Parkinson Disease
Conditions
Keywords
Parkinson Disease, Dyskinesia, ropinirole, implant, ProNeura, movement disorders, dopamine agonist, extended-release, Parkinsonian disorders, brain diseases, central nervous system diseases, Neurodegenerative Diseases, Antiparkinson agents, Anti-dyskinesia agents, dopamine agents, neurotransmitter agents, REQUIP, subdermal
Brief summary
Subjects stable on L-Dopa and oral ropinirole will have their ropinirole replaced with the Ropinirole Implant(s). The Ropinirole Implant was designed using the ProNeura™ implant technology where the implant is inserted under the skin. This study will measure how much ropinirole is released in the blood during 12 weeks of ropinirole implant treatment, and evaluate the side effects of this new formulation.
Interventions
DRUGRopinirole oral product
oral immediate-release ropinirole
DRUGRopinirole Implant
ropinirole hydrochloride/ethylene vinyl acetate
Sponsors
Titan Pharmaceuticals
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
Subjects receive oral immediate release (IR) ropinirole for 7-10 days, and then are switched to ropinirole implant(s) for 12 weeks.
Eligibility
Sex/Gender
ALL
Age
30 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
Key Inclusion Criteria: * Voluntarily provided informed consent * Meet diagnostic criteria for idiopathic Parkinson's Disease * On L-Dopa and oral ropinirole * If female of child-bearing potential, willing to practice contraception from time of informed consent to Follow-Up Visit Key
Exclusion criteria
* Pregnant, breastfeeding, or planning to become pregnant * Active epilepsy within the past year * Severe dementia or cognitive impairment * Donated or lost \> 400 mL of blood within 1 month prior to Screening * History of alcohol or substance use disorder within the prior 12 months * Recent episodes of moderate to severe dizziness or syncope * Definite or suspected hypersensitivity to ropinirole or ethylene vinyl acetate * Used any other investigational drug within 60 days or 5 half-lives prior to Screening, or plan to take any such drug any time during the study
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| AUC0-24 Hours of Ropinirole | 0-24 hours | Area under the plasma drug concentration-time curve of ropinirole |
| Total Number of Adverse Events Across Participants | 0-12 weeks | Safety and tolerability of ropinirole implant(s) presented as the total number of adverse events experienced by the analysis population. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Mean Change From Baseline in MDS-UPDRS Total Score | Baseline and Weeks 4, 8 and 12 | Efficacy of ropinirole implants presented as the mean change from baseline in MDS-UPDRS total score. Movement Disorder Society-Sponsored Revision of the Unified Parkinson's Disease Scale \[MDS-UPDRS\] is a questionnaire and examination rating motor and non-motor experiences, and motor complications. Score is summed to range from 0 to 272. Higher score indicates more severe symptoms/outcome. |
| AUC0-24 Hours of N-despropyl Ropinirole | 0-24 hours | Area under the plasma drug concentration-time curve of N-despropyl ropinirole |
| Mean Change From Baseline of Awake Time Off | Baseline and Weeks 1, 2, 3, 4, 6, 8, 10, 12 | Efficacy of ropinirole implants presented as mean change from baseline of awake time Off. Diaries were completed for 2 consecutive days prior to the visit, used to record motor state in half-hour intervals over a 24-hour period (during waking hours). Off refers to when medication has worn off and is no longer providing benefit with regard to mobility, slowness and stiffness. Daily totals for waking hours were normalized to a 16-hour waking day and averaged across the 2 days |
| Mean Change From Baseline of Awake Time On | Baseline and Weeks 1, 2, 3, 4, 6, 8, 10, 12 | Efficacy of ropinirole implants presented as mean change from baseline of awake time on. Diaries were completed for 2 consecutive days prior to the visit, used to record motor state in half-hour intervals over a 24-hour period (during waking hours). On refers to when medication is providing benefit with regard to mobility, slowness and stiffness, regardless of dyskinesia. Daily totals for waking hours were normalized to a 16-hour waking day and averaged across the 2 days. |
| AUC0-24 Hours of 7-hydroxy Ropinirole | 0-24 hours | Area under the plasma drug concentration-time curve of 7-hydroxy ropinirole |
Countries
United States
Participant flow
Pre-assignment details
Of 6 screened patients, 3 did not meet eligibility criteria for cohort assignment.
Participants by arm
| Arm | Count |
|---|---|
| Cohort 1 Requip; One Ropinirole Implant | 3 |
| Total | 3 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Ropinirole Implant 12 Weeks | At request of Sponsor, regulatory agencies, or the IRB | 1 | 0 | 0 | 0 |
Baseline characteristics
| Characteristic | Cohort 1 |
|---|---|
| Age, Continuous | 52.7 years |
| Awake Time Off | 5.02 hours |
| Awake Time On | 11.54 hours |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 3 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| MDS-UPDRS Total Score | 60.7 units on a scale |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 1 Participants |
| Sex: Female, Male Female | 1 Participants |
| Sex: Female, Male Male | 2 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 3 |
| other Total, other adverse events | 2 / 3 |
| serious Total, serious adverse events | 0 / 3 |
Outcome results
Primary
AUC0-24 Hours of Ropinirole
Area under the plasma drug concentration-time curve of ropinirole
Time frame: 0-24 hours
Population: Subjects who received at least 1 ropinirole implant and for whom at least 1 PK parameter of interest can be calculated were to be included in this analysis. Analysis not performed due to insufficient representative samples from each cohort.
Primary
Total Number of Adverse Events Across Participants
Safety and tolerability of ropinirole implant(s) presented as the total number of adverse events experienced by the analysis population.
