Parkinson's Disease
Conditions
Keywords
Parkinsons, L-dopa, levodopa, ON, OFF, PD, POD device, I231, benserazide, Precision olfactory delivery, MDS-UPDRS, Carbidopa, DCI, Decarboxylase Inhibitor
Brief summary
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
Detailed description
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.
Interventions
COMBINATION_PRODUCTPlacebo
Delivered via the I231 POD (Precision Olfactory Delivery) device
COMBINATION_PRODUCTL-dopa 35 mg
Delivered via the I231 POD (Precision Olfactory Delivery) device via one puff to one nostril
COMBINATION_PRODUCTL-dopa 70mg
Delivered via the I231 POD (Precision Olfactory Delivery) device with two puffs, one to each nostril
COMBINATION_PRODUCTL-dopa 140 mg
Delivered via the I231 POD (Precision Olfactory Delivery) device with four puffs, two to each nostril
COMBINATION_PRODUCTL-dopa 70mg/carbidopa 7mg
Delivered via the I231 POD (Precision Olfactory Delivery) device with two puffs, one to each nostril
Sponsors
Impel Pharmaceuticals
Study design
Allocation
RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Masking description
Double blind
Intervention model description
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.
Eligibility
Sex/Gender
ALL
Age
40 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
1. Adult males and females, 40 to 80 years of age (inclusive) at the time of Screening (Visit1) 2. 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 3. Subjects who are prone to (and recognize) OFF episodes (when their usual PD medication has worn off) 4. 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) 5. 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. 6. 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. 7. If female and of childbearing potential must agree to use adequate contraception (see Section 4.4) during the study 8. Able and willing to attend the necessary visits at the study centre 9. Willing to provide voluntary written informed consent signed prior to entry into the study
Exclusion criteria
1. Severe dyskinesia (defined as per MDS-UPDRS) during a 'normal day' that would significantly interfere with the subject's ability to perform study assessments 2. In receipt of L-dopa containing medication at \> 1200 mg/day 3. History of significant psychotic episode(s) within the previous 12 months in the opinion of the Investigator, or currently receiving anti-psychotic medication at a moderate dose (quetiapine \>50 mg/day, risperidone \>1 mg/day or olanzapine \>2.5 mg/day) 4. Mini Mental State Examination (MMSE) ≤ 25 as documented within the previous 36 months or as assessed by Investigator during Screening 5. History of suicidal ideation or attempted suicide within previous 12 months 6. Narrow-angle glaucoma 7. Presence of skin lesions that, in the opinion of the Investigator, may be cancerous 8. Females who are pregnant, planning a pregnancy or lactating 9. Subjects with any underlying physical condition that, in the opinion of the Investigator, would make it unlikely that the subject will comply with or be able to complete the study requirements 10. Use of any medication likely to interact with benserazide, carbidopa or INP103 (see Appendix 5) 11. Laboratory test abnormalities at Screening (Visit 1) deemed clinically significant by the Investigator. 12. History or presence of alcoholism or drug abuse within the 2 years prior to INP103 or placebo dosing 13. Administration of an investigational product in another trial within 30 days or 5 half-lives (whichever is longer) prior to INP103 or placebo dosing 14. Significant nasal congestion, physical blockage in either nostril, or significantly deviated nasal septum as evaluated by the PI or other suitably trained healthcare professional 15. Subjects who have previously shown hypersensitivity to L-dopa or benserazide (for Cohorts 1, 2 and 3), or L-dopa or carbidopa (for Cohort 4) or any of their excipients
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Treatment Emergent Adverse Events | 7 days | Assessment of treatment emergent adverse events after single dosing with INP103 (L-dopa or L-dopa/carbidopa) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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. | 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. |
| Tmax 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. | Time to Reach the Maximum Plasma Concentration (Cmax) of L-dopa |
| 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 | 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. | 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. |
| Time to Response (Defined as Improvement of 30% in MDS-UPDRS Part III Score From Baseline) | 2 hours | 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. |
