Parkinson's Disease
Conditions
Keywords
Rotigotine, Rotigotine nasal spray, Efficacy, safety and tolerability, Parkinson's disease
Brief summary
The objective of this trial is to evaluate safety and efficacy of rotigotine nasal spray (SPM 952) in a single dose application scheme. Subjects will undergo a 2 - 28 days screening period in which eligibility criteria will be checked. Subjects will then be hospitalized for one night. In the morning of the next day, subjects will be randomly assigned either to rotigotine or placebo nasal spray and will then receive a single dose of trial medication. Safety assessments after application include adverse events, 12-lead electrocardiograms, blood pressure and heart rate assessments, and laboratory checks. Efficacy will be assessed by application of motor examination scores. The first subject is planned to be enrolled in February 2006. The last subject is planned to be enrolled in May 2006. Last subject out is expected for August 2006.
Detailed description
The objective of this trial is to evaluate safety and efficacy of rotigotine nasal spray (SPM 952)in a single dose application scheme. Subjects will undergo a 2-28 days screening period in which eligibility criteria will be checked. Subjects will then be hospitalized for one night. In the morning of the next day, subjects will be randomly assigned either to rotigotine or placebo nasal spray and will then receive a single dose of trial medication. Safety assessments after application include adverse events, 12-lead electrocardiograms, blood pressure and heart rate assessments, and laboratory checks. Efficacy will be assessed by application of motor examination scores.
Interventions
Rotigotine- HCl 2.5mg/mL nasal spray, dosage per puff of 275µg per 110µg administered in up to 4 deliveries
OTHERPlacebo
placebo nasal spray 1, 2 3, and 4 puffs
Sponsors
UCB Pharma
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
30 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Male and female subjects with idiopathic Parkinson's disease for at least 3 years in duration * At least 30 years of age
Exclusion criteria
* Patients with atypical Parkinson's or clinically relevant concomitant diseases or medical conditions
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Number of Subjects Who Complete the Trial | 15 days |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline at 24 Minutes Post-dose in Unified Parkinson Disease Rating Scale (UPDRS) Part III Motor Examination | Baseline, and 24 minutes post-dose | The Unified Parkinson's Disease Rating Scale (UPDRS) is a scale for the assessment of function in Parkinson's disease. UPDRS Part III measures Motor Examination. Range: 0 (Best score possible) to 56 (Worst score possible) Change = 24 minute value minus baseline value. |
| Change From Baseline to 34 Minutes Post-dose in Tapping Rate (Taps/Min) | Baseline and 34 minutes post-dose | One-minute tapping rate will be calculated as the number of times a subject could tap on two 4 x 4 cm marks placed on a board 30 cm apart during 1 minute (30 cm measured from the inner border of the two boxes). |
| Success Rate (Percentage of Subjects Achieving Off Reversals) | Up to 6 hours post-dose | Subjects reversing from off to on following initiation of treatment. On and off state refer to periods where Parkinson's disease symptoms are not present (on) and periods where symptoms are present (off); the on/off determination at each assessment timepoint was made by the investigator. |
| Time of First Off Reversal | Up to 6 hours post-dose | Number of minutes to first reversal of symptoms from off to on. Estimated via Kaplan-Meier estimation method. On and off state refer to periods where Parkinson's disease symptoms are not present (on) and periods where symptoms are present (off); the on/off determination at each assessment timepoint was made by the investigator. |
Participant flow
Pre-assignment details
Participants flow shows all subjects randomized. Safety analyses are based on actual treatment received; 4 subjects randomized to placebo were mistreated (1 subject each in the rotigotine 1 puff, rotigotine 2 puffs, rotigotine 3 puffs, and rotigotine 4 puffs treatment arms).
