Showing papers by "Sunovion published in 2009"

Interpreting score differences in the Insomnia Severity Index: using health-related outcomes to define the minimally important difference.

Abstract: Objective:To estimate the minimally important difference (MID) for the Insomnia Severity Index (ISI) by examining the association of score differences of the ISI with health-related outcomes including health-related quality of life, productivity, and fatigue.Methods:Data came from a randomized, placebo-controlled clinical trial evaluating the long-term efficacy of eszopiclone for primary insomnia (N = 828). Logistic regression models were used to characterize the relationship between ISI change scores (from baseline to 6 months post-treatment) and outcomes/anchors from the SF-36 Health Survey, Work Limitations Questionnaire (WLQ), and Fatigue Severity Scale (FSS). Odds ratios were derived from the regression coefficients to calculate the probability of a given outcome being associated with different ISI change scores. Convergence between anchor- and distribution-based estimates was assessed.Results:Higher ISI scores (indicating more severe insomnia) were significantly associated with higher probab...

Dissociating anxiolytic and sedative effects of GABAAergic drugs using temperature and locomotor responses to acute stress

Abstract: Rationale The stress-induced hyperthermia (SIH) model is an anxiety model that uses the transient rise in body temperature in response to acute stress. Benzodiazepines produce anxiolytic as well as sedative side effects through nonselective binding to GABAA receptor subunits. The GABAA receptor α1 subunit is associated with sedation, whereas the GABAA receptor α2 and α3 subunits are involved in anxiolytic effects.

The Effect of Eszopiclone in Patients With Insomnia and Coexisting Rheumatoid Arthritis: A Pilot Study

Abstract: Objective: To evaluate the efficacy and safety of eszopiclone 3 mg, a nonbenzodiazepine medication/hypnotic indicated for the treatment of insomnia with comorbid rheumatoid arthritis (RA).

Practical methods for improving flow properties of active pharmaceutical ingredients

Abstract: Objective: The essential aim of this article is to develop effective methods for improving the flow properties of active pharmaceutical ingredients (APIs) without requiring particle size or shape m...

A validation analysis of two self-reported HAM-D6 versions.

Abstract: Objective The six items of the clinician-administrated Hamilton Depression Scale (HAM-D(6)) cover the core items of depressive states reflecting the antidepressive effect of medication. In this study, the two self-reported versions of the HAM-D(6) have been psychometrically validated to ensure the unidimensionality of this administration form in patients with mild-to-moderate depression. Method The item response theory analysis of Mokken was used to test the unidimensionality of both the Interactive Voice Recording System (IVRS) version of the HAM-D(6) and a paper-and-pencil self-reported version (S-HAM-D(6)). Patients with typical major depression and with seasonal affective disorder were included. Results The Mokken analysis showed that the two self-reported versions of the HAM-D(6) obtained coefficients of homogeneity above 0.40, similar to the clinician-rated HAM-D(6) and thus implying unidimensionality. By contrast, the full HAM-D(17) versions (self-reported as well as clinician-rated) obtained coefficients of homogeneity below 0.40, implying that the HAM-D(17) is a multidimensional scale. Conclusion The analysis show that both the IVRS version and the S-HAM-D(6) version are unidimensional self-rating scales for the measurement of depressive states.

Dopamine-Agonist Combination Therapy For Improving Sleep Quality

Abstract: The present invention generally relates to pharmaceutical compositions comprising a dopamine agonist and sedative agent. In a preferred embodiment, the dopamine agonist is optically pure (S)-didesmethylsibutramine. In a preferred embodiment, the sedative agent is optically pure (S)-zopiclone or optically pure (S)—N-desmethylzopiclone. In a preferred embodiment, the dopamine agonist is optically pure (S)-didesmethylsibutramine; and the sedative agent is optically pure (S)-zopiclone or optically pure (S)—N-desmethylzopiclone. The pharmaceutical compositions of the invention are useful in the treatment of restless-leg syndrome and periodic-limb-movement disorder, as well as various sleep disorders. In addition, the present invention relates to a method of treating a patient suffering from restless-leg syndrome, periodic-limb-movement disorder, a sleep abnormality, or insomnia, comprising coadministering a therapeutically effective amount of a dopamine agonist and a therapeutically effective amount of a sedative agent. In a preferred embodiment, the dopamine agonist is optically pure (S)-didesmethylsibutramine. In a preferred embodiment, the sedative agent is optically pure (S)-zopiclone or optically pure (S)—N-desmethylzopiclone. In a preferred embodiment, the dopamine agonist is optically pure (S)-didesmethylsibutramine; and the sedative agent is optically pure (S)-zopiclone or optically pure (S)—N-desmethylzopiclone.

