Dataset Information

Extended Release Guanfacine in Pediatric Anxiety Disorders: A Pilot, Randomized, Placebo-Controlled Trial.

ABSTRACT: OBJECTIVE:This is a feasibility study evaluating the safety, tolerability, and potential anxiolytic efficacy of the ?2 agonist guanfacine extended-release (GXR) in children and adolescents with generalized anxiety disorder (GAD), separation anxiety disorder (SAD), or social phobia/social anxiety disorder. METHODS:Youth aged 6-17 years with a primary diagnosis of GAD, SAD, and/or social anxiety disorder were treated with flexibly dosed GXR (1-6?mg daily, n?=?62) or placebo (n?=?21) for 12 weeks. The primary aim of this study was to determine the safety and tolerability of GXR in youth with anxiety disorders, which involved the analysis of treatment-emergent adverse events (TEAEs), the emergence of suicidal ideation and behaviors, vital signs, and electrocardiographic/laboratory parameters. Exploratory efficacy measures included dimensional anxiety scales (Pediatric Anxiety Rating Scale [PARS] and Screen for Child Anxiety Related Emotional Disorders [SCARED]), as well as the Clinical Global Impression-Improvement (CGI-I) scale. As this was an exploratory study, no inferential statistical analyses were performed. RESULTS:GXR was safe and well tolerated. Treatment-related mean?±?standard deviation changes in heart rate (GXR: 1.8?±?12 beats per minute [bpm] decrease; placebo: 0.5?±?11?bpm decrease), systolic blood pressure (GXR: 2.3?±?11?mm Hg decrease; placebo: 1.7?±?11?mm Hg decrease), or diastolic blood pressure (GXR: 1.3?±?9?mm Hg decrease; placebo: 0.9?±?7?mm Hg increase) were similar between treatment groups. TEAEs, including headache, somnolence/fatigue, abdominal pain, and dizziness, were consistent with the known safety profile of GXR. No differences were observed between treatment groups for PARS and SCARED scores, although at endpoint, a higher proportion of subjects receiving GXR versus placebo demonstrated CGI-I scores ?2 (54.2% vs. 31.6%), as rated by the clinician investigator. CONCLUSIONS:GXR was well tolerated in pediatric subjects with GAD, SAD, and/or social anxiety disorder. ClinicalTrials.gov Identifier: NCT01470469.

SUBMITTER: Strawn JR

PROVIDER: S-EPMC5695796 | biostudies-literature | 2017 Feb

REPOSITORIES: biostudies-literature

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Extended Release Guanfacine in Pediatric Anxiety Disorders: A Pilot, Randomized, Placebo-Controlled Trial.

Strawn Jeffrey R JR Compton Scott N SN Robertson Brigitte B Albano Anne Marie AM Hamdani Mohamed M Rynn Moira A MA

Journal of child and adolescent psychopharmacology 20170206 1

<h4>Objective</h4>This is a feasibility study evaluating the safety, tolerability, and potential anxiolytic efficacy of the α<sub>2</sub> agonist guanfacine extended-release (GXR) in children and adolescents with generalized anxiety disorder (GAD), separation anxiety disorder (SAD), or social phobia/social anxiety disorder.<h4>Methods</h4>Youth aged 6-17 years with a primary diagnosis of GAD, SAD, and/or social anxiety disorder were treated with flexibly dosed GXR (1-6 mg daily, n = 62) or place ...[more]

PMID: 28165762

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Project description:Backgroundα2-Adrenoceptor agonists are used adjunctively to psychostimulants in treating attention-deficit/hyperactivity disorder (ADHD) when psychostimulants alone do not sufficiently reduce symptoms. However, data on the pharmacokinetic profiles and safety of combination treatments in ADHD are needed.ObjectiveThe primary objective of this study was to evaluate the pharmacokinetic profiles of guanfacine extended release (GXR) and methylphenidate hydrochloride (MPH) extended release, alone and in combination.Study designThis was an open-label, randomized, three-period crossover, drug-drug interaction study.SettingThe study was conducted at a single clinical research center.ParticipantsThirty-eight healthy adults were randomized in this study.InterventionsSubjects were administered single oral doses of GXR (Intuniv(®); Shire Development LLC, Wayne, PA, USA) 4 mg, MPH (Concerta(®); McNeil Pediatrics, Titusville, NJ, USA) 36 mg, or GXR and MPH combined.Main outcome measuresGuanfacine, dexmethylphenidate (d-MPH), and l-methylphenidate (l-MPH) levels were measured with blood samples collected predose and up to 72 h postdose. Safety evaluations included treatment-emergent adverse events (TEAEs), vital signs, and electrocardiograms (ECGs).ResultsThirty-five subjects completed the study. Analyses of the 90 % confidence intervals (CIs) for the geometric mean ratios of the maximum plasma concentration (Cmax) and area under the concentration-time curve extrapolated to infinity (AUC∞) values for guanfacine and d-MPH following administration of GXR or MPH alone or combined met strict bioequivalence criteria (90 % CIs within the interval of 0.80-1.25). Overall, combining GXR and MPH did not alter the pharmacokinetic parameters of either medication. Sixteen subjects (42.1 %) had at least one TEAE. The most commonly reported TEAEs included headache and dizziness following GXR, MPH, and GXR and MPH combined. Two subjects had clinically significant abnormalities in ECG results following coadministration: both events were mild and resolved the same day.ConclusionsIn this short-term, open-label study of healthy adults, coadministration of GXR and MPH did not result in significant pharmacokinetic drug-drug interactions. No unique TEAEs were observed with coadministration of GXR and MPH compared with either treatment alone.