Participants by arm
| Arm | Count |
|---|---|
| Placebo 1-4 Puffs Placebo nasal spray 1 - 4 puffs | 17 |
| Rotigotine 1 Puff Rotigotine Nasal Spray 1 puff (0.25 mg Rotigotine) | 16 |
| Rotigotine 2 Puffs Rotigotine Nasal Spray - 2 puffs (0.49 mg Rotigotine) | 16 |
| Rotigotine 3 Puffs Rotigotine Nasal Spray - 3 puffs (0.74 mg Rotigotine) | 17 |
| Rotigotine 4 Puffs Rotigotine Nasal Spray - 4 puffs (0.99 mg Rotigotine) | 16 |
| Total | 82 |
Baseline characteristics
| Characteristic | Placebo 1-4 Puffs | Rotigotine 1 Puff | Rotigotine 2 Puffs | Rotigotine 3 Puffs | Rotigotine 4 Puffs | Total |
|---|---|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 8 Participants | 8 Participants | 11 Participants | 8 Participants | 6 Participants | 41 Participants |
| Age, Categorical Between 18 and 65 years | 9 Participants | 8 Participants | 5 Participants | 9 Participants | 10 Participants | 41 Participants |
| Age, Continuous | 63.9 years STANDARD_DEVIATION 6.94 | 67.1 years STANDARD_DEVIATION 7.54 | 66.8 years STANDARD_DEVIATION 9.67 | 63.9 years STANDARD_DEVIATION 8.28 | 60.5 years STANDARD_DEVIATION 8.04 | 64.4 years STANDARD_DEVIATION 8.28 |
| Region of Enrollment Austria | 2 participants | 2 participants | 1 participants | 4 participants | 1 participants | 10 participants |
| Region of Enrollment Germany | 11 participants | 12 participants | 12 participants | 10 participants | 13 participants | 58 participants |
| Region of Enrollment Spain | 3 participants | 1 participants | 1 participants | 3 participants | 0 participants | 8 participants |
| Region of Enrollment United Kingdom | 1 participants | 1 participants | 2 participants | 0 participants | 2 participants | 6 participants |
| Sex: Female, Male Female | 4 Participants | 5 Participants | 4 Participants | 7 Participants | 4 Participants | 24 Participants |
| Sex: Female, Male Male | 13 Participants | 11 Participants | 12 Participants | 10 Participants | 12 Participants | 58 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk |
|---|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 3 / 13 | 9 / 17 | 5 / 17 | 9 / 18 | 9 / 17 |
| serious Total, serious adverse events | 0 / 13 | 0 / 17 | 1 / 17 | 0 / 18 | 1 / 17 |
Outcome results
Primary
Number of Subjects Who Complete the Trial
Time frame: 15 days
Population: Full Analysis Set: Subjects receiving at least one delivery of trial medication and with at least one post-baseline efficacy measurement.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo 1-4 Puffs | Number of Subjects Who Complete the Trial | 17 participants |
| Rotigotine 1 Puff | Number of Subjects Who Complete the Trial | 16 participants |
| Rotigotine 2 Puffs | Number of Subjects Who Complete the Trial | 16 participants |
| Rotigotine 3 Puffs | Number of Subjects Who Complete the Trial | 17 participants |
| Rotigotine 4 Puffs | Number of Subjects Who Complete the Trial | 16 participants |
Secondary
Change From Baseline at 24 Minutes Post-dose in Unified Parkinson Disease Rating Scale (UPDRS) Part III Motor Examination
The Unified Parkinson's Disease Rating Scale (UPDRS) is a scale for the assessment of function in Parkinson's disease. UPDRS Part III measures Motor Examination. Range: 0 (Best score possible) to 56 (Worst score possible) Change = 24 minute value minus baseline value.
