Papers by Andrea Navarria
Annales d'Endocrinologie, 2018
Diabetologie Und Stoffwechsel, May 1, 2019
Expert Opinion on Drug Metabolism & Toxicology, Jun 30, 2018
Diabetes, Jun 1, 2019
The GLP-1 analog semaglutide has been co-formulated with the absorption enhancer sodium N-(8-[2-h... more The GLP-1 analog semaglutide has been co-formulated with the absorption enhancer sodium N-(8-[2-hydroxybenzoyl] amino) caprylate (SNAC) to allow oral administration. Since oral semaglutide is absorbed in the stomach, the effect of upper gastrointestinal disease (UGD) on exposure to oral semaglutide has been investigated in an open-label, parallel-group trial (NCT02877355). Subjects aged 18-80 years with T2D and with UGD (N=36; chronic gastritis [n=5], gastroesophageal reflux disease [GERD; n=8] or both [n=23]) or without UGD (N=19) received oral semaglutide 3 mg once-daily for 5 days followed by 7 mg for 5 days. Key endpoints were area under the semaglutide plasma concentration-time curve (AUC) (primary) and maximum semaglutide plasma concentration (Cmax) from 0-24 h after the 10th dose. Semaglutide exposure was not statistically significantly different in subjects with vs. without UGD (Figure; estimated group ratios with/without UGD [95% CI] AUC: 1.18 [0.80; 1.75]and Cmax: 1.16 [0.77; 1.76]). Time to maximum plasma concentration and half-life of semaglutide were similar in subjects with vs. without UGD. Oral semaglutide was well tolerated. All adverse events (AEs) were mild or moderate with no withdrawals due to AEs. In conclusion, no significant difference in exposure to oral semaglutide in subjects with vs. without UGD was found; hence, no dose adjustment is expected to be required. Disclosure J.J. Meier: Advisory Panel; Self; AstraZeneca, Boehringer Ingelheim International GmbH, Eli Lilly and Company, Merck Sharp & Dohme Corp., Novo Nordisk A/S, Sanofi. C. Granhall: Employee; Self; Novo Nordisk A/S. Stock/Shareholder; Self; Novo Nordisk A/S. U. Hoevelmann: None. A. Navarria: Employee; Self; Novo Nordisk A/S. Employee; Spouse/Partner; Novo Nordisk A/S. L. Plum-Moerschel: None. C. Ramesh: None. A. Tannapfel: None. C. Kapitza: Research Support; Self; ADOCIA, Biocon, Boehringer Ingelheim Pharmaceuticals, Inc., Dance Biopharm Holdings Inc., Eli Lilly and Company, Gan & Lee Pharmaceuticals, MedImmune, Mylan, Nestlé, Nordic Bioscience, Novo Nordisk A/S, Poxel SA, Sanofi-Aventis, Wockhardt, Xeris Pharmaceuticals, Inc., Zealand Pharma A/S. Funding Novo Nordisk A/S
Diabetes, Obesity and Metabolism, Jan 17, 2022
AimTo investigate whether upper gastrointestinal (GI) disease has any effect on the exposure of o... more AimTo investigate whether upper gastrointestinal (GI) disease has any effect on the exposure of oral semaglutide, an important consideration given that its absorption occurs primarily in the stomach.Materials and MethodsIn an open‐label, parallel‐group trial (NCT02877355), subjects aged 18‐80 years with type 2 diabetes with mild‐to‐moderate upper GI disease (N = 36; chronic gastritis [n = 5], gastroesophageal reflux disease [n = 8], and both [n = 23]) or without upper GI disease (N = 19) received oral semaglutide 3 mg once daily for 5 days, followed by 7 mg for 5 days. The primary and key supportive endpoints were the area under the semaglutide plasma concentration–time curve (AUC) from 0 to 24 hours after last trial product administration on day 10 (AUC0−24h,day10) and the maximum semaglutide plasma concentration (Cmax,day10), respectively.ResultsSemaglutide exposure was not statistically significantly different between subjects with and without upper GI disease. Estimated group ratios (subjects with/without upper GI disease) were 1.18 (95% confidence interval [CI], 0.80, 1.75) for AUC0−24h,day10 and 1.16 (95% CI, 0.77, 1.76) for Cmax. Time to Cmax and semaglutide half‐life were similar in subjects with and without upper GI disease. Oral semaglutide was well tolerated; all adverse events were mild‐to‐moderate, with no withdrawals because of adverse events.ConclusionsThere was no significant difference in exposure to oral semaglutide in subjects with or without upper GI disease, hence no dose adjustment is required.
Canadian Journal of Diabetes, Oct 1, 2019
Nephrology Dialysis Transplantation
Background and Aims Setmelanotide is an approved treatment for chronic weight management and cont... more Background and Aims Setmelanotide is an approved treatment for chronic weight management and control of hunger in patients aged ≥6 years with specific forms of obesity including Bardet-Biedl syndrome (BBS). Setmelanotide may be considered for patients with renal impairment, including those with BBS, who often experience impaired renal function as a primary feature of the syndrome. This study evaluated the pharmacokinetics (PK) and safety of a single dose of setmelanotide in individuals without BBS who have renal impairment. Method This Phase 1, open-label study (NCT04348175) was conducted in 3 centers in the United States. Eligible individuals were aged 18-83 years and had general obesity with a body mass index (BMI) of 22-40 kg/m2. Individuals were assigned to a study cohort according to renal function, determined by estimated glomerular filtration rate (normal renal function [healthy volunteers]: ≥90 mL/min/1.73 m2; mild renal impairment: 60-89 mL/min/1.73 m2; moderate renal impai...
