A Study to Evaluate the Safety and Efficacy of IPX203 in Parkinson's Disease Participants With Motor Fluctuations

NCT ID: NCT03670953

Last Updated: 2023-02-09

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 630 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2018-11-06
• Study Completion Date: 2021-06-15

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 participants with Parkinson's disease (PD) who have motor fluctuations.

Detailed Description

This was a multicenter, randomized, double-blind, double-dummy, active-controlled, parallel-group study. The study consisted 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 participants 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).

Conditions

Parkinson's Disease (Disorder)

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

IR CD-LD - Dose Adjustment

Participants started on the same dose as the pre-study dosing regimen of IR CD-LD and then received dose adjusted IR CD-LD tablets daily orally, for a period of 3 weeks. If the participant was taking controlled release carbidopa-levodopa (CR CD-LD), the CR CD-LD was discontinued and substituted with a 1:1 milligram-equivalent dose of IR CD-LD.

Group Type: ACTIVE_COMPARATOR

IR CD-LD

Intervention Type: DRUG

Active comparator - IR CD-LD

IPX203 - Dose Conversion

Participants received extended release (ER) CD-LD (IPX203) capsules orally, every 6 - 12 hours for a period of 4 weeks at a dose based on their most frequent stable dose of IR CD-LD in dose adjustment period. Participant with most frequent stable dose of 25-100 milligrams (mg) IR CD-LD received 70 - 280 mg IPX203 thrice daily (TID); \>25-100 - 37.5-150 mg IR CD-LD received 105-420 mg IPX203 TID; \>37.5-150 - 50-200 mg IR CD-LD received 140-560 mg IPX203 TID; \>50 - 200 mg IR CD-LD received 175-700 mg IPX203 TID. Participants who received a daily total dose of less than 125-500 mg IR CD-LD in dose adjustment received IPX203 every 12 hours. After initial dose conversion from IR CD-LD to IPX203 as per above mentioned dose conversion schedule, the dose of IPX203 could be further adjusted during the 4 week dose conversion period.

Group Type: EXPERIMENTAL

IPX203 ER CD-LD

Intervention Type: DRUG

Investigational formulation - ER CD-LD

IPX203 - Double-Blind Maintenance

Participants received IPX203 capsules orally, every 6 - 12 hours for 13 weeks at a stable dose established at the end of dose conversion period along with placebo matched to IR CD-LD.

Group Type: EXPERIMENTAL

IPX203 ER CD-LD

Intervention Type: DRUG

Investigational formulation - ER CD-LD

Placebo Matching IPX203

Intervention Type: OTHER

Double dummy placebo capsules

IR CD-LD - Double -Blind Maintenance

Participants received IR CD-LD tablets daily orally, for 13 weeks at a stable dose established at the end of dose adjustment period along with placebo matched to IPX203.

Group Type: ACTIVE_COMPARATOR

IR CD-LD

Intervention Type: DRUG

Active comparator - IR CD-LD

Placebo Matching IR CD-LD

Intervention Type: OTHER

Double dummy placebo tablets

Interventions

IR CD-LD

Active comparator - IR CD-LD

Intervention Type: DRUG

IPX203 ER CD-LD

Investigational formulation - ER CD-LD

Intervention Type: DRUG

Placebo Matching IPX203

Double dummy placebo capsules

Intervention Type: OTHER

Placebo Matching IR CD-LD

Double dummy placebo tablets

Intervention Type: OTHER

Other Intervention Names

Generic for Sinemet tablets

Eligibility Criteria

Inclusion Criteria

• Male or female participants 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 participants 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 participant 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 participant 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 participants 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 participants 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.
• Participant 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.
• Participants who have previously participated in an IPX203 study.
• Participants who, in the opinion of the clinical investigator, should not participate in the study.
• Based on clinical assessment, participant does not adequately comprehend the terminology needed to complete the PD diary.

• Minimum Eligible Age: 40 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Impax Laboratories, LLC

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Impax Study Director

Role: STUDY_DIRECTOR

Impax Laboratories, LLC

Locations

Xenoscience, Inc. (102)

Phoenix, Arizona, United States

St. Joseph's Hospital & Medical Center/ Barrow Neurological Institute (156)

Phoenix, Arizona, United States

Clinical Trials, Inc. (113)

Little Rock, Arkansas, United States

University of Arkansas for Medical Sciences (117)

Little Rock, Arkansas, United States

Loma Linda University Health Care, Department of Neurology (137)

Loma Linda, California, United States

Keck School of Medicine of USC/University of Southern California (106)

Los Angeles, California, United States

Hoag Memorial Hospital Presbyterian (134)

Newport Beach, California, United States

SC3 Research - Pasadena (148)

Pasadena, California, United States

SC3 Research - Reseda (146)

Reseda, California, United States

University of Colorado Hospital Anschutz Outpatient Pavilion (120)

Aurora, Colorado, United States

Rocky Mountain Movement Disorders Center (116)

