Parkinson Disease
Conditions
Keywords
Parkinson's Disease, Parkinson Disease, Motor Fluctuations, OFF Time, Wearing-Off, Dyskinesia, AP-472, Adjunctive Therapy, Levodopa Adjunct, Positive Allosteric Modulator, Metabotropic Glutamate Receptor 4
Brief summary
This is a Phase 2 study in people with Parkinson's disease who experience motor fluctuations while taking levodopa. The study will evaluate how effective two different doses of the study drug AP-472 are when added to levodopa treatment, compared with a placebo. The study will last about 12 weeks. Participants will be randomly assigned to receive one of the two doses of AP-472 or a placebo. Neither the participants nor the study staff will know which treatment is given. The study includes a screening period, a 4-week period during which Parkinson's medications must remain stable, and an 8-week treatment period. During the treatment period, limited adjustments to levodopa are allowed if needed.
Interventions
DRUGAP-472
Oral tablet
OTHERPlacebo
Oral tablet
Sponsors
Appello Pharmaceuticals, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
30 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
Key Inclusion Criteria: Participants must meet all of the following criteria to take part in the study: 1. Be a man or woman between 30 and 80 years of age at the time of screening. 2. Have a diagnosis of Parkinson's disease, confirmed using standard medical criteria, including slowness of movement and symptoms that affect one side of the body more than the other. 3. Have mild to moderate Parkinson's disease, defined as stage 3 or lower on the Hoehn and Yahr scale when medications are working ("ON" state). 4. Experience an average of at least 3 hours of OFF time per day, based on home symptom diaries, with at least 2.5 hours of OFF time each day during the baseline period. 5. Have a Montreal Cognitive Assessment (MoCA) score of 24 or higher at screening. 6. Be able to walk independently, with or without the use of a walking aid. 7. Be able to swallow oral medication. 8. Have been on a stable Parkinson's medication regimen for at least 4 weeks before screening. Medications known as MAO-B inhibitors must have been stable for at least 12 weeks. 9. Be taking levodopa at least four times daily (immediate- or controlled-release formulations) or three times daily (extended-release formulations such as Rytary or Crexont). Key
Exclusion criteria
Participants cannot take part in the study if any of the following apply: 1. Have a form of parkinsonism that is not typical Parkinson's disease, such as secondary or atypical parkinsonism. 2. Have previously received, or plan to receive during the study, advanced Parkinson's therapies such as continuous levodopa or dopamine delivery systems, or Parkinson's disease-related brain surgery. 3. Have dyskinesias (involuntary movements) that are severe enough, in the study doctor's opinion, to interfere with participation. 4. Have a history of only certain types of dyskinesias (such as OFF-state, diphasic, myoclonic, or dystonic dyskinesias) without typical peak-dose dyskinesias. 5. Are currently taking medications that block dopamine, except for low-dose quetiapine (up to 50 mg per day) used for insomnia. 6. Routinely use on-demand "rescue" Parkinson's medications more than three times per week.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Change from Baseline in average daily OFF time on motor diaries for AP-472 compared to placebo (normalized to 16-hour awake time) | Week 12 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change from baseline in ON time without troublesome dyskinesia (normalized to 16 hours) | Week 12 | — |
| Change from baseline in Movement Disorder Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS) Part 2 (Motor Experiences of Daily Living (M-EDL)) score | Week 12 | For MDS-UPDRS Part II (Motor Experiences of Daily Living, M-EDL) there are 13 items each scored from 0 to 4. The total score range is from 0-52. A higher score indicates worse motor impact on daily activities; lower scores are better. |
| Change from baseline in Parkinson's Disease Questionnaire-39 (PDQ-39) summary index | Week 12 | For the Parkinson's Disease Questionnaire-39 (PDQ-39) Summary Index the score is calculated by averaging the 8 domain scores and converting them to a 0-100 scale. A higher score indicates worse health-related quality of life; lower scores are better. |
| Change from baseline in MDS-UPDRS Part III (Motor Examination) score in the best ON state | Week 12 | The MDS-UPDRS Part III includes 33 items, each scored from 0 to 4. The total score range is from 0-132. A higher score indicates worse motor impairment; lower scores are better. |
| Change from baseline in Epworth Sleepiness Scale (ESS) total score | Week 12 | The ESS consists of 8 items, each scored from 0 to 3. The total score range is from 0-24. Higher scores indicate greater daytime sleepiness; lower scores are better. |
Countries
United States
Contacts
CONTACTAnnie Blobaum, Ph.D.
Outcome results
None listed