A randomized phase 1 study of safety, tolerability, and pharmacokinetics of MK-1088, a novel dual adenosine receptor antagonist, in healthy adult participants.

This phase 1 first-in-human study evaluated the safety, tolerability, and pharmacokinetics of MK-1088, a novel, small-molecule dual inhibitor of adenosine A and A receptors. Healthy adult participants were enrolled in two panels (n = 8 each) and randomly assigned to receive MK-1088 (n = 6) or placebo (n = 2) orally in each of five treatment periods. Participants in panel A received single ascending doses of MK-1088 at 1, 10, 50, and 150 mg or placebo in a fasted or fed (50 mg only) state.

Phase 1 Study of MK-5475, an Inhaled Soluble Guanylate Cyclase Stimulator, in Participants with Pulmonary Hypertension Associated with Chronic Obstructive Pulmonary Disease.

Purpose: This phase 1 study (NCT04370873) evaluated safety and pharmacokinetics/pharmacodynamics (PK/PD) of MK-5475 in participants with pulmonary hypertension associated with COPD (PH-COPD).

Methods: Eligible participants were 40-80 years old with COPD (FEV/FVC <0.7; FEV >30% predicted) and PH (mean pulmonary arterial pressure ≥25 mmHg).

Evaluation of a stabilized RSV pre-fusion F mRNA vaccine: Preclinical studies and Phase 1 clinical testing in healthy adults.

Human respiratory syncytial virus (RSV) causes a substantial proportion of respiratory tract infections worldwide. Although RSV reinfections occur throughout life, older adults, particularly those with underlying comorbidities, are at risk for severe complications from RSV. There is no RSV vaccine available to date, and treatment of RSV in adults is largely supportive.

Effects of an inhaled soluble guanylate cyclase (sGC) stimulator MK-5475 in pulmonary arterial hypertension (PAH).

Background: Novel therapeutics for pulmonary arterial hypertension (PAH) with improved safety/tolerability profiles are needed to address continued high rates of morbidity/mortality.

Methods: This Phase 1 study evaluated efficacy/safety of inhaled single-dose MK-5475, an investigational, small-molecule stimulator of soluble guanylate cyclase designed for inhaled delivery via a dry-powder inhaler device, in participants with PAH (Clinicaltrials.gov: NCT03744637).

Safety and immunogenicity of intramuscular, single-dose V590 (rVSV-SARS-CoV-2 Vaccine) in healthy adults: Results from a phase 1 randomised, double-blind, placebo-controlled, dose-ranging trial.

Background: Vaccines against COVID-19 are needed to overcome challenges associated with mitigating the global pandemic. We report the safety and immunogenicity of V590, a live recombinant vesicular stomatitis virus-based COVID-19 vaccine candidate.

Methods: In this placebo-controlled, double-blind, three-part phase 1 study, healthy adults were randomised to receive a single intramuscular dose of vaccine or placebo.

Safety and immunogenicity of the measles vector-based SARS-CoV-2 vaccine candidate, V591, in adults: results from a phase 1/2 randomised, double-blind, placebo-controlled, dose-ranging trial.

Background: We report on the safety and immunogenicity of V591, a measles vector-based SARS-CoV-2 vaccine candidate.

Methods: In this multicentre, randomised, placebo-controlled, double-blind, phase 1/2 trial, healthy adults with no history of COVID-19 disease were assigned to intramuscular injection of V591 or placebo (4:1 ratio). In part 1, younger adults (18-55 years) received V591 median tissue culture infectious dose (TCID)-levels of 1×10 or 1×10 or placebo, 56 days apart.

Forward and reverse translational approaches to predict efficacy of neutralizing respiratory syncytial virus (RSV) antibody prophylaxis.

Background: Neutralizing mAbs can prevent communicable viral diseases. MK-1654 is a respiratory syncytial virus (RSV) F glycoprotein neutralizing monoclonal antibody (mAb) under development to prevent RSV infection in infants. Development and validation of methods to predict efficacious doses of neutralizing antibodies across patient populations exposed to a time-varying force of infection (i.

A Phase 1 Randomized, Double-Blind, Placebo-Controlled Trial to Assess the Safety, Tolerability, and Pharmacokinetics of a Respiratory Syncytial Virus Neutralizing Monoclonal Antibody MK-1654 in Healthy Adults.

Respiratory syncytial virus (RSV) is the leading cause of acute lower respiratory tract infection and related morbidity and mortality in infants. Passive immunization with an RSV-neutralizing antibody can provide rapid protection to this vulnerable population. Proof-of-concept for this approach has been demonstrated by palivizumab; however, the use of this antibody is generally restricted to the highest-risk infants due to monthly dosing requirements and its cost.

