Therapeutic potential for intranasal levodopa in Parkinson’s Disease – Off Reversal (THOR 201)
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
Clinical Network Services (CNS) Pty Ltd
32 participants
May 29, 2018
Interventional
Conditions
Summary
This research project is designed to test the safety, tolerability, the effect on movement and pharmacokinetics (how the body processes the study drug) of INP103. INP103 is a drug-device combination product; the drug is L-dopa (levo-dopamine); the device is the I231 Precision Olfactory Delivery (POD) device, which is a novel nasal (nose) spray. This study will measure the results of administration of L-dopa given by the intra-nasal POD device, against the effect of placebo, also given by the intra-nasal POD device. Participants will be given either L-dopa or placebo to determine how effective the new POD device is at delivering the drug to the body.
Eligibility
Inclusion Criteria11
- Adult males and females, 40 to 80 years of age (inclusive) at the time of Screening (Visit 1)
- Diagnosed with Idiopathic PD (per 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 (more than or equal to 30% improvement in MDS-UPDRS Part III Motor Examination score) as assessed during Screening
- On a stable dose of L-dopa containing medication for at least 2 weeks prior to Visit 1 (up to 1200 mg per 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, but WILL take oral benserazide 25 mg on arrival at the research site (at 60 to 65 minutes before dosing with INP103 or placebo)
- Subjects in Cohorts 1, 2 and 3 ONLY will take oral benserazide 25 mg 60 ± 5 minutes before Visit 3 dosing with INP103 or placebo)..
- Cohorts 4 will OMIT oral benserazide and may dose subjects once OFF episode confirmed and all baseline assessments have been completed.
- If female and of childbearing potential must agree to use adequate contraception 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
Exclusion Criteria16
- Severe dyskinesia (defined as per MDS-UPDRS) during a ‘normal day’ that would significantly interfere with the participant’s ability to perform study assessments
- In receipt of L-dopa containing medication at more than 1200 mg per 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 more than 50 mg per day, risperidone more than 1 mg per day or olanzipine more than 2.5 mg per day)
- Mini Mental State Examination (MMSE) less than or equal to 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
- 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 participant will comply with or be able to complete the study requirements
- Use of any medication likely to interact with INP103
- Clinically significant laboratory test abnormalities at screening. Participants must have clinical laboratory values less than 2 SD below upper limit of normal (ULN) or more than 2 SD above the lower limit of normal AND considered of no clinical significance by the PI
- History or presence of alcoholism or drug abuse within the 2 years prior to the first INP103 or placebo administration
- Administration of an investigational product in another trial within 30 days or 5 half-lives (whichever is longer) prior to the first INP103 or placebo administration
- 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
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Interventions
Phase IIa randomized, double-blind, placebo controlled, single dose study to compare the safety, tolerability and PK/pharmacodynamic of intranasal L-dopa following administration of INP103 (L-dopa via I231 POD device ) to that of placebo participants (placebo via I231 POD device) in L-dopa Responsive PD patients in the presence of Decarboxylase Inhibitor during an OFF episode. 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 intranasally. Dosing will take place once OFF episode is confirmed and will not include predosing with oral benserazide. Two hours post study dosing, participants will take their usual anti-OFF medication (e.g. Madopar rapid) if they have not returned to ON, and their usual morning dose of PD medications (e.g. their regular Madopar morning dose). Participants will remain under observation for another 2 hours before they can be allowed to leave (health status permitting). At various times during this 2 hour period, the subjects will have the following assessments to monitor safety: vital signs, ECG, physical exam, adverse event and dyskinesia checks. Participants will visit the clinic on day 7 for a follow-up assessment which will include the following assessments: vital signs, ECG, physical exam, blood tests, adverse event and dyskinesia checks
Locations(5)
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ACTRN12618000427279