CONDUCTING THE RIGHT PROOF OF CONCEPT STUDY. Michael F. Egan, MD Clinical Neuroscience, Merck
|
|
- Betty Stevenson
- 5 years ago
- Views:
Transcription
1 CONDUCTING THE RIGHT PROOF OF CONCEPT STUDY Michael F. Egan, MD Clinical Neuroscience, Merck
2 Introduction Drugs for some CNS targets (e.g. alpha7, PDE10, glutamate targets, muscarinic M1/M4 agonist, etc) could demonstrate efficacy in more than one disorder. Drugs for cognition: schizophrenia & AD Drugs for psychosis/agitation: schizophrenia, bipolar disorder, AD What is the optimal strategy for demonstrating efficacy for targets with pleiotropic effects, given constraints in pharma? The development program for an H3 inverse agonist (H3IA) provides a case study (and lessons learned). histamine 3 receptor: release modulating autoreceptor. Possible therapeutic indications Attention/wake promoting: ADHD, excessive daytime somnolence Cognition: AD, schizophrenia Others: obesity, tremor, etc
3 Which indication to target: factors to consider Evidence for target validation Evidence for relevant target engagement and pharmacodynamic effect. Medical need & approved products POC study design: E.g. cost, duration of treatment, internal expertise, probability of failed trial Development Path: compare Ph 2 & Ph 3 requirements for approval Regulatory issues Commercial considerations Company considerations: risk tolerance, pipeline, etc
4 Background on histamine and H3 receptor: evidence for target validation Clinical evidence implicating histamine, a biogenic amine, in human disease: First generation H1 antagonist antihistamines are sedating and impair cognition (primarily attention) Suggests that increased histamine could reduce sedation, increase alertness. Genetic: weak evidence for association with weight gain Preclinical Histamine releasing neurons are active only in wake, H1 agonists promote wakefulness. H1 and H2 receptor-mediated actions are mostly excitatory; H3 receptors act as inhibitory auto- and heteroreceptors. Efficacy of H3 antagonists in psychosis and cognition models Amphetamine hyperactivity, PPI 5 choice serial reaction time task (attention) Radial arm maze and Y maze (working memory Morris Water Maze (episodic memory) Social recognition Task Other: H3 IA inhibits feeding & wt gain, reduces tremor, etc
5 H3 receptor function H3 IA H3R signaling and Histamine Esbenshade, 2006
6 H3 antagonists exhibit broad efficacy in preclinical models of cognition, making cognition indications attractive Esbenshade, 2006
7 Merck approach Consider H3 IA (MK-0249) for multiple indications, based on prior reports of efficacy in preclinical models, including: Excessive daytime sleepiness (EDS) Attention deficit hyperactivity disorder (ADHD) Cognition in Schizophrenia Alzheimer s disease (AD) Essential tremor (ET): Obesity (OB) Replicate results from preclinical models showing efficacy. Develop translatable biomarkers for target engagement and pharmacodynamic effects PET ligand for occupancy in preclinical studies and humans Alerting effects: qeeg Alerting effects: sleep deprivation study Cognition effects: scopolamine model Based on these results, consider optimal development strategy
8 MK-0249 Phase I PK Summary Single doses up to 150 mg well tolerated t½ ~ 14 hours; Tmax ~ 3-4 hours Dose-related insomnia >50 mg single doses Multiple doses (x 7 d) up to 12.5 mg well tolerated Higher doses associated with insomnia Alerting effects noted at 5-20 mg after single dose
9 Target engagement: model of receptor occupancy following multiple MK-0249 doses Predicted Receptor Occupancy (%) mg Predicted Steady State RO between Dosing Interval 2 mg 3 mg 4 mg 5 mg 90 6 mg 7 mg 8 mg 9 mg 10 mg Time (hr)
10 qeeg pharmacodynamic measures -related to wake promoting effects- show dose response to H3 IA with receptor occupancy as low as 60% qeeg dose-response for MK-3134 (~6h post-dose) Predicted Brain H3 RO Following Single MK-3134 Dose 20mg 5mg 1mg Predicted Receptor Occupancy (%) mg MK mg MK mg MK Time (hr) Conclusion: 1. H3 IA produces dose-dependent increase in power for higher frequencies on qeeg 2. Suggests H3IA may improve attention &, possibly, other aspects of cognition. AJ Verma et al., unpublished.
11 Phase 1 study: excessive daytime somnolence model shows wake promoting effects of 10 and 50 mg; less effective than modafinil Mean (min) Treatment Mean AUC (sd) MK mg (6181) MK mg (n=24) MK mg (6333) MK mg (n=24) Modafinil 200 mg (6350) Modafinil 200 mg (n=24) Placebo 7846 (4331) Placebo (n=24) am Hours
12 Scopolamine results: using Cogstate, 10 mg MK-0249 showed efficacy alone and combined with dopenezil (non-memory measures only) Cho, Maruff, Verma et al., 2011 Reaction time (RT) Choice RT Exec function Episodic memory Learning & memory Results support notion that H3IA has alerting effects (alone and with donepezil) but do not show improvement in episodic memory, important for AD,
13 What to do next? Proof of concept studies considered for several indications include the following Excessive daytime sleepiness (EDS) in sleep apnea: supported by qeeg results But MK-0249 was less effective than Modafinil POC trial in subjects with sleep apnea feasible Adult ADHD: supported by qeeg, scopolamine results POC trials are relatively expensive Cognition in AD, schizophrenia: Other supported by scopolamine results Large unmet medical need but POC trials are relatively expensive and POS less certain Essential tremor (ET): preclinical support only Ph 1B study in essential tremor has good face validity, ETHOH as active comparator Obesity (OB): preclinical support only 4-week Ph IIA weight loss study: relatively inexpensive, good predictive validity compared to Ph 3 trials.
