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Background: IPX203 is a novel oral extended‐release formulation of carbidopa/levodopa (CD/LD) developed to address the short half‐life of immediate‐release CD/LD. In the phase 3 RISE‐PD trial, IPX203 significantly improved "Good On" time in patients with Parkinson's disease compared with immediate‐release CD/LD. Objectives: To evaluate the safety and efficacy of IPX203 in an open‐label extension of the pivotal phase 3 study. Methods: This 9‐month extension enrolled patients who completed the randomized, double‐blind trial. Key efficacy endpoints included Movement Disorder Society‐Unified Parkinson's Disease Rating Scale and Patient and Clinical Global Impression scores. Adverse events (AEs) were recorded. Results: Improvements in efficacy were maintained and dosing frequency and total daily dose remained stable through the trial. A total of 52.7% of patients experienced ≥1 treatment‐emergent AE, mostly mild or moderate and occurred within the first 90 days of treatment. Conclusions: In this phase 3 open‐label extension, IPX203 exhibited a favorable safety and tolerability profile and sustained efficacy of comparable magnitude to the end of the double‐blind study. © 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the efficacy and safety of zolmitriptan nasal spray (ZNS) in the acute treatment of migraine headache in patients aged 6 to 11 years. Background: Triptans have demonstrated efficacy in adults, but pediatric studies of these agents have largely failed and there are few triptan options for these patients. Because lack of response to 1 triptan does not necessarily preclude response to an alternate triptan, additional triptan options for pediatric patients are desirable. Methods: This Phase 3, randomized, double‐blind, placebo‐controlled, multicenter crossover trial with an open‐label extension enrolled patients aged 6 to 11 years with a diagnosis of migraine for ≥6 months and ≥16 headache‐free days/month (N = 373). After a run‐in period to eliminate placebo responders, 186 patients were randomized within their body weight stratum to ZNS followed by matching placebo, or placebo followed by matching ZNS. Patients <50 kg who were randomly allocated to ZNS were randomized to 5:1 to ZNS 2.5 or 1.0 mg; those ≥50 kg were randomized 5:1 to ZNS 5.0 or 2.5 mg. Patients had 6 weeks to treat 1 moderate to severe migraine headache and then crossed over to the alternate arm, during which they had 6 weeks to treat a second migraine attack. Patients could participate in a subsequent 6‐month outpatient open‐label extension. The primary efficacy endpoint was pain‐free status at 2 h in patients treated with the high dose from each stratum. Results: The trial was terminated early due to slow enrollment. Three hundred patients (mean age, 9 years) entered the placebo run‐in period and 186 entered the double‐blind period. Pain‐free status at 2 h postdose was achieved by 45/133 (33.8%) and 30/128 (23.4%) of patients who received high‐dose ZNS and placebo, respectively (p = 0.0777; odds ratio [OR] 1.51; 95% confidence interval [CI] 0.96, 2.38). Several secondary endpoints achieved statistical significance. There were few treatment‐related adverse events and none led to discontinuation. ZNS retained efficacy and demonstrated a consistent safety profile throughout the 6‐month open‐label extension. Conclusion: The effect of high‐dose ZNS on the primary endpoint of pain‐free status at 2 h did not achieve statistical significance. ZNS was safe and well tolerated in this pediatric population. [ABSTRACT FROM AUTHOR]

Tissue‐nonspecific alkaline phosphatase (TNAP) hydrolyzes and inactivates inorganic pyrophosphate (PPi), a potent inhibitor of calcification; therefore, TNAP inhibition is a potential target to treat ectopic calcification. These two first‐in‐human studies evaluated safety, tolerability, pharmacokinetics (PKs), and pharmacodynamics (PDs) of single (SAD) and multiple‐ascending doses (MAD) of DS‐1211, a TNAP inhibitor. Healthy adults were randomized 6:2 to DS‐1211 or placebo, eight subjects per dose cohort. SAD study subjects received one dose of DS‐1211 (range, 3–3000 mg) or placebo, whereas MAD study subjects received DS‐1211 (range, 10–300 mg) once daily, 150 mg twice daily (b.i.d.), or placebo for 10 days. Primary end points were safety and tolerability. PK and PD assessments included plasma concentrations of DS‐1211, alkaline phosphatase (ALP) activity, and TNAP substrates (PPi, pyridoxal 5′‐phosphate [PLP], and phosphoethanolamine [PEA]). A total of 56 (DS‐1211: n = 42; placebo: n = 14) and 40 (DS‐1211: n = 30; placebo: n = 10) subjects enrolled in the SAD and MAD studies, respectively. In both studies, adverse events were mild or moderate and did not increase with dose. PKs of DS‐1211 were linear up to 100 mg administered as a single dose and 150 mg b.i.d. administered as a multiple‐dose regimen. In multiple dosing, there was minimal accumulation of DS‐1211. Increased DS‐1211 exposure correlated with dose‐dependent ALP inhibition and concomitant increases in PPi, PLP, and PEA. In two phase I studies, DS‐1211 appeared safe and well‐tolerated. Post‐treatment PD assessments were consistent with exposure‐dependent TNAP inhibition. These data support further evaluation of DS‐1211 for ectopic calcification diseases. [ABSTRACT FROM AUTHOR]

To facilitate access to the left hilum during off-pump bilateral lung transplantation we used the Xpose 4™ apical suction device (Guidant Corp., Indianapolis, IN), an off-pump coronary bypass device to luxate the heart out of the pericardium. The effects on circulation and possible myocardial injury were studied in retrospect. We found the device to provide us with an elegant and nondamaging method to visualize the left hilum. [Copyright &y& Elsevier]