Farnier M.,Point Medical |
Marcereuil D.,Laboratoires SMB SA |
De Niet S.,Laboratoires SMB SA |
Ducobu J.,University of Mons |
And 5 more authors.
Clinical Drug Investigation | Year: 2012
Background: Fenofibrate can be prescribed concomitantly with an HMGCoA reductase inhibitor (statin) to improve achievement of lipid goals in patients with atherogenic mixed hyperlipidaemia. However, some safety concerns, particularly an increased risk of myopathy, have been reported when these drugs are taken together. Objective: The aim of this analysis was to assess the general safety and tolerability of a fenofibrate/pravastatin (FF/PRA) 160mg/40 mg fixed-dose combination (FDC) capsule based on a pooled database of phase III clinical trials in patients with mixed hyperlipidaemia. Methods: Safety data were pooled from five phase III studies (four doubleblind with an uncontrolled extension and one open) of ≥12 to 64 weeks' duration. Adverse event (AE) profiles of FF/PRA 160mg/40mg (n = 645 in the double-blind cohort) were evaluated relative to comparators (statins, n = 519 or fenofibrate, n = 122). Absolute incidence rates were calculated in both the double-blind cohort and the all-studies cohort (FF/PRA 160mg/40 mg, n = 1566) for all AEs, drug-related AEs, serious AEs, discontinuations due to AEs, AEs of specific interest including abnormal laboratory data, and deaths. Results: The frequency and/or intensity of overall AEs, drug-related AEs, serious AEs and discontinuations due to AEs were not significantly increased for the FDC (36.0%, 12.3%, 1.7% and 5.1%, respectively) versus the statin (28.7%, 8.9%, 0.8% and 2.7%, respectively) and fenofibrate (59.0%, 21.3%, 0% and 4.9%, respectively) monotherapies. No deaths were reported during the course of treatment in clinical trials. Nevertheless, three deaths were reported more than 30 days after the patients completed the study; none of these deaths were assessed as being related to FF/PRA 160mg/40 mg treatment. Among the AEs of special interest, no myopathy or rhabdomyolysis were reported; no patients were considered to have experienced a druginduced liver injury; no case of pancreatitis occurred in the double-blind cohort and four patients reported pancreatitis in the all-studies cohort, two of them being study-treatment related; no case of pulmonary embolism was reported in the double-blind cohort and two patients presented with pulmonary embolism, unrelated to the study drug, in the all-studies cohort; there were more cases of decreased creatinine clearance in the FF/PRA 160mg/40mg group (1.7%) than in the statin group (0.6%). Conclusion: Within the limitations of this database (notably low percentage of very elderly patients, limited sample size of patients with mild renal insufficiency, and mode of selection in the clinical trials), no particular safety concern was raised with FF/PRA 160mg/40 mg in the double-blind cohort as compared with statin and fenofibrate monotherapies. The acceptable long-term safety profile of FF/PRA 160mg/40mg was confirmed with a low frequency of AEs of interest, comparable to that observed in the 12-week double-blind cohort. Emergent effects possibly related to FF/PRA 160mg/40mg were mainly those attributable to fenofibrate (decrease in creatinine clearance and pancreatitis). © 2012 Adis Data Information BV. All rights reserved.
Cavalier E.,University of Liège |
Jandrain B.,ATC SA |
Coffiner M.,Laboratoires SMB SA |
Da Silva S.,Laboratoires SMB SA |
And 3 more authors.
Nutrients | Year: 2016
Vitamin D3 is known to be liposoluble and its release could be a factor limiting the rate of absorption. It was presumed that the presence of fat could favor absorption of vitamin D3. However, as bioavailability is related not only to the active molecules but also to the formulations and excipients used, the optimization of the pharmaceutical form of vitamin D3 is also important. The objective of this study was to evaluate if there is a food effect on absorption when a high dose of vitamin D3 is completely solubilized in an oily solution. In the present cross-over study, 88 subjects were randomized and received a single dose of 50,000 IU of vitamin D3 in fasting state or with a standardized high-fat breakfast. Assessment of serum concentrations of 25 hydroxyvitamin D3 (25(OH)D3) was performed three, five, seven, 14, 30 and 60 days after supplementation. In fed and fast conditions, the 25(OH)D3 serum concentrations were significantly higher than the baseline value three days after administration and remained significantly higher during the first month. No significant difference between fasting vs. fed conditions was observed. It is therefore concluded that the vitamin D3 absorption from an oily solution was not influenced by the presence or absence of a meal. © 2016 by the authors; licensee MDPI, Basel, Switzerland.
A randomized, double-blind, parallel study to evaluate the dose-response of three different vitamin D treatment schemes on the 25-hydroxyvitamin D serum concentration in patients with vitamin D deficiency
Schleck M.-L.,University of Liège |
Souberbielle J.-C.,Laboratoire Dexplorations Fonctionnelles |
Jandrain B.,ATC SA |
Da Silva S.,Laboratoires SMB SA |
And 4 more authors.
