Time-course of treatment-emergent adverse events in a long-term safety study of lisdexamfetamine dimesylate in children and adolescents with ADHD

2016 ◽  
Vol 33 (S1) ◽  
pp. S132-S132
Author(s):  
I. Hernández Otero ◽  
T. Banaschewski ◽  
P. Nagy ◽  
C.A. Soutullo ◽  
A. Zuddas ◽  
...  
Keyword(s):  
Adverse Events ◽  
Children And Adolescents ◽  
Time Course ◽  
Open Label ◽  
Lisdexamfetamine Dimesylate ◽  
Safety Population ◽  
First Onset ◽  
Stimulant Medications ◽  
Competing Interest

IntroductionThe long-term safety and efficacy of lisdexamfetamine dimesylate (LDX) in children and adolescents with attention deficit/hyperactivity disorder (ADHD) was evaluated in a European 2-year, open-label study (SPD489-404).ObjectiveTo evaluate the time-course of treatment-emergent adverse events (TEAEs) in SPD489-404.MethodsParticipants aged 6–17 years received open-label LDX (30, 50 or 70 mg/day) for 104 weeks (4 weeks dose-optimization; 100 weeks dose-maintenance).ResultsAll enrolled participants (n = 314) were included in the safety population and 191 (60.8%) completed the study. TEAEs occurred in 282 (89.8%) participants; most were mild or moderate. TEAEs considered by the investigators as related to LDX were reported by 232 (73.9%) participants with the following reported for ≥ 10% of participants: decreased appetite (49.4%), weight decreased (18.2%), insomnia (13.1%). TEAEs leading to discontinuation and serious TEAEs occurred in 39 (12.4%) and 28 (8.9%) participants, respectively. The median (range) time to first onset and duration, respectively, of TEAEs identified by the sponsor as being of special interest were: insomnia (insomnia, initial insomnia, middle insomnia, terminal insomnia), 17.0 (1–729) and 42.8 (1–739) days; weight decreased, 29.0 (1–677) and 225.0 (26–724) days; decreased appetite, 13.5 (1–653) and 169.0 (1–749) days; headache, 22.0 (1–718) and 2.0 (1–729) days. Reports of insomnia, weight decreased, decreased appetite and headache were highest in the first 4–12 weeks.ConclusionsTEAEs associated with long-term LDX treatment were characteristic of stimulant medications, with the greatest incidence observed during the first 4–12 weeks.Disclosure of interestThe authors have not supplied their declaration of competing interest.

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

CNS Drugs ◽  
2017 ◽  
Vol 31 (7) ◽  
pp. 625-638 ◽  
Author(s):  
David R. Coghill ◽  
Tobias Banaschewski ◽  
Peter Nagy ◽  
Isabel Hernández Otero ◽  
César Soutullo ◽  
...  
Keyword(s):  
Children And Adolescents ◽  
Open Label ◽  
Lisdexamfetamine Dimesylate ◽  
Open Label Study ◽  
Label Study ◽  
Safety And Efficacy ◽  
Phase Iv

scholarly journals Long-Term Safety and Effectiveness of Lisdexamfetamine Dimesylate in Adults With Attention-Deficit/Hyperactivity Disorder

CNS Spectrums ◽  
2009 ◽  
Vol 14 (10) ◽  
pp. 573-586 ◽  
Author(s):  
Richard Weisler ◽  
Joel Young ◽  
Greg Mattingly ◽  
Joseph Gao ◽  
Liza Squires ◽  
...  
Keyword(s):  
Attention Deficit Hyperactivity Disorder ◽  
Adverse Events ◽  
Attention Deficit ◽  
Rating Scale ◽  
Upper Respiratory Tract ◽  
Open Label ◽  
Lisdexamfetamine Dimesylate ◽  
Double Blind ◽  
Hyperactivity Disorder