| Cumulative Number of Responders (Defined as Improvement of 30% in MDS-UPDRS Part III Score From Baseline) | From time = 0 to 2 hours post-dose | 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. |
| Area Under the Curve (AUC) of Change From Baseline in MDS-UPDRS Part III Scores | 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. | 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. |
| AUC0-2hr for 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 min | 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. |
| Subjective Time to ON as Evaluated by the Investigator | 4 hours | 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. |
| Assessment of Time to ON as Evaluated by Subject Self-assessment | 4 hours | 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. |
| AUC0-2h 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. | Area under the concentration time curve for carbidopa |
| Cmax 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. | Maximum concentration of carbidopa |
| Tmax 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. | Time to reach the maximum concentration of carbidopa |
| Duration of Response, Where Response is Defined as an Improvement of 30% in MDS-UPDRS Part III Score From Baseline. | 2 hours | 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. |
| Mean Maximum Change From Baseline in MDS-UPDRS Part III Score | From time = 0 to 2 hours post-dose | 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. |
Countries
Australia
Participant flow
Recruitment details
Parkinson's disease patients at movement disorder clinics in Australia
Pre-assignment details
Confirmation of L-dopa responsiveness at Visit 2, prior to randomization
Participants by arm
| Arm | Count |
|---|---|
| Placebo Placebo: Delivered via the I231 POD (Precision Olfactory Delivery) device | 8 |
| L-dopa 35 mg L-dopa 35 mg: Delivered via the I231 POD (Precision Olfactory Delivery) device via one puff to one nostril | 6 |
| L-dopa 70 mg L-dopa 70mg: Delivered via the I231 POD (Precision Olfactory Delivery) device with two puffs, one to each nostril | 6 |
| L-dopa 140 mg L-dopa 140 mg: Delivered via the I231 POD (Precision Olfactory Delivery) device with four puffs, two to each nostril | 6 |
| 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 | 6 |
| Total | 32 |
Baseline characteristics
| Characteristic | Placebo | L-dopa 35 mg | L-dopa 70 mg | L-dopa 140 mg | L-dopa 70 mg/Carbidopa 7 mg | Total |
|---|---|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 2 Participants | 3 Participants | 5 Participants | 3 Participants | 1 Participants | 14 Participants |
| Age, Categorical Between 18 and 65 years | 6 Participants | 3 Participants | 1 Participants | 3 Participants | 5 Participants | 18 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 8 Participants | 6 Participants | 6 Participants | 6 Participants | 6 Participants | 32 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 2 Participants | 2 Participants | 0 Participants | 0 Participants | 0 Participants | 4 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 6 Participants | 4 Participants | 6 Participants | 6 Participants | 6 Participants | 28 Participants |
| Region of Enrollment Australia | 8 participants | 6 participants | 6 participants | 6 participants | 6 participants | 32 participants |
| Sex: Female, Male Female | 3 Participants | 2 Participants | 2 Participants | 2 Participants | 3 Participants | 12 Participants |
| Sex: Female, Male Male | 5 Participants | 4 Participants | 4 Participants | 4 Participants | 3 Participants | 20 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk |
|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 8 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 6 |
| other Total, other adverse events | 5 / 8 | 5 / 6 | 3 / 6 | 4 / 6 | 5 / 6 |
| serious Total, serious adverse events | 0 / 8 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 6 |
Outcome results
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)
Time frame: 7 days
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Placebo | Number of Participants With Treatment Emergent Adverse Events | 5 Participants |
| L-dopa 35 mg | Number of Participants With Treatment Emergent Adverse Events | 5 Participants |
| L-dopa 70 mg | Number of Participants With Treatment Emergent Adverse Events | 3 Participants |
| L-dopa 140 mg | Number of Participants With Treatment Emergent Adverse Events | 4 Participants |
| L-dopa 70 mg/Carbidopa 7 mg | Number of Participants With Treatment Emergent Adverse Events | 5 Participants |
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.
Time frame: 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.
