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Safety and Efficacy of Repeat Open-Label AbobotulinumtoxinA Treatment in Pediatric Cerebral Palsy.

ABSTRACT: This was a prospective, repeat-treatment, open-label study (NCT01251380) of abobotulinumtoxinA for the management of lower limb spasticity in children who had completed a double-blind study. Children (2-17 years) received injections into the gastrocnemius-soleus complex, and other distal and proximal muscles as required (maximum total dose per injection cycle: 30 U/kg or 1000U). A total of 216 of the 241 double-blind patients entered the extension study and 207 received ?1 open label injection into the gastrocnemius-soleus; 17-24% of patients also had injections into the hamstrings. The most frequent adverse events were related to common childhood infections and the most frequent treatment-related adverse event was injection site pain (n = 10). There was no evidence of a cumulative effect on adverse events. Sustained significant clinical improvements in muscle tone (Modified Ashworth Scale), spasticity (Tardieu Scale), overall clinical benefit (Physicians Global Assessment), and goal attainment (Goal Attainment Scale) were also observed across treatment cycles.

SUBMITTER: Delgado MR

PROVIDER: S-EPMC5652649 | biostudies-literature | 2017 Nov

REPOSITORIES: biostudies-literature

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Safety and Efficacy of Repeat Open-Label AbobotulinumtoxinA Treatment in Pediatric Cerebral Palsy.

Delgado Mauricio R MR Bonikowski Marcin M Carranza Jorge J Dabrowski Edward E Matthews Dennis D Russman Barry B Tilton Ann A Velez Juan Carlos JC Grandoulier Anne-Sophie AS Picaut Philippe P

Journal of child neurology 20170915 13

This was a prospective, repeat-treatment, open-label study (NCT01251380) of abobotulinumtoxinA for the management of lower limb spasticity in children who had completed a double-blind study. Children (2-17 years) received injections into the gastrocnemius-soleus complex, and other distal and proximal muscles as required (maximum total dose per injection cycle: 30 U/kg or 1000U). A total of 216 of the 241 double-blind patients entered the extension study and 207 received ≥1 open label injection i ...[more]

PMID: 28914131

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Project description:AimTo assess the efficacy and safety of repeat abobotulinumtoxinA injections in reducing upper limb spasticity in children with cerebral palsy (CP).MethodThis was a double-blind, repeat-cycle study (NCT02106351) in children with CP (2-17y). Children were randomized to receive 2U/kg (control), 8U/kg, or 16U/kg abobotulinumtoxinA injections into the target muscle group (wrist or elbow flexors) and additional muscles alongside occupational therapy via a home-exercise therapy program (HETP; minimum five 15min sessions/wk). Children received 8U/kg or 16U/kg plus HETP in cycles 2 to 4.ResultsDuring cycle 1, 210 children (126 males, 84 females; mean age [SD] 9y [4y 5mo], range 2-17y; n=70/group) had at least one upper limb abobotulinumtoxinA injection and 209 complied with the HETP. At week 6 of cycle 1, children in the 8U/kg or 16U/kg groups had significantly lower Modified Ashworth scale scores versus the 2U/kg group (primary outcome: treatment differences of -0.4 [p=0.012] and -0.7 [p<0.001] respectively). All groups improved on Physician Global Assessment and children in all groups achieved their treatment goals at least as expected. Therapeutic benefits were sustained during cycles 2 to 4; muscular weakness was the only treatment-related adverse event reported in at least one child/group (4.3% and 5.7% vs 1.4% respectively).InterpretationTreatment with 8U/kg or 16U/kg abobotulinumtoxinA significantly reduced upper limb spasticity versus the 2U/kg control dose. Therapeutic benefits of abobotulinumtoxinA plus HETP were sustained with repeat treatment cycles.What this paper addsAbobotulinumtoxinA injections significantly reduced upper limb spasticity in children with cerebral palsy. Children treated with abobotulinumtoxinA and targeted home exercises showed global improvement and goal attainment. Benefits were sustained over 1 year with repeat cycles of abobotulinumtoxinA and home exercises. AbobotulinumtoxinA injections into the upper limb were well tolerated over 1 year.