Time frame: Baseline, and 24 minutes post-dose
Population: Full Analysis Set: Subjects receiving at least one delivery of trial medication and with at least one post-baseline efficacy measurement. Missing values at 24 minutes post-dose timepoint were not imputed; number of observations at 24 minutes post-dose timepoint may be less than that for baseline timepoint.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo 1-4 Puffs | Change From Baseline at 24 Minutes Post-dose in Unified Parkinson Disease Rating Scale (UPDRS) Part III Motor Examination | Baseline | 35.1 score on a scale | Standard Deviation 7.77 |
| Placebo 1-4 Puffs | Change From Baseline at 24 Minutes Post-dose in Unified Parkinson Disease Rating Scale (UPDRS) Part III Motor Examination | Change from baseline to 24 minutes post-dose | -9.8 score on a scale | Standard Deviation 7.8 |
| Placebo 1-4 Puffs | Change From Baseline at 24 Minutes Post-dose in Unified Parkinson Disease Rating Scale (UPDRS) Part III Motor Examination | 24 minutes post-dose | 25.3 score on a scale | Standard Deviation 12.44 |
| Rotigotine 1 Puff | Change From Baseline at 24 Minutes Post-dose in Unified Parkinson Disease Rating Scale (UPDRS) Part III Motor Examination | 24 minutes post-dose | 30.0 score on a scale | Standard Deviation 11.35 |
| Rotigotine 1 Puff | Change From Baseline at 24 Minutes Post-dose in Unified Parkinson Disease Rating Scale (UPDRS) Part III Motor Examination | Baseline | 37.2 score on a scale | Standard Deviation 10.68 |
| Rotigotine 1 Puff | Change From Baseline at 24 Minutes Post-dose in Unified Parkinson Disease Rating Scale (UPDRS) Part III Motor Examination | Change from baseline to 24 minutes post-dose | -7.2 score on a scale | Standard Deviation 10.32 |
| Rotigotine 2 Puffs | Change From Baseline at 24 Minutes Post-dose in Unified Parkinson Disease Rating Scale (UPDRS) Part III Motor Examination | 24 minutes post-dose | 29.2 score on a scale | Standard Deviation 13.53 |
| Rotigotine 2 Puffs | Change From Baseline at 24 Minutes Post-dose in Unified Parkinson Disease Rating Scale (UPDRS) Part III Motor Examination | Baseline | 39.5 score on a scale | Standard Deviation 12.94 |
| Rotigotine 2 Puffs | Change From Baseline at 24 Minutes Post-dose in Unified Parkinson Disease Rating Scale (UPDRS) Part III Motor Examination | Change from baseline to 24 minutes post-dose | -10.3 score on a scale | Standard Deviation 6.17 |
| Rotigotine 3 Puffs | Change From Baseline at 24 Minutes Post-dose in Unified Parkinson Disease Rating Scale (UPDRS) Part III Motor Examination | Baseline | 36.2 score on a scale | Standard Deviation 7.6 |
| Rotigotine 3 Puffs | Change From Baseline at 24 Minutes Post-dose in Unified Parkinson Disease Rating Scale (UPDRS) Part III Motor Examination | Change from baseline to 24 minutes post-dose | -7.1 score on a scale | Standard Deviation 6.47 |
| Rotigotine 3 Puffs | Change From Baseline at 24 Minutes Post-dose in Unified Parkinson Disease Rating Scale (UPDRS) Part III Motor Examination | 24 minutes post-dose | 29.1 score on a scale | Standard Deviation 8.51 |
| Rotigotine 4 Puffs | Change From Baseline at 24 Minutes Post-dose in Unified Parkinson Disease Rating Scale (UPDRS) Part III Motor Examination | 24 minutes post-dose | 26.4 score on a scale | Standard Deviation 12.95 |
| Rotigotine 4 Puffs | Change From Baseline at 24 Minutes Post-dose in Unified Parkinson Disease Rating Scale (UPDRS) Part III Motor Examination | Baseline | 37.6 score on a scale | Standard Deviation 9.3 |
| Rotigotine 4 Puffs | Change From Baseline at 24 Minutes Post-dose in Unified Parkinson Disease Rating Scale (UPDRS) Part III Motor Examination | Change from baseline to 24 minutes post-dose | -11.6 score on a scale | Standard Deviation 10.65 |
Comparison: Analysis of covariance modeling change from baseline at 24 minutes post-dose in UPDRS Part III, controlling for treatment group and baseline value.95% CI: [-2.9, 8.7]ANCOVA
Comparison: Analysis of covariance modeling change from baseline at 24 minutes post-dose in UPDRS Part III, controlling for treatment group and baseline value.95% CI: [-5.7, 6]ANCOVA
Comparison: Analysis of covariance modeling change from baseline at 24 minutes post-dose in UPDRS Part III, controlling for treatment group and baseline value.95% CI: [-2.8, 8.6]ANCOVA
Comparison: Analysis of covariance modeling change from baseline at 24 minutes post-dose in UPDRS Part III, controlling for treatment group and baseline value.95% CI: [-7.4, 4.6]ANCOVA
Secondary
Change From Baseline to 34 Minutes Post-dose in Tapping Rate (Taps/Min)
One-minute tapping rate will be calculated as the number of times a subject could tap on two 4 x 4 cm marks placed on a board 30 cm apart during 1 minute (30 cm measured from the inner border of the two boxes).
