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A Phase IIa, Randomized, Double Blind, Placebo Controlled, Single Dose, Safety and Pharmacokinetic/Pharmacodynamic Study of INP103 (POD L-dopa) Administered in the Presence of Decarboxylase Inhibitor to L-dopa Responsive Parkinson's Disease Patients
This is a Phase IIa randomized, double-blind, placebo-controlled, single dose study to compare the safety, tolerability and PK/PDyn of intranasal L-dopa following administration of INP103 in the presence of L-dopa decarboxylase inhibitor (DCI) during an OFF episode.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Placebo | Placebo Comparator |
| |
| L-dopa 35 mg | Active Comparator |
| |
| L-dopa 70 mg | Active Comparator |
| |
| L-dopa 140 mg | Active Comparator |
| |
| L-dopa 70 mg/carbidopa 7 mg | Active Comparator |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Placebo | Combination Product | Delivered via the I231 POD (Precision Olfactory Delivery) device |
| |
| Measure | Description | Time Frame |
|---|---|---|
| Number of Participants With Treatment Emergent Adverse Events | Assessment of treatment emergent adverse events after single dosing with INP103 (L-dopa or L-dopa/carbidopa) | 7 days |
| Measure | Description | Time Frame |
|---|---|---|
| AUC0-2hr for L-dopa | Area under the Plasma Concentration-time Curve for L-dopa from Time = 0 to Time = 2 hours post dose. For the L-dopa 35 mg, L-dopa 70 mg, L-dopa 140 mg plasma samples were taken at pre-dose, 30, 60, 90 and 120 minutes post-dose. For the L-dopa 70 mg/carbidopa 7 mg treatment arm, plasma samples were taken at pre-dose, 5, 10, 15, 30, 45, 60, 90 and 120 minutes post-dose. | For L-dopa 35 mg, 70 mg, 140 mg plasma samples were taken at pre-dose, 30, 60, 90 and 120 minutes post-dose. For L-dopa 70 mg/carbidopa 7 mg, plasma samples were taken at pre-dose, 5, 10, 15, 30, 45, 60, 90 and 120 min |
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Inclusion Criteria:
Adult males and females, 40 to 80 years of age (inclusive) at the time of Screening (Visit1)
Diagnosed with Idiopathic PD (by UK Brain Bank Criteria) with Modified Hoehn & Yahr (H&Y) Stage I-III during an ON period at Visit 1
Subjects who are prone to (and recognize) OFF episodes (when their usual PD medication has worn off)
Shown to be responsive to L-dopa medication (≥ 30% improvement in MDS-UPDRS Part III Motor Examination score) as assessed during the Screening period (Visit 2)
On a stable dose of L-dopa containing medication for at least 2 weeks prior to Visit 1 (up to 1200 mg/day) with no single dose exceeding 250 mg. All other anti-PD medication (e.g. dopamine agonists [DAs], monoamine oxidase-B inhibitor (MAOB-I) or catechol-O-methyl transferase (COMT) inhibitors ARE allowed if the subject has been on a stable dose for at least 30 days prior to Visit 1.
Willing to omit their (usual) PD drugs (e.g. usual regular anti-PD medication including any L-dopa containing medication, DAs and/or COMT inhibitors and any required anti-OFF treatment) from 22:00 pm the evening prior to study dosing until 120 minutes post study treatment dosing.
Cohorts 1, 2 and 3 ONLY WILL take oral benserazide 25 mg on arrival at the research site (at 60 ± 5 minutes before dosing with INP103 or placebo).
Cohort 4 will omit oral benserazide and subjects may be dosed once OFF episode has been confirmed and all baseline assessments have been completed.
