Virtualized clinical studies to assess the natural history and impact of gut microbiome modulation in non-hospitalized patients with mild to moderate COVID-19 a randomized, open-label, prospective study with a parallel group study evaluating the physiologic effects of KB109 on gut microbiota structure and function: a structured summary of a study protocol for a randomized controlled study.

Objectives: These 2 parallel studies (K031 and K032) aim to evaluate the safety of KB109 in addition to supportive self-care (SSC) compared with SSC alone in outpatients with mild to moderate coronavirus disease 2019 (COVID-19). KB109 is a novel synthetic glycan that was formulated to modulate the gut microbiome composition and metabolic output in order to increase beneficial short-chain fatty acid (SCFA) production in the gut. The K031 study is designed to evaluate the safety of KB109 and characterize its impact on the natural progression of COVID-19 in patients with mild to moderate disease.

Next-day residual effects of gabapentin, diphenhydramine, and triazolam on simulated driving performance in healthy volunteers: a phase 3, randomized, double-blind, placebo-controlled, crossover trial.

Objective: Next-day residual effects of a nighttime dose of gabapentin 250 mg were evaluated on simulated driving performance in healthy participants in a randomized, placebo-controlled, double-blind, multicenter, four-period crossover study that included diphenhydramine citrate 76 mg and triazolam 0.5 mg.

Methods: At treatment visits, participants (n = 59) were dosed at ~23:30, went to bed immediately, and awakened 6.

Impact of cough and common cold on productivity, absenteeism, and daily life in the United States: ACHOO Survey.

Background: Although the common cold is among the most frequent ailments encountered in clinical practice, little is known about its impact on productivity, absenteeism, and daily life.

Objective: The United States Attitudes of Consumers Toward Health, Cough, and Cold (ACHOO) survey was developed to inform healthcare providers on patients' experience of cough/cold. This analysis focuses on the impact of cough/cold on daily activity, productivity, and absenteeism; other results are reported elsewhere.

Over-the-Counter Agents for the Treatment of Occasional Disturbed Sleep or Transient Insomnia: A Systematic Review of Efficacy and Safety.

Objective: To investigate the level of evidence supporting the use of common over-the-counter (OTC) agents (diphenhydramine, doxylamine, melatonin, and valerian) for occasional disturbed sleep or insomnia.

Data Sources: A systematic review of the literature was conducted on July 31, 2014, using MEDLINE (PubMed) and the search terms (insomnia OR sleep) AND (over*the*counter OR OTC OR non*prescription OR antihistamine OR doxylamine OR diphenhydramine OR melatonin OR valerian) with the filters English, human, and clinical trials.

Study Selection: Identified publications (from 2003 to July 31, 2014, following previous published literature reviews) that met the inclusion criteria were selected.

Burden of allergic rhinitis: allergies in America, Latin America, and Asia-Pacific adult surveys.

Allergic rhinitis (AR; also nasal allergies or "hay fever") is a chronic upper airway inflammatory disease that affects ∼60 million adults and children in the United States. The duration and severity of AR symptoms contribute to a substantial burden on patients' quality of life (QoL), sleep, work productivity, and activity. This study was designed to examine symptoms, QoL, productivity, comorbidities, disease management, and pharmacologic treatment of AR in United States and ex-U.

An investigation of the pharmacokinetics, pharmacodynamics, safety, and tolerability of ciclesonide hydrofluoroalkane nasal aerosol in healthy subjects and subjects with perennial allergic rhinitis.

Ciclesonide hydrofluoroalkane nasal aerosol (CIC-HFA) is currently in development for treatment of allergic rhinitis. This Phase I study evaluated the pharmacokinetics, pharmacodynamics, safety, and tolerability of CIC-HFA in healthy subjects (N = 18) and subjects with perennial allergic rhinitis (PAR, N = 18) in a double-blind, placebo-controlled, 3-period crossover design following treatment with 282 μg or 148 μg CIC-HFA or placebo once-daily for 14 days. The concentrations of desisobutyryl-ciclesonide (des-CIC), the pharmacologically active metabolite of CIC were measured by a validated high performance liquid chromatography with tandem mass spectrometry.

Ciclesonide, a hypotonic intranasal corticosteroid.

Intranasal corticosteroids (INCSs) are established as the first-line treatment of moderate to severe allergic rhinitis (AR) in both adults and children. Compared with other nasal allergy medications, INCSs are the most effective at providing symptom relief and increasing quality of life. Ciclesonide nasal spray is the most recently approved INCS.

