Long-Term Safety and Efficacy of Lisdexamfetamine Dimesylate in Children and Adolescents with ADHD: A Phase IV, 2-Year, Open-Label Study in EuropeReport as inadecuate




Long-Term Safety and Efficacy of Lisdexamfetamine Dimesylate in Children and Adolescents with ADHD: A Phase IV, 2-Year, Open-Label Study in Europe - Download this document for free, or read online. Document in PDF available to download.

CNS Drugs

, Volume 31, Issue 7, pp 625–638

First Online: 30 June 2017

Abstract

BackgroundAttention-deficit-hyperactivity disorder ADHD is increasingly recognized as a persistent disorder requiring long-term management.

ObjectivesOur objective was to evaluate the 2-year safety and efficacy of lisdexamfetamine dimesylate LDX in children and adolescents with ADHD.

MethodsParticipants aged 6–17 years with ADHD received open-label, dose-optimized LDX 30, 50, or 70 mg-day for 104 weeks. Safety monitoring included treatment-emergent adverse events TEAEs, vital signs, electrocardiography, and growth. The TEAEs decreased appetite, weight decrease, insomnia events including insomnia, initial insomnia, middle insomnia, and terminal insomnia, headache, and psychiatric TEAEs were pre-defined as being of special interest. Efficacy was assessed as a secondary objective using the ADHD Rating Scale IV ADHD-RS-IV, the Clinical Global Impressions-Improvement CGI-I scale, and the CGI-Severity CGI-S scale.

ResultsOf 314 participants enrolled, 191 completed the study. TEAEs were reported in 89.8% of participants, led to discontinuation in 12.4%, and were reported as serious in 8.9%. TEAEs that were reported by ≥5% of participants and considered by investigators as related to LDX were decreased appetite 49.4%, weight decrease 18.2%, insomnia 13.1%, initial insomnia 8.9%, irritability 8.6%, nausea 6.7%, headache 5.7%, and tic 5.1%. The median time to first onset and duration, respectively, of TEAEs of special interest were as follows: decreased appetite, 13.5 and 169.0 days; weight decrease, 29.0 and 225.0 days; insomnia, 17.0 and 42.8 days; and headache, 22.0 and 2.0 days. Reports of decreased appetite, weight decrease, insomnia, and headache were highest in the first 4–12 weeks. Psychiatric TEAEs were infrequent: psychosis and mania n = 1, suicidal events suicidal ideation, n = 2; suicide attempt, n = 1, and aggression events aggression, n = 14; anger, n = 2; hostility, n = 1. At the last on-treatment assessment LOTA, mean increases from baseline in vital signs were as follows: pulse rate, 7.0 bpm 95% confidence interval CI 5.7–8.2; systolic blood pressure SBP, 3.4 mmHg 95% CI 2.2–4.5; and diastolic blood pressure DBP, 3.2 mmHg 95% CI 2.2–4.2. Pre-defined thresholds for a potentially clinically important PCI high pulse rate were met at one or more visits by 22 participants 7.0%, for PCI high SBP were met by 45 children 22.4% and 17 adolescents 15.2%, and for PCI high DBP were met by 78 children 38.8% and 24 adolescents 21.4%. The mean QT interval corrected using Fridericia’s formula QTcF decreased from baseline to LOTA −0.6 ms 95% CI −2.3 to 1.2; range −50 to +53. Mean changes in growth from baseline to LOTA were weight, 2.1 kg 95% CI 1.5–2.8; height, 6.1 cm 95% CI 5.6–6.7; and body mass index BMI, −0.5 kg-m 95% CI −0.7 to −0.3. There was a general shift to lower z score categories for height, weight, and BMI from baseline to LOTA. The mean change in ADHD-RS-IV from baseline to LOTA was −25.8 95% CI −27.0 to −24.5 for total score, −12.6 95% CI −13.4 to −11.9 for the hyperactivity-impulsivity subscale score, and −13.1 95% CI −13.8 to −12.4 for the inattention subscale score. At LOTA, 77.9% of participants had a CGI-I score of 1 or 2. In addition, 77.3 and 69.2% of participants were classified as treatment responders, based on a CGI-I score of 1 or 2 and a ≥30% or ≥50% reduction from baseline in ADHD-RS-IV total score, respectively.

ConclusionsThe safety profile of LDX in this longer-term study was similar to that reported in previous studies. The efficacy of LDX was maintained throughout the 2-year study period.

ClinicalTrials.gov IdentifierNCT01328756.

Electronic supplementary materialThe online version of this article doi:10.1007-s40263-017-0443-y contains supplementary material, which is available to authorized users.

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Author: David R. Coghill - Tobias Banaschewski - Peter Nagy - Isabel Hernández Otero - César Soutullo - Brian Yan - Beatriz Cab

Source: https://link.springer.com/







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