Trial Outcomes & Findings for A Study to Evaluate the Safety and Efficacy of IPX203 in Parkinson's Disease Participants With Motor Fluctuations (NCT NCT03670953)

Last Updated: 2023-02-09

Results Overview

"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).

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

630 participants

Primary outcome timeframe

Baseline (Week 7) and Week 20/ET

Results posted on

2023-02-09

Participant Flow

A total of 630 enrolled participants entered the immediate release carbidopa-levodopa (IR CD-LD) dose adjustment period of which 589 participants entered IPX203 conversion period of which 506 participants entered double-blind maintenance period. Participants were randomized in a 1:1 ratio in double blind period.

Participants with parkinsons disease (PD) who were treated with stable regimens of carbidopa - levodopa (CD - LD) were enrolled in this study.

Participant milestones

Participant milestones
Measure	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.	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.	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.	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.
Dose Adjustment (Weeks 1- 3) STARTED	630	0	0	0
Dose Adjustment (Weeks 1- 3) COMPLETED	589	0	0	0
Dose Adjustment (Weeks 1- 3) NOT COMPLETED	41	0	0	0
Dose Conversion (Weeks 4 - 7) STARTED	0	589	0	0
Dose Conversion (Weeks 4 - 7) COMPLETED	0	506	0	0
Dose Conversion (Weeks 4 - 7) NOT COMPLETED	0	83	0	0
Double Blind Maintenance (Weeks 8 - 20) STARTED	0	0	256	250
Double Blind Maintenance (Weeks 8 - 20) COMPLETED	0	0	222	227
Double Blind Maintenance (Weeks 8 - 20) NOT COMPLETED	0	0	34	23

Reasons for withdrawal

Reasons for withdrawal
Measure	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.	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.	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.	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.
Dose Adjustment (Weeks 1- 3) Adverse Event	4	0	0	0
Dose Adjustment (Weeks 1- 3) Lack of Efficacy	1	0	0	0
Dose Adjustment (Weeks 1- 3) Protocol Violation	6	0	0	0
Dose Adjustment (Weeks 1- 3) Withdrawal by Subject	9	0	0	0
Dose Adjustment (Weeks 1- 3) Miscellaneous	21	0	0	0
Dose Conversion (Weeks 4 - 7) Adverse Event	0	35	0	0
Dose Conversion (Weeks 4 - 7) Lack of Efficacy	0	10	0	0
Dose Conversion (Weeks 4 - 7) Protocol Violation	0	1	0	0
Dose Conversion (Weeks 4 - 7) Non compliance	0	2	0	0
Dose Conversion (Weeks 4 - 7) Lost to Follow-up	0	1	0	0
Dose Conversion (Weeks 4 - 7) Withdrawal by Subject	0	32	0	0
Dose Conversion (Weeks 4 - 7) Miscellaneous	0	2	0	0
Double Blind Maintenance (Weeks 8 - 20) Adverse Event	0	0	14	3
Double Blind Maintenance (Weeks 8 - 20) Lack of Efficacy	0	0	5	8
Double Blind Maintenance (Weeks 8 - 20) Protocol Violation	0	0	3	1
Double Blind Maintenance (Weeks 8 - 20) Non compliance	0	0	1	0
Double Blind Maintenance (Weeks 8 - 20) Withdrawal by Subject	0	0	10	11
Double Blind Maintenance (Weeks 8 - 20) Miscellaneous	0	0	1	0