Nasal allergies in the Latin American population: results from the Allergies in Latin America survey.

Allergies in Latin America is the first cross-national survey that describes the symptoms, impact, and treatment of nasal allergies (NAs) in individuals >or=4 years old in Latin America (LA). In total, 22,012 households across the Latin American countries of Argentina, Brazil, Chile, Colombia, Ecuador, Mexico, Peru, and Venezuela were screened for children, adolescents, and adults with a diagnosis of NA and either symptoms or treatment in the past 12 months. A total of 1088 adults and 457 children and adolescents were included and the sample was probability based to ensure valid statistical inference to the population.

Pharmacokinetics of ciclesonide and desisobutyryl ciclesonide after administration via aqueous nasal spray or hydrofluoroalkane nasal aerosol compared with orally inhaled ciclesonide: an open-label, single-dose, three-period crossover study in healthy volunteers.

Background: Ciclesonide, an intranasal corticosteroid, is administered as a prodrug and is converted to the active metabolite, desisobutyryl ciclesonide, in the upper and lower airways. Previous studies have assessed systemic exposure with the ciclesonide hydrofluoroalkane metered dose inhaler (CIC HFA-MDI) and the ciclesonide aqueous nasal spray (CIC-AQ) formulations. However, systemic exposure with ciclesonide HFA nasal aerosol (CIC-HFA) developed for the treatment of allergic rhinitis has not been investigated.

Efficacy and safety of ciclesonide hydrofluoroalkane nasal aerosol once daily for the treatment of seasonal allergic rhinitis.

Background: Aerosol-based corticosteroid nasal formulations may be preferred over current aqueous nasal sprays by some patients because they traditionally cause less pharyngeal and anterior nose runoff.

Objective: To determine the optimal dose, safety, and tolerability of ciclesonide hydrofluoroalkane nasal aerosol in patients with seasonal allergic rhinitis (SAR).

Methods: Patients 12 years or older with a history of SAR received ciclesonide hydrofluoroalkane nasal aerosol to a total dose of 75, 150, or 300 microg or placebo once daily (half dose per nostril) for 2 weeks.

Burden of allergic rhinitis: results from the Pediatric Allergies in America survey.

Allergic rhinitis (AR), a chronic inflammatory disease of the upper airway, is one of the most common chronic diseases in the United States and is estimated to affect up to 60 million people. Pediatric Allergies in America is the largest and most comprehensive survey to date of pediatric patients and parents of patients with allergy, as well as health care providers (HCPs), regarding AR in children and its treatment. The goals of the survey were to determine the prevalence of AR in the US pediatric population and to collect information on what effect the condition has on patients in terms of symptom burden, quality of life, productivity, disease management, and pharmacologic treatment.

Onset of action of ciclesonide once daily in the treatment of seasonal allergic rhinitis.

Background: Ciclesonide is an intranasal corticosteroid approved for the treatment of allergic rhinitis (AR).

Objective: To evaluate the time to onset of action of ciclesonide, 200 microg/d, in patients with seasonal AR (SAR).

Methods: In a double-blind, randomized, placebo-controlled study conducted in an environmental exposure chamber, 509 adults with at least a 2-year history of SAR completed 1 to 5 priming sessions of ragweed pollen exposure (mean [SD] of 3,500 [500] grains/m3).

Onset of action of ciclesonide once daily in the treatment of seasonal allergic rhinitis.

Ciclesonide is an intranasal corticosteroid approved for the treatment of allergic rhinitis. We conducted a randomized, double-blind, parallel-group, placebo-controlled study to evaluate the time to onset of action of ciclesonide 200 microg once daily in 502 adults with seasonal allergic rhinitis of at least 2 years' duration. To trigger immunologic priming, patients underwent between one and five priming sessions with exposure to 3,500 grains/m(3) (+/-500) of ragweed pollen in an environmental exposure chamber.

Ciclesonide and beclomethasone dipropionate coadministration: effect on cortisol in perennial allergic rhinitis.

Coexisting asthma and allergic rhinitis (AR) are often treated with both intranasal and inhaled corticosteroids. This study investigated whether intranasal ciclesonide 200 microg once daily has an additional effect on cortisol suppression when coadministered with inhaled hydrofluoroalkane-beclomethasone dipropionate (HFA-BDP). Adult patients (n = 150) with perennial AR received HFA-BDP 320 microg twice daily and placebo once daily during a run-in period.