Project description:ObjectiveTo assess long-term (up to 2 years) efficacy, tolerability, and safety of erenumab for the prevention of episodic migraine (EM) in Japanese patients.BackgroundPreviously published results from the double-blind treatment phase (DBTP) of a phase 2 clinical study have demonstrated the efficacy and safety of erenumab in Japanese patients with EM.MethodsPatients completing the 24-week placebo-controlled DBTP could continue into the 76-week open-label treatment phase (OLTP), receiving erenumab 70 mg or 140 mg subcutaneously once monthly. The initial dose in the OLTP was erenumab 70 mg monthly, which was later changed to 140 mg. After study completion, the following were assessed: change from baseline in monthly migraine days (MMD), change from baseline in monthly acute migraine-specific medication days (MSMD), percentage of patients achieving ≥50% and ≥75% reduction in MMD, change from baseline in the 6-item Headache Impact Test (HIT-6™) score, and safety (exposure-adjusted patient-incidence of adverse events [AEs], calculated as number of patients per 100 patient-years).ResultsOf 475 patients enrolled in the DBTP, 459 (96.6%) continued in the OLTP. The mean (SD) MMD was 7.9 (2.3) at baseline with the overall change from baseline at week 100 of -2.9 (4.1) days. The monthly acute MSMD was 5.7 (2.8) at baseline with change from baseline at week 100 of -1.7 (3.7) days. The proportion of patients who achieved ≥50% and ≥75% reduction in MMD from baseline at week 100 was 177/398 (44.5%) and 94/398 (23.6%), respectively. The HIT-6™ score was 58.4 (5.4) at baseline with a change of -6.4 (8.2) at week 100. The exposure-adjusted patient-incidence of AEs during the OLTP was 207.1/100 patient-years for the combined erenumab group, similar to that observed for either erenumab (271.0/100 patient-years) or placebo (257.3/100 patient-years) during the DBTP, and no new safety signals were detected during the OLTP.ConclusionLong-term erenumab treatment in Japanese patients with EM demonstrated sustained efficacy for up to 2 years, with a safety profile similar to previous studies, supporting erenumab as a potential new therapy for EM prevention in Japan.

Project description:Oral antipyretics are commonly used to treat pediatric patients who develop fevers. However, patients presenting to the emergency department or undergoing surgery are frequently unable to tolerate oral antipyretics. Rectal formulations are available; however, this route of administration is unpredictable. The main objectives of this randomized controlled study was to evaluate the efficacy and safety of single or multiple doses of intravenous ibuprofen to acetaminophen (oral or suppository) in pediatric patients with fever and to assess plasma ibuprofen concentrations.This multi-center study was conducted in hospitalized patients, ? 16 years, with a new onset of fever ? 38.3°C. Patients were randomly assigned to receive either 10 mg/kg intravenous ibuprofen or acetaminophen. Study drug was administered at hour 0, and thereafter every 4 h as needed, up to 5 days. The primary outcome was to evaluate the effect of a single dose of intravenous ibuprofen compared to acetaminophen in reducing temperature in the first 2 h after administration. Data were compared using an analysis of variance model for continuous measurements and Cochran-Mantel-Haenszel test of general association for categorical data. A two-sided testing was used and a p-value ? 0.05 was considered significant.A total of 103 patients received study medication. Intravenous ibuprofen resulted in a greater reduction in temperature as measured by the area under the change from baseline at 2 h (p = 0.005) and 4 h (<0.001); in a greater reduction in change from baseline temperature compared to treatment with acetaminophen, and it reduced fever throughout a 24 h dosing period. There were no differences in safety parameters or serious adverse events.A single 10 mg/kg dose of intravenous ibuprofen provided a significant reduction of temperature for febrile pediatric patients compared to those that received 10 mg/kg acetaminophen at 2 h and 4 h post-treatment. A reduction in temperature was also demonstrated over 24 h; however the reduction was not considered statically significant. Intravenous ibuprofen provides an effective option for reducing fever in hospitalized pediatric patients.The study was registered on ClinicalTrials.gov on 26 October 2009, Study Identifier: NCT01002573.