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	IPX203 - Double-Blind Maintenance n=256 Participants 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.	IR CD-LD - Double -Blind Maintenance n=250 Participants 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.	Not Randomized n=124 Participants Participants who discontinued from dose adjustment and dose conversion.	Total n=630 Participants Total of all reporting groups
Age, Continuous	66.1 years STANDARD_DEVIATION 9.02 • n=93 Participants	66.5 years STANDARD_DEVIATION 8.85 • n=4 Participants	67.3 years STANDARD_DEVIATION 9.00 • n=27 Participants	66.5 years STANDARD_DEVIATION 8.95 • n=483 Participants
Sex: Female, Male Female	97 Participants n=93 Participants	73 Participants n=4 Participants	64 Participants n=27 Participants	234 Participants n=483 Participants
Sex: Female, Male Male	159 Participants n=93 Participants	177 Participants n=4 Participants	60 Participants n=27 Participants	396 Participants n=483 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	32 Participants n=93 Participants	31 Participants n=4 Participants	14 Participants n=27 Participants	77 Participants n=483 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	223 Participants n=93 Participants	215 Participants n=4 Participants	106 Participants n=27 Participants	544 Participants n=483 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	1 Participants n=93 Participants	4 Participants n=4 Participants	4 Participants n=27 Participants	9 Participants n=483 Participants
Race (NIH/OMB) American Indian or Alaska Native	3 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants	3 Participants n=483 Participants
Race (NIH/OMB) Asian	5 Participants n=93 Participants	3 Participants n=4 Participants	2 Participants n=27 Participants	10 Participants n=483 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants	0 Participants n=483 Participants
Race (NIH/OMB) Black or African American	2 Participants n=93 Participants	3 Participants n=4 Participants	1 Participants n=27 Participants	6 Participants n=483 Participants
Race (NIH/OMB) White	244 Participants n=93 Participants	242 Participants n=4 Participants	120 Participants n=27 Participants	606 Participants n=483 Participants
Race (NIH/OMB) More than one race	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants	0 Participants n=483 Participants
Race (NIH/OMB) Unknown or Not Reported	2 Participants n=93 Participants	2 Participants n=4 Participants	1 Participants n=27 Participants	5 Participants n=483 Participants

PRIMARY outcome

Timeframe: Baseline (Week 7) and Week 20/ET

Population: 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.

Outcome measures

Outcome measures
Measure	IPX203 - Double-Blind Maintenance n=249 Participants 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.	IR CD-LD - Double -Blind Maintenance n=246 Participants 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.
Mean Change From Baseline in "Good on" Time Per Day at Week 20/Early Termination (ET) Baseline (Week 7)	11.67 hours/day Standard Deviation 2.943	11.72 hours/day Standard Deviation 2.759
Mean Change From Baseline in "Good on" Time Per Day at Week 20/Early Termination (ET) Change at Week 20/ET	-0.39 hours/day Standard Deviation 2.706	-0.97 hours/day Standard Deviation 3.081

SECONDARY outcome

Timeframe: Baseline (Week 7) and Week 20/ET

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

"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.

Outcome measures

Outcome measures
Measure	IPX203 - Double-Blind Maintenance n=249 Participants 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.	IR CD-LD - Double -Blind Maintenance n=246 Participants 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.
Change From Baseline in "Off" Time Per Day at Week 20/ET Baseline (Week 7)	3.95 hours/day Standard Deviation 2.524	4.02 hours/day Standard Deviation 2.466
Change From Baseline in "Off" Time Per Day at Week 20/ET Change at Week 20/ET	0.29 hours/day Standard Deviation 2.235	0.76 hours/day Standard Deviation 2.901

SECONDARY outcome

Timeframe: Week 20/ET

Population: 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.

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.

Outcome measures

Outcome measures
Measure	IPX203 - Double-Blind Maintenance n=256 Participants 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.	IR CD-LD - Double -Blind Maintenance n=250 Participants 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.
Percentage of Participants With Either "Much Improved" or "Very Much Improved" in Patient Global Impression of Change (PGI-C) Scores at Week 20/ET	29.7 percentage of participants	18.8 percentage of participants

SECONDARY outcome

Timeframe: Baseline (Week 7) and Week 20/ET

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

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.

Outcome measures

Outcome measures
Measure	IPX203 - Double-Blind Maintenance n=256 Participants 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.	IR CD-LD - Double -Blind Maintenance n=250 Participants 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.
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)	26.9 score on a scale Standard Deviation 16.62	27.0 score on a scale Standard Deviation 16.83
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 Change at Week 20/ET	1.1 score on a scale Standard Deviation 11.07	0.9 score on a scale Standard Deviation 10.10

SECONDARY outcome

Timeframe: Baseline (Week 7) and Week 20/ET

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

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.

