Randomized, Double-Blind, Multicenter, Placebo-Controlled, Proof-of-Concept Trialto Assess the Efficacy and Safety of 4-Weeks Treatment with AUS-131 (S-Equol) on Benign Prostatic Hyperplasia
试验速览
- 阶段
- 2 期
- 状态
- Other
- 入组人数
- 124
- 试验地点
- 5
- 主要终点
- The primary efficacy endpoint is the change from Baseline in PSA concentration at the Week 4
研究概览
简要总结
The preclinical and clinical data available indicate that AUS-131 is well tolerated and presents an
acceptable risk-to-benefit ratio to the patient.
Two Phase 1 clinical studies have been completed. An acceptable safety profile was reported in both these studies. The TEAE for study drug were similar to placebo and only 2 mild TEAE
(abdominal cramps and nausea) were considered related to study drug for both studies. Since the safety data is blinded it is not known if these TEAE are in the placebo or drug groups. The potential benefits of a potent ER-β agonist to effectively treat the symptoms of benign prostatic hyperplasia while providing minimal risk to the patient would be unprecedented.
The PK data from the single dose Phase 1 study AUS-CT01, indicate that, based on the T1/2 for
AUS-131, a BID dosing regimen is appropriate to ensure adequate systemic exposure at steady state. The PK data from the multidose Phase 1 study, AUS-CT02, confirmed a BID dosing regimen is appropriate. The 10, 50, and 150-mg BID doses in the current study are comparable to
the dosing regimen in the 14-day AUS-CT02 study with dosing cohorts of 10, 20, 40, 80, or 160 mg BID. The older individuals (45-65 years) had different PK profiles compared to the younger group (18-44 years) in the single-dose Phase 1 study, AUS-CT01. However, the safety profile was similar between groups. Dose-normalized AUC0-12 and Cmax were not significantly different between the younger and older age groups, for single and steady state doses in the multidose Phase 1 study, AUS-CT02. The safety profile was similar between the older individuals compared to the younger individuals for both studies which suggest the safety profile
for the Phase 2 studies will be similar to those reported in the Phase 1 studies.
研究设计
- 研究类型
- Interventional
- 分配方式
- Other
- 盲法
- Participant and Investigator Blinded
入排标准
- 年龄范围
- 50.00 Year(s) 至 70.00 Year(s)（—）
- 性别
- Male
入选标准
- •Inclusion Criteria A patient will be eligible for study entry if all of the following inclusion criteria are met:
- •Is male > 50 and ≤70 years of age at Screening.
- •Has a normal digital rectal exam with the exception of prostate enlargement.
- •Has suffered from symptoms of BPH for at least the 6 months before Screening (e.g., micturition disturbances such as daytime frequency, nocturia, urgency, difficulty initiating micturition, impaired quality of the urinary stream, feeling of incomplete voiding, or interruption of the urinary stream).
- •Has a prostate volume ≥ 20 mL and ≤ 70 mL as assessed by ultrasound.
- •Has a serum PSA concentration > 1.5 ng/mL and ≤ 10 ng/mL at Screening.
- •Has an IPSS ≥ 13 at Screening and Baseline.
- •Has a Qmax > 5 cc/sec and < 15 cc/sec with a voided volume ≥ 125 cc at Screening (and Baseline, if applicable).
- •Is able to provide written informed consent to participate in the study and able to understand the procedures and study requirements.
- •Must voluntarily sign and date an informed consent form (ICF) that is approved by an Institutional Review Board (IRB) or Independent Ethics Committee (IEC) before the conduct of any study procedure.
- •Is willing and able to comply with all study requirements and instructions of the site study staff.
排除标准
- •Exclusion Criteria A patient will not be eligible for study entry if any of the following exclusion criteria are met:
- •Has a known history of allergic reaction or clinically significant intolerance to ingredients of the study drug.
- •Neurogenic bladder dysfunction.
- •Has bladder neck contracture or urethral stricture.
- •Has acute or chronic prostatitis or urinary tract infection.
- •Has, or has a history of, prostate cancer or carcinoma of the prostate suspected on digital rectal exam or transrectal ultrasound, or has a serum PSA concentration > 10 ng/mL; patients with a PSA concentration > 4 ng/mL and ≤ 10 ng/mL must have prostate cancer ruled out to the satisfaction of the investigator.
- •Has a residual void volume > 250 mL.
- •Has any clinically significant unstable cardiac, respiratory, neurological, immunological, hematological, hepatic, renal, endocrine, or gastric disease or any other condition that, in the opinion of the investigator, could compromise the patient’s welfare, ability to communicate with the study staff, or otherwise contraindicate study participation.
- •Shows presence of any manifest premalignant or malignant disease except treated skin cancers (except melanoma).
- •Has a history of smoking more than 5 cigarettes daily within the year before Screening.
- •Has resting systolic blood pressure (BP) > 160 mmHg or < 90 mmHg, or diastolic BP > 90 mmHg or < 60 mmHg at Screening.
- •Has bladder stones as detected by ultrasound.
- •Had previous prostate surgery or other invasive treatment for BPH.
- •Has Parkinson’s disease or multiple sclerosis.
- •Had stroke or myocardial infarction within 5 months before Baseline.
- •Has clinically significant abnormal screening electrocardiogram (ECG) or unstable angina or severe congestive heart failure.
- •Has active liver disease with aspartate aminotransferase (AST) > 2 times the upper limit of normal (ULN), alanine aminotransferase (ALT) > 2 times ULN, unexplained alkaline phosphatase > 3 times ULN, total bilirubin > ULN, renal insufficiency with creatinine > 1.7 mg/dL, or clinically significant abnormal hemoglobin, white blood cell count, or platelet count.
- •Has a history of postural hypotension or has a fall in systolic BP > 20 mm Hg after 2 minutes in a standing position.
- •Received alpha blocker therapy within 28 days before Baseline.
- •Received androgens, anti-androgens, 5-alpha reductase inhibitors, or luteinizing hormone-releasing hormone (LHRH) analogs within 3 months before Baseline.
- •Received tricyclic antidepressants or plant extracts (e.g., saw palmetto) within 1 month before Baseline.
- •Has initiated new use (i.e., within the past 4 weeks before Screening) or otherwise are not on stable doses of phosphodiesterase-5 inhibitors during the 4 weeks before Screening.
- •Has known or suspected history of alcoholism or drug abuse or misuse within the last 5 years.
- •Is considered by the investigator, for any reason (including, but not limited to, the risks described as precautions, warnings, and contraindications in the current version of the Clinical Investigator’s Brochure for AUS-131 [S-equol]), to be an unsuitable candidate to receive the study drug.
- •Patients who test positive at Screening and can produce documentation from their physician for the medication that caused the positive test may be considered for study enrollment at the discretion of the investigator.
- •Has significant difficulties swallowing capsules or is unable to tolerate oral medication.
- •Has participated in another clinical trial or received any investigational drug or device or investigational therapy within 30 days before Screening.
结局指标
主要结局
The primary efficacy endpoint is the change from Baseline in PSA concentration at the Week 4
时间窗: Day 28 ±2 days
Visit (V5).
时间窗: Day 28 ±2 days
次要结局
- The secondary endpoints are the following: • Change from Baseline in prostate size (assessed by transrectal ultrasonography)(• Change from Baseline in Qmax)