Fifty- three patients with long standing IC were enrolled in the study. All completed the trial and had 10 instillations in total. Results demonstrated that Uracyst® was effective in reducing the symptoms of IC.
After six (6) weekly instillations, the responder rate was 47.2%. Responders were defined as a patient having a moderate or marked improvement on the seven point Global Response Assessment (GRA) scale.
Pain, urgency and frequency scores (each measured on visual analogue scales) demonstrated significant reduction in scores (p<0.001)1.
This pilot Phase II, a multi-center, randomized, double-blind placebo controlled study, was the first in this class of therapies (intravesical GAG replenishment therapies) to demonstrate a positive result versus placebo. Sixty five (65) patients with a clinical diagnosis of IC were randomized to receive six once weekly doses of either Uracyst® or the intravesical placebo control.
The results showed that the almost twice as many patients reported a clinically significant benefit with Uracyst® compared to placebo. Both Uracyst® and placebo were well tolerated by the participants.
The results of this pilot were quite positive and provided the rationale to move forward to design a well-powered study16.
Responders in this study were classified as patients with a moderate or marked improvement on the seven point Global Response Assessment (GRA) scale.
A second, small Phase II pilot, multi-center, randomized, double-blind placebo controlled study was conducted in the USA in subjects with IC/BPS. Women were randomized to receive either 8 weekly bladder instillations of 20 mL 2% chondroitin sulfate or 20 mL of inactive control solution. More patients in the chondroitin sulfate group (38.0%) reported moderate or marked improvement (considered responders) compared with the inactive group (31.1%) at the 11 week endpoint visit. Similarly, more subjects in the active treatment group were classified as ICSA and VAS pain responders and reported a greater decrease in ICSI and VAS pain scores than the control group; however, none of these differences were statistically significant. The magnitude of benefit in this study does not support the use of Uracyst as monotherapy. It was suggested that better strategies for selecting patients with bladder-specific clinical phenotype might improve the overall response to this product17.
A total of 213 patients were included in the IPD (Independent Patient Data) meta-analysis. At the end of the treatment period, the overall GRA response rates were 43.2 (95% CI: 35.0, 51.5) and 27.4 (95% CI: 17.6, 37.2) for the chondroitin sulfate and vehicle control groups, respectively. Pooled data RR was 1.565 (p=0.014, 95% CI:1.09, 2.22). The chance of being an ICPI responder was similarly 54% higher in the chondroitin sulfate group. The conclusion was that benefits from intravesical chondroitin sulfate treatment in IC/PBS patients can be confirmed by increasing the power of the available data using a IPD meta-analysis approach. This analysis highlights the importance of choosing the right patient for this organ-specific treatment18.