Uptake and metabolism of ciclesonide and retention of desisobutyryl-ciclesonide for up to 24 hours in rabbit nasal mucosa.

Background: The nasal tissue uptake and metabolism of ciclesonide, a new-generation corticosteroid under investigation for treatment of allergic rhinitis, to its active metabolite, desisobutyryl-ciclesonide (des-CIC), was evaluated when administered to rabbits in a hypotonic versus an isotonic ciclesonide suspension. Nasal mucosa extracts from normal Japanese white rabbits were evaluated by high-performance liquid chromatography with tandem mass spectrometry detection after a single 143-mug dose of ciclesonide. Retention and formation of fatty acid conjugates of des-CIC were also measured in nasal mucosa extracts postadministration of a hypotonic ciclesonide suspension (143-mug single dose).

Optimization of intranasal corticosteroid formulations for the treatment of allergic rhinitis.

Intranasal corticosteroids (INCSs) provide safe and effective treatment of allergic rhinitis (AR). Currently available INCSs differ in terms of the components included in each formulation that may influence efficacy, tolerability, and patient preference for treatment. Patient preference for a specific INCS is largely attributable to the sensory attributes that are dependent on characteristics of the formulation.

Efficacy and safety of ciclesonide, 200 microg once daily, for the treatment of perennial allergic rhinitis.

Background: Ciclesonide is an intranasal corticosteroid approved for the treatment of allergic rhinitis (AR).

Objective: To evaluate the efficacy, safety, and quality-of-life benefits of intranasal ciclesonide, 200 microg once daily, for the treatment of perennial AR (PAR).

Methods: In this multicenter, randomized, double-blind, placebo-controlled study, adults and adolescents with at least a 2-year history of PAR received intranasal ciclesonide, 200 microg, or placebo once daily for 6 weeks.

Effectiveness of ciclesonide nasal spray in the treatment of seasonal allergic rhinitis.

Background: Ciclesonide is an investigational corticosteroid under development for treatment of allergic rhinitis. Ciclesonide is converted to active metabolite, desisobutyryl-ciclesonide (des-CIC), by upper and lower airway esterases. In vitro studies in human nasal epithelial cells and bronchial epithelial cells have demonstrated a long duration of anti-inflammatory activity of des-CIC.

Efficacy and safety of ciclesonide nasal spray for the treatment of seasonal allergic rhinitis.

Background: Allergic rhinitis (AR), an inflammatory disease of the nasal mucosa, affects approximately 25% of adults and 40% of children in the United States. Ciclesonide nasal spray is a corticosteroid being developed as a hypotonic formulation for AR.

Objective: We sought to evaluate the efficacy, safety, and tolerability of ciclesonide nasal spray in adult and adolescent patients with seasonal AR (SAR).

Safety, tolerability, and exposure of ciclesonide nasal spray in healthy and asymptomatic subjects with seasonal allergic rhinitis.

Ciclesonide is an intranasal corticosteroid in development for the treatment of allergic rhinitis. To assess the safety, tolerability, and pharmacokinetics of ciclesonide, adult healthy volunteers and asymptomatic subjects with seasonal allergic rhinitis were randomized to receive intranasal ciclesonide or placebo for 14 days. Serum concentrations of ciclesonide and its active metabolite, desisobutyryl-ciclesonide, were measured using high-performance liquid chromatography assay with tandem mass spectrometric detection, with lower limits of quantification of 25 and 10 pg/mL, respectively.

Gum arabic (GA) modifies paracellular water and electrolyte transport in the small intestine.

Previous experiments have shown that a soluble fiber, gum arabic (GA), enhances water, electrolyte, and glucose absorption in animal models of diarrhea. The mechanisms implicated in this effect have not been fully elucidated. This study examined the possibility that paracellular transport is modulated by luminal GA, resulting in an enhanced rate of absorption in the small intestine.

Zinc as a potential enteroprotector in oral rehydration solutions: its role in nitric oxide metabolism.

Zinc has been recognized as an antioxidant with potential for chronic and acute effects. Oxidative damage produced by free radicals, including nitric oxide (NO), is responsible for certain types of intestinal malabsorption syndromes and diarrhea. Under physiologic or mildly stimulatory conditions for NO synthesis, the small intestine characteristically is in a proabsorptive state; however, an excessive production of NO triggers formation of cyclic nucleotides, which cause secretion and malabsorption.