Advanced Idiopathic Parkinson's Disease
Conditions
Keywords
Rotigotine, Neupro, Switch, Dopamine agonists
Brief summary
The purpose of this study is to assess the safety and feasibility of switching subjects with advanced Parkinson's Disease (PD) from Pramipexole or Ropinirole to Rotigotine and to assess the effects of Rotigotine on motor and non-motor symptoms of Parkinson's Disease in subjects switched from previous treatment with either Pramipexole or Ropinirole.
Interventions
DRUGRotigotine
Rotigotine up to 16 mg / 24 hours, 4 weeks.
Sponsors
Otsuka Pharmaceutical Co., Ltd.
UCB BIOSCIENCES GmbH
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
30 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
* Subject has idiopathic Parkinson's Disease of more than 3 years duration, as defined by the cardinal sign, bradykinesia, plus the presence of at least 1 of the following: resting tremor, rigidity, impairment of postural reflexes and is without any other known or suspected cause of Parkinsonism * Subject has motor fluctuations * Subject is not satisfactorily controlled following the investigator´s assessment on a total daily dose of Pramipexole or Ropinirole * Subject has sleep disturbance or early morning motor impairment * Subject has experienced nocturia for at least 3 nights within 7 days prior to the Baseline Visit * Subject is taking L-dopa in combination with Benserazide or Carbidopa and has been on a stable dose of L-dopa for at least 28 days prior to the Baseline Visit
Exclusion criteria
* Subject has had therapy with Tolcapone or Budipine * Subject is receiving therapy with one of the following drugs either concurrently or within 28 days prior to Baseline (Visit 2): alpha-methyl dopa, metoclopramide, reserpine, neuroleptics, monoamine oxidase A (MAO-A) inhibitors, methylphenidate, or amphetamine * Subject has a history of symptomatic (not asymptomatic) orthostatic hypotension in the 6 months prior to Baseline (Visit 2) * Subject has a history of significant skin hypersensitivity to adhesive or other transdermal preparations, or recent unsolved contact dermatitis * Subject has a history of seizures or stroke within 1 year, or a history of myocardial infarction within the last 6 months prior to enrollment * Subject is pregnant or nursing, or is of childbearing potential but (i) not surgically sterile or (ii) not using adequate birth control methods (including at least 1 barrier method) or (iii) not sexually abstinent or (iv) not at least 2 years postmenopausal * Subject has a previous diagnosis of narcolepsy, sleep apnea syndrome, restless legs syndrome, or periodic limb movement disorder
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Clinical Global Impression (CGI) Item 4 (Side Effects) at the End of the Treatment Period or Early Withdrawal Visit | Day 28 (Visit 5) of the 28 days Treatment Period or Early Withdrawal Visit | The CGI Item 4 was used to assess side effects. It ranges from 0 to 4 as follows: * 0 = Side effects not assessable * 1 = No side effects * 2 = Side effects do not significantly interfere with subject's functioning * 3 = Side effects significantly interfere with the subject's functioning * 4 = Side effects outweigh therapeutic efficacy. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Patients Global Impressions of Change (PGIC) at the End of the Treatment Period or Early Withdrawal Visit | Day 28 (Visit 5) of the 28 days Treatment Period or Early Withdrawal Visit | The PGIC is a 7-point categorical rating scale in which the subject rates the changes in functioning over time as follows: * 1 = Very much improved * 2 = Much improved * 3 = Minimally improved * 4 = No change * 5 = Minimally worse * 6 = Much worse * 7 = Very much worse. |
Countries
Malaysia, Singapore, South Korea, Taiwan, United States
Participant flow
Recruitment details
This multicenter study started to enroll subjects in September 2012 in order to enroll 87 subjects in 5 countries. Participant Flow refers to the Safety Set (SS). SS consists of all subjects who were enrolled and had at least 1 patch applied during the Treatment Period.
Participants by arm
| Arm | Count |
|---|---|
| Rotigotine First application of Rotigotine patch for 24 hours on Day 1, followed by application of a new patch each day of the Treatment Period.
* Subjects on lower doses switch from Pramipexole or Ropinirole to equivalence doses of Rotigotine on Day 1 of the 28 days Treatment Period. On Day 8 (Visit 3) the dose will be evaluated and potentially adjusted up to a maximum dose of 8 mg / 24 hours.
* Subjects on higher doses switch from the equivalent dose to 8 mg / 24 hours Rotigotine of Pramipexole or Ropinirole to 8 mg / 24 hours Rotigotine on Day 1 and the remainder of the dose of Pramipexole or Ropinirole is to be switched on Day 8 of the 28 days Treatment Period. On Day 15 (Visit 4) the dose will be evaluated and potentially adjusted up to a maximum dose of 16 mg / 24 hours.