A phase 1, randomized, placebo-controlled study to evaluate the safety and immunogenicity of an mRNA-based RSV prefusion F protein vaccine in healthy younger and older adults.

Respiratory Syncytial Virus (RSV) causes lower respiratory tract infections that can be severe and sometimes fatal. The risk for severe RSV infection is highest in infants and older adults. A safe and effective RSV vaccine for older adults represents a serious unmet medical need due to higher morbidity and mortality in this age group.

Pharmacokinetic-pharmacodynamic (dipeptidyl peptidase-4 inhibition) model to support dose rationale in diabetes patients, including those with renal impairment, for once-weekly administered omarigliptin.

Aims: To characterize the population pharmacokinetics (PK) and pharmacodynamics (PD) of the once-weekly dipeptidyl peptidase-4 (DPP-4) inhibitor omarigliptin in healthy subjects and patients with type 2 diabetes mellitus, and use these models to support the dosing recommendation for patient labelling including patients with renal impairment.

Methods: PK and PD were assessed from a total of 9827 omarigliptin concentrations collected from 1387 healthy subjects and patients participating in Phase 1, 2 and 3 studies examining single- or multiple-dose weekly administration of omarigliptin at doses ranging from 0.25 to 400 mg.

A randomized, placebo-controlled clinical trial evaluating the safety and efficacy of the once-weekly DPP-4 inhibitor omarigliptin in patients with type 2 diabetes mellitus inadequately controlled by glimepiride and metformin.

Background: Type 2 diabetes (T2D) is a progressive disease that often requires a patient to use multiple antihyperglycemic agents to achieve glycemic control with disease progression. Omarigliptin is a once-weekly dipeptidyl peptidase-4 inhibitor. The purpose of this trial was to assess the efficacy and safety of adding omarigliptin to the treatment regimen of patients with T2D inadequately controlled by dual therapy with metformin and glimepiride.

A randomized, double-blind trial evaluating the efficacy and safety of monotherapy with the once-weekly dipeptidyl peptidase-4 inhibitor omarigliptin in people with type 2 diabetes.

Aims: To assess the efficacy and safety of once-weekly omarigliptin as monotherapy in people with type 2 diabetes mellitus (T2DM).

Methods: People with T2DM not on glucose-lowering medications, or who were washed off monotherapy or low-dose dual therapy, were randomized double-blind to omarigliptin 25 mg (n=165) or matching omarigliptin placebo (n=164) for 24 weeks, followed by a 30-week period to assess continuing efficacy and safety longer-term of omarigliptin during which metformin was added to the placebo group and metformin placebo to the omarigliptin group.

Results: From a mean baseline HbA1c of 8.

Use of Prohibited Medication, a Potentially Overlooked Confounder in Clinical Trials: Omarigliptin (Once-weekly DPP-4 Inhibitor) Monotherapy Trial in 18- to 45-year-olds.

Purpose: The objective of this clinical trial was to assess the efficacy and safety of omarigliptin monotherapy in young adult patients with type 2 diabetes mellitus (T2DM). Unexpected efficacy results in this trial led to a series of investigations that identified the use of prohibited medication by a substantial number of trial patients.

Methods: Patients with T2DM who were ≥18 to <45 years of age and either drug-naive or not on an antihyperglycemic agent for ≥12 weeks with inadequate glycemic control were randomized in a double-blind manner to receive omarigliptin 25 mg once weekly (n = 102) or placebo once weekly (n = 101) for 24 weeks.

A randomized, placebo-controlled study of the cardiovascular safety of the once-weekly DPP-4 inhibitor omarigliptin in patients with type 2 diabetes mellitus.

Background: Omarigliptin is a once-weekly (q.w.) oral DPP-4 inhibitor that is approved for the treatment of patients with type 2 diabetes mellitus (T2DM) in Japan.

A Randomized, Placebo-Controlled Trial Evaluating the Safety and Efficacy of Adding Omarigliptin to Antihyperglycemic Therapies in Japanese Patients with Type 2 Diabetes and Inadequate Glycemic Control.

Introduction: Daily dipeptidyl peptidase-4 (DPP-4) inhibitors are commonly used with other orally administered antihyperglycemic agents (AHA), as combination therapy, to treat Japanese patients with type 2 diabetes. When combination therapy is indicated, use of a once-weekly (q.w.

A randomized, double-blind, non-inferiority trial evaluating the efficacy and safety of omarigliptin, a once-weekly DPP-4 inhibitor, or glimepiride in patients with type 2 diabetes inadequately controlled on metformin monotherapy.

