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.

Daily Intake of a Functional Synbiotic Yogurt Increases Calcium Absorption in Young Adult Women.

Background: Foods containing both prebiotics and probiotics (synbiotics) might enhance calcium bioavailability.

Objectives: We investigated the acute effect in young adult women on calcium absorption of consuming (185 mL) a synbiotic yogurt (SYN) containing inulin (4 g) and Lactobacillus rhamnosus GG (>1 × 107 CFU/mL) compared with a control yogurt (CON).

Methods: Adult normal-weight women (25.

The Efficacy, Safety, and Pharmacology of a Ghrelin O-Acyltransferase Inhibitor for the Treatment of Prader-Willi Syndrome.

Context: Acylated ghrelin (AG) stimulates appetite and is elevated compared to its unacylated (UAG) counterpart in Prader-Willi syndrome (PWS). GLWL-01 is a selective, reversible inhibitor of ghrelin O-acyltransferase (GOAT), the enzyme that converts UAG into AG.

Objective: This work aimed to assess the efficacy, pharmacokinetics, pharmacodynamics, and safety of GLWL-01 in the treatment of PWS patients.

Aurora kinase A inhibitor, LY3295668 erbumine: a phase 1 monotherapy safety study in patients with locally advanced or metastatic solid tumors.

Background Aurora A kinase (AurA) overexpression likely contributes to tumorigenesis and therefore represents an attractive target for cancer therapeutics. This phase 1 study aimed to determine the safety, pharmacokinetics, and antitumor activity of LY3295668 erbumine, an AurA inhibitor, in patients with locally advanced or metastatic solid tumors. Methods Patients with locally advanced or metastatic solid tumors, Eastern Cooperative Oncology Group performance status 0-1, and disease progression after one to four prior treatment regimens were enrolled.

Tracking the Sugar Rush: Incorporating Continuous Glucose Monitoring Into Multisite Early Clinical Research With Type 2 Diabetes Subjects.

Continuous glucose monitoring (CGM) systems allow patients with diabetes mellitus to closely track glucose concentrations over several days, identify trends in glucose levels, and avoid glucose excursions. This technology has not only advanced diabetes mellitus management but has increased patient safety through greater glycemic awareness. Due to these attributes, CGM is now being applied in therapeutic research as a pharmacodynamic tool to support early clinical drug development programs.

Baricitinib in adult patients with moderate-to-severe atopic dermatitis: A phase 2 parallel, double-blinded, randomized placebo-controlled multiple-dose study.

Background: Baricitinib, an oral selective inhibitor of Janus kinase 1 and Janus kinase 2, modulates proinflammatory cytokine signaling.

Objectives: The efficacy and safety of baricitinib were evaluated in patients with moderate-to-severe atopic dermatitis (AD).

Methods: In this phase 2, randomized, double-blind, placebo-controlled study, 124 patients with moderate-to-severe AD applied topical corticosteroids (TCSs) for 4 weeks before randomization to once-daily placebo, 2 mg of baricitinib, or 4 mg of baricitinib for 16 weeks.

No Dose Adjustment is Recommended for Digoxin, Warfarin, Atorvastatin or a Combination Oral Contraceptive When Coadministered with Dulaglutide.

Background: Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) for the treatment of type 2 diabetes mellitus are known to delay gastric emptying (GE). The potential effect of the GLP-1 RA dulaglutide on the pharmacokinetics (PK) of four orally administered drugs and on the pharmacodynamic (PD) effect of warfarin was investigated.

Methods: In four separate clinical pharmacology studies, digoxin, warfarin, atorvastatin and Ortho-Cyclen were orally administered to healthy subjects with and without a subcutaneous dose of dulaglutide 1.

Once-weekly dulaglutide 1.5 mg restores insulin secretion in response to intravenous glucose infusion.

Aims: To evaluate the effects of dulaglutide 1.5 mg on first- and second-phase insulin secretion in response to an intravenous (i.v.

Bioequivalence and comparative pharmacodynamics of insulin lispro 200 U/mL relative to insulin lispro (Humalog®) 100 U/mL.

