A Study in Men With Benign Prostatic Hyperplasia

A Phase 2 Clinical Study to Evaluate Daily Oral Doses of LY500307 for 24 Weeks in Men With Lower Urinary Tract Symptoms (LUTS) and Prostatic Enlargement Secondary to Benign Prostatic Hyperplasia (BPH)

Status

Terminated

Phases

Phase 2

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT01097707

Enrollment

414

Registered

2010-04-02

Start date

2010-04-30

Completion date

2011-10-31

Last updated

2019-04-08

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Benign Prostatic Hyperplasia

Brief summary

The purpose of the study is to determine whether LY500307 helps symptoms of Benign Prostatic Hyperplasia (BPH)

Interventions

DRUGLY500307

Administered orally, daily for 24 weeks

DRUGPlacebo

Administered orally, daily for 24 weeks

Study design

Allocation

RANDOMIZED

Intervention model

PARALLEL

Primary purpose

TREATMENT

Masking

TRIPLE (Subject, Caregiver, Investigator)

Eligibility

Sex/Gender

MALE

Age

45 Years to No maximum

Healthy volunteers

Inclusion criteria

* Present at screening with a history of benign prostatic hyperplasia (BPH) for \>6 months. * Have an International Prostate Symptom Score (IPSS) greater than or equal to 13 at screening. * Have a total prostate volume by transrectal ultrasound greater than or equal to 30 milliliter (mL) at screening. * Show signs of bladder outlet obstruction as defined by a peak urinary flow rate (Qmax) greater than or equal to 4 and less than or equal to 15 milliliter/second (mL/sec) (from a prevoid total bladder volume \[assessed by ultrasound\] of greater than or equal to 150 to less than or equal to 550 ml and a minimum voided volume of 125 ml) at screening. * Have a prostate-specific antigen (PSA) greater than or equal to 1.4 and less than or equal to 10 nanogram/milliliter (ng/mL) at screening. * Demonstrate a Post Void Residual less than or equal to 300 mL by ultrasound at screening. * Have not received the following treatments within the specified time period: 1. Finasteride or dutasteride for at least 6 months prior to screening. 2. Any alpha-adrenergic antagonists for at least 4 weeks prior to screening. 3. Any other non-experimental BPH therapy (including an herbal preparation) for at least 4 weeks prior to screening. 4. Any other experimental or off-label BPH therapy such as injectable therapies with a protracted effect for at least 6 months prior to screening. 5. Any overactive bladder treatment for at least 4 weeks prior to screening. 6. Any Erectile Dysfunction treatment which may include oral phosphodiesterase type 5 inhibitors or devices for at least 4 weeks prior to screening. * Have a morning fasting Total Testosterone concentration greater than or equal to 300 nanogram/deciliter (ng/dL) at screening. * If hyperlipidemic, based on history, be stable on statin treatment as determined by the investigator for at least 2 months prior to screening.

Exclusion criteria

* Have completed or withdrawn from this study or have completed or withdrawn from any other study investigating LY500307. * Have any history of BPH-related invasive procedures (for example, Transurethral Resection of the Prostate, open prostatectomy, and minimally invasive procedures that include thermal-based therapies, transurethral microwave treatment, transurethral needle ablation, and stents). * Have active cardiovascular disease as evidenced by the following: 1. Recent Myocardial infarction, unstable angina, stroke or Transient ischemic attack within 6 months of screening. 2. Recent coronary intervention that includes coronary artery bypass surgery, percutaneous coronary artery intervention, or stent placement within 6 months of screening. 3. Recent history of positive stress tests without any written documentation of effective intervention within 6 months of screening. 4. Evidence of heart disease categorized as greater than or equal to Class III functional classification of New York Heart Association (NYHA) within 6 months of screening. * Have known or suspected history of prostate cancer, breast cancer, or other clinically significant neoplastic disease (other than squamous cell or basal cell carcinoma of skin). * Have a history of deep venous thrombosis or pulmonary embolism disease. * Have moderate to severe renal insufficiency. * Have a hemoglobin A1c (HbA1c) greater than 9.0%. * Are on testosterone replacement therapy, or drugs that influence the hypothalamus-pituitary-gonadal axis. * Are on pharmacological treatment other than statins for hyperlipidemia.

