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

NCT03670953 | Completed Phase 3 Results FDA Drug

• 2 other identifiers: IPX203-B16-022018-002233-37
• Study Type: interventional
• Target: 630
• Locations: 8 countries
• Sites: 108

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.

Conditions

Parkinson's Disease (Disorder)

Keywords

Idiopathic Parkinson's Disease; Lewy Body Parkinson's Disease; Paralysis Agitans; Primary Parkinsonism

Outcome Measures

Primary Outcomes (1)

• Mean Change From Baseline in "Good on" Time Per Day at Week 20/Early Termination (ET)

  "Good on" time was derived from the 3-day PD Diaries. For each day, "Good on" time was calculated by adding the number of half-hour intervals in which either an "On" without dyskinesia or "On" with nontroublesome dyskinesia was checked. Baseline was defined as data obtained from PD Diary collected over 3 days prior to Week 7/Randomization. Least square mean (LSM), standard error (SE), confidence interval (CI), Mixed model repeated measures (MMRM), Change from baseline (CFB).

  Baseline (Week 7) and Week 20/ET

Secondary Outcomes (4)

• Change From Baseline in "Off" Time Per Day at Week 20/ET

  Baseline (Week 7) and Week 20/ET

• Percentage of Participants With Either "Much Improved" or "Very Much Improved" in Patient Global Impression of Change (PGI-C) Scores at Week 20/ET

  Week 20/ET

• Change From Baseline in The Movement Disorders Society Version of the Unified Parkinson's Disease Rating Scale (MDS-UPDRS) Part III at Week 20/ET

  Baseline (Week 7) and Week 20/ET

• Change From Baseline in The Sum of MDS-UPDRS Part II and Part III at Week 20/ET

  Baseline (Week 7) and Week 20/ET

Study Arms (4)

IR CD-LD - Dose Adjustment

ACTIVE COMPARATOR

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.

Drug: IR CD-LD

IPX203 - Dose Conversion

EXPERIMENTAL

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.

Drug: IPX203 ER CD-LD

IPX203 - Double-Blind Maintenance

EXPERIMENTAL

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.

Drug: IPX203 ER CD-LD; Other: Placebo Matching IPX203

IR CD-LD - Double -Blind Maintenance

ACTIVE COMPARATOR

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.

Drug: IR CD-LD; Other: Placebo Matching IR CD-LD

Interventions

IR CD-LD DRUG

Active comparator - IR CD-LD

Also known as: Generic for Sinemet tablets

IR CD-LD - Dose Adjustment; IR CD-LD - Double -Blind Maintenance

IPX203 ER CD-LD DRUG

Investigational formulation - ER CD-LD

IPX203 - Dose Conversion; IPX203 - Double-Blind Maintenance

Placebo Matching IPX203 OTHER

Double dummy placebo capsules

IPX203 - Double-Blind Maintenance

Placebo Matching IR CD-LD OTHER

Double dummy placebo tablets

IR CD-LD - Double -Blind Maintenance

Eligibility Criteria

• Age: 40 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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 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),

Sponsors & Collaborators

• Impax Laboratories, LLC: lead

Study Sites (108)

Xenoscience, Inc. (102)

Phoenix, Arizona, 85004, United States

Location

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

Phoenix, Arizona, 85013, United States

Location

Clinical Trials, Inc. (113)

Little Rock, Arkansas, 72205, United States

Location

University of Arkansas for Medical Sciences (117)

Little Rock, Arkansas, 72205, United States

Location

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

Loma Linda, California, 92354, United States

Location

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

Los Angeles, California, 90033, United States

Location

Hoag Memorial Hospital Presbyterian (134)

Newport Beach, California, 92663, United States

Location

SC3 Research - Pasadena (148)

Pasadena, California, 91105, United States

Location

SC3 Research - Reseda (146)

Reseda, California, 91335, United States

Location

University of Colorado Hospital Anschutz Outpatient Pavilion (120)

Aurora, Colorado, 80045, United States

Location

Rocky Mountain Movement Disorders Center (116)

Englewood, Colorado, 80113, United States

Location

Christiana Care Neurology Specialists (153)

Newark, Delaware, 19713, United States

Location

JEM Research Institute (136)

Atlantis, Florida, 33462, United States

Location

Visionary Investigators Network (168)

Aventura, Florida, 33180, United States

Location

University of Miami-UHealth at Boca Raton (152)

Boca Raton, Florida, 33131, United States

Location

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

Boca Raton, Florida, 33486, United States

Location

MD Clinical (111)

Hallandale, Florida, 33009, United States

Location

Infinity Clinical Research (104)