Project description:BackgroundIn clinical practice, α₂-adrenoceptor agonists have been adjunctively administered with psychostimulants for the treatment of attention-deficit/hyperactivity disorder (ADHD). Two studies have examined the adjunctive use of guanfacine extended release (GXR, Intuniv®; Shire Development LLC, Wayne, PA, USA) with psychostimulants in children and adolescents with a suboptimal response to psychostimulant treatment. However, the potential for pharmacokinetic drug-drug interactions (DDIs) between GXR and lisdexamfetamine dimesylate (LDX, Vyvanse®; Shire US LLC, Wayne, PA, USA) has not been thoroughly evaluated.ObjectiveThe primary objective of this study was to examine the pharmacokinetics of GXR 4 mg and LDX 50 mg given as single doses alone and in combination.Study designThis was an open-label, randomized, three-period crossover, DDI study.SettingThe study was conducted in a single clinical research center.ParticipantsForty-two healthy adults were randomized in this study.InterventionsSubjects were administered single oral doses of GXR 4 mg, LDX 50 mg, or GXR and LDX in combination.Main outcome measuresBlood samples collected predose and up to 72 h postdose assessed guanfacine, LDX, and d-amphetamine levels. Bioequivalence was defined as the 90% confidence intervals (CIs) of the geometric mean ratios of the area under the plasma concentration-time curve extrapolated to infinity (AUC0-∞) and maximum plasma concentration (Cmax) falling within the bioequivalence reference interval (0.80-1.25). Safety measures included adverse events, vital signs, and electrocardiograms (ECGs).ResultsForty subjects completed the study. Following administration of LDX alone or in combination with GXR, the statistical comparisons of the AUC0-∞ and Cmax of d-amphetamine fell entirely within the reference interval. For guanfacine, the 90% CI of the geometric mean ratio of AUC∞ for the two treatments was within the bioequivalence criteria, but for Cmax the upper bound of the 90% CI exceeded the standard range for bioequivalence by 7%. This relatively small change is unlikely to be clinically meaningful. Treatment-emergent adverse events (TEAEs) were reported by 42.9% of subjects; the most commonly reported TEAEs included dizziness (5.0, 7.3, and 7.3%) and headache (7.5, 4.9, and 7.3%) following administration of GXR, LDX, and GXR and LDX in combination, respectively. Clinically significant ECG abnormalities occurred in one subject following administration of LDX and in one subject following coadministration of GXR and LDX.ConclusionsIn healthy adults, coadministration of GXR and LDX did not result in a clinically meaningful pharmacokinetic DDI compared with either treatment alone. No unique TEAEs were observed with coadministration of GXR and LDX compared with either treatment alone.

Project description:ObjectiveTo determine if men who have sex with men (MSM) with cocaine use disorder (CUD) and actively-using cocaine could be enrolled and retained in a pharmacologic intervention trial of lorcaserin-a novel 5-HT2cR agonist-and determine the degree to which participants would adhere to study procedures.MethodsThis was a phase II randomized, double-blind, placebo-controlled pilot study with 2:1 random parallel group assignment to daily extended-release oral lorcaserin 20 mg versus placebo (clinicaltrials.gov identifier-NCT03192995). Twenty-two of a planned 45 cisgender MSM with CUD were enrolled and had weekly follow-up visits during a 12-week treatment period, with substance use counseling, urine specimen collection, and completion of audio-computer assisted self-interview (ACASI) behavioral risk assessments. Adherence was measured by medication event monitoring systems (MEMS) caps and self-report. This study was terminated early because of an FDA safety alert for lorcaserin's long-term use.ResultsEighty-six percent completed the trial, with 82% of weekly study follow-up visits completed. Adherence was 55.3% (lorcaserin 51.6% vs. placebo 66.2%) by MEMS cap and 56.9% (56.5% vs. placebo 57.9%) by self-report and did not differ significantly by treatment assignment. Intention-to-treat analyses (ITT) did not show differences in cocaine positivity by urine screen between the lorcaserin and placebo groups by 12 week follow-up (incidence risk ratio [IRR]: 0.96; 95%CI = 0.24-3.82, P = 0.95). However, self-reported cocaine use in timeline follow-back declined more significantly in the lorcaserin group compared to placebo (IRR: 0.66; 95%CI = 0.49-0.88; P = 0.004).ConclusionWe found that it is feasible, acceptable, and tolerable to conduct a placebo-controlled pharmacologic trial for MSM with CUD who are actively using cocaine. Lorcaserin was not associated with significant reductions in cocaine use by urine testing, but was associated with significant reductions in self-reported cocaine use. Future research may be needed to continue to explore the potential utility of 5-HT2cR agonists.

Dataset Information

Extended Release Guanfacine in Pediatric Anxiety Disorders: A Pilot, Randomized, Placebo-Controlled Trial.

Publications

Extended Release Guanfacine in Pediatric Anxiety Disorders: A Pilot, Randomized, Placebo-Controlled Trial.

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