14 Daytime sleepiness in patients with obstructive sleep apnea: no beneficial effect of MK-0249 on sleep latency using Maintenance of Wakefulness Test Design: 3 period X over 2 week treatment Doses: 5-12 mg/d; adaptive allocation Primary outcome: sleep latency using Maintenance of Wakefulness Test Results: modafinil but not MK-0249 increased latency to sleep during daytime test of sleepiness vs placebo Conclusion: MK-0249 not effective in sleep apnea from J. Herring et al., unpublished Baseline Week 2 Change From Baseline Mean Mean at Week 2 Treatment N (SE) (SE) Mean (95% CI) Placebo (0.61) MK mg MK mg MK mg MK mg MK-0249 (top 2 doses ) (0.61) (0.61) (0.61) (0.61) (0.61) Modafinil (0.61) (0.75) (2.00) (1.39) (1.09) (1.13) (0.85) (0.75) 1.06 ( -0.22, 2.34) ( -4.84, 3.03) 2.86 ( 0.15, 5.58) 1.54 ( -0.56, 3.65) 2.23 ( 0.04, 4.41) 1.88 ( 0.28, 3.49) 5.55 ( 4.08, 7.02)
15 Adult ADHD POC study: No effect of MK-0249 after 4 weeks of treatment on the ADHD Investigator Symptom Rating Scale Design: 2 period cross over incomplete block design Two 4 wk treatment periods with 1 wk washout Dose: 10 mg/d N= ~40/group Primary outcome : AISRC= ADHD Investigator Symptom Rating Scale Results AISRC at week 4: MK-0249 vs PBO p=0.341 Concerta vs PBO p=.001 Exploratory cognition measures: MK improved scores on the Stroop and CPT vs placebo, Concerta did not. Conclusion: MK-0249 not effective in adult ADHD Placebo MK-0249 Concerta from J. Herring et al., unpublished
16 Cognitive impairment in schizophrenia: no effect of MK-0129 on BACS cognition score after 4 weeks of treatment 50 MK-0249 / Placebo Placebo / MK Plac MK Mean BACS Total Score MK Plac Period 1 Period Practice effects over 1 st 3 administrations suggest assay sensitivity Visit
17 Mild-moderate AD: no effect of MK-0129 on cognition score after 4 weeks of treatment Randomized, double-blind, placebo controlled, parallel-group, ~ 70/arm Dose: 5 mg/d (predicted r/o ~ 85%) Outcome measures: 1) CNTB summary score (RT, list learning, visual memory); 2) ADAS cog 11 2 CNTB summary score Deterioration Improvement MK-0249 Placebo p= Week p=.28 N=52 N=62
18 MK-0249: Phase 2 Summary Excessive daytime sleepiness (EDS) Results : MK-0249 not effective (modafnil superior to placebo) Attention deficit hyperactivity disorder (ADHD ): Ph IIA study Results: MK-0249 not effective (Concerta superior to placebo) Trends for improvement in some cognitive domains insufficient to improve clinical outcome Dementia of the Alzheimer s type (DAT): Ph IIA study Results: MK-0249 not effective after 4 wks ~85% r/o Questions re dose & duration, Cognition in Schizophrenia : Ph IIA study Results: MK-0249 not effective when added to atypical antipsychotics Essential tremor (ET): POC in single dose Ph IB model in patients with ET Results: ETOH effective, MK-0249 not effective Obesity (OB): 4-week Ph IIA weight loss study Results: Sibutramine effective, MK-0249 not effective,
19 Lessons learned by indication Excessive daytime sleepiness (EDS) & ADHD Good translational path but Biomarkers not predictive Active comparators: confirm trial validity Target validation: lacking AD study Scopolamine model not predictive. Target validation: lacking Cognition in Schizophrenia Study Protocol issues: crossover design, use of antipsychotics with H1 affinity. Clinical & preclinical models not predictive. Target validation: lacking Essential tremor & Obesity Models not predictive Target validation: lacking
20 Lessons learned regarding overall strategy Multiple POC studies using one compound and overlapping biomarker set was efficient and provided useful lessons learned for multiple indications Target validation: not good enough Future target selection criteria should be revised: stronger support needed for primary indications Animal models: poorly predictive of efficacy in humans clearly not sufficient; unclear if efficacy in animal models is necessary for human efficacy should not be used for target validation. Biomarker development: For CNS, showing target engagement is useful for dose selection and suggesting that hypotheses were adequately tested. Recommendation: pick one indication with best evidence for target validation.