If female and of childbearing potential must agree to use adequate contraception (see Section 4.4) during the study
Able and willing to attend the necessary visits at the study centre
Willing to provide voluntary written informed consent signed prior to entry into the study
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Stephen B Shrewsbury, MD | Impel NeuroPharma, Seattle, WA (USA) | Study Chair |
| Terry O'Brien, MD/Prof | The Alfred Hospital, Melbourne, VIC (AUS) | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| The Brain and Mind Centre / Scientia Clinical Research | Sydney | New South Wales | 2031 | Australia | ||
| Q-Pharm |
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Confirmation of L-dopa responsiveness at Visit 2, prior to randomization
Parkinson's disease patients at movement disorder clinics in Australia
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| ID | Title | Description |
|---|---|---|
| FG000 | Placebo | Placebo: Delivered via the I231 POD (Precision Olfactory Delivery) device |
| FG001 | L-dopa 35 mg | L-dopa 35 mg: Delivered via the I231 POD (Precision Olfactory Delivery) device via one puff to one nostril |
| FG002 | L-dopa 70 mg | L-dopa 70mg: Delivered via the I231 POD (Precision Olfactory Delivery) device with two puffs, one to each nostril |
| FG003 | L-dopa 140 mg | L-dopa 140 mg: Delivered via the I231 POD (Precision Olfactory Delivery) device with four puffs, two to each nostril |
| FG004 | L-dopa 70 mg/Carbidopa 7 mg | L-dopa 70mg/carbidopa 7mg: Delivered via the I231 POD (Precision Olfactory Delivery) device with two puffs, one to each nostril |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
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| ID | Title | Description |
|---|---|---|
| BG000 | Placebo | Placebo: Delivered via the I231 POD (Precision Olfactory Delivery) device |
| BG001 | L-dopa 35 mg | L-dopa 35 mg: Delivered via the I231 POD (Precision Olfactory Delivery) device via one puff to one nostril |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants |
| 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 | Number of Participants With Treatment Emergent Adverse Events | Assessment of treatment emergent adverse events after single dosing with INP103 (L-dopa or L-dopa/carbidopa) | Posted | Count of Participants | Participants | 7 days |
|
7 days
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Placebo | Placebo: Delivered via the I231 POD (Precision Olfactory Delivery) device |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| upper respiratory tract infection | Respiratory, thoracic and mediastinal disorders | MedDRA (19.0) | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Karen Craig, PhD (Medical Writer) | Impel NeuroPharma | 206-568-1466 | kcraig@impelnp.com |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot | Yes | No | No | Study Protocol | Feb 1, 2019 | May 26, 2020 | Prot_000.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | Jun 10, 2019 | May 26, 2020 | SAP_001.pdf |
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| ID | Term |
|---|---|
| D010300 | Parkinson Disease |
| ID | Term |
|---|---|
| D020734 | Parkinsonian Disorders |
| D001480 | Basal Ganglia Diseases |
| D001927 | Brain Diseases |
| D002493 | Central Nervous System Diseases |
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| ID | Term |
|---|---|
| D007980 | Levodopa |
| D002230 | Carbidopa |
| ID | Term |
|---|---|
| D004295 | Dihydroxyphenylalanine |
| D002395 | Catecholamines |
| D000588 | Amines |
| D009930 | Organic Chemicals |
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Thirty-Two (32) to Thirty-Six (36) subjects will be randomized to treatment or placebo. INP103 is a drug-device combination product containing a drug component, L-dopa, and device component, the I231 Precision Olfactory Delivery (POD) device. In Cohorts 1, 2, and 3, L-dopa will be administered intranasally in single doses of one (35 mg), two (70 mg) or four (140 mg) puffs of INP103, 60 minutes after oral benserazide hydrochloride 25 mg.
In Cohort 4 the INP103 formulation will contain L-dopa:carbidopa administered nasally. Dosing will take place once OFF episode is confirmed and will not include predosing with oral benserazide.
