A novel design for a dose finding, safety, and drug interaction study of an antiepileptic drug (retigabine) in early clinical development

International Journal of Clinical Pharmacology and Therapeutics

Volumn 52, Issue 6, 2014, Pages 509-518

  Sachdeo, Rajesh ^a   Partiot, Arnaud ^b,h   Biton, Victor ^c   Rosenfeld, William E ^d   Nohria, Virinder ^e   Tompson, Debra ^f   DeRossett, Sarah ^g   Porter, Roger J ^b,i  

^a NJ Comp Epilepsy Center Capital Health Neuroscience Department   (United States)

^b PFIZER INC   (United States)

^c Arkansas Epilepsy Program   (United States)

^d Comprehensive Epilepsy Care Center for Children and Adults ^*  (United States)

^e GlaxoSmithKline ^*  (United States)

^f GLAXOSMITHKLINE   (United Kingdom)

^g GLAXOSMITHKLINE   (United States)

^h SHIRE   (United States)

ⁱ UNIVERSITY OF PENNSYLVANIA   (United States)

Author keywords

Antiepileptic drug; Epilepsy; Ezogabine; Retigabine; Seizure

Indexed keywords

ALANINE AMINOTRANSFERASE; ASPARTATE AMINOTRANSFERASE; CARBAMAZEPINE; PHENYTOIN; RETIGABINE; TOPIRAMATE; VALPROIC ACID;

ABDOMINAL PAIN; ABNORMAL VISION; ADULT; AGED; AMNESIA; ANXIETY NEUROSIS; AREA UNDER THE CURVE; ARTICLE; ASTHENIA; CAUSE OF DEATH; CEREBROVASCULAR ACCIDENT; CONFUSION; COORDINATION DISORDER; DIPLOPIA; DISEASE CLASSIFICATION; DISEASE CONTROL; DIZZINESS; DOSE CALCULATION; DRUG ANTAGONISM; DRUG CLEARANCE; DRUG DESIGN; DRUG DOSE INCREASE; DRUG DOSE REDUCTION; DRUG DOSE REGIMEN; DRUG DOSE TITRATION; DRUG EFFICACY; DRUG SAFETY; DRUG TOLERABILITY; DYSARTHRIA; DYSPEPSIA; DYSPNEA; ELECTROCARDIOGRAM; FATIGUE; FEMALE; FOCAL EPILEPSY; GENERALIZED EPILEPSY; HEADACHE; HEALING IMPAIRMENT; HUMAN; HYPESTHESIA; HYPOXIA; LABORATORY TEST; MAJOR CLINICAL STUDY; MALE; MAXIMUM TOLERATED DOSE; MORBIDITY; NAUSEA; NEUROLOGIC EXAMINATION; OPEN STUDY; PARANOIA; PHYSICAL EXAMINATION; PLEURA DISEASE; PNEUMONIA; RASH; RISK REDUCTION; SEIZURE; SOMNOLENCE; SPEECH DISORDER; TREATMENT DURATION; TREMOR; UNSPECIFIED SIDE EFFECT;

ADOLESCENT; ADULT; ANTICONVULSANTS; CARBAMATES; DRUG ADMINISTRATION SCHEDULE; DRUG DOSAGE CALCULATIONS; DRUG INTERACTIONS; DRUG THERAPY, COMBINATION; EPILEPSIES, PARTIAL; EPILEPSY, GENERALIZED; FEMALE; HUMANS; MALE; MAXIMUM TOLERATED DOSE; MIDDLE AGED; PATIENT SAFETY; PHENYLENEDIAMINES; RESEARCH DESIGN; RISK ASSESSMENT; TIME FACTORS; TREATMENT OUTCOME; UNITED STATES; YOUNG ADULT;

EID: 84902126805     PISSN: 09461965     EISSN: None     Source Type: Journal    
DOI: 10.5414/CP202081     Document Type: Article

References (12)

1. Dailey JW, Cheong JH, Ko KH, Adams-Curtis LE, Jobe PC. Anticonvulsant properties of D-20443 in genetically epilepsy-prone rats: prediction of clinical response. Neurosci Lett. 1995; 195: 77-80. CrossRef PubMed
2. Rostock A, Tober C, Rundfeldt C, Bartsch R, Engel J, Polymeropoulos EE, Kutscher B, Löscher W, Hönack D, White HS, Wolf HH. D-23129: a new anticonvulsant with a broad spectrum activity in animal models of epileptic seizures. Epilepsy Res. 1996; 23: 211-223. CrossRef PubMed (Pubitemid 26176549)
3. Tober C, Rostock A, Rundfeldt C, Bartsch R. D-23129: a potent anticonvulsant in the amygdala kindling model of complex partial seizures. Eur J Pharmacol. 1996; 303: 163-169. CrossRef PubMed (Pubitemid 26200668)
4. Porter RJ, Nohria V, Rundfeldt C. Retigabine. Neurotherapeutics. 2007; 4: 149-154. CrossRef PubMed (Pubitemid 46107330)
5. Rundfeldt C, Netzer R. The novel anticonvulsant retigabine activates M-currents in Chinese hamster ovary-cells tranfected with human KCNQ2/3 subunits. Neurosci Lett. 2000; 282: 73-76. Cross-Ref PubMed (Pubitemid 30129172)
6. Porter RJ, Baulac M, Nohria V. Clinical development of drugs for epilepsy: a review of approaches in the United States and Europe. Epilepsy Res. 2010; 89: 163-175. CrossRef PubMed
7. Sachdeo RC, Ferron GM, Partiot AM, Biton V, Rosenfeld WE, Porter RJ, Fritz T, Althouse S, Troy SM. An early determination of drug-drug interactions between valproic acid, phenytoin, carbamazepine, or topiramate and retigabine in epileptic patients. Neurology. 2001; 56: A331-A332.
8. Sachdeo RC, Sachdeo SK, Walker SA, Kramer LD, Nayak RK, Doose DR. Steady-state pharmacokinetics of topiramate and carbamazepine in patients with epilepsy during monotherapy and concomitant therapy. Epilepsia. 1996; 37: 774-780. CrossRef PubMed (Pubitemid 26276948)
9. Ferron GM, Paul J, Fruncillo R, Richards L, Knebel N, Getsy J, Troy S. Multiple-dose, linear, dose-proportional pharmacokinetics of retigabine in healthy volunteers. J Clin Pharmacol. 2002; 42: 175-182. CrossRef PubMed (Pubitemid 34101350)
10. Porter RJ, Partiot A, Sachdeo R, Nohria V, Alves WM; 205 Study Group. Randomized, multicenter, dose-ranging trial of retigabine for partial-onset seizures. Neurology. 2007; 68: 1197-1204. Cross-Ref PubMed (Pubitemid 46608467)
11. Brodie MJ, Lerche H, Gil-Nagel A, Elger C, Hall S, Shin P, Nohria V, Mansbach H; on behalf of the RESTORE 2 Study Group. Efficacy and safety of adjunctive retigabine/ezogabine in refractory partial epilepsy. Neurology. 2010; 75: 1817-1824. CrossRef PubMed
12. French JA, Abou-Khalil BW, Leroy RF, Yacubian EM, Shin P, Hall S, Mansbach H, Nohria V; RESTORE 1/Study 301 Investigators. Randomized, double-blind, placebo-controlled trial of ezogabine (retigabine) in partial epilepsy. Neurology. 2011; 76: 1555-1563. CrossRef PubMed