Time frame: Baseline and 34 minutes post-dose
Population: Full Analysis Set: Subjects receiving at least one delivery of trial medication and with at least one post-baseline efficacy measurement. Missing values at 34 minutes post-dose timepoint were not imputed; number of observations at 34 minutes post-dose timepoint may be less than that for baseline timepoint.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo 1-4 Puffs | Change From Baseline to 34 Minutes Post-dose in Tapping Rate (Taps/Min) | Baseline | 112.7 taps per minute | Standard Deviation 47.08 |
| Placebo 1-4 Puffs | Change From Baseline to 34 Minutes Post-dose in Tapping Rate (Taps/Min) | Change from baseline to 34 minutes post-dose | 28.5 taps per minute | Standard Deviation 27.83 |
| Placebo 1-4 Puffs | Change From Baseline to 34 Minutes Post-dose in Tapping Rate (Taps/Min) | 34 minutes post-dose | 141.2 taps per minute | Standard Deviation 50.92 |
| Rotigotine 1 Puff | Change From Baseline to 34 Minutes Post-dose in Tapping Rate (Taps/Min) | 34 minutes post-dose | 131.0 taps per minute | Standard Deviation 30.01 |
| Rotigotine 1 Puff | Change From Baseline to 34 Minutes Post-dose in Tapping Rate (Taps/Min) | Baseline | 109.8 taps per minute | Standard Deviation 28.94 |
| Rotigotine 1 Puff | Change From Baseline to 34 Minutes Post-dose in Tapping Rate (Taps/Min) | Change from baseline to 34 minutes post-dose | 21.2 taps per minute | Standard Deviation 26.69 |
| Rotigotine 2 Puffs | Change From Baseline to 34 Minutes Post-dose in Tapping Rate (Taps/Min) | 34 minutes post-dose | 138.7 taps per minute | Standard Deviation 44.42 |
| Rotigotine 2 Puffs | Change From Baseline to 34 Minutes Post-dose in Tapping Rate (Taps/Min) | Baseline | 127.2 taps per minute | Standard Deviation 44.33 |
| Rotigotine 2 Puffs | Change From Baseline to 34 Minutes Post-dose in Tapping Rate (Taps/Min) | Change from baseline to 34 minutes post-dose | 11.5 taps per minute | Standard Deviation 11.27 |
| Rotigotine 3 Puffs | Change From Baseline to 34 Minutes Post-dose in Tapping Rate (Taps/Min) | Baseline | 115.9 taps per minute | Standard Deviation 41.05 |
| Rotigotine 3 Puffs | Change From Baseline to 34 Minutes Post-dose in Tapping Rate (Taps/Min) | Change from baseline to 34 minutes post-dose | 27.1 taps per minute | Standard Deviation 25.25 |
| Rotigotine 3 Puffs | Change From Baseline to 34 Minutes Post-dose in Tapping Rate (Taps/Min) | 34 minutes post-dose | 142.9 taps per minute | Standard Deviation 51.2 |
| Rotigotine 4 Puffs | Change From Baseline to 34 Minutes Post-dose in Tapping Rate (Taps/Min) | 34 minutes post-dose | 144.4 taps per minute | Standard Deviation 57.64 |
| Rotigotine 4 Puffs | Change From Baseline to 34 Minutes Post-dose in Tapping Rate (Taps/Min) | Baseline | 118.3 taps per minute | Standard Deviation 40.41 |
| Rotigotine 4 Puffs | Change From Baseline to 34 Minutes Post-dose in Tapping Rate (Taps/Min) | Change from baseline to 34 minutes post-dose | 22.9 taps per minute | Standard Deviation 27.75 |
Comparison: Analysis of covariance modeling change from baseline to 34 minutes post-dose in tapping rate, controlling for treatment group and baseline value.95% CI: [-25.7, 8.5]ANCOVA
Comparison: Analysis of covariance modeling change from baseline to 34 minutes post-dose in tapping rate, controlling for treatment group and baseline value.95% CI: [-34, 0.4]ANCOVA
Comparison: Analysis of covariance modeling change from baseline to 34 minutes post-dose in tapping rate, controlling for treatment group and baseline value.95% CI: [-18.2, 15.4]ANCOVA
Comparison: Analysis of covariance modeling change from baseline to 34 minutes post-dose in tapping rate, controlling for treatment group and baseline value.95% CI: [-23.3, 12.2]ANCOVA
Secondary
Success Rate (Percentage of Subjects Achieving Off Reversals)
Subjects reversing from off to on following initiation of treatment. On and off state refer to periods where Parkinson's disease symptoms are not present (on) and periods where symptoms are present (off); the on/off determination at each assessment timepoint was made by the investigator.
