Healthy
Conditions
Keywords
Rotigotine, Neupro®, Transdermal Patch
Brief summary
The major aim of this study is to investigate and compare the drug amount delivered to the body after sequential application of 2 rotigotine transdermal patches from 2 different manufacturing processes.
Interventions
Rotigotine 4.5mg/10cm\^2 patch applied for 24 hours
Sponsors
UCB Pharma
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
BASIC_SCIENCE
Masking
NONE
Eligibility
Sex/Gender
MALE
Age
18 Years to 55 Years
Healthy volunteers
Yes
Inclusion criteria
* Healthy White, male volunteers between 18 and 55 years of age (inclusive). * BMI between 19 and 28 kg/m² (inclusive).
Exclusion criteria
* Previous participation in a clinical study with rotigotine * History or current condition of epilepsy and/or seizures. * Known clinically relevant allergy or known/suspected clinically relevant drug hypersensitivity. * History of significant skin hypersensitivity to adhesives or other transdermal products or recently unresolved contact dermatitis. * History or present condition of an atopic or eczematous dermatitis, psoriasis, and/or an active skin disease. * Clinically relevant abnormality in physical examination, ECG, vital signs or safety laboratory examinations. * Positive HIV, hepatitis B or C test or positive alcohol or drug test. * Relevant hepatic or renal dysfunction * Intake of medication that might interfere with the test drug within 2 weeks prior to dosing. * Thickly hair-covered abdomen resulting in difficulties in finding appropriate patch application sites
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| AUC(0-tz) of Unconjugated Rotigotine | Pharmacokinetic samples were taken predose, after 1, 2, 3, 4, 6, 8, 12, 16, 24 (before patch removal), 25, 26, 28, 30, 32, 36, 40 and 48 hours after patch application | The AUC(0-tz) is the area under the plasma concentration- time curve from zero up to the last analytically quantifiable concentration. |
| Cmax of Unconjugated Rotigotine | Pharmacokinetic samples were taken predose, after 1, 2, 3, 4, 6, 8, 12, 16, 24 (before patch removal), 25, 26, 28, 30, 32, 36, 40 and 48 hours after patch application. | The Cmax is the maximum plasma concentration. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| AUC(0-tz)Norm (BW) of Unconjugated Rotigotine | Pharmacokinetic samples were taken predose, after 1, 2, 3, 4, 6, 8, 12, 16, 24 (before patch removal), 25, 26, 28, 30, 32, 36, 40 and 48 hours after patch application. | The AUC(0-tz)Norm (BW) is the area under the plasma concentration- time curve from zero up to the last analytically quantifiable concentration normalized by body weight (kg). |
| Cmax,Norm (Apparent Dose) of Unconjugated Rotigotine | Pharmacokinetic samples were taken predose, after 1, 2, 3, 4, 6, 8, 12, 16, 24 (before patch removal), 25, 26, 28, 30, 32, 36, 40 and 48 hours after patch application. | The Cmax,Norm (Apparent dose) is the maximum plasma concentration normalized by apparent dose. |
| Cmax,Norm (BW) of Unconjugated Rotigotine | Pharmacokinetic samples were taken predose, after 1, 2, 3, 4, 6, 8, 12, 16, 24 (before patch removal), 25, 26, 28, 30, 32, 36, 40 and 48 hours after patch application. | The Cmax,Norm (BW) is the maximum plasma concentration normalized by body weight (kg). |
| Tmax of Unconjugated Rotigotine | Pharmacokinetic samples were taken predose, after 1, 2, 3, 4, 6, 8, 12, 16, 24 (before patch removal), 25, 26, 28, 30, 32, 36, 40 and 48 hours after patch application. | The Tmax is the time to reach a maximum plasma concentration after patch application. |
