary

The purpose of this study is to evaluate the efficacy, dose-response and safety of udenafil 25 mg, 50 mg and 75 mg every day (q.d.) for 12 weeks in the treatment of lower urinary tract symptoms (LUTS) associated with benign prostatic hyperplasia (BPH and for the treatment of erectile dysfunction (ED).

Detailed Description

The drug being tested in this study is called Udenafil. Udenafil is being tested to treat lower urinary tract symptoms (LUTS) associated with benign prostatic hyperplasia (BPH) and for the treatment of erectile dysfunction (ED). This study will look at the change in lower urinary tract symptoms (LUTS) associated with benign prostatic hyperplasia (BPH) and in erectile dysfunction (ED) in people who take Udenafil.

The study will enroll approximately 950 patients. Participants taking BPH or ED medication will enter a 4-week wash out period. Patients not previously treated and those who accomplished the wash out period will enter a placebo (dummy inactive pill) lead-in period of another 4 weeks. Participants will then be randomly assigned (by chance, like flipping a coin) to one of the four treatment groups-which will remain undisclosed to the patient and study doctor during the study (unless there is an urgent medical need):

* Udenafil 25 mg

* Udenafil 50 mg

* Udenafil 75 mg

* Placebo (dummy inactive pill) - this is a tablet that looks like the study drug but has no active ingredient

All participants will be asked to take one tablet at the same time each day throughout the study, and will be asked to keep a Sexual Encounter Profile (SEP) diary.

This multi-centre trial will be conducted in Mexico. The overall time to participate in this study is up to 20 weeks. Participants will make 6 visits to the clinic.

Study Timeline

• Study First Submitted: 2013-10-17
• Study First Submitted QC: 2013-10-17
• Study First Posted: 2013-10-22
• Study Start: 2015-09
• Status Verified: 2016-03
• Last Update Submitted: 2016-03-03
• Last Update Posted: 2016-03-04
• Primary Completion: 2016-09
• Study Completion: 2016-09

Recruitment & Eligibility

• Status: WITHDRAWN
• Sex: Male
• Target Recruitment: Not specified

Inclusion Criteria

1. Men ≥ 45 years of age.
2. Sexually active, with a stable female partner with whom the participant expects to have a relationship for the entire duration of the study.
3. The participant has benign prostatic hyperplasia with lower urinary tract symptoms (BPH-LUTS) according to clinical diagnostic criteria, with ≥ 6 months of evolution at the screening visit.
4. Clinical history of erectile dysfunction (ED) (defined as the inability to achieve or maintain the penile erection to achieve a satisfactory sexual relationship) of at least 3 months of evolution.
5. Freely given informed consent at the screening visit (an essential requirement to participate in the study).
6. Bladder obstruction defined by maximal flow rate (Qmax) of 4-15 mI/sec (with a premicturition volume of 150 to 550 mL evaluated by ultrasound, with a minimum micturition volume of 125 mL) at Visit I immediately prior to active treatment initiation.
7. Total score of ≥ 13 points in the InternationaI Prostate Symptom Score (IPSS) questionnaire at Visit 1, immediately prior to active treatment initiation.

Exclusion Criteria

1. Participants that are currently taking nitrates, antiandrogens, estrogens, luteninizing hormone-releasing hormone agonist/antagonist, or anabolic steroids at study entry. Participants that are taking a stable dose level of testosterone are not excluded.
2. Post-void residual (PVR) volume ≥ 300 mL, as assessed by ultrasound at the Visit 1.
3. Prostate-specific antigen (PSA) ≥ 10.0 ng/mL at the Visit 1.
4. PSA of 4.0 - 10.0 ng/ml if free PSA is < 0,25 (25%) at Visit 1.
5. Clinical evidence of prostate cancer.
6. Glycosylated hemoglobin (Hb1Ac) > 10 % at study entry.
7. Patients who have undergone bladder catheterization due to acute urine retention.
8. Medical history or clinical evidence of any pelvic, bladder or urinary tract condition, or urinary retention that, as judged by the urologist, might compromise protocol compliance.
9. Any surgical procedure in the lower urinary tract (including prostate biopsy) within 30 days prior to the Screening Visit.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Placebo	Placebo	Udenafil placebo-matching tablets, orally, once daily for 12 weeks.
Udenafil 25 mg	Udenafil	Udenafil 25 mg, tablets, orally, once daily for 12 weeks.
Udenafil 50 mg	Udenafil	Udenafil 50 mg, tablets, orally, once daily for 12 weeks.
Udenafil 75 mg	Udenafil	Udenafil 75 mg, tablets, orally, once daily for 12 weeks.

Primary Outcome Measures

Name	Time	Method
Change from Baseline in Total International Prostate Symptom Score (IPSS)	Baseline to Week 12	The IPSS is an 8 question (7 symptom questions + 1 quality of life question) tool used to screen for, rapidly diagnose, track the symptoms of, and suggest management of the symptoms of the disease benign prostatic hyperplasia (BPH). The 7 symptoms questions include feeling of incomplete bladder emptying, frequency, intermittency, urgency, weak stream, straining and nocturia, each referring to during the last month, and each involving assignment of a score from 1 to 5 for a total of maximum 35 points. The 8th question of quality of life is assigned a score of 1 to 6. The total score correlates as follows: 0-7 mildly symptomatic; 8-19 moderately symptomatic; 20-35 severely symptomatic.
Change from Baseline in Erectile Function Domain of the International Index of Erectile Function (IIEF)	Baseline and Week 12	The IIEF is a standardised and validated 15-item self-evaluation scale that provides pre-post treatment clinic evaluations of erectile function, orgasmic function, sexual desire, satisfaction in sexual intercourse and general satisfaction. The Erectile Function domain (6-item) provides pre-post treatment evaluations of erectile function.

Secondary Outcome Measures

Name	Time	Method
Participants with Adverse Events	12 weeks	AEs will be evaluated by monitoring participants vital signs, laboratory tests (blood chemistry, hematology, coagulation and serology tests, urianalysis), electrocardiography (ECG).