Neoplasms

Urinary Tract, Sexual Organs, and Pregnancy Conditions

All Conditions

Prostatic Neoplasms

Genital Neoplasms, Male

Urogenital Neoplasms

Genital Diseases

Genital Diseases, Male

Urogenital Diseases

Prostatic Diseases

Male Urogenital Diseases

All Drugs and Chemicals

Dutasteride

5-alpha Reductase Inhibitors

Enzyme Inhibitors

Hormones

Hormone Antagonists

Eligible subjects will complete a 4-week placebo run-in followed by randomization to matched placebo in a 1:1 ratio.

Eligible subjects will complete a 4-week placebo run-in followed by randomization to 0.5mg dutasteride in a 1:1 ratio. Randomization will be stratified by center.

After successful completion of the placebo run-in phase, subjects who continue to meet eligibility requirements will be randomized into the double-blind phase of the study and issued a 6-month supply of study drug. Subjects will self-administer study drug once daily dosing of 0.5mg of dutasteride orally for up to 4 years.

After successful completion of the placebo run-in phase, subjects who continue to meet eligibility requirements will be randomized into the double-blind phase of the study and issued a 6-month supply of study drug. Subjects will self-administer study drug once daily orally for up to 4 years.

Placebo

GSK Clinical Trials

This 4-year study will compare how safe and effective an oral investigational medicine is (compared to placebo) in preventing the development of prostate cancer in men that are defined by the study entrance criteria as being at an increased risk for prostate cancer. Study visits to the clinic will occur every 6 months for up to 4 years (10 clinic visits), and a prostate biopsy will be performed at 2 and 4 years of treatment.

"REDUCE" - A Clinical Research Study To Reduce The Incidence Of Prostate Cancer In Men Who Are At Increased Risk

A Randomized, Double-Blind, Placebo-Controlled, Parallel Group Study of the Efficacy and Safety of Dutasteride 0.5 mg Administered Orally Once Daily for Four Years to Reduce the Risk of Biopsy-Detectable Prostate Cancer

Patient-level data for this study will be made available through www.clinicalstudydatarequest.com following the timelines and process described on this site.

Study biopsies consisted of 10 biopsy samples (cores) in a pre-defined pattern. Biopsies were read at the central pathology laboratory (CPL, which processed the majority, 94%, of biopsies). Biopsy cases that were positive for prostate cancer or precancerous lesions (high-grade prostatic intraepithelial neoplasia\[HGPIN\] or typical small acinar proliferation \[ASAP\]) and prostate surgeries were reviewed by the lead pathologist.

Study biopsies (biop.) consisted of 10 biop. samples (cores) in a pre-defined pattern and were read at the central pathology laboratory. Biop. cases that were positive for prostate cancer or precancerous lesions (HGPIN or ASAP) and prostate surgeries were reviewed by the lead pathologist. Participants included in the risk sets at Years 1-2 and Years 3-4 included those with a positive biop. at Years 1-2 or a biop. after Months 18-24, and those with a positive biop. at Years 3-4 or a biop. after Month 42, respectively. Overall included participants with a positive biop. or biop. after Month 42.

Study biopsies consisted of 10 biopsy samples (cores) in a pre-defined pattern. Biopsies were read at the central pathology laboratory (which processed the majority, 94%, of biopsies). Biopsy cases that were positive for prostate cancer or precancerous lesions (HGPIN or ASAP) and prostate surgeries were reviewed by the lead pathologist. Participants included in the risk set at Years 1-2, Years 3-4, and Overall (Years 1-4) were those who had a biopsy during the specified time period.

Gleason score was determined by examining prostate biopsies and surgical samples. The Gleason scoring system sums the two most common Gleason grade patterns in order to predict the likelihood of a participant doing well or badly with their cancer. Gleason grades range from 1 (normal) to 5 (advanced cancer). The lowest Gleason score is 2 (1+1), and the highest Gleason score is 10 (5+5). A Gleason score of 2-6 is a low-grade cancer; a Gleason score of 7-10 is high-grade cancer. The most severe high-grade cancers are the subset of Gleason scores 8-10.

The occurrence and quantity of high-grade prostatic intraepithelial neoplasia (HGPIN) and atypical small acinar proliferation (ASAP) at biopsy were measured. HGPIN and ASAP are considered precancerous conditions. A participant diagnosed with prostate cancer only (i.e., no HGPIN or ASAP) was counted in both the first category ("HGPIN or prostate cancer diagnosis") and again in the last category ("HGPIN, ASAP, or prostate cancer diagnosis").

The amount of prostate biopsy tissue with HGPIN was measured.