Population: All participants were included in the analysis
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Area Under the Curve (AUC) of Change From Baseline in MDS-UPDRS Part III Scores | 60 minutes | -573.88 change in score*minutes | Standard Deviation 371.782 |
| Placebo | Area Under the Curve (AUC) of Change From Baseline in MDS-UPDRS Part III Scores | 15 minutes | -26.25 change in score*minutes | Standard Deviation 29.144 |
| Placebo | Area Under the Curve (AUC) of Change From Baseline in MDS-UPDRS Part III Scores | 45 minutes | -264.92 change in score*minutes | Standard Deviation 178.969 |
| Placebo | Area Under the Curve (AUC) of Change From Baseline in MDS-UPDRS Part III Scores | 30 minutes | -237.63 change in score*minutes | Standard Deviation 276.197 |
| Placebo | Area Under the Curve (AUC) of Change From Baseline in MDS-UPDRS Part III Scores | 90 minutes | -919.75 change in score*minutes | Standard Deviation 530.872 |
| Placebo | Area Under the Curve (AUC) of Change From Baseline in MDS-UPDRS Part III Scores | 120 minutes | -1215.75 change in score*minutes | Standard Deviation 765.287 |
| L-dopa 35 mg | Area Under the Curve (AUC) of Change From Baseline in MDS-UPDRS Part III Scores | 15 minutes | -33.50 change in score*minutes | Standard Deviation 33.697 |
| L-dopa 35 mg | Area Under the Curve (AUC) of Change From Baseline in MDS-UPDRS Part III Scores | 60 minutes | -296.50 change in score*minutes | Standard Deviation 241.271 |
| L-dopa 35 mg | Area Under the Curve (AUC) of Change From Baseline in MDS-UPDRS Part III Scores | 30 minutes | -138.58 change in score*minutes | Standard Deviation 138.105 |
| L-dopa 35 mg | Area Under the Curve (AUC) of Change From Baseline in MDS-UPDRS Part III Scores | 120 minutes | -903.67 change in score*minutes | Standard Deviation 804.196 |
| L-dopa 35 mg | Area Under the Curve (AUC) of Change From Baseline in MDS-UPDRS Part III Scores | 90 minutes | -575.17 change in score*minutes | Standard Deviation 486.241 |
| L-dopa 35 mg | Area Under the Curve (AUC) of Change From Baseline in MDS-UPDRS Part III Scores | 45 minutes | -201.92 change in score*minutes | Standard Deviation 162.256 |
| L-dopa 70 mg | Area Under the Curve (AUC) of Change From Baseline in MDS-UPDRS Part III Scores | 15 minutes | 7.00 change in score*minutes | Standard Deviation 69.206 |
| L-dopa 70 mg | Area Under the Curve (AUC) of Change From Baseline in MDS-UPDRS Part III Scores | 30 minutes | -50.50 change in score*minutes | Standard Deviation 203.053 |
| L-dopa 70 mg | Area Under the Curve (AUC) of Change From Baseline in MDS-UPDRS Part III Scores | 45 minutes | -210.50 change in score*minutes | Standard Deviation 334.216 |
| L-dopa 70 mg | Area Under the Curve (AUC) of Change From Baseline in MDS-UPDRS Part III Scores | 60 minutes | -424.25 change in score*minutes | Standard Deviation 464.545 |
| L-dopa 70 mg | Area Under the Curve (AUC) of Change From Baseline in MDS-UPDRS Part III Scores | 90 minutes | -896.67 change in score*minutes | Standard Deviation 671.116 |
| L-dopa 70 mg | Area Under the Curve (AUC) of Change From Baseline in MDS-UPDRS Part III Scores | 120 minutes | -1324.83 change in score*minutes | Standard Deviation 863.122 |
| L-dopa 140 mg | Area Under the Curve (AUC) of Change From Baseline in MDS-UPDRS Part III Scores | 45 minutes | -426.83 change in score*minutes | Standard Deviation 274.566 |
| L-dopa 140 mg | Area Under the Curve (AUC) of Change From Baseline in MDS-UPDRS Part III Scores | 90 minutes | -968.08 change in score*minutes | Standard Deviation 587.629 |
| L-dopa 140 mg | Area Under the Curve (AUC) of Change From Baseline in MDS-UPDRS Part III Scores | 15 minutes | -67.50 change in score*minutes | Standard Deviation 46.233 |
| L-dopa 140 mg | Area Under the Curve (AUC) of Change From Baseline in MDS-UPDRS Part III Scores | 30 minutes | -232.83 change in score*minutes | Standard Deviation 153.638 |
| L-dopa 140 mg | Area Under the Curve (AUC) of Change From Baseline in MDS-UPDRS Part III Scores | 60 minutes | -630.58 change in score*minutes | Standard Deviation 401.947 |
| L-dopa 140 mg | Area Under the Curve (AUC) of Change From Baseline in MDS-UPDRS Part III Scores | 120 minutes | -1210.58 change in score*minutes | Standard Deviation 714.512 |
| L-dopa 70 mg/Carbidopa 7 mg | Area Under the Curve (AUC) of Change From Baseline in MDS-UPDRS Part III Scores | 45 minutes | NA change in score*minutes | — |
| L-dopa 70 mg/Carbidopa 7 mg | Area Under the Curve (AUC) of Change From Baseline in MDS-UPDRS Part III Scores | 90 minutes | -362.75 change in score*minutes | Standard Deviation 676.456 |
| L-dopa 70 mg/Carbidopa 7 mg | Area Under the Curve (AUC) of Change From Baseline in MDS-UPDRS Part III Scores | 30 minutes | -230.08 change in score*minutes | Standard Deviation 250.832 |
| L-dopa 70 mg/Carbidopa 7 mg | Area Under the Curve (AUC) of Change From Baseline in MDS-UPDRS Part III Scores | 60 minutes | -295.25 change in score*minutes | Standard Deviation 412.042 |
| L-dopa 70 mg/Carbidopa 7 mg | Area Under the Curve (AUC) of Change From Baseline in MDS-UPDRS Part III Scores | 15 minutes | NA change in score*minutes | — |
| L-dopa 70 mg/Carbidopa 7 mg | Area Under the Curve (AUC) of Change From Baseline in MDS-UPDRS Part III Scores | 120 minutes | -465.25 change in score*minutes | Standard Deviation 932.842 |
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.
