A MULTICENTRIC, DOUBLE BLIND, PLACEBO CONTROLLED, PARALLEL GROUP, 3 ARM, BIOEQUIVALENCE STUDY COMPARING PENTOSAN POLYSULFATE SODIUM, ORAL CAPSULE 100 mg (WATSON PHARMA PVT. LTD.), TO ELMIRON ORAL CAPSULE 100 mg (ORTHO−MCNEIL−JANSSEN PHARMACEUTICALS, INC) AND BOTH ACTIVE TREATMENTS TO PLACEBO (WATSON PHARMA PVT. LTD.) IN THE TREATMENT OF INTERSTITIAL CYSTITIS / BLADDER PAIN SYNDROME
试验速览
- 阶段
- 不适用
- 状态
- 尚未招募
- 发起方
- 入组人数
- 528
- 试验地点
- 22
- 主要终点
- 1. To evaluate the therapeutic equivalence of the efficacy and safety of Pentosan Polysulfate Sodium, Oral Capsule 100 mg (Watson Pharma Pvt. Ltd) and Elmiron Oral Capsule 100 mg (Ortho−McNeil−Janssen Pharmaceuticals, Inc) in the treatment of interstitial cystitis/bladder pain syndrome and
研究概览
简要总结
The proposed study is a Bioequivalence Study With Clinical Endpoint with a randomized, double blind, three-arm, parallel group, placebo controlled design, at approximately 20 sites in India designed to establish bioequivalence of Pentosan Polysulfate Sodium, Oral Capsule 100 mg (WATSON PHARMA PVT. LTD.) and Elmiron Oral Capsule 100 mg (Ortho ’McNeil ’Janssen Pharmaceuticals, Inc) in the treatment of interstitial cystitis/bladder pain syndrome. xml:namespace prefix = o ns = "urn:schemas-microsoft-com:office:office" /
The objectives of this proposed trial are as below:
Ø To evaluate the therapeutic equivalence of the efficacy and safety of Pentosan Polysulfate Sodium, Oral Capsule 100 mg (WATSON PHARMA PVT. LTD.) and Elmiron Oral Capsule 100 mg (Ortho ’McNeil ’Janssen Pharmaceuticals, Inc) in the treatment of interstitial cystitis / bladder pain syndrome.
Ø To assess the superiority of the efficacy of Pentosan Polysulfate Sodium, Oral Capsule 100 mg (WATSON PHARMA PVT. LTD.) and Elmiron Oral Capsule 100 mg (Ortho ’McNeil ’Janssen Pharmaceuticals, Inc) in the treatment of interstitial cystitis / bladder pain syndrome.
In this trial a total of 528 patients (176:176:176), with bladder pain associated with interstitial cystitis, need to be enrolled and randomized in the treatment allocation ratio of 1:1:1 for Test vs. Ref vs. Placebo in order to achieve 420 (140:140:140) patients in the PP population assuming that the overall dropout rate from the randomized patients to PP population is about 20%. Number of PPS non-naïve subjects enrolled in study should not exceed 264.
For this trial the patient participation will last for 91 days (90 days of double-blind study treatment).
In this trial each patient will receive Investigational Medicinal Product (IMP) one capsule each orally three times daily as per randomization. The capsules should be taken with water at least 1 hour before meals or 2 hour after meals. The patients receiving IMP will undergo visit wise assessment throughout the study for the efficacy and safety. For each patient the primary endpoint evaluation will be assessed after 3 months of treatment (i.e., at visit no. 6, Day 90 ± 4 days).
A stratified randomization will be used for this study where the patient population will be divided into two sub-populations of PPS naïve & PPS non-naïve. Thereafter, patients will be randomly assigned in a treatment allocation ratio of 1:1:1 to receive the Test product or the Reference Product or the Placebo, respectively in each stratum. The randomization assignment will be generated by a non-study assigned, independent expert using Medidata® solutions and will be generated by the third party vendor of the CRO i.e. Medidata Solutions, Inc., USA. A sealed copy of the randomization scheme will be retained at the study site and should be available to FDA investigators at the time of site inspection to allow for verification of the treatment assigned to each subject.
CLINICAL ENDPOINTS:
TEST OF THERAPEUTIC EQUIVALENCE:
For the primary efficacy parameter, i.e. the proportion of patients in the per protocol population identified as “treatment success†occurring after three months of treatment and evaluated from baseline to end of treatment visit, a two-sided 90% confidence interval for the difference in success proportions (PT – PR) between test and reference products should be contained within [+0.20, -0.20] in order to establish equivalence.
TEST OF SUPERIORITY:
As a parameter for determining adequate study sensitivity, the test product and RLD should both be statistically superior to placebo with regard to the “treatment success†rate occurring after 3 months of treatment (at the visit no. 6, Day 90 ± 4days) using the modified intent-to-treat (mITT) study population, with and without last observation carried forward (LOCF).
Thus, each active arm will be compared to the placebo (vehicle control) to establish superiority of active arms over the placebo for the treatment success rate at the end of treatment visit. The tests for superiority will be conducted independently for test and reference treatments and superiority will be claimed if the two-sided p-value is < 0.05 at 5% level of significance for both, test and reference products separately.