Time frame: Up to 6 hours post-dose
Population: Full Analysis Set: Subjects receiving at least one delivery of trial medication and with at least one post-baseline efficacy measurement.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo 1-4 Puffs | Success Rate (Percentage of Subjects Achieving Off Reversals) | Reversed from off to on (success) | 70.6 percentage of participants |
| Placebo 1-4 Puffs | Success Rate (Percentage of Subjects Achieving Off Reversals) | Did not reverse from off to on | 29.4 percentage of participants |
| Rotigotine 1 Puff | Success Rate (Percentage of Subjects Achieving Off Reversals) | Reversed from off to on (success) | 50.0 percentage of participants |
| Rotigotine 1 Puff | Success Rate (Percentage of Subjects Achieving Off Reversals) | Did not reverse from off to on | 50.0 percentage of participants |
| Rotigotine 2 Puffs | Success Rate (Percentage of Subjects Achieving Off Reversals) | Reversed from off to on (success) | 75.0 percentage of participants |
| Rotigotine 2 Puffs | Success Rate (Percentage of Subjects Achieving Off Reversals) | Did not reverse from off to on | 25.0 percentage of participants |
| Rotigotine 3 Puffs | Success Rate (Percentage of Subjects Achieving Off Reversals) | Did not reverse from off to on | 29.4 percentage of participants |
| Rotigotine 3 Puffs | Success Rate (Percentage of Subjects Achieving Off Reversals) | Reversed from off to on (success) | 70.6 percentage of participants |
| Rotigotine 4 Puffs | Success Rate (Percentage of Subjects Achieving Off Reversals) | Reversed from off to on (success) | 75.0 percentage of participants |
| Rotigotine 4 Puffs | Success Rate (Percentage of Subjects Achieving Off Reversals) | Did not reverse from off to on | 25.0 percentage of participants |
Comparison: 95% confidence interval in difference in success rate95% CI: [-53.3, 12.1]Confidence interval
Comparison: 95% confidence interval in difference in success rate95% CI: [-25.9, 34.7]95% confidence interval
Comparison: 95% confidence interval in difference in success rate95% CI: [-30.6, 30.6]95% confidence interval
Comparison: 95% confidence interval in difference in success rate95% CI: [-25.9, 34.7]95% confidence interval
Secondary
Time of First Off Reversal
Number of minutes to first reversal of symptoms from off to on. Estimated via Kaplan-Meier estimation method. On and off state refer to periods where Parkinson's disease symptoms are not present (on) and periods where symptoms are present (off); the on/off determination at each assessment timepoint was made by the investigator.
Time frame: Up to 6 hours post-dose
Population: Full Analysis Set: Subjects receiving at least one delivery of trial medication and with at least one post-baseline efficacy measurement.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Placebo 1-4 Puffs | Time of First Off Reversal | 50 minutes |
| Rotigotine 1 Puff | Time of First Off Reversal | 60 minutes |
| Rotigotine 2 Puffs | Time of First Off Reversal | 51 minutes |
| Rotigotine 3 Puffs | Time of First Off Reversal | 50 minutes |
| Rotigotine 4 Puffs | Time of First Off Reversal | 59 minutes |