Outcome measures

Outcome measures
Measure	IPX203 - Double-Blind Maintenance n=256 Participants 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.	IR CD-LD - Double -Blind Maintenance n=250 Participants 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.
Change From Baseline in The Sum of MDS-UPDRS Part II and Part III at Week 20/ET Baseline (Week 7)	38.9 score on a scale Standard Deviation 22.20	39.3 score on a scale Standard Deviation 21.65
Change From Baseline in The Sum of MDS-UPDRS Part II and Part III at Week 20/ET Change at Week 20/ET	2.0 score on a scale Standard Deviation 13.54	1.8 score on a scale Standard Deviation 12.39

Adverse Events

IR CD-LD - Dose Adjustment

Serious events: 7 serious events

Other events: 40 other events

Deaths: 0 deaths

IPX203 - Dose Conversion

Serious events: 12 serious events

Other events: 130 other events

Deaths: 0 deaths

IPX203 - Double-Blind Maintenance

Serious events: 8 serious events

Other events: 35 other events

Deaths: 0 deaths

IR CD-LD - Double -Blind Maintenance

Serious events: 4 serious events

Other events: 32 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Other adverse events
Measure	IR CD-LD - Dose Adjustment n=630 participants at risk 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.	IPX203 - Dose Conversion n=589 participants at risk 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.	IPX203 - Double-Blind Maintenance n=256 participants at risk 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.	IR CD-LD - Double -Blind Maintenance n=250 participants at risk 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.
Gastrointestinal disorders Constipation	1.1% 7/630 • From first dose up to 30 days after last dose (Up to Weeks 24)	2.0% 12/589 • From first dose up to 30 days after last dose (Up to Weeks 24)	1.6% 4/256 • From first dose up to 30 days after last dose (Up to Weeks 24)	0.40% 1/250 • From first dose up to 30 days after last dose (Up to Weeks 24)
Gastrointestinal disorders Dry mouth	0.32% 2/630 • From first dose up to 30 days after last dose (Up to Weeks 24)	4.2% 25/589 • From first dose up to 30 days after last dose (Up to Weeks 24)	1.2% 3/256 • From first dose up to 30 days after last dose (Up to Weeks 24)	0.80% 2/250 • From first dose up to 30 days after last dose (Up to Weeks 24)
Gastrointestinal disorders Nausea	1.1% 7/630 • From first dose up to 30 days after last dose (Up to Weeks 24)	4.9% 29/589 • From first dose up to 30 days after last dose (Up to Weeks 24)	4.3% 11/256 • From first dose up to 30 days after last dose (Up to Weeks 24)	0.80% 2/250 • From first dose up to 30 days after last dose (Up to Weeks 24)
Gastrointestinal disorders Vomiting	0.48% 3/630 • From first dose up to 30 days after last dose (Up to Weeks 24)	2.2% 13/589 • From first dose up to 30 days after last dose (Up to Weeks 24)	1.2% 3/256 • From first dose up to 30 days after last dose (Up to Weeks 24)	0.00% 0/250 • From first dose up to 30 days after last dose (Up to Weeks 24)
Injury, poisoning and procedural complications Fall	0.95% 6/630 • From first dose up to 30 days after last dose (Up to Weeks 24)	2.2% 13/589 • From first dose up to 30 days after last dose (Up to Weeks 24)	2.0% 5/256 • From first dose up to 30 days after last dose (Up to Weeks 24)	3.6% 9/250 • From first dose up to 30 days after last dose (Up to Weeks 24)
Nervous system disorders Dizziness	0.48% 3/630 • From first dose up to 30 days after last dose (Up to Weeks 24)	2.9% 17/589 • From first dose up to 30 days after last dose (Up to Weeks 24)	2.3% 6/256 • From first dose up to 30 days after last dose (Up to Weeks 24)	0.80% 2/250 • From first dose up to 30 days after last dose (Up to Weeks 24)
Nervous system disorders Dyskinesia	1.7% 11/630 • From first dose up to 30 days after last dose (Up to Weeks 24)	6.8% 40/589 • From first dose up to 30 days after last dose (Up to Weeks 24)	2.0% 5/256 • From first dose up to 30 days after last dose (Up to Weeks 24)	0.40% 1/250 • From first dose up to 30 days after last dose (Up to Weeks 24)
Psychiatric disorders Insomnia	0.95% 6/630 • From first dose up to 30 days after last dose (Up to Weeks 24)	2.2% 13/589 • From first dose up to 30 days after last dose (Up to Weeks 24)	0.78% 2/256 • From first dose up to 30 days after last dose (Up to Weeks 24)	0.40% 1/250 • From first dose up to 30 days after last dose (Up to Weeks 24)
Infections and infestations Urinary tract infection	0.16% 1/630 • From first dose up to 30 days after last dose (Up to Weeks 24)	1.2% 7/589 • From first dose up to 30 days after last dose (Up to Weeks 24)	1.6% 4/256 • From first dose up to 30 days after last dose (Up to Weeks 24)	3.2% 8/250 • From first dose up to 30 days after last dose (Up to Weeks 24)
Musculoskeletal and connective tissue disorders Back pain	0.48% 3/630 • From first dose up to 30 days after last dose (Up to Weeks 24)	1.0% 6/589 • From first dose up to 30 days after last dose (Up to Weeks 24)	0.78% 2/256 • From first dose up to 30 days after last dose (Up to Weeks 24)	2.8% 7/250 • From first dose up to 30 days after last dose (Up to Weeks 24)
Psychiatric disorders Anxiety	0.16% 1/630 • From first dose up to 30 days after last dose (Up to Weeks 24)	1.5% 9/589 • From first dose up to 30 days after last dose (Up to Weeks 24)	2.7% 7/256 • From first dose up to 30 days after last dose (Up to Weeks 24)	0.00% 0/250 • From first dose up to 30 days after last dose (Up to Weeks 24)

