A CE-marked polycaprolactone-based bioresorbable bulking agent is evaluated for safety and efficacy in female patients with mild to moderate SUI who attempted and failed prior pelvic floor muscle training. Polycaprolactone (PCL) is a well-known polymer which has been used successfully in numerous Food and Drug Administration (FDA) approved and Conformité Européenne (CE) marked medical devices and is fully bioresorbable.

In this multicentre study, a total of 50 female subjects were treated by transurethral sub-mucosal injection. The mean age of these subjects was 47.5 ± 12.2 ranging from 26-81 years with a median age of 47 years and 49, 47 and 39 subjects completed the 3-, 6- and 12-month follow-up. Efficacy was assessed with the Stamey Grading System (SGS), International Consultation on Incontinence Questionnaire – Short Form (ICIQ-SF), Patient Global Impression of Severity and improvement (PGI-S, PGI-I) and Incontinence-Quality of Life (I-QoL). ICIQ-SF severity was divided into the following categories: slight (1 – 5), moderate (6 – 12), severe (13 – 18) and very severe (19 – 21) according to Klovning et al. [1]. A comparison for the mean I-QoL and ICIQ-SF between the 3-, 6- and 12-month data versus baseline was done using a paired-samples Student t-test with the online calculator www.socscistatistics.com/tests/ttestdependent/Default2.aspx. Efficacy analysis was performed using a Per-Protocol (PP) approach on all subjects that completed the 3-, 6- and 12-month follow-up. An additional analysis using a Last Observation Carried Forward (LOCF) was performed to account for drop-outs at follow-up to support the PP analysis.

The mean (± sd) initial injection volume was 1.5 ± 0.5 cc with a median of 1.6 cc. The mean (± sd) re-treatment injection volume was 1.3 ± 0.4 cc and a median of 1.3 cc. Total mean injection volume (n=50, initial volume + re-treatment) was 1.9 ± 0.9 cc and a median of 1.6 cc. Per Protocol (PP) efficacy analysis shows a total SGS improvement (improvement + cure) for 31/49 (63.3%), 25/46 (54.3%) and 22/38 (57.9%) subjects that completed the 3-, 6-, and 12-month follow-up visits, respectively. 21/49 (42.9%), 19/46 (41.3%) and 15/38 (39.5%) subjects were cured (SGS 0) that completed the 3-, 6-, and 12-month follow-up visits, respectively. Similar but slightly lower SGS results were found when using a LOCF analysis where 31/50 (62.0%), 27/50 (54.0%) and 26/50 (52.0%) subjects showed total improvement of which 21/50 (42.0%), 19/50 (38.0%) and 16/50 (32.0%) subjects were cured at 3-, 6-, and 12-month follow-up, respectively. Results are summarized in Table 1.
Additional efficacy data was obtained with the PGI-S questionnaire, where total improvement was shown for 37/49 (75.5%), 34/46 (72.3%) and 24/38 (63.2%) subjects that completed the 3-, 6-, and 12-month follow-up visits, respectively. 26/49 (53.1%), 20/47 (42.6%) and 17/38 (44.7%) subjects that completed the 3-, 6-, and 12-month follow-up visits, respectively, rated their urinary tract condition as being normal again (cured). Similar but slightly lower PGI-S results were found when using a LOCF analysis where 37/50 (74.0%), 35/50 (70.0%) and 33/50 (66.0%) subjects showed total improvement of which 26/50 (52.0%), 20/50 (40.0%) and 21/50 (42.0%) subjects were cured at 3-, 6-, and 12-month follow-up, respectively. Results are summarized in Table 1.
Treatment success was measured with the PGI-I. PGI-I results showed a treatment success for 42/49 (85.7%), 35/47 (74.5%) and 31/39 (79.5%) subjects that completed the 3-, 6-, and 12-month follow-up visits. Similar but slightly lower PGI-I results were found when using a LOCF analysis where 42/50 (84.0%), 36/50 (72.0%) and 35/50 (70.0%) subjects that completed the 3-, 6-, and 12-month follow-up visits showed a treatment success. Results are summarized in Table 1.
Quality of life (QoL), measured with the ICIQ-SF and I-QoL, was also improved. At baseline the median ICIQ-SF scores were moderate/severe (12/13) which were reduced to a moderate median ICIQ-SF score of 7, 6 and 6 at the 3-, 6- and 12-month follow-up time point, respectively. Furthermore, the mean differences (improvement) compared to baseline of 5.3, 6.0 and 5.2 at the 3-, 6- and 12-month follow-up time point, respectively, were significant improvements (p < 0.05). Results are summarized in Table 2A. Similar but slightly lower ICIQ-SF values were found when using a LOCF analysis where at baseline the median ICIQ-SF score was severe (13), which was reduced to a moderate median ICIQ-SF score of 7, 6 and 7 at the 3-, 6- and 12-month follow-up time point, respectively. Furthermore, the mean differences (improvement) compared to baseline of 5.2, 5.6 and 4.7 at the 3-, 6- and 12-month follow-up time point, respectively, were significant improvements (p < 0.01). Results are summarized in Table 2B. 
I-QoL results show a significant (p < 0.01) mean difference (improvement) of 15.4%, 16.0% and 15.6% in I-QoL value at 3-, 6-, and 12-month follow-up compared to baseline. Similar but slightly lower I-QoL values were found when using a LOCF analysis where results show a significant (p < 0.01) mean difference (improvement) of 15.0%, 15.1% and 13.9% in I-QoL value at 3-, 6-, and 12-month follow-up compared to baseline. 
Five subjects reported a total of 7 mild adverse events (AE) of which 3 were related to 1 subject (sensation of post-void urinary retention, urinary retention and bladder cramps caused by catheterization). The other 4 subjects reported transient urge incontinence, urinary tract infection, hematuria and dysuria. All AE were mild in nature and resolved spontaneously by providing relevant medication and/or catheterization. One subject experienced transient urinary retention which required in-patient hospitalization. Due to the required hospitalization, the event was recorded as an serious adverse event (SAE). However, the event itself was mild in nature and was resolved with the use of a catheter. At 12-month follow-up, all subjects received an additional cystoscopic examination. No abnormalities were found at the injection sites.

Twelve month follow-up results of a novel PCL-based bioresorbable bulking agent used for the treatment of female mild to moderate SUI are presented. For the subjects that completed the 3-, 6- and 12-month follow-up, the efficacy analysis shows that the treatment was experienced as successful by the subjects (PGI-I) and resulted in improvements on both the severity of the subjects incontinence (SGS, PGI-S)  as well on their QoL (ICIQ-SF, I-QoL). The results of the LOCF analysis were similar to the PP analysis and no substantial differences were found. These results support the efficacy results found in the initial PP analysis. 
Additional preliminary data (data not shown) suggests that the above improvements are sustained up to 18-months follow-up.

The study shows that the PCL-based bioresorbable bulking agent treatment is safe and effective for women with mild to moderate SUI, resulting in improvements in both SUI severity and QoL. As the study is ongoing (up-to 2 years follow-up), data is subject to change.

Klovning A, Avery K, Sandvik H, Hunskaar S. Comparison of two questionnaires for assessing the severity of urinary incontinence: The ICIQ-UI SF versus the incontinence severity index. Neurourol Urodyn. 2009;28(5):411-415.