ABSTRACTObjective: To evaluate the long-term safety and effectiveness of lisdexamfetamine dimesylate (LDX) in the treatment of adults with attention-deficit/hyperactivity disorder (ADHD).Methods: Following a 4-week, placebo-controlled, double-blind trial, 349 adults with ADHD were enrolled into an open-label, single-arm study for up to 12 months. Treatment was initiated at 30 mg/day and titrated up to 70 mg/day at subsequent visits to achieve optimal effectiveness and tolerability. Safety assessments included adverse events inquiries, vital signs, and electrocardiograms while the primary effectiveness assessment was the ADHD Rating Scale (ADHD-RS) total score.Results: A total of 191 (54.7%) subjects completed the study. The most common treatment-emergent adverse events (TEAEs) were upper respiratory tract infection (21.8%), insomnia (19.5%), headache (17.2%), dry mouth (16.6%), decreased appetite (14.3%), and irritability (11.2%). Most TEAEs were mild to moderate in severity. At endpoint, small but statistically significant increases in pulse and blood pressure were noted. Significant improvements in mean ADHD-RS total scores were observed at week 1 and sustained throughout the study (P<.0001 at all postbaseline visits). At endpoint, the mean improvement from baseline ADHD-RS total score was 24.8 (P<.0001).Conclusions: LDX demonstrated a safety profile consistent with long-acting stimulant use and provided continued effectiveness in adults with ADHD for up to 12 months.

Growth and Sexual Maturation in a 2-year, Open-label Clinical Study of Lisdexamfetamine Dimesylate in Children and Adolescents with ADHD

2017 ◽  
Vol 41 (S1) ◽  
pp. S130-S130
Author(s):  
I. Hernández Otero ◽  
T. Banaschewski ◽  
M. Johnson ◽  
P. Nagy ◽  
C.A. Soutullo ◽  
...  
Keyword(s):  
Children And Adolescents ◽  
Sexual Maturation ◽  
Tanner Stage ◽  
Open Label ◽  
Lisdexamfetamine Dimesylate ◽  
Stage Of Development ◽  
Control And Prevention ◽  
Z Scores ◽  
The Impact

IntroductionIndividuals with attention-deficit/hyperactivity disorder (ADHD) may require long-term medication.ObjectivesTo measure growth and sexual maturation of children and adolescents with ADHD receiving lisdexamfetamine dimesylate (LDX) in a 2-year trial (SPD489-404).AimsTo investigate the impact of long-term LDX treatment on growth and maturation.MethodsParticipants (6–17 years) received dose-optimized, open-label LDX (30–70 mg/day) for 104 weeks. Weight, height and BMI z-scores were derived using the Centers for Disease Control and Prevention norms [1]. Sexual maturation was assessed using the Tanner scale (participant-rated as closest to their stage of development based on standardized drawings).ResultsOf 314 enrolled participants, 191 (60.8%) completed the study. Mean z-scores at baseline and last on-treatment assessment (LOTA) were 0.53 (standard deviation, 0.963) and 0.02 (1.032) for weight, 0.61 (1.124) and 0.37 (1.131) for height, and 0.32 (0.935) and–0.27 (1.052) for BMI. In general, z-scores shifted lower over the first 36 weeks and then stabilized. At LOTA, most participants remained at their baseline Tanner stage or shifted higher, based on development of hair (males, 95.5%; females, 92.1%) or genitalia/breasts (males, 94.7%; females, 98.4%).ConclusionsConsistent with previous studies of stimulants used to treat ADHD [2], z-scores for weight, height and BMI decreased, mostly in the first year, then stabilized. No clinically concerning trends of LDX treatment on sexual maturation or the onset of puberty were observed.Disclosure of interestStudy funded by Shire Development LLC.Dr Isabel Hernández Otero (Alicia Koplowitz Foundation, Eli Lilly, Forest, Janssen-Cilag, Junta de Andalucia, Roche, Shire, Shire Pharmaceuticals Iberica S.L., and Sunovion).

Safety and tolerability of aripiprazole in the treatment of irritability associated with autistic disorder in pediatric patients: Results from a 52-week open-label study

2011 ◽  
Vol 26 (S2) ◽  
pp. 319-319
Author(s):  
W. Landsberg ◽  
J.-Y. Loze ◽  
G. Lau ◽  
G. Manos ◽  
R. McQuade ◽  
...  
Keyword(s):  
Autistic Disorder ◽  
Time Course ◽  
De Novo ◽  
Nasal Congestion ◽  
Open Label ◽  
Open Label Study ◽  
Upper Respiratory Infection ◽  
First Onset ◽  
Short Time

