A Study to Evaluate the Safety and Efficacy of IPX203 in... | NCT03670953

ID	Type	Description	Link
2018-002233-37	EudraCT Number

Status Module

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
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

Name	Type	Description	Arm Group Labels	Other Names
IR CD-LD	Drug	Active comparator - IR CD-LD	IR CD-LD - Dose Adjustment IR CD-LD - Double -Blind Maintenance

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
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

Measure	Description	Time Frame
Change From Baseline in "Off" Time Per Day at Week 20/ET	"Off" time was derived from the 3-day PD Diaries. For each day, "Off" time was calculated by adding the number of half-hour intervals in which the Status "Off" was checked. Baseline was defined as data obtained from PD Diary collected over 3 days prior to Week 7/Randomization.	Baseline (Week 7) and Week 20/ET

Eligibility Module

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.

Name	Affiliation	Role
Impax Study Director	Impax Laboratories, LLC	Study Director

Facility	Status	City	State	ZIP	Country	Contacts
Xenoscience, Inc. (102)		Phoenix	Arizona	85004	United States
St. Joseph's Hospital & Medical Center/ Barrow Neurological Institute (156)

PubMed Identifier	Type	Citation	Retractions
37578800	Derived	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.

Results Section

Participant Flow Module

Arm/Group Information

ID	Title	Description
FG000	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.

Baseline Characteristics Module

Outcome Measures Module

Adverse Events Module

More Info Module

Type	Includes Protocol	Includes SAP	Includes ICF	Document Label	Document Date	Document Uploaded Date	Document File Name
Prot	Yes	No	No	Study Protocol	Sep 28, 2018	Jan 13, 2023

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Primary

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).

The Modified Intent-to-Treat (mITT) Analysis Set included all participants who were randomized and treated and had a valid baseline PD Diary and at least one valid post-randomization PD Diary. Participants with available data at specified time point were included in analysis. Data was planned to be reported only for double-blind Maintenance period.

Posted

Mean

Standard Deviation

hours/day

Baseline (Week 7) and Week 20/ET

ID	Title	Description
OG000	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.
OG001	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.

Units	Counts
Participants	OG000249 OG001246

Title

Denominators

Categories

Baseline (Week 7)

- ParticipantsOG000249
- ParticipantsOG001246

Title	Measurements
	OG00011.67± 2.943

Group IDs	Group Description	Statistical Method	Statistical Comment	P-Value	P-Value Comment	Parameter Type	Parameter Value	Dispersion Type	Dispersion Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	CI Lower Limit Comment	CI Upper Limit Comment	Estimate Comment	Tested Non-Inferiority	Non-Inferiority Type	Non-Inferiority Comment	Other Analysis Description
OG000 OG001		MMRM	The degree-of-freedom of the denominator is estimated using the Kenward-Roger method. Unstructured covariance structure is assumed.	0.0194	LSM, SE, CI and p-value from a MMRM with CFB in "Good on" time as outcome, baseline "Good on" time as a covariate, treatment and visit as fixed effects, pooled center as random effect and a treatment-by-visit interaction.	Least Squares Mean difference	0.53	Standard Error of the Mean	0.226	2-Sided	95	0.09	0.97					Superiority	2-sided at a significance level of alpha = 0.05

Secondary

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

"Off" time was derived from the 3-day PD Diaries. For each day, "Off" time was calculated by adding the number of half-hour intervals in which the Status "Off" was checked. Baseline was defined as data obtained from PD Diary collected over 3 days prior to Week 7/Randomization.

mITT population with available data at specified time point. Data was planned to be reported only for double-blind Maintenance period.

Posted

Mean

Standard Deviation

hours/day

Baseline (Week 7) and Week 20/ET

ID	Title	Description
OG000	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.
OG001	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.

Units	Counts
Participants

Secondary

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

The Patient Global Impression of Change (PGIC) is self assessment questionnaire which was used by participants to compare his/her condition on a 7-point scale ranging from 1-Very Much Worse, 2-Much Worse, 3-Minimally Worse, 4-No Change, 5-Minimally Improved, 6-Much Improved, 7-Very Much Improved. Percentage of participants with either "Much Improved" or "Very Much Improved" was reported.

The Intent-to-treat (ITT) Analysis Set included all participants who were randomized and treated with any study drug and had a baseline and at least one post-baseline efficacy assessment.

Posted

Number

percentage of participants

Week 20/ET

ID	Title	Description
OG000	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.
OG001	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.