21 Acknowledgments Strategy Darryle Schoepp Bill Potter David Michelson Richard Hargreaves Clinical Pharmacology Robert Iannone Keith Gottesdiener Gail Murphy Experimental medicine AJ Verma Bill Cho Gary Herman Sabrina Fox-Bosetti Basic John Renger Nicole Calder Kristine Cerchio Clinical Neuroscience Joe Herring Mike Egan Michael Ryan Christopher Lines Regina Gottwald Lyn Harper-Mozley David Michelson Basic John Renger Nicole Calder Kristine Cerchio Imaging Richard Hargreaves Statistics John Placza Cynthia Gargano Lian Liu Yahong Peng Xin Zhao Ying Zhang, Duane Snavely
22 Back up slides
23 Possible short term effect on ADAS-Cog Total Score Lack of 4 wks and failure on primary endpoint suggest lack of clinically relevant, persistent efficacy. Questions: Was 4 week treatment too short? Was dose too low? Was half life too long? Deterioration Improvement p=.004** p=.72 N=65 N=68 2 MK-0249 Placebo Week
24 Phase 1B study in subjects with essential tremor after a single dose of MK-0249 compared to ETOH Single dose design, N = 18 subjects with > 18 years (mean) with ET 3-period crossover MK-0249 (25 mg), Pbo and IV EtOH Primary Endpoint: Accelerometry-based laboratory tremorography Conclusion: Single dose MK-0249 did not improve tremor in ET patients Max Power Glove B-F (uv) Kinetic (%) Time (min) MK-0249 Pbo EtOH
25 Design of POC study in schizophrenia for cognitive impairment 2 period cross over with 1 wk washout & 1 wk placebo run in Dose: 10 mg/d 40 stable outpatients with schizophrenia Primary outcome measure: BACS
26 MK week Obesity Phase IIA Results 3 Mean Weight Change Over Time Change in Body Weight (kg) = Placebo = MK-0249 = Sibutramine Week
27 Summary of 3 EM qeeg studies with H3 Inverse agonists : Spectral ratios are shown comparing drug vs. placebo Data are shown for the highlighted electrodes. There was significant regional heterogeneity if spectral ratio pattern seem for different electrodes. Fitted mean value 95% CI
28 Target occupancy vs. qeeg pharmacodynamics for MK-3134 qeeg dose-response for MK-3134 (~6h post-dose) Predicted Brain H3 RO Following Single Oral MK-3134 Doses in Healthy Yong Male Subjects (Fast) 20mg 5mg 1mg Dark symbols on line indicate statistical significance, even after correcting for multiplicity (60 frequencies). Predicted Receptor Occupancy (%) mg MK mg MK mg MK Time (hr)
29 Study Design Summary Design Double-blind, two period crossover study MK vs placebo Each arm=4 wks, one wk washout in between Single blind 8 day run in to allow practice test sessions (3 total) for cognitive battery to maximize practice effect. Patients: stable outpatients with mild-moderate sx, 6 th grade reading (or better). Concomitant antipsychotic medication: stable dose x 2mos or more. Dose: MK-0249: >85% RO at 10 mg/d, down titration (after 3 d) to 7mg (>80% RO). MK-0577: >90% RO at 10 mg/d, down titration (after 3 d) to 5mg (>90% RO). Increase back to 10 mg/d not permitted. Results for MK-0249: 6 MK and 3 placebo pts reduced dose. Screening Period: Days -30 to -14.
30 Outcome measures Primary: Global summary score from Brief Assessment of Cognition in Schizophrenia (BACS) Secondary (compiled from BACS and Penn s CNP) MK-0557 Working Memory Executive Function Episodic Memory MK-0249 Attention Episodic Memory Working Memory Tertiary Positive and Negative Syndrome Scale (PANSS) Clinical Global Impression Severity of Illness Scale (CGI-S)
31 MK-0249: Demographics MK mg / PBO PBO / MK mg Total Gender n (%) n (%) n (%) Male 20 (71.4) 20 (74.1) 40 (72.7) Female 8 (28.6) 7 (25.9) 15 (27.3) Age (YEARS) Mean 30.7 yr 32.5 yr 31.6 yr SD Race n (%) n (%) n (%) ASIAN 10 (35.7) 10 (37.0) 20 (36.4) WHITE 18 (64.3) 17 (63.0) 35 (63.6)
ACTELION S NEW DUAL OREXIN RECEPTOR ANTAGONIST
ACTELION S NEW DUAL OREXIN RECEPTOR ANTAGONIST Investor Webcast July 2016 Copyright The following information contains certain forward-looking statements, relating to the company s business, which can
More informationAdaptive Design in CIAS
Adaptive Design in CIAS or If you don t know where you re going, any road will get you there Michael Sand, PhD, MPH Senior Clinical Program Leader, CNS Boehringer Ingelheim Disclosures I m an employee
More informationCHALLENGES OF RECOGNIZING AND TREATING EXCESSIVE SLEEPINESS
CHALLENGES OF RECOGNIZING AND TREATING EXCESSIVE SLEEPINESS Russell Rosenberg, Ph.D. Neurotrials Research and Atlanta School of Sleep Medicine DISCLOSURES Research grant funds from: Merck Jazz Pharmaceuticals
More informationCorporate Presentation August 6, 2015
Corporate Presentation August 6, 2015 Creating the Next Generation of CNS Drugs Forward-Looking Statement This presentation contains forward-looking statements. These statements relate to future events
More informationCognitive Neuroscience Treatment Research to Improve Cognition in Schizophrenia
Cognitive Neuroscience Treatment Research to Improve Cognition in Schizophrenia Anatomy of A Translation: A Proposed Framework for Optimizing a Cognitive Task for Use in a Clinical Trial or how the heck
More informationAdvisory Boards -- Dainippon Sumito Pharma; Takeda and Lundbeck. Off-label data included for Mirapex (pramipexole)
Disclosures Advisory Boards -- Dainippon Sumito Pharma; Takeda and Lundbeck Off-label data included for Mirapex (pramipexole) Funding from NIMH; Stanley Medical Research Institute; NARSAD A Brief History
More informationAugust 7, Q Financial Results
August 7, 2018 Q2 2018 Financial Results 1 Agenda Today s Speakers Paul Cox, Senior Director, Investor Relations Jeff Jonas, M.D., Chief Executive Officer Steve Kanes, M.D., Ph.D., Chief Medical Officer
More informationIndex. sleep.theclinics.com. Note: Page numbers of article titles are in boldface type.