Additional Information

Pamela Fitzpatrick, Senior Director, Specialty Regulatory Affairs

Impax Laboratories, LLC

Phone: 631-633-2104

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Measure	IR CD-LD - Dose Adjustment n=630 participants at risk 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.	IPX203 - Dose Conversion n=589 participants at risk 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.	IPX203 - Double-Blind Maintenance n=256 participants at risk 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.	IR CD-LD - Double -Blind Maintenance n=250 participants at risk 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.
Blood and lymphatic system disorders Anameia	0.00% 0/630 • From first dose up to 30 days after last dose (Up to Weeks 24)	0.17% 1/589 • From first dose up to 30 days after last dose (Up to Weeks 24)	0.00% 0/256 • From first dose up to 30 days after last dose (Up to Weeks 24)	0.00% 0/250 • From first dose up to 30 days after last dose (Up to Weeks 24)
Cardiac disorders Atrioventricular block complete	0.00% 0/630 • From first dose up to 30 days after last dose (Up to Weeks 24)	0.00% 0/589 • From first dose up to 30 days after last dose (Up to Weeks 24)	0.00% 0/256 • From first dose up to 30 days after last dose (Up to Weeks 24)	0.40% 1/250 • From first dose up to 30 days after last dose (Up to Weeks 24)
Cardiac disorders Bradycardia	0.00% 0/630 • From first dose up to 30 days after last dose (Up to Weeks 24)	0.00% 0/589 • From first dose up to 30 days after last dose (Up to Weeks 24)	0.39% 1/256 • From first dose up to 30 days after last dose (Up to Weeks 24)	0.00% 0/250 • From first dose up to 30 days after last dose (Up to Weeks 24)
Cardiac disorders Cardiac failure	0.00% 0/630 • From first dose up to 30 days after last dose (Up to Weeks 24)	0.00% 0/589 • From first dose up to 30 days after last dose (Up to Weeks 24)	0.00% 0/256 • From first dose up to 30 days after last dose (Up to Weeks 24)	0.40% 1/250 • From first dose up to 30 days after last dose (Up to Weeks 24)
Gastrointestinal disorders Duodenitis	0.16% 1/630 • From first dose up to 30 days after last dose (Up to Weeks 24)	0.00% 0/589 • From first dose up to 30 days after last dose (Up to Weeks 24)	0.00% 0/256 • From first dose up to 30 days after last dose (Up to Weeks 24)	0.00% 0/250 • From first dose up to 30 days after last dose (Up to Weeks 24)
Gastrointestinal disorders Inguinal hernia	0.16% 1/630 • From first dose up to 30 days after last dose (Up to Weeks 24)	0.00% 0/589 • From first dose up to 30 days after last dose (Up to Weeks 24)	0.00% 0/256 • From first dose up to 30 days after last dose (Up to Weeks 24)	0.00% 0/250 • From first dose up to 30 days after last dose (Up to Weeks 24)
General disorders Asthenia	0.00% 0/630 • From first dose up to 30 days after last dose (Up to Weeks 24)	0.00% 0/589 • From first dose up to 30 days after last dose (Up to Weeks 24)	0.39% 1/256 • From first dose up to 30 days after last dose (Up to Weeks 24)	0.00% 0/250 • From first dose up to 30 days after last dose (Up to Weeks 24)
