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Trial details imported from ClinicalTrials.gov
For full trial details, please see the original record at
https://clinicaltrials.gov/study/NCT03541356
Registration number
NCT03541356
Ethics application status
Date submitted
5/04/2018
Date registered
30/05/2018
Titles & IDs
Public title
Therapeutic Potential for Intranasal Levodopa in Parkinson's Disease -Off Reversal
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Scientific title
A Phase IIa, Randomized, Double Blind, Placebo Controlled, Single Ascending Dose, Safety and Pharmacokinetic/Pharmacodynamic Study of INP103 (POD L-dopa) Administered in the Presence of DCI to L-dopa Responsive Parkinson's Disease Patients
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Secondary ID [1]
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INP103-201
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Universal Trial Number (UTN)
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Trial acronym
THOR201
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Linked study record
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Health condition
Health condition(s) or problem(s) studied:
Parkinson's Disease
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Condition category
Condition code
Neurological
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Parkinson's disease
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Intervention/exposure
Study type
Interventional
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Description of intervention(s) / exposure
Other interventions - Placebo
Other interventions - L-dopa 35 mg
Other interventions - L-dopa 70mg
Other interventions - L-dopa 140 mg
Other interventions - L-dopa 70mg/carbidopa 7mg
Placebo comparator: Placebo -
Active 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 -
Other interventions: Placebo
Delivered via the I231 POD (Precision Olfactory Delivery) device
Other interventions: L-dopa 35 mg
Delivered via the I231 POD (Precision Olfactory Delivery) device via one puff to one nostril
Other interventions: L-dopa 70mg
Delivered via the I231 POD (Precision Olfactory Delivery) device with two puffs, one to each nostril
Other interventions: L-dopa 140 mg
Delivered via the I231 POD (Precision Olfactory Delivery) device with four puffs, two to each nostril
Other interventions: L-dopa 70mg/carbidopa 7mg
Delivered via the I231 POD (Precision Olfactory Delivery) device with two puffs, one to each nostril
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Intervention code [1]
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Other interventions
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Comparator / control treatment
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Control group
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Outcomes
Primary outcome [1]
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Number of Participants With Treatment Emergent Adverse Events
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Assessment method [1]
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Assessment of treatment emergent adverse events after single dosing with INP103 (L-dopa or L-dopa/carbidopa)
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Timepoint [1]
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7 days
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Secondary outcome [1]
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AUC0-2hr for L-dopa
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Assessment method [1]
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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.
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Timepoint [1]
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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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Secondary outcome [2]
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Cmax of L-dopa
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Assessment method [2]
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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.
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Timepoint [2]
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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.
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Secondary outcome [3]
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Tmax of L-dopa
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Assessment method [3]
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Time to Reach the Maximum Plasma Concentration (Cmax) of L-dopa
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Timepoint [3]
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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.
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Secondary outcome [4]
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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
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Assessment method [4]
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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.
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Timepoint [4]
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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.
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Secondary outcome [5]
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Time to Response (Defined as Improvement of 30% in MDS-UPDRS Part III Score From Baseline)
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Assessment method [5]
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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.
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Timepoint [5]
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2 hours
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Secondary outcome [6]
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Cumulative Number of Responders (Defined as Improvement of 30% in MDS-UPDRS Part III Score From Baseline)
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Assessment method [6]
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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.
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Timepoint [6]
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From time = 0 to 2 hours post-dose
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Secondary outcome [7]
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Area Under the Curve (AUC) of Change From Baseline in MDS-UPDRS Part III Scores
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Assessment method [7]
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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.
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Timepoint [7]
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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.
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Secondary outcome [8]
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Mean Maximum Change From Baseline in MDS-UPDRS Part III Score
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Assessment method [8]
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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.
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Timepoint [8]
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From time = 0 to 2 hours post-dose
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Secondary outcome [9]
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Subjective Time to "ON" as Evaluated by the Investigator
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Assessment method [9]
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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".
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Timepoint [9]
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4 hours
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Secondary outcome [10]
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Assessment of Time to "ON" as Evaluated by Subject Self-assessment
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Assessment method [10]
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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".
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Timepoint [10]
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4 hours
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Secondary outcome [11]
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AUC0-2h for Carbidopa
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Assessment method [11]
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Area under the concentration time curve for carbidopa
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Timepoint [11]
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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.
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Secondary outcome [12]
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Cmax of Carbidopa
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Assessment method [12]
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Maximum concentration of carbidopa
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Timepoint [12]
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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 outcome [13]
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Tmax of Carbidopa
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Assessment method [13]
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Time to reach the maximum concentration of carbidopa
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Timepoint [13]
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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 outcome [14]
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Duration of Response, Where Response is Defined as an Improvement of 30% in MDS-UPDRS Part III Score From Baseline.
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Assessment method [14]
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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.
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Timepoint [14]
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2 hours
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Eligibility
Key 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
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Minimum age
40
Years
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Maximum age
80
Years
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Sex
Both males and females
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Can healthy volunteers participate?
No
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Key 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
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Study design
Purpose of the study
Treatment
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Allocation to intervention
Randomised controlled trial
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Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
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Methods used to generate the sequence in which subjects will be randomised (sequence generation)
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Masking / blinding
Blinded (masking used)
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Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data
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Intervention assignment
Other
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Other design features
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Phase
Phase 2
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Type of endpoint/s
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Statistical methods / analysis
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Recruitment
Recruitment status
Completed
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Data analysis
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Reason for early stopping/withdrawal
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Other reasons
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Date of first participant enrolment
Anticipated
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Actual
8/05/2018
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Date of last participant enrolment
Anticipated
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Actual
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Date of last data collection
Anticipated
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Actual
11/06/2019
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Sample size
Target
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Accrual to date
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Final
32
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Recruitment in Australia
Recruitment state(s)
NSW,QLD,VIC,WA
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Recruitment hospital [1]
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The Brain and Mind Centre / Scientia Clinical Research - Sydney
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Recruitment hospital [2]
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Q-Pharm - Brisbane
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Recruitment hospital [3]
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The Mater Hospital - Brisbane
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Recruitment hospital [4]
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The Alfred Hospital - Melbourne
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Recruitment hospital [5]
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Perron Institute - Perth
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Recruitment postcode(s) [1]
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2031 - Sydney
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Recruitment postcode(s) [2]
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- Brisbane
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Recruitment postcode(s) [3]
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- Melbourne
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Recruitment postcode(s) [4]
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6009 - Perth
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Funding & Sponsors
Primary sponsor type
Commercial sector/industry
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Name
Impel Pharmaceuticals
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Address
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Country
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Ethics approval
Ethics application status
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Summary
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
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Trial website
https://clinicaltrials.gov/study/NCT03541356
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Trial related presentations / publications
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Public notes
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Contacts
Principal investigator
Name
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Stephen B Shrewsbury, MD
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Address
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Impel NeuroPharma, Seattle, WA (USA)
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Country
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Phone
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Fax
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Email
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Contact person for public queries
Name
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Address
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Country
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Phone
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Fax
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Email
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Contact person for scientific queries
Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
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No/undecided IPD sharing reason/comment
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What supporting documents are/will be available?
No Supporting Document Provided
Type
Other Details
Attachment
Study protocol
https://cdn.clinicaltrials.gov/large-docs/56/NCT03541356/Prot_000.pdf
Statistical analysis plan
https://cdn.clinicaltrials.gov/large-docs/56/NCT03541356/SAP_001.pdf
Results publications and other study-related documents
No documents have been uploaded by study researchers.
Results are available at
https://clinicaltrials.gov/study/NCT03541356