Nutrients | Year: 2015
Many people worldwide are vitamin D (VTD) deficient or insufficient, and there is still no consensus on the dose of VTD that should be administered to achieve a 25(OH)D concentration of 20 or 30 ng/mL. In this study, we aimed to determine an adapted supplementation of VTD able to quickly and safely increase the vitamin D status of healthy adults with low 25(OH)D. One hundred and fifty (150) subjects were randomized into three groups, each to receive, orally, a loading dose of 50,000, 100,000 or 200,000 IU of VTD3 at Week 0, followed by 25,000, 50,000 or 100,000 IU at Week 4 and Week 8. Whereas 25(OH)D baseline values were not different between groups (p = 0.42), a significant increase was observed at Week 12 (p < 0.0001) with a mean change from baseline of 7.72 ± 5.08, 13.3 ± 5.88 and 20.12 ± 7.79 ng/mL. A plateau was reached after eight weeks. No related adverse event was recorded. This study demonstrated a linear dose-response relationship with an increase in 25(OH)D levels proportional to the dose administered. In conclusion, a loading dose of 200,000 IU VTD3 followed by a monthly dose of 100,000 IU is the best dosing schedule to quickly and safely correct the VTD status. © 2015 by the authors; licensee MDPI, Basel, Switzerland.
Popov T.A.,Medical University-Sofia |
De Niet S.,Laboratoires SMB SA |
Vanderbist F.,Laboratoires SMB SA
Expert Review of Respiratory Medicine | Year: 2016
Fixed dose combinations (FDC) of inhaled corticosteroid (ICS) and long-acting beta agonist (LABA) are well established in asthma treatment. The budesonide/salmeterol (B/S) FDC is now about to reach the market. It is provided as powder in hard capsules of two strengths: 120/20g and 240/20g when expressed as delivered doses, equivalent to 150/25g and 300/25g when expressed as nominal doses. Its development involved 9 pharmacokinetic (320 subjects), 3 phase II (123 subjects) and 4 phase III (1206 patients with different asthma severity) studies. Delivery is effectuated via low resistance inhaler device, Axahaler®, generating also fine particles targeting the small airways. B/S safety, assessed in 1401 subjects, did not outline novel concerns specific for this FDC. In conclusion, the B/S dry powder FDC can be used for asthma treatment in adults not adequately controlled on ICS alone, or to maintain control of ICS/LABA treated patients, in whom switching to alternative FDC is indicated. © 2016 Taylor & Francis.
Duret C.,Free University of Colombia |
Wauthoz N.,Free University of Colombia |
Sebti T.,Laboratoires SMB S.A. |
Vanderbist F.,Laboratoires SMB S.A. |
Amighi K.,Free University of Colombia
Pharmaceutical Research | Year: 2012
Purpose Novel itraconazole (ITZ)-based dry powders for inhalation (DPI) were optimized for aerodynamic and dissolution properties and contained excipients that are acceptable for inhalation. Methods The DPI were produced by spray drying solutions. The drug content, crystallinity state, and morphological evaluation of the dry powders were determined by high performance liquid chromatography, powder X-ray diffraction, differential scanning calorimetry, and scanning electron microscopy, respectively. A particle size analysis was conducted using laser light scattering. The aerodynamic behaviors of the powders were characterized by impaction tests. ITZ dissolution rates were evaluated using a dissolution method adapted to inhaled products. Results The DPI presented very high fine particle fractions that ranged from 46.9% to 67.0% of the nominal dose. The formulations showed very fast dissolution rates compared to unformulated crystalline ITZ with the possibility of modulating the dissolution rate by varying the quantity of phospholipids (PL) incorporated. ITZ remained amorphous while the mannitol was crystalline. The a, β and d-mannitol polymorph ratios varied depending on the formulation compositions. Conclusion This formulation strategy could be an attractive alternative for treating invasive pulmonary aspergillosis. The ITZ and PL content are key characteristics because of their influence on the dissolution rate and aerosol performance. ©Springer Science+Business Media, LLC 2012.
Laboratoires SMB SA | Date: 2013-06-12
A spray dried-powder composition for inhalation comprising particles (X) containing (a) between 5 and 50% by weight of at least one azole derivative in amorphous state but not in crystalline structure and (b) at least one matricial agent to the composition selected from a group consisting of polyol such as sorbitol, mannitol and xylitol; a monosaccharides such as glucose and arabinose; disaccharide such as lactose, maltose, saccharose and dextrose; cholesterol, and any mixture thereof, wherein the composition provides a dissolution rate of said azole derivative of at least, 5 % within 10 minutes, 10 % within 20 minutes and 40 % within 60 minutes when tested in the dissolution apparatus type 2 of the United States Pharmacopoeia at 50 rotation per minute, 37 C in 900 milliters of an aqueous dissolution medium adjusted at pH 1.2 and containing 0.3 % of sodium laurylsulfate.
PubMed | ATC SA, Laboratoire dExplorations Fonctionnelles, Laboratoires SMB SA and University of Liège
Type: Journal Article | Journal: Nutrients | Year: 2016
Vitamin D is known to be liposoluble and its release could be a factor limiting the rate of absorption. It was presumed that the presence of fat could favor absorption of vitamin D. However, as bioavailability is related not only to the active molecules but also to the formulations and excipients used, the optimization of the pharmaceutical form of vitamin D is also important. The objective of this study was to evaluate if there is a food effect on absorption when a high dose of vitamin D is completely solubilized in an oily solution. In the present cross-over study, 88 subjects were randomized and received a single dose of 50,000 IU of vitamin D in fasting state or with a standardized high-fat breakfast. Assessment of serum concentrations of 25 hydroxyvitamin D (25(OH)D) was performed three, five, seven, 14, 30 and 60 days after supplementation. In fed and fast conditions, the 25(OH)D serum concentrations were significantly higher than the baseline value three days after administration and remained significantly higher during the first month. No significant difference between fasting vs. fed conditions was observed. It is therefore concluded that the vitamin D absorption from an oily solution was not influenced by the presence or absence of a meal.