Clinical trial NCT03670953: A Study to Evaluate the Safety and Efficacy of IPX203 in Parkinson's Disease Participants With Motor Fluctuations
Official title: A Randomized Controlled Study to Compare the Safety and Efficacy of IPX203 With Immediate-Release Carbidopa-Levodopa in Parkinson's Disease Patients With Motor Fluctuations
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Parkinson's Disease (Disorder)
Keywords: Idiopathic Parkinson's Disease
Lewy Body Parkinson's Disease
Paralysis Agitans
Primary Parkinsonism
Lead sponsor: Impax Laboratories, LLC
Sponsor class: INDUSTRY
First posted: 2018-09-14
Enrollment: 630
Sex: ALL
Minimum age (years): 40
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Multicenter, randomized, double-blind, double-dummy, active-controlled, parallel-group study.
Primary purpose: TREATMENT

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).

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.

Primary outcomes:
measure: Mean Change From Baseline in "Good on" Time Per Day at Week 20/Early Termination (ET)
timeFrame: Baseline (Week 7) and Week 20/ET
Secondary outcomes:
measure: Change From Baseline in "Off" Time Per Day at Week 20/ET
timeFrame: Baseline (Week 7) and Week 20/ET
measure: Percentage of Participants With Either "Much Improved" or "Very Much Improved" in Patient Global Impression of Change (PGI-C) Scores at Week 20/ET
timeFrame: Week 20/ET
measure: 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
timeFrame: Baseline (Week 7) and Week 20/ET
measure: Change From Baseline in The Sum of MDS-UPDRS Part II and Part III at Week 20/ET
timeFrame: Baseline (Week 7) and Week 20/ET
Other outcomes:
Locations:
city: Phoenix
country: United States
facility: Xenoscience, Inc. (102)
state: Arizona
city: Phoenix
country: United States
facility: St. Joseph's Hospital & Medical Center/ Barrow Neurological Institute (156)
state: Arizona
city: Little Rock
country: United States
facility: Clinical Trials, Inc. (113)
state: Arkansas
city: Little Rock
country: United States
facility: University of Arkansas for Medical Sciences (117)
state: Arkansas
city: Loma Linda
country: United States
facility: Loma Linda University Health Care, Department of Neurology (137)
state: California
city: Los Angeles
country: United States
facility: Keck School of Medicine of USC/University of Southern California (106)
state: California
city: Newport Beach
country: United States
facility: Hoag Memorial Hospital Presbyterian (134)
state: California
city: Pasadena
country: United States
facility: SC3 Research - Pasadena (148)
state: California
city: Reseda
country: United States
facility: SC3 Research - Reseda (146)
state: California
city: Aurora
country: United States
facility: University of Colorado Hospital Anschutz Outpatient Pavilion (120)
state: Colorado
city: Englewood
country: United States
facility: Rocky Mountain Movement Disorders Center (116)
state: Colorado
city: Newark
country: United States
facility: Christiana Care Neurology Specialists (153)
state: Delaware
city: Atlantis
country: United States
facility: JEM Research Institute (136)
state: Florida
city: Aventura
country: United States
facility: Visionary Investigators Network (168)
state: Florida
city: Boca Raton
country: United States
facility: University of Miami-UHealth at Boca Raton (152)
state: Florida
city: Boca Raton
country: United States
facility: Parkinson's Disease and Movement Disorders Center of Boca Raton (121)
state: Florida
city: Hallandale Beach
country: United States
facility: MD Clinical (111)
state: Florida
city: Hollywood
country: United States
facility: Infinity Clinical Research (104)
state: Florida
city: Jacksonville
country: United States
facility: University of Florida Health Science Center(129)
state: Florida
city: Maitland
country: United States
facility: Neurology Associates, P.A. (125)
state: Florida
city: Miami
country: United States
facility: University of Miami (149)
state: Florida
city: Miami
country: United States
facility: Medical Professional Clinical Research Center, INC (163)
state: Florida
city: Port Charlotte
country: United States
facility: Parkinsons's Disease Treatment Center of Southwest Florida (131)
state: Florida
city: Sunrise
country: United States
facility: Infinity Clinical Research, LLC (105)
state: Florida
city: Tampa
country: United States
facility: University of South Florida (114)
