Showing papers by "Kapil D. Sethi published in 2014"

Observational Study of IncobotulinumtoxinA for Cervical Dystonia or Blepharospasm (XCiDaBLE): Interim Results for the First 170 Subjects with Blepharospasm

Abstract: Background : XCiDaBLE is a large, prospective, observational “naturalistic” study evaluating Xeomin® for Cervical Dystonia or BLEpharospasm in the United States. We report the interim results from the blepharospasm cohort of XCiDaBLE. Methods : Subjects (≥18 years old) with blepharospasm were followed for two treatment cycles of incobotulinumtoxinA and monitored for 4 weeks after injection via interactive voice/web response system (IVRS/IWRS). The investigator‐reported scale includes the Clinical Global Impression Scale‐Severity subscale (CGI‐S). Patient‐reported outcome measures include the Patient Global Impression Scale‐Severity (PGI‐S) and ‐Improvement (PGI‐I) subscales, Jankovic Rating Scale (JRS), SF‐12v2® health survey, and Work Productivity and Activity Impairment questionnaire. Subjects are seen by the investigator at baseline (including the first injection), during the second injection, and at a final study visit (12 weeks after the second injection). Results : One hundred seventy subjects were included in this interim analysis. The majority of subjects were female (77.1%) and white (91.8%), and had previously been treated with botulinum toxins (96.5%). The mean total dose (both eyes) was 71.5 U of incobotulinumtoxinA for the first injection. PGI‐S, PGI‐I, and JRS scores were significantly improved 4 weeks after treatment (all p<0.0001). No differences were noted in either quality of life (QoL) or work productivity in this short assessment period. No unexpected adverse events occurred. Discussion : This is an interim study and assessment method based on an IVRS/IWRS. In this predominantly toxin‐experienced cohort, significant benefits in specific and global measures of disease severity were seen in the immediate post‐incobotulinumtoxinA injection period. It will be interesting to see if there are improvements in QoL with consistent individualized injections over a longer period.

Safety and Efficacy Study of ADS-5102 (Amantadine HCl) Extended Release Capsules in Levodopa-Induced Dyskinesia (EASED Study) (P4.053)

Abstract: OBJECTIVE: Investigate the safety and efficacy of 3 doses of once-nightly administration of ADS-5102 (amantadine HCl) extended release capsules for the treatment of levodopa-induced dyskinesia (LID) in Parkinson’s disease (PD) BACKGROUND: LID is a dose limiting adverse effect of PD treatment. Pharmacokinetic profile of ADS-5102 may improve tolerability and permit higher doses than immediate release amantadine leading to better LID treatment. DESIGN/METHODS: Randomized, double-blind, placebo-controlled, parallel-group study was conducted at 31 U.S. sites (NCT 01397422). PD patients with troublesome LID were randomized to placebo or one of 3 doses of ADS-5102 (260 mg, 340 mg, 420 mg), dosed once nightly for 8 weeks. The primary outcome measure was the change from baseline to week 8 in the Unified Dyskinesia Rating Scale (UDysRS) total score. Secondary outcome measures were: change from baseline in 24-hour PD patient diaries, the Movement Disorder Society-Unified Parkinson’s Disease Rating Scale (MDS-UPDRS) and the Clinician’s Global Impression of Change (CGI-C). RESULTS: 83 subjects were randomized. The study met its primary endpoint; both the 340 mg and 420 mg dose levels significantly reduced LID as measured by change in the UDysRS total score over 8 weeks vs placebo (p=0.005 and p=0.013, respectively). ON time without troublesome dyskinesia, as measured by diaries, increased by approximately 3 hours over 8 weeks vs placebo (260 mg p=0.004, 340 mg p=0.008 and 420 mg p=0.018). ADS-5102 at the 340 mg and 420 mg dose levels reduced motor complications of PD as measured by change from baseline to week 8 in MDS-UPDRS, Part IV (p=0.03, p=0.003, respectively). 75% of subjects assigned to the 340 mg dose level had a moderate to marked improvement in the CGI-C at week 8, versus 32% of placebo subjects. The most frequent AEs were constipation, dizziness, dry mouth and hallucinations. CONCLUSION: ADS-5102 in once nightly doses up to 420 mg was generally well tolerated and resulted in significant and dose-dependent improvements in LID. Study Supported by: Adamas Pharmaceuticals Disclosure: Dr. Pahwa has received personal compensation for activities with Teva Neuroscience, Merck Serono, Novartis, Medtronic Inc., GE Healthcare, Impax Laboratories, Ceregene, Noven, Adamas, and St. Jude Medical as a consultant. Dr. Pahwa has received personal compensation in an editorial capacity for the International Journal of Neuroscience. Dr. Tanner has received personal compensation for activities with AbbVie and Adamas Pharmaceuticals as a scientific advisor. Dr. Hauser has received personal compensation for activities with Abbott Laboratories, Allergan, Inc., AstraZeneca, Biotie Therapeutics Inc., Ceregene, Inc., Chelsea Therapeutics, Inc., GE Healthcare, Impax Laboratories, Inc., Ipsen Biopharmaceuticals, Inc., Lundbeck, Merck/MSD, Noven Pharmaceuticals, Inc., Strakan Pharmaceuticals. Dr. Hauser has received royalty, or license fee, or contractual rights payments from University of South Florida. Dr. Hauser has received research support from Abbott Laboratories, Addex Therapeutics, Allergan, Inc., AstraZeneca, Biotie Therapeutics Inc., Chelsea Therapeutics, Inc., GE Healthcare, and Impax Laboratories. Dr. Sethi has received personal compensation for activities with Synosia and Veloxis, ADAMAS, Impax Laboratories and Teva Neuroscience as a consultant, and with Merz Pharmaceuticals as an employee. Dr. Sethi has received research support from GlaxoSmithKline Inc., Teva Neuroscience, Acadia, and Impax Laboratories. Dr. Isaacson has received personal compensation for activities with Acadia, Allergan Inc., Brittania, Chelsea, General Electric, GlaxoSmithKline Inc., Impax Laboratories, Ipsen, Lundbeck, Medtronic Inc., Merz Pharma, Novartis, Teva Neuroscience, UCB Pharma, US World Meds. Dr. Isaacson has received research support from AbbVie, Acadia, ADAMAS, Addex, Allergan Inc., Allon, AstraZeneca, Biotie, Chelsea, Civitas, Eisai Inc., GlaxoSmithKline Inc., Ipsen, Kyowa, Eli Lilly & Co., Merck Schering, Merz Pharma, Michael J Fox Foundation, Novartis, Neurocrine, National Institutes of Health, Novartis, and Orion. Dr. Truong has received personal compensation for activities with Ipsen, Allergan Inc., Schering-Plough Corp., and Novartis as a consultant. Dr. Struck has nothing to disclose. Dr. Stempien has nothing to disclose. Dr. McClure has nothing to disclose. Dr. Went has received personal compensation for activities with Adamas Pharmaceuticals as an employee. Dr. Went holds stock and/or stock options in Adamas Pharmaceuticals which sponsored research in which Dr. Went was involved as an investigator.