General disorders Chest pain	0.00% 0/630 • From first dose up to 30 days after last dose (Up to Weeks 24)	0.17% 1/589 • From first dose up to 30 days after last dose (Up to Weeks 24)	0.00% 0/256 • From first dose up to 30 days after last dose (Up to Weeks 24)	0.00% 0/250 • From first dose up to 30 days after last dose (Up to Weeks 24)
General disorders Fatigue	0.00% 0/630 • From first dose up to 30 days after last dose (Up to Weeks 24)	0.00% 0/589 • From first dose up to 30 days after last dose (Up to Weeks 24)	0.39% 1/256 • From first dose up to 30 days after last dose (Up to Weeks 24)	0.00% 0/250 • From first dose up to 30 days after last dose (Up to Weeks 24)
Infections and infestations Cystitis	0.00% 0/630 • From first dose up to 30 days after last dose (Up to Weeks 24)	0.17% 1/589 • From first dose up to 30 days after last dose (Up to Weeks 24)	0.00% 0/256 • From first dose up to 30 days after last dose (Up to Weeks 24)	0.00% 0/250 • From first dose up to 30 days after last dose (Up to Weeks 24)
Infections and infestations Epididymitis	0.16% 1/630 • From first dose up to 30 days after last dose (Up to Weeks 24)	0.00% 0/589 • From first dose up to 30 days after last dose (Up to Weeks 24)	0.00% 0/256 • From first dose up to 30 days after last dose (Up to Weeks 24)	0.00% 0/250 • From first dose up to 30 days after last dose (Up to Weeks 24)
Infections and infestations Influenza	0.00% 0/630 • From first dose up to 30 days after last dose (Up to Weeks 24)	0.17% 1/589 • From first dose up to 30 days after last dose (Up to Weeks 24)	0.00% 0/256 • From first dose up to 30 days after last dose (Up to Weeks 24)	0.00% 0/250 • From first dose up to 30 days after last dose (Up to Weeks 24)
Infections and infestations Pneumonia	0.00% 0/630 • From first dose up to 30 days after last dose (Up to Weeks 24)	0.17% 1/589 • From first dose up to 30 days after last dose (Up to Weeks 24)	0.00% 0/256 • From first dose up to 30 days after last dose (Up to Weeks 24)	0.00% 0/250 • From first dose up to 30 days after last dose (Up to Weeks 24)
Infections and infestations Pyelonephritis	0.00% 0/630 • From first dose up to 30 days after last dose (Up to Weeks 24)	0.00% 0/589 • From first dose up to 30 days after last dose (Up to Weeks 24)	0.39% 1/256 • From first dose up to 30 days after last dose (Up to Weeks 24)	0.00% 0/250 • From first dose up to 30 days after last dose (Up to Weeks 24)
Infections and infestations Sepsis	0.00% 0/630 • From first dose up to 30 days after last dose (Up to Weeks 24)	0.17% 1/589 • From first dose up to 30 days after last dose (Up to Weeks 24)	0.00% 0/256 • From first dose up to 30 days after last dose (Up to Weeks 24)	0.00% 0/250 • From first dose up to 30 days after last dose (Up to Weeks 24)
Infections and infestations Urinary tract infection	0.00% 0/630 • From first dose up to 30 days after last dose (Up to Weeks 24)	0.17% 1/589 • From first dose up to 30 days after last dose (Up to Weeks 24)	0.00% 0/256 • From first dose up to 30 days after last dose (Up to Weeks 24)	0.40% 1/250 • From first dose up to 30 days after last dose (Up to Weeks 24)
Injury, poisoning and procedural complications Contusion	0.00% 0/630 • From first dose up to 30 days after last dose (Up to Weeks 24)	0.17% 1/589 • From first dose up to 30 days after last dose (Up to Weeks 24)	0.00% 0/256 • From first dose up to 30 days after last dose (Up to Weeks 24)	0.00% 0/250 • From first dose up to 30 days after last dose (Up to Weeks 24)
