Open Label Extension (OLE) Study of the Safety and Clinical Utility of IPX203 in Parkinson's Disease (PD) Participants With Motor Fluctuations

Study Overview
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Brief Summary
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The purpose of this study is to evaluate the long-term safety and clinical utility of IPX203 in the treatment of participants with advanced Parkinson's disease (PD) who have motor fluctuations.

Detailed Description
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This is a 9-month, multicenter open-label safety extension study. Participants who have successfully completed Study NCT03670953 [A Randomized Controlled Study to Compare the Safety and Efficacy of IPX203 with Immediate-Release (IR) Carbidopa-Levodopa (CD-LD) in Parkinson's Disease Patients with Motor Fluctuations] may have the opportunity to enroll in this open-label study.

Official Title
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An Open-label Extension Study of the Safety and Clinical Utility of IPX203 in Parkinson's Disease Patients With Motor Fluctuations

Conditions
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Parkinson Disease

Intervention / Treatment
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* Drug: IPX203


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Successfully completed Study IPX203-B16-02 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 the baseline visit (Visit 1). Agrees to use a medically acceptable method of contraception throughout the study and for 6 weeks after completing the study. Exclusion Criteria: Intends to use any doses of Rytary® or Duopa™ during this study. Plans to use an investigational treatment other than IPX203 during the course of this study. Neurosurgical ablation treatment for PD is planned or anticipated during the study period. Implantation of a deep brain stimulator (DBS) for the treatment of PD is permitted during this study. Participants who, in the opinion of the clinical investigator, should not participate in the study.