The average amount of cancer seen by the pathologist in the prostate tissue samples taken during the biopsy was measured. A core is a prostate biopsy sample.

The average number of prostate biopsy samples (cores) determined to be cancerous by the pathologist was measured. Normally, 10 cores were taken per biopsy for each participant.

The treatment alteration score is a measure of the cellular changes due to treatment (effect of male hormone withdrawal) on the nucleus and cytoplasm of the prostate cancer cell. The treatment alteration score is the sum of two scores (the nuclear alteration score and the cytoplasmic architectural score), each ranging from 0 to 3, with 0 indicating no change and 3 indicating severe changes.

The number of participants who received treatment for prostate cancer was measured. Prostate cancer interventions included surgical interventions (e.g., prostatectomy, adenomectomy, transurethral resection) and non-surgical interventions (e.g., chemotherapy, hormone therapy, radiation therapy).

The IPSS is a 7-item questionnaire that measures urinary symptoms. It measures the level of urinary symptoms (including incomplete emptying, frequency, intermittency, urgency, weak stream, straining, and nocturia) reported as the total IPSS score. Each of the 7 questions has a 6-point response scale (0=none/not at all to 5=almost always) with a total score that can range from 0-35: mild (0-7), moderate (8-19), or severe (20-35). Estimates are based on adjusted means from the general linear model: change from baseline = baseline value and cluster and treatment.

Prostate volume was measured by transrectal ultrasound (TRUS) when biopsies were performed at Year 2 and Year 4. The investigator calculated the prostate volume using three prostate measurements (anteroposterior, cephalocaudal, and transverse diameters). Estimates are based on the adjusted means from the general linear model: log(Post-Baseline/Baseline value) = treatment and cluster and log (baseline value).

Maximum urinary flow was measured at selected sites using a Dantec Uroflow meter with a Thompson filter. Change from baseline was calculated as Month 12, 24, 36, and 48 values minus the baseline value. Estimates are based on the adjusted means from the general linear model: change from baseline = baseline Qmax and treatment. This measurement was performed at selected centers.

Medication taken during the study, including alpha blockers, was recorded at each 6-month study visit and during phone calls that occurred 3 months after each visit.

A participant was considered to have AUR when he reported being unable to urinate and required catherization. Participants were asked to report any events of AUR during the study.

A participant was considered to have a UTI if the investigator noted that the participant had UTI symptoms and had been prescribed antibiotics. Participants were asked to report any events of UTI during the study.

Participants reported events of macroscopic hematuria (visible blood in the urine) throughout the study.

Participants reported events of macroscopic hematospermia (visible blood in semen) throughout the study.

Overall survival is assessed as the number of deaths reported throughout the study.

The BII is a 4-item questionnaire that rates the level of BPH-related physical discomfort, worry, and interference with normal activities the participant has experienced. The total BII score ranges from 1 (no impact on symptoms) to 13 (major impact on symptoms). Participants completed the questionnaire at Baseline and at each 6-month visit. Participants whose language did not have a validated translation of the questionnaire did not participate. Estimates are based on the adjusted means from the general linear model:change from baseline = baseline value and cluster and treatment.

The MOS Sleep-6S is a 6-item questionnaire measuring quality of sleep. Scores range from 1 (all of the time) to 6 (none of the time) and are converted to a 1-100 scale and then averaged; a higher score indicates greater negative impact, which indicates more sleep disturbance. Participants completed the questionnaire at Baseline and at each 6-month visit. Participants whose language did not have a validated translation of the questionnaire did not participate. Estimates are based on the adjusted means from the general linear model: change from baseline=baseline value and cluster and treatment.

The NIH CSPI is a 9-item questionnaire that measures chronic prostatitis symptoms. The total score ranges from 0 to 43. A higher score indicates greater negative impact of prostatitis. Participants completed the questionnaire at Baseline and at each 6-month visit. Participants whose language did not have a validated translation of the questionnaire did not participate. Estimates are based on the adjusted means from the general linear model: change from Baseline = Baseline Value and Cluster and Treatment.

The QOL Q8 is the last question of the IPSS Questionnaire. It is a question about the participant's quality of life as it relates to prostate symptoms. Responses range from 0 (most positive) to 6 (most negative). A higher score indicates worse quality of life. Participants completed the questionnaire at Screening, Baseline, and at each 6-month visit. Estimates are based on the adjusted means from the general linear model: change from baseline = baseline value and cluster and treatment.

The PASSFI is a 3-item questionnaire that measures sexual function. Responses range from 0 (big problem) to 4 (no problem), with a total score of 12. A higher score indicates fewer problems with sexual functioning. Participants completed the questionnaire at Baseline and then yearly . Participants whose language did not have a validated translation of the questionnaire did not participate. Estimates are based on the adjusted means from the general linear model: change from baseline = baseline value and cluster and treatment.