Objective: To evaluate the efficacy and safety of adding the once-weekly DPP-4 inhibitor omarigliptin or the sulfonylurea glimepiride to the treatment regimen of patients with type 2 diabetes (T2DM) and inadequate glycemic control on metformin monotherapy.

Methods: Patients with T2DM and HbA1c ≥6.5% to ≤9.

A randomized clinical trial evaluating the efficacy and safety of the once-weekly dipeptidyl peptidase-4 inhibitor omarigliptin in patients with type 2 diabetes inadequately controlled on metformin monotherapy.

Objective: To examine the efficacy and safety of the once-weekly (q.w.) dipeptidyl peptidase-4 inhibitor, omarigliptin, in patients with type 2 diabetes (T2DM) and inadequate glycemic control on metformin monotherapy.

A randomized, placebo- and sitagliptin-controlled trial of the safety and efficacy of omarigliptin, a once-weekly dipeptidyl peptidase-4 inhibitor, in Japanese patients with type 2 diabetes.

Aims: To assess the safety and efficacy of omarigliptin in Japanese patients with type 2 diabetes (T2D).

Methods: In a 24-week double-blind trial, 414 patients with T2D were randomized to omarigliptin 25 mg once weekly, sitagliptin 50 mg once daily or placebo. The double-blind period was followed by a 28-week open-label extension during which all patients received omarigliptin 25 mg once weekly.

A randomised, double-blind, trial of the safety and efficacy of omarigliptin (a once-weekly DPP-4 inhibitor) in subjects with type 2 diabetes and renal impairment.

Aims: To assess the safety and efficacy of omarigliptin in subjects with type 2 diabetes mellitus (T2DM) and chronic renal impairment (RI).

Methods: Patients with T2DM with moderate RI (estimated glomerular filtration rate [eGFR] ≥30 to <60 mL/min/1.73 m ) (N=114), severe RI (eGFR <30 mL/min/1.

Randomized clinical trial comparing the efficacy and safety of treatment with the once-weekly dipeptidyl peptidase-4 (DPP-4) inhibitor omarigliptin or the once-daily DPP-4 inhibitor sitagliptin in patients with type 2 diabetes inadequately controlled on metformin monotherapy.

Aim: To compare the efficacy and safety of the once-weekly oral dipeptidyl peptidase-4 (DPP-4) inhibitor omarigliptin or once-daily DPP-4 inhibitor sitagliptin in patients with type 2 diabetes (T2DM) and inadequate glycaemic control on metformin.

Materials And Methods: Patients with T2DM with a glycated haemoglobin (HbA1c) concentration ≥6.5% to ≤9.

Effects of Extended-Release Niacin and Extended-Release Niacin/Laropiprant on the Pharmacokinetics of Simvastatin in Healthy Subjects.

The use of multiple lipid-modifying agents with different mechanisms of action is often required to regulate lipid levels in patients with dyslipidemia. During combination therapy, alterations in the pharmacokinetics of any of the drugs used and their metabolites may occur. Three separate open-label, randomized, crossover studies evaluated the potential for pharmacokinetic interaction between extended-release niacin (with and without concomitant laropiprant) and simvastatin in healthy subjects.

Influence of renal and hepatic impairment on the pharmacokinetics of anacetrapib.

Two open-label, parallel-group studies evaluated the influence of renal and hepatic insufficiency on the pharmacokinetics of a single-dose anacetrapib 100 mg. Eligible participants included adult men and women with moderate hepatic impairment (assessed by Child-Pugh criteria) or severe renal impairment (CrCl <30 mL/min/1.73 m(2)).

Single therapeutic and supratherapeutic doses of anacetrapib, a cholesteryl ester transfer protein inhibitor, do not prolong the QTcF interval in healthy volunteers.

Anacetrapib is a cholesteryl ester transfer protein inhibitor in Phase III development. This double-blind, double-dummy, randomized, placebo- and active-comparator-controlled, 4-period, balanced crossover study evaluated the effects of anacetrapib (100 mg and 800 mg) on QTcF interval in healthy subjects. QTcF measurements were made up to 24 h following administration of single doses of anacetrapib 100 or 800 mg, moxifloxacin 400 mg, or placebo in the fed state.

The effects of laropiprant on the antiplatelet activity of co-administered clopidogrel and aspirin.

Laropiprant is an antagonist of the prostaglandin PGD2 receptor DP1. Laropiprant has a weak affinity for the thromboxane A2 receptor TP. Two double-blinded, randomized, placebo-controlled, crossover studies evaluated the effects of multiple-dose laropiprant at steady state on the antiplatelet effects of multiple-dose aspirin and clopidogrel.