Note: Page numbers of article titles are in boldface type. A Accidents, risk of, with insufficient sleep, 318 Acquired immunodeficiency syndrome (AIDS), comorbid with narcolepsy, 298 299 Actigraphy, in
More informationPerspective on methodological challenges: How Phase 2 studies influence design & conduct of Phase 3
Perspective on methodological challenges: How Phase 2 studies influence design & conduct of Phase 3 Ilise Lombardo, M.D. Vice President, Clinical Research FORUM Pharmaceuticals 1 Objective: Overview Describe
More informationSchizophrenia Battery
Schizophrenia Battery Cantab Schizophrenia Battery A c c e l e r a t e t h e d e v e l o p m e n t o f s a f e a n d e f f e c t i v e m e d i c i n e s Fast, reliable and highly sensitive, the Cantab
More informationThe Opportunity: Superior treatment of narcolepsy and cataplexy SKL-N05
The Opportunity: Superior treatment of narcolepsy and cataplexy SKL-N05 1 TABLE OF CONTENTS Highlights Clinical Trials Narcolepsy Profile Ancillary Pharmacology Mechanism of Action Preclinical Pharmacology
More informationDrug Review Rozerem (ramelteon)
Drug Review Rozerem (ramelteon) Introduction 1 Ramelteon is a melatonin receptor agonist with affinity for MT 1 and MT 2 and selectivity over the MT 3 receptor. The activity at the MT 1 and MT 2 receptors
More informationUpdate on First Psychotic Episodes in Childhood and Adolescence. Cheryl Corcoran, MD Assistant Professor of Psychiatry Columbia University
Update on First Psychotic Episodes in Childhood and Adolescence Cheryl Corcoran, MD Assistant Professor of Psychiatry Columbia University Childhood-Onset Psychosis 8% of psychiatrically referred youth
More informationThe wake-promoting agent modafinil is an effective
Excessive sleepiness associated with narcolepsy lasts throughout the waking day. The authors conducted two randomized, double-blind studies to compare the efficacy of modafinil once-daily versus split
More information) and serotonin Type 2 (5-HT 2A
Latuda (lurasidone HCl) Fact Sheet Schizophrenia FREQUENTLY ASKED QUESTIONS What type of patient with schizophrenia is appropriate for LATUDA? LATUDA is an atypical antipsychotic agent indicated for the
More informationSurveillance report Published: 26 October 2017 nice.org.uk
Surveillance report 2017 Bipolar disorder: assessment and management (2014) NICE guideline Surveillance report Published: 26 October 2017 nice.org.uk NICE 2017. All rights reserved. Subject to Notice of
More informationAXOVANT SCIENCES LTD. JEFFERIES HEALTHCARE CONFERENCE. Axovant Sciences Corporate Presentation -- June 2017 For Investor Use Only
AXOVANT SCIENCES LTD. JEFFERIES HEALTHCARE CONFERENCE JUNE 7, 2017 FORWARD-LOOKING STATEMENTS Statements made in this presentation contain forward-looking statements, including statements regarding Axovant
More informationExperimental Medicine and Psychiatry Drug Development. John H. Krystal, M.D. Yale University
Experimental Medicine and Psychiatry Drug Development John H. Krystal, M.D. Yale University Four problems We don t know the disorders sufficiently The biology is complex and heterogeneous We have animal
More informationSwitching antipsychotics: Basing practice on pharmacology & pharmacokinetics
Switching antipsychotics: Basing practice on pharmacology & pharmacokinetics John Donoghue Liverpool L imagination est plus important que le savoir Albert Einstein Switching Antipsychotics: Objectives
More informationPharmacotherapy of psychosis and schizophrenia in youth
Pharmacotherapy of psychosis and schizophrenia in youth Benedetto Vitiello Pavia, 2 December 2017 Disclosure Benedetto Vitiello, M.D. Professor of Child and Adolescent Neuropsychiatry University of Turin,
More informationInsomnia Agents (Sherwood Employer Group)
Insomnia Agents (Sherwood Employer Group) BCBSKS will review Prior Authorization requests Prior Authorization Form: https://www.bcbsks.com/customerservice/forms/pdf/priorauth-6058ks-st-ippi.pdf Link to
More informationCorporate Presentation. September 25, 2017
Corporate Presentation September 25, 2017 Safe Harbor Statement This presentation contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. These forward-looking
More informationCariprazine is a newly approved
Cariprazine for schizophrenia and bipolar I disorder Gregory Mattingly, MD, and Richard Anderson, MD, PhD Cariprazine is a newly approved (September 2015) dopamine D3/D2 receptor partial agonist with higher
More informationGanaxolone as a Treatment for Drug-Resistant Epilepsy in Children
Ganaxolone as a Treatment for Drug-Resistant Epilepsy in Children ANTIEPILEPTIC DRUG and DEVICE TRIALS XIII May 13-15, 2015 Turnberry Isle Miami Hotel Gail M. Farfel, PhD Chief Development & Regulatory
More informationThe difficulties in going from P2 to P3 in CNS trials Red flags from a recent CIS program. ISCTM February 2017
The difficulties in going from P2 to P3 in CNS trials Red flags from a recent CIS program ISCTM February 2017 1 CIS Phase 3 study design (EVP-6124-015/016) Two identical, global, placebo controlled, 6-month
More information3/19/2018. Cynthia King, MD Associate Professor of Psychiatry UNMSOM. Autism Spectrum Disorder
Cynthia King, MD Associate Professor of Psychiatry UNMSOM Autism Spectrum Disorder 1 Identify three behavioral health concerns in ASD Identify three common families of medication that may be supportive
More information3/19/2018. Cynthia King, MD Associate Professor of Psychiatry UNMSOM
Cynthia King, MD Associate Professor of Psychiatry UNMSOM 1 2 Autism Spectrum Disorder 3 Identify three behavioral health concerns in ASD Identify three common families of medication that may be supportive
More informationStudy No.: Title: Rationale: Phase: Study Period: Study Design: Centers: Indication: Treatment: Objectives: Primary Outcome/Efficacy Variable:
The study listed may include approved and non-approved uses, formulations or treatment regimens. The results reported in any single study may not reflect the overall results obtained on studies of a product.
