Advances in Therapy Journal Impact Factor & Information

Publisher: Springer Verlag

Journal description

Advances in Therapy is an international peer reviewed journal dedicated to the rapid publication of studies in clinical medicine, including research on existing drugs and drugs in development across a range of therapeutic areas. The journal is of interest to a broad audience of pharmaceutical and healthcare professionals and publishes original research papers, drug reviews, case reports and other contributions to drug therapy, diagnosis, instrtumentation and related fields.

Current impact factor: 2.44

Impact Factor Rankings

2015 Impact Factor Available summer 2015
2013 / 2014 Impact Factor 2.438
2012 Impact Factor 2.125
2011 Impact Factor 2.105
2010 Impact Factor 1.668
2009 Impact Factor 0.936
2008 Impact Factor 0.973
2007 Impact Factor 0.719
2006 Impact Factor 0.712
2005 Impact Factor 0.667
2004 Impact Factor 0.829
2003 Impact Factor 1.047
2002 Impact Factor 0.828
2001 Impact Factor 0.468
2000 Impact Factor 0.896
1999 Impact Factor 0.403
1998 Impact Factor 0.385
1997 Impact Factor 0.408
1996 Impact Factor 0.301
1995 Impact Factor 0.169
1994 Impact Factor 0.324
1993 Impact Factor 0.115

Impact factor over time

Impact factor

Additional details

5-year impact 1.71
Cited half-life 4.40
Immediacy index 0.37
Eigenfactor 0.00
Article influence 0.45
Website Advances in Therapy website
ISSN 1865-8652
OCLC 220889595
Material type Series, Periodical
Document type Journal / Magazine / Newspaper

Publisher details

Springer Verlag

  • Pre-print
    • Author can archive a pre-print version
  • Post-print
    • Author can archive a post-print version
  • Conditions
    • Author's pre-print on pre-print servers such as
    • Author's post-print on author's personal website immediately
    • Author's post-print on any open access repository after 12 months after publication
    • Publisher's version/PDF cannot be used
    • Published source must be acknowledged
    • Must link to publisher version
    • Set phrase to accompany link to published version (see policy)
    • Articles in some journals can be made Open Access on payment of additional charge
  • Classification
    ​ green