Time frame: 4 hours
Population: All participants were included in the analysis.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Placebo | Assessment of Time to ON as Evaluated by Subject Self-assessment | 40.0 minutes |
| L-dopa 35 mg | Assessment of Time to ON as Evaluated by Subject Self-assessment | 240.0 minutes |
| L-dopa 70 mg | Assessment of Time to ON as Evaluated by Subject Self-assessment | 39.0 minutes |
| L-dopa 140 mg | Assessment of Time to ON as Evaluated by Subject Self-assessment | 30.0 minutes |
| L-dopa 70 mg/Carbidopa 7 mg | Assessment of Time to ON as Evaluated by Subject Self-assessment | 232.5 minutes |
Secondary
AUC0-2h for Carbidopa
Area under the concentration time curve for carbidopa
Time frame: 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.
Population: Subjects who received the combination of L-dopa/carbidopa
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | AUC0-2h for Carbidopa | 114.80 hours*ng/mL | Standard Deviation 30.384 |
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.
Time frame: 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
Population: Subjects who received L-dopa or L-dopa/carbidopa. Placebo subjects therefore not included.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | AUC0-2hr for L-dopa | 240.71 hours*ng/mL | Standard Deviation 117.819 |
| L-dopa 35 mg | AUC0-2hr for L-dopa | 463.49 hours*ng/mL | Standard Deviation 260.093 |
| L-dopa 70 mg | AUC0-2hr for L-dopa | 725.29 hours*ng/mL | Standard Deviation 456.566 |
| L-dopa 140 mg | AUC0-2hr for L-dopa | 552.75 hours*ng/mL | Standard Deviation 177.979 |
Secondary
Cmax of Carbidopa
Maximum concentration of carbidopa
Time frame: 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.
Population: Subjects who received L-dopa/carbidopa
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Cmax of Carbidopa | 80.23 ng/mL | Standard Deviation 22.945 |
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.
Time frame: 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.
Population: Subjects who received L-dopa. Placebo subjects not included.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Cmax of L-dopa | 185.80 ng/mL | Standard Deviation 78.144 |
| L-dopa 35 mg | Cmax of L-dopa | 362.68 ng/mL | Standard Deviation 195.265 |
| L-dopa 70 mg | Cmax of L-dopa | 643.65 ng/mL | Standard Deviation 462.469 |
| L-dopa 140 mg | Cmax of L-dopa | 445.75 ng/mL | Standard Deviation 183.746 |
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.