Time frame: 0-12 weeks
Population: Subjects who received a least 1 ropinirole implant
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cohort 1 | Total Number of Adverse Events Across Participants | 4 Events |
Secondary
AUC0-24 Hours of 7-hydroxy Ropinirole
Area under the plasma drug concentration-time curve of 7-hydroxy ropinirole
Time frame: 0-24 hours
Population: Subjects who received at least 1 ropinirole implant and for whom at least 1 PK parameter of interest can be calculated were to be included in this analysis. Analysis not performed due to insufficient representative samples from each cohort.
Secondary
AUC0-24 Hours of N-despropyl Ropinirole
Area under the plasma drug concentration-time curve of N-despropyl ropinirole
Time frame: 0-24 hours
Population: Subjects who received at least 1 ropinirole implant and for whom at least 1 PK parameter of interest can be calculated were to be included in this analysis. Analysis not performed due to insufficient representative samples from each cohort.
Secondary
Mean Change From Baseline in MDS-UPDRS Total Score
Efficacy of ropinirole implants presented as the mean change from baseline in MDS-UPDRS total score. Movement Disorder Society-Sponsored Revision of the Unified Parkinson's Disease Scale \[MDS-UPDRS\] is a questionnaire and examination rating motor and non-motor experiences, and motor complications. Score is summed to range from 0 to 272. Higher score indicates more severe symptoms/outcome.
Time frame: Baseline and Weeks 4, 8 and 12
Population: Subjects who receive at least 1 ropinirole implant and complete at least 1 post-baseline efficacy assessment. Three subjects were in the analysis population at Week 4. Two subjects were in the analysis population at Weeks 8 and 12.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Cohort 1 | Mean Change From Baseline in MDS-UPDRS Total Score | Week 4 | 4.0 units on a scale | Standard Error 3.28 |
| Cohort 1 | Mean Change From Baseline in MDS-UPDRS Total Score | Week 8 | 10.6 units on a scale | Standard Error 13.42 |
| Cohort 1 | Mean Change From Baseline in MDS-UPDRS Total Score | Week 12 | 7.3 units on a scale | Standard Error 4.04 |
Secondary
Mean Change From Baseline of Awake Time Off
Efficacy of ropinirole implants presented as mean change from baseline of awake time Off. Diaries were completed for 2 consecutive days prior to the visit, used to record motor state in half-hour intervals over a 24-hour period (during waking hours). Off refers to when medication has worn off and is no longer providing benefit with regard to mobility, slowness and stiffness. Daily totals for waking hours were normalized to a 16-hour waking day and averaged across the 2 days
Time frame: Baseline and Weeks 1, 2, 3, 4, 6, 8, 10, 12
Population: Subjects who receive at least 1 ropinirole implant and complete at least 1 post-baseline efficacy assessment. Three subjects were in the analysis population for Weeks 1-6. Two subjects were in the analysis population for Weeks 8-12.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Cohort 1 | Mean Change From Baseline of Awake Time Off | Week 1 | -1.36 hours | Standard Error 0.974 |
| Cohort 1 | Mean Change From Baseline of Awake Time Off | Week 2 | -1.67 hours | Standard Error 0.921 |
| Cohort 1 | Mean Change From Baseline of Awake Time Off | Week 3 | -2.26 hours | Standard Error 1.062 |
| Cohort 1 | Mean Change From Baseline of Awake Time Off | Week 4 | -1.33 hours | Standard Error 1.094 |
| Cohort 1 | Mean Change From Baseline of Awake Time Off | Week 6 | -1.22 hours | Standard Error 1.506 |
| Cohort 1 | Mean Change From Baseline of Awake Time Off | Week 8 | -0.83 hours | Standard Error 2.068 |
| Cohort 1 | Mean Change From Baseline of Awake Time Off | Week 10 | -1.77 hours | Standard Error 1.598 |
| Cohort 1 | Mean Change From Baseline of Awake Time Off | Week 12 | -1.43 hours | Standard Error 1.943 |
Secondary
Mean Change From Baseline of Awake Time On
Efficacy of ropinirole implants presented as mean change from baseline of awake time on. Diaries were completed for 2 consecutive days prior to the visit, used to record motor state in half-hour intervals over a 24-hour period (during waking hours). On refers to when medication is providing benefit with regard to mobility, slowness and stiffness, regardless of dyskinesia. Daily totals for waking hours were normalized to a 16-hour waking day and averaged across the 2 days.
Time frame: Baseline and Weeks 1, 2, 3, 4, 6, 8, 10, 12
Population: Subjects who receive at least 1 ropinirole implant and complete at least 1 post-baseline efficacy assessment. Three subjects were in the analysis population for Weeks 1-6. Two subjects were in the analysis population for Weeks 8-12.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Cohort 1 | Mean Change From Baseline of Awake Time On | Week 1 | 0.80 hours | Standard Error 1.078 |
| Cohort 1 | Mean Change From Baseline of Awake Time On | Week 2 | 1.11 hours | Standard Error 0.457 |
| Cohort 1 | Mean Change From Baseline of Awake Time On | Week 3 | 1.70 hours | Standard Error 0.908 |
| Cohort 1 | Mean Change From Baseline of Awake Time On | Week 4 | 0.77 hours | Standard Error 0.608 |
| Cohort 1 | Mean Change From Baseline of Awake Time On | Week 6 | 0.66 hours | Standard Error 1.175 |
| Cohort 1 | Mean Change From Baseline of Awake Time On | Week 8 | 0.11 hours | Standard Error 1.344 |
| Cohort 1 | Mean Change From Baseline of Awake Time On | Week 10 | 0.93 hours | Standard Error 0.756 |
| Cohort 1 | Mean Change From Baseline of Awake Time On | Week 12 | 0.58 hours | Standard Error 1.101 |