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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
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
Secondary ID [1] 0 0
INP103-201
Universal Trial Number (UTN)
Trial acronym
THOR201
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Parkinson's Disease 0 0
Condition category
Condition code
Neurological 0 0 0 0
Parkinson's disease

Intervention/exposure
Study type
Interventional
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
Intervention code [1] 0 0
Other interventions
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Number of Participants With Treatment Emergent Adverse Events
Timepoint [1] 0 0
7 days
Secondary outcome [1] 0 0
AUC0-2hr for L-dopa
Timepoint [1] 0 0
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 outcome [2] 0 0
Cmax of L-dopa
Timepoint [2] 0 0
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 outcome [3] 0 0
Tmax of L-dopa
Timepoint [3] 0 0
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 outcome [4] 0 0
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
Timepoint [4] 0 0
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 outcome [5] 0 0
Time to Response (Defined as Improvement of 30% in MDS-UPDRS Part III Score From Baseline)
Timepoint [5] 0 0
2 hours
Secondary outcome [6] 0 0
Cumulative Number of Responders (Defined as Improvement of 30% in MDS-UPDRS Part III Score From Baseline)
Timepoint [6] 0 0
From time = 0 to 2 hours post-dose
Secondary outcome [7] 0 0
Area Under the Curve (AUC) of Change From Baseline in MDS-UPDRS Part III Scores
Timepoint [7] 0 0
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 outcome [8] 0 0
Mean Maximum Change From Baseline in MDS-UPDRS Part III Score
Timepoint [8] 0 0
From time = 0 to 2 hours post-dose
Secondary outcome [9] 0 0
Subjective Time to "ON" as Evaluated by the Investigator
Timepoint [9] 0 0
4 hours
Secondary outcome [10] 0 0
Assessment of Time to "ON" as Evaluated by Subject Self-assessment
Timepoint [10] 0 0
4 hours
Secondary outcome [11] 0 0
AUC0-2h for Carbidopa
Timepoint [11] 0 0
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 outcome [12] 0 0
Cmax of Carbidopa
Timepoint [12] 0 0
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 outcome [13] 0 0
Tmax of Carbidopa
Timepoint [13] 0 0
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 outcome [14] 0 0
Duration of Response, Where Response is Defined as an Improvement of 30% in MDS-UPDRS Part III Score From Baseline.
Timepoint [14] 0 0
2 hours

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
Minimum age
40 Years
Maximum age
80 Years
Sex
Both males and females
Can healthy volunteers participate?
No
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

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
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
Intervention assignment
Other
Other design features
Phase
Phase 2
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
8/05/2018
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
11/06/2019
Sample size
Target
Accrual to date
Final
32
Recruitment in Australia
Recruitment state(s)
NSW,QLD,VIC,WA
Recruitment hospital [1] 0 0
The Brain and Mind Centre / Scientia Clinical Research - Sydney
Recruitment hospital [2] 0 0
Q-Pharm - Brisbane
Recruitment hospital [3] 0 0
The Mater Hospital - Brisbane
Recruitment hospital [4] 0 0
The Alfred Hospital - Melbourne
Recruitment hospital [5] 0 0
Perron Institute - Perth
Recruitment postcode(s) [1] 0 0
2031 - Sydney
Recruitment postcode(s) [2] 0 0
- Brisbane
Recruitment postcode(s) [3] 0 0
- Melbourne
Recruitment postcode(s) [4] 0 0
6009 - Perth

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Impel Pharmaceuticals
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Stephen B Shrewsbury, MD
Address 0 0
Impel NeuroPharma, Seattle, WA (USA)
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment


What supporting documents are/will be available?




Results publications and other study-related documents

No documents have been uploaded by study researchers.


Results are available at https://clinicaltrials.gov/study/NCT03541356