Forest Research Institute Inc.

Jersey City, NJ, United States

Forest Research Institute Inc.

Jersey City, NJ, United States
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Findling R.L.,University Hospitals Case Medical Center | Mckenna K.,University of California at Los Angeles | Earley W.R.,Forest Research Institute Inc. | Stankowski J.,ICON Clinical Research | Pathak S.,Astrazeneca
Journal of Child and Adolescent Psychopharmacology | Year: 2012

Objective: The purpose of this study was to evaluate the efficacy and safety of acute quetiapine monotherapy in adolescents with schizophrenia. Methods: Patients ages 13-17 years with an American Psychiatric Association, Diagnostic and Statistical Manual of Mental Disorders, 4th ed., Text Revision (DSM-IV-TR) diagnosis of schizophrenia and a Positive and Negative Syndrome Scale (PANSS) total score ≥60 were randomized to 6 weeks of quetiapine (400 or 800mg/day) or placebo treatment. The primary efficacy measure was change in PANSS total score from baseline to day 42. Safety endpoints included adverse events and assessments of clinical chemistry values, suicidality, and extrapyramidal symptoms. Results: The intent-to-treat population included 220 patients. Least-squares mean change in PANSS total score from baseline to endpoint was -27.31 with quetiapine 400mg/day, -28.44 with quetiapine 800mg/day, and -19.15 with placebo (p=0.043 and 0.009 for quetiapine 400 and 800mg/day, respectively, vs. placebo; mixed-model, repeated-measures analysis). Several secondary efficacy outcomes, including Clinical Global Impressions-Improvement score, supported the primary outcome measure in demonstrating significantly greater improvement in quetiapine groups than in the placebo group. Mean changes in body weight at day 42 were 2.2kg and 1.8kg for quetiapine 400 and 800mg/day, respectively, and -0.4kg for placebo. Mean changes in certain clinical chemistry parameters, including total cholesterol and triglycerides, were numerically greater in the quetiapine groups than in the placebo group. Adverse events associated with quetiapine were mostly mild to moderate in intensity and were consistent with its known profile in adults with schizophrenia. Conclusions: In this 6-week study of adolescent patients, quetiapine at doses of 400 and 800mg/day provided significant improvements in symptoms associated with schizophrenia in adolescent patients, including the primary efficacy measure of PANSS total score change. Quetiapine was generally well tolerated with a profile broadly similar to that reported in adult and adolescent populations. Clinical trial registration information: Quetiapine Fumarate (SEROQUEL ™) Compared to Placebo in the Treatment of Adolescent Patients With Schizophrenia (ANCHOR 112). Available at: ct2/show/NCT00090324?term=quetiapine+112&rank=1 © Copyright 2012, Mary Ann Liebert, Inc. 2012.

Fuhr R.,Parexel International | Magnussen H.,Hospital Grosshansdorf | Sarem K.,Parexel International | Ribera Llovera A.,Almirall SA | And 4 more authors.
Chest | Year: 2012

Background: The efficacy and safety of aclidinium bromide bid, a novel, long-acting, muscarinic antagonist, was assessed in patients with moderate to severe COPD. Methods: In this phase IIa randomized, double-blind, double-dummy, crossover trial, patients with moderate to severe COPD received aclidinium 400 μg bid, tiotropium 8 μg once daily, and placebo for 15 days, with a 9- to 15-day washout between treatment periods. Treatments were administered through the Genuair or HandiHaler dry powder inhalers. The primary end point was mean change from baseline in FEV 1AUC 0-12/12h (area under the curve where the numbers represent the time period for which data were collected divided by the number of hours over which the data are averaged [eg, 0-12 h postdose divided by 12 h]) on day 15. Secondary end points were changes from baseline in FEV 1AUC 12-24/12h, FEV 1AUC 0-24/24h, morning predose FEV 1, peak FEV 1, and COPD symptom scores. Results: Thirty patients with COPD were randomized, and 27 completed the study. Mean change from baseline in FEV 1AUC 0-12/12h at day 15 was significantly greater for aclidinium and tiotropium over placebo (P<.0001). Mean changes from baseline in FEV 1AUC 12-24/12h, FEV 1AUC 0-24/24h, morning predose FEV 1, and peak FEV 1 at day 15 were significantly greater for aclidinium and tiotropium over placebo (P<.0001 for all except P<.001 for FEV 1AUC 12-24/12h tiotropium vs placebo). Improvements were significantly greater with aclidinium vs tiotropium on day 1 for all of the normalized AUC values of FEV 1 as well as on day 15 for FEV 1 AUC 12-24/12h (P<.05 for all). COPD symptoms were significantly improved from baseline with aclidinium vs placebo (P<.05) but not with tiotropium. Conclusions: In patients with COPD, aclidinium 400 μg bid compared with placebo provided clinically meaningful improvements in 24-h bronchodilation that generally were comparable to tiotropium 18 μg daily but with significant differences in favor of aclidinium observed in the average nighttime period. Larger studies with longer treatment duration are ongoing to confirm the efficacy of aclidinium 400 μg bid on bronchodilation and COPD symptoms. Trial registry:; No.: NCT00868231; URL: © 2012 American College of Chest Physicians.

