Supplementary webappendix
This webappendix formed part of the original submission and has been peer reviewed.
We post it as supplied by the authors.
Supplement to: Hauser RA, Hsu A, Kell S, et al, for the IPX066 ADVANCE-PD
investigators. Extended-release carbidopa-levodopa (IPX066) compared with
immediate-release carbidopa-levodopa in patients with Parkinson’s disease and motor
fluctuations: a phase 3 randomised, double-blind trial. Lancet Neurol 2013; published
online Feb 26. http://dx.doi.org/10.1016/S1474-4422(13)70025-5.
Investigators list
Canada
Mandar Jog (London Health Sciences Centre, London, ON); Tilak Mendis (Parkinson's and
Neurodegenerative Disorder Clinic, Ottawa, ON); Emmanuelle Pourcher (Clinique Sainte-Anne Memoire
and Mouvement, Quebec, QC)
France
Jean-Christophe Corvol (Hôpital de la Pitié Salpêtrière, Paris Cedex, 13 ILE-DE-FRANCE); Alain
Destée (Centre Hospitalier Regional Universitaire de Lille – Hôpital Salengro, Lille, NORD PAS-DECALAIS); Christine Tranchant (Centre Hospitalier Universitaire de Strasbourg – Hôpital Civil,
Strasbourg Cedex, ALSACE)
Germany
Reinhard Ehret (Neurologiepraxis, Berlin, BERLIN); Andreas Kupsch (Charité Campus Virchow
Klinikum, Berlin, BERLIN); Veneta Siefjediers (Praxis Dr. Veneta Siefjediers, Berlin, BERLIN);
Joachim Springub (Praxis für Neurologie und Psychiatrie, Westerstede, NIEDERSACHSEN; Martin
Wolz (Medizinische Fakultaet der TU Dresden, Fachbereich Neurologie, Dresden, SACHSEN)
Poland
Tomasz Hasiec (Wojewódzki Szpital Specjalistyczny im, Stefana Kardynała Wyszyńskiego, SPZOZ w
Lublinie, Lublin, LUBELSKIE); Gabriela Kłodowska-Duda (Gabriela Kłodowska-Duda Neuro-Care
NZOZ Site Management Organization, Katowice, SLASKIE); Robert Kucharski (PALLMED Sp. z o.o.,
Bydgoszcz, KUJAWSKO-POMORSKIE); Anatol Mickielewicz (Centrum Leczenia Chorób
Cywilizacyjnych Sp. z o. o. S. K. A., Warszawa, MAZOWIECKIE); Andrzej Potemkowski (Euromedis
Sp. z o.o., Szczecin, ZACHODNIOPOMORSKIE); Danuta Pruchnik-Wolińska (Gabinet Neurologiczny,
Indywidualna Specjalistyczna Praktyka Lekarska, Mosina, WIELKOPOLSKIE); Monika Rudzińska
(Krakowska Akademia Neurologii Sp. z o. o., Kraków, MALOPOLSKIE)
Romania
Rodica Balasa (Spitalul Clinic Judetean de Urgenta Targu Mures, Târgu Mureş, MURES); Magdalena
Ditu (Neomed Research, Brasov, BRASOV); Jozsef Szasz (Spitalul Clinic Judetean de Urgenta TarguMures, Clinica Neurologie I, Tirgu Mures, MURES)
Spain
Miguel Aguilar (Hospital Mutua de Terrassa, Unidad de Demencias, Terrassa, BARCELONA); Ernest
Balaguer (Hospital General de Cataluña, Sant Cugat Del Valles, BARCELONA); Juan Jose Lopez
Lozano (Clinica Ruber SA, Madrid, MADRID); Berta Pascual (Institut Universitari Dexeus, Barcelona,
BARCELONA); Eduardo Tolosa Sarro (Hospital Clinic i Provincial de Barcelona, Barcelona,
BARCELONA)
Ukraine
Elena Anatolievna Statinova (Donetsk National Medical University, Donetsk, DONETSK); Nataliya
Buchakchyys'ka (Zaporozhye Regional Clinical Hospital, Zaporozhye, ZAPORIZHZHYA); Lydmila
Dzyak (Regional Clinical Hospital n.a. I.I. Mechnikov, Dnepropetrovsk DNIPROPETROVSK); Alla
Goloborodko (Odessa Regional Clinical Hospital, Odessa, ODESSA); Olexandr Kozyolkin (Zaporozhye
State Medical University based at Zaporozhye State Clinical Hospital #6, Zaporozhye,
ZAPORIZHZHYA); Sergii Moskovko (Vinnitsa State Medical University, Vinnitsa, VINNYTSYA);
Nataliya Voloshina (Institute of Neurology, Psychiatry and Narcology of the AMS of Ukraine, Kharkiv,
KHARKIV)
United States
Victor Biton (Clinical Trials, Inc., Little Rock, AR); Steven Cohen (Suncoast Neuroscience Associates,
Inc., Saint Petersburg, FL); Aaron Ellenbogen (Quest Research Institute, Bingham Farms, MI); Lawrence
Elmer (University of Toledo, Toledo, OH); Alberto Espay (University Neurology, Inc., Cincinnati, OH);