Time frame: From time = 0 to 2 hours post-dose
Population: All participants were analyzed.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Placebo | Cumulative Number of Responders (Defined as Improvement of 30% in MDS-UPDRS Part III Score From Baseline) | 30 minutes | 3 Participants |
| Placebo | Cumulative Number of Responders (Defined as Improvement of 30% in MDS-UPDRS Part III Score From Baseline) | 120 minutes | 6 Participants |
| Placebo | Cumulative Number of Responders (Defined as Improvement of 30% in MDS-UPDRS Part III Score From Baseline) | 90 minutes | 6 Participants |
| Placebo | Cumulative Number of Responders (Defined as Improvement of 30% in MDS-UPDRS Part III Score From Baseline) | 60 minutes | 6 Participants |
| Placebo | Cumulative Number of Responders (Defined as Improvement of 30% in MDS-UPDRS Part III Score From Baseline) | 15 minutes | 0 Participants |
| Placebo | Cumulative Number of Responders (Defined as Improvement of 30% in MDS-UPDRS Part III Score From Baseline) | 45 minutes | 4 Participants |
| L-dopa 35 mg | Cumulative Number of Responders (Defined as Improvement of 30% in MDS-UPDRS Part III Score From Baseline) | 120 minutes | 2 Participants |
| L-dopa 35 mg | Cumulative Number of Responders (Defined as Improvement of 30% in MDS-UPDRS Part III Score From Baseline) | 15 minutes | 0 Participants |
| L-dopa 35 mg | Cumulative Number of Responders (Defined as Improvement of 30% in MDS-UPDRS Part III Score From Baseline) | 30 minutes | 1 Participants |
| L-dopa 35 mg | Cumulative Number of Responders (Defined as Improvement of 30% in MDS-UPDRS Part III Score From Baseline) | 45 minutes | 1 Participants |
| L-dopa 35 mg | Cumulative Number of Responders (Defined as Improvement of 30% in MDS-UPDRS Part III Score From Baseline) | 60 minutes | 1 Participants |
| L-dopa 35 mg | Cumulative Number of Responders (Defined as Improvement of 30% in MDS-UPDRS Part III Score From Baseline) | 90 minutes | 2 Participants |
| L-dopa 70 mg | Cumulative Number of Responders (Defined as Improvement of 30% in MDS-UPDRS Part III Score From Baseline) | 45 minutes | 3 Participants |
| L-dopa 70 mg | Cumulative Number of Responders (Defined as Improvement of 30% in MDS-UPDRS Part III Score From Baseline) | 15 minutes | 1 Participants |
| L-dopa 70 mg | Cumulative Number of Responders (Defined as Improvement of 30% in MDS-UPDRS Part III Score From Baseline) | 120 minutes | 5 Participants |
| L-dopa 70 mg | Cumulative Number of Responders (Defined as Improvement of 30% in MDS-UPDRS Part III Score From Baseline) | 90 minutes | 5 Participants |
| L-dopa 70 mg | Cumulative Number of Responders (Defined as Improvement of 30% in MDS-UPDRS Part III Score From Baseline) | 30 minutes | 1 Participants |
| L-dopa 70 mg | Cumulative Number of Responders (Defined as Improvement of 30% in MDS-UPDRS Part III Score From Baseline) | 60 minutes | 4 Participants |
| L-dopa 140 mg | Cumulative Number of Responders (Defined as Improvement of 30% in MDS-UPDRS Part III Score From Baseline) | 60 minutes | 5 Participants |
| L-dopa 140 mg | Cumulative Number of Responders (Defined as Improvement of 30% in MDS-UPDRS Part III Score From Baseline) | 15 minutes | 2 Participants |
| L-dopa 140 mg | Cumulative Number of Responders (Defined as Improvement of 30% in MDS-UPDRS Part III Score From Baseline) | 120 minutes | 5 Participants |
| L-dopa 140 mg | Cumulative Number of Responders (Defined as Improvement of 30% in MDS-UPDRS Part III Score From Baseline) | 30 minutes | 5 Participants |
| L-dopa 140 mg | Cumulative Number of Responders (Defined as Improvement of 30% in MDS-UPDRS Part III Score From Baseline) | 45 minutes | 5 Participants |
| L-dopa 140 mg | Cumulative Number of Responders (Defined as Improvement of 30% in MDS-UPDRS Part III Score From Baseline) | 90 minutes | 5 Participants |
| L-dopa 70 mg/Carbidopa 7 mg | Cumulative Number of Responders (Defined as Improvement of 30% in MDS-UPDRS Part III Score From Baseline) | 60 minutes | 2 Participants |
| L-dopa 70 mg/Carbidopa 7 mg | Cumulative Number of Responders (Defined as Improvement of 30% in MDS-UPDRS Part III Score From Baseline) | 45 minutes | NA Participants |
| L-dopa 70 mg/Carbidopa 7 mg | Cumulative Number of Responders (Defined as Improvement of 30% in MDS-UPDRS Part III Score From Baseline) | 15 minutes | NA Participants |
| L-dopa 70 mg/Carbidopa 7 mg | Cumulative Number of Responders (Defined as Improvement of 30% in MDS-UPDRS Part III Score From Baseline) | 120 minutes | 3 Participants |
| L-dopa 70 mg/Carbidopa 7 mg | Cumulative Number of Responders (Defined as Improvement of 30% in MDS-UPDRS Part III Score From Baseline) | 90 minutes | 3 Participants |
| L-dopa 70 mg/Carbidopa 7 mg | Cumulative Number of Responders (Defined as Improvement of 30% in MDS-UPDRS Part III Score From Baseline) | 30 minutes | 1 Participants |
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.