Kim H.,Forest Research Institute Inc | Shults J.,University of Pennsylvania
Journal of Statistical Software | Year: 2010

Quasi-least squares (QLS) is an alternative computational approach for estimation of the correlation parameter in the framework of generalized estimating equations (GEE). QLS overcomes some limitations of GEE that were discussed in Crowder (1995). In addition, it allows for easier implementation of some correlation structures that are not available for GEE. We describe a user written SAS macro called %QLS, and demonstrate application of our macro using a clinical trial example for the comparison of two treatments for a common toenail infection. %QLS also computes the lower and upper boundaries of the correlation parameter for analysis of longitudinal binary data that were described by Prentice (1988). Furthermore, it displays a warning message if the Prentice constraints are violated. This warning is not provided in existing GEE software packages and other packages that were recently developed for application of QLS (in Stata, MATLAB, and R). %QLS allows for analysis of continuous, binary, or count data with one of the following working correlation structures: the first-order autoregressive, equicorrelated, Markov, or tri-diagonal structures.

Gommoll C.,Forest Research Institute Inc. | Durgam S.,Forest Research Institute Inc. | Mathews M.,Forest Research Institute Inc. | Forero G.,Forest Research Institute Inc. | And 3 more authors.
Depression and Anxiety | Year: 2015

Background Vilazodone, a selective serotonin reuptake inhibitor and 5-HT1A receptor partial agonist, is approved for treating major depressive disorder in adults. This study (NCT01629966 evaluated the efficacy and safety of vilazodone in adults with generalized anxiety disorder (GAD). Methods A multicenter, double-blind, parallel-group, placebo-controlled, fixed-dose study in patients with GAD randomized (1:1:1) to placebo (n = 223), or vilazodone 20 mg/day (n = 230) or 40 mg/day (n = 227). Primary and secondary efficacy parameters were total score change from baseline to week 8 on the Hamilton Rating Scale for Anxiety (HAMA) and Sheehan Disability Scale (SDS), respectively, analyzed using a predefined mixed-effect model for repeated measures (MMRM). Safety outcomes were presented by descriptive statistics. Results The least squares mean difference (95% confidence interval) in HAMA total score change from baseline (MMRM) was statistically significant for vilazodone 40 mg/day versus placebo (-1.80 [-3.26, -0.34]; P =.0312 [adjusted for multiple comparisons]), but not for vilazodone 20 mg/day versus placebo. Mean change from baseline in SDS total score was not significantly different for either dose of vilazodone versus placebo when adjusted for multiplicity; significant improvement versus placebo was noted for vilazodone 40 mg/day without adjustment for multiplicity (P =.0349). The incidence of adverse events was similar for vilazodone 20 and 40 mg/day (∼71%) and slightly lower for placebo (62%). Nausea, diarrhea, dizziness, vomiting, and fatigue were reported in ≥5% of patients in either vilazodone group and at least twice the rate of placebo. Conclusions Vilazodone was effective in treating anxiety symptoms of GAD. No new safety concerns were identified. © 2015 The Authors. Depression and Anxiety published by Wiley Periodicals, Inc.

