Safety Findings in Pediatric Patients During Long-Term Treatment With Teduglutide for Short-Bowel Syndrome-Associated Intestinal Failure : Pooled Analysis of 4 Clinical Studies

Background This analysis assessed combined safety data from 4 clinical studies of teduglutide in pediatric patients with short-bowel syndrome-associated intestinal failure (SBS-IF). Methods Safety data from teduglutide-treated patients in 4 clinical trials were pooled. The completed 12-week and 24-week phase 3 core studies (NCT01952080/EudraCT 2013-004588-30 and NCT02682381/EudraCT 2015-002252-27) enrolled children aged 1-17 years with SBS-IF. Patients could elect to enroll in ongoing open-label extensions (NCT02949362/EudraCT 2016-000863-17 and NCT02954458/EudraCT 2016-000849-30). Interim data from ongoing studies were included. Results Safety data are reported for 89 pediatric patients treated with teduglutide for a median (range) of 51.7 (5.0-94.7) weeks. Adverse events (AEs) were reported in all patients; the most common were vomiting (51.7%), pyrexia (43.8%), upper respiratory tract infection (41.6%), and cough (33.7%). Thirty-five patients (39.3%) had AEs considered related to teduglutide treatment; abdominal pain and vomiting were most frequent (5.6% each). Three serious AEs in 3 patients (3.4%) were considered related to teduglutide treatment: ileus, d-lactic acidosis, and gastrointestinal obstruction due to hard stools. All 3 events resolved. One cecal polyp was detected, which was not biopsied or found on repeat colonoscopy. No cases of neoplasia occurred. Conclusion Based on integrated data from 4 clinical studies, including long-term follow-up forPeer reviewe

Outcomes from a 12-Week, Open-Label, Multicenter Clinical Trial of Teduglutide in Pediatric Short Bowel Syndrome

Objective To determine safety and pharmacodynamics/efficacy of teduglutide in children with intestinal failure associated with short bowel syndrome (SBS-IF). Study design This 12-week, open-label study enrolled patients aged 1-17 years with SBS-IF who required parenteral nutrition (PN) and showed minimal or no advance in enteral nutrition (EN) feeds. Patients enrolled sequentially into 3 teduglutide cohorts (0.0125 mg/kg/d [n = 8], 0.025 mg/kg/d [n = 14], 0.05 mg/kg/d [n = 15]) or received standard of care (SOC, n = 5). Descriptive summary statistics were used. Results All patients experienced ≥1 treatment-emergent adverse event; most were mild or moderate. No serious teduglutide-related treatment-emergent adverse events occurred. Between baseline and week 12, prescribed PN volume and calories (kcal/kg/d) changed by a median of −41% and −45%, respectively, with 0.025 mg/kg/d teduglutide and by −25% and −52% with 0.05 mg/kg/d teduglutide. In contrast, PN volume and calories changed by 0% and −6%, respectively, with 0.0125 mg/kg/d teduglutide and by 0% and −1% with SOC. Per patient diary data, EN volume increased by a median of 22%, 32%, and 40% in the 0.0125, 0.025, and 0.05 mg/kg/d cohorts, respectively, and by 11% with SOC. Four patients achieved independence from PN, 3 in the 0.05 mg/kg/d cohort and 1 in the 0.025 mg/kg/d cohort. Study limitations included its short-term, open-label design, and small sample size. Conclusions Teduglutide was well tolerated in pediatric patients with SBS-IF. Teduglutide 0.025 or 0.05 mg/kg/d was associated with trends toward reductions in PN requirements and advancements in EN feeding in children with SBS-IF

ANAEROBIC PERFORMANCE IMPROVEMENTS FOLLOWING INGESTION OF R-1,3-BUTANEDIOL (KETONEIQ)

BACKGROUND: Current evidence demonstrates that ketone supplements have made it possible to ingest ketone molecules, elevating blood b-hydroxybutyrate (BHB) despite consuming carbohydrates (CHO). The purpose of this investigation was to determine the effects of R-1,3-butanediol (BDO) commercially available as KETONEIQ. METHODS: A randomized repeated measures placebo-controlled design was used to compare BDO and placebo (PLA). Performance testing consisted of ingestion of 0.5g/kg of BDO or PLA and a standard meal (31g CHO, 2.5g fat, 13g protein). Participants then conducted a 5km time-trial on a treadmill while breath gases were analyzed. BHB and GLU were determined at baseline, midpoint and post run. Following aerobic testing participants completed five 10-second sprints against resistance (7.5% body mass). Repeated-measures analysis of variance (ANOVA) was performed to test for differences in the various outcome variables. Main effects were evaluated by Fisher’s least significant difference post hoc testing. A significance level of p ≤ 0.05 was chosen. Smallest worthwhile change (SWC) in performance variables was calculated using Excel, the SWC was determined using 0.2 multiplied by between subject standard deviations during the PLA trial. RESULTS: BDO resulted in increased BHB at all time-points following baseline (20-minute p\u3c0.001 and 40-minute). On the performance day, BDO supplementation resulted in significantly higher average power (BDO: 479.90 ± 282.60 watts; PLA: 414.86 ± 206.40 watts; p\u3c0.0001 ) and average peak power (BDO: 597.42 ± 307.2 watts; PLA: 543.98 ± 270.80 watts; p\u3c0.001)outputs across the five 10-second cycle sprints. Peak power was the highest wattage determined, while average peak power is the mean peak power across the five trials. Additionally, individuals supplemented with BDO demonstrated significantly higher pedal velocity max (BDO: 130.71± 13.3 RPM; PLA: 121.07 ± 25.7 RPM; p\u3c0.05) Lastly, supplementation resulted in less fatigue as determined by Fatigue Index. SWC was determined to be 2.36 watts. Significantly less wattage decline was observed in the BDO (22.99 ± 11.8 watts) group compared to PLA (29.75 ± 5.5 watts) group (p\u3c0.01). CONCLUSION: Acute supplementation with KETONEIQ significantly increases blood ketones and significantly improved anaerobic performance on a repeated cycle ergometer assessment. Funding: Health Via Modern Nutrition (HVMN