Treatment of Involuntary Movements with Carbamazepine in Dystonic‐Choreoathetoid Cerebral Palsy

Abstract: Choreoathetoid movements are quite common in cerebral palsy (CP). This is the first report of a patient with choreoathetoid CP who was successfully treated with carbamazepine. Therefore, clinicians should try carbamazepine for involuntary movements in CP patients before pursuing other procudures.

Tacrolimus-Induced Tremor: Switching from Immediate-Release (IR-TAC) to LCP-Tacro Extended-Release Tacrolimus (LCPT) Reduces Tremor and Improves Quality of Life (P4.072)

Abstract: OBJECTIVE: : To determine if switching from (IR-TAC) to LCPT reduces TAC-associated tremor in kidney transplant recipients (KTR). BACKGROUND: TAC-associated tremor is common and most evident at peak concentrations. Reduction or cessation of TAC reduces tremor but may increase the risk for transplant rejection. LCP-Tacro (Veloxis Pharmaceuticals) is a novel MeltDose formulation of TAC that is administered once-daily with reduced peak andcomparable exposure, allowing it to be administered at ~30% less than IR-TAC. DESIGN/METHODS: We examined if converting stable IR-TAC patients who complain of tremor to LCPT results in improvement in hand tremor. Written informed consent was obtained from all subjects in this multicenter study. Tremor pre- and 7 days post-conversion was evaluated by independent, blinded neurologists using the Fahn-Tolosa-Marin (FTM) tremor rating scale and by accelerometry. The primary outcome measure was the change in the FTM total score. PGI-I (Patient Global Impression of Improvement) and the QUEST (Quality of Life in Essential Tremor) questionnaires were also obtained. RESULTS: 38/44 subjects had evaluable pre- and post FTM scores. The mean (SD) absolute change in FTM was -5.35 ([7.50]; P P P <0.0005) and the QUEST also showed improvement (mean (SD) absolute change was -7.04 (9.41), mean percent change was -39.08% (39.43) (P< 0.001)). CONCLUSIONS: : Results suggest IR-TAC-induced tremor may be ameliorated by switching to LCPT. The improvement in tremor appears clinically meaningful to neurologists based upon the FTM and accelerometry measurements and also meaningful to patients (PGI-I and QUEST). Study Supported by: Veloxis Pharmaceuticals Disclosure: Dr. Morgan has received personal compensation for activities with Teva Neuroscience, Veloxis, Oakstone, UCB Pharma, and as an expert witness in litigation involving neurological issues. Dr. Morgan has received research support from National Institutes of Health and National Parkinson Foundation. Dr. Langone has nothing to disclose. Dr. Nigro has nothing to disclose. Dr. Sethi has received personal compensation for activities with Synosia and Veloxis, ADAMAS, Impax Laboratories and Teva Neuroscience as a consultant, and with Merz Pharmaceuticals as an employee. Dr. Sethi has received research support from GlaxoSmithKline Inc., Teva Neuroscience, Acadia, and Impax Laboratories.