Therapeutic Potential for Intranasal Levodopa in Parkinson's Disease -Off Reversal (THOR201)

Impel Pharmaceuticals

Status and phase: Completed; Phase 2

Conditions: Parkinson's Disease

Treatments: Combination Product: L-dopa 35 mg; Combination Product: Placebo; Combination Product: L-dopa 70mg/carbidopa 7mg; Combination Product: L-dopa 70mg; Combination Product: L-dopa 140 mg

Study type: Interventional

Funder types: Industry

Identifiers

NCT03541356

INP103-201

Details and patient eligibility

About

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

Full 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.

Enrollment: 32 patients

Sex: All

Ages: 40 to 80 years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Sequential Assignment

Masking: Quadruple Blind

---

32 participants in 5 patient groups, including a placebo group

Placebo

Placebo Comparator group

Treatment:

Combination Product: Placebo

L-dopa 35 mg

Active Comparator group

Treatment:

Combination Product: L-dopa 35 mg

L-dopa 70 mg

Active Comparator group

Treatment:

Combination Product: L-dopa 70mg

L-dopa 140 mg

Active Comparator group

Treatment:

Combination Product: L-dopa 140 mg

L-dopa 70 mg/carbidopa 7 mg

Active Comparator group

Treatment:

Combination Product: L-dopa 70mg/carbidopa 7mg