ObjectiveEvaluate the time-course, severity and resolution patterns of adverse events (AEs) occurring with long-term aripiprazole treatment for irritability associated with autistic disorder.MethodsParticipants were treated with aripiprazole in a 52-week, open-label, flexibly dosed (2–15 mg/day) study. Subjects had either completed one of two 8-week randomised trials or were de novo. AEs with an incidence of ≥10% were evaluated by incidence, peak first onset, severity, percent resolved and time to resolution.ResultsA total of 330 subjects entered open-label treatment; 199 completed 52 weeks. Mean dose for the population stabilised at around 10 mg/day after approximately 4 months. Thirteen AEs had an incidence of ≥10%; most were mild or moderate in severity. Vomiting, diarrhoea and headache had an early first onset and tended to resolve fairly quickly.Sedation, fatigue and insomnia also appeared early and resolved in a majority of cases, but not as quickly. Increased appetite appeared early (followed by increased weight) and fewer weight-related AEs resolved. More than half of the subjects increased their weight by at least one percentile category rank; nevertheless, only a small proportion of subjects with normal baseline metabolic or glucose measures had a treatment-emergent, clinically relevant laboratory abnormality. Nasopharyngitis, upper respiratory infection, cough, nasal congestion and pyrexia all had peak onset at variable times during the study, resolving in nearly all cases, with short time to resolution.ConclusionAEs were mostly mild or moderate and of variable duration. Increased weight was observed.

Long-Term, Open-Label Venlafaxine Extended-Release Treatment in Children and Adolescents with Major Depressive Disorder

CNS Spectrums ◽  
2007 ◽  
Vol 12 (3) ◽  
pp. 223-233 ◽  
Author(s):  
Graham J. Emslie ◽  
Paul P. Yeung ◽  
Nadia R. Kunz
Keyword(s):  
Major Depressive Disorder ◽  
Adverse Events ◽  
Depressive Disorder ◽  
Children And Adolescents ◽  
Extended Release ◽  
Pediatric Patients ◽  
Term Treatment ◽  
Open Label ◽  
Major Depressive

ABSTRACTIntroduction: Because major depressive disorder (MDD) is often chronic and recurrent, even pediatric patients who are treated successfully during an acute episode may need longer-term treatment. Yet, data on long-term treatment with antidepressants in pediatric MDD are limited.Objective: To evaluate long-term effectiveness and safety of treatment with venlafaxine extended-release (ER) in children and adolescents with MDD.Methods: Subjects (n=86) 7–17 years of age with MDD entered a multicenter, open-label study of flexible-dose venlafaxine ER for 6 weeks of acute treatment, followed by continuation treatment for up to 6 months total treatment. The primary efficacy variable was the Children's Depression Rating Scale-Revised (CDRS-R) total score (intent-to-treat population).Results: Mean CDRS-R total score decreased from 60.1±10.0 at baseline to 36.3±13.1 at week 6, and to 33.8±15.0 at 6 months (last observation carried forward). Among completers (n=36), the mean CDRS-R total score was 24.3±7.6 at the end of 6 months of treatment. The most frequent treatment-emergent adverse events were headache (53%), nausea (26%), infection (24%), abdominal pain (22%), vomiting (21%), and pharyngitis (19%). Fifteen (17%) participants discontinued due to adverse events, 9 of whom did so within the first 6 weeks. Serious adverse events (suicide attempt [two], hostility [two], hallucinations, depression, and pharyngitis) occurred in seven patients. There were no suicides.Conclusion: Most improvement with venlafaxine ER occurs during the first 6 weeks of treatment. Prescribers should be alert to signs of suicidal ideation and hostility in pediatric patients.

scholarly journals 134 Long-Term Deutetrabenazine Treatment Is Associated with Sustained Treatment Response in Tardive Dyskinesia: Results from an Open-Label Extension Study

CNS Spectrums ◽  
2020 ◽  
Vol 25 (2) ◽  
pp. 284-285 ◽  
Author(s):  
Robert A. Hauser ◽  
Hadas Barkay ◽  
Hubert H. Fernandez ◽  
Stewart A. Factor ◽  
Joohi Jimenez-Shahed ◽  
...  
Keyword(s):  
Adverse Events ◽  
Percentage Change ◽  
Extension Study ◽  
Total Daily Dose ◽  
Open Label ◽  
Daily Dose ◽  
Open Label Extension ◽  
The Mean ◽  
Over Time