Publications in this journal

  • [Show abstract] [Hide abstract]
    ABSTRACT: Canagliflozin is a sodium glucose co-transporter 2 inhibitor approved worldwide for the treatment of patients with type 2 diabetes mellitus (T2DM). The present study evaluated pharmacokinetics, pharmacodynamics, and safety of canagliflozin in Japanese patients with T2DM. Canagliflozin, at doses of 25, 100, 200, or 400 mg, was administered as a single dose and, after a washout of 1 day, in repeated doses for 14 consecutive days to 61 subjects in a randomized, double-blind, placebo-controlled study. Plasma concentrations of canagliflozin and urinary glucose excretion (UGE) were measured, and renal threshold for glucose excretion (RTG) was calculated. Safety was evaluated on the basis of adverse event (AE) reports, blood and urine laboratory parameters, and vital signs. Plasma canagliflozin maximum concentration and area under the concentration-time curve (AUC) values increased in a dose-dependent manner with the time to maximum concentration (t max) of 1.0 h and elimination half-life (t 1/2) of 10.22-13.26 h on Day 1. No significant changes in t max and t 1/2 were observed after multiple-dose administration. The linearity factors, as calculated from the ratios of AUC0-24h on Day 16 to AUC0-∞ on Day 1, were close to 1 in all canagliflozin groups. Canagliflozin increased UGE0-24h (80-110 g/day with canagliflozin ≥100 mg) and decreased RTG from the first day of treatment; these effects were sustained during the entire period of multiple administration. No significant AEs were noted. Urine volume was slightly increased on Day 1, but subsequent changes after repeated doses for 14 days were small. Urinary sodium tended to be higher in the early treatment period, whereas no particular change was observed in serum osmolality and hematocrit. Canagliflozin increased UGE, decreased RTG, and was well tolerated throughout the entire period of multiple administrations in Japanese patients with T2DM. Mitsubishi Tanabe Pharma Corporation.
    Advances in Therapy 08/2015; DOI:10.1007/s12325-015-0234-0
  • [Show abstract] [Hide abstract]
    ABSTRACT: The aim of this analysis was to describe in real-world settings the clinical outcomes and safety associated with daptomycin treatment in patients with neutropenia and Gram-positive infections. Patients with an absolute neutrophil count (ANC) ≤1000 cells/mm(3) who received at least one dose of daptomycin between 2006 and 2012 were selected from a non-interventional, multicenter, retrospective registry (European Cubicin(®) Outcome Registry and Experience; EU-CORE(SM)). Of the 6075 patients enrolled in EU-CORE, 446 (7.3%) had an ANC ≤ 1000 cells/mm(3) at baseline or during daptomycin therapy; they were all included in efficacy and safety populations. Half of the patients had severe neutropenia (ANC ≤ 100 cells/mm(3)). Most patients had hematologic malignancy (60.5%), an immunosuppressed state (39.7%) or had undergone a transplant (27.8%). The most common primary infections were bacteremia (42.2%) and complicated skin and soft tissue infection (13.9%). Cultures were positive for 68.6% (254/370) of patients with available culture results; coagulase-negative staphylococci (43.7%; 111/254) and Staphylococcus aureus (18.9%; 48/254) were the most commonly isolated primary pathogens. Median duration of daptomycin therapy was 10.0 (range 1-98) days. Most patients (82.8%) received antibiotics concomitantly with daptomycin; the most common were carbapenems (51.2%), penicillins (42.1%), and aminoglycosides (19.9%). The overall clinical success rate (cured or improved) associated with daptomycin was 77.1%. Adverse events possibly related to daptomycin treatment were reported in seven (1.6%) patients and led to drug discontinuation in 27 (6.1%) patients. The study results suggest that daptomycin is an effective therapeutic option for the treatment of a broad range of Gram-positive infections in patients with neutropenia, and has a good safety profile. This study was funded by Novartis Pharma AG.
    Advances in Therapy 08/2015; DOI:10.1007/s12325-015-0231-3
  • [Show abstract] [Hide abstract]
    ABSTRACT: Primary cardiovascular (CV) prevention may be achieved by lifestyle/nutrition changes, although a relevant role is now emerging for specific, functional foods and nutraceutical compounds (NCs). The aim of this study was to investigate the efficacy and safety of NCs in lowering blood pressure (BP) and improving lipid profile, when added to diet and lifestyle management versus diet alone in a group of patients with hypertension (HT) and hypercholesterolemia (HCh) with low CV risk. Sixty-six patients with HT and HCh with grade 1 essential HT (mean age 56.0 ± 4.6 years) without history of CV diseases or organ damage were analyzed. These subjects were started on one tablet of an NC-containing red yeast rice, policosanol, berberine, folic