Muvalaplin, an Oral Small Molecule Inhibitor of Lipoprotein(a) Formation: A Randomized Clinical Trial.

Importance: Lipoprotein(a) (Lp[a]) is associated with atherosclerotic disease and aortic stenosis. Lp(a) forms by bonding between apolipoprotein(a) (apo[a]) and apo B100. Muvalaplin is an orally administered small molecule that inhibits Lp(a) formation by blocking the apo(a)-apo B100 interaction while avoiding interaction with a homologous protein, plasminogen.

Erratum: Erratum.

[This corrects the article DOI: 10.1177/11795484221119316.].

Efficacy and Safety of LY3127804, an Anti-Angiopoietin-2 Antibody, in a Randomized, Double-Blind, Placebo-Controlled Clinical Trial in Patients Hospitalized with Pneumonia and Presumed or Confirmed COVID-19.

Background: Severe cases of coronavirus disease 2019 (COVID-19) are characterized by progressive respiratory failure and the development of acute respiratory distress syndrome (ARDS), with high mortality rates for patients requiring mechanical ventilation. Levels of the vascular growth factor Angiopoietin 2 (Ang2) in plasma have been strongly correlated with increased ARDS risk in patients with pneumonia or sepsis. The intent of this study was to determine whether LY3127804, an anti-Ang2 monoclonal antibody, could reduce the need for mechanical ventilation among patients admitted to the hospital with pneumonia and presumed or confirmed COVID-19.

Effects of lasmiditan on simulated driving performance: Results of two randomized, blinded, crossover studies with placebo and active controls.

Objective: To evaluate the impact of lasmiditan, an oral, centrally-penetrant, selective serotonin 1F (5-HT ) receptor agonist developed for the acute treatment of migraine, on simulated driving.

Methods: Healthy adult volunteers enrolled in two randomized, placebo and active comparator-controlled, crossover studies. Study 1 (N = 90) tested lasmiditan (50-, 100-, 200-mg), alprazolam (1-mg), and placebo at 1.

Issues Impacting Adverse Event Frequency and Severity: Differences Between Randomized Phase 2 and Phase 3 Clinical Trials for Lasmiditan.

Objective: We explore factors that may have contributed to differences in treatment-emergent adverse events in the phase 2 and phase 3 lasmiditan clinical trials.

Background: Phase 2 and phase 3 trials showed that the centrally penetrant 5-HT agonist, lasmiditan, was effective; higher frequency and severity of adverse events (AEs) were seen in phase 2.

Methods: This work represents a hybrid of a review of primary documents and study reports with additional post hoc analyses.

Abuse Potential of Lasmiditan: A Phase 1 Randomized, Placebo- and Alprazolam-Controlled Crossover Study.

Lasmiditan is a centrally penetrant, highly selective 5-hydroxytryptamine (serotonin) receptor 1F (5HT ) agonist under development as a novel therapy for acute treatment of migraine. A phase 1 randomized, placebo- and positive-controlled crossover study assessed the abuse potential of lasmiditan in adult recreational polydrug users. Following a qualification phase, subjects were randomized into treatment sequences, each consisting of 5 study treatments: placebo, alprazolam 2 mg, lasmiditan 100, 200 (lasmiditan 100 and 200 mg are proposed therapeutic doses), and 400 mg (supratherapeutic).

Lasmiditan for acute treatment of migraine in patients with cardiovascular risk factors: post-hoc analysis of pooled results from 2 randomized, double-blind, placebo-controlled, phase 3 trials.

Background: In addition to the increased risk for cardiovascular (CV) disease and CV events associated with migraine, patients with migraine can also present with a number of CV risk factors (CVRFs). Existing treatment options can be limited due to contraindications, increased burden associated with monitoring, or patient avoidance of side effects. Safe and effective migraine treatment options are needed for patients with migraine and a history of CV or cerebrovascular disease or with increased risk for CV events.

Targeting the hepcidin-ferroportin pathway in anaemia of chronic kidney disease.

Aims: Erythropoiesis-stimulating agents used to treat anaemia in patients with chronic kidney disease (CKD) have been associated with cardiovascular adverse events. Hepcidin production, controlled by bone morphogenic protein 6 (BMP6), regulates iron homeostasis via interactions with the iron transporter, ferroportin. High hepcidin levels are thought to contribute to increased iron sequestration and subsequent anaemia in CKD patients.

