No abstract

Background and objectives: Fibroblast growth factor-23 (FGF23) levels are elevated in ESRD and have been associated with adverse outcomes. The effects of various treatments for secondary hyperparathyroidism on FGF23 levels in ESRD have not been examined in a clinical trial.Design, setting, participants, & measurements: We assessed intact FGF23 levels in 91 subjects over the course of the ACHIEVE trial, which was designed to compare escalating doses of Cinacalcet plus fixed low-dose calcitriol analogs (Cinaclcet-D) with titration of calcitriol analogs alone (Flex-D) to suppress parathyroid hormone. Between-group and withingroup changes in log-transformed FGF23 levels were analyzed. Factors associated with change in FGF23 were assessed using a multiple regression model.Results: Intact FGF23 levels were markedly elevated in subjects at baseline. A statistically significant difference in percent change in log FGF23 levels was observed between treatment groups (P < 0.002). The Cinacalcet-D group had a significant decrease in percent change in log FGF23 levels (corrected P ‫؍‬ 0.021), whereas FGF23 levels trended toward an increase in the Flex-D group. Change in FGF23 level was significantly associated with changes in levels of phosphate (P < 0.0001) and calcium (P ‫؍‬ 0.0002) but not parathyroid hormone.Conclusions: Treatment with Cinacalcet plus low-dose calcitriol analogs results in lower FGF23 levels compared with a treatment regimen using calcitriol analogs alone in ESRD. The mechanisms underlying the differential effects of these treatment regimens on FGF23 levels and the clinical impact of these changes on FGF23 remain to be defined.

The eSLD and CD provided clinically meaningful weight loss over 18 months in adults with intellectual and developmental disabilities.

IMPORTANCE Switching between generic antiepileptic drugs is a highly debated issue that affects both clinical care and overall health care costs.OBJECTIVE To evaluate the single-dose pharmacokinetic bioequivalence of 3 (1 branded and 2 generic drugs) on-market, immediate-release lamotrigine drug products. DESIGN, SETTING, AND PARTICIPANTSThe Equivalence Among Antiepileptic Drug Generic and Brand Products in People With Epilepsy (EQUIGEN) single-dose study is a crossover, prospective, sequence-randomized, replicate pharmacokinetic study conducted at 5 US academic epilepsy centers. Fifty adults (Ն18 years) with epilepsy who were taking concomitant antiepileptic drugs and not currently receiving lamotrigine were enrolled between July 18, 2013, and January 19, 2015. Every participant was randomly assigned to 1 of 3 equivalent sequences, each comprising 6 study periods, during which they had blood draws before and after medication administration. Forty-nine participants were included in intention-to-treat analyses.INTERVENTIONS Participants received a single 25-mg dose of immediate-release lamotrigine at the start of each period, with the branded and the 2 most disparate generic products each studied twice. Lamotrigine was selected as the antiepileptic drug of interest because of its wide use, publications indicating problems with generic switches, and complaints to the US Food and Drug Administration regarding generic products. Both participants and study personnel were blinded to the specific generic products selected. MAIN OUTCOMES AND MEASURESThe primary outcome was bioequivalence between products. Maximum plasma concentration (Cmax) and area under the concentration-time curve (AUC) were compared, and average bioequivalence (ABE) was established if the 90% CIs of the ratios of the 2 products were within equivalence limits (80%-125%). RESULTSOf the 50 randomized participants, 49 (98%) received all 3 lamotrigine products and completed at least 3 pharmacokinetic assessments and 46 (92%) completed all 6 pharmacokinetic assessments. Among the 49 participants, 28 (57%) were men and 21 (43%) were women, 42 (86%) self-identified as white, and 46 (16) years was the mean (SD) age. The 3 drug products were considered bioequivalent because the 90% CIs were within equivalence limits (lowest and highest CI limits for Cmax, 92.6% and 110.4%; for AUC 0-96 , 96.9% and 101.9%). Replicate testing demonstrated no significant differences in within-subject variability across the 3 products (likelihood ratios, χ 2 2 for log-transformed variables: AUC 0-96 , 2.58; Cmax, 0.64; and AUC 0-ϱ , 4.05; P Ն .13) and that the 3 products were also bioequivalent according to scaled ABE and individual bioequivalence criteria with no subject × formulation interaction (Cmax, 0.00; AUC 0-96 , 0.54; and AUC 0-ϱ , 0.36; P Ն .76). CONCLUSIONS AND RELEVANCEThis study provides evidence that the disparate lamotrigine products studied are bioequivalent when tested in people with epilepsy taking concomitant antiepileptic drugs.