acid and coenzyme Q10 once daily for 6 months and were age and gender matched with subjects following a diet program. Differences in clinic BP, 24-h ambulatory BP (24 h-ABPM), serum total cholesterol, low-density and high-density lipoprotein cholesterol (LDL-C and HDL-C) and triglyceride values were compared by analysis of variance. In the treatment group, a significant reduction of systolic 24 h-ABPM (141.6 ± 6.4 vs. 136.2 ± 4.8 mmHg; p < 0.05) and pulse pressure 24 h-ABPM (52.6 ± 7.2 vs. 47.3 ± 5.4 mmHg; p < 0.05) was found at the end of follow-up. A reduction of total cholesterol (-19.2%), LDL-C (-17.4%) and triglycerides (-16.3%) was observed (p < 0.001 for all); HDL-C remained unchanged. No difference was found in the control group. The tested NCs was found to be safe, well tolerated and effective in reducing mean 24-h systolic and 24-h pulse pressure and in improving lipid pattern.
    Advances in Therapy 07/2015; DOI:10.1007/s12325-015-0229-x
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Orbital decompression is the indicated procedure for addressing exophthalmos and compressive optic neuropathy in thyroid eye disease. There are an abundance of techniques for removal of orbital bone, fat, or a combination published in the scientific literature. The relative efficacy and complications of these interventions in relation to the specific indications remain as yet undocumented. We performed a systematic review of the current published evidence for the effectiveness of orbital decompression, possible complications, and impact on quality of life. We searched the current databases for medical literature and controlled trials, oculoplastic textbooks, and conference proceedings to identify relevant data up to February 2015. We included randomized controlled trials (RCTs) comparing two or more interventions for orbital decompression. We identified only two eligible RCTs for inclusion in the review. As a result of the significant variability between studies on decompression, i.e., methodology and outcome measures, we did not perform a meta-analysis. One study suggests that the transantral approach and endonasal technique had similar effects in reducing exophthalmos but the latter is safer. The second study provides evidence that intravenous steroids may be superior to primary surgical decompression in the management of compressive optic neuropathy requiring less secondary surgical procedures. Most of the published literature on orbital decompression consists of retrospective, uncontrolled trials. There is evidence from those studies that removal of the medial and lateral wall (balanced) and the deep lateral wall decompression, with or without fat removal, may be the most effective surgical methods with only few complications. There is a clear unmet need for controlled trials evaluating the different techniques for orbital decompression. Ideally, future studies should address the effectiveness, possible complications, quality of life, and cost of each intervention.
    Advances in Therapy 07/2015; DOI:10.1007/s12325-015-0228-y
  • [Show abstract] [Hide abstract]
    ABSTRACT: Diabetes-related healthcare costs are increasing in the United States, with inpatient hospitalization the largest component of medical expenditures. The aims of this study were to characterize hospitalized type 2 diabetes mellitus (T2DM) patients, understand the relationship between hospitalization and healthcare costs, and explore treatment modification after inpatient hospitalization. A retrospective cohort analysis of Humana Medicare Advantage and commercial members with T2DM was conducted. T2DM members were identified and assigned to three groups: (1) inpatient hospitalization (IPH) without a 30-day readmit (IPH group); (2) IPH with a 30-day readmission (IPH readmission group); and, (3) matched non-IPH group. Demographics, clinical characteristics, comorbidities and healthcare costs were measured based on enrollment data and claims. Descriptive statistics were used and the relationship between IPH and costs was assessed using generalized linear models. A total of 15,555 IPH patients, 1757 IPH readmission patients, and 17,312 matched non-IPH patients were included in the study. The IPH readmission group had the highest adjusted mean all-cause total costs ($76,806), followed by the IPH group ($42,011), and the non-IPH group ($9624). A similar trend was observed for adjusted all-cause mean medical and pharmacy costs. DM-related total healthcare costs were highest for the IPH readmission group ($13,714), followed by the IPH group ($7477), and non-IPH group ($1620). While overall therapy modification (discontinuation, addition, switch) was low, T2DM patients with an IPH (with or without a readmission) had greater rates of therapy modification relative to the non-IPH patients. Adjusted all-cause and DM-related total costs were greatest for IPH readmission patients. Rates of treatment modification within 10 days of discharge after IPH were generally low. Identifying T2DM patients at high risk of readmission and employing methods to decrease that risk during the index hospitalization could have a significant impact on health system costs. Novo Nordisk.