state: Florida
city: West Palm Beach
country: United States
facility: Premiere Research Institute at Palm Beach Neurology (174)
state: Florida
city: Winter Park
country: United States
facility: Charter Research (166)
state: Florida
city: Atlanta
country: United States
facility: Emory Brain Health Center (110)
state: Georgia
city: Decatur
country: United States
facility: NeuroStudies.net, LLC (155)
state: Georgia
city: Chicago
country: United States
facility: Northwestern Medical Group Neurology Clinic(145)
state: Illinois
city: Winfield
country: United States
facility: Central DuPage Hospital (151)
state: Illinois
city: Indianapolis
country: United States
facility: Indiana University Health Neuroscience Center (164)
state: Indiana
city: Kansas City
country: United States
facility: University of Kansas Medical Center (118)
state: Kansas
city: Farmington Hills
country: United States
facility: Quest Research Institute (103)
state: Michigan
city: West Bloomfield
country: United States
facility: Henry Ford West Bloomfield Hospital (100)
state: Michigan
city: Golden Valley
country: United States
facility: Struthers Parkinson's Center (130)
state: Minnesota
city: Saint Louis
country: United States
facility: Washington University (109)
state: Missouri
city: Las Vegas
country: United States
facility: Cleveland Clinic Lou Ruvo Center for Brain Health (142)
state: Nevada
city: Las Vegas
country: United States
facility: Roseman Medical Research Institute/Roseman Medical Group (154)
state: Nevada
city: Albany
country: United States
facility: Albany Medical College (139)
state: New York
city: New York
country: United States
facility: Mount Sinai West-Department of Neurology(172)
state: New York
city: Winston-Salem
country: United States
facility: Wake Forest Baptist Health Sciences (127)
state: North Carolina
city: Cincinnati
country: United States
facility: Ucgni (133)
state: Ohio
city: Cleveland
country: United States
facility: University Hospitals Cleveland Medical Center (123)
state: Ohio
city: Cleveland
country: United States
facility: Cleveland Clinic (144)
state: Ohio
city: Toledo
country: United States
facility: University of Toledo, Gardner-McMaster Parkinson Center (122)
state: Ohio
city: Tulsa
country: United States
facility: Movement Disorder Clinic of Oklahoma (115)
state: Oklahoma
city: Charleston
country: United States
facility: Medical University of South Carolina (150)
state: South Carolina
city: Nashville
country: United States
facility: The Vanderbilt Clinic(158)
state: Tennessee
city: Dallas
country: United States
facility: Neurology Consultants of Dallas, PA (108)
state: Texas
city: Dallas
country: United States
facility: University of Texas Southwestern Medical Center (143)
state: Texas
city: Houston
country: United States
facility: Houston Methodist Neurological Institute/Movement Disorders Clinic (135)
state: Texas
city: Alexandria
country: United States
facility: Inova Medical Group-Neurology I (147)
state: Virginia
city: Henrico
country: United States
facility: VCU Health - Neuroscience, Orthopaedic and Wellness Center (124)
state: Virginia
city: Kirkland
country: United States
facility: Booth Gardner Parkinson's Care Center (112)
state: Washington
city: Spokane
country: United States
facility: Inland Northwest Research (119)
state: Washington
city: Brno
country: Czechia
facility: Fakultni nemocnice u sv. Anny v Brne, I. neurologicka klinika (704)
city: Choceň
country: Czechia
facility: Neurohk, s.r.o (701)
city: Pardubice
country: Czechia
facility: Nemocnice Pardubickeho kraje, a.s., Pardubicka nemocnice, Neurologicka klinika (702)
city: Praha 10
country: Czechia
facility: Clintrial s.r.o. (703)
city: Praha 5
country: Czechia
facility: AXON Clinical, s.r.o. (700)
city: Praha 6
country: Czechia
facility: Neurologicka ordinace FORBELI s.r.o.(706)
city: Clermont-Ferrand Cedex 1
country: France
facility: CHU de Clermont-Ferrand - Hopital Gabriel Montpied (404)
city: Montpellier Cedex 5
country: France
facility: CHU de Montpellier, Hopital Gui de Chauliac(405)
city: Nice
country: France
facility: Centre Hospitalier Universitaire de Nice (400)
city: Poitiers Cedex
country: France
facility: INSERM, Centre d'investigation Clinique 1402, CHU de Poitiers (402)
city: Toulouse Cedex 9
country: France
facility: Centre d'Investigation Clinique 1436-CHU Purpan-Hopital Pierre Paul Riquet (403)
city: München
country: Germany