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Double blind
| L-dopa 35 mg |
| Combination Product |
Delivered via the I231 POD (Precision Olfactory Delivery) device via one puff to one nostril |
|
| L-dopa 70mg | Combination Product | Delivered via the I231 POD (Precision Olfactory Delivery) device with two puffs, one to each nostril |
|
| L-dopa 140 mg | Combination Product | Delivered via the I231 POD (Precision Olfactory Delivery) device with four puffs, two to each nostril |
|
| L-dopa 70mg/carbidopa 7mg | Combination Product | Delivered via the I231 POD (Precision Olfactory Delivery) device with two puffs, one to each nostril |
|
| Cmax of L-dopa | Maximum Observed Plasma Concentration of L-dopa from Time = 0 to Time = 2 hours post dose. For the L-dopa 35 mg, L-dopa 70 mg, L-dopa 140 mg plasma samples were taken at pre-dose, 30, 60, 90 and 120 minutes post-dose. For the L-dopa 70 mg/carbidopa 7 mg treatment arm, plasma samples were taken at pre-dose, 5, 10, 15, 30, 45, 60, 90 and 120 minutes post-dose. | For L-dopa 35 mg, 70 mg, 140 mg plasma samples were taken at pre-dose, 30, 60, 90 and 120 minutes post-dose. For L-dopa 70 mg/carbidopa 7 mg, plasma samples were taken at pre-dose, 5, 10, 15, 30, 45, 60, 90 and 120 minutes post-dose. |
| Tmax of L-dopa | Time to Reach the Maximum Plasma Concentration (Cmax) of L-dopa | For L-dopa 35 mg, 70 mg, 140 mg plasma samples were taken at pre-dose, 30, 60, 90 and 120 minutes post-dose. For L-dopa 70 mg/carbidopa 7 mg, plasma samples were taken at pre-dose, 5, 10, 15, 30, 45, 60, 90 and 120 minutes post-dose. |
| Mean Change From Baseline in MDS-UPDRS Score Over 2 Hours for C1, C2, C3 and Change From Baseline at 30, 60, 90, 120 Minutes for C4, in MDS-UPDRS Part III Score | MDS-UPDRS is a clinimetric assessment of subjective and objective symptoms and signs of Parkinson's disease created by the Movement Disorder Society with high internal consistency. MDS-UPDRS retains the four-scale structure with a reorganization of the various subscales. The subscale used in this study is Part III, motor examination (18 items). The subscale has 0-4 ratings, where 0 = normal, 1 = slight, 2 = mild, 3 = moderate, and 4 = severe. Maximum score is 132, minimum is zero. High score means worse outcome. For the L-dopa 35 mg, L-dopa 70 mg, L-dopa 140 mg treatment groups, assessment occurred at pre-dose, 15, 30, 45, 60, 90 and 120 minutes post-dose. For the L-dopa 70 mg/carbidopa 7 mg treatment arm, assessment occurred at pre-dose, 30, 60, 90 and 120 minutes post-dose. | For L-dopa 35 mg, 70 mg, 140 mg, assessment occurred at pre-dose, 15, 30, 45, 60, 90 and 120 minutes post-dose. For L-dopa 70 mg/carbidopa 7 mg, assessment occurred at pre-dose, 30, 60, 90 and 120 minutes post-dose. |
| Time to Response (Defined as Improvement of 30% in MDS-UPDRS Part III Score From Baseline) | MDS-UPDRS is a clinimetric assessment of subjective and objective symptoms and signs of Parkinson's disease created by the Movement Disorder Society with high internal consistency. MDS-UPDRS retains the four-scale structure with a reorganization of the various subscales. The subscale used in this study is Part III, motor examination (18 items). The subscale now has 0-4 ratings, where 0 = normal, 1 = slight, 2 = mild, 3 = moderate, and 4 = severe. | 2 hours |
