Motor Fluctuations, Parkinson's Disease
Conditions
Keywords
Parkinson's disease, PD, stage2/3Parkinson's, Advanced Parkinson's Disease with Motor Fluctuations
Brief summary
The primary objective of this study is to explore the efficacy and tolerability of DM-1992 compared to a standard carbidopa/Levodopa Immediate-Release (CD/LD IR) tablet (Sinemet IR) as measured by: * ON time with no dyskinesia or non-troublesome dyskinesia * OFF time
Interventions
DRUGDM-1992
72.5mg carbidopa/230mg levodopa
DRUGSinemet IR
Immediate-release tablet containing 25mg carbidopa and 100mg levodopa
Sponsors
Depomed
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
30 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Men and women at least 30 years and older at the time of informed consent with advanced idiopathic Parkinson's disease with predictable wearing-off motor fluctuations with Hoehn and Yahr Stage II-III when on. 2. Patients should be able to differentiate between the ON and OFF states with an average daily OFF time of ≥ 2.5 hours at study entry. 3. On a stable daily dose of LD of ≥ 400 mg but ≤1600 mg for at least 1 month prior to the screening visit. 4. Non CD/LD containing anti-Parkinson's medications should be kept at stable doses for 1 month prior to screening visit. Patients should be willing to keep their non LD containing medications consistently throughout the study duration. 5. Female patients of childbearing potential should be abstinent or continuing to practice and willing to continue throughout the study with appropriate contraceptives (defined as Nova ring, oral, injected, transdermal patch, implanted, or barrier). 6. Mini Mental State Examination (MMSE) ≥ 26 at screening visit. 7. Able to provide informed consent and willing to sign Health Insurance Portability and Accountability Act (HIPAA) authorization. 8. Able and willing to comply with the protocol, including availability for all scheduled study visits and blood sample collections. Must be under the observation of a competent care giver throughout the study participation.
Exclusion criteria
1. Patients with atypical or drug-induced Parkinson's disease. 2. Patients with a known history of hypersensitivity to levodopa or carbidopa. 3. Patients who receive treatments with dopamine receptor blocking agents 4. Patients with a history of seizures except of childhood febrile seizure. 5. Patients with dementia. 6. Patients with a significant history of GI diseases (severe inflammatory bowel disease, irritable bowel disease, dyspepsia, gastro-esophageal reflux disease etc.) in the past five years. 7. Patients with any history of gastric surgery other than vagotomy and pyloroplasty. 8. Patients with an immune-compromised state. 9. Patients with clinically significant hepatic insufficiency with Child-Pugh total score of ≥ 5. 10. Patients with a calculated creatinine clearance (Clcr) \< 50 mL/min using the Cockcroft-Gault equation. 11. Patients who have a difficulty swallowing tablets. 12. Patient has participated in a clinical trial of an investigational drug or device within 30 days of the screening visit. 13. Patients with any other serious medical condition that, in the opinion of the Investigator would jeopardize the safety of the patient or affect the validity of the study results.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| The Primary Objective of This Study is to Explore the Efficacy and Tolerability of DM-1992 Compared to a Standard CD/LD IR Formulation as Measured by Percent OFF Time. | Baseline and 10 days for each of the 2 study periods | OFF indicates wearing off motor fluctuations before the next levodopa dose. Percent OFF time is calculated as the total OFF time divided by the total awake time for each day and multiplied by 100. Patient diary-every 30min while awake for 3days prior to initial Day1 as baseline & during the last 3days before Day10 for both treatments for dyskinesia state. Baseline is the average of the 3 days recorded in the patient diary prior to Day 1 of Period 1. End of Period is the average of the 3 days recorded in the patient diary prior to Day 10 in each period. Clinician-Assess efficacy at pre-dose, every 30min for Day1 and hourly for Day10 for dyskinesia state & motor fluctuations at clinic visits. |
Countries
United States
Participant flow
Pre-assignment details
A total of 34 subjects were randomly assigned to treatment in this crossover study: 19 in the DM-1992 for Period 1 and Sinemet IR for Period 2 sequence, and 15 in the Sinemet IR for Period 1 and DM-1992 for Period 2 sequence. All 34 subjects received study treatment and were included in the safety and intent-to-treat (ITT) populations.
Participants by arm
| Arm | Count |
|---|---|
| Overall Study DM-1992 first, then Sinemet IR; Sinemet IR first, then DM-1992 | 34 |
| Total | 34 |
Baseline characteristics
| Characteristic | Overall Study |
|---|---|
| Age, Continuous | 61.4 years STANDARD_DEVIATION 8.41 |
| Percent OFF Time (%) | 32.50 percentage of time STANDARD_DEVIATION 9.962 |
| Race/Ethnicity, Customized Afro-Caribbean | 2 participants |
| Race/Ethnicity, Customized American Indian or Alaskan Native | 0 participants |
| Race/Ethnicity, Customized Asian | 0 participants |
| Race/Ethnicity, Customized Hispanic or Latino | 0 participants |
| Race/Ethnicity, Customized Native Hawaiian or Other Pacific Islander | 0 participants |
| Race/Ethnicity, Customized Other | 0 participants |
| Race/Ethnicity, Customized White | 32 participants |
| Sex: Female, Male Female | 8 Participants |
| Sex: Female, Male Male | 26 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 12 / 34 | 4 / 34 |
| serious Total, serious adverse events | 0 / 34 | 0 / 34 |
Outcome results
Primary
The Primary Objective of This Study is to Explore the Efficacy and Tolerability of DM-1992 Compared to a Standard CD/LD IR Formulation as Measured by Percent OFF Time.
OFF indicates wearing off motor fluctuations before the next levodopa dose. Percent OFF time is calculated as the total OFF time divided by the total awake time for each day and multiplied by 100. Patient diary-every 30min while awake for 3days prior to initial Day1 as baseline & during the last 3days before Day10 for both treatments for dyskinesia state. Baseline is the average of the 3 days recorded in the patient diary prior to Day 1 of Period 1. End of Period is the average of the 3 days recorded in the patient diary prior to Day 10 in each period. Clinician-Assess efficacy at pre-dose, every 30min for Day1 and hourly for Day10 for dyskinesia state & motor fluctuations at clinic visits.
Time frame: Baseline and 10 days for each of the 2 study periods
Population: Modified Intent-to-treat (ITT) Population
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| DM-1992 | The Primary Objective of This Study is to Explore the Efficacy and Tolerability of DM-1992 Compared to a Standard CD/LD IR Formulation as Measured by Percent OFF Time. | -5.52 percentage of time |
| Sinemet IR | The Primary Objective of This Study is to Explore the Efficacy and Tolerability of DM-1992 Compared to a Standard CD/LD IR Formulation as Measured by Percent OFF Time. | 1.33 percentage of time |
Comparison: Percent OFF Time (%)p-value: 0.047195% CI: [-13.62, -0.09]ANCOVA