Secondary

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

MDS-UPDRS is a multimodal scale assessing impairment and disability consisting of 4 parts. (Part I; 13 items) non-motor experiences of daily living, (Part II; 13 items) motor experiences of daily living completed by the participants, (Part III; 34 items) motor examination of PD and was administered by the rater, and (Part IV; 6 items) motor complication integrates participant-derived information with the rater's clinical observations and judgements and is completed by the rater. For each question a numeric score was assigned between 0-4, where 0 = Normal, 1 = Slight, 2 = Mild, 3 = Moderate, 4 = Severe. MDS-UPDRS Total Score equals the sum of Parts I, II, and III and IV (Range 0-234). Part III score ranges from 0 to 136. A higher score indicated more severe symptoms of PD. Baseline was defined as data obtained from PD Diary collected over 3 days prior to Week 7/Randomization.

ITT population with available data at specified time point. Data was planned to be reported only for double-blind Maintenance period.

Posted

Mean

Standard Deviation

score on a scale

Baseline (Week 7) and Week 20/ET

ID	Title	Description
OG000	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.
OG001	IR CD-LD - Double -Blind Maintenance

Secondary

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

MDS-UPDRS is a multimodal scale assessing impairment and disability consisting of 4 parts. (Part I; 13 items) non-motor experiences of daily living, (Part II; 13 items) motor experiences of daily living completed by the participants, (Part III; 34 items) motor examination of PD and was administered by the rater, and (Part IV; 6 items) motor complication integrates participant-derived information with the rater's clinical observations and judgements and is completed by the rater. For each question a numeric score was assigned between 0-4, where 0 = Normal, 1 = Slight, 2 = Mild, 3 = Moderate, 4 = Severe. MDS-UPDRS Total Score equals the sum of Parts I, II, and III and IV (Range 0-234). The scale range for Part II+III score is 0-188. A higher score indicated more severe symptoms of PD. Baseline was defined as data obtained from PD Diary collected over 3 days prior to Week 7/Randomization.

ITT population with available data at specified time point. Data was planned to be reported only for double-blind Maintenance period.

Posted

Mean

Standard Deviation

score on a scale

Baseline (Week 7) and Week 20/ET

ID	Title	Description
OG000	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.
OG001	IR CD-LD - Double -Blind Maintenance

Arm/Groups

ID	Title	Description	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	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 CR CD-LD, the CR CD-LD was discontinued and substituted with a 1:1 milligram-equivalent dose of IR CD-LD.	630	7	630	40	630
EG001	IPX203 - Dose Conversion	Participants received 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 mg IR CD-LD received 70 - 280 mg IPX203 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.	589	12	589	130	589
EG002	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.	256	8	256	35	256
EG003	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.	250	4	250	32	250