More informationCurriculum Vitae, David P. Walling, Ph.D. David P. Walling, Ph.D. Collaborative Neuroscience Network, LLC
CONTACT INFORMATION: Site Selection and Information: Bobbie Theodore, Alliance Director Tel. (916) 939-6696 Fax (208) 575-3169 Email: clinicaltrials@alliancesites.com AFFILIATIONS: Collaborative Neuroscience
More informationClinical Trial Synopsis TL , NCT#
Clinical Trial Synopsis, NCT#00492011 Title of Study: A Randomized, Double-Blind, Placebo-Controlled, Parallel-Group Study to Evaluate the Ability of Ramelteon 1 mg, 4 mg, and 8 mg to Alleviate the Insomnia
More informationCollaborating to Develop Digital Biomarkers with Passive Data Collection
Collaborating to Develop Digital Biomarkers with Passive Data Collection Iain Simpson IXICO June 2018 1 Setting of Data Collection Market evolution: biosensors and digital biomarkers Clinic Home Digital
More informationStudy Centers: This study was conducted in 2 centers in Italy.
Title of Trial: A randomised, double-blind, placebo-controlled, two-period, two-sequence-crossover interaction study to assess the effect of safinamide on levodopa pharmacokinetics in subjects with Parkinson
More informationRestful Sleep or Getting Up to Eat? Suvorexant (Belsomra )
Restful Sleep or Getting Up to Eat? Suvorexant (Belsomra ) Alyssa Penick, PharmD PGY1 Pharmacy Resident UC Health- University of Cincinnati Medical Center Insomnia Most common sleep disorder Defined as
More informationThe clinical trial information provided in this public disclosure synopsis is supplied for informational purposes only.
The clinical trial information provided in this public disclosure synopsis is supplied for informational purposes only. Please note that the results reported in any single trial may not reflect the overall
More informationIan McKeith MD, F Med Sci, Professor of Old Age Psychiatry, Newcastle University
Ian McKeith MD, F Med Sci, Professor of Old Age Psychiatry, Newcastle University Design of trials in DLB and PDD What has been learnt from previous trials in these indications and other dementias? Overview
More informationPharmacy Benefit Determination Policy
Policy Subject: CNS Stimulant Medications Policy Number: SHS PBD06 Category: CNS Drugs Policy Type: Medical Pharmacy Department: Pharmacy Product (check all that apply): Group HMO/POS ASO PPO Individual
More informationEvaluating Drug Effects on the Ability to Operate a Motor Vehicle Guidance for Industry
Evaluating Drug Effects on the Ability to Operate a Motor Vehicle Guidance for Industry DRAFT GUIDANCE This guidance document is being distributed for comment purposes only. Comments and suggestions regarding
More informationAbbreviated Class Review: Long-Acting Injectable Antipsychotics
Copyright 2012 Oregon State University. All Rights Reserved Drug Use Research & Management Program Oregon State University, 500 Summer Street NE, E35, Salem, Oregon 97301-1079 Phone 503-947-5220 Fax 503-947-1119
More informationCorporate Presentation April 2018
NASDAQ: GNMX Corporate Presentation April 2018 2018, Aevi Genomic Medicine Forward-Looking Statement This presentation includes certain estimates and other forward-looking statements within the meaning
More informationADNI Experience on Developing Biomarker Tools as Example of An Approach to Catalyzing Dry AMD Drug Development
ADNI Experience on Developing Biomarker Tools as Example of An Approach to Catalyzing Dry AMD Drug Development Wm Z Potter, MD, PhD Sr. Advisor, NIMH IOM, Nov 15, 2014 Disclosures Former employee of Lilly
More informationStudy No: Title : Rationale: Phase: Study Period: Study Design: Centres: Indication: Treatment: Objectives: Statistical Methods:
Study No: MNK111587 Title : A healthy volunteer repeat dose study to evaluate; the safety, tolerability, pharmacokinetics, effects on the pharmacokinetics of midazolam and the neurokinin-1 (NK1) receptor
More informationSection 2: Multivariate or Multiple Domain Methods Aldurazyme Responder Index
Disclaimer: Presentation slides from the Rare Disease Workshop Series are posted by the Kakkis EveryLife Foundation, for educational purposes only. They are for use by drug development professionals and
More information2017 Year-end Results and Corporate Update
NASDAQ: GNMX 2017 Year-end Results and Corporate Update March 13, 2018 2018, Aevi Genomic Medicine Forward-Looking Statement This presentation includes certain estimates and other forward-looking statements
More informationPimavanserin Top-Line Results Phase III Parkinson s Disease Psychosis Trial (-020 Study) Creating the Next Generation of CNS Drugs
Pimavanserin Top-Line Results Phase III Parkinson s Disease Psychosis Trial (-020 Study) Creating the Next Generation of CNS Drugs Forward-Looking Statement This presentation contains forward-looking statements.
More informationCurriculum Vitae, Michael J. Downing, M.D.