Kerwin E.M.,Clinical Research Institute | D'Urzo A.D.,University of Toronto | Gelb A.F.,Southern California Clinical Trials | Lakkis H.,Forest Research Institute Inc. | And 2 more authors.
COPD: Journal of Chronic Obstructive Pulmonary Disease | Year: 2012

Background: This Phase III study evaluated the efficacy and safety of twice-daily aclidinium 200 μg and 400 μg versus placebo in the treatment of moderate-to-severe COPD. Methods: In this 12-week, double-blind, multicenter trial, patients were randomized (1:1:1) to inhaled twice-daily aclidinium 200 μg, aclidinium 400 μg, or placebo. Primary and secondary endpoints were changes from baseline in trough FEV1 and peak FEV1 at Week 12, respectively. Health status (St. George's Respiratory Questionnaire [SGRQ]), COPD symptoms (Transitional Dyspnea Index [TDI], night and early morning symptoms), and safety were also assessed. Results: A total of 561 patients (mean age, 64 ± 9 years) with a mean baseline FEV1 of 1.36 ± 0.54 L (47.2% of predicted value) were randomized. At Week 12, aclidinium 200 μg and 400 μg showed significant improvements from baseline in mean (95% CI) trough FEV1 compared with placebo by 86 (45, 127) mL and 124 (83,164) mL, respectively, and in peak FEV1 by 146 (101, 190) mL and 192 (148, 236) mL, respectively (p ≤ 0.0001 for all). Both aclidinium doses also provided significant improvements in SGRQ, TDI and almost all COPD symptom scores compared with placebo (p < 0.05 for all). Incidences of adverse events (AEs) were similar across treatment groups. The incidence of anticholinergic AEs was low and similar across groups (dry mouth: 0.5%1.6%; constipation: 0%-1.1%). Conclusions: Treatment of moderate-to-severe COPD patients with twice-daily aclidinium 200 μg and 400 μg was associated with significant improvements in bronchodilation, health status, and COPD symptoms. Both doses were well tolerated and had safety profiles similar to placebo. © 2012 Informa Healthcare USA, Inc.

Biek D.,Cerexa Inc. | Critchley I.A.,Cerexa Inc. | Riccobene T.A.,Forest Research Institute Inc. | Thye D.A.,Cerexa Inc.
Journal of Antimicrobial Chemotherapy | Year: 2010

Ceftaroline fosamil is a novel cephalosporin with broad-spectrum activity against Gram-positive pathogens, including methicillin-resistant Staphylococcus aureus (MRSA) and multidrug-resistant Streptococcus pneumoniae, and common Gram-negative organisms. The activity of ceftaroline against MRSA is attributed to its ability to bind to penicillin-binding protein (PBP) 2a with high affinity and inhibit the biochemical activity of PBP 2a more efficiently than other presently available β-lactams. The activity of ceftaroline against MRSA and the β-haemolytic streptococci makes it an attractive monotherapy agent for the treatment of complicated skin and skin structure infections (cSSSIs). Recent profiling and surveillance studies have shown that ceftaroline is active against contemporary skin pathogens collected from US and European medical centres in 2008. The mean free drug %T>MIC (percentage of time the drug concentration remains above the MIC) needed for stasis ranged from 26% for S. aureus to 39% for S. pneumoniae in the murine thigh infection model. Pharmacokinetic and pharmacodynamic target attainment predictions for 600 mg of ceftaroline fosamil every 12 h showed that the mean %T>MICs for which plasma free-drug concentrations exceeded an MIC of 1 and 2 mg/L were 71% and 51% of the dosing interval, respectively. For a 40% T>MIC target, the predicted attainments for infections due to pathogens for which ceftaroline MICs were 1 or 2 mg/L were 100% and 90%, respectively. Clinical and microbiological successes of ceftaroline fosamil in treating cSSSIs were demonstrated in two Phase III clinical studies, in which 96.8% of all baseline cSSSI isolates from the microbiologically evaluable population were inhibited by ceftaroline at ≤2mg/L. Ceftaroline fosamil is a promising broad-spectrum agent for the treatment of cSSSIs. © The Author 2010. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved.