Hollywood, Florida, 33024, United States

Location

University of Florida Health Science Center(129)

Jacksonville, Florida, 32209, United States

Location

Neurology Associates, P.A. (125)

Maitland, Florida, 32751, United States

Location

University of Miami (149)

Miami, Florida, 33136, United States

Location

Medical Professional Clinical Research Center, INC (163)

Miami, Florida, 33165, United States

Location

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

Port Charlotte, Florida, 33980, United States

Location

Infinity Clinical Research, LLC (105)

Sunrise, Florida, 33351, United States

Location

University of South Florida (114)

Tampa, Florida, 33613, United States

Location

Premiere Research Institute at Palm Beach Neurology (174)

West Palm Beach, Florida, 33407, United States

Location

Charter Research (166)

Winter Park, Florida, 32792, United States

Location

Emory Brain Health Center (110)

Atlanta, Georgia, 30329, United States

Location

NeuroStudies.net, LLC (155)

Decatur, Georgia, 30033, United States

Location

Northwestern Medical Group Neurology Clinic(145)

Chicago, Illinois, 60611, United States

Location

Central DuPage Hospital (151)

Winfield, Illinois, 60190, United States

Location

Indiana University Health Neuroscience Center (164)

Indianapolis, Indiana, 46202, United States

Location

University of Kansas Medical Center (118)

Kansas City, Kansas, 66160, United States

Location

Quest Research Institute (103)

Farmington Hills, Michigan, 48334, United States

Location

Henry Ford West Bloomfield Hospital (100)

West Bloomfield, Michigan, 483222, United States

Location

Struthers Parkinson's Center (130)

Golden Valley, Minnesota, 55427, United States

Location

Washington University (109)

St Louis, Missouri, 63110, United States

Location

Cleveland Clinic Lou Ruvo Center for Brain Health (142)

Las Vegas, Nevada, 89106, United States

Location

Roseman Medical Research Institute/Roseman Medical Group (154)

Las Vegas, Nevada, 89118, United States

Location

Albany Medical College (139)

Albany, New York, 12208, United States

Location

Mount Sinai West-Department of Neurology(172)

New York, New York, 10019, United States

Location

Wake Forest Baptist Health Sciences (127)

Winston-Salem, North Carolina, 27157, United States

Location

Ucgni (133)

Cincinnati, Ohio, 45219, United States

Location

University Hospitals Cleveland Medical Center (123)

Cleveland, Ohio, 44106, United States

Location

Cleveland Clinic (144)

Cleveland, Ohio, 44195, United States

Location

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

Toledo, Ohio, 43614, United States

Location

Movement Disorder Clinic of Oklahoma (115)

Tulsa, Oklahoma, 74136, United States

Location

Medical University of South Carolina (150)

Charleston, South Carolina, 29425, United States

Location

The Vanderbilt Clinic(158)

Nashville, Tennessee, 37232, United States

Location

Neurology Consultants of Dallas, PA (108)

Dallas, Texas, 75251, United States

Location

University of Texas Southwestern Medical Center (143)

Dallas, Texas, 75390-9184, United States

Location

Houston Methodist Neurological Institute/Movement Disorders Clinic (135)

Houston, Texas, 77030, United States

Location

Inova Medical Group-Neurology I (147)

Alexandria, Virginia, 22311, United States

Location

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

Henrico, Virginia, 23233, United States

Location

Booth Gardner Parkinson's Care Center (112)

Kirkland, Washington, 98034, United States

Location

Inland Northwest Research (119)

Spokane, Washington, 99202, United States

Location

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

Brno, 65691, Czechia

Location

Neurohk, s.r.o (701)

Choceň, 56501, Czechia

Location

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

Pardubice, 53203, Czechia

Location

Clintrial s.r.o. (703)

Prague, 10000, Czechia

Location

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

Prague, 15000, Czechia

Location

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

Prague, 160 00, Czechia

Location

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

Clermont-Ferrand, 63003, France

Location

CHU de Montpellier, Hopital Gui de Chauliac(405)

Montpellier, 34295, France

Location

Centre Hospitalier Universitaire de Nice (400)

Nice, 06002, France

Location

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

Poitiers, 86021, France

Location

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

Toulouse, 31059, France

Location

Curiositas ad sanum, Studien und Beratungs GmbH(311)

München, Bavaria, 80331, Germany

Location

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

München, Bavaria, 81675, Germany

Location

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

Beelitz-Heilstätten, Brandenburg, 14547, Germany

Location

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

Westerstede, Lower Saxony, 26655, Germany

Location

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

Bochum, North Rhine-Westphalia, 44791, Germany

Location

Klinik Haag i. OB, Geriatric Hospital (305)

