Therapeutic Potential for Intranasal Levodopa in Parkinson's Disease -Off Reversal

NCT ID: NCT03541356

Last Updated: 2020-08-12

Study Results

Results available

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE2

Total Enrollment

32 participants

Study Classification

INTERVENTIONAL

Study Start Date

2018-05-08

Study Completion Date

2019-06-11

Brief Summary

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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

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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.

Conditions

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Parkinson's Disease

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

SEQUENTIAL

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.
Primary Study Purpose

TREATMENT

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors
Double blind

Study Groups

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Placebo

Group Type PLACEBO_COMPARATOR

Placebo

Intervention Type COMBINATION_PRODUCT

Delivered via the I231 POD (Precision Olfactory Delivery) device

L-dopa 35 mg

Group Type ACTIVE_COMPARATOR

L-dopa 35 mg

Intervention Type COMBINATION_PRODUCT

Delivered via the I231 POD (Precision Olfactory Delivery) device via one puff to one nostril

L-dopa 70 mg

Group Type ACTIVE_COMPARATOR

L-dopa 70mg

Intervention Type COMBINATION_PRODUCT

Delivered via the I231 POD (Precision Olfactory Delivery) device with two puffs, one to each nostril

L-dopa 140 mg

Group Type ACTIVE_COMPARATOR

L-dopa 140 mg

Intervention Type COMBINATION_PRODUCT

Delivered via the I231 POD (Precision Olfactory Delivery) device with four puffs, two to each nostril

L-dopa 70 mg/carbidopa 7 mg

Group Type ACTIVE_COMPARATOR

L-dopa 70mg/carbidopa 7mg

Intervention Type COMBINATION_PRODUCT

Delivered via the I231 POD (Precision Olfactory Delivery) device with two puffs, one to each nostril

Interventions

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Placebo

Delivered via the I231 POD (Precision Olfactory Delivery) device

Intervention Type COMBINATION_PRODUCT

L-dopa 35 mg

Delivered via the I231 POD (Precision Olfactory Delivery) device via one puff to one nostril

Intervention Type COMBINATION_PRODUCT

L-dopa 70mg

Delivered via the I231 POD (Precision Olfactory Delivery) device with two puffs, one to each nostril

Intervention Type COMBINATION_PRODUCT

L-dopa 140 mg

Delivered via the I231 POD (Precision Olfactory Delivery) device with four puffs, two to each nostril

Intervention Type COMBINATION_PRODUCT

L-dopa 70mg/carbidopa 7mg

Delivered via the I231 POD (Precision Olfactory Delivery) device with two puffs, one to each nostril

Intervention Type COMBINATION_PRODUCT

Eligibility Criteria

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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
Minimum Eligible Age

40 Years

Maximum Eligible Age

80 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Impel Pharmaceuticals

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Stephen B Shrewsbury, MD

Role: STUDY_CHAIR

Impel NeuroPharma, Seattle, WA (USA)

Terry O'Brien, MD/Prof

Role: PRINCIPAL_INVESTIGATOR

The Alfred Hospital, Melbourne, VIC (AUS)

Locations

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The Brain and Mind Centre / Scientia Clinical Research

Sydney, New South Wales, Australia

Site Status

Q-Pharm

Brisbane, Queensland, Australia

Site Status

The Mater Hospital

Brisbane, Queensland, Australia

Site Status

The Alfred Hospital

Melbourne, Victoria, Australia

Site Status

Perron Institute

Perth, Western Australia, Australia

Site Status

Countries

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Australia

Provided Documents

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Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

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INP103-201

Identifier Type: -

Identifier Source: org_study_id

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