Abstract:Background:In the 12-week ARM-TD and AIM-TD studies evaluating deutetrabenazine for the treatment of tardive dyskinesia (TD), the percentage of patients achieving ≥50% response was higher in the deutetrabenazine-treated group than in the placebo group. These studies also showed low rates of overall adverse events (AEs) and discontinuations associated with deutetrabenazine. The current open-label study evaluated the long-term efficacy and safety of deutetrabenazine in patients with TD.Methods:Patients with TD who completed ARM-TD or AIM-TD could enroll in this open-label, single-arm extension study, titrating up over 6 weeks to a maximum total daily dose of deutetrabenazine 48 mg/day on the basis of dyskinesia control and tolerability. The proportion of Abnormal Involuntary Movement Scale (AIMS; items 1-7) responders was assessed based on response rates for achieving ≥50% improvement from baseline in the open-label extension study. AlMS score was assessed by local site raters for this analysis.Results:343 patients enrolled in the extension study. At Week 54 (n=249; total daily dose [mean ± standard error]: 38.6±0.66 mg), the mean percentage change from baseline in AIMS score was –40%; 48% of patients achieved a ≥50% response and 59% of those had already achieved a ≥50% response at Week 15. Further, 34% of those who had not achieved a ≥50% response at Week 15 achieved a ≥50% response at Week 54. At Week 106 (n=169; total daily dose: 39.6±0.77 mg), the mean percentage change from baseline in AIMS score was –45%; 55% of patients achieved a ≥50% response, 59% of those patients had already achieved a ≥50% response at Week 15, and 41% of those who had not achieved a ≥50% response at Week 15 but who reached Week 106 achieved a ≥50% response. At Week 132 (n=109; total daily dose: 39.7±0.97 mg), the mean percentage change from baseline in AIMS score was –61%; 55% of patients achieved a ≥50% response, 61% of those patients had already achieved a ≥50% response at Week 15, and 43% of those who had not achieved a ≥50% response at Week 15 but who reached Week 132 achieved a ≥50% response. Completer analysis suggests that long-term efficacy was not due to dose increases over time. Treatment with deutetrabenazine was generally well tolerated. There were 623 patient-years of exposure through Week 158, and exposure-adjusted incidence rates (incidence/patient-years) of adverse events of special interest were 0.01 for akathisia and restlessness, 0.07 for somnolence and sedation, 0.04 for parkinsonism, and 0.05 for depression.Conclusions:Patients who received long-term treatment with deutetrabenazine achieved response rates that were indicative of clinically meaningful long-term benefit. Results from this open-label trial suggest the possibility of increasing benefit over time with individual dose titration of deutetrabenazine.Funding Acknowledgements:This study was funded by Teva Pharmaceuticals, Petach Tikva, Israel.

scholarly journals DOP60 Vedolizumab treatment persistence and safety in an extended access program (XAP)

2020 ◽  
Vol 14 (Supplement_1) ◽  
pp. S099-S100
Author(s):  
S Danese ◽  
K Subramanian ◽  
J Van Zyl ◽  
S Adsul ◽  
D Lindner ◽  
...  
Keyword(s):  
Data Analysis ◽  
Adverse Events ◽  
Dose Escalation ◽  
Open Label ◽  
Dose Escalation Study ◽  
Extended Access ◽  
Dosing Frequency ◽  
Access Program

