A Study to Evaluate the Safety and Efficacy of IPX203 in Parkinson's Disease Patients With Motor Fluctuations
Study Details
Study Description
Brief Summary
To evaluate the safety and efficacy of IPX203 (carbidopa and levodopa) extended-release capsules (IPX203 ER CD-LD) in comparison to immediate release (IR) CD-LD in the treatment of CD-LD-experienced subjects with Parkinson's disease (PD) who have motor fluctuations.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 3 |
Detailed Description
This is a multicenter, randomized, double-blind, double-dummy, active-controlled, parallel-group study. The study will consist of a 3-week, open-label IR CD-LD dose adjustment period; a 4-week, open-label period for conversion to IPX203; followed by a 13-week double-blind treatment period with subjects randomized in a 1:1 ratio, stratified by center, to receive either IPX203 (with matching IR CD-LD placebo) or IR CD-LD (with matching IPX203 placebo). Approximately 510 subjects will be enrolled to randomize 420 subjects.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: IPX203 ER CD-LD Following IR CD-LD dose adjustment and conversion to IPX203 ER CD-LD, subjects will be randomized to investigational product IPX203 ER CD-LD and IR CD-LD placebo. IR CD-LD active and placebo are tablets and IPX203 ER CD-LD active is capsules. Dosage and frequency is patient specific. |
Drug: IR CD-LD
Active comparator - IR CD-LD
Other Names:
Drug: IPX203 ER CD-LD
Investigational formulation - ER CD-LD
Other Names:
Other: IR CD-LD placebo
Double dummy placebo tablets
Other Names:
|
| Active Comparator: IR CD-LD Following IR CD-LD dose adjustment and conversion to IPX203 ER CD-LD, subjects will be randomized to IPX203 placebo and IR CD-LD active comparator. IR CD-LD active is tablets and IPX203 active and placebo are capsules. Dosage and frequency is patient specific. |
Drug: IR CD-LD
Active comparator - IR CD-LD
Other Names:
Drug: IPX203 ER CD-LD
Investigational formulation - ER CD-LD
Other Names:
Other: IPX203 placebo
Double dummy placebo capsules
Other Names:
|
Outcome Measures
Primary Outcome Measures
- Change in "Good on" time [13 weeks]
Change from baseline in "Good on" time in hours per day, at the end of double-blind treatment period. "Good on" time is defined as the sum of "On" time without dyskinesia and "On" time with nontroublesome dyskinesia.
Secondary Outcome Measures
- Change in "Off" time [13 weeks]
Change from baseline in "Off" time in hours per day, at the end of double-blind treatment period.
- Patients with "much improved" or "very much improved" on PGI-C [13 weeks]
Proportion of subjects with either "much improved" or "very much improved" in Patient Global Impression of Change (PGI-C) scores at the end of double-blind treatment period.
- Change in MDS-UPDRS Part III [13 weeks]
Change from baseline in the MDS-UPDRS Part III at the end of double-blind treatment period.
- Change in MDS-UPDRS Parts II and III [13 weeks]
Change from baseline in the sum of MDS-UPDRS Parts II and III at the end of double-blind treatment period.
Eligibility Criteria
Criteria
Inclusion Criteria:
-
Male or female subjects diagnosed at age ≥ 40 years with PD, consistent with the United Kingdom Parkinson's Disease Society Brain Bank Diagnostic Criteria and who are being treated with stable regimens of CD-LD but experiencing motor fluctuations.
-
Able to provide written informed consent prior to the conduct of any study-specific procedures.
-
Female subjects of childbearing potential must have a negative urine pregnancy test at Screening Visit.
-
Negative urine screen for drugs of abuse and negative alcohol breath test at Screening.
-
Hoehn and Yahr Stages 1, 2, 3, or 4 in the "On" state (part of Movement Disorders Society version of the Unified Parkinson's Disease Rating Scale [MDS-UPDRS] Part III)
-
Agrees to use a medically acceptable method of contraception throughout the study and for 6 weeks after completing the study. Medically acceptable methods of contraception that may be used by the subject and/or partner include but are not limited to: abstinence, oral contraception, NuvaRing or transdermal systems, diaphragm with vaginal spermicide, intrauterine device, condom and partner using vaginal spermicide, surgical sterilization (6 months), progestin implant or injection, or postmenopausal female (no menstrual period for ˃ 2 years) or vasectomy (˃ 6 months).