Ages Eligible for Study
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Minimum Age: 40 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Open Label IPX203<br>All participants received oral administration of extended-release capsules IPX203 dosing regimen that was determined at the end of the IPX203 dose conversion period of Study IPX203-B16-02 (NCT03670953) for nine months of open-label therapy. The dose and dosing frequency was determined by the investigator to achieve the optimal balance of efficacy and safety. | Drug: IPX203<br>* IPX203 extended release capsules<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Treatment-Emergent Adverse Events | An adverse event (AE) is any untoward medical occurrence in a participant or clinical trial participant administered a medicinal product and which does not necessarily have to have a causal relationship with this treatment. An adverse event can therefore be any unfavorable and unintended sign (e.g., an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. An AE was considered as treatment-emergent if the date of onset was on or after the date of the first open-label study drug administration in this Study IPX203-B16-03 and no later than 1 day after the last study drug dose in the study. | From first dose up to 1 day after last dose (Up to 9 months/Early Termination [ET]) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in Parkinson Anxiety Scale (PAS): Total | The PAS is a three part participant answered assessment. Part 1 has 5 questions measuring persistent anxiety. Each question ranges from 0 - not at all, or never to 4 severe, or nearly always. Best score is 0; worst score is 20. Part 2 has 4 questions measuring episodic anxiety. Each question ranges from 0 - never to 4 - nearly always. Best score is 0; worst score is 16. Part 3 has 3 questions measuring avoidance behavior. Each question ranges from 0, never to 4 nearly always. Best score is 0; worst score is 12. Totals for all three parts are summed and ranges from 0 to 48, higher scores are associated with the more severe symptoms. | Baseline, Month 9/ET | 
| Non-Motor Symptom Assessment Scale (NMSS) for Parkinson's Disease (PD): Total | The NMSS assesses non-motor symptoms in Parkinson's Disease. It consists of 30 questions grouped into 9 domains: cardiovascular, sleep/fatigue, mood/cognition, perceptual problems/hallucinations, attention/memory, gastro-intestinal tract, urinary, sexual function, and miscellaneous. Severity symptoms are rated on a scale of 0-3 with 3 being most severe; and frequency on a scale of 1-4 with 4 being most frequent. Each question is answered with a severity and frequency rating which are then multiplied. The sum of the products gives the total score which ranges from 0 to 360 with a lower score more desirable than a higher score. | Baseline, Month 3, Month 6, and Month 9/ET | 
| Change From Baseline in Non-Motor Symptom Assessment Scale (NMSS) for Parkinson's Disease (PD): Total | The NMSS assesses non-motor symptoms in Parkinson's Disease. It consists of 30 questions grouped into 9 domains: cardiovascular, sleep/fatigue, mood/cognition, perceptual problems/hallucinations, attention/memory, gastro-intestinal tract, urinary, sexual function, and miscellaneous. Severity symptoms are rated on a scale of 0-3 with 3 being most severe; and frequency on a scale of 1-4 with 4 being most frequent. Each question is answered with a severity and frequency rating which are then multiplied. The sum of the products gives the total score which ranges from 0 to 360 with a lower score more desirable than a higher score. | Baseline, Month 9/ET | 
| Parkinson's Disease Sleep Scale-2 (PDSS-2) Total | The PDSS-2 is a 15 question participant response scale measuring the severity of sleep disturbance. Three domains are defined: disturbed sleep (Questions 1-3, 8, 14), motor symptoms at night (Questions 4-6, 12, 13), PD symptoms at night (Questions 7, 9-11, 15). Each question is rated as very often to never on a scale of 0-4. The best overall score is 0; the worst overall score is 60. | Baseline, Month 3, Month 6, and Month 9/ET | 
| Change From Baseline in Parkinson's Disease Sleep Scale-2 (PDSS-2):Total | The PDSS-2 is a 15 question participant response scale measuring the severity of sleep disturbance. Three domains are defined: disturbed sleep (Questions 1-3, 8, 14), motor symptoms at night (Questions 4-6, 12, 13), PD symptoms at night (Questions 7, 9-11, 15). Each question is rated as very often to never on a scale of 0-4. The best overall score is 0; the worst overall score is 60. | Baseline, Month 9/ET | 
| Treatment Satisfaction Assessment (TSA) | The TSA is a participant answered assessment rating treatment satisfaction on a scale of 1 to 7; 1 = Very much dissatisfied being least satisfied and 7 = Very much satisfied. | Month 3, Month 6 and Month 9/ET | 
| Percentage of Participants With TSA Scores 5-7 (Satisfied) Versus Scores 1-4 (Dissatisfied or Neutral) | The TSA is a participant answered assessment rating treatment satisfaction on a scale of 1 to 7; 1 = Very much dissatisfied being least satisfied and 7 = Very much satisfied. | Month 3, Month 6, and Month 9/ET | 
| Movement Disorders Society Version of the Unified Parkinson's Disease Rating Scale (MDS-UPDRS): Total | 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; 33 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 0-260). | Baseline, Month 3, Month 6, and Month 9/ET | 
| Change From Baseline in Movement Disorders Society Version of the Unified Parkinson's Disease Rating Scale (MDS-UPDRS): Total | 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; 33 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 0-260). | Baseline, Month 9/ET | 
| Movement Disorders Society Version of the Unified Parkinson's Disease Rating Scale (MDS-UPDRS): Part I | 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; 33 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 0-260). Part I score ranges from 0 to 52. A higher score indicated more severe symptoms of PD. | Baseline, Month 3, Month 6, and Month 9/ET | 
| Change From Baseline in Movement Disorders Society Version of the Unified Parkinson's Disease Rating Scale (MDS-UPDRS): Part I | 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; 33 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 0-260). Part I score ranges from 0 to 52. A higher score indicated more severe symptoms of PD. | Baseline, Month 9/ET | 
| Movement Disorders Society Version of the Unified Parkinson's Disease Rating Scale (MDS-UPDRS): Part II | 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; 33 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 0-260). Part II score ranges from 0 to 52. A higher score indicated more severe symptoms of PD. | Baseline, Month 3, Month 6, and Month 9/ET | 