Design outcomes

Primary

Measure	Time frame	Description
Change From Baseline to 24-Week Endpoint in International Prostate Symptom Score (IPSS) Total Score	Baseline, 24 weeks	IPSS Total Score is the sum of Questions 1 through 7 of the IPSS questionnaire. Each question is scored from 0 (none/no symptoms) to 5 (frequent symptoms) with an IPSS Total Score range of 0-35 points. Higher numerical scores from the IPSS questionnaire represent greater severity of symptoms.

Secondary

Measure	Time frame	Description
Change From Baseline to 24-Week Endpoint in Peak Urinary Flow Rate (Qmax)	Baseline, 24 weeks	Qmax is defined as the peak urine flow rate measured using standard calibrated uroflowmeter.
Change From Baseline to 24-Week Endpoint in International Prostate Symptom Score-Quality of Life Index (IPSS-QoL)	Baseline, 24 weeks	IPSS QoL assesses participant's response to the following question: If you were to spend the rest of your life with your urinary condition just the way it is now, how would you feel about that? Response options are Delighted (0), Pleased (1); Mostly satisfied (2); Mixed-about equally satisfied and dissatisfied (3); Mostly dissatisfied (4); Unhappy (5); Terrible (6), with a total range of 0-6.
Change From Baseline to 24-Week Endpoint in International Prostate Symptom Score (IPSS) Storage, Voiding and Nocturia Subscores	Baseline, 24 weeks	IPSS Storage (Irritative) subscore is the sum of Questions 2, 4 and 7 of the IPSS questionnaire. Scores range from 0 (no irritative symptoms) to 5 (frequent irritative symptoms), with a total subscore of the 3 questions for irritative subscore ranging from 0 to 15. IPSS Voiding (Obstructive) subscore is the sum of Questions 1, 3, 5 and 6 of the IPSS questionnaire. Scores range from 0 (no obstructive symptoms) to 5 (frequent obstructive symptoms), with a total subscore of the 4 questions of the obstructive score ranging from 0 to 20. Nocturia Subscore is IPSS Question 7, which assesses how many times over the last month a participant gets up to urinate from the time they went to bed at night until the time they got up in the morning. Scores range from 0=None; 1=1 time; 2= 2 times; 3=3 times; 4=4 times; 5=5 or more times.
Percentage Change From Baseline to 24-Week Endpoint in Total Prostate Volume (TPV)	Baseline, 24 weeks	The TPV measurement (milliliters) by transrectal ultrasound (TRUS) is an established diagnostic test for men with lower urinary tract symptoms (LUTS) due to benign prostatic hyperplasia (BPH).
Change From Baseline to 24-Week Endpoint in Fasting Total Testosterone	Baseline, 24 weeks	—
Change From Baseline to 24-Week Endpoint in Lipid Profile	Baseline, 24 weeks	The lipid profile consisted of low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), and triglycerides.
Percentage Change From Baseline to 24-Week Endpoint in Prostate Specific Antigen (PSA)	Baseline, 24 weeks	The units of PSA measurement are nanograms per milliliter (ng/mL).