-
Montreal Cognitive Assessment (MoCA) score ≥ 24 at Screening Visit in "On" state.
-
Able to differentiate "On" state from "Off" state as determined by at least 75% concordance with a trained rater in "On/Off" ratings for 8 ratings over a 4-hour training period. The concordance must include at least 1 "On" and 1 "Off" rating and must be achieved within two 4-hour training sessions.
-
Able and willing to comply with the protocol, including completion of diaries and availability for all study visits.
-
Responsive to CD-LD therapy and currently being treated on a stable regimen with CD-LD for at least 4 weeks prior to Visit 1.
-
At Screening, the subject has predictable "Off" periods.
Exclusion Criteria:
-
Received any investigational medications within 30 days or 5 times the half-life, whichever is longer, prior to Visit 1.
-
Female subjects who are currently breastfeeding or lactating.
-
Had prior neurosurgical treatment for PD or if such procedure is planned or anticipated during the study period.
-
Allergic to any excipient in the study drugs.
-
History of medical conditions or of a prior surgical procedure that would interfere with LD absorption, such as gastrectomy, proximal small-bowel resection, or bariatric surgery.
-
History of upper gastrointestinal hemorrhage in patients with peptic ulcer disease within the past 5 years.
-
History of glaucoma with intraocular pressures that are elevated despite appropriate medical management.
-
History of seizure or epilepsy and experienced at least 1 seizure during the past 12 months or has not been compliant with medically recommended therapy or visits.
-
History of myocardial infarction with residual atrial, nodal, or ventricular arrhythmias that are not controlled with medical and/or surgical interventions. A recent (≤ 12 months) history of myocardial infarction with secondary arrhythmias is exclusionary regardless of the therapeutic control.
-
History of neuroleptic malignant syndrome or of nontraumatic rhabdomyolysis.
-
Liver enzyme values ≥ 2.5 times the upper limit of normal; or history of severe hepatic impairment.
-
Serum creatinine level ≥ 1.75 times the upper limit of normal; or requires dialysis at the time of Screening.
-
Subject with a history of malignant melanoma or with a suspicious undiagnosed skin lesion which in the opinion of the investigator could be melanoma.
-
History of drug or alcohol abuse within the 12 months prior to Screening.
-
Received within 4 weeks of Screening or planning to take during participation in the clinical study:
-
Any doses of a CR CD-LD apart from a single daily bedtime dose, any doses of Rytary, additional CD (eg, Lodosyn) or benserazide (eg, Serazide), or catechol-O-methyl transferase inhibitors (entacapone or tolcapone) or medications containing these inhibitors (Stalevo),
-
Nonselective monoamine oxidase inhibitors (MAOI), apomorphine, or antidopaminergic agents, including antiemetics.
-
Employees or family members of the investigator, study site, or sponsor.
-
Subjects who have previously participated in an IPX203 study.
-
Subjects who, in the opinion of the clinical investigator, should not participate in the study.
