Drug delivery device shows efficacy in interstitial cystitis in early study

Atlanta-One little study could make a big difference for interstitial cystitis patients.

In just 18 patients, a multicenter phase Ib trial of an intravesical lidocaine-delivery device, called LiRIS (lidocaine-releasing intravesical system), produced some remarkable results that were presented at the AUA annual meeting in Atlanta. The treatment not only knocked down pain and other symptoms for the 2 weeks the device was in the bladders of severely symptomatic patients, but in addition, the effects lasted 4 weeks and longer for many patients. Even more surprising, Hunner's lesions disappeared from six of the seven patients who had them.

The small, flexible pretzel-shaped device, not much bigger than a quarter, is designed to float in the bladder with little bother for the patient. It is inserted through a cystoscope, although a better delivery system is on the way, noted first author J. Curtis Nickel, MD, professor of urology at Queen's University in Kingston, Ontario, who presented the results. He explained that water permeates the device's silicone tubing, dissolves the drug core, and the drug is driven through an orifice into the urine by osmotic pressure and passive diffusion.

The current study looked at the effects of delivering 200 mg and 650 mg of lidocaine with LiRIS devices (the 650-mg device is slightly larger) for 2 weeks, after which the device was removed.

The patients had more of a "bladder phenotype," noted Dr. Nickel, with either Hunner's lesions or significant glomerulations, similar to the old NIDDK research criteria. The patients were older and had high pain scores. Mean ages were 59 and 60 years for the 200- and 650-mg treatment groups, respectively; baseline pain scores were 7.5 and 6.2, urgency scores (on a visual analog scale [VAS]) were 7.6 and 6.9, 24-hour frequencies were 19 and 21 times, and nocturia five and six times. Patients were followed up by phone between insertion and removal of the device and were also assessed at removal (day 14), day 21, and day 28.

Pain dropped significantly at the end of the 2-week treatment period to a mean of 2.6 in both groups. At day 28, the mean pain score rose somewhat in the 200-mg group to about 4, whereas the mean score dropped slightly more to about 2 in the 650-mg group. At day 14, urgency scores on the VAS dropped to 1.4 for the 200-mg group and to 3.4 for the 650-mg group. These reductions were also durable, with both groups ending at about 3 on the VAS at day 28. On the global response assessment scale, those receiving the higher dose noted more improvement at day 14, but at day 28, the results were similar, with both groups reporting from 70% to 80% improvement.

Scores on the Interstitial Cystitis Symptom Index also dropped significantly-from 14 and 13 at baseline for the 200-mg and 650-mg groups, respectively, to 8.6 for both at day 14, and 7.0 and 5.8, respectively, on day 28. IC Problem Index scores followed a similar pattern, dropping from 12 for both groups to 6.9 for the 200-mg group and 8.1 for the 650-mg group at day 14, and to 6.0 and 4.4, respectively, at day 28.

Standard deviations for all these measures were wide, with modest responses for some but near-complete resolution for others, even at day 28. Dr. Nickel noted that patients in the 650-mg group were followed further-to 90 days-and two-thirds of those who responded to LiRIS maintained a meaningful reduction in pain.

Patients reported no difficulties with tolerability and no adverse events attributable to lidocaine exposure. With the somewhat larger device for the 650-mg dose, there was a slight increase in the incidence and severity of adverse events, primarily urethral pain and dysuria. No patients discontinued the therapy because of adverse events, however.