| Cumulative Number of Responders (Defined as Improvement of 30% in MDS-UPDRS Part III Score From Baseline) | MDS-UPDRS is a clinimetric assessment of subjective and objective symptoms and signs of Parkinson's disease created by the Movement Disorder Society with high internal consistency. MDS-UPDRS retains the four-scale structure with a reorganization of the various subscales. The subscale used in this study is Part III, motor examination (18 items). The subscale now has 0-4 ratings, where 0 = normal, 1 = slight, 2 = mild, 3 = moderate, and 4 = severe. | From time = 0 to 2 hours post-dose |
| Area Under the Curve (AUC) of Change From Baseline in MDS-UPDRS Part III Scores | MDS-UPDRS is a clinimetric assessment of subjective and objective symptoms and signs of Parkinson's disease created by the Movement Disorder Society with high internal consistency. MDS-UPDRS retains the four-scale structure with a reorganization of the various subscales. The subscale used in this study is Part III, motor examination (18 items). The subscale now has 0-4 ratings, where 0 = normal, 1 = slight, 2 = mild, 3 = moderate, and 4 = severe. | For L-dopa 35 mg, 70 mg, 140 mg, assessments were made at pre-dose, 15, 30, 45, 60, 90, 120 minutes post-dose. For L-dopa 70 mg/carbidopa 7 mg, assessments were made at pre-dose, 50, 60, 90, 120 minutes post-dose. |
| Mean Maximum Change From Baseline in MDS-UPDRS Part III Score | MDS-UPDRS is a clinimetric assessment of subjective and objective symptoms and signs of Parkinson's disease created by the Movement Disorder Society with high internal consistency. MDS-UPDRS retains the four-scale structure with a reorganization of the various subscales. The subscale used in this study is Part III, motor examination (18 items). The subscale now has 0-4 ratings, where 0 = normal, 1 = slight, 2 = mild, 3 = moderate, and 4 = severe. The total of the subscales has a maximum value of 132 and a minimum value of zero. Lower scores indicate better motor function. A negative change from baseline indicates improved motor function. | From time = 0 to 2 hours post-dose |
| Subjective Time to "ON" as Evaluated by the Investigator | Investigators will evaluate subjects' fluctuations in motor functions at 15, 30, 45, 60, 90, 120, and 240 minutes post-dose to determine if they are "ON". | 4 hours |
| Assessment of Time to "ON" as Evaluated by Subject Self-assessment | Subjects were asked to provide self-assessments at 15, 30, 45, 60, 90, 120, and 240 minutes post-dose as to whether they considered themselves to be "ON". | 4 hours |
| AUC0-2h for Carbidopa | Area under the concentration time curve for carbidopa | Plasma samples were taken at pre-dose, 5, 10, 15, 30, 45, 60, 90 and 120 minutes post-dose and AUC calculated from these from time 0 to 120 minutes. |
| Cmax of Carbidopa | Maximum concentration of carbidopa | For L-dopa 70 mg/carbidopa 7 mg, plasma samples were taken at pre-dose, 5, 10, 15, 30, 45, 60, 90 and 120 minutes post-dose. |
| Tmax of Carbidopa | Time to reach the maximum concentration of carbidopa | For L-dopa 70 mg/carbidopa 7 mg, plasma samples were taken at pre-dose, 5, 10, 15, 30, 45, 60, 90 and 120 minutes post-dose. |
| Duration of Response, Where Response is Defined as an Improvement of 30% in MDS-UPDRS Part III Score From Baseline. | MDS-UPDRS is a clinimetric assessment of subjective and objective symptoms and signs of Parkinson's disease created by the Movement Disorder Society with high internal consistency. MDS-UPDRS retains the four-scale structure with a reorganization of the various subscales. The subscale used in this study is Part III, motor examination (18 items). The subscale has 0-4 ratings, where 0 = normal, 1 = slight, 2 = mild, 3 = moderate, and 4 = severe. Maximum score is 132, minimum is zero. High score means worse outcome. | 2 hours |
| Brisbane |
| Queensland |
| Australia |