Ramon Gil (Parkinson's Disease Treatment Center of South West Florida, Port Charlotte, FL); Paul
Ginsberg (Sunrise Clinical Research, Inc., Hollywood, FL); Robert Hauser (University of South Florida,
Parkinson's Disease and Movement Disorders Center, Tampa, FL); Vanessa Hinson (Medical University
of South Carolina, Charleston, SC); Patrick Hogan, III (South Puget Sound Neurology, Tacoma, WA);
Keith Hull, Jr. (Raleigh Neurology Associates, P.A., Raleigh NC); Bahman Jabbari (Yale University
School of Medicine, New Haven, CT); Olga Klepitskaya (University of Colorado Health Sciences Center
School of Medicine, Aurora, CO); Kevin Klos (The Movement Disorder Clinic of Oklahoma, Tulsa, OK);
David Kreitzman (Parkinson's Disease and Movement Disorders Center of Long Island, Commack, NY);
Grace Liang (The Parkinson's Institute, Sunnyvale, CA); Abraham Lieberman (Mohammed Ali
Parkinson's Center, Phoenix, AZ); Margery Mark (UMDNJ Robert Wood Johnson Medical Center, New
Brunswick, NJ); William McElveen (Bradenton Research Center, Inc., Bradenton, FL); Eric Molho
(Albany Medical College, Parkinson's Disease and Movement Disorders Center, Albany, NY); Paul
Nausieda (Wisconsin Institute for Neurologic and Sleep Disorders, Milwaukee, WI); Annette Nieves
(Renstar Medical Research, Ocala, FL); Omid Omidvar (Collaborative NeuroScience Network, Inc.,
Torrance, CA); William Ondo (Baylor College of Medicine, Parkinson's Disease Center, Houston, TX);
Padraig O'Suilleabhain (University of Texas Southwestern Medical Center at Dallas, Dallas, TX); Rajesh
Pahwa (Landon Center on Aging, Parkinson's Disease Center, Kansas City, KS); Lauren Seeberger (Idaho
Elks Rehabilitation Hospital, Boise, ID); Kapil Sethi (Georgia Health Sciences University, Movements
Disorders Clinic, Augusta, GA); Dee Silver (Coastal Neurological Medical Group, La Jolla, CA); Tanya
Simuni (Northwestern University, Feinberg School of Medicine, Chicago, IL); Mark Stacy (Duke
University Medical Center, Movement Disorders Center, Durham, NC); Natividad Stover (University of
Alabama at Birmingham, Birmingham, AL); Lynn Struck (Iowa Methodist Medical Center, Des Moines,
IA); Leonard Verhagen (Rush University Medical Center, Chicago, IL); Cheryl Waters (Columbia
University Neurological Institute, New York, NY).
Supplementary Table A. Suggested initial dose conversion to IPX066
Total daily IR LD
dose (mg)
400–550
551–750
751–950
951–1250
1251–1650
>1650
Suggested initial IPX066 dosage (LD in mg)*
Morning dose
Midday dose
Evening dose
3 capsules x 95
3 capsules x 95
3 capsules x 95
4 capsules x 95
4 capsules x 95
4 capsules x 95
3 capsules x 145
3 capsules x 145
3 capsules x 145
3 capsules x 195
3 capsules x 195
3 capsules x 195
4 capsules x 195
4 capsules x 195
4 capsules x 195
OR
OR
OR
3 capsules x 245
3 capsules x 245
3 capsules x 245
4 capsules x 245
4 capsules x 245
4 capsules x 245
IR=immediate release. LD=levodopa.
*Each dose approximately 6 hours apart during waking hours.
Supplementary Table B. Concomitant medications*
Medication
Dose adjustment
Dose conversion
category
(N=471)
(N=450)
Maintenance (N=393)
No concomitant
medication
Dopamine
agonists
23 (4.9%)
20 (4.4%)
IPX066
(N=201)
9 (4.5%)
IR CD-LD
(N=192)
13 (6.8%)
259 (55.0%)
244 (54.2%)
110 (54.7%)
100 (52.1%)
MAO-B
inhibitors
Anticholinergics
Antidepressants
Amantadine
Other
124 (26.3%)
117 (26.0%)
48 (23.9%)
48 (25.0%)
28 (5.9%)
118 (25.1%)
96 (20.4%)
389 (82.6%)
28 (6.2%)
115 (25.6%)
92 (20.4%)
373 (82.9%)
13 (6.5%)
58 (28.9%)
44 (21.9%)
163 (81.1%)
13 (6.8%)
44 (22.9%)
39 (20.3%)
160 (83.3%)
CD-LD=carbidopa-levodopa. MAO-B=monoamine oxidase B.
*A subject may be counted in more than one concomitant-medication category.