Sleep and Quality of Life Under Prolonged Release Oxycodone/Naloxone for Severe Restless Legs Syndrome: An Analysis of Secondary Efficacy Variables of a Double-Blind, Randomized, Placebo-Controlled Study with an Open-Label Extension

BackgroundData on the relationship between core symptoms and daily functioning in adults with attention deficit hyperactivity disorder (ADHD) are limited. Daily functioning was assessed as part of an open-label extension, and associations with symptom scores were evaluated.MethodAfter a 5-week double-blind study with adults with ADHD receiving osmotic-controlled release oral delivery system (OROS) methylphenidate (MPH) 18, 36 or 72 mg/day, or placebo, participants were eligible for a 7-week open-label extension in which all patients received OROS MPH. Data for the Conners' Adult ADHD Rating Scale – Observer: Screening Version (CAARS-O:SV) (primary endpoint) have been presented previously. Secondary endpoints included the observer self-reported short version of the CAARS (CAARS-S:S) and the Clinical Global Impressions – Severity Scale (CGI-S). Daily functioning and quality of life were assessed using the Sheehan Disability Scale (SDS) and the Quality of Life Enjoyment and Satisfaction Questionnaire (Q-LES-Q) respectively. In post-hoc analyses, changes in CAARS-O:SV were evaluated in subgroups. Relationships between symptom and functional outcomes were evaluated in a multivariate regression analysis.ResultsA total of 370 patients entered the open-label extension. Significant improvements from baseline in CAARS-O:SV were similar regardless of sex, ADHD subtype, prior treatment or psychiatric co-morbidity. Significant improvements from double-blind baseline were also seen for the CAARS-S:S, CGI-S, SDS and Q-LES-Q. Improvements in the CAARS-O:SV Hyperactivity/Impulsivity subscale were associated with improvements in SDS total and subscale scores, and in the Q-LES-Q score at open-label endpoint. Improvements in CAARS-O:SV Inattention subscale and CGI-S scores were not significantly associated with functional changes.ConclusionsImprovements in ADHD symptoms relating to hyperactivity and impulsivity in adults receiving OROS MPH are associated with improvements in daily functioning and quality of life.

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Erenumab (AMG 334) in episodic migraine

Neurology ◽

10.1212/wnl.0000000000004391 ◽

2017 ◽

Vol 89 (12) ◽

pp. 1237-1243 ◽

Cited By ~ 83

Author(s):

Messoud Ashina ◽

David Dodick ◽

Peter J. Goadsby ◽

Uwe Reuter ◽

Stephen Silberstein ◽

...

Keyword(s):

Quality Of Life ◽

Safety Data ◽

Preventive Treatment ◽

Episodic Migraine ◽

Controlled Clinical Trial ◽

Open Label ◽

Double Blind ◽

Open Label Extension

Objective:To assess long-term safety and efficacy of anti–calcitonin gene-related peptide receptor erenumab in patients with episodic migraine (EM).Methods:Patients enrolled in a 12-week, double-blind, placebo-controlled clinical trial (NCT01952574) who continued in an open-label extension (OLE) study will receive erenumab 70 mg every 4 weeks for up to 5 years. This preplanned interim analysis, conducted after all participants had completed the 1-year open-label follow-up, evaluated changes in monthly migraine days (MMD), achievement of ≥50%, ≥75%, and 100% reductions, Headache Impact Test (HIT-6) score, Migraine-Specific Quality of Life (MSQ), Migraine Disability Assessment (MIDAS), and safety. Data reported as observed without imputation for missing data.Results:Of 472 patients enrolled in the parent study, 383 continued in the OLE with a median exposure to erenumab of 575 days (range 28–822 days). Mean (SD) MMD were 8.8 (2.6) at parent study baseline, 6.3 (4.2) at week 12 (beginning of OLE), and 3.7 (4.0) at week 64 (mean change from baseline [reduction] of 5.0 days). At week 64, 65%, 42%, and 26% achieved ≥50%, ≥75%, and 100% reduction in MMD, respectively. Mean HIT-6 scores were 60.2 (6.3) at baseline and 51.7 (9.2) at week 64. MSQ and MIDAS improvements from baseline were maintained through week 64. Safety profiles during the OLE were similar to those in the double-blind phase, which overall were similar to placebo.Conclusions:One-year efficacy, supported by functional improvements and favorable safety and tolerability profiles, supports further investigation of erenumab as a preventive treatment in patients with EM.Clinicaltrials.gov identifier:NCT01952574.Classification of evidence:This study provides Class IV evidence that for patients with episodic migraine, erenumab reduces long-term MMD and improves headache-related disability and migraine-specific quality of life.