Englewood, Colorado, United States

Christiana Care Neurology Specialists (153)

Newark, Delaware, United States

JEM Research Institute (136)

Atlantis, Florida, United States

Visionary Investigators Network (168)

Aventura, Florida, United States

University of Miami-UHealth at Boca Raton (152)

Boca Raton, Florida, United States

Parkinson's Disease and Movement Disorders Center of Boca Raton (121)

Boca Raton, Florida, United States

MD Clinical (111)

Hallandale, Florida, United States

Infinity Clinical Research (104)

Hollywood, Florida, United States

University of Florida Health Science Center(129)

Jacksonville, Florida, United States

Neurology Associates, P.A. (125)

Maitland, Florida, United States

University of Miami (149)

Miami, Florida, United States

Medical Professional Clinical Research Center, INC (163)

Miami, Florida, United States

Parkinsons's Disease Treatment Center of Southwest Florida (131)

Port Charlotte, Florida, United States

Infinity Clinical Research, LLC (105)

Sunrise, Florida, United States

University of South Florida (114)

Tampa, Florida, United States

Premiere Research Institute at Palm Beach Neurology (174)

West Palm Beach, Florida, United States

Charter Research (166)

Winter Park, Florida, United States

Emory Brain Health Center (110)

Atlanta, Georgia, United States

NeuroStudies.net, LLC (155)

Decatur, Georgia, United States

Northwestern Medical Group Neurology Clinic(145)

Chicago, Illinois, United States

Central DuPage Hospital (151)

Winfield, Illinois, United States

Indiana University Health Neuroscience Center (164)

Indianapolis, Indiana, United States

University of Kansas Medical Center (118)

Kansas City, Kansas, United States

Quest Research Institute (103)

Farmington Hills, Michigan, United States

Henry Ford West Bloomfield Hospital (100)

West Bloomfield, Michigan, United States

Struthers Parkinson's Center (130)

Golden Valley, Minnesota, United States

Washington University (109)

St Louis, Missouri, United States

Cleveland Clinic Lou Ruvo Center for Brain Health (142)

Las Vegas, Nevada, United States

Roseman Medical Research Institute/Roseman Medical Group (154)

Las Vegas, Nevada, United States

Albany Medical College (139)

Albany, New York, United States

Mount Sinai West-Department of Neurology(172)

New York, New York, United States

Wake Forest Baptist Health Sciences (127)

Winston-Salem, North Carolina, United States

Ucgni (133)

Cincinnati, Ohio, United States

University Hospitals Cleveland Medical Center (123)

Cleveland, Ohio, United States

Cleveland Clinic (144)

Cleveland, Ohio, United States

University of Toledo, Gardner-McMaster Parkinson Center (122)

Toledo, Ohio, United States

Movement Disorder Clinic of Oklahoma (115)

Tulsa, Oklahoma, United States

Medical University of South Carolina (150)

Charleston, South Carolina, United States

The Vanderbilt Clinic(158)

Nashville, Tennessee, United States

Neurology Consultants of Dallas, PA (108)

Dallas, Texas, United States

University of Texas Southwestern Medical Center (143)

Dallas, Texas, United States

Houston Methodist Neurological Institute/Movement Disorders Clinic (135)

Houston, Texas, United States

Inova Medical Group-Neurology I (147)

Alexandria, Virginia, United States

VCU Health - Neuroscience, Orthopaedic and Wellness Center (124)

Henrico, Virginia, United States

Booth Gardner Parkinson's Care Center (112)

Kirkland, Washington, United States

Inland Northwest Research (119)

Spokane, Washington, United States

Fakultni nemocnice u sv. Anny v Brne, I. neurologicka klinika (704)

Brno, , Czechia

Neurohk, s.r.o (701)

Choceň, , Czechia

Nemocnice Pardubickeho kraje, a.s., Pardubicka nemocnice, Neurologicka klinika (702)

Pardubice, , Czechia

Clintrial s.r.o. (703)

Prague, , Czechia

AXON Clinical, s.r.o. (700)

Prague, , Czechia

Neurologicka ordinace FORBELI s.r.o.(706)

Prague, , Czechia

CHU de Clermont-Ferrand - Hopital Gabriel Montpied (404)

Clermont-Ferrand, , France

CHU de Montpellier, Hopital Gui de Chauliac(405)

Montpellier, , France

Centre Hospitalier Universitaire de Nice (400)

Nice, , France

INSERM, Centre d'investigation Clinique 1402, CHU de Poitiers (402)

Poitiers, , France

Centre d'Investigation Clinique 1436-CHU Purpan-Hopital Pierre Paul Riquet (403)

Toulouse, , France

Curiositas ad sanum, Studien und Beratungs GmbH(311)

München, Bavaria, Germany

Klinikum rechts der lsar der TUM, Klinik und Poliklinik fur Neurologie (303)

München, Bavaria, Germany

Kliniken Beelitz GmbH, Neurologisches Fachkrankenhaus fUr Bewegungsstorungen/Parkinson (300)