-
Based on clinical assessment, subject does not adequately comprehend the terminology needed to complete the PD diary.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Xenoscience, Inc. (102) | Phoenix | Arizona | United States | 85004 |
| 2 | St. Joseph's Hospital & Medical Center/ Barrow Neurological Institute (156) | Phoenix | Arizona | United States | 85013 |
| 3 | Clinical Trials, Inc. (113) | Little Rock | Arkansas | United States | 72205 |
| 4 | University of Arkansas for Medical Sciences (117) | Little Rock | Arkansas | United States | 72205 |
| 5 | Loma Linda University Health Care, Department of Neurology (137) | Loma Linda | California | United States | 92354 |
| 6 | Keck School of Medicine of USC/University of Southern California (106) | Los Angeles | California | United States | 90033 |
| 7 | Hoag Memorial Hospital Presbyterian (134) | Newport Beach | California | United States | 92663 |
| 8 | SC3 Research - Pasadena (148) | Pasadena | California | United States | 91105 |
| 9 | SC3 Research - Reseda (146) | Reseda | California | United States | 91335 |
| 10 | University of Colorado Hospital Anschutz Outpatient Pavilion (120) | Aurora | Colorado | United States | 80045 |
| 11 | Rocky Mountain Movement Disorders Center (116) | Englewood | Colorado | United States | 80113 |
| 12 | Christiana Care Neurology Specialists (153) | Newark | Delaware | United States | 19713 |
| 13 | JEM Research Institute (136) | Atlantis | Florida | United States | 33462 |
| 14 | Visionary Investigators Network (168) | Aventura | Florida | United States | 33180 |
| 15 | University of Miami-UHealth at Boca Raton (152) | Boca Raton | Florida | United States | 33131 |
| 16 | Parkinson's Disease and Movement Disorders Center of Boca Raton (121) | Boca Raton | Florida | United States | 33486 |
| 17 | MD Clinical (111) | Hallandale Beach | Florida | United States | 33009 |
| 18 | Infinity Clinical Research (104) | Hollywood | Florida | United States | 33024 |
| 19 | University of Florida Health Science Center(129) | Jacksonville | Florida | United States | 32209 |
| 20 | Neurology Associates, P.A. (125) | Maitland | Florida | United States | 32751 |
| 21 | University of Miami (149) | Miami | Florida | United States | 33136 |
| 22 | Medical Professional Clinical Research Center, INC (163) | Miami | Florida | United States | 33165 |
| 23 | Parkinsons's Disease Treatment Center of Southwest Florida (131) | Port Charlotte | Florida | United States | 33980 |
| 24 | Infinity Clinical Research, LLC (105) | Sunrise | Florida | United States | 33351 |
| 25 | University of South Florida (114) | Tampa | Florida | United States | 33613 |
| 26 | Premiere Research Institute at Palm Beach Neurology (174) | West Palm Beach | Florida | United States | 33407 |
| 27 | Charter Research (166) | Winter Park | Florida | United States | 32792 |
| 28 | Emory Brain Health Center (110) | Atlanta | Georgia | United States | 30329 |
| 29 | NeuroStudies.net, LLC (155) | Decatur | Georgia | United States | 30033 |
| 30 | Northwestern Medical Group Neurology Clinic(145) | Chicago | Illinois | United States | 60611 |
| 31 | Central DuPage Hospital (151) | Winfield | Illinois | United States | 60190 |
| 32 | Indiana University Health Neuroscience Center (164) | Indianapolis | Indiana | United States | 46202 |
| 33 | University of Kansas Medical Center (118) | Kansas City | Kansas | United States | 66160 |
| 34 | Quest Research Institute (103) | Farmington Hills | Michigan | United States | 48334 |
| 35 | Henry Ford West Bloomfield Hospital (100) | West Bloomfield | Michigan | United States | 483222 |
| 36 | Struthers Parkinson's Center (130) | Golden Valley | Minnesota | United States | 55427 |