Cost-effectiveness of eszopiclone for the treatment of adults with primary chronic insomnia.

Abstract: INSOMNIA IS ASSOCIATED WITH REDUCTIONS IN PRODUCTIVITY, PHYSICAL AND SOCIAL FUNCTIONING, AND HEALTH-RELATED QUALITY OF LIFE (HRQoL), as well as increased health care costs and risk of occupational and vehicular accidents.1–8 Direct medical costs of insomnia in the United States have been estimated to be as high as $13.9 billion annually (in 1995), and indirect costs are estimated to range from $77 to $92 billion annually (in 1990).9 In the coming decade, health care spending is projected to increase from 16% of the gross domestic product (GDP) in 2006 to 19.5% of GDP by 2017.10 For the same period, prescription drug spending growth is projected to accelerate as well. In this context, it has been argued that drug coverage decisions should be made on both clinical evidence and cost-effectiveness criteria (i.e., does an effective drug therapy produce sufficient benefits given its costs?).11 Therefore, coverage and formulary decisions would be guided by information about a drug's overall value,12 which can be measured in a number of ways. The most universally accepted, recommended, and, in some countries, mandated method to assess value is the cost utility analysis, a form of cost-effectiveness analysis in which health effects (the effectiveness) are measured in terms of quality-adjusted life years (QALYs) gained.12,13 In order to make coverage decisions based on value, payers and policy makers must have access to reliable cost-effectiveness information. However, as highlighted by Neumann et al. (2006), there is a paucity of published cost-utility data available to formulary committees.12 This lack of information is particularly striking in the field of insomnia treatment. Despite numerous publications over the past decade on the economic4,6,7,14–19 and humanistic1,3,5,8,14,20–23 burden of insomnia, almost no information is available on the cost utility of insomnia therapies. In the United Kingdom, the National Institute for Clinical Excellence (NICE) Assessment Group, which advises the National Heath System on the economic value of medical interventions and drugs, was unable to identify any comparative evaluations of insomnia drugs in the health economics literature.24 The 2005 National Institutes of Health State of the Science Conference Statement25 also recognized this fact and pointed out that the societal and economic benefits of managing insomnia have not been fully estimated. Thus, historically, coverage decisions in the area of insomnia treatment have been made largely on the basis of efficacy, rather than value arguments. To the best of our knowledge, only one cost-utility analysis of insomnia pharmacotherapy has been published to date.26 While that analysis, based on an initial clinical trial of eszopiclone in adult patients with chronic primary insomnia,27 provided evidence that the pharmacologic treatment of insomnia with eszopiclone for 6 months was cost-effective, it suffered from a number of methodological limitations: (1) there was no direct validated measure of the severity of insomnia collected in the study; (2) there was no direct measure of quality of life collected in the study; (3) there was no direct measure of work productivity collected; and (4) the assessment of uncertainty surrounding the study results was limited. Thus, this initial analysis relied on a number of limiting assumptions based on the efficacy results of the Krystal et al.27 clinical trial and the existing literature. Since that publication, a second, 6-month eszopiclone study28 was published. This second trial provided an opportunity to confirm the validity of the original model results and further refine the economic evaluation of insomnia pharmacotherapy. In particular, this study included an assessment of the impact of therapy on insomnia severity, quality of life, resource use, and work limitations. Therefore, rather than using assumptions about the effect of therapy on some of the key outcomes, as was done in the first economic analysis,26 this trial allowed for a significantly more definitive economic analysis based on patient-level data, including an extensive assessment of the degree of uncertainty associated with the results. It is hoped that the results from this new analysis can in turn be used to help make more informed coverage decisions.

