MCS in Treating Lower Urinary Tract Symptoms (LUTS) Suggestive of Benign Prostatic Hyperplasia

Double-Blind, Randomized, Placebo-Controlled Study to Investigate the Efficacy and Safety of MCS in Treating Lower Urinary Tract Symptoms Suggestive of Benign Prostatic Hyperplasia

Phase III, Randomized, double-blind, parallel placebo-controlled study. Two arms: MCS (30mg/day) vs. placebo.

Subproject MCS-2: alpha-blocker naïve subjects

Subproject MCS-3: subjects responding poorly to alpha-blocker

For MCS-2 This is a double-blind, randomized, placebo-controlled, parallel study where eligible male subjects (age 40, N=188), after a two-week washout period, will be randomized at 1:1 ratio to receive either MCS 30 mg/day or placebo for 12 weeks.

Group A: MCS 30 mg/day for 12 weeks Group B: placebo for 12 weeks

Subjects are limited to those who are currently not being treated medically for BPH or LUTS with alpha-blockers, anti-cholinergics, 5-alpha reductase inhibitors, or hormonal therapeutic agents. For each treatment arm, about 85 subjects eligible for final per protocol analysis will be recruited. Concerning an expected dropout rate of 10%, 188 subjects in total will be recruited onto the study.

For MCS-3 This is a double-blind, randomized, placebo-controlled, add-on, parallel study where eligible male subjects (age 40, N=242), after a two-week washout period, will be randomized at 1:1 ratio to receive either MCS 30 mg/day plus alpha-blocker or placebo plus alpha-blocker for 12 weeks.

Group A: alpha-blocker plus MCS 30 mg/day Group B: alpha-blocker plus placebo

Subjects are limited to those who are currently not being treated medically for BPH or LUTS with anti-cholinergics, 5-alpha reductase inhibitors, or hormonal therapeutic agents. For each treatment arm, about 220 subjects eligible for final per protocol analysis will be recruited. Concerning an expected dropout rate of 10%, 242 subjects in total will be recruited onto the study.

All participating subjects will be advised to maintain a normal diet as they do before joining the study. However, participating subjects are advised to refrain from extra source of carotenoids supplementation and MCS extracts made into a capsule, soft gel, or crude granule extracts.

Inclusion criteria for subproject MCS-2

• Age ≧ 40 years old.
• Not being treated for BPH or LUTS with Alpha-blocker, anti-cholinergics, 5-alpha reductase inhibitors, or hormonal agents.
• PSA≦4 ng/ml within 4 weeks of V1 and no pathologically-proven prostate cancer.
• No known malignancy, except cancers without signs of recurrence for > 5 years and no need for further anti-cancer treatment.
• AST/ALT≦3X UNL.
• creatinine≦3X UNL.
• Subjects who sign the informed consent form.

Exclusion criteria

• Subjects' LUTS are not BPH-related but are associated with such conditions as urethral stricture, prostatitis, neurogenic bladder, or pelvic treatment procedures.
• Have been treated with pelvis irradiation or pelvic surgery.
• Plan to undergo any invasive procedures within the study period, such as, prostate surgery, prostate biopsy, cystourethroscopy, pelvic surgery, laparotomy, or any procedures needing urethral catheterization.
• Participating in another investigational agent study in the past 12 weeks or are going to do so during the study period.
• Active infection or inflammation.
• Considered ineligible by the investigators.

Inclusion criteria for subproject MCS-3

• Age≧40 years old.
• The alpha-blocker dosage used should be as high as subjects can tolerate.
• No known malignancy, except cancers without signs of recurrence for > 5 years and no need for further anti-cancer treatment.
• PSA≦10.0 ng/ml without pathologically-proven prostate cancer or other cancers. Prostate biopsy is mandatory > 12 weeks before screening, if PSA is≧4 ng/ml to rule out prostate cancer.
• AST/ALT≦3X UNL.
• Creatinine≦3X UNL.
• Subjects who sign the informed consent form.

Exclusion criteria

• Subjects' LUTS are not BPH-related but associated with such conditions as urethral stricture, prostatitis, neurogenic bladder, or pelvic treatment procedures.
• Subjects who have been treated with pelvis irradiation or pelvic surgery.
• PSA > 10.0 ng/ml, abnormal DRE of the prostate or any suspicion of prostate malignancy. However, those who have a negative prostate biopsy are allowed.
• Active infection or inflammation.
• Considered ineligible by the investigators.