Project description:INTRODUCTION:The aim of this work is to assess the safety and efficacy of repeat administration of triamcinolone acetonide extended-release (TA-ER) in patients with symptomatic knee osteoarthritis (OA), including those with advanced radiographic severity. METHODS:In this phase 3b, single-arm, open-label study, patients aged ≥ 40 years received the first intra-articular TA-ER injection on day 1. Patients received the second injection timed to the response to the first injection (at either week 12, 16, 20, or 24). Patients who received two injections were evaluated every 4 weeks for 52 weeks. Safety was evaluated via treatment-emergent adverse events and any change at 52 weeks in index-knee radiographs (chondrolysis, osteonecrosis, insufficiency fractures, subchondral bone changes). Exploratory efficacy endpoints included Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC)-A (pain), -B (stiffness), -C (function), and Knee Injury and Osteoarthritis Outcome Score-Quality of Life (KOOS-QoL) after each injection. Initiative in Methods, Measurements and Pain Assessment in Clinical Trials (IMMPACT) criteria were used to determine moderate and substantial treatment response. RESULTS:A total of 208 patients were enrolled and received the first injection of TA-ER; 179 (86.1%) received the second injection (median time to second injection: 16.6 weeks). Both injections were well tolerated, with no unexpected adverse events or significant radiographic changes at week 52. The magnitude and duration of clinical benefit after the first and second injections were similar, and most patients reported a substantial (≥ 50%) analgesic response after both doses. CONCLUSIONS:Repeat administration of TA-ER using a flexible dosing schedule timed to patient response was well tolerated, with no radiographic evidence of cartilage impact. Both injections resulted in similar improvements in OA symptoms across a broad spectrum of disease severity reflective of that seen in clinical practice. TRIAL REGISTRATION INFORMATION:ClinicalTrials.gov identifier: NCT03046446. FUNDING:Flexion Therapeutics, Inc. Plain language summary available for this article.

Project description:Background/aimsNeonatal onset Urea cycle disorders (UCDs) can be life threatening with severe hyperammonemia and poor neurological outcomes. Glycerol phenylbutyrate (GPB) is safe and effective in reducing ammonia levels in patients with UCD above 2 months of age. This study assesses safety, ammonia control and pharmacokinetics (PK) of GPB in UCD patients below 2 months of age.MethodsThis was an open-label study in UCD patients aged 0 - 2 months, consisting of an initiation/transition period (1 - 4 days) to GPB, followed by a safety extension period (6 months to 2 years). Patients presenting with a hyperammonemic crisis (HAC) did not initiate GPB until blood ammonia levels decreased to below 100 µmol/L while receiving sodium phenylacetate/sodium benzoate and/or hemodialysis. Ammonia levels, PK analytes and safety were evaluated during transition and monthly during the safety extension for 6 months and every 3 months thereafter.ResultsAll 16 patients with UCD (median age 0.48 months, range 0.1 to 2.0 months) successfully transitioned to GPB within 3 days. Average plasma ammonia level excluding HAC was 94.3 µmol/L at baseline and 50.4 µmol/L at the end of the transition period (p = 0.21). No patient had a HAC during the transition period. During the safety extension, the majority of patients had controlled ammonia levels, with mean plasma ammonia levels lower during GPB treatment than baseline. Mean glutamine levels remained within normal limits throughout the study. PK analyses indicate that UCD patients <2 months are able to hydrolyze GPB with subsequent absorption of phenylbutyric acid (PBA), metabolism to phenylacetic acid (PAA) and conjugation with glutamine. Plasma concentrations of PBA, PAA, and phenylacetylglutamine (PAGN) were stable during the safety extension phase and mean plasma phenylacetic acid: phenylacetylglutamine ratio remained below 2.5 suggesting no accumulation of GPB. All patients reported at least 1 treatment emergent adverse event with gastroesophageal reflux disease, vomiting, hyperammonemia, diaper dermatitis (37.5% each), diarrhea, upper respiratory tract infection and rash (31.3% each) being the most frequently reported.ConclusionsThis study supports safety and efficacy of GPB in UCD patients aged 0 -2 months who cannot be managed by dietary protein restriction and/or amino acid supplementation alone. GPB undergoes intestinal hydrolysis with no accumulation in this population.

Dataset Information

Safety and Efficacy of Repeat Open-Label AbobotulinumtoxinA Treatment in Pediatric Cerebral Palsy.

Publications

Safety and Efficacy of Repeat Open-Label AbobotulinumtoxinA Treatment in Pediatric Cerebral Palsy.

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