Beelitz-Heilstätten, Brandenburg, Germany

Gemeinschaftspraxis Dr. med. Joachim Springub/ Wolfgang Schwarz, Studienzentrum Nord-West (306)

Westerstede, Lower Saxony, Germany

St. Josef-Hospital, Universitatsklinik fur Neurologie, Klinisches Forschungszentrum fur Neurodegeneration (301)

Bochum, North Rhine-Westphalia, Germany

Klinik Haag i. OB, Geriatric Hospital (305)

Haag in Oberbayern, Oberbayern (Upper Bavaria), Germany

Universitatsklinikum Carl Gustav Carus, Klinik und Poliklinik fur Neurologie (307)

Dresden, Saxony, Germany

Dr. med. REINHARDT Ehret Neurologie Berlin Schlobstr. 29 (309)

Berlin, , Germany

Department "G.F. Ingrassia" Section of neuroscience-Policlinico "Vittorio Emanuele" (608)

Catania, Italy/Catania/Sicily, Italy

Universita G. D'annunzio CeSi Met (604)

Chieti, Italy/Chieti/Abbruzzo, Italy

Centro Ricerca Parkinson San Raffaele Cassino (601)

Cassino, Italy/Frosinone/Lazio, Italy

Fondazione lstituto Neurologico Nazionale "C. Mondino" (606)

Pavia, Italy/Pavia/Lombardia, Italy

Azienda Ospedaliero-Universitaria Pisana (602)

Pisa, Italy/Pisa/Toscana, Italy

University of Rome Tor Vergata/Hospital Tor Vergata (605)

Roma, Italy/Roma/Lazio, Italy

IRCCS San Raffaele Pisana (600)

Roma, Italy/Roma/Lazio, Italy

Department of Neuroscience, Mental Health and Sensory System (NeSMOS), Sapienza University (603)

Roma, Italy/Roma/Lazio, Italy

Centrum Medyczne Neuromed (803)

Bydgoszcz, , Poland

Szpital Sw. Rozy (805)

Krakow, , Poland

Krakowska Akademia Neurologii Sp. z o.o.(802)

Krakow, , Poland

NZOZ Neuromed M. i M Nastaj Spolka Partnerska(800)

Lublin, , Poland

NZOZ Neuro-Kard Ilkowski i Partnerzy Spolka Partnerska Lekarzy (801)

Poznan, , Poland

Neuro-Care Sp. z o.o. sp. k.(804)

Siemianowice Śląskie, , Poland

Centrum Medyczne NeuroProtect (806)

Warsaw, , Poland

Hospital Genral Universitario de Elche (509)

Elche, Alicante, Spain

Hospital Universitari General de Catalunya (504)

Sant Cugat del Vallès, Barcelona, Spain

Hospital Universitari Mutua Terrassa (506)

Terrassa, Barcelona, Spain

Policlinica Gipuzkoa, S.A.,(511)

Donostia / San Sebastian, Gipuzkoa, Spain

Clinica Universidad de Navarra (512)

Pamplona, Navarre, Spain

Hospital Universitario Quiron Dexeus (501)

Barcelona, , Spain

Hospital Universitario Vall d' Hebron (505)

Barcelona, , Spain

Hospitalaries Del Sagrat Cor De Jesus Hospital Sant Rafael (516)

Barcelona, , Spain

Hospital Clinic de Barcelona (507)

Barcelona, , Spain

Hospital De La Santa Creu i Sant Pau (502)

Barcelona, , Spain

Hospital Universitario de la Princesa (508)

Madrid, , Spain

Hospital Universitario Ramon y Cajal (500)

Madrid, , Spain

Hospital Universitario Infanta Sofia (513)

Madrid, , Spain

Hospital Universitario Virgen del Rocio (503)

Seville, , Spain

Hospital Universitario y politecnico La Fe (515)

Valencia, , Spain

Re: Cognition Health Ltd(205)

Plymouth, Devon, United Kingdom

Re:Cognition Health Ltd (202)

London, , United Kingdom

Imperial College Healthcare NHS Trust (200)

London, , United Kingdom

Countries

United States; Czechia; France; Germany; Italy; Poland; Spain; United Kingdom

References

Hauser RA, Espay AJ, Ellenbogen AL, Fernandez HH, Isaacson SH, LeWitt PA, Ondo WG, Pahwa R, Schwarz J, Stocchi F, Zeitlin L, Banisadr G, Fisher S, Visser H, D'Souza R. IPX203 vs Immediate-Release Carbidopa-Levodopa for the Treatment of Motor Fluctuations in Parkinson Disease: The RISE-PD Randomized Clinical Trial. JAMA Neurol. 2023 Oct 1;80(10):1062-1069. doi: 10.1001/jamaneurol.2023.2679.

Reference Type: DERIVED

PMID: 37578800 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

2018-002233-37

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

IPX203-B16-02

Identifier Type: -

Identifier Source: org_study_id