| The Mater Hospital | Brisbane | Queensland | Australia |
| The Alfred Hospital | Melbourne | Victoria | Australia |
| Perron Institute | Perth | Western Australia | 6009 | Australia |
| BG002 | L-dopa 70 mg | L-dopa 70mg: Delivered via the I231 POD (Precision Olfactory Delivery) device with two puffs, one to each nostril |
| BG003 | L-dopa 140 mg | L-dopa 140 mg: Delivered via the I231 POD (Precision Olfactory Delivery) device with four puffs, two to each nostril |
| BG004 | L-dopa 70 mg/Carbidopa 7 mg | L-dopa 70mg/carbidopa 7mg: Delivered via the I231 POD (Precision Olfactory Delivery) device with two puffs, one to each nostril |
| BG005 | Total | Total of all reporting groups |
| Participants |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Ethnicity (NIH/OMB) | Count of Participants | Participants |
|
| Race (NIH/OMB) | Count of Participants | Participants |
|
| Region of Enrollment | Number | participants |
|
L-dopa 70mg: Delivered via the I231 POD (Precision Olfactory Delivery) device with two puffs, one to each nostril
| OG003 | L-dopa 140 mg | L-dopa 140 mg: Delivered via the I231 POD (Precision Olfactory Delivery) device with four puffs, two to each nostril |
| OG004 | L-dopa 70 mg/Carbidopa 7 mg | L-dopa 70mg/carbidopa 7mg: Delivered via the I231 POD (Precision Olfactory Delivery) device with two puffs, one to each nostril |
|
|
| Secondary | AUC0-2hr for L-dopa | Area under the Plasma Concentration-time Curve for L-dopa from Time = 0 to Time = 2 hours post dose. For the L-dopa 35 mg, L-dopa 70 mg, L-dopa 140 mg plasma samples were taken at pre-dose, 30, 60, 90 and 120 minutes post-dose. For the L-dopa 70 mg/carbidopa 7 mg treatment arm, plasma samples were taken at pre-dose, 5, 10, 15, 30, 45, 60, 90 and 120 minutes post-dose. | Subjects who received L-dopa or L-dopa/carbidopa. Placebo subjects therefore not included. | Posted | Mean | Standard Deviation | hours*ng/mL | For L-dopa 35 mg, 70 mg, 140 mg plasma samples were taken at pre-dose, 30, 60, 90 and 120 minutes post-dose. For L-dopa 70 mg/carbidopa 7 mg, plasma samples were taken at pre-dose, 5, 10, 15, 30, 45, 60, 90 and 120 min |
|
|
|
| Secondary | Cmax of L-dopa | Maximum Observed Plasma Concentration of L-dopa from Time = 0 to Time = 2 hours post dose. For the L-dopa 35 mg, L-dopa 70 mg, L-dopa 140 mg plasma samples were taken at pre-dose, 30, 60, 90 and 120 minutes post-dose. For the L-dopa 70 mg/carbidopa 7 mg treatment arm, plasma samples were taken at pre-dose, 5, 10, 15, 30, 45, 60, 90 and 120 minutes post-dose. | Subjects who received L-dopa. Placebo subjects not included. | Posted | Mean | Standard Deviation | ng/mL | For L-dopa 35 mg, 70 mg, 140 mg plasma samples were taken at pre-dose, 30, 60, 90 and 120 minutes post-dose. For L-dopa 70 mg/carbidopa 7 mg, plasma samples were taken at pre-dose, 5, 10, 15, 30, 45, 60, 90 and 120 minutes post-dose. |
|
|
|
| Secondary | Tmax of L-dopa | Time to Reach the Maximum Plasma Concentration (Cmax) of L-dopa | Subjects who received L-dopa. Placebo subjects not included. | Posted | Mean | Standard Deviation | minutes | For L-dopa 35 mg, 70 mg, 140 mg plasma samples were taken at pre-dose, 30, 60, 90 and 120 minutes post-dose. For L-dopa 70 mg/carbidopa 7 mg, plasma samples were taken at pre-dose, 5, 10, 15, 30, 45, 60, 90 and 120 minutes post-dose. |
|
|
|