Haag in Oberbayern, Oberbayern (Upper Bavaria), 83527, Germany

Location

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

Dresden, Saxony, 01307, Germany

Location

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

Berlin, 12163, Germany

Location

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

Catania, Italy/Catania/Sicily, 95123, Italy

Location

Universita G. D'annunzio CeSi Met (604)

Chieti, Italy/Chieti/Abbruzzo, 66100, Italy

Location

Centro Ricerca Parkinson San Raffaele Cassino (601)

Cassino, Italy/Frosinone/Lazio, 03043, Italy

Location

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

Pavia, Italy/Pavia/Lombardia, 27100, Italy

Location

Azienda Ospedaliero-Universitaria Pisana (602)

Pisa, Italy/Pisa/Toscana, 56126, Italy

Location

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

Roma, Italy/Roma/Lazio, 00133, Italy

Location

IRCCS San Raffaele Pisana (600)

Roma, Italy/Roma/Lazio, 00163, Italy

Location

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

Roma, Italy/Roma/Lazio, 00189, Italy

Location

Centrum Medyczne Neuromed (803)

Bydgoszcz, 85-163, Poland

Location

Szpital Sw. Rozy (805)

Krakow, 30-394, Poland

Location

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

Krakow, 31-505, Poland

Location

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

Lublin, 20-064, Poland

Location

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

Poznan, 61-853, Poland

Location

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

Siemianowice Śląskie, 41-100, Poland

Location

Centrum Medyczne NeuroProtect (806)

Warsaw, 01-684, Poland

Location

Hospital Genral Universitario de Elche (509)

Elche, Alicante, 03203, Spain

Location

Hospital Universitari General de Catalunya (504)

Sant Cugat del Vallès, Barcelona, 08190, Spain

Location

Hospital Universitari Mutua Terrassa (506)

Terrassa, Barcelona, 08222, Spain

Location

Policlinica Gipuzkoa, S.A.,(511)

Donostia / San Sebastian, Gipuzkoa, 20014, Spain

Location

Clinica Universidad de Navarra (512)

Pamplona, Navarre, 31008, Spain

Location

Hospital Universitario Quiron Dexeus (501)

Barcelona, 08028, Spain

Location

Hospital Universitario Vall d' Hebron (505)

Barcelona, 08035, Spain

Location

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

Barcelona, 08035, Spain

Location

Hospital Clinic de Barcelona (507)

Barcelona, 08036, Spain

Location

Hospital De La Santa Creu i Sant Pau (502)

Barcelona, 08041, Spain

Location

Hospital Universitario de la Princesa (508)

Madrid, 28006, Spain

Location

Hospital Universitario Ramon y Cajal (500)

Madrid, 28034, Spain

Location

Hospital Universitario Infanta Sofia (513)

Madrid, 28703, Spain

Location

Hospital Universitario Virgen del Rocio (503)

Seville, 41013, Spain

Location

Hospital Universitario y politecnico La Fe (515)

Valencia, 46026, Spain

Location

Re: Cognition Health Ltd(205)

Plymouth, Devon, PL68BT, United Kingdom

Location

Re:Cognition Health Ltd (202)

London, W1G9JF, United Kingdom

Location

Imperial College Healthcare NHS Trust (200)

London, W68RF, United Kingdom

Location

Related Publications (1)

• 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.

  PMID: 37578800 DERIVED

MeSH Terms

Conditions

Parkinson Disease

Interventions

Drugs, Generic; carbidopa, levodopa drug combination

Condition Hierarchy (Ancestors)

Parkinsonian Disorders; Basal Ganglia Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Movement Disorders; Synucleinopathies; Neurodegenerative Diseases

Intervention Hierarchy (Ancestors)

Pharmaceutical Preparations

Results Point of Contact

• Title: Pamela Fitzpatrick, Senior Director, Specialty Regulatory Affairs
• Organization: Impax Laboratories, LLC

pfitzpatrick@amneal.com

631-633-2104

Study Officials

• Impax Study Director

  Impax Laboratories, LLC

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Double dummy, blinded drug
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Multicenter, randomized, double-blind, double-dummy, active-controlled, parallel-group study.

Study Record Dates

• First Submitted: September 12, 2018
• First Posted: September 14, 2018
• Study Start: November 6, 2018
• Primary Completion: June 15, 2021
• Study Completion: June 15, 2021
• Last Updated: February 9, 2023
• Results First Posted: February 9, 2023

Record last verified: 2022-09

Data Sharing

• IPD Sharing: Will not share

Locations

CZ (6); DE (8); IT (8); FR (5); US (56); GB (3); ES (15); PL (7)