Insulin lispro 200 U/mL (IL200) is a new strength formulation of insulin lispro (Humalog®, IL100), developed as an option for diabetic patients on higher daily mealtime insulin doses. This phase 1, open-label, 2-sequence, 4-period crossover, randomized, 8-hour euglycemic clamp study aimed to demonstrate the bioequivalence of IL200 and IL100 after subcutaneous administration of 20 U (U) to healthy subjects (n = 38). Pharmacokinetic (PK) and pharmacodynamic (PD) responses were similar in both formulations.

Methods and strategies for assessing uncontrolled drug-drug interactions in population pharmacokinetic analyses: results from the International Society of Pharmacometrics (ISOP) Working Group.

The purpose of this work was to present a consolidated set of guidelines for the analysis of uncontrolled concomitant medications (ConMed) as a covariate and potential perpetrator in population pharmacokinetic (PopPK) analyses. This white paper is the result of an industry-academia-regulatory collaboration. It is the recommendation of the working group that greater focus be given to the analysis of uncontrolled ConMeds as part of a PopPK analysis of Phase 2/3 data to ensure that the resulting outcome in the PopPK analysis can be viewed as reliable.

Clinical Pharmacokinetics of Dulaglutide in Patients with Type 2 Diabetes: Analyses of Data from Clinical Trials.

Background And Objective: Dulaglutide is a long-acting glucagon-like peptide-1 receptor agonist administered as once-weekly subcutaneous injections for the treatment of type 2 diabetes (T2D). The clinical pharmacokinetics of dulaglutide were characterized in patients with T2D and healthy subjects.

Methods: The pharmacokinetics of dulaglutide were assessed throughout clinical development, including conventional pharmacokinetic analysis in clinical pharmacology studies and population pharmacokinetic analyses of data from combined phase 2 and phase 3 studies in patients with T2D.

Subcutaneous Injection Depth Does Not Affect the Pharmacokinetics or Glucodynamics of Insulin Lispro in Normal Weight or Healthy Obese Subjects.

Background: An 8-mm needle length is commonly used for insulin injections; however, recent recommendations suggest shorter needles may help patients avoid intramuscular injections and reduce pain, while maintaining adequate glucose control. The goal of these analyses was to compare the pharmacokinetics (PK) and glucodynamics (GD) of insulin lispro after a 5-mm or an 8-mm injection depth administration in 2 populations: normal weight (study 1) or obese (study 2).

Methods: In both open-label, randomized, 2-period crossover euglycemic clamp studies, subjects received single 0.

Application of PK/PD modeling and simulation to dosing regimen optimization of high-dose human regular U-500 insulin.

Pharmacokinetic/pharmacodynamic (PK/PD) studies of human regular U-500 insulin (U-500R) at high doses commonly used in clinical practice (>100 units) have not been performed. The current analysis applied PK/PD modeling/simulation to fit the data and simulate single-dose and steady-state PK/PD of U-500R high-dose regimens. Data from 3 single-dose euglycemic clamp studies in healthy obese and normal-weight patients, and normal-weight patients with type 1 diabetes were used to build the model.

The effects on metabolic clearance when administering a potent CYP3A autoinducer with the prototypic CYP3A inhibitor, ketoconazole.

Ketoconazole is recognized as the prototypical CYP3A inhibitor and is often used to determine the metabolic CYP3A liabilities of new chemical entities in preclinical and clinical studies. Ketoconazole has been commercially available for approximately 30 years and was marketed before drug-metabolizing enzymes were well characterized; consequently, little is known about its metabolic profile. Semagacestat, a γ-secretase inhibitor investigated as a potential therapy for Alzheimer's disease, was determined to be a potent CYP3A autoinducer in human hepatocytes.

Pharmacokinetics and pharmacodynamics of high-dose human regular U-500 insulin versus human regular U-100 insulin in healthy obese subjects.

Objective: Human regular U-500 (U-500R) insulin (500 units/mL) is increasingly being used clinically, yet its pharmacokinetics (PK) and pharmacodynamics (PD) have not been well studied. Therefore, we compared PK and PD of clinically relevant doses of U-500R with the same doses of human regular U-100 (U-100R) insulin (100 units/mL).

Research Design And Methods: This was a single-site, randomized, double-blind, crossover euglycemic clamp study.

Semagacestat pharmacokinetics are not significantly affected by formulation, food, or time of dosing in healthy participants.