Injury, poisoning and procedural complications Hip fracture	0.00% 0/630 • From first dose up to 30 days after last dose (Up to Weeks 24)	0.17% 1/589 • From first dose up to 30 days after last dose (Up to Weeks 24)	0.00% 0/256 • From first dose up to 30 days after last dose (Up to Weeks 24)	0.00% 0/250 • From first dose up to 30 days after last dose (Up to Weeks 24)
Injury, poisoning and procedural complications Radiation neuropathy	0.16% 1/630 • From first dose up to 30 days after last dose (Up to Weeks 24)	0.00% 0/589 • From first dose up to 30 days after last dose (Up to Weeks 24)	0.00% 0/256 • From first dose up to 30 days after last dose (Up to Weeks 24)	0.00% 0/250 • From first dose up to 30 days after last dose (Up to Weeks 24)
Injury, poisoning and procedural complications Skin laceration	0.00% 0/630 • From first dose up to 30 days after last dose (Up to Weeks 24)	0.17% 1/589 • From first dose up to 30 days after last dose (Up to Weeks 24)	0.00% 0/256 • From first dose up to 30 days after last dose (Up to Weeks 24)	0.00% 0/250 • From first dose up to 30 days after last dose (Up to Weeks 24)
Injury, poisoning and procedural complications Subdural haematoma	0.00% 0/630 • From first dose up to 30 days after last dose (Up to Weeks 24)	0.17% 1/589 • From first dose up to 30 days after last dose (Up to Weeks 24)	0.00% 0/256 • From first dose up to 30 days after last dose (Up to Weeks 24)	0.00% 0/250 • From first dose up to 30 days after last dose (Up to Weeks 24)
Investigations Ejection fraction descreased	0.00% 0/630 • From first dose up to 30 days after last dose (Up to Weeks 24)	0.00% 0/589 • From first dose up to 30 days after last dose (Up to Weeks 24)	0.39% 1/256 • From first dose up to 30 days after last dose (Up to Weeks 24)	0.00% 0/250 • From first dose up to 30 days after last dose (Up to Weeks 24)
Metabolism and nutrition disorders Hypokalaemia	0.00% 0/630 • From first dose up to 30 days after last dose (Up to Weeks 24)	0.17% 1/589 • From first dose up to 30 days after last dose (Up to Weeks 24)	0.00% 0/256 • From first dose up to 30 days after last dose (Up to Weeks 24)	0.00% 0/250 • From first dose up to 30 days after last dose (Up to Weeks 24)
Metabolism and nutrition disorders Hyponatraemia	0.16% 1/630 • From first dose up to 30 days after last dose (Up to Weeks 24)	0.00% 0/589 • From first dose up to 30 days after last dose (Up to Weeks 24)	0.00% 0/256 • From first dose up to 30 days after last dose (Up to Weeks 24)	0.00% 0/250 • From first dose up to 30 days after last dose (Up to Weeks 24)
Musculoskeletal and connective tissue disorders Back pain	0.00% 0/630 • From first dose up to 30 days after last dose (Up to Weeks 24)	0.00% 0/589 • From first dose up to 30 days after last dose (Up to Weeks 24)	0.00% 0/256 • From first dose up to 30 days after last dose (Up to Weeks 24)	0.40% 1/250 • From first dose up to 30 days after last dose (Up to Weeks 24)