Number of participants whose DHT, the active form of the male sex hormone testosterone, was less than 0.555 nanomoles/liter and below the level of detection at Month 48 was measured. It was measured by taking blood samples at screening and yearly thereafter.

Testosterone, a male sex hormone, was measured by taking blood samples at screening and yearly thereafter.

GlaxoSmithKline

Placebo, repeat oral once daily dosing for 4 years. Placebo supplied as matching dutasteride capsules.

Dutasteride 0.5 milligrams (mg), repeat oral once daily dosing for 4 years. Dutasteride supplied as gelatin capsule.

Dutasteride 0.5 mg

Total

Age, Continuous

Sex: Female, Male

White

Black

Asian

American Hispanic

Other

Missing

Race/Ethnicity, Customized

GSK Response Center

Years 1- 2, n=4073, 4049

Years 3- 4, n=2815, 2844

Overall, n=4073, 4049

Efficacy Population: all randomized participants with a negative entry biopsy, as determined by the CPL, who received at least 1 dose of study drug. The crude rate approach included all participants at risk at the beginning of each time period .

Number of Participants With Biopsy-detectable Prostate Cancer at Years 2 and 4 (Crude Rate Approach)

Years 1-2, n=3319, 3209

Years 3-4, n=2325, 2434

Overall, n=2903, 2869

Efficacy Population, modified crude rate: participants who either were diagnosed with prostate cancer during the study or had an end of time period biopsy. N for each time period is the number who either had at least 1 biopsy in the final 6 months of the time period or had a positive biopsy anytime during the time period.

Number of Participants With Biopsy-detectable Prostate Cancer at Years 2 and 4 (Modified Crude Rate Approach)

Years 1-2, n=3364, 3244

Years 3- 4, n=2359, 2451

Overall, n=3424, 3305

Efficacy Population, restricted crude rate: the number of prostate cancer events is based on the the number of participants who had at least one biopsy during the time period. Ns at Years 1-2 and Years 3-4 are the number who had a biopsy in those time periods; the overall n is the number of participants who had 1 or more biopsy during Years 1-4.

Number of Participants With Biopsy-detectable Prostate Cancer at Years 2 and 4 (Restricted Crude Rate Approach)

Between 2 and 6

Between 7 and 10

Between 8 and 10

Biopsied Population: all randomized participants with a negative entry biopsy who received at least 1 dose of study treatment and who had at least 1 biopsy reviewed by the central pathology lab. Only needle biopsies are included (surgeries are excluded). The number analyzed is smaller than the total number in the population due to missing values.

Number of Participants With the Indicated Gleason Score at Diagnosis

HGPIN or prostate cancer diagnosis

HGPIN and no prostate cancer

HGPIN and no ASAP and no prostate cancer

HGPIN or ASAP

HGPIN or ASAP and no prostate cancer

HGPIN, ASAP, or prostate cancer diagnosis

Biopsied Population: the number analyzed is the total number in the population

Number of Participants With HGPIN, ASAP, and Prostate Cancer at Biopsy

Biopsied Population. Only needle biopsies are included (surgeries are excluded). The number analyzed is smaller than the total number in the population due to missing values.

Volume of HGPIN at Biopsy

Prostate Cancer Population: all participants in the Efficacy Population who received a post-baseline diagnosis of prostate cancer by the central pathology laboratory. Only needle biopsies are included (surgeries are excluded). The number analyzed is smaller than the total number in the population due to missing values.

Percentage of Core Involved at Diagnosis

Prostate Cancer Population. Only needle biopsies are included (surgeries are excluded). The number analyzed is smaller than the total number in the population due to missing values.

Number of Cancer-positive Cores

Nuclear, n=3357, 3256

Architectural, n=3357, 3258

Total, n=3357, 3256

Treatment Alteration Score

Any intervention

Any surgical intervention

Any non-surgical intervention

Number of Participants Undergoing Intervention (Surgical and Non-surgical) for Prostate Cancer Treatment

Efficacy Population, last observation carried forward (LOCF). In the LOCF approach, missing values at post-baseline assessments are replaced with the participant's previous non-missing post-baseline assessment. The number analyzed is smaller than the total number in the population due to missing values.

Adjusted Mean Change From Baseline in the International Prostate Symptom Score (IPSS) at Month 48

Month 24, n=3192, 3116

Month 48, n=3289, 3194

Efficacy Population (LOCF). The number analyzed is smaller than the total number in the population due to missing values.