Time frame: 2 hours
Population: All participants were analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Duration of Response, Where Response is Defined as an Improvement of 30% in MDS-UPDRS Part III Score From Baseline. | 66.9 minutes | Standard Deviation 48.35 |
| L-dopa 35 mg | Duration of Response, Where Response is Defined as an Improvement of 30% in MDS-UPDRS Part III Score From Baseline. | 23.3 minutes | Standard Deviation 36.7 |
| L-dopa 70 mg | Duration of Response, Where Response is Defined as an Improvement of 30% in MDS-UPDRS Part III Score From Baseline. | 57.3 minutes | Standard Deviation 42.72 |
| L-dopa 140 mg | Duration of Response, Where Response is Defined as an Improvement of 30% in MDS-UPDRS Part III Score From Baseline. | 37.5 minutes | Standard Deviation 42.25 |
| L-dopa 70 mg/Carbidopa 7 mg | Duration of Response, Where Response is Defined as an Improvement of 30% in MDS-UPDRS Part III Score From Baseline. | 15.0 minutes | Standard Deviation 25.1 |
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.
Time frame: 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.
Population: All participants were analyzed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | 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 | 30 minutes | -8.5 score on a scale | Standard Deviation 6.52 |
| Placebo | 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 | 120 minutes | -8.8 score on a scale | Standard Deviation 10.61 |
| Placebo | 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 | 45 minutes | -13.5 score on a scale | Standard Deviation 7.09 |
| Placebo | 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 | 60 minutes | -12.5 score on a scale | Standard Deviation 7.87 |
| Placebo | 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 | 15 minutes | -3.5 score on a scale | Standard Deviation 3.89 |
| Placebo | 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 | 90 minutes | -10.8 score on a scale | Standard Deviation 9.35 |
| L-dopa 35 mg | 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 | 90 minutes | -10.3 score on a scale | Standard Deviation 13.56 |
| L-dopa 35 mg | 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 | 60 minutes | -6.8 score on a scale | Standard Deviation 4.54 |
| L-dopa 35 mg | 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 | 15 minutes | -4.5 score on a scale | Standard Deviation 4.46 |
| L-dopa 35 mg | 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 | 30 minutes | -6.7 score on a scale | Standard Deviation 4.89 |
| L-dopa 35 mg | 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 | 120 minutes | -11.0 score on a scale | Standard Deviation 9.47 |
| L-dopa 35 mg | 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 | 45 minutes | -4.7 score on a scale | Standard Deviation 4.03 |
| L-dopa 70 mg | 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 | 60 minutes | -15.7 score on a scale | Standard Deviation 9.58 |
| L-dopa 70 mg | 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 | 15 minutes | 0.8 score on a scale | Standard Deviation 9.2 |
| L-dopa 70 mg | 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 | 30 minutes | -8.5 score on a scale | Standard Deviation 9.09 |
| L-dopa 70 mg | 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 | 45 minutes | -12.8 score on a scale | Standard Deviation 11.05 |
| L-dopa 70 mg | 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 | 120 minutes | -13.8 score on a scale | Standard Deviation 11.97 |
| L-dopa 70 mg | 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 | 90 minutes | -15.5 score on a scale | Standard Deviation 10.03 |
| L-dopa 140 mg | 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 | 120 minutes | -7.2 score on a scale | Standard Deviation 9.09 |
| L-dopa 140 mg | 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 | 45 minutes | -13.7 score on a scale | Standard Deviation 8.91 |
| L-dopa 140 mg | 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 | 30 minutes | -12.7 score on a scale | Standard Deviation 7.79 |
| L-dopa 140 mg | 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 | 15 minutes | -9.0 score on a scale | Standard Deviation 6.16 |
| L-dopa 140 mg | 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 | 60 minutes | -13.5 score on a scale | Standard Deviation 8.29 |
| L-dopa 140 mg | 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 | 90 minutes | -9.0 score on a scale | Standard Deviation 5.76 |
| L-dopa 70 mg/Carbidopa 7 mg | 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 | 60 minutes | -0.8 score on a scale | Standard Deviation 10.63 |
| L-dopa 70 mg/Carbidopa 7 mg | 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 | 90 minutes | -3.7 score on a scale | Standard Deviation 10.76 |
| L-dopa 70 mg/Carbidopa 7 mg | 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 | 30 minutes | -3.7 score on a scale | Standard Deviation 3.83 |
| L-dopa 70 mg/Carbidopa 7 mg | 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 | 120 minutes | -3.2 score on a scale | Standard Deviation 9.22 |
| L-dopa 70 mg/Carbidopa 7 mg | 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 | 15 minutes | NA score on a scale | — |
| L-dopa 70 mg/Carbidopa 7 mg | 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 | 45 minutes | NA score on a scale | — |
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.