Musculoskeletal and connective tissue disorders Osteoarthritis	0.16% 1/630 • From first dose up to 30 days after last dose (Up to Weeks 24)	0.00% 0/589 • From first dose up to 30 days after last dose (Up to Weeks 24)	0.00% 0/256 • From first dose up to 30 days after last dose (Up to Weeks 24)	0.00% 0/250 • From first dose up to 30 days after last dose (Up to Weeks 24)
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Bladder transitional cell carcinoma	0.00% 0/630 • From first dose up to 30 days after last dose (Up to Weeks 24)	0.17% 1/589 • From first dose up to 30 days after last dose (Up to Weeks 24)	0.00% 0/256 • From first dose up to 30 days after last dose (Up to Weeks 24)	0.00% 0/250 • From first dose up to 30 days after last dose (Up to Weeks 24)
Nervous system disorders Cognitive disorder	0.16% 1/630 • From first dose up to 30 days after last dose (Up to Weeks 24)	0.00% 0/589 • From first dose up to 30 days after last dose (Up to Weeks 24)	0.00% 0/256 • From first dose up to 30 days after last dose (Up to Weeks 24)	0.00% 0/250 • From first dose up to 30 days after last dose (Up to Weeks 24)
Nervous system disorders Dyskinesia	0.16% 1/630 • From first dose up to 30 days after last dose (Up to Weeks 24)	0.00% 0/589 • From first dose up to 30 days after last dose (Up to Weeks 24)	0.00% 0/256 • From first dose up to 30 days after last dose (Up to Weeks 24)	0.00% 0/250 • From first dose up to 30 days after last dose (Up to Weeks 24)
Nervous system disorders Epilepsy	0.00% 0/630 • From first dose up to 30 days after last dose (Up to Weeks 24)	0.00% 0/589 • From first dose up to 30 days after last dose (Up to Weeks 24)	0.39% 1/256 • From first dose up to 30 days after last dose (Up to Weeks 24)	0.00% 0/250 • From first dose up to 30 days after last dose (Up to Weeks 24)
Nervous system disorders Neuralgia	0.16% 1/630 • From first dose up to 30 days after last dose (Up to Weeks 24)	0.00% 0/589 • From first dose up to 30 days after last dose (Up to Weeks 24)	0.00% 0/256 • From first dose up to 30 days after last dose (Up to Weeks 24)	0.00% 0/250 • From first dose up to 30 days after last dose (Up to Weeks 24)
Nervous system disorders On and off phenomenon	0.16% 1/630 • From first dose up to 30 days after last dose (Up to Weeks 24)	0.00% 0/589 • From first dose up to 30 days after last dose (Up to Weeks 24)	0.00% 0/256 • From first dose up to 30 days after last dose (Up to Weeks 24)	0.00% 0/250 • From first dose up to 30 days after last dose (Up to Weeks 24)
Nervous system disorders Syncope	0.00% 0/630 • From first dose up to 30 days after last dose (Up to Weeks 24)	0.00% 0/589 • From first dose up to 30 days after last dose (Up to Weeks 24)	0.39% 1/256 • From first dose up to 30 days after last dose (Up to Weeks 24)	0.00% 0/250 • From first dose up to 30 days after last dose (Up to Weeks 24)
Nervous system disorders Transient ischaemic attack	0.00% 0/630 • From first dose up to 30 days after last dose (Up to Weeks 24)	0.34% 2/589 • From first dose up to 30 days after last dose (Up to Weeks 24)	0.00% 0/256 • From first dose up to 30 days after last dose (Up to Weeks 24)	0.00% 0/250 • From first dose up to 30 days after last dose (Up to Weeks 24)