Adjusted Mean Percentage Change From Baseline in Prostate Volume at Months 24 and 48

Month 12, n=1178, 1168

Month 24, n=1337, 1295

Month 36, n=1375, 1334

Month 48, n=1390, 1359

Adjusted Mean Change From Baseline in Maximum Urinary Flow (Qmax) at Months 12, 24, 36, and 48

Years 1-2

Overall

Number of Participants Starting Alpha Blockers to Control Benign Prostatic Hyperplasia (BPH) Symptoms

Number of Participants With at Least One Event of Acute Urinary Retention (AUR)

Years 1-2, n=4073, 4049

Years 3-4, n=3363, 3318

Number of Participants With at Least One Urinary Tract Infection (UTI)

Number of Participants With Post-biopsy Macroscopic Hematuria

Number of Participants With Post-biopsy Macroscopic Hematospermia

Overall Survival

Efficacy Population (LOCF). The numbers presented are less than the overall population, as data were not available for all participants.

Adjusted Mean Change From Baseline in the Benign Prostatic Hypertrophy (BPH) Impact Index (BII) at Month 48

Adjusted Mean Change From Baseline in The Medical Outcomes Study Sleep Problems Index 6-item Standard Version (MOS Sleep-6S) at Month 48

Adjusted Mean Change From Baseline in the National Institutes of Health Chronic Prostatitis Symptom Index (NIH CPSI) at Month 48

Adjusted Mean Change From Baseline in Quality of Life Question 8 (QOL Q8) at Month 48

Adjusted Mean Change From Baseline in the Problem Assessment Scale of the Sexual Function Index (PASSFI) at Month 48

<0.555 nanomoles/Liter

<level of detection

Number of Participants With the Indicated Serum Dihydrotestosterone (DHT) Concentration at Month 48

Mean Change From Baseline in Testosterone at Month 48

Overall Study

Infections

Symptoms and General Pathology

Nervous System Diseases

Wounds and Injuries

Rare Diseases

Communicable Diseases

Spinal Cord Injuries

Urinary Bladder, Neurogenic

Urinary Tract Infections

Urinary Retention

Urologic Diseases

Urination Disorders

Female Urogenital Diseases

Pregnancy Complications

Female Urogenital Diseases and Pregnancy Complications

Neurologic Manifestations

Urinary Bladder Diseases

Chronic Graft Versus Host Disease

Patients will use the Connected Catheter to empty the bladder during the course of treatment.

Connected Urinary Catheter

The Connected Catheter is a fully internal, urethral indwelling urinary prosthesis designed for improved bladder management in males with urinary retention disorders requiring catheterization. It is a sterile, extended-use device that resides fully internally to the male lower urinary tract for an intended use life of up to 7 days per catheter.

Spinal Singularity has developed the Connected Catheter System to address several drawbacks of urinary catheters. The Connected Catheter is fully internal, indwelling urinary prosthesis designed for improved bladder management in males with urinary retention disorders requiring catheterization. Each subject will use the Connected Catheter for up to 35-40 days. This includes five device exchange appointments. The appointments are spaced 7 days apart and at each appointment the catheter will be replaced with a new one. Additionally, weekly follow-up will occur for 14 days following the final appointment after the subject discontinues use of study device and reverts to his original catheter.

Connected Catheter- Safety and Effectiveness Study

Evaluation of the Safety and Clinical Performance of the Gen 2 Connected Catheter - Wireless Urinary Prosthesis for Management of Chronic Urinary Retention

Rate of participants with successful voiding using the Connected Catheter as assessed by Post-Residual Volume (PVR) measurement via ultrasound

A subject is considered a responder to the treatment if a minimum of 80% of their PVR values met the following criteria

PVR is ≤ 50 mL OR PVR is ≤ baseline PVR with the standard of care catheter

Rate of participants treated with the Connected Catheter reported with a serious device related adverse event

Rate of Connected Catheter successfully inserted, anchored and removed

Rate of Connected Catheter valves sealed successfully

Rate of participants treated with the Connected Catheter with improved overall quality of life as measured by the SCI-QOL Survey and other surveys

Rate of participants treated with the Connected Catheter reported with a urinary tract infection

Rate of participants treated with the Connected Catheter that experience a lower urinary tract injury

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization	Link
"REDUCE" - A Clinical Research Study To Reduce The Incidence Of Prostate Cancer In Men Who Are At Increased Risk	NCT00056407	Neoplasms, Pros...	Dutasteride Placebo	50 Years - 75 Years	GlaxoSmithKline
Connected Catheter- Safety and Effectiveness Study	NCT03843073	Urinary Retenti... Neurogenic Blad... Urologic Diseas...	Connected Urina...	18 Years -	Spinal Singularity

Spots Global Cancer Trial Database for enlarged prostate