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Parkinson's DiseasePhase 2THOR201NCT03541356

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

A Phase 2 study testing L-dopa 35 mg, L-dopa 70mg and L-dopa 140 mg in people with Parkinson's Disease, run by Impel Pharmaceuticals at 5 sites in Australia.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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 Read more about this study

Who is it for?
Ages 40 to 80 years
Conditions the study is for
Parkinson's Disease
What is being tested?
L-dopa 35 mg, L-dopa 70mg and L-dopa 140 mg
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
32 participants
Where
5 sitesAustralia
Study dates
8 May 2018to 11 Jun 2019
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 40 to 80 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Adult males and females, 40 to 80 years of age (inclusive) at the time of Screening (Visit1)
  • 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
  • Subjects who are prone to (and recognize) OFF episodes (when their usual PD medication has worn off)
  • 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)
  • 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.
  • 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.
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  • 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.
  • If female and of childbearing potential must agree to use adequate contraception (see Section 4.4) during the study
  • Able and willing to attend the necessary visits at the study centre
  • Willing to provide voluntary written informed consent signed prior to entry into the study

Who cannot join

  • Severe dyskinesia (defined as per MDS-UPDRS) during a 'normal day' that would significantly interfere with the subject's ability to perform study assessments
  • In receipt of L-dopa containing medication at > 1200 mg/day
  • 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)
  • Mini Mental State Examination (MMSE) ≤ 25 as documented within the previous 36 months or as assessed by Investigator during Screening
  • History of suicidal ideation or attempted suicide within previous 12 months
  • Narrow-angle glaucoma
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  • Presence of skin lesions that, in the opinion of the Investigator, may be cancerous
  • Females who are pregnant, planning a pregnancy or lactating
  • 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
  • Use of any medication likely to interact with benserazide, carbidopa or INP103 (see Appendix 5)
  • Laboratory test abnormalities at Screening (Visit 1) deemed clinically significant by the Investigator.
  • History or presence of alcoholism or drug abuse within the 2 years prior to INP103 or placebo dosing
  • Administration of an investigational product in another trial within 30 days or 5 half-lives (whichever is longer) prior to INP103 or placebo dosing
  • Significant nasal congestion, physical blockage in either nostril, or significantly deviated nasal septum as evaluated by the PI or other suitably trained healthcare professional
  • 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

Trial locations and contacts

5 sites in 1 country.

5 sites in 1 country

Australia5 sites
  • Q-Pharm

    Brisbane, Queensland

  • The Mater Hospital

    Brisbane, Queensland

  • The Alfred Hospital

    Melbourne, Victoria

  • Perron Institute

    Perth, Western Australia, 6009

  • The Brain and Mind Centre / Scientia Clinical Research

    Sydney, New South Wales, 2031

Other trials in Australia

About this study

Official 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

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

Read the detailed description

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.

Being tested
Placebo, L-dopa 35 mg, L-dopa 70mg, L-dopa 140 mg, L-dopa 70mg/carbidopa 7mg
Keywords
Parkinsons, L-dopa, levodopa, ON, OFF, PD, POD device, I231, benserazide, Precision olfactory delivery, MDS-UPDRS, Carbidopa, DCI, Decarboxylase Inhibitor
Medical subject headings
Parkinson Disease

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • PlaceboCombination product

    Delivered via the I231 POD (Precision Olfactory Delivery) device

  • L-dopa 35 mgCombination product

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

  • L-dopa 70mgCombination product

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

  • L-dopa 140 mgCombination product

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

  • L-dopa 70mg/carbidopa 7mgCombination product

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

Study groups in NCT03541356
Study groupRoleWhat they receive
PlaceboPlacebo comparatorNot described
Receives: Combination Product: Placebo
L-dopa 35 mgActive comparatorNot described
Receives: Combination Product: L-dopa 35 mg
L-dopa 70 mgActive comparatorNot described
Receives: Combination Product: L-dopa 70mg
L-dopa 140 mgActive comparatorNot described
Receives: Combination Product: L-dopa 140 mg
L-dopa 70 mg/carbidopa 7 mgActive comparatorNot described
Receives: Combination Product: L-dopa 70mg/carbidopa 7mg

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Number of Participants With Treatment Emergent Adverse Events

    Assessment of treatment emergent adverse events after single dosing with INP103 (L-dopa or L-dopa/carbidopa)

    Measured: 7 days

Secondary outcomes (14)
  1. AUC0-2hr for L-dopa

    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.

    Measured: 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

  2. Cmax of L-dopa

    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.

    Measured: 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.

  3. Tmax of L-dopa

    Time to Reach the Maximum Plasma Concentration (Cmax) of L-dopa

    Measured: 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.

  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

    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.

    Measured: 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.

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

    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.

    Measured: 2 hours

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

    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.

    Measured: From time = 0 to 2 hours post-dose

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

    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.

    Measured: 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.

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

    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.

    Measured: From time = 0 to 2 hours post-dose

  9. Subjective 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".

    Measured: 4 hours

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

    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".

    Measured: 4 hours

  11. AUC0-2h for Carbidopa

    Area under the concentration time curve for carbidopa

    Measured: 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.

  12. Cmax of Carbidopa

    Maximum concentration of carbidopa

    Measured: 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.

  13. Tmax of Carbidopa

    Time to reach the maximum concentration of carbidopa

    Measured: 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.

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

    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.

    Measured: 2 hours

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted30 May 2018
  2. Study start8 May 2018
  3. Primary completion11 Jun 2019
  4. Study completion11 Jun 2019

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Sequential
Model description
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.
Masking
Quadruple blind
Who is masked
Participant, Care provider, Investigator, Outcomes assessor
Enrolment
32 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03541356
Sponsor's protocol ID
INP103-201
Acronym
THOR201
Status last verified
Jul 2020
First submitted
5 Apr 2018
Last updated
12 Aug 2020
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
Yes
Individual data sharing
No

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing L-dopa 35 mg, L-dopa 70mg and L-dopa 140 mg in people with Parkinson's Disease, run by Impel Pharmaceuticals at 5 sites in Australia.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 11 inclusion and 15 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 12 Aug 2020. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 5 sites in Australia. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 12 Aug 2020). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Number of Participants With Treatment Emergent Adverse Events (time frame: 7 days). It is what the study was designed to measure, not a finding.

Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 12 Aug 2020.

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