Nervous system disorders Vertebral artery aneurysm	0.00% 0/630 • From first dose up to 30 days after last dose (Up to Weeks 24)	0.00% 0/589 • From first dose up to 30 days after last dose (Up to Weeks 24)	0.39% 1/256 • From first dose up to 30 days after last dose (Up to Weeks 24)	0.00% 0/250 • From first dose up to 30 days after last dose (Up to Weeks 24)
Psychiatric disorders Hallucinations, mixed	0.00% 0/630 • From first dose up to 30 days after last dose (Up to Weeks 24)	0.00% 0/589 • From first dose up to 30 days after last dose (Up to Weeks 24)	0.39% 1/256 • From first dose up to 30 days after last dose (Up to Weeks 24)	0.00% 0/250 • From first dose up to 30 days after last dose (Up to Weeks 24)
Renal and urinary disorders Acute kidney injury	0.16% 1/630 • From first dose up to 30 days after last dose (Up to Weeks 24)	0.00% 0/589 • From first dose up to 30 days after last dose (Up to Weeks 24)	0.00% 0/256 • From first dose up to 30 days after last dose (Up to Weeks 24)	0.00% 0/250 • From first dose up to 30 days after last dose (Up to Weeks 24)
Renal and urinary disorders Nephrolithiasis	0.00% 0/630 • From first dose up to 30 days after last dose (Up to Weeks 24)	0.17% 1/589 • From first dose up to 30 days after last dose (Up to Weeks 24)	0.00% 0/256 • From first dose up to 30 days after last dose (Up to Weeks 24)	0.00% 0/250 • From first dose up to 30 days after last dose (Up to Weeks 24)
Renal and urinary disorders Urinary retention	0.00% 0/630 • From first dose up to 30 days after last dose (Up to Weeks 24)	0.17% 1/589 • From first dose up to 30 days after last dose (Up to Weeks 24)	0.00% 0/256 • From first dose up to 30 days after last dose (Up to Weeks 24)	0.00% 0/250 • From first dose up to 30 days after last dose (Up to Weeks 24)
Renal and urinary disorders Urinary tract obstruction	0.16% 1/630 • From first dose up to 30 days after last dose (Up to Weeks 24)	0.00% 0/589 • From first dose up to 30 days after last dose (Up to Weeks 24)	0.00% 0/256 • From first dose up to 30 days after last dose (Up to Weeks 24)	0.00% 0/250 • From first dose up to 30 days after last dose (Up to Weeks 24)
Reproductive system and breast disorders Benign prostatic hyperplasia	0.00% 0/630 • From first dose up to 30 days after last dose (Up to Weeks 24)	0.00% 0/589 • From first dose up to 30 days after last dose (Up to Weeks 24)	0.00% 0/256 • From first dose up to 30 days after last dose (Up to Weeks 24)	0.40% 1/250 • From first dose up to 30 days after last dose (Up to Weeks 24)
Respiratory, thoracic and mediastinal disorders Chronic obstructive pulmonary disease	0.00% 0/630 • From first dose up to 30 days after last dose (Up to Weeks 24)	0.17% 1/589 • From first dose up to 30 days after last dose (Up to Weeks 24)	0.00% 0/256 • From first dose up to 30 days after last dose (Up to Weeks 24)	0.00% 0/250 • From first dose up to 30 days after last dose (Up to Weeks 24)
Surgical and medical procedures Inguinal hernia repair	0.00% 0/630 • From first dose up to 30 days after last dose (Up to Weeks 24)	0.17% 1/589 • From first dose up to 30 days after last dose (Up to Weeks 24)	0.00% 0/256 • From first dose up to 30 days after last dose (Up to Weeks 24)	0.00% 0/250 • From first dose up to 30 days after last dose (Up to Weeks 24)