| Secondary | Mean Change From Baseline in MDS-UPDRS Score Over 2 Hours for C1, C2, C3 and Change From Baseline at 30, 60, 90, 120 Minutes for C4, in MDS-UPDRS Part III Score | MDS-UPDRS is a clinimetric assessment of subjective and objective symptoms and signs of Parkinson's disease created by the Movement Disorder Society with high internal consistency. MDS-UPDRS retains the four-scale structure with a reorganization of the various subscales. The subscale used in this study is Part III, motor examination (18 items). The subscale has 0-4 ratings, where 0 = normal, 1 = slight, 2 = mild, 3 = moderate, and 4 = severe. Maximum score is 132, minimum is zero. High score means worse outcome. For the L-dopa 35 mg, L-dopa 70 mg, L-dopa 140 mg treatment groups, assessment occurred at pre-dose, 15, 30, 45, 60, 90 and 120 minutes post-dose. For the L-dopa 70 mg/carbidopa 7 mg treatment arm, assessment occurred at pre-dose, 30, 60, 90 and 120 minutes post-dose. | All participants were analyzed. | Posted | Mean | Standard Deviation | score on a scale | For L-dopa 35 mg, 70 mg, 140 mg, assessment occurred at pre-dose, 15, 30, 45, 60, 90 and 120 minutes post-dose. For L-dopa 70 mg/carbidopa 7 mg, assessment occurred at pre-dose, 30, 60, 90 and 120 minutes post-dose. |
|
|
|
| Secondary | Time to Response (Defined as Improvement of 30% in MDS-UPDRS Part III Score From Baseline) | MDS-UPDRS is a clinimetric assessment of subjective and objective symptoms and signs of Parkinson's disease created by the Movement Disorder Society with high internal consistency. MDS-UPDRS retains the four-scale structure with a reorganization of the various subscales. The subscale used in this study is Part III, motor examination (18 items). The subscale now has 0-4 ratings, where 0 = normal, 1 = slight, 2 = mild, 3 = moderate, and 4 = severe. | All participants were analyzed. | Posted | Median | 95% Confidence Interval | minutes | 2 hours |
|
|
|
| Secondary | Cumulative Number of Responders (Defined as Improvement of 30% in MDS-UPDRS Part III Score From Baseline) | MDS-UPDRS is a clinimetric assessment of subjective and objective symptoms and signs of Parkinson's disease created by the Movement Disorder Society with high internal consistency. MDS-UPDRS retains the four-scale structure with a reorganization of the various subscales. The subscale used in this study is Part III, motor examination (18 items). The subscale now has 0-4 ratings, where 0 = normal, 1 = slight, 2 = mild, 3 = moderate, and 4 = severe. | All participants were analyzed. | Posted | Count of Participants | Participants | From time = 0 to 2 hours post-dose |
|
|
|
| Secondary | Area Under the Curve (AUC) of Change From Baseline in MDS-UPDRS Part III Scores | MDS-UPDRS is a clinimetric assessment of subjective and objective symptoms and signs of Parkinson's disease created by the Movement Disorder Society with high internal consistency. MDS-UPDRS retains the four-scale structure with a reorganization of the various subscales. The subscale used in this study is Part III, motor examination (18 items). The subscale now has 0-4 ratings, where 0 = normal, 1 = slight, 2 = mild, 3 = moderate, and 4 = severe. | All participants were included in the analysis | Posted | Mean | Standard Deviation | change in score*minutes | For L-dopa 35 mg, 70 mg, 140 mg, assessments were made at pre-dose, 15, 30, 45, 60, 90, 120 minutes post-dose. For L-dopa 70 mg/carbidopa 7 mg, assessments were made at pre-dose, 50, 60, 90, 120 minutes post-dose. |
|
|
|