| Change From Baseline in Movement Disorders Society Version of the Unified Parkinson's Disease Rating Scale (MDS-UPDRS): Part II | 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; 33 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 0-260). Part II score ranges from 0 to 52. A higher score indicated more severe symptoms of PD. | Baseline, Month 9/ET | 
| Movement Disorders Society Version of the Unified Parkinson's Disease Rating Scale (MDS-UPDRS): Part III | 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; 33 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 0-260). Part III score ranges from 0 to 132. A higher score indicated more severe symptoms of PD. | Baseline, Month 3, Month 6, and Month 9/ET | 
| Change From Baseline in Movement Disorders Society Version of the Unified Parkinson's Disease Rating Scale (MDS-UPDRS): Part III | 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; 33 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 0-260). Part III score ranges from 0 to 132. A higher score indicated more severe symptoms of PD. | Baseline, Month 9/ET | 
| Movement Disorders Society Version of the Unified Parkinson's Disease Rating Scale (MDS-UPDRS): Part IV | 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; 33 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 0-260). Part IV score ranges from 0 to 24. A higher score indicated more severe symptoms of PD. | Baseline, Month 3, Month 6, and Month 9/ET | 
| Change From Baseline in Movement Disorders Society Version of the Unified Parkinson's Disease Rating Scale (MDS-UPDRS): Part IV | 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; 33 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 0-260). Part IV score ranges from 0 to 24. A higher score indicated more severe symptoms of PD. | Baseline, Month 9/ET | 
| Movement Disorders Society Version of the Unified Parkinson's Disease Rating Scale (MDS-UPDRS): Sums of Part II and Part III | 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; 33 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 0-260). The scale range for Part II+III score is 0-184. A higher score indicated more severe symptoms of PD. | Baseline, Month 3, Month 6, and Month 9/ET | 
| Change From Baseline in Movement Disorders Society Version of the Unified Parkinson's Disease Rating Scale (MDS-UPDRS): Sums of Part II and Part III | 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; 33 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 0-260). The scale range for Part II+III score is 0-184. A higher score indicated more severe symptoms of PD. | Baseline, Month 9/ET | 
| Patient Global Impression of Severity (PGI-S) | The PGI-S is a participant answered assessment rating Parkinson's disease severity on a scale of 1 to 7; 1-Normal, not at all ill, 2-Borderline ill, 3-Mildly ill, 4-Moderately ill, 5-Markedly ill, 6-Severely ill, 7-Extremely severely ill. | Baseline, Month 3, Month 6, and Month 9/ET | 
| Change From Baseline in Patient Global Impression of Severity (PGI-S) | The PGI-S is a participant answered assessment rating Parkinson's disease severity on a scale of 1 to 7; 1-Normal, not at all ill, 2-Borderline ill, 3-Mildly ill, 4-Moderately ill, 5-Markedly ill, 6-Severely ill, 7-Extremely severely ill. | Baseline, Month 9/ET | 
| Percentage of Participants With a PGI-S ≥ 4 and PGI-S ≥ 5 | The PGI-S is a participant answered assessment rating Parkinson's disease severity on a scale of 1 to 7; 1-Normal, not at all ill, 2-Borderline ill, 3-Mildly ill, 4-Moderately ill, 5-Markedly ill, 6-Severely ill, 7-Extremely severely ill. | Baseline, Month 3, Month 6, and Month 9/ET | 
| Clinical Global Impression of Severity (CGI-S) | The CGI-S is a clinician scale rating the severity of the participant's illness on a scale of 1 to 7; 1-Normal, not at all ill, 2-Borderline ill, 3-Mildly ill, 4-Moderately ill, 5-Markedly ill, 6-Severely ill, 7-Among the most extremely ill of participants. | Baseline, Month 3, Month 6, Month 9/ET | 
| Change From Baseline in Clinical Global Impression of Severity (CGI-S) | The CGI-S is a clinician scale rating the severity of the participant's illness on a scale of 1 to 7; 1-Normal, not at all ill, 2-Borderline ill, 3-Mildly ill, 4-Moderately ill, 5-Markedly ill, 6-Severely ill, 7-Among the most extremely ill of participants. | Baseline, Month 9/ET | 
| Percentage of Participants With a CGI-S ≥ 4 and CGI-S ≥ 5 | The CGI-S is a clinician scale rating the severity of the participant's illness on a scale of 1 to 7; 1-Normal, not at all ill, 2-Borderline ill, 3-Mildly ill, 4-Moderately ill, 5-Markedly ill, 6-Severely ill, 7-Among the most extremely ill of participants. | Baseline, Month 3, Month 6, and Month 9/ET | 
| 39-item Parkinson's Disease Questionnaire (PDQ-39): Total | The PDQ-39 is a self-reported outcome of 39 questions relating to 8 domains: mobility (Questions 1-10), activities of daily living (ADL) (Questions 11-16), emotional well-being (Questions 17-22), stigma (Questions 23-26), social support (Questions 27-29), cognition (Questions 30-33), communication (Questions 34-36) and bodily discomfort (Questions 37-39). Each question is answered on a 5-point scale from 0 (Never) to 4 (Always / Cannot Do At All). Scores are calculated by summing the answers to the questions in the domain and converting to a scale from 0 to 100. Higher scores are associated with the more severe symptoms of the disease such as tremor and stiffness. | Baseline, Month 3, Month 6, and Month 9/ET | 
| Change From Baseline in PDQ-39: Total | The PDQ-39 is a self-reported outcome of 39 questions relating to 8 domains: mobility (Questions 1-10), activities of daily living (ADL) (Questions 11-16), emotional well-being (Questions 17-22), stigma (Questions 23-26), social support (Questions 27-29), cognition (Questions 30-33), communication (Questions 34-36) and bodily discomfort (Questions 37-39). Each question is answered on a 5-point scale from 0 (Never) to 4 (Always / Cannot Do At All). Scores are calculated by summing the answers to the questions in the domain and converting to a scale from 0 to 100. Higher scores are associated with the more severe symptoms of the disease such as tremor and stiffness. | Baseline, Month 9/ET | 
| Parkinson Anxiety Scale (PAS): Total | The PAS is a three part participant answered assessment. Part 1 has 5 questions measuring persistent anxiety. Each question ranges from 0 - not at all, or never to 4 severe, or nearly always. Best score is 0; worst score is 20. Part 2 has 4 questions measuring episodic anxiety. Each question ranges from 0 - never to 4 - nearly always. Best score is 0; worst score is 16. Part 3 has 3 questions measuring avoidance behavior. Each question ranges from 0, never to 4 nearly always. Best score is 0; worst score is 12. Totals for all three parts are summed and ranges from 0 to 48, higher scores are associated with the more severe symptoms. | Baseline, Month 3, Month 6, and Month 9/ET | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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motor fluctuations, IPX203