A secondary subgroup analysis of the difference in means of the primary efficacy outcome variable between PPS naïve vs PPS non-naïve patients. Number of PPS non-naïve subjects enrolled in study should not exceed 264.
Comparison of the number of patients needing add-on/rescue therapy in each arm and mean times to add-on/rescue therapy in each arm can be compared, supporting superiority of the active arms over placebo.
研究设计
- 研究类型
- Interventional
- 分配方式
- Stratified randomization
- 盲法
- Participant and Investigator Blinded
入排标准
- 年龄范围
- 18.00 Year(s) 至 65.00 Year(s)（—）
- 性别
- All
入选标准
- •Males and females aged more than 18 years with moderate to severe interstitial cystitis
- •Patient has experienced bladder pain, urinary urgency and urinary frequency, each not related to a urinary tract infection, for at least the previous 6 months prior to entry into the study.
- •An average voided bladder volume of 50 to 200 mL (as determined over 3 consecutive days documented in the urinary frequency diary).
- •Urine culture negative for clinically significant urinary tract infection (at baseline or within 2 weeks prior to baseline visit).
- •Urine cytology negative for neoplastic cells (at baseline or within 2 months prior to baseline visit).
- •Cystoscopic examination under anesthesia by the investigator showing petechial hemorrhages or ulcers following one or two distentions of the bladder at 80 cm of water pressure for one minute performed within 6 months prior to baseline visit and at least 6 weeks prior to baseline visit.
- •Patients that enter remission after their cystoscopic examination should not be scheduled for their baseline visit until the symptoms reappear.
- •Patients currently being treated with Pentosan Polysulfate Sodium may be enrolled in the study if Pentosan Polysulfate Sodium treatment is stopped at least for 4 weeks (wash-out period) prior to baseline visit.
排除标准
- •More than 25 voids per day
- •Bladder capacity of more than 350 mL during awake exam
- •Patient is planning to use intravesical therapy for interstitial cystitis within one month prior to baseline visit.
- •Patient planning to use medical treatment for interstitial cystitis within one month prior to baseline visit.
- •Patient taking any anticoagulants
- •Patient with known aneurysm, thrombocytopenia, hemorrhagic disease, hemophilia, or gastrointestinal ulceration (e.g., active bleeding peptic ulcer disease), polyps, or diverticula.
- •Patient with known hypersensitivity to Pentosan Polysulfate Sodium, including excipients (microcrystalline cellulose and magnesium stearate), or heparin.
- •Patient who has a history of, or currently has, any of these: Neurogenic bladder or diabetic cystopathy, Pelvic irradiation or chemical cystitis, including that due to cyclophosphamide, Presence of urethral, pelvic, or rectal carcinoma, Benign or malignant bladder tumors, Tuberculous cystitis, Urinary schistosomiasis, Bladder or ureteral calculi, Active genital herpes within 3 months prior to study entry, Urethral and/or bladder obstruction, Augmentation cystoplasty, cystectomy, cystolysis, neurectomy or implanted peripheral nerve stimulator that has affected bladder function.
- •Patient has microscopic hematuria as defined as 5 RBC/high power field at baseline visit without a negative workup within the last year.
- •Patient has current chronic pain condition
- •Patient has clinically significant hepatic disease or clinically significant abnormal liver function tests.
- •Gender specific exclusion criteria: Male: 1) Patient has a post-void residual volume of 150 cc by ultrasound.
- •Patient had a Trans Urethral Resection of Prostate (TURP), Trans Urethral Incision of Prostate (TUIP), Trans Urethral Incision of Bladder Neck (TUIBN), Trans Urethral Microwave Thermotherapy (TUMT), Trans Urethral Needle Ablation (TUNA), balloon dilation of the prostate, open prostatectomy or any other prostate surgery or treatment such as cryotherapy or thermal therapy.
- •Patient has a history of prostate cancer.
- •Patient is currently being treated for chronic bacterial prostatitis.
- •Female: 1) Patient has a positive pregnancy test at the baseline visit, is pregnant or lactating, or is planning to become pregnant during the study period.
- •Patient has a history of uterine, cervical or vaginal cancer during the past 3 years.
- •Patient has clinically significant vaginitis at baseline visit.
结局指标
主要结局
1. To evaluate the therapeutic equivalence of the efficacy and safety of Pentosan Polysulfate Sodium, Oral Capsule 100 mg (Watson Pharma Pvt. Ltd) and Elmiron Oral Capsule 100 mg (Ortho−McNeil−Janssen Pharmaceuticals, Inc) in the treatment of interstitial cystitis/bladder pain syndrome and
时间窗: Patient participation will last for 91 days (90 days of double-blind study treatment). | Clinical Evaluations will be performed at: | Visit 1: Pre-screening (Day-3) | Visit 2: Baseline / Randomization Visit (Day 1) | Visit 3: First Interim Visit (Day 15 ± 4 Days) | Visit 4: Second Interim Visit (Day 30 ± 4 Days) | Visit 5: Third Interim Visit (Day 60 ± 4 Days) | Visit 6: End of Treatment Visit (Day 90 ± 4 Days)
次要结局
- 1. To assess the superiority of the efficacy of Pentosan Polysulfate Sodium, Oral(Patient participation will last for 91 days (90 days of double-blind study treatment).)