CONTACT INFORMATION: Site Selection and Information: Bobbie Theodore, Alliance Director Tel. (916) 939-6696 Fax (208) 575-3169 Email: clinicaltrials@alliancesites.com PROFESSIONAL AFFILIATIONS: Michael
More informationSedative-Hypnotics. Sedative Agents (General Considerations)
Sedative Agents (General Considerations) No best sedative agent Any agent given in sufficient dosage can produce any level of sedation Intravenous dosing is more predictable then intramuscular or oral
More informationPOPULATION PHARMACOKINETICS RAYMOND MILLER, D.Sc. Daiichi Sankyo Pharma Development
POPULATION PHARMACOKINETICS RAYMOND MILLER, D.Sc. Daiichi Sankyo Pharma Development Definition Population Pharmacokinetics Advantages/Disadvantages Objectives of Population Analyses Impact in Drug Development
More information- The safety and efficacy of oral, once-daily VRAYLAR was established in a clinical trial program involving more than 2,700 patients
Allergan and Gedeon Richter Plc. Receive FDA Approval of VRAYLAR TM (cariprazine) for Treatment of Manic or Mixed Episodes of Bipolar I Disorder and Schizophrenia in Adults - The safety and efficacy of
More informationESSENTIAL PSYCHOPHARMACOLOGY, Neurobiology of Schizophrenia Carl Salzman MD Montreal
ESSENTIAL PSYCHOPHARMACOLOGY, 2011 Neurobiology of Schizophrenia Carl Salzman MD Montreal EVOLVING CONCEPTS OF SCHIZOPHRENIA Psychotic illness with delusions, hallucinations, thought disorder and deterioration;
More informationLurasidone: A New Antipsychotic For Schizophrenia. Objectives. Introduction. Pharmacology/Pharmacokinetics. Mechanism of Action. Mechanism of Action
Lurasidone: A New Antipsychotic For Schizophrenia Theodore Pikoulas, PharmD PGY2 Psychiatric Pharmacy Resident Louis Stokes Cleveland VAMC Objectives Review the pharmacology and the pharmacokinetics Identify
More informationCorporate Presentation
Corporate Presentation March 2018 Safe Harbor Statement Factors Affecting Future Performance This presentation contains "forward-looking" statements within the meaning of the United States Private Securities
More informationChallenges in Meeting International Requirements for Clinical Bioequivalence of Inhaled Drug Products
Challenges in Meeting International Requirements for Clinical Bioequivalence of Inhaled Drug Products Tushar Shah, M.D. Sr. VP, Global Respiratory Research and Development TEVA Pharmaceuticals 1 Presentation
More informationAlcoholism. Psychiatry. Alcoholism. Alcoholism. Certification. Certification
Alcoholism Psychiatry Liz Clark, D.O., MPH & TM FAOCOPM MY-2012 Except where absolute criteria exist (i.e., a current clinical diagnosis of alcoholism), as a medical examiner, you make the final determination
More informationIris Manor, MD. UK Adult ADHD Network 4th Annual Congress London, England September 11, 2014
Metadoxine Extended Release in Adults With Predominantly Inattentive Attention-Deficit/ Hyperactivity Disorder: A Randomized, Double-Blind, Placebo-Controlled, Single-Dose, Crossover Trial Disclosures
More informationLiz Clark, D.O., MPH & TM FAOCOPM
Liz Clark, D.O., MPH & TM FAOCOPM Except where absolute criteria exist (i.e., a current clinical diagnosis of alcoholism), as a medical examiner, you make the final determination as to whether the driver
More informationStudy No Title: Rationale: Phase: Study Period: Study Design: Centers: Indication: Treatment: Objectives: Study Endpoints: Pharmacokinetics:
The study listed may include approved and non-approved uses, formulations or treatment regimens. The results reported in any single study may not reflect the overall results obtained on studies of a product.
More informationEfficacy of Levetiracetam: A Review of Three Pivotal Clinical Trials
Epilepsia, 42(Suppl. 4):31 35, 2001 Blackwell Science, Inc. International League Against Epilepsy Efficacy of : A Review of Three Pivotal Clinical Trials Michael Privitera University of Cincinnati Medical
More informationSHORTENING TIMELINES AND IMPROVING EFFICIENCY IN DRUG DEVELOPMENT -Seamless drug development paradigms
SHORTENING TIMELINES AND IMPROVING EFFICIENCY IN DRUG DEVELOPMENT -Seamless drug development paradigms Claudia Filozof, MD PhD Executive Medical Director Covance Challenges in Clinical Development in NASH
More informationTherapeutic Uses of Noninvasive Brain Stimulation Current & Developing
Therapeutic Uses of Noninvasive Brain Stimulation Current & Developing Alvaro Pascual-Leone, MD, PhD Berenson-Allen Center for Noninvasive Brain Stimulation Harvard Catalyst Beth Israel Deaconess Medical
More informationNovember 2, Q Financial Results
November 2, 2017 Q3 2017 Financial Results Agenda Today s Speakers Paul Cox, Senior Director, Investor Relations Jeff Jonas, M.D., Chief Executive Officer Steve Kanes, M.D., Ph.D., Chief Medical Officer
More informationINVESTOR PRESENTATION JEFFERIES 2013 HEALTHCARE CONFERENCE. June 2013
INVESTOR PRESENTATION JEFFERIES 2013 HEALTHCARE CONFERENCE June 2013 Company disclaimer This presentation contains forward-looking statements that provide our expectations or forecasts of future events
More informationDrug Class Review. Pharmacologic Treatments for Attention Deficit Hyperactivity Disorder
Drug Class Review Pharmacologic Treatments for Attention Deficit Hyperactivity Disorder Final Update 5 Report July 2015 The purpose of reports is to make available information regarding the comparative
More informationClass Update: Oral Antipsychotics
Copyright 2012 Oregon State University. All Rights Reserved Drug Use Research & Management Program Oregon State University, 500 Summer Street NE, E35 Salem, Oregon 97301-1079 Phone 503-947-5220 Fax 503-947-1119
More informationSedative-Hypnotics & the Treatment of Hypersomnia October 22, 2018 Pharm 9002 Mark Beenhakker, Pharmacology
Sedative-Hypnotics & the Treatment of Hypersomnia October 22, 2018 Pharm 9002 Mark Beenhakker, Pharmacology markbeen@virginia.edu Glossary Anxiolytic: decreases anxiety Sedative: (1) decreases activity,
More informationStudy No.: Title: Rationale: Phase: Study Period: Study Design: Centres: Indication: Treatment: Objectives: Primary Outcome/Efficacy Variable:
The study listed may include approved and non-approved uses, formulations or treatment regimens. The results reported in any single study may not reflect the overall results obtained on studies of a product.
