Safety, tolerability, and efficacy of LiRIS 400 mg in women with interstitial cystitis/bladder pain syndrome with or without Hunner lesions

Abstract

Aims Two phase 2 studies were conducted to assess the efficacy and safety of lidocaine‐releasing intravesical system (LiRIS) in patients with interstitial cystitis/bladder pain syndrome (IC/BPS) with (Study 001; NCT02395042) or without, (Study 002; NCT02411110) Hunner lesions (HL). Methods Both were multicenter, randomized, double‐blind, placebo‐controlled, and enrolled women aged ≥18 years. In Study 001, patients were randomized 2:1:1 to LiRIS 400 mg/LiRIS 400 mg, placebo/LiRIS 400 mg, or placebo/placebo for a continuous 28 (2 × 14)‐day period. In Study 002, patients were randomized 1:1 to LiRIS 400 mg or placebo for a continuous (single treatment) 14‐day period. Results In total, 59 and 131 patients received treatment in Studies 001 and 002, respectively. There was no statistically significant difference in the primary endpoint, the change from baseline to Week 4 of follow‐up post‐removal in mean daily average bladder numeric rating scale (NRS) pain score in either study (Study 001: placebo/placebo, −1.6; LiRIS/LiRIS, −2.7, p = 0.142; placebo/LiRIS, −2.5, p = 0.319; Study 002: LiRIS −1.2; placebo, −1.5, p = 0.505). There was no statistically significant difference between groups in daily worst NRS pain score, number of micturitions/day or urgency episodes/day. There was no clear trend for reduction in number of HL for LiRIS vs placebo. The frequency of treatment‐emergent adverse events was similar between treatment groups in both studies; most were mild or moderate intensity. Conclusion These studies did not demonstrate a treatment effect of LiRIS 400 mg compared with placebo, either in patients with IC/BPS with HL, or in those without HL.

Intravesical indwelling lidocaine‑releasing devices for IC/BPS (Review)

“…To achieve a longer anesthetic effect of lidocaine, various indwelling bladder devices have been developed. The present study conducted a literature search as mentioned in the 'Literature selection' chapter above and identified a device (LIRIS™; TARIS Biomedical Lexington, LLC) which is the only indwelling bladder lidocaine-releasing device that has advanced to clinical trials (Table I) (36,37). Prior to LIRIS™, an intravesical indwelling oxybutynin-releasing device (UROS™; Situs Corporation, Houston, TX, USA) was developed (38,39).…”

“…Improving on this device, LIRIS™ was developed and tested in clinical trials (36,37). Its structure was similar to the device aforementioned and it was loaded with solid-formed lidocaine (40).…”

“…In a 2-center, open-label phase Ib study, a LIRIS™ 400 mg device (not only 200 and 650 mg), also exhibited long-lasting improvement in lesions, pain, voiding frequency and the ICSI/ICPI score with favorable tolerance and safety (41). With these results, two phase II multicenter, randomized, double-bind, placebo-controlled studies were conducted to evaluate the efficacy of a LIRIS™ 400 mg device in female patients with HIC (study 001) and BPS without Hunner's lesions (study 002) (37). Both studies involved two treatment parts.…”

“…Both studies involved two treatment parts. Patients in the treatment 1 part were randomly divided into the LIRIS™ 400 mg device and placebo groups, and all participants who requested additional treatment were eligible to participate in the treatment 2 part, an open-label evaluation of a LIRIS™ 400 mg device as a second treatment at any time point from day 28 of follow-up to week 20 for study 001 and week 22 for study 002 (37). In total, 59 of 72 patients in study 001 were randomly divided and received treatment [LIRIS™/LIRIS™ (n=31), placebo/placebo (n=12) and placebo/LIRIS™ (n=16)].…”

Intravesical drug delivery approaches for improved therapy of urinary bladder diseases

“…Pain relief and reduction in voiding urgency and frequency have been reported after a two-week treatment together with signs of bladder healing. Two phase 2 studies have also been carried out, in which no significant treatment effect was assessed with lidocaine hydrochloride 400 mg LiRIS ΤΜ as compared with placebo ( Evans et al, 2021 ).…”