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.

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.