More informationAbbreviated Class Review: Long-Acting Injectable Antipsychotics
Copyright 2012 Oregon State University. All Rights Reserved Drug Use Research & Management Program Oregon State University, 500 Summer Street NE, E35, Salem, Oregon 97301-1079 Phone 503-947-5220 Fax 503-947-1119
More informationPhase 2b dose selection, leveraging comparator data through multidisciplinary modeling & simulation
Phase 2b dose selection, leveraging comparator data through multidisciplinary modeling & simulation Thomas Kerbusch Thomas Kerbusch* (1), Russ Wada (2), Anthe Zandvliet (1), Kuenhi Tsai (6), Jing Su (6),
More informationMISCELLANEOUS AGENTS - ALPHA-AGONISTS
Documentation A. FDA Approved Indications ADHD (Clonidine, Guanfacine) Documentation B. Non-FDA approved, commonly used psychiatric indications 1. Alcohol and opiate dependence 2. Opioid withdrawal 3.
More informationIn February 2013, the FDA approved a
Long-acting injectable aripiprazole for adult schizophrenia Jana Lincoln, MD Depot formulation and once-monthly dosing might improve adherence in patients with schizophrenia 46 May 2013 In February 2013,
More informationTrial No.: RIS-USA-102 Clinical phase: III
SYNOPSIS Trial identification and protocol summary Company: Johnson & Johnson Pharmaceutical Research and Development, a division of Janssen Pharmaceutica, N.V. Finished product: Risperdal Active ingredient:
More informationIs Asenapine More Effective than Other Interventions in the Treatment of Adult Patients with Bipolar I Disorder?
Philadelphia College of Osteopathic Medicine DigitalCommons@PCOM PCOM Physician Assistant Studies Student Scholarship Student Dissertations, Theses and Papers 2012 Is Asenapine More Effective than Other
More informationSYNOPSIS. Risperidone-R064766: Clinical Study Report RIS-INT-24 (FOR NATIONAL AUTHORITY USE ONLY)
SYNOPSIS Protocol No.: RIS-INT-24 Psychosis in Alzheimer s disease (PAD) analysis Title of Study: Risperidone in the treatment of behavioral disturbances in demented patients: an international, multicenter,
More information+81-(0)
FOR IMMEDIATE RELEASE Contacts: Eisai Co., Ltd. Purdue Pharma L.P. Public Relations Department Danielle Lewis +81-(0)3-3817-5120 +1-203-588-7653 Positive New Data on Investigational Lemborexant Presented
More informationSYNOPSIS. Study Coordinator. Study centre(s)
Drug product: Seroquel Drug substance(s): Quetiapine Document No.: 1 Edition No.: 1 Study code: D1449C00005 Date: 02 January 2007 SYNOPSIS A Randomized, Parallel Group, Open Trial Examining the Safety,
More informationThe Opportunity: c-ibs and pain relief with confidence YKP10811
The Opportunity: c-ibs and pain relief with confidence YKP10811 1 TABLE OF CONTENTS Profile Summary Clinical Data Mode of Action Pharmacologic Profile Safety and Toxicity Profile ADME Overview vs. Competitors
More informationSupernus Pharmaceuticals
Supernus Pharmaceuticals Jefferies 2016 Healthcare Conference May 2016 1 Safe Harbor Statement This presentation and other matters discussed today or answers that may be given to questions asked include
More informationClinical Efficacy and Safety of Achieving Very Low LDL-C Levels With the PCSK9 Inhibitor Evolocumab in the FOURIER Outcomes Trial
Clinical Efficacy and Safety of Achieving Very Low LDL-C Levels With the PCSK9 Inhibitor Evolocumab in the FOURIER Outcomes Trial RP Giugliano, TR Pedersen, AC Keech, PS Sever, JG Park, and MS Sabatine,
More informationMonograph. Saphris /Sycrest (asenapine) Bipolar I disorder
Monograph Saphris /Sycrest (asenapine) Bipolar I disorder Contents 1. Overview 1.1 Disease background 1.2 2. Mechanism of action 2.1 Chemical structure 2.1 Receptor binding profile 2.1 3. Efficacy in manic
More informationAustedo. (deutetrabenazine) New Product Slideshow
Austedo (deutetrabenazine) New Product Slideshow Introduction Brand name: Austedo Generic name: Deutetrabenazine Pharmacological class: Vesicular monoamine transporter 2 (VMAT2) inhibitor Strength and
More informationPaliperidone: Clinical Protocol R076477SCH4012, CR Amendment INT-1
Paliperidone: Clinical Protocol R076477SCH4012, CR013771 Amendment INT-1 A Randomized, Double-Blind, Placebo- and Active-Controlled, Parallel-Group Study to Evaluate the Efficacy and Safety of a Fixed
More informationAtomoxetine (First known as Tomoxetine) (Adopted by the CCG until review and further notice)
New Medicine Report Document Status Atomoxetine (First known as Tomoxetine) (Adopted by the CCG until review and further notice) Post Suffolk D&TC Traffic Light Decision RED Date of Last Revision 12.07.04
More informationOpen Translational Science in Schizophrenia. Harvard Catalyst Workshop March 24, 2015
Open Translational Science in Schizophrenia Harvard Catalyst Workshop March 24, 2015 1 Fostering Use of the Janssen Clinical Trial Data The goal of this project is to foster collaborations around Janssen
More informationMerrill Lynch's Global Pharmaceutical, Biotechnology, and Medical Device Conference. February 7, 2007
Merrill Lynch's Global Pharmaceutical, Biotechnology, and Medical Device Conference February 7, 2007 Information related to forward-looking statements This presentation includes forward-looking statements
More informationSIFROL â. Contraindications Hypersensitivity to pramipexole or any other component of the product.