| Secondary | Mean Maximum Change From Baseline in MDS-UPDRS Part III Score | MDS-UPDRS is a clinimetric assessment of subjective and objective symptoms and signs of Parkinson's disease created by the Movement Disorder Society with high internal consistency. MDS-UPDRS retains the four-scale structure with a reorganization of the various subscales. The subscale used in this study is Part III, motor examination (18 items). The subscale now has 0-4 ratings, where 0 = normal, 1 = slight, 2 = mild, 3 = moderate, and 4 = severe. The total of the subscales has a maximum value of 132 and a minimum value of zero. Lower scores indicate better motor function. A negative change from baseline indicates improved motor function. | All subjects were included in this analysis | Posted | Mean | Standard Deviation | score on a scale | From time = 0 to 2 hours post-dose |
|
|
|
| Secondary | Subjective Time to "ON" as Evaluated by the Investigator | Investigators will evaluate subjects' fluctuations in motor functions at 15, 30, 45, 60, 90, 120, and 240 minutes post-dose to determine if they are "ON". | All participants were included in the analysis | Posted | Median | Full Range | minutes | 4 hours |
|
|
|
| Secondary | Assessment of Time to "ON" as Evaluated by Subject Self-assessment | Subjects were asked to provide self-assessments at 15, 30, 45, 60, 90, 120, and 240 minutes post-dose as to whether they considered themselves to be "ON". | All participants were included in the analysis. | Posted | Median | Full Range | minutes | 4 hours |
|
|
|
| Secondary | AUC0-2h for Carbidopa | Area under the concentration time curve for carbidopa | Subjects who received the combination of L-dopa/carbidopa | Posted | Mean | Standard Deviation | hours*ng/mL | Plasma samples were taken at pre-dose, 5, 10, 15, 30, 45, 60, 90 and 120 minutes post-dose and AUC calculated from these from time 0 to 120 minutes. |
|
|
|
| Secondary | Cmax of Carbidopa | Maximum concentration of carbidopa | Subjects who received L-dopa/carbidopa | Posted | Mean | Standard Deviation | ng/mL | For L-dopa 70 mg/carbidopa 7 mg, plasma samples were taken at pre-dose, 5, 10, 15, 30, 45, 60, 90 and 120 minutes post-dose. |
|
|
|
| Secondary | Tmax of Carbidopa | Time to reach the maximum concentration of carbidopa | Subjects who received L-dopa/carbidopa | Posted | Mean | Standard Deviation | minutes | For L-dopa 70 mg/carbidopa 7 mg, plasma samples were taken at pre-dose, 5, 10, 15, 30, 45, 60, 90 and 120 minutes post-dose. |
|
|
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| Secondary | Duration of Response, Where Response is Defined as an Improvement of 30% in MDS-UPDRS Part III Score From Baseline. | MDS-UPDRS is a clinimetric assessment of subjective and objective symptoms and signs of Parkinson's disease created by the Movement Disorder Society with high internal consistency. MDS-UPDRS retains the four-scale structure with a reorganization of the various subscales. The subscale used in this study is Part III, motor examination (18 items). The subscale has 0-4 ratings, where 0 = normal, 1 = slight, 2 = mild, 3 = moderate, and 4 = severe. Maximum score is 132, minimum is zero. High score means worse outcome. | All participants were analyzed. | Posted | Mean | Standard Deviation | minutes | 2 hours |
|
|
|
| 0 |
| 8 |
| 0 |
| 8 |
| 5 |
| 8 |
| EG001 | L-dopa 35 mg | L-dopa 35 mg: Delivered via the I231 POD (Precision Olfactory Delivery) device via one puff to one nostril | 0 | 6 | 0 | 6 | 5 | 6 |
| EG002 | L-dopa 70 mg | L-dopa 70mg: Delivered via the I231 POD (Precision Olfactory Delivery) device with two puffs, one to each nostril | 0 | 6 | 0 | 6 | 3 | 6 |
| EG003 | L-dopa 140 mg | L-dopa 140 mg: Delivered via the I231 POD (Precision Olfactory Delivery) device with four puffs, two to each nostril | 0 | 6 | 0 | 6 | 4 | 6 |
| EG004 | L-dopa 70 mg/Carbidopa 7 mg | L-dopa 70mg/carbidopa 7mg: Delivered via the I231 POD (Precision Olfactory Delivery) device with two puffs, one to each nostril | 0 | 6 | 0 | 6 | 5 | 6 |
