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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/ct2/show/NCT03541356

Registration number

NCT03541356

Ethics application status

Date submitted

5/04/2018

Date registered

30/05/2018

Date last updated

12/08/2020

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]

INP103-201

Universal Trial Number (UTN)

Trial acronym

THOR201

Linked study record

Health condition

Health condition(s) or problem(s) studied:

Parkinson's Disease

Condition category

Condition code

Neurological

Parkinson's disease

Intervention/exposure

Study type

Interventional

Description of intervention(s) / exposure

Combination Product - Placebo
Combination Product - L-dopa 35 mg
Combination Product - L-dopa 70mg
Combination Product - L-dopa 140 mg
Combination Product - 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 -

Combination Product: Placebo
Delivered via the I231 POD (Precision Olfactory Delivery) device

Combination Product: L-dopa 35 mg
Delivered via the I231 POD (Precision Olfactory Delivery) device via one puff to one nostril

Combination Product: L-dopa 70mg
Delivered via the I231 POD (Precision Olfactory Delivery) device with two puffs, one to each nostril

Combination Product: L-dopa 140 mg
Delivered via the I231 POD (Precision Olfactory Delivery) device with four puffs, two to each nostril

Combination Product: L-dopa 70mg/carbidopa 7mg
Delivered via the I231 POD (Precision Olfactory Delivery) device with two puffs, one to each nostril

Intervention code [1]

Combination Product

Comparator / control treatment

Control group

Outcomes

Primary outcome [1]

Number of Participants With Treatment Emergent Adverse Events

Timepoint [1]

7 days

Secondary outcome [1]

AUC0-2hr for L-dopa

Timepoint [1]

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]

Cmax of L-dopa

Timepoint [2]

Secondary outcome [3]

Tmax of L-dopa

Timepoint [3]

Secondary outcome [4]

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]

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]

Time to Response (Defined as Improvement of 30% in MDS-UPDRS Part III Score From Baseline)

Timepoint [5]

2 hours

Secondary outcome [6]

Cumulative Number of Responders (Defined as Improvement of 30% in MDS-UPDRS Part III Score From Baseline)

Timepoint [6]

From time = 0 to 2 hours post-dose

Secondary outcome [7]

Area Under the Curve (AUC) of Change From Baseline in MDS-UPDRS Part III Scores

Timepoint [7]

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]

Mean Maximum Change From Baseline in MDS-UPDRS Part III Score

Timepoint [8]

From time = 0 to 2 hours post-dose

Secondary outcome [9]

Subjective Time to "ON" as Evaluated by the Investigator

Timepoint [9]

4 hours

Secondary outcome [10]

Assessment of Time to "ON" as Evaluated by Subject Self-assessment

Timepoint [10]

4 hours

Secondary outcome [11]

AUC0-2h for Carbidopa

Timepoint [11]

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]

Cmax of Carbidopa

Timepoint [12]

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]

Tmax of Carbidopa

Timepoint [13]

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]

Duration of Response, Where Response is Defined as an Improvement of 30% in MDS-UPDRS Part III Score From Baseline.

Timepoint [14]

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?

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

Recruitment in Australia

Recruitment state(s)

NSW,QLD,VIC,WA

Recruitment hospital [1]

The Brain and Mind Centre / Scientia Clinical Research - Sydney

Recruitment hospital [2]

Q-Pharm - Brisbane

Recruitment hospital [3]

The Mater Hospital - Brisbane

Recruitment hospital [4]

The Alfred Hospital - Melbourne

Recruitment hospital [5]

Perron Institute - Perth

Recruitment postcode(s) [1]

2031 - Sydney

Recruitment postcode(s) [2]

- Brisbane

Recruitment postcode(s) [3]

- Melbourne

Recruitment postcode(s) [4]

6009 - Perth

Funding & Sponsors

Primary sponsor type

Commercial sector/Industry

Name

Impel Pharmaceuticals

Address

Country

Ethics approval

Ethics application status

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

Trial website

https://clinicaltrials.gov/ct2/show/NCT03541356

Trial related presentations / publications

Public notes

Contacts

Principal investigator

Name

Stephen B Shrewsbury, MD

Address

Impel NeuroPharma, Seattle, WA (USA)

Country

Phone

Fax

Contact person for public queries

Name

Address

Country

Phone

Fax

Contact person for scientific queries

Trial Review

For full trial details, please see the original record at https://clinicaltrials.gov/ct2/show/NCT03541356