| 37 | Washington University (109) | Saint Louis | Missouri | United States | 63110 |
| 38 | Cleveland Clinic Lou Ruvo Center for Brain Health (142) | Las Vegas | Nevada | United States | 89106 |
| 39 | Roseman Medical Research Institute/Roseman Medical Group (154) | Las Vegas | Nevada | United States | 89118 |
| 40 | Albany Medical College (139) | Albany | New York | United States | 12208 |
| 41 | Mount Sinai West-Department of Neurology(172) | New York | New York | United States | 10019 |
| 42 | Wake Forest Baptist Health Sciences (127) | Winston-Salem | North Carolina | United States | 27157 |
| 43 | Ucgni (133) | Cincinnati | Ohio | United States | 45219 |
| 44 | University Hospitals Cleveland Medical Center (123) | Cleveland | Ohio | United States | 44106 |
| 45 | Cleveland Clinic (144) | Cleveland | Ohio | United States | 44195 |
| 46 | University of Toledo, Gardner-McMaster Parkinson Center (122) | Toledo | Ohio | United States | 43614 |
| 47 | Movement Disorder Clinic of Oklahoma (115) | Tulsa | Oklahoma | United States | 74136 |
| 48 | Medical University of South Carolina (150) | Charleston | South Carolina | United States | 29425 |
| 49 | The Vanderbilt Clinic(158) | Nashville | Tennessee | United States | 37232 |
| 50 | Neurology Consultants of Dallas, PA (108) | Dallas | Texas | United States | 75251 |
| 51 | University of Texas Southwestern Medical Center (143) | Dallas | Texas | United States | 75390-9184 |
| 52 | Houston Methodist Neurological Institute/Movement Disorders Clinic (135) | Houston | Texas | United States | 77030 |
| 53 | Inova Medical Group-Neurology I (147) | Alexandria | Virginia | United States | 22311 |
| 54 | VCU Health - Neuroscience, Orthopaedic and Wellness Center (124) | Henrico | Virginia | United States | 23233 |
| 55 | Booth Gardner Parkinson's Care Center (112) | Kirkland | Washington | United States | 98034 |
| 56 | Inland Northwest Research (119) | Spokane | Washington | United States | 99202 |
| 57 | Fakultni nemocnice u sv. Anny v Brne, I. neurologicka klinika (704) | Brno | Czechia | 65691 | |
| 58 | Neurohk, s.r.o (701) | Choceň | Czechia | 56501 | |
| 59 | Nemocnice Pardubickeho kraje, a.s., Pardubicka nemocnice, Neurologicka klinika (702) | Pardubice | Czechia | 53203 | |
| 60 | Clintrial s.r.o. (703) | Praha 10 | Czechia | 10000 | |
| 61 | AXON Clinical, s.r.o. (700) | Praha 5 | Czechia | 15000 | |
| 62 | Neurologicka ordinace FORBELI s.r.o.(706) | Praha 6 | Czechia | 160 00 | |
| 63 | CHU de Clermont-Ferrand - Hopital Gabriel Montpied (404) | Clermont-Ferrand Cedex 1 | France | 63003 | |
| 64 | CHU de Montpellier, Hopital Gui de Chauliac(405) | Montpellier Cedex 5 | France | 34295 | |
| 65 | Centre Hospitalier Universitaire de Nice (400) | Nice | France | 06002 | |
| 66 | INSERM, Centre d'investigation Clinique 1402, CHU de Poitiers (402) | Poitiers Cedex | France | 86021 | |
| 67 | Centre d'Investigation Clinique 1436-CHU Purpan-Hopital Pierre Paul Riquet (403) | Toulouse Cedex 9 | France | 31059 | |
| 68 | Curiositas ad sanum, Studien und Beratungs GmbH(311) | München | Bavaria | Germany | 80331 |
| 69 | Klinikum rechts der lsar der TUM, Klinik und Poliklinik fur Neurologie (303) | München | Bavaria | Germany | 81675 |
| 70 | Kliniken Beelitz GmbH, Neurologisches Fachkrankenhaus fUr Bewegungsstorungen/Parkinson (300) | Beelitz-Heilstatten | Brandenburg | Germany | 14547 |
| 71 | Gemeinschaftspraxis Dr. med. Joachim Springub/ Wolfgang Schwarz, Studienzentrum Nord-West (306) | Westerstede | Lower Saxony | Germany | 26655 |
| 72 | St. Josef-Hospital, Universitatsklinik fur Neurologie, Klinisches Forschungszentrum fur Neurodegeneration (301) | Bochum | North Rhine-Westphalia | Germany | 44791 |