| rhinorrhoea | Respiratory, thoracic and mediastinal disorders | MedDRA (19.0) | Systematic Assessment |
|
| sinus pain | Respiratory, thoracic and mediastinal disorders | MedDRA (19.0) | Systematic Assessment |
|
| cough | Respiratory, thoracic and mediastinal disorders | MedDRA (19.0) | Systematic Assessment |
|
| dry throat | Respiratory, thoracic and mediastinal disorders | MedDRA (19.0) | Systematic Assessment |
|
| dyspnoea | Respiratory, thoracic and mediastinal disorders | MedDRA (19.0) | Systematic Assessment |
|
| nasal congestion | Respiratory, thoracic and mediastinal disorders | MedDRA (19.0) | Systematic Assessment |
|
| nasal discomfort | Respiratory, thoracic and mediastinal disorders | MedDRA (19.0) | Systematic Assessment |
|
| nasal dryness | Respiratory, thoracic and mediastinal disorders | MedDRA (19.0) | Systematic Assessment |
|
| nasal oedema | Respiratory, thoracic and mediastinal disorders | MedDRA (19.0) | Systematic Assessment |
|
| paranasal sinus discomfort | Respiratory, thoracic and mediastinal disorders | MedDRA (19.0) | Systematic Assessment |
|
| paranasal sinus hyposecretion | Respiratory, thoracic and mediastinal disorders | MedDRA (19.0) | Systematic Assessment |
|
| sneezing | Respiratory, thoracic and mediastinal disorders | MedDRA (19.0) | Systematic Assessment |
|
| headache | Nervous system disorders | MedDRA (19.0) | Systematic Assessment |
|
| somnolence | Nervous system disorders | MedDRA (19.0) | Systematic Assessment |
|
| dizziness | Nervous system disorders | MedDRA (19.0) | Systematic Assessment |
|
| fatigue | General disorders | MedDRA (19.0) | Systematic Assessment |
|
| feeling abnormal | General disorders | MedDRA (19.0) | Systematic Assessment |
|
| hyperthermia | General disorders | MedDRA (19.0) | Systematic Assessment |
|
| hypertension | Vascular disorders | MedDRA (19.0) | Systematic Assessment |
|
| orthostatic hypotension | Vascular disorders | MedDRA (19.0) | Systematic Assessment |
|
| rhinitis | Infections and infestations | MedDRA (19.0) | Systematic Assessment |
|
| urinary tract infection | Infections and infestations | MedDRA (19.0) | Systematic Assessment |
|
| joint noise | Musculoskeletal and connective tissue disorders | MedDRA (19.0) | Systematic Assessment |
|
| muscle spasms | Musculoskeletal and connective tissue disorders | MedDRA (19.0) | Systematic Assessment |
|
| tachycardia | Cardiac disorders | MedDRA (19.0) | Systematic Assessment |
|
| lacrimation increased | Eye disorders | MedDRA (19.0) | Systematic Assessment |
|
| procedural pain | Injury, poisoning and procedural complications | MedDRA (19.0) | Systematic Assessment |
|
Not provided
Not provided
| D009422 | Nervous System Diseases |
| D009069 | Movement Disorders |
| D000080874 | Synucleinopathies |
| D019636 | Neurodegenerative Diseases |
| D002396 |
| Catechols |
| D010636 | Phenols |
| D001555 | Benzene Derivatives |
| D006841 | Hydrocarbons, Aromatic |
| D006844 | Hydrocarbons, Cyclic |
| D006838 | Hydrocarbons |
| D010649 | Phenylalanine |
| D024322 | Amino Acids, Aromatic |
| D000598 | Amino Acids, Cyclic |
| D000596 | Amino Acids |
| D000602 | Amino Acids, Peptides, and Proteins |
| D014443 | Tyrosine |
| D008750 | Methyldopa |
| D006834 | Hydrazines |
|
| 30 minutes |
|
|
| 45 minutes |
|
|
| 60 minutes |
|
|
| 90 minutes |
|
|
| 120 minutes |
|
|
|
| 30 minutes |
|
|
| 45 minutes |
|
|
| 60 minutes |
|
|
| 90 minutes |
|
|
| 120 minutes |
|
|
|
| 30 minutes |
|
|
| 45 minutes |
|
|
| 60 minutes |
|
|
| 90 minutes |
|
|
| 120 minutes |
|
|