Diabetes, Obesity and Metabolism, 2021
AimTo investigate whether upper gastrointestinal (GI) disease has any effect on the exposure of o... more AimTo investigate whether upper gastrointestinal (GI) disease has any effect on the exposure of oral semaglutide, an important consideration given that its absorption occurs primarily in the stomach.Materials and MethodsIn an open‐label, parallel‐group trial (NCT02877355), subjects aged 18‐80 years with type 2 diabetes with mild‐to‐moderate upper GI disease (N = 36; chronic gastritis [n = 5], gastroesophageal reflux disease [n = 8], and both [n = 23]) or without upper GI disease (N = 19) received oral semaglutide 3 mg once daily for 5 days, followed by 7 mg for 5 days. The primary and key supportive endpoints were the area under the semaglutide plasma concentration–time curve (AUC) from 0 to 24 hours after last trial product administration on day 10 (AUC0−24h,day10) and the maximum semaglutide plasma concentration (Cmax,day10), respectively.ResultsSemaglutide exposure was not statistically significantly different between subjects with and without upper GI disease. Estimated group ra...
Clinical drug investigation, Jan 30, 2017
According to the Italian National Report on drug use, thienopyridines (ticlopidine, clopidogrel a... more According to the Italian National Report on drug use, thienopyridines (ticlopidine, clopidogrel and prasugrel) and ticagrelor represent the most prescribed antiplatelet agents, beside aspirin. The aim of this study was to analyse the safety profile of these drugs using data from spontaneous reporting of suspected adverse reactions (ADRs). Suspected ADRs for ticlopidine, clopidogrel, prasugrel and ticagrelor, reported on the Italian National Pharmacovigilance Network between January 2009 and December 2016, were included in the analysis. All suspected ADRs were classified by frequency, seriousness, outcome, age and system organ class. Clopidogrel showed the highest absolute number of suspected ADRs, followed by ticlopidine. However, these data need to be contextualized in view of the differences in marketing authorization dates, prescription rates and a characterization of the relative seriousness of ADRs per each drug. After the correction for prescription rate, ticagrelor showed the...
European Neuropsychopharmacology, 2014
Pharmacological Research, 2014
In recent years, several studies have explored the involvement of the deregulation of the hypotha... more In recent years, several studies have explored the involvement of the deregulation of the hypothalamus-pituitary-adrenal (HPA) axis in the pathophysiology of stress-related disorders. HPA hyper-activation as a consequence of acute/chronic stress has been found to play a major role in the neurobiological changes that are responsible for the onset of such states. Currently available medications for depression, one of the most relevant stress-related disorders, present several limitations, including a time lag for treatment response and low rates of efficacy. N-Arachidonoylserotonin (AA-5-HT), a dual blocker at fatty acid amide hydrolase (FAAH, the enzyme responsible for the inactivation of the endocannabinoid anandamide) and transient receptor potential vanilloid type-1 channel (TRPV1), produces anxiolytic-like effects in mice. The present study was designed to assess the capability of AA-5-HT to reverse the behavioral despair following exposure to stress in rats and the role of the HPA-axis. Behavioral tasks were performed, and corticosterone and endocannabinoid (anandamide and 2-arachidonoylglycerol) levels were measured in selected brain areas critically involved in the pathophysiology of stress-related disorders (medial PFC and hippocampus) under basal and stress conditions, and in response to treatment with AA-5-HT. Our data show that AA-5-HT reverses the rat behavioral despair in the forced swim test under stress conditions, and this effect is associated with the normalization of the HPA-axis deregulation that follows stress application and only in part with elevation of anandamide levels. Blockade of FAAH and TRPV1 may thus represent a novel target to design novel therapeutic strategies for the treatment of stress-related disorders.
International Journal of Neuropsychopharmacology, 2012
These experiments were undertaken to assess the mechanisms underlying the antidepressant-like eff... more These experiments were undertaken to assess the mechanisms underlying the antidepressant-like effects of the neurokinin-2 (NK2) receptor antagonist saredutant (SR48968) in rats tested in the forced swim test (FST), by analysing hippocampal brain-derived neurotrophic factor (BDNF) and plasma corticosterone [as index of hypothalamic-pituitary-adrenal (HPA) axis activity]. Male Wistar rats received three intraperitoneal injections over 24 h of vehicle, saredutant (5 mg/kg), citalopram (15 mg/kg), clomipramine (50 mg/kg). Rats were subjected to restraint stress (4 h) 24 h prior to the FST procedure. This stress procedure increased immobility and decreased swimming behaviour in the FST; furthermore, it lowered hippocampal BDNF protein expression and increased plasma corticosterone levels. Saredutant and clomipramine or citalopram, used here as positive controls, reduced the immobility time in the FST both under basal conditions and after stress exposure. This effect was not attributable ...
Progress in Neuro-Psychopharmacology and Biological Psychiatry, 2009
Clinical Pharmacokinetics
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Papers by Andrea Navarria