Riccobene T.A.,Forest Research Institute Inc. | Su S.F.,Forest Research Institute Inc. | Rank D.,Cerexa Inc.
Antimicrobial Agents and Chemotherapy | Year: 2013

This study was conducted to determine the safety, tolerability, and pharmacokinetics of intravenous doses of ceftaroline fosamil administered in combination with the novel non-β-lactam β-lactamase inhibitor avibactam in healthy adults. In the single-dose, open-label arm, 12 subjects received single 1-h intravenous infusions of ceftaroline fosamil alone (600 mg), avibactam alone (600 mg), and ceftaroline fosamil in combination with avibactam (600/600 mg) separated by 5-day washout periods. In the multiple-dose, placebo-controlled, double-blind arm, 48 subjects received intravenous infusions of ceftaroline fosamil/avibactam at 600/600 mg every 12 h (q12h), 400/400 mg q8h, 900/900 mg q12h, 600/600 mg q8h, or placebo for 10 days. Ceftaroline and avibactam levels in plasma and urine were measured by liquid chromatography coupled with tandem mass spectrometry. No significant differences in systemic exposure of ceftaroline or avibactam were observed when the drugs were administered alone versus concomitantly, indicating that there was no apparent pharmacokinetic interaction between ceftaroline fosamil and avibactam administered as a single dose. No appreciable accumulation of either drug occurred with multiple intravenous doses of ceftaroline fosamil/avibactam, and pharmacokinetic parameters for ceftaroline and avibactam were similar on days 1 and 10. Infusions of ceftaroline fosamil/avibactam were well tolerated at total daily doses of up to 1,800 mg of each compound, and all adverse events (AEs) were mild to moderate in severity. Infusion-site reactions were the most common AEs reported with multiple dosing. The pharmacokinetic and safety profiles of ceftaroline fosamil/avibactam demonstrate that the 2 drugs can be administered concomitantly to provide an important broad-spectrum antimicrobial treatment option. Copyright © 2013, American Society for Microbiology.

Arnold L.M.,University of Cincinnati | Palmer R.H.,Forest Research Institute Inc. | Ma Y.,Forest Research Institute Inc.
Clinical Journal of Pain | Year: 2013

OBJECTIVES:: To evaluate the effects of long-term milnacipran treatment in fibromyalgia patients. METHODS:: Patients completing a previous milnacipran study were eligible to participate in this long-term (up to 3.25 y), open-label study. After washout, dose escalation, and 8 weeks of stable-dose treatment (100 mg/d), patients received flexible doses of milnacipran (50 to 200 mg/d) for the remainder of the study. Safety evaluations included adverse events and vital signs. Clinical measures included weekly recall pain (visual analog scale [VAS]), Patient Global Disease Status (PGDS), and the Short Form-36 Health Survey (SF-36, including the Physical Component Summary [PCS] and Mental Component Summary scores). Cohort analyses were conducted to assess the effects of milnacipran over varying periods of time. RESULTS:: Of 1227 patients entering the study, 585 (47.7%) were classified as completers, including 379 (30.9%) patients who were currently enrolled when the study was administratively terminated. Mean duration of treatment was 19 months, with 206 patients reaching the final visit and receiving 36 to 38 months of study treatment. The percentage of patients with ≥1 treatment-emergent adverse event was 88.3%, with nausea (25.9%) and headache (13.4%) being the most common events. Discontinuations due to adverse events occurred in 20.9% of patients. Potentially clinically significant increases in blood pressure or heart rate occurred in ≤1.1% of patients. Mean improvement from baseline in weekly recall VAS pain was 17.6; improvements in global status (PGDS) and physical functioning (SF-36 PCS) were also observed. In all patient cohorts, these improvements were observed by month 3 and remained relatively constant over time. At final study visit in the 3-year cohort, 70.3% of patients rated their overall fibromyalgia as "much improved" or "very much improved." DISCUSSION:: No new safety concerns were identified in this long-term study. Sustained symptom improvements were found in fibromyalgia patients who received up to 3.25 years of milnacipran treatment. © 2013 by Lippincott Williams & Wilkins.

