First-in-Human Evaluation of Safety, Pharmacokinetics and Muscle Glycogen Lowering of a Novel Glycogen Synthase 1 Inhibitor for the Treatment of Pompe Disease.

Pompe disease is a rare glycogen storage disease caused by mutations in the enzyme acid α-glucosidase (GAA) resulting in pathological accumulation of glycogen in muscle tissues leading to progressive weakness and respiratory dysfunction. Enzyme replacement therapy (ERT) with GAA is currently the sole treatment option for patients with Pompe disease. ERT burdens patients with frequent intravenous infusions while insufficiently halting disease progression due to incomplete ERT skeletal muscle distribution.

Safety and efficacy of rodatristat ethyl for the treatment of pulmonary arterial hypertension (ELEVATE-2): a dose-ranging, randomised, multicentre, phase 2b trial.

Background: The role of serotonin in pulmonary arterial hypertension has been extensively studied in recent decades, with preclinical data strongly indicating involvement in disease pathogenesis; however, clinical studies have yielded mixed results.

Methods: ELEVATE-2 was a phase 2b dose-ranging, randomised, double-blind, placebo-controlled, multicentre trial investigating rodatristat ethyl as a treatment for patients with pulmonary arterial hypertension. The study was conducted at 64 sites across 16 countries in Europe and North America.

Development and evaluation of the Acromegaly Symptom Diary.

Background: Patient-reported outcome (PRO) measures are important to consider when evaluating treatments, yet there are no PRO measures for patients with acromegaly that have been developed in accordance with US Food and Drug Administration guidance. Acromegaly is a rare, chronic condition caused by hypersecretion of growth hormone. Disease activity is monitored by measurement in serum of growth hormone and insulin-like growth factor-I.

ACROBAT Edge: Safety and Efficacy of Switching Injected SRLs to Oral Paltusotine in Patients With Acromegaly.

Context: Paltusotine is a once-daily, oral, nonpeptide small-molecule somatostatin receptor type 2 (SST2) agonist in clinical development for treatment of acromegaly.

Objective: This work aimed to evaluate change in insulin-like growth factor I (IGF-I) levels in patients switched from octreotide long-acting release or lanreotide depot monotherapy to paltusotine.

Methods: A phase 2, open-label, prospective, multicenter, multinational, nonrandomized, single-arm exploratory study was conducted in which dosage uptitrations were performed in a double-blinded manner.

Safety and Tolerability of Multiple Ascending Doses of PRX002/RG7935, an Anti-α-Synuclein Monoclonal Antibody, in Patients With Parkinson Disease: A Randomized Clinical Trial.

Importance: Aggregated α-synuclein is believed to be central to the pathogenesis of Parkinson disease (PD). PRX002/RG7935 (PRX002) is a humanized monoclonal antibody designed to target aggregated forms of α-synuclein, thereby inhibiting neuron-to-neuron transfer of presumed pathogenic forms of α-synuclein, potentially resulting in neuronal protection and slowing disease progression.

Objective: To evaluate the safety and tolerability of multiple intravenous infusions of PRX002 in patients with idiopathic PD.

Clinical application of the GLOBE and United Kingdom-primary biliary cholangitis risk scores in a trial cohort of patients with primary biliary cholangitis.

The GLOBAL Primary Biliary Cholangitis (PBC) Study Group and United Kingdom-PBC (UK-PBC) Consortium have demonstrated that dichotomous response criteria are not as accurate as continuous equations at predicting mortality or liver transplantation in PBC. The aim of this analysis was to assess the clinical utility of the GLOBE and UK-PBC risk scores using data from POISE, a phase 3 trial investigating obeticholic acid (OCA) in patients with PBC. Data (N = 216) at baseline and month 12 were used to calculate the GLOBE and UK-PBC risk scores to assess the projected change in risk with OCA versus placebo.

A Placebo-Controlled Trial of Obeticholic Acid in Primary Biliary Cholangitis.

Background: Primary biliary cholangitis (formerly called primary biliary cirrhosis) can progress to cirrhosis and death despite ursodiol therapy. Alkaline phosphatase and bilirubin levels correlate with the risk of liver transplantation or death. Obeticholic acid, a farnesoid X receptor agonist, has shown potential benefit in patients with this disease.

Randomized, double-blind, placebo-controlled study of the abuse potential of different formulations of oral oxycodone.

Objective: The objective of this study was to evaluate the pharmacokinetics and abuse potential of different formulations of oxycodone.

Design: The participants completed an 8-day, placebo-controlled trial with four phases: naloxone challenge, double-blind drug discrimination, double-blind abuse liability, and discontinuation.

Subjects: Nineteen healthy, male, recreational drug abusers participated in this study.

Pharmacotherapy of pain in depressed older adults.

Objectives: To examine pharmacotherapy for pain in a sample of 1,801 depressed older primary care patients.

Design: Cross-sectional survey data collected from 1999 to 2001.

Setting: Eighteen primary care clinics belonging to eight healthcare organizations in five states.

Cognitive impairment, chronic medical illness, and risk of mortality in an elderly cohort.

Objective: The mortality risk for older persons with chronic medical illness and cognitive impairment is relatively unknown. The authors assessed 6-year mortality risks for cognitive impairment and six chronic diseases in 7,482 subjects from the East Boston, Massachusetts, and rural Iowa cohorts of the Established Populations for Epidemiologic Studies in the Elderly (EPESE).

Methods: Cognitive impairment was identified with a modified form of Pfeiffer's Short Portable Mental Status Questionnaire.

Depressive symptoms and mortality in a prospective study of 2,558 older adults.

Objective: The authors report results from a 7-year prospective study of depression and mortality in 2,558 Medicare recipients age 65 and older.

Methods: This report is based on a secondary data analysis of a randomized controlled trial that evaluated the cost-effectiveness of preventive services for older enrollees in an HMO.

Results: Subjects with mild-to-moderate depression at baseline did not have an increased risk of mortality compared with those without significant depression.