SIFROL â Composition 1 tablet contains 0.088, 0.18 & 0.7 mg (S) 2 amino 4,5,6,7-tetrahydro-6-propylamino-benzothiazole (= pramipexole base) equivalent to 0.125, 0.25 & 1 mg of pramipexole dihydrochloride
More informationClinical Trial Designs for RCTs focussing on the Treatment of Agitation in people with Alzheimer s disease
Clinical Trial Designs for RCTs focussing on the Treatment of Agitation in people with Alzheimer s disease Professor Clive Ballard Dr Byron Creese University of Exeter, UK Guardian guide for 2018: Top
More informationOverview of epidemiology of sleep and obesity risk
Overview of epidemiology of sleep and obesity risk Sanjay R. Patel MD, MS Director, Center for Sleep and Cardiovascular Outcomes Research Visiting Professor of Medicine University of Pittsburgh What is
More information475 GERIATRIC PSYCHOPHARMACOLOGY (p.1)
475 GERIATRIC PSYCHOPHARMACOLOGY (p.1) I. General Information? Use lower doses? Start low and go slow? Expect prolonged elimination ½ lives? Expect sedative-hypnotics to be dementing, to impair cognitive
More informationDrugs, Sleep & Wakefulness. Brian Koo Reena Mehra MD MS Kingman Strohl MD
Drugs, Sleep & Wakefulness Brian Koo Reena Mehra MD MS Kingman Strohl MD Things To Keep In Mind Many drugs effect sleep either causing insomnia or sedation Disruption of sleep and wakefulness may not be
More informationBELLUS Health and NEOMED Institute Transaction Licensing of BLU-5937 for Chronic Cough
BELLUS Health and NEOMED Institute Transaction Licensing of BLU-5937 for Chronic Cough February 28, 2017 r Investment Thesis BLU-5937: potential to be best-in-class drug addressing high unmet need Orally
More informationAntipsychotic Medications
TRAIL: Team Review of EVIDENCE REVIEW & RECOMMENDATIONS FOR LTC Behavioural and psychological symptoms of dementia (BPSD) refer to the non-cognitive symptoms of disturbed perception, thought content, mood
More informationMeccanismi fisiopatologici e trattamento dei disturbi metabolici in soggetti affetti da disturbo mentale grave
Meccanismi fisiopatologici e trattamento dei disturbi metabolici in soggetti affetti da disturbo mentale grave Francesco Bartoli, MD, PhD Università degli Studi di Milano Bicocca Ospedale San Gerardo di
More informationFDA Perspective on Disease Modification in Schizophrenia
FDA Perspective on Disease Modification in Schizophrenia Robert Levin, M.D. Clinical Team Leader Division of Psychiatry Products Food and Drug Administration Goals and Expectations Develop treatments that
More informationStudy Center(s): The study was conducted at 39 study sites in Japan.
SYNOPSIS Issue Date: 20 NOVEMBER 2012 Name of Sponsor/Company Janssen Pharmaceutical K. K. Name of Finished Product CONCERTA Name of Active Ingredient(s) Methylphenidate HCl Protocol No.: JNS001-JPN-A01
More informationPlease Join Us. International Psychogeriatric Association. Dependency Ratio. Geriatric Psychiatry in the 21st Century: A Global Perspective
International Psychogeriatric Association Please Join Us Geriatric Psychiatry in the 21st Century: A Global Perspective Jacobo Mintzer M.D. Executive Director Roper Saint Frances Clinical and Biotechnology
More informationIndex SLEEP MEDICINE CLINICS. Note: Page numbers of article titles are in boldface type. Cerebrospinal fluid analysis, for Kleine-Levin syndrome,
165 SLEEP MEDICINE CLINICS Index Sleep Med Clin 1 (2006) 165 170 Note: Page numbers of article titles are in boldface type. A Academic performance, effects of sleepiness in children on, 112 Accidents,
More informationLIHR La ricerca sulle malattie rare e le prospettive di cura per la malattia di Huntington. Neuroscience, the Future is Bright
LIHR La ricerca sulle malattie rare e le prospettive di cura per la malattia di Huntington Neuroscience, the Future is Bright Mauro Patroncini, MD Pipeline Product Strategy Leader Luisa De Stefano Head
More informationSYSTEMATIC REVIEW. Introduction. L. Citrome
SYSTEMATIC REVIEW for insomnia: a systematic review of the efficacy and safety profile for this newly approved hypnotic what is the number needed to treat, number needed to harm and likelihood to be helped
More informationInsomnia Treatment in Brief
Insomnia Treatment in Brief Project ECHO May 7, 2015 Jonathan Emens, M.D. Associate Professor, Departments of Psychiatry and Internal Medicine Oregon Health & Science University Staff Physician and Sleep
More informationWhat is Augmentation? How to diagnose? What to do?
What is Augmentation? How to diagnose? What to do? Diego Garcia-Borreguero Madrid, SPAIN Dopaminergics do work: The case of L-dopa 100 80.005.031.002.025 ns ns p-values PLM/h 60 40 Placebo L-Dopa 20 0
More information