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Changes in dermatology quality of life, sleep, and symptoms during the 24-week open-label period of XTEND-CIU: A phase IV, multicenter, randomized, double-blind, placebo-controlled study to evaluate the efficacy and safety of omalizumab through 48 weeks

Journal of the American Academy of Dermatology ◽

10.1016/j.jaad.2017.04.268 ◽

2017 ◽

Vol 76 (6) ◽

pp. AB65

Keyword(s):

Quality Of Life ◽

Controlled Study ◽

Efficacy And Safety ◽

Open Label ◽

Double Blind ◽

Double Blind Placebo ◽

Phase Iv

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A randomised, placebo-controlled study of RIPK1 inhibitor GSK2982772 in patients with active ulcerative colitis

BMJ Open Gastroenterology ◽

10.1136/bmjgast-2021-000680 ◽

2021 ◽

Vol 8 (1) ◽

pp. e000680

Author(s):

Kathy Weisel ◽

Nicola Scott ◽

Scott Berger ◽

Susanne Wang ◽

Kurt Brown ◽

...

Keyword(s):

Quality Of Life ◽

Ulcerative Colitis ◽

Disease Activity ◽

Controlled Study ◽

Experimental Medicine ◽

Open Label ◽

Double Blind ◽

Treatment Groups ◽

To Receive

ObjectiveTumour necrosis factor signalling via the receptor-interacting protein kinase 1 (RIPK1) pathway regulates colonic inflammation suggesting that RIPK1 inhibition may be a potential therapeutic target in ulcerative colitis (UC). This phase IIa, randomised, double-blind experimental medicine study investigated the safety, pharmacokinetics (PK), pharmacodynamics (PD) and preliminary efficacy of the RIPK1 inhibitor GSK2982772 in patients with active UC.DesignIn part A, prior to a protocol amendment, one patient was randomised to receive GSK2982772 60 mg twice daily for 42 days. After the amendment, patients were randomised 2:1 to receive GSK2982772 60 mg or placebo three times daily for 42 days. In part B, all patients switched to open-label GSK2982772 60 mg three times daily for 42 days. Safety, PK, PD biomarkers, histological disease activity, clinical efficacy and quality of life were assessed at days 43 and 85.ResultsThirty-six patients were randomised (n=12, placebo/open-label GSK2982772; n=24, GSK2982772/open-label GSK2982772). Most adverse events were mild, with headache reported the most frequently across groups (placebo/open-label GSK2982772, n=2 (17%); GSK2982772/open-label GSK2982772, n=8 (33%)). GSK2982772 was well distributed into colonic tissue, with generally higher concentrations in colonic biopsy samples versus plasma. No apparent differences between treatment groups were observed for PD, histological disease activity, clinical disease activity or quality-of-life measures. At screening, all patients had Mayo endoscopic scores of 2 or 3. At day 43, no patients in the placebo/open-label GSK2982772 group achieved Mayo endoscopic scores of 0 or 1 vs 3/24 (13%) for GSK2982772/open-label GSK2982772. At day 85, 1/9 (11%) achieved scores of 0 or one for placebo/open-label GSK2982772 vs 3/22 (14%) for GSK2982772/open-label GSK2982772.ConclusionGSK2982772 was generally well tolerated, with no treatment-related safety concerns identified. However, no significant differences in efficacy were observed between treatment groups, suggesting that GSK2982772 as monotherapy is not a promising treatment for patients with active UC.Trial registration numberNCT02903966.

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Botulinum Toxin in Restless Legs Syndrome—A Randomized Double-Blind Placebo-Controlled Crossover Study

Toxins ◽

10.3390/toxins10100401 ◽

2018 ◽

Vol 10 (10) ◽

pp. 401 ◽

Cited By ~ 3

Author(s):

Shivam Mittal ◽

Duarte Machado ◽

Diana Richardson ◽

Divyanshu Dubey ◽

Bahman Jabbari

Keyword(s):

Quality Of Life ◽

Crossover Study ◽

Pain Score ◽

Restless Legs Syndrome ◽

Biceps Femoris ◽

Life Questionnaire ◽

Double Blind ◽

Restless Legs ◽

Global Impression Of Change

Background: Restless Legs Syndrome (RLS) is a common movement disorder with an estimated prevalence of up to 12%. Previous small studies with onabotulinumtoxin A (OnaA) for RLS have shown inconsistent results. Methods: Twenty-four patients with an International RLS score (IRLS) of >11 (moderate-severe) were enrolled in this blinded, placebo-controlled crossover study. Twenty-one patients completed the evaluations at 4, 6, and 8 weeks after each injection. One-hundred units of Incobotulinumtoxin A (IncoA) or normal saline were injected into tibialis anterior, gastrocnemius, and biceps femoris muscles each side. Results: Improvement from a severe (IRLS >21) to a mild/moderate (IRLS ≤20) score was significant at four weeks (p = 0.0036) and six weeks (p = 0.0325) following IncoA administration compared to placebo. Additionally, there was significant improvement in pain score at six weeks as measured by Visual Analogue Scale (p = 0.04) and the Johns Hopkins Quality of Life Questionnaire (p = 0.01) in the IncoA group. Definite or marked improvement on Patient Global Impression of Change was seen in 7 out of 21 patients in the IncoA group vs. 1 out of 21 patients in the placebo group at 4 weeks (p = 0.012). Conclusion: IncoA injection lead to a reduction in severity of RLS symptoms, pain score, and quality of life, without any adverse effects.

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