Countries

Australia, Canada, France, Germany, Greece, Italy, Russia, United States

Participant flow

Participants by arm

Arm	Count
1 mg LY500307 LY500307: Administered orally, daily for 24 weeks	83
3 mg LY500307 LY500307: Administered orally, daily for 24 weeks	80
10 mg LY500307 LY500307: Administered orally, daily for 24 weeks	82
25 mg LY500307 LY500307: Administered orally, daily for 24 weeks	84
Placebo Placebo: Administered orally, daily for 24 weeks	85
Total	414

Withdrawals & dropouts

Period	Reason	FG000	FG001	FG002	FG003	FG004
Overall Study	Abnormal Lab/Electrocardiogram Result	0	0	1	1	1
Overall Study	Adverse Event	4	2	3	1	3
Overall Study	Entry Criteria Not Met	2	1	1	0	1
Overall Study	Lack of Efficacy	1	0	0	1	0
Overall Study	Lost to Follow-up	1	1	2	0	3
Overall Study	Protocol Violation	2	2	3	2	2
Overall Study	Reason unknown	0	0	0	0	1
Overall Study	Sponsor Decision	31	31	34	35	36
Overall Study	Withdrawal by Subject	3	6	1	4	3

Baseline characteristics

Characteristic	3 mg LY500307	10 mg LY500307	25 mg LY500307	1 mg LY500307	Placebo	Total
Age, Continuous	67.67 years STANDARD_DEVIATION 7.34	67.21 years STANDARD_DEVIATION 7.1	63.18 years STANDARD_DEVIATION 7.34	66.97 years STANDARD_DEVIATION 7.55	64.11 years STANDARD_DEVIATION 7.92	65.80 years STANDARD_DEVIATION 7.64
Ethnicity (NIH/OMB) Hispanic or Latino	1 Participants	2 Participants	4 Participants	4 Participants	1 Participants	12 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	79 Participants	80 Participants	80 Participants	79 Participants	84 Participants	402 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants	0 Participants	1 Participants	0 Participants	0 Participants	1 Participants
Race (NIH/OMB) Asian	2 Participants	1 Participants	0 Participants	1 Participants	0 Participants	4 Participants
Race (NIH/OMB) Black or African American	3 Participants	2 Participants	0 Participants	4 Participants	5 Participants	14 Participants
Race (NIH/OMB) More than one race	0 Participants	0 Participants	1 Participants	0 Participants	0 Participants	1 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) White	75 Participants	79 Participants	82 Participants	78 Participants	80 Participants	394 Participants
Region of Enrollment Australia	3 Participants	3 Participants	3 Participants	3 Participants	3 Participants	15 Participants
Region of Enrollment Canada	5 Participants	5 Participants	5 Participants	5 Participants	6 Participants	26 Participants
Region of Enrollment France	2 Participants	2 Participants	2 Participants	2 Participants	3 Participants	11 Participants
Region of Enrollment Germany	11 Participants	12 Participants	12 Participants	12 Participants	11 Participants	58 Participants
Region of Enrollment Greece	1 Participants	2 Participants	2 Participants	2 Participants	2 Participants	9 Participants
Region of Enrollment Italy	5 Participants	5 Participants	5 Participants	5 Participants	5 Participants	25 Participants
Region of Enrollment Russia	12 Participants	12 Participants	12 Participants	12 Participants	13 Participants	61 Participants
Region of Enrollment United States	41 Participants	41 Participants	43 Participants	42 Participants	42 Participants	209 Participants
Sex: Female, Male Female	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Sex: Female, Male Male	80 Participants	82 Participants	84 Participants	83 Participants	85 Participants	414 Participants

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk	EG002 affected / at risk	EG003 affected / at risk	EG004 affected / at risk
deaths Total, all-cause mortality	— / —	— / —	— / —	— / —	— / —
other Total, other adverse events	32 / 83	32 / 80	31 / 82	30 / 84	37 / 85
serious Total, serious adverse events	4 / 83	3 / 80	3 / 82	2 / 84	3 / 85

Outcome results

Primary

Change From Baseline to 24-Week Endpoint in International Prostate Symptom Score (IPSS) Total Score

IPSS Total Score is the sum of Questions 1 through 7 of the IPSS questionnaire. Each question is scored from 0 (none/no symptoms) to 5 (frequent symptoms) with an IPSS Total Score range of 0-35 points. Higher numerical scores from the IPSS questionnaire represent greater severity of symptoms.