Semagacestat, a γ-secretase inhibitor, reduces formation of amyloid beta peptide. Two single-dose (140 mg), open-label, randomized, 3-period, crossover studies evaluated the effect of formulation, food, and time of dosing on the pharmacokinetics and pharmacodynamics of semagacestat in healthy participants. The first study (n = 14) compared tablet to capsules.

AIR insulin capsules of different dose strengths may be combined to yield equivalent pharmacokinetics and glucodynamics.

Background: In order to assess pharmacokinetic (PK) and glucodynamic (GD) attributes relevant to the end user of an inhaled insulin, this study examined the exposure and GD effect of doses of AIR inhaled insulin (Eli Lilly and Co., Indianapolis, IN) (AIR is a registered trademark of Alkermes, Inc., Cambridge, MA) by combining capsules of different strengths in healthy subjects.

Inhaled growth hormone (GH) compared with subcutaneous GH in children with GH deficiency: pharmacokinetics, pharmacodynamics, and safety.

Background: Delivery of GH via inhalation is a potential alternative to injection. Previous studies of inhaled GH in adults have demonstrated safety and tolerability.

Objective: We sought to assess safety and tolerability of inhaled GH in children and to estimate relative bioavailability and biopotency between inhaled GH and sc GH.

Pharmacokinetics, pharmacodynamics, tolerability, and safety of exenatide in Japanese patients with type 2 diabetes mellitus.

In this single-blind, parallel, placebo-controlled study, the pharmacokinetics, pharmacodynamics, tolerability, and safety of subcutaneous exenatide were evaluated in 40 Japanese patients with type 2 diabetes. Patients were allocated to 4 groups and randomized to receive exenatide (n = 8/group) or placebo (n = 2/group), with all receiving placebo on day 1. On day 2, patients received single-dose exenatide (2.

AIR inhaled insulin versus subcutaneous insulin: pharmacokinetics, glucodynamics, and pulmonary function in asthma.

Objective: This study evaluated pharmacokinetic and glucodynamic responses to AIR inhaled insulin relative to subcutaneous insulin lispro, safety, pulmonary function, and effects of salbutamol coadministration.

Research Design And Methods: Healthy, mildly asthmatic, and moderately asthmatic subjects (n = 13/group, aged 19-58 years, nonsmoking, and nondiabetic) completed this phase I, open-label, randomized, crossover euglycemic clamp study. Subjects received 12 units equivalent AIR insulin or 12 units subcutaneous insulin lispro or salbutamol plus AIR insulin (moderate asthma group only) before the clamp.

Effects of smoking cessation, acute re-exposure and nicotine replacement in smokers on AIR inhaled insulin pharmacokinetics and glucodynamics.

What Is Already Known About This Subject: * Only one other study (Becker et al.) has reported on the influence of smoking cessation and smoking resumption on inhaled insulin pharmacokinetics and glucodynamics, concluding that the rapid changes associated with smoking resumption carry the risk for hypoglycaemia and thus should not be used by active smokers.

What This Study Adds: * This is the first euglycaemic clamp study on the impact of smoking cessation, acute smoking re-exposure and nicotine replacement on AIR((R)) inhaled insulin pharmacokinetics and glucodynamics.

The AIR inhaled insulin system: system components and pharmacokinetic/glucodynamic data.

The diabetes epidemic and lack of adequate glycemic control in patients with diabetes emphasize the need for alternative diabetes treatment strategies. Although many new compounds have been developed, insulin remains the most potent agent for controlling glycemia. Inhaled insulin systems have been developed to alleviate the fear of insulin injections and to improve the convenience of insulin administration.

AIR inhaled insulin in subjects with chronic obstructive pulmonary disease: pharmacokinetics, glucodynamics, safety, and tolerability.

Objective: In this open-label, randomized, crossover study, pharmacokinetic and glucodynamic responses were compared in healthy subjects versus subjects with moderate chronic obstructive pulmonary disease (COPD), following administration of 12 units equivalent AIR inhaled insulin versus 12 units subcutaneous insulin lispro.

Research Design And Methods: Three nonsmoking groups (n = 15 each)--healthy subjects (baseline mean +/- SD age 38 +/- 13 years, forced expiratory volume in 1 s [FEV1] 4.06 +/- 1.