| 73 | Klinik Haag i. OB, Geriatric Hospital (305) | Haag In Oberbayern | Oberbayern (Upper Bavaria) | Germany | 83527 |
| 74 | Universitatsklinikum Carl Gustav Carus, Klinik und Poliklinik fur Neurologie (307) | Dresden | Saxony | Germany | 01307 |
| 75 | Dr. med. REINHARDT Ehret Neurologie Berlin Schlobstr. 29 (309) | Berlin | Germany | 12163 | |
| 76 | Department "G.F. Ingrassia" Section of neuroscience-Policlinico "Vittorio Emanuele" (608) | Catania | Italy/Catania/Sicily | Italy | 95123 |
| 77 | Universita G. D'annunzio CeSi Met (604) | Chieti | Italy/Chieti/Abbruzzo | Italy | 66100 |
| 78 | Centro Ricerca Parkinson San Raffaele Cassino (601) | Cassino | Italy/Frosinone/Lazio | Italy | 03043 |
| 79 | Fondazione lstituto Neurologico Nazionale "C. Mondino" (606) | Pavia | Italy/Pavia/Lombardia | Italy | 27100 |
| 80 | Azienda Ospedaliero-Universitaria Pisana (602) | Pisa | Italy/Pisa/Toscana | Italy | 56126 |
| 81 | University of Rome Tor Vergata/Hospital Tor Vergata (605) | Roma | Italy/Roma/Lazio | Italy | 00133 |
| 82 | IRCCS San Raffaele Pisana (600) | Roma | Italy/Roma/Lazio | Italy | 00163 |
| 83 | Department of Neuroscience, Mental Health and Sensory System (NeSMOS), Sapienza University (603) | Roma | Italy/Roma/Lazio | Italy | 00189 |
| 84 | Centrum Medyczne Neuromed (803) | Bydgoszcz | Poland | 85-163 | |
| 85 | Szpital Sw. Rozy (805) | Kraków | Poland | 30-394 | |
| 86 | Krakowska Akademia Neurologii Sp. z o.o.(802) | Kraków | Poland | 31-505 | |
| 87 | NZOZ Neuromed M. i M Nastaj Spolka Partnerska(800) | Lublin | Poland | 20-064 | |
| 88 | NZOZ Neuro-Kard Ilkowski i Partnerzy Spolka Partnerska Lekarzy (801) | Poznań | Poland | 61-853 | |
| 89 | Neuro-Care Sp. z o.o. sp. k.(804) | Siemianowice Śląskie | Poland | 41-100 | |
| 90 | Centrum Medyczne NeuroProtect (806) | Warszawa | Poland | 01-684 | |
| 91 | Hospital Genral Universitario de Elche (509) | Elche | Alicante | Spain | 03203 |
| 92 | Hospital Universitari General de Catalunya (504) | Sant Cugat Del Vallès | Barcelona | Spain | 08190 |
| 93 | Hospital Universitari Mutua Terrassa (506) | Terrassa | Barcelona | Spain | 08222 |
| 94 | Policlinica Gipuzkoa, S.A.,(511) | San Sebastian | Gipuzkoa | Spain | 20014 |
| 95 | Clinica Universidad de Navarra (512) | Pamplona | Navarra | Spain | 31008 |
| 96 | Hospital Universitario Quiron Dexeus (501) | Barcelona | Spain | 08028 | |
| 97 | Hospital Universitario Vall d' Hebron (505) | Barcelona | Spain | 08035 | |
| 98 | Hospitalaries Del Sagrat Cor De Jesus Hospital Sant Rafael (516) | Barcelona | Spain | 08035 | |
| 99 | Hospital Clinic de Barcelona (507) | Barcelona | Spain | 08036 | |
| 100 | Hospital De La Santa Creu i Sant Pau (502) | Barcelona | Spain | 08041 | |
| 101 | Hospital Universitario de la Princesa (508) | Madrid | Spain | 28006 | |
| 102 | Hospital Universitario Ramon y Cajal (500) | Madrid | Spain | 28034 | |
| 103 | Hospital Universitario Infanta Sofia (513) | Madrid | Spain | 28703 | |
| 104 | Hospital Universitario Virgen del Rocio (503) | Sevilla | Spain | 41013 | |
| 105 | Hospital Universitario y politecnico La Fe (515) | Valencia | Spain | 46026 | |
| 106 | Re: Cognition Health Ltd(205) | Plymouth | Devon | United Kingdom | PL68BT |
| 107 | Re:Cognition Health Ltd (202) | London | United Kingdom | W1G9JF | |
| 108 | Imperial College Healthcare NHS Trust (200) | London | United Kingdom | W68RF |
Sponsors and Collaborators
- Impax Laboratories, LLC
Investigators
- Study Director: Impax Study Director, Impax Laboratories, LLC
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- IPX203-B16-02
- 2018-002233-37