IMIDAZO[1,2-a]PYRIDINE COMPOUNDS

Abstract: Imidazo[1,2-a]pyridines are disclosed. Compounds of the invention are useful therapeutic agents and their inclusion in pharmaceutical formulations and use in methods of treatment are disclosed.

PH INDEPENDENT FORMULATIONS OF 6-(5-CHLORO-2-PYRIDYL)-5-[(4-METHYL-1-PIPERAZINYL)CARBONYLOXY]-7-OXO-6,7-DIHYDRO-5H-PYRROLO[3,4-b]PYRAZINE

Abstract: Pharmaceutical compositions of zopiclone [(6-(5-chloro-2-pyridyl)-5-[(4-methyl-1-piperazinyl)carbonyloxy]-7-oxo-6,7-dihydro-5H-pyrrolo[3,4-b]pyrazine)] that render the aqueous solubility/dissolution of the free base independent of the pH of the gastrointestinal tract are disclosed. The compositions are useful for oral administration.

Triple reuptake inhibitors and methods of their use

Abstract: Provided herein are bicyclic compounds and methods of synthesis thereof. The compounds provided herein are useful for the treatment, prevention, and/or management of various neurological disorders. Compounds provided herein inhibit reuptake of endogenous monoamines, such as dopamine, serotonin and norepinephrine (e.g., from the synaptic cleft) and modulate one or more monoamine transporter. Pharmaceutical formulations containing the compounds are also provided.

In vivo saturation binding of GABA-A receptor ligands to estimate receptor occupancy using liquid chromatography/tandem mass spectrometry.

Abstract: Typically, the dose-occupancy curves for GABA-A receptor ligands are determined using in vivo binding of [3H]flumazenil. This study describes in vivo binding experiments without the use of tracer ligands. Bound and free fractions were measured directly using a highly sensitive LC/MS/MS detection method after in vivo administration of the GABA-A ligands zolpidem, (RS)-zopiclone, L-838417 and flumazenil, to demonstrate affinity and saturation of the filter-retained, membrane-bound fraction. The in vivo binding of flumazenil and L-838417 both saturated around 200 nM, at a similar level to the specific binding of (S)-zopiclone after doses of the racemic zopiclone, using (R)-zopiclone to estimate non-specific binding. This saturable component represented an estimate of benzodiazepine binding sites available on GABA-A receptors in vivo (200 nM). Dose-occupancy curves were constructed to estimate the dose required to achieve 50% occupancy and matched estimates obtained with tracer methods. In contrast to tracer methods, this method is uniquely suitable to the demonstration of stereoselective binding of the (S)-isomer in vivo after doses of racemic zopiclone. These results demonstrate that the LC/MS/MS measurements of total drug concentrations typically used in early drug development can be adapted to provide information about receptor occupancy in vivo.

Arformoterol and tiotropium compositions and methods for use

Abstract: Compositions and methods for the prevention and/or treatment of airway and/or respiratory disorders are provided The compositions comprise arformoterol (the (R,R)-formoterol isomer) and tiotropium

Combinations of eszopiclone and trans 4-(3,4-dichlorophenyl)-1,2,3,4-tetrahydro-n-methyl-1-napthalenamine or trans 4-(3,4-dichlorophenyl)-1,2,3,4-tetrahydro-1-napthalenamine, and methods of treatment

Abstract: One aspect of the present invention relates to pharmaceutical compositions containing two or more active agents that when taken together can be used to treat, e.g., menopause, mood disorders, anxiety disorders, or cognitive disorders. The first component of the pharmaceutical composition is a sedative eszopiclone. The second component of the pharmaceutical composition is trans 4-(3,4-dichlorophenyl)-1,2,3,4-tetrahydro-N-methyl-1-napthalenamine or trans 4-(3,4-dichlorophenyl)-1,2,3,4-tetrahydro-1-napthalenamine. The present invention also relates to a method of treating menopause, perimenopause, mood disorders, anxiety disorders, and cognitive disorders.

Imidazo [1, 2-a] pyridine compounds as GABA-A receptor modulators

Abstract: Imidazo[1,2-a]pyridines are disclosed. Compounds of the invention are useful therapeutic agents and their inclusion in pharmaceutical formulations and use in methods of treatment are disclosed.