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Anameia	Blood and lymphatic system disorders	MedDRA (22.0)	Non-systematic Assessment	EG0000 affected630 at risk EG0011 affected589 at risk EG0020 affected256 at risk EG0030 affected250 at risk
Atrioventricular block complete	Cardiac disorders	MedDRA (22.0)	Non-systematic Assessment	EG0000 affected630 at risk EG0010 affected589 at risk EG0020 affected256 at risk EG003
Bradycardia	Cardiac disorders	MedDRA (22.0)	Non-systematic Assessment	EG0000 affected630 at risk EG0010 affected589 at risk EG0021 affected256 at risk EG003
Cardiac failure	Cardiac disorders	MedDRA (22.0)	Non-systematic Assessment	EG0000 affected630 at risk EG0010 affected589 at risk EG0020 affected256 at risk EG003
Duodenitis	Gastrointestinal disorders	MedDRA (22.0)	Non-systematic Assessment	EG0001 affected630 at risk EG0010 affected589 at risk EG0020 affected256 at risk EG003
Inguinal hernia	Gastrointestinal disorders	MedDRA (22.0)	Non-systematic Assessment	EG0001 affected630 at risk EG0010 affected589 at risk EG0020 affected256 at risk EG003
Asthenia	General disorders	MedDRA (22.0)	Non-systematic Assessment	EG0000 affected630 at risk EG0010 affected589 at risk EG0021 affected256 at risk EG003
Chest pain	General disorders	MedDRA (22.0)	Non-systematic Assessment	EG0000 affected630 at risk EG0011 affected589 at risk EG0020 affected256 at risk EG003
Fatigue	General disorders	MedDRA (22.0)	Non-systematic Assessment	EG0000 affected630 at risk EG0010 affected589 at risk EG0021 affected256 at risk EG003
Cystitis	Infections and infestations	MedDRA (22.0)	Non-systematic Assessment	EG0000 affected630 at risk EG0011 affected589 at risk EG0020 affected256 at risk EG003
Epididymitis	Infections and infestations	MedDRA (22.0)	Non-systematic Assessment	EG0001 affected630 at risk EG0010 affected589 at risk EG0020 affected256 at risk EG003
Influenza	Infections and infestations	MedDRA (22.0)	Non-systematic Assessment	EG0000 affected630 at risk EG0011 affected589 at risk EG0020 affected256 at risk EG003
Pneumonia	Infections and infestations	MedDRA (22.0)	Non-systematic Assessment	EG0000 affected630 at risk EG0011 affected589 at risk EG0020 affected256 at risk EG003
Pyelonephritis	Infections and infestations	MedDRA (22.0)	Non-systematic Assessment	EG0000 affected630 at risk EG0010 affected589 at risk EG0021 affected256 at risk EG003
Sepsis	Infections and infestations	MedDRA (22.0)	Non-systematic Assessment	EG0000 affected630 at risk EG0011 affected589 at risk EG0020 affected256 at risk EG003
Urinary tract infection	Infections and infestations	MedDRA (22.0)	Non-systematic Assessment	EG0000 affected630 at risk EG0011 affected589 at risk EG0020 affected256 at risk EG003
Contusion	Injury, poisoning and procedural complications	MedDRA (22.0)	Non-systematic Assessment	EG0000 affected630 at risk EG0011 affected589 at risk EG0020 affected256 at risk EG003
Hip fracture	Injury, poisoning and procedural complications	MedDRA (22.0)	Non-systematic Assessment	EG0000 affected630 at risk EG0011 affected589 at risk EG0020 affected256 at risk EG003
Radiation neuropathy	Injury, poisoning and procedural complications	MedDRA (22.0)	Non-systematic Assessment	EG0001 affected630 at risk EG0010 affected589 at risk EG0020 affected256 at risk EG003
Skin laceration	Injury, poisoning and procedural complications	MedDRA (22.0)	Non-systematic Assessment	EG0000 affected630 at risk EG0011 affected589 at risk EG0020 affected256 at risk EG003
Subdural haematoma	Injury, poisoning and procedural complications	MedDRA (22.0)	Non-systematic Assessment	EG0000 affected630 at risk EG0011 affected589 at risk EG0020 affected256 at risk EG003
Ejection fraction descreased	Investigations	MedDRA (22.0)	Non-systematic Assessment	EG0000 affected630 at risk EG0010 affected589 at risk EG0021 affected256 at risk EG003
Hypokalaemia	Metabolism and nutrition disorders	MedDRA (22.0)	Non-systematic Assessment	EG0000 affected630 at risk EG0011 affected589 at risk EG0020 affected256 at risk EG003
Hyponatraemia	Metabolism and nutrition disorders	MedDRA (22.0)	Non-systematic Assessment	EG0001 affected630 at risk EG0010 affected589 at risk EG0020 affected256 at risk EG003
Back pain	Musculoskeletal and connective tissue disorders	MedDRA (22.0)	Non-systematic Assessment	EG0000 affected630 at risk EG0010 affected589 at risk EG0020 affected256 at risk EG003
Osteoarthritis	Musculoskeletal and connective tissue disorders	MedDRA (22.0)	Non-systematic Assessment	EG0001 affected630 at risk EG0010 affected589 at risk EG0020 affected256 at risk EG003
Bladder transitional cell carcinoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA (22.0)	Non-systematic Assessment	EG0000 affected630 at risk EG0011 affected589 at risk EG0020 affected256 at risk EG003
Cognitive disorder	Nervous system disorders	MedDRA (22.0)	Non-systematic Assessment	EG0001 affected630 at risk EG0010 affected589 at risk EG0020 affected256 at risk EG003
Dyskinesia	Nervous system disorders	MedDRA (22.0)	Non-systematic Assessment	EG0001 affected630 at risk EG0010 affected589 at risk EG0020 affected256 at risk EG003
Epilepsy	Nervous system disorders	MedDRA (22.0)	Non-systematic Assessment	EG0000 affected630 at risk EG0010 affected589 at risk EG0021 affected256 at risk EG003
Neuralgia	Nervous system disorders	MedDRA (22.0)	Non-systematic Assessment	EG0001 affected630 at risk EG0010 affected589 at risk EG0020 affected256 at risk EG003
On and off phenomenon	Nervous system disorders	MedDRA (22.0)	Non-systematic Assessment	EG0001 affected630 at risk EG0010 affected589 at risk EG0020 affected256 at risk EG003
Syncope	Nervous system disorders	MedDRA (22.0)	Non-systematic Assessment	EG0000 affected630 at risk EG0010 affected589 at risk EG0021 affected256 at risk EG003
Transient ischaemic attack	Nervous system disorders	MedDRA (22.0)	Non-systematic Assessment	EG0000 affected630 at risk EG0012 affected589 at risk EG0020 affected256 at risk EG003
Vertebral artery aneurysm	Nervous system disorders	MedDRA (22.0)	Non-systematic Assessment	EG0000 affected630 at risk EG0010 affected589 at risk EG0021 affected256 at risk EG003
Hallucinations, mixed	Psychiatric disorders	MedDRA (22.0)	Non-systematic Assessment	EG0000 affected630 at risk EG0010 affected589 at risk EG0021 affected256 at risk EG003
Acute kidney injury	Renal and urinary disorders	MedDRA (22.0)	Non-systematic Assessment	EG0001 affected630 at risk EG0010 affected589 at risk EG0020 affected256 at risk EG003
Nephrolithiasis	Renal and urinary disorders	MedDRA (22.0)	Non-systematic Assessment	EG0000 affected630 at risk EG0011 affected589 at risk EG0020 affected256 at risk EG003
Urinary retention	Renal and urinary disorders	MedDRA (22.0)	Non-systematic Assessment	EG0000 affected630 at risk EG0011 affected589 at risk EG0020 affected256 at risk EG003
Urinary tract obstruction	Renal and urinary disorders	MedDRA (22.0)	Non-systematic Assessment	EG0001 affected630 at risk EG0010 affected589 at risk EG0020 affected256 at risk EG003
Benign prostatic hyperplasia	Reproductive system and breast disorders	MedDRA (22.0)	Non-systematic Assessment	EG0000 affected630 at risk EG0010 affected589 at risk EG0020 affected256 at risk EG003
Chronic obstructive pulmonary disease	Respiratory, thoracic and mediastinal disorders	MedDRA (22.0)	Non-systematic Assessment	EG0000 affected630 at risk EG0011 affected589 at risk EG0020 affected256 at risk EG003
Inguinal hernia repair	Surgical and medical procedures	MedDRA (22.0)	Non-systematic Assessment	EG0000 affected630 at risk EG0011 affected589 at risk EG0020 affected256 at risk EG003