Time frame: From time = 0 to 2 hours post-dose
Population: All subjects were included in this analysis
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Mean Maximum Change From Baseline in MDS-UPDRS Part III Score | -15.5 score on a scale | Standard Deviation 6.35 |
| L-dopa 35 mg | Mean Maximum Change From Baseline in MDS-UPDRS Part III Score | -14.0 score on a scale | Standard Deviation 11.15 |
| L-dopa 70 mg | Mean Maximum Change From Baseline in MDS-UPDRS Part III Score | -20.3 score on a scale | Standard Deviation 11.18 |
| L-dopa 140 mg | Mean Maximum Change From Baseline in MDS-UPDRS Part III Score | -15.3 score on a scale | Standard Deviation 8.12 |
| L-dopa 70 mg/Carbidopa 7 mg | Mean Maximum Change From Baseline in MDS-UPDRS Part III Score | -7.5 score on a scale | Standard Deviation 6.72 |
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.
Time frame: 4 hours
Population: All participants were included in the analysis
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Placebo | Subjective Time to ON as Evaluated by the Investigator | 45.0 minutes |
| L-dopa 35 mg | Subjective Time to ON as Evaluated by the Investigator | 240.0 minutes |
| L-dopa 70 mg | Subjective Time to ON as Evaluated by the Investigator | 30.0 minutes |
| L-dopa 140 mg | Subjective Time to ON as Evaluated by the Investigator | 30.0 minutes |
| L-dopa 70 mg/Carbidopa 7 mg | Subjective Time to ON as Evaluated by the Investigator | 240.0 minutes |
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.
Time frame: 2 hours
Population: All participants were analyzed.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Placebo | Time to Response (Defined as Improvement of 30% in MDS-UPDRS Part III Score From Baseline) | 45.0 minutes |
| L-dopa 35 mg | Time to Response (Defined as Improvement of 30% in MDS-UPDRS Part III Score From Baseline) | NA minutes |
| L-dopa 70 mg | Time to Response (Defined as Improvement of 30% in MDS-UPDRS Part III Score From Baseline) | 54.0 minutes |
| L-dopa 140 mg | Time to Response (Defined as Improvement of 30% in MDS-UPDRS Part III Score From Baseline) | 30.0 minutes |
| L-dopa 70 mg/Carbidopa 7 mg | Time to Response (Defined as Improvement of 30% in MDS-UPDRS Part III Score From Baseline) | NA minutes |
Secondary
Tmax of Carbidopa
Time to reach the maximum concentration of carbidopa
Time frame: 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.
Population: Subjects who received L-dopa/carbidopa
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Tmax of Carbidopa | 44.50 minutes | Standard Deviation 13.882 |
Secondary
Tmax of L-dopa
Time to Reach the Maximum Plasma Concentration (Cmax) of L-dopa
Time frame: 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.
Population: Subjects who received L-dopa. Placebo subjects not included.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Tmax of L-dopa | 60.17 minutes | Standard Deviation 37.95 |
| L-dopa 35 mg | Tmax of L-dopa | 66.00 minutes | Standard Deviation 38.735 |
| L-dopa 70 mg | Tmax of L-dopa | 70.00 minutes | Standard Deviation 15.505 |
| L-dopa 140 mg | Tmax of L-dopa | 92.00 minutes | Standard Deviation 27.481 |