Riccobene T.A.,Forest Research Institute Inc. | Rekeda L.,Cerexa Inc. | Rank D.,Cerexa Inc. | Llorens L.,Cerexa Inc.
Antimicrobial Agents and Chemotherapy | Year: 2013

A randomized, double-blind, placebo-controlled, 3-period crossover study was conducted in 54 healthy adults to assess the effect of ceftaroline fosamil on the corrected QT (QTc) interval. The QT interval, corrected for heart rate using an individual correction formula (QTcIb), was determined predose and at 1, 1.25, 1.5, 2, 4, 8, 12, and 24.5 h after intravenous dosing with a supratherapeutic dose (1,500 mg) of ceftaroline fosamil, 400 mg moxifloxacin (positive control), and placebo. The pharmacokinetic profile of ceftaroline was also evaluated. At each time point following ceftaroline fosamil administration, the upper limit of the 90% confidence interval (CI) for the placebo-corrected change from predose baseline in QTcIb (ΔΔQTcIb) was below 10 ms (maximum, 3.4 ms at 1.5 h after dosing), indicating an absence of clinically meaningful QTc increase. The lower limit of the 90% CI of ΔΔQTcIb for moxifloxacin versus placebo was greater than 5 ms at 5 time points (maximum, 12.8 ms at 1 h after dosing), demonstrating assay sensitivity. There was no apparent correlation between ceftaroline plasma concentrations and ΔΔQTcIb. The supratherapeutic dose of ceftaroline fosamil (1,500 mg) resulted in substantially greater systemic exposure to ceftaroline than previously observed with standard therapeutic doses. Ceftaroline fosamil was well tolerated after a single 1,500-mg intravenous dose, and no clinically meaningful abnormalities in laboratory values or vital signs were observed. Copyright © 2013, American Society for Microbiology. All Rights Reserved.

Arnold L.M.,University of Cincinnati | Michael Gendreau R.,Cypress Bioscience | Palmer R.H.,Forest Research Institute Inc. | Gendreau J.F.,Cypress Bioscience | Wang Y.,Forest Research Institute Inc.
Arthritis and Rheumatism | Year: 2010

Objective. To assess the efficacy and safety of milnacipran at a dosage of 100 mg/day (50 mg twice daily) for monotherapy treatment of fibromyalgia. Methods. A double-blind, placebo-controlled trial was performed to assess 1,025 patients with fibromyalgia who were randomized to receive milnacipran 100 mg/day (n = 516) or placebo (n = 509). Patients underwent 4-6 weeks of flexible dose escalation followed by 12 weeks of stable-dose treatment. Two composite responder definitions were used as primary end points to classify the response to treatment. The 2-measure composite response required achievement of ≥30% improvement from baseline in the pain score and a rating of "very much improved" or "much improved" on the Patient's Global Impression of Change (PGIC) scale. The 3-measure composite response required satisfaction of these same 2 improvement criteria for pain and global status as well as improvement in physical function on the Short Form 36 (SF-36) physical component summary (PCS) score. Results. After 12 weeks of stable-dose treatment, a significantly greater proportion of milnacipran-treated patients compared with placebo-treated patients showed clinically meaningful improvements, as evidenced by the proportion of patients meeting the 2-measure composite responder criteria (P < 0.001 in the baseline observation carried forward [BOCF] analysis) and 3-measure composite responder criteria (P < 0.001 in the BOCF). Milnacipran-treated patients also demonstrated significantly greater improvements from baseline on multiple secondary outcomes, including 24-hour and weekly recall pain score, PGIC score, SF-36 PCS and mental component summary scores, average pain severity score on the Brief Pain Inventory, Fibromyalgia Impact Questionnaire total score (all P < 0.001 versus placebo), and Multidimensional Fatigue Inventory total score (P = 0.036 versus placebo). Milnacipran was well tolerated by most patients, with nausea being the most commonly reported adverse event (placebo-adjusted rate of 15.8%). Conclusion. Milnacipran administered at a dosage of 100 mg/day improved pain, global status, fatigue, and physical and mental function in patients with fibromyalgia. © 2010, American College of Rheumatology.

Loading Forest Research Institute Inc. collaborators
Loading Forest Research Institute Inc. collaborators