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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT03541356




Registration number
NCT03541356
Ethics application status
Date submitted
5/04/2018
Date registered
17/05/2018
Date last updated
12/12/2018

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 Benserazide to L-dopa Responsive Parkinson's Disease Patients
Secondary ID [1] 0 0
INP103-201
Universal Trial Number (UTN)
Trial acronym
THOR 201
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
Combination Product - Experimental: INP103
Combination Product - Placebo

Active Comparator: Experimental: INP103-201 (L-dopa) - Ascending doses of active drug INP103 (L-dopa) delivered via the I231 Precision Olfactory Device (POD)

Placebo Comparator: Placebo - Ascending doses of placebo delivered via the I231 Precision Olfactory Device (POD)


Combination Product: Experimental: INP103
Delivered via the I231 POD (Precision Olfactory Delivery) device with one puff to one nostril

Combination Product: Placebo
Delivered via the I231 POD (Precision Olfactory Delivery) device with one puff to one nostril

Intervention code [1] 0 0
Combination Product
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Explore the safety and tolerability of single ascending doses of INP103 versus placebo - Assessment of safety and tolerability based on reported AE/SAE post-dosing with levodopa or placebo
Timepoint [1] 0 0
7 days
Secondary outcome [1] 0 0
Characterize the PK (AUC0-2h) of single ascending doses of INP103 - Area under the Plasma Concentration-time Curve for INP103
Timepoint [1] 0 0
2 hours
Secondary outcome [2] 0 0
Characterize the PK (Cmax) of single ascending doses of INP103 - Maximum Observed Plasma Concentration for INP103
Timepoint [2] 0 0
2 hours
Secondary outcome [3] 0 0
Characterize the PK (Tmax) of single ascending doses of INP103 - Time to Reach the Maximum Plasma Concentration (Cmax) of INP103
Timepoint [3] 0 0
2 hours
Secondary outcome [4] 0 0
Evaluate change from baseline to 30 minutes post-dose in MDS-UPDRS Part III score (primary motor function endpoint) - 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.
Timepoint [4] 0 0
30 minutes
Secondary outcome [5] 0 0
Evaluate time to response (defined as improvement of 30% in MDS-UPDRS Part III score from baseline) post dose of INP103 or placebo - 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.
Timepoint [5] 0 0
2 hours
Secondary outcome [6] 0 0
Evaluate duration of response (defined as improvement of 30% in MDS-UPDRS Part III score from baseline) post dose of INP103 or placebo - 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.
Timepoint [6] 0 0
7 days
Secondary outcome [7] 0 0
Evaluate Under the Curve (AUC) changes in MDS-UPDRS Part III scores from pre-dose at 15, 30, 45, 60, 90, and 120 minutes post-dose of INP103 or placebo - 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.
Timepoint [7] 0 0
2 hours
Secondary outcome [8] 0 0
Evaluate Maximum response in MDS-UPDRS Part III scores from pre-dose at 15, 30, 45, 60, 90, and 120 minutes post-dose of INP103 or placebo - 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.
Timepoint [8] 0 0
2 hours
Secondary outcome [9] 0 0
Explore subjective assessments of "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" (ON meaning when medication - namely levodopa - is working optimally.
Timepoint [9] 0 0
4 hours
Secondary outcome [10] 0 0
Explore subjective assessments of "Time to ON" as evaluated by subject self-assessment - Subjects will be asked to provide self-assessments at 15, 30, 45, 60, 90, 120, and 240 minutes post-dose if they consider they are "ON" (ON meaning when medication - namely levodopa - is working optimally.
Timepoint [10] 0 0
4 hours
Secondary outcome [11] 0 0
Explore PK/pharmacodynamic relationship of single ascending doses of INP103 and motor function - Changes in motor function will be measured (MDS-UPDRS Part III assessment) and compared against the overall PK profile findings following ascending doses of INP103 (or placebo)
Timepoint [11] 0 0
7 days

Eligibility
Key inclusion criteria
1. Adult males and females, 40 to 80 years of age (inclusive) at the time of Screening
(Visit 1)

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 1200mg/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, but WILL take oral benserazide 25 mg on arrival
at the research site (at 60 ± 5 minutes before dosing with INP103 or placebo)

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 center

9. Willing to provide voluntary written informed consent signed prior to entry into the
study
Minimum age
40 Years
Maximum age
80 Years
Gender
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 >1200mg/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 >50mg/day, risperidone >1mg/day or olanzapine >2.5mg/day)

4. Mini Mental State Examination (MMSE) = 25

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 or INP103(see Appendix 5)

11. Clinically significant laboratory test abnormalities at Screening (Visit 1). Subjects
must have clinical laboratory values < 2 SD below upper limit of normal (ULN) or > 2
SD above lower limit of normal (LLN) AND considered of no clinical significance by the
Principal 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 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
Recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
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 NeuroPharma Inc.
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
This is a Phase IIa randomized, double-blind, placebo controlled, single ascending dose (SAD)
study to compare the safety, tolerability and PK/pharmacodynamic of intranasal L-dopa
following administration of INP103 to that of placebo in PD patients in the presence of
benserazide during an OFF episode.
Trial website
https://clinicaltrials.gov/show/NCT03541356
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
Jacki D Campbell
Address 0 0
Country 0 0
Phone 0 0
206-489-2471
Fax 0 0
Email 0 0
jcampbell@impelnp.com
Contact person for scientific queries

No data has been provided for results reporting
Summary results
Not applicable