Rotigotine: Rotigotine up to 16 mg / 24 hours, 4 weeks. | 87 |
| Total | 87 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 2 |
| Overall Study | Noncompliant | 3 |
| Overall Study | Withdrawal by Subject | 3 |
Baseline characteristics
| Characteristic | Rotigotine |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 27 Participants |
| Age, Categorical Between 18 and 65 years | 60 Participants |
| Age, Continuous | 59.5 years STANDARD_DEVIATION 8.5 |
| Region of Enrollment Korea, Republic of | 69 participants |
| Region of Enrollment Malaysia | 1 participants |
| Region of Enrollment Singapore | 2 participants |
| Region of Enrollment Taiwan | 9 participants |
| Region of Enrollment United States | 6 participants |
| Sex: Female, Male Female | 47 Participants |
| Sex: Female, Male Male | 40 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 30 / 87 |
| serious Total, serious adverse events | 1 / 87 |
Outcome results
Primary
Clinical Global Impression (CGI) Item 4 (Side Effects) at the End of the Treatment Period or Early Withdrawal Visit
The CGI Item 4 was used to assess side effects. It ranges from 0 to 4 as follows: * 0 = Side effects not assessable * 1 = No side effects * 2 = Side effects do not significantly interfere with subject's functioning * 3 = Side effects significantly interfere with the subject's functioning * 4 = Side effects outweigh therapeutic efficacy.
Time frame: Day 28 (Visit 5) of the 28 days Treatment Period or Early Withdrawal Visit
Population: All 87 subjects of the Safety Set are included in the analysis of this outcome measure. Last Observation Carried Forward (LOCF) was used as a method of imputation for missing observations.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Rotigotine | Clinical Global Impression (CGI) Item 4 (Side Effects) at the End of the Treatment Period or Early Withdrawal Visit | CGI Item 4 score of 1 | 58 participants |
| Rotigotine | Clinical Global Impression (CGI) Item 4 (Side Effects) at the End of the Treatment Period or Early Withdrawal Visit | CGI Item 4 score of 2 | 26 participants |
| Rotigotine | Clinical Global Impression (CGI) Item 4 (Side Effects) at the End of the Treatment Period or Early Withdrawal Visit | CGI Item 4 score of 3 | 3 participants |
| Rotigotine | Clinical Global Impression (CGI) Item 4 (Side Effects) at the End of the Treatment Period or Early Withdrawal Visit | CGI Item 4 score of 4 | 0 participants |
| Rotigotine | Clinical Global Impression (CGI) Item 4 (Side Effects) at the End of the Treatment Period or Early Withdrawal Visit | CGI Item 4 score of 3 or 4 | 3 participants |
Secondary
Patients Global Impressions of Change (PGIC) at the End of the Treatment Period or Early Withdrawal Visit
The PGIC is a 7-point categorical rating scale in which the subject rates the changes in functioning over time as follows: * 1 = Very much improved * 2 = Much improved * 3 = Minimally improved * 4 = No change * 5 = Minimally worse * 6 = Much worse * 7 = Very much worse.
Time frame: Day 28 (Visit 5) of the 28 days Treatment Period or Early Withdrawal Visit
Population: Full Analysis Set (FAS) with Last Observation Carried Forward (LOCF) as a method of imputation for missing observations. FAS includes all subjects with at least 1 patch application during Treatment Period, and with an evaluable UPDRS Part III total score at Baseline and at least 1 valid value after Baseline to Day 35.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Rotigotine | Patients Global Impressions of Change (PGIC) at the End of the Treatment Period or Early Withdrawal Visit | PGIC category 1 | 5 participants |
| Rotigotine | Patients Global Impressions of Change (PGIC) at the End of the Treatment Period or Early Withdrawal Visit | PGIC category 2 | 17 participants |
| Rotigotine | Patients Global Impressions of Change (PGIC) at the End of the Treatment Period or Early Withdrawal Visit | PGIC category 3 | 30 participants |
| Rotigotine | Patients Global Impressions of Change (PGIC) at the End of the Treatment Period or Early Withdrawal Visit | PGIC category 4 | 18 participants |
| Rotigotine | Patients Global Impressions of Change (PGIC) at the End of the Treatment Period or Early Withdrawal Visit | PGIC category 5 | 10 participants |
| Rotigotine | Patients Global Impressions of Change (PGIC) at the End of the Treatment Period or Early Withdrawal Visit | PGIC category 6 | 3 participants |
| Rotigotine | Patients Global Impressions of Change (PGIC) at the End of the Treatment Period or Early Withdrawal Visit | PGIC category 7 | 1 participants |
| Rotigotine | Patients Global Impressions of Change (PGIC) at the End of the Treatment Period or Early Withdrawal Visit | PGIC category ≥ 5 | 14 participants |
| Rotigotine | Patients Global Impressions of Change (PGIC) at the End of the Treatment Period or Early Withdrawal Visit | PGIC category ≥ 6 | 4 participants |