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Constipation	Gastrointestinal disorders	MedDRA (22.0)	Non-systematic Assessment	EG0007 affected630 at risk EG00112 affected589 at risk EG0024 affected256 at risk EG0031 affected250 at risk
Dry mouth	Gastrointestinal disorders	MedDRA (22.0)	Non-systematic Assessment	EG0002 affected630 at risk EG00125 affected589 at risk EG0023 affected256 at risk EG003
Nausea	Gastrointestinal disorders	MedDRA (22.0)	Non-systematic Assessment	EG0007 affected630 at risk EG00129 affected589 at risk EG00211 affected256 at risk EG003
Vomiting	Gastrointestinal disorders	MedDRA (22.0)	Non-systematic Assessment	EG0003 affected630 at risk EG00113 affected589 at risk EG0023 affected256 at risk EG003
Fall	Injury, poisoning and procedural complications	MedDRA (22.0)	Non-systematic Assessment	EG0006 affected630 at risk EG00113 affected589 at risk EG0025 affected256 at risk EG003
Dizziness	Nervous system disorders	MedDRA (22.0)	Non-systematic Assessment	EG0003 affected630 at risk EG00117 affected589 at risk EG0026 affected256 at risk EG003
Dyskinesia	Nervous system disorders	MedDRA (22.0)	Non-systematic Assessment	EG00011 affected630 at risk EG00140 affected589 at risk EG0025 affected256 at risk EG003
Insomnia	Psychiatric disorders	MedDRA (22.0)	Non-systematic Assessment	EG0006 affected630 at risk EG00113 affected589 at risk EG0022 affected256 at risk EG003
Urinary tract infection	Infections and infestations	MedDRA (22.0)	Non-systematic Assessment	EG0001 affected630 at risk EG0017 affected589 at risk EG0024 affected256 at risk EG003
Back pain	Musculoskeletal and connective tissue disorders	MedDRA (22.0)	Non-systematic Assessment	EG0003 affected630 at risk EG0016 affected589 at risk EG0022 affected256 at risk EG003
Anxiety	Psychiatric disorders	MedDRA (22.0)	Non-systematic Assessment	EG0001 affected630 at risk EG0019 affected589 at risk EG0027 affected256 at risk EG003

ID	Term
D020734	Parkinsonian Disorders
D001480	Basal Ganglia Diseases
D001927	Brain Diseases
D002493	Central Nervous System Diseases
D009422	Nervous System Diseases
D009069	Movement Disorders
D000080874	Synucleinopathies
D019636	Neurodegenerative Diseases

ID	Term
D016568	Drugs, Generic
C009265	carbidopa, levodopa drug combination

ID	Title	Description
BG000	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.
BG001	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.
BG002	Not Randomized	Participants who discontinued from dose adjustment and dose conversion.
BG003	Total	Total of all reporting groups