    Advances in Therapy 07/2015; DOI:10.1007/s12325-015-0223-3
  • [Show abstract] [Hide abstract]
    ABSTRACT: The present study aimed to identify preoperative factors that predispose the development of subretinal fluid (SRF) following successful macular hole (MH) surgery. Thirty-four eyes of 33 consecutive patients that underwent pars plana vitrectomy for idiopathic full-thickness MH surgery were included in this retrospective study. Best corrected visual acuity (BCVA), and spectral domain-optical coherence tomography (OCT) images were evaluated pre- and postoperatively in all cases. Patient's demographic characteristics, stage of MH, measurements of base diameter and minimum aperture diameter of the MH, preoperative foveal vitreomacular traction and selected intra-operative parameters were correlated with the development of postoperative SRF. Postoperative SRF was observed in 15 cases (48%). Total absorption of SRF was observed in 73% of affected eyes and was most commonly seen between the third and the fifth postoperative month. One patient developed lamellar hole leading to full-thickness MH. Postoperative BCVA was similar between the eyes that did and the eyes that did not develop postoperative SRF (0.31 ± 0.2 vs 0.35 ± 0.2; p ≥ 0.05). Development of postoperative SRF was significantly associated with the presence of preoperative foveal vitreomacular traction (p = 0.048), stage II MH (p = 0.017) and smaller size of the closest distance between the MH edges (p = 0.046). Postoperative SRF is a common occurrence following successful MH surgery. Meticulous evaluation of preoperative clinical and OCT findings may disclose risk factors associated with this condition. Based on our observations, idiopathic holes of early stage appear to be at a higher risk of developing postoperative SRF. This could be a point of interest with the advancing use of enzymatic proteolysis.
    Advances in Therapy 07/2015; DOI:10.1007/s12325-015-0227-z
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: This analysis aimed to investigate the effectiveness and safety profile of pirfenidone for the treatment of idiopathic pulmonary fibrosis (IPF) in clinical practice. Clinical records of patients diagnosed with mild-to-moderate IPF (as per European Medicines Agency indication) and receiving pirfenidone treatment across three centers in Belgium and the Netherlands between April 2011 and October 2013 were retrospectively collected from patient notes at 3-month intervals. Pulmonary function measurements, including % predicted forced vital capacity (%FVC) and % predicted diffusing capacity of the lungs for carbon monoxide (%DLCO), were analyzed from 6 months prior to pirfenidone treatment up to 12 months of treatment. Decline in lung function, defined as an absolute ≥10% decline in FVC from baseline or death at 12 months, was also analyzed. Safety data were included for all follow-up visits. In the pooled cohort (n = 63), patients were mostly men (84.1%) and current or former smokers (79.4%). Average baseline %FVC and %DLCO were 75.0% and 47.9%, respectively. 69.8% of patients had a high-resolution computed tomography scan with a definite usual interstitial pneumonia pattern, and 46% had a surgical lung biopsy. The mean decline in %FVC for 32 patients with available data was 4.8% from -6 months to baseline (p = 0.002) and 0.8% from baseline to 6 months (p = 0.516). Across these time intervals, a lesser decline in DLCO was similarly observed during therapy. At 12 months, ten patients had an %FVC decline ≥10% or died. Loss of appetite (25.3%) and nausea (11.1%) were the most frequent gastrointestinal side effects. Nausea was the most highly cited reason for discontinuation (7.9%). In this clinical practice cohort, pirfenidone showed effectiveness and safety profiles consistent with those seen in the Phase III clinical study ASCEND ( #NCT01366209). These results highlight the challenges and benefits associated with pirfenidone treatment in clinical practice.
    Advances in Therapy 07/2015; DOI:10.1007/s12325-015-0225-1
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Fingolimod 0.5 mg is an orally active sphingosine 1-phosphate receptor modulator approved for use in adults with relapsing multiple sclerosis (MS). The efficacy and safety profile of fingolimod has been well characterized in a large clinical development program. Here, we report the safety and tolerability of fingolimod in relapsing-remitting MS (RRMS) patients from Latin America. A total of 162 patients with RRMS, predominantly from Latin American countries (138/162), were enrolled in this 16-week, single treatment arm, open-label, multi-center study. Unlike the phase III pivotal studies, this study permitted enrollment of patients with controlled diabetes, certain cardiac and pulmonary conditions, older age, and higher baseline Expanded Disability Status Scale. All patients were monitored clinically for a minimum of 6 hours after the first dose. Safety and tolerability assessments were based on adverse events, clinically notable laboratory abnormalities, vital signs, ophthalmic examinations, and electrocardiograms. Overall, the safety and tolerability profile was consistent with that reported previously in phase 3 studies and the FIRST study. Adverse events (AEs) were predominantly mild (n = 49, 35.5%) or moderate (n = 27, 19.6%). Three patients (2.2%) discontinued fingolimod due to AEs. Infections were reported in 33 patients (23.9%) and were predominantly mild in nature (n = 28, 20.3%). Increases in alanine aminotransferase enzymes of ≥3, ≥5 and ≥10 upper limit of normal were reported in five (3.7%), three (2.2%) and one (0.7%) patients, respectively. Hypertension cases (n = 3; 2.2%) did not result in treatment discontinuation and were controlled with antihypertensive therapy. Following first-dose administration, the majority of patients (90.6%) were discharged at 6 h. During the first-dose monitoring, 5 cases of bradycardia were reported; none required extended monitoring or treatment for symptomatic bradycardia. The first dose of fingolimod 0.5 mg was well tolerated in RRMS patients from Latin America. The overall safety profile was clinically manageable and consistent with previous fingolimod studies. Novartis. #NCT01497262.
    Advances in Therapy 07/2015; DOI:10.1007/s12325-015-0224-2
  • [Show abstract] [Hide abstract]
    ABSTRACT: Small peptides are approved as treatments for type 2 diabetes mellitus and may have utility in metabolic diseases. These peptides often have short half-lives requiring delivery either as a sustained-release formulation or via a device. The opportunity to study their pharmacokinetics using simple solution formulations delivered by continuous subcutaneous infusion may facilitate the drug development process. Here, we investigated the systemic exposure of an exemplar peptide (exenatide) when infused in healthy subjects using a Paradigm(®) Revel™ insulin infusion pump (Medtronic MiniMed). Four infusion regimens were tested: Constant 24-h infusion (16.5 μg/day), constant 7-day infusion (25.5 μg/day in Cohort 2), and two different 7-day escalation regimens (ranging from 7 to 58.5 μg/day in Cohort 1 and 25.5-58.5 μg/day in Cohort 3). While the overall exenatide pharmacokinetics were in line with those expected, the observed within-subject concentration variability was considerable. Our work identifies sources of potential pharmacokinetic variability relating to the method of delivery and the drug's formulation that will be valuable to investigators contemplating the delivery of peptides via insulin infusion pumps. GlaxoSmithKline. number, NCT01857895.
    Advances in Therapy 07/2015; DOI:10.1007/s12325-015-0222-4
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Oral daclatasvir (DCV; pangenotypic NS5A inhibitor) plus asunaprevir (ASV; NS3 protease inhibitor) is approved in Japan and Korea for treatment of chronic hepatitis C virus (HCV) genotype 1. Response to DCV + ASV is affected by DCV resistance-associated polymorphisms (RAPs) in HCV NS5A. The prevalence and influence of these RAPs on 12-week sustained virologic response (SVR12) to DCV + ASV was evaluated in Asian and non-Asian patients. Data were pooled from 5 national and international studies of patients with HCV genotype 1b (GT-1b) receiving DCV + ASV at their recommended doses. Baseline NS5A RAPs and their effect on SVR12 were assessed overall, in older (≥65 years) patients, patients with cirrhosis, and in patients stratified by baseline HCV RNA or prior treatment experience with interferon-based therapy. Baseline NS5A sequences were available from 988 patients (374 Japanese; 125 Korean/Taiwanese; 489 from non-Asian countries), 979 of whom were assessed for SVR12. Pretreatment NS5A-L31F/I/M/V and/or NS5A-Y93H polymorphisms were present in 18% of Japanese and 12-13% of non-Japanese patients; these RAPs reduced SVR12 by 54.9% overall (93.9% [787/838] SVR12 when absent, 39.0% [55/141] SVR12 when present), with comparable reductions observed in Asians and non-Asians and across all categories of treatment experience, age, and cirrhosis. RAP-associated SVR12 rates declined with increasing baseline HCV RNA (SVR12 with RAPs: 64.7% [11/17] at 5-6 log10 IU/mL, 29.8% [14/47] at 7-8 log10). Without baseline RAPs, very high SVR12 rates (92-100%) were observed in older patients and patients with cirrhosis irrespective of national origin, with similarly high rates observed among treatment-naïve and interferon-experienced patients and those with high baseline HCV RNA. Following DCV + ASV treatment, the SVR12 rates in GT-1b patients without baseline NS5A-L31F/I/M/V and/or NS5A-Y93H polymorphisms were very high (approximately 90-100%), irrespective of age, cirrhosis, prior interferon treatment, or baseline HCV RNA. Bristol-Myers Squibb.
    Advances in Therapy 07/2015; DOI:10.1007/s12325-015-0221-5
  • [Show abstract] [Hide abstract]
    ABSTRACT: New inhalers propelled by hydrofluoroalkanes (HFAs) have improved plume characteristics: higher fine particle fraction, and warmer plumes with reduced force and velocity. Together, this may avoid reflex interruption of inhalation and improve lung deposition of the inhaled drugs. However, even with HFA-propelled pressurized metered-dose inhalers (pMDIs), there are notable differences in device properties. Here we compared the duration, velocity, force, and temperature of two inhaled corticosteroid/long-acting β2-agonist combination therapies, administered via HFA pMDIs: fluticasone propionate/formoterol 125/5 µg (FP/FORM; flutiform(®)) and fluticasone propionate/salmeterol 125/25 µg (FP/SAL; Seretide(®) Evohaler(®)). Inhalers were fired into ambient air. Plume duration and velocity were recorded with a high-speed camera and a pulsed laser light source. A copper disc attached to a sensitive load cell measured the plume force at various distances from the device. A thermal imaging video camera recorded impaction temperature in line with the device. The average plume duration for FP/FORM was longer than that of FP/SAL: 168.3 vs. 114.0 ms, respectively. The mean maximum plume velocities observed at 95 mm (the approximate distance between mouthpiece and throat) was consistently slower for FP/FORM (10.08 m/s) compared to FP/SAL (15.55 m/s). FP/FORM had a slower velocity at the outset, remaining relatively constant before declining steadily over the plume duration. The force of the FP/SAL plume was greater than that of FP/FORM at all distances: maximum force for FP/FORM was 138.2 vs. 278.9 mN for FP/SAL. The minimum impaction temperature was +5.9 °C for FP/FORM and -37.8 °C for FP/SAL; this difference became less pronounced over distance. There were substantial differences between the plumes of the two pMDIs. FP/FORM was warmer, less forceful, had a longer plume duration and slower maximal velocity. These plume characteristics of FP/FORM may lead to improved lung deposition. Mundipharma Research Limited, Cambridge, UK.
    Advances in Therapy 06/2015; DOI:10.1007/s12325-015-0219-z
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Among patients with chronic obstructive pulmonary disease (COPD), the frequency and severity of past exacerbations potentiates future events. The impact of current therapies on exacerbation frequency and severity in patients with different exacerbation risks is not well known. A post hoc analysis of patients at low (≤1 exacerbation [oral steroids/antibiotics requirement] and no COPD-related hospitalization in the year preceding trial entry) or high (≥2 exacerbations [oral steroids/antibiotics requirement] or ≥1 COPD-related hospitalization[s] in the year preceding trial entry) exacerbation risk, from the Prevention of Exacerbations with Tiotropium in Chronic Obstructive Pulmonary Disease (POET-COPD(®)) database. Compared with salmeterol, tiotropium significantly increased time to first COPD exacerbation (hazard ratio 0.84; 95% confidence interval [CI] 0.76-0.92; p = 0.0002) and reduced the number of COPD exacerbations (rate ratio 0.90; 95% CI 0.81-0.99; p = 0.0383) in patients at high exacerbation risk. With treatment, the risk of remaining in the high-risk exacerbator subgroup was statistically lower with tiotropium versus salmeterol (risk ratio [RR] 0.89; 95% CI 0.80-1.00; p = 0.0478). For low-risk patients, time to first COPD exacerbation and number of COPD exacerbations were numerically lower with tiotropium versus salmeterol. With treatment, the risk of transitioning from a low to a high exacerbation risk was lower with tiotropium versus salmeterol (RR 0.87; 95% CI 0.71-1.07; p = 0.1968). This analysis confirms the higher efficacy of tiotropium versus salmeterol in prolonging time to first COPD exacerbation and reducing number of exacerbations in patients both at low and high exacerbation risk. Boehringer Ingelheim and Pfizer. NCT00563381.
    Advances in Therapy 06/2015; DOI:10.1007/s12325-015-0216-2
  • [Show abstract] [Hide abstract]
    ABSTRACT: The oral, potent poly(ADP-ribose) polymerase (PARP) inhibitor, olaparib, is well tolerated at doses of ≤400 mg twice daily (BID) (administered as capsules), and has shown efficacy in patients with advanced BRCA-mutated ovarian and breast cancer. This Phase I, open-label, randomized trial investigates the effect of food on the pharmacokinetics of olaparib in patients with refractory/resistant advanced solid tumors. In Part A, a three-period crossover study, patients received a single oral dose of olaparib 400 mg (8 × 50 mg capsules) in three prandial states: fasted, a high-fat meal or a standard meal (with a 5-14 day washout). Blood samples for pharmacokinetic (PK) assessments were taken pre-dose and up to 72 h post-dose. After completing Part A, patients could enter Part B, where they would receive olaparib 400 mg BID. 32 patients were randomized; 31 contributed to the PK statistical analysis and entered Part B. The presence of food slowed the rate of absorption (time to maximal plasma concentration [t max] was delayed by ~2 h). Maximum plasma concentration (C max) was increased by 10% following a standard meal and was unchanged with a high-fat meal (ratio of geometric means [90% confidence interval (CI)]: 1.10 [1.02-1.20] for standard and 1.00 [0.92-1.09] for high-fat meal). The extent of olaparib absorption (AUC) was increased by ~20% in the fed state (ratio of geometric means: 1.21 [1.10-1.33] for standard and 1.19 [1.08-1.31] for high-fat meal). The presence of food decreased the rate and increased the extent of absorption of olaparib following oral dosing of the capsule formulation. However, the effects of food on olaparib PK were not deemed clinically important, according to predefined criteria. Safety data were consistent with the known safety profile of olaparib. AstraZeneca.
    Advances in Therapy 06/2015; DOI:10.1007/s12325-015-0214-4
  • [Show abstract] [Hide abstract]
    ABSTRACT: The aim of this study was to establish the feasibility of using computed tomography (CT) in a multicenter setting to assess structural airway changes. This was a 12-week, randomized, double-blind, placebo-controlled, Phase IIb trial using CT to investigate the effect of a novel, oral, reversible neutrophil elastase inhibitor, AZD9668 60 mg twice daily (BID), on structural airway changes in patients aged 50-80 years with chronic obstructive pulmonary disease (COPD) (ex-smokers). Primary outcome variable: airway wall thickness at an extrapolated interior perimeter of 10 mm (AWT-Pi10). Secondary outcome variables: fifth-generation wall area %; air trapping index; pre- and post-bronchodilator forced expiratory volume in 1 s (FEV1); morning and evening peak expiratory flow and FEV1; body plethysmography; EXAcerbations of Chronic pulmonary disease Tool (EXACT); Breathlessness, Cough, and Sputum Scale (BCSS); St George's Respiratory Questionnaire for COPD; and proportion of reliever-medication-free trial days. Safety variables were also assessed. There was no difference between placebo (n = 19) and AZD9668 (n = 17) for AWT-Pi10 at treatment end. This was consistent with results for most secondary variables. However, patients randomized to AZD9668 experienced an improvement versus placebo for morning and evening FEV1, and EXACT and BCSS cough and sputum scores. AZD9668 60 mg BID was well tolerated and no new safety concerns were identified. This study confirmed the feasibility of using CT to assess structural airway changes in COPD. However, there was no evidence of improvements in CT structural measures following 12 weeks' treatment with AZD9668 60 mg BID. AstraZeneca.
    Advances in Therapy 06/2015; DOI:10.1007/s12325-015-0215-3
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Acute pain, prevalent as part of postoperative and traumatic pain, is often sub-optimally or inadequately treated. Fixed-dose combination analgesic products that combine a reduced amount of opioid with a nonopioid analgesic such as acetaminophen (paracetamol) in a single tablet offer potential pharmacodynamic and/or pharmacokinetic benefits, and may also result in an opioid-sparing effect. A new analgesic product (XARTEMIS™ XR, Mallinckrodt Brand Pharmaceuticals, Dublin, Ireland) combines oxycodone (7.5 mg) with acetaminophen (325 mg) in an immediate-release/extended-release (ER) formulation that is indicated for the treatment of acute pain. The ER formulation of this product provides stable serum drug concentrations that in this case lasts 12 h. Oxycodone/acetaminophen is a drug combination that offers safe and effective pain relief in a variety of acute pain syndromes such as postoperative pain. The combination formulation allows a smaller amount of oxycodone per tablet and the biphasic-layered matrix of the pill for ER may present obstacles to potential abusers. No opioid is totally abuse resistant, but the lower opioid content and tamper-resistant formulation of this product might discourage abuse. Clinicians must still be mindful of the acetaminophen part of this product in the patient's overall daily intake (in light of acetaminophen hepatotoxicity). The new product appears to provide an important new choice in the armamentarium against acute pain.
    Advances in Therapy 05/2015; DOI:10.1007/s12325-015-0213-5