Abstract Background Vedolizumab, a gut-selective, α 4β 7 integrin antagonist, has been established as an effective and safe treatment for patients with UC or CD in the GEMINI phase 3 program and long-term safety (LTS) study. An extended access program (XAP) was initiated to provide continued access to patients who were benefiting from vedolizumab in GEMINI LTS and to monitor safety. We now report persistence and safety results from a 2-year data analysis. Methods Vedolizumab XAP (NCT02743806) is a phase 3b/4 prospective, open-label, multinational interventional study. A rollover from GEMINI LTS (NCT00790933) to the XAP, patients reduced dosing frequency from vedolizumab 300 mg IV every 4 weeks (Q4W) to every 8 weeks (Q8W) or remained on vedolizumab 300 mg IV Q4W if medically indicated. This 2-year data analysis assessed persistence on Q8W dosing after dosing frequency reduction, need for escalation to Q4W dosing, incidence of relapse (defined as dose escalation, study withdrawal due to adverse event, loss of adequate benefit from vedolizumab, or increased corticosteroid [CS] or immunomodulator dose), and safety 2 years after rollover from GEMINI LTS. Results A total of 311 patients (142 UC, 169 CD) from GEMINI LTS enrolled in the XAP. Median (range) duration of exposure to vedolizumab prior to the XAP was 8.0 years (5.2–10.0) for patients with UC and 7.5 years (5.4–9.9) for patients with CD. Of patients with UC and CD, 93.0% and 84.6%, respectively, reduced dosing frequency to Q8W at XAP start, and 87.3% and 77.5%, respectively, remained on Q8W after 2 years. At baseline, 93.0% of all patients with UC and 88.2% of all patients with CD were in CS-free remission; patients who maintained Q4W dosing at baseline had lower CS-free remission rates (62.5% in UC and 69.2% in CD). Of patients who initiated Q8W dosing at enrolment in the XAP, 95% had no relapse for ≥6 months (97.0% UC, 93.7% CD; Table 1). Only 7.3% of patients required dose escalation to Q4W, and 11.6% experienced relapse during the 2-year follow-up. Times to dose escalation and relapse were similar in patients with UC and CD (Figures 1 and 2). At 2 years, 4 of 8 patients with UC and 4 of 12 patients with CD who required dose escalation to Q4W discontinued vedolizumab early due to loss of benefit or adverse events. Adverse events related to vedolizumab were infrequent; no new or serious events attributed to vedolizumab were reported. Conclusion High patient persistence on Q8W vedolizumab was observed in the first 2 years after reduction of dosing frequency in the XAP. Overall, there were low rates of Q4W dose escalation and CD or UC disease relapse. The safety profile was consistent with previous reports with no new signals observed.

scholarly journals Safety and effectiveness of lurasidone in adolescents with schizophrenia: results of a 2-year, open-label extension study

CNS Spectrums ◽  
2020 ◽  
pp. 1-11
Author(s):  
Christoph U. Correll ◽  
Robert L. Findling ◽  
Michael Tocco ◽  
Andrei Pikalov ◽  
Ling Deng ◽  
...  
Keyword(s):  
Body Weight ◽  
Adverse Events ◽  
Rating Scales ◽  
Extension Study ◽  
Open Label ◽  
Double Blind ◽  
Syndrome Scale ◽  
Open Label Extension ◽  
Glycemic Indices

Abstract Background Minimal long-term benefit: Risk data are available regarding antipsychotic treatments for schizophrenia in pediatric populations. This study evaluated the long-term safety, tolerability, and effectiveness of lurasidone in adolescents with schizophrenia. Methods Patients aged from 13 to 17 who completed 6 weeks of double-blind (DB), placebo-controlled treatment with lurasidone were enrolled in a 2-year, open-label (OL), flexible dose (20-80 mg/day) lurasidone treatment study. Safety was assessed via spontaneous reporting, rating scales, body weight measurement, metabolic, and prolactin testing. Effectiveness measures included the Positive and Negative Syndrome Scale (PANSS) total score. Results About 271 patients completed 6 weeks of DB treatment and entered the 2-year OL extension study. Altogether, 42.4% discontinued prematurely, 10.7% due to adverse events. During OL treatment, the most common adverse events were headache (24.0%); anxiety (12.9%), schizophrenia, and nausea (12.5%); sedation/somnolence (12.2%); and nasopharyngitis (8.9%). Minimal changes were observed on metabolic parameters and prolactin. Mean change from DB baseline in weight at week 52 and week 104 was +3.3 kg and + 4.9 kg, respectively, compared to an expected weight gain of +3.4 kg and + 5.7 kg, respectively, based on the sex- and age-matched US Center for Disease Control normative data. Continued improvement was observed in PANSS total score, with mean change from OL baseline of −15.6 at week 52 and −18.4 at week 104. Conclusion In adolescents with schizophrenia, long-term lurasidone treatment was associated with minimal effects on body weight, lipids, glycemic indices, and prolactin. Continued improvement in symptoms of schizophrenia was observed over 2 years of lurasidone treatment.

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