Lasmiditan is an effective acute treatment for migraine: A phase 3 randomized study.

Objective: To assess the efficacy and safety of lasmiditan in the acute treatment of migraine.

Methods: Adult patients with migraine were randomized (1:1:1) to a double-blind dose of oral lasmiditan 200 mg, lasmiditan 100 mg, or placebo and were asked to treat their next migraine attack within 4 hours of onset. Over 48 hours after dosing, patients used an electronic diary to record headache pain and the presence of nausea, phonophobia, and photophobia, one of which was designated their most bothersome symptom (MBS).

Anti-TGF-1 Antibody Therapy in Patients with Diabetic Nephropathy.

TGF- has been implicated as a major pathogenic factor in diabetic nephropathy. This randomized, double-blind, phase 2 study assessed whether modulating TGF-1 activity with a TGF-1-specific, humanized, neutralizing monoclonal antibody (TGF-1 mAb) is safe and more effective than placebo in slowing renal function loss in patients with diabetic nephropathy on chronic stable renin-angiotensin system inhibitor treatment. We randomized 416 patients aged ≥25 years with type 1 or type 2 diabetes, a serum creatinine (SCr) level of 1.

The effect of the oral PKC β inhibitor ruboxistaurin on vision loss in two phase 3 studies.

Purpose: To assess the effect of ruboxistaurin (RBX) on vision loss through a prospectively defined combined analysis of two phase 3 trials (MBDL and MBCU).

Methods: Patients in both of these 3-year randomized, placebo-controlled, double-masked trials had best-corrected Early Treatment Diabetic Retinopathy Study (ETDRS) visual acuity (VA) ≥ 75 letters (∼20/32 Snellen), ETDRS retinopathy level 20 to 47D (MBDL) or 35B to 53E (MBCU), and no prior panretinal or focal photocoagulation in at least one eye at baseline. Patients received oral placebo (N = 508 total from both studies) or RBX 32 mg/d (N = 520 total).

Clinical safety of the selective PKC-beta inhibitor, ruboxistaurin.

The aim of this manuscript is to report the safety profile of patients treated with ruboxistaurin mesylate (RBX; LY333531), a selective protein kinase C-beta (PKC-beta) inhibitor, for up to 4 years. Data from patients with diabetes (1396 RBX 32 mg/day; 1408 placebo) were combined from 11 placebo-controlled, double-masked studies. The proportion of patients who reported one or more serious adverse events was greater in the placebo group than in the RBX-treated group (23.

Comparison of treatment-emergent extrapyramidal symptoms in patients with bipolar mania or schizophrenia during olanzapine clinical trials.

Background: Previous research on pharmacotherapy with conventional antipsychotics has suggested that patients with affective disorders have higher rates of treatment-emergent extrapyramidal symptoms (EPS) than patients with schizophrenia. It is not known whether this differential vulnerability holds true for treatment with atypical antipsychotics such as olanzapine. The present analysis retrospectively examined olanzapine clinical trial data for incidence of treatment-emergent EPS in patients with either schizophrenia or bipolar disorder.

Olanzapine versus ziprasidone: results of a 28-week double-blind study in patients with schizophrenia.

Objective: The efficacy and safety of olanzapine were compared with those of ziprasidone.

Method: This was a multicenter randomized, double-blind, parallel-group, 28-week study of patients with schizophrenia. Patients were randomly assigned to treatment with 10-20 mg/day of olanzapine or 80-160 mg/day of ziprasidone.

An integrated analysis of acute treatment-emergent extrapyramidal syndrome in patients with schizophrenia during olanzapine clinical trials: comparisons with placebo, haloperidol, risperidone, or clozapine.

Background: The frequency and severity of extrapyramidal syndrome (EPS) were evaluated in patients with DSM-III or DSM-IV schizophrenia in the acute phase (- 8 weeks) of randomized, double-blind, controlled trials from the integrated olanzapine clinical trial database.

Method: This retrospective analysis included 23 clinical trials and 4611 patients from November 11, 1991, through July 31, 2001. Incidences of dystonic, parkinsonian, and akathisia events were compared using treatment-emergent adverse-event data.