facility: Curiositas ad sanum, Studien und Beratungs GmbH(311)
state: Bavaria
city: München
country: Germany
facility: Klinikum rechts der lsar der TUM, Klinik und Poliklinik fur Neurologie (303)
state: Bavaria
city: Beelitz-Heilstatten
country: Germany
facility: Kliniken Beelitz GmbH, Neurologisches Fachkrankenhaus fUr Bewegungsstorungen/Parkinson (300)
state: Brandenburg
city: Westerstede
country: Germany
facility: Gemeinschaftspraxis Dr. med. Joachim Springub/ Wolfgang Schwarz, Studienzentrum Nord-West (306)
state: Lower Saxony
city: Bochum
country: Germany
facility: St. Josef-Hospital, Universitatsklinik fur Neurologie, Klinisches Forschungszentrum fur Neurodegeneration (301)
state: North Rhine-Westphalia
city: Haag In Oberbayern
country: Germany
facility: Klinik Haag i. OB, Geriatric Hospital (305)
state: Oberbayern (Upper Bavaria)
city: Dresden
country: Germany
facility: Universitatsklinikum Carl Gustav Carus, Klinik und Poliklinik fur Neurologie (307)
state: Saxony
city: Berlin
country: Germany
facility: Dr. med. REINHARDT Ehret Neurologie Berlin Schlobstr. 29 (309)
city: Catania
country: Italy
facility: Department "G.F. Ingrassia" Section of neuroscience-Policlinico "Vittorio Emanuele" (608)
state: Italy/Catania/Sicily
city: Chieti
country: Italy
facility: Universita G. D'annunzio CeSi Met (604)
state: Italy/Chieti/Abbruzzo
city: Cassino
country: Italy
facility: Centro Ricerca Parkinson San Raffaele Cassino (601)
state: Italy/Frosinone/Lazio
city: Pavia
country: Italy
facility: Fondazione lstituto Neurologico Nazionale "C. Mondino" (606)
state: Italy/Pavia/Lombardia
city: Pisa
country: Italy
facility: Azienda Ospedaliero-Universitaria Pisana (602)
state: Italy/Pisa/Toscana
city: Roma
country: Italy
facility: University of Rome Tor Vergata/Hospital Tor Vergata (605)
state: Italy/Roma/Lazio
city: Roma
country: Italy
facility: IRCCS San Raffaele Pisana (600)
state: Italy/Roma/Lazio
city: Roma
country: Italy
facility: Department of Neuroscience, Mental Health and Sensory System (NeSMOS), Sapienza University (603)
state: Italy/Roma/Lazio
city: Bydgoszcz
country: Poland
facility: Centrum Medyczne Neuromed (803)
city: Kraków
country: Poland
facility: Szpital Sw. Rozy (805)
city: Kraków
country: Poland
facility: Krakowska Akademia Neurologii Sp. z o.o.(802)
city: Lublin
country: Poland
facility: NZOZ Neuromed M. i M Nastaj Spolka Partnerska(800)
city: Poznań
country: Poland
facility: NZOZ Neuro-Kard Ilkowski i Partnerzy Spolka Partnerska Lekarzy (801)
city: Siemianowice Śląskie
country: Poland
facility: Neuro-Care Sp. z o.o. sp. k.(804)
city: Warszawa
country: Poland
facility: Centrum Medyczne NeuroProtect (806)
city: Elche
country: Spain
facility: Hospital Genral Universitario de Elche (509)
state: Alicante
city: Sant Cugat Del Vallès
country: Spain
facility: Hospital Universitari General de Catalunya (504)
state: Barcelona
city: Terrassa
country: Spain
facility: Hospital Universitari Mutua Terrassa (506)
state: Barcelona
city: San Sebastian
country: Spain
facility: Policlinica Gipuzkoa, S.A.,(511)
state: Gipuzkoa
city: Pamplona
country: Spain
facility: Clinica Universidad de Navarra (512)
state: Navarra
city: Barcelona
country: Spain
facility: Hospital Universitario Quiron Dexeus (501)
city: Barcelona
country: Spain
facility: Hospital Universitario Vall d' Hebron (505)
city: Barcelona
country: Spain
facility: Hospitalaries Del Sagrat Cor De Jesus Hospital Sant Rafael (516)
city: Barcelona
country: Spain
facility: Hospital Clinic de Barcelona (507)
city: Barcelona
country: Spain
facility: Hospital De La Santa Creu i Sant Pau (502)
city: Madrid
country: Spain
facility: Hospital Universitario de la Princesa (508)
city: Madrid
country: Spain
facility: Hospital Universitario Ramon y Cajal (500)
city: Madrid
country: Spain
facility: Hospital Universitario Infanta Sofia (513)
city: Sevilla
country: Spain
facility: Hospital Universitario Virgen del Rocio (503)
city: Valencia
country: Spain
facility: Hospital Universitario y politecnico La Fe (515)
city: Plymouth
country: United Kingdom
facility: Re: Cognition Health Ltd(205)
state: Devon
city: London
country: United Kingdom
facility: Re:Cognition Health Ltd (202)
city: London
country: United Kingdom
facility: Imperial College Healthcare NHS Trust (200)
Study officials:
affiliation: Impax Laboratories, LLC
name: Impax Study Director
role: STUDY_DIRECTOR
References: