Prospective switch study comparing two irrigation systems for transanal irrigation in children

Background and study aims: Transanal irrigation (TAI) is used in children to treat constipation and incontinence. Belgium has 2 systems available: Colotip® (cheaper, however not designed for TAI) or Peristeen®. Patients and methods: This patient-control switch study is the first to compare 2 TAI systems. Children regularly using Colotip® for TAI were asked to participate, after consent, a visual analogue scale (VAS) rating the system and a 2-week diary (fecal continence, self-reliance, time spent on the toilet, pain, Bristol stool scale, irrigation volume and frequency of enema) were completed. Non-parametric statistics were used. Results: Out of 26 children using Colotip®, 18 (69%) children participated and 5 refused (fear n=1, satisfaction Colotip® system n=7). Of these 18 children (interquartile range: 3-18 years, median 12.5 years, 9 girls) 5 patients stopped Peristeen® (pain n=1, fear n=1 and balloon loss n=3) and 2 were lost from follow up. Dropouts and included patients showed no statistical difference. In the 11 remaining patients, pseudo-continence (p 0.015), independence (p 0.01) and VAS score (p 0.007) were significantly better with Peristeen®, no difference was found in time spent on the toilet (p 0.288) and presence of pain (p 0.785). Conclusions: In children Peristeen® offered significantly higher pseudo-continence and independency. 30% refused participation because of satisfaction with the Colotip® and 30% spina bifida patients reported rectal balloon loss due to sphincter hypotony. To diminish Peristeen® failure, a test-catheter could be of value. Considering Colotip® satisfaction, both systems should be available. Patient selection for Peristeen® needs further research.

Characterization of viral rebounds on dual etravirine/raltegravir maintenance therapy (ANRS-163 ETRAL trial)

Background The ANRS-163 ETRAL trial, a switch study to an etravirine 200 mg/raltegravir 400 mg twice-daily regimen in 165 patients with HIV-1 infection, showed durable efficacy until Week 96. The aim of this work was to investigate in detail the virological rebounds (VRs), defined as at least one plasma HIV viral load (VL) >50 copies/mL. Methods Quantification of HIV-DNA level was assessed at baseline, Week 48 and Week 96 (n = 157). VLs were measured in seminal plasma at Week 48 (n = 26). Genotypic resistance testing by ultra-deep sequencing (UDS) for reverse transcriptase (RT) and integrase regions was performed at baseline and at the time of VR. Results In this study, 19 patients experienced VR, with 2 patients having virological failure (VF; two consecutive VLs >50 copies/mL). For the first patient with VF, UDS detected minority resistant variants only in RT (K103N, 9.6%; Y181C, 4.9%) at baseline. Some RT variants became dominant at VF (K101E, 86.3%; Y181C, 100.0%; G190A, 100.0%) and others emerged in integrase (Y143C, 2.4%; Q148R, 6.2%; N155H, 18.8%). For the second patient with VF, neither RT nor integrase mutations were detected at baseline and VF. Median HIV-DNA level was similar at baseline, Week 48 and Week 96 (2.17, 2.06 and 2.11 log10 copies/106 cells, respectively). Only one patient had a detectable seminal HIV VL (505 copies/mL). Conclusions The dual etravirine/raltegravir regimen as maintenance therapy was effective and the emergence of mutations in cases of VF was similar to that seen in other dual-regimen studies. No HIV-DNA level modification was evidenced by Week 96.

0747 Study Design of an Open-Label Extension and Switch Study for Once Nightly Sodium Oxybate, FT218, in NT1 and NT2 Patients

Introduction Avadel Pharmaceuticals has developed FT218, a once nightly sodium oxybate (SO) formulation for the treatment of excessive daytime sleepiness (EDS) and cataplexy in narcoleptic patients. REST-ON, a pivotal efficacy/safety study is expected to be completed in the first half of 2020. Previous Phase 1 studies have demonstrated FT218 delivers a pharmacokinetic profile needed for once-nightly dosing. The purpose of this study is to evaluate long-term safety of FT218 in REST-ON completers and dosing strategy when switching from twice-nightly SO to FT218. Methods The study will enroll NT1/NT2 patients who completed REST-ON or patients switching from stable dose of twice-nightly SO to FT218. REST-ON completers will initiate FT218 at 4.5 g and increase by 1.5 g to the highest tolerated dose or the dose deemed effective (up to 9 g). Switch patients will initiate FT218 at the equivalent/closest dose to their current twice-nightly SO and titrate in accord with safety/efficacy. The study will enroll approximately 250 patients for a duration of two years. Results The primary endpoint for REST-ON completers will be safety and tolerability. Secondary endpoints for REST-ON completers will include changes in ESS, reported cataplexy and other REM associated phenomena as well as changes in clinician and patient global impression. For switch patients, endpoints will include percentage of subjects that stay on the same, higher or lower dose of FT218 compared to twice-nightly SO, as well as the percentage of subjects who report a preference for the once-nightly dosing regimen. Conclusion The results of this open label extension/switch study will further elucidate the potential benefits of once-nightly FT218 regarding long term safety/tolerability, nocturnal safety/tolerability and efficacy, and importantly provide dosing and preference data for patients switching from twice-nightly SO to once-nightly FT218. Support This work was supported by Avadel Pharmaceuticals.