| AUC(0-∞) of Unconjugated Rotigotine | Pharmacokinetic samples were taken predose, after 1, 2, 3, 4, 6, 8, 12, 16, 24 (before patch removal), 25, 26, 28, 30, 32, 36, 40 and 48 hours after patch application. | The AUC(0-∞) is the area under the plasma concentration- time curve from zero up to infinity. |
| λz of Unconjugated Rotigotine | Pharmacokinetic samples were taken predose, after 1, 2, 3, 4, 6, 8, 12, 16, 24 (before patch removal), 25, 26, 28, 30, 32, 36, 40 and 48 hours after patch application. | The λz is the rate constant of elimination. |
| t1/2 of Unconjugated Rotigotine | Pharmacokinetic samples were taken predose, after 1, 2, 3, 4, 6, 8, 12, 16, 24 (before patch removal), 25, 26, 28, 30, 32, 36, 40 and 48 hours after patch application. | The t1/2 is the terminal half- life. |
| CL/f of Unconjugated Rotigotine | Pharmacokinetic samples were taken predose, after 1, 2, 3, 4, 6, 8, 12, 16, 24 (before patch removal), 25, 26, 28, 30, 32, 36, 40 and 48 hours after patch application. | The CL/f is the apparent total body clearance. |
| Apparent Dose | 48 hours | Apparent dose of unconjugated rotigotine in mg. The Apparent dose of unconjugated rotigotine was determined from the patches removed on Day 2. |
| MRT of Unconjugated Rotigotine | Pharmacokinetic samples were taken predose, after 1, 2, 3, 4, 6, 8, 12, 16, 24(before patch removal), 25, 26, 28, 30, 32, 36, 40 and 48 hours after patch application. | The MRT is the mean residence time. |
| AUC(0-tz)Norm (Apparent Dose) of Unconjugated Rotigotine | Pharmacokinetic samples were taken predose, after 1, 2, 3, 4, 6, 8, 12, 16, 24 (before patch removal), 25, 26, 28, 30, 32, 36, 40 and 48 hours after patch application. | The AUC(0-tz)Norm (Apparent dose) is the area under the plasma concentration- time curve from zero up to the last analytically quantifiable concentration normalized by apparent dose (mg). |
Countries
Germany
Participant flow
Recruitment details
A total of 52, healthy, male subjects has been randomized in order to complete the trial with at least 44 subjects eligible for the Pharmacokinetic Set (PKS). Baseline characteristics refer to the PKS.
Pre-assignment details
Patients with an insufficient patch adhesiveness were excluded from the PKS.
Participants by arm
| Arm | Count |
|---|---|
| Sequence A-B (Test: PR2.1.1 - Reference: PR1.0) Two single applications of rotigotine patches from two different manufacturing processes in the order A-B separated by a washout phase of at least 5 days | 23 |
| Sequence B-A (Reference: PR1.0 - Test: PR2.1.1) Two single applications of rotigotine patches from two different manufacturing processes in the order B-A separated by a washout phase of at least 5 days | 21 |
| Total | 44 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Consent withdrawn | 0 | 1 |
| Overall Study | Other reasons for premature termination | 1 | 2 |
Baseline characteristics
| Characteristic | Sequence A-B (Test: PR2.1.1 - Reference: PR1.0) | Total | Sequence B-A (Reference: PR1.0 - Test: PR2.1.1) |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 23 Participants | 44 Participants | 21 Participants |
| Age, Continuous | 38.7 years STANDARD_DEVIATION 9.8 | 39.0 years STANDARD_DEVIATION 9.3 | 39.3 years STANDARD_DEVIATION 9.1 |
| Region of Enrollment Germany | 23 participants | 44 participants | 21 participants |
| Sex: Female, Male Female | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Male | 23 Participants | 44 Participants | 21 Participants |
| Weight | 78.98 kg STANDARD_DEVIATION 7.08 | 79.45 kg STANDARD_DEVIATION 7.57 | 79.98 kg STANDARD_DEVIATION 8.2 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 21 / 51 | 21 / 51 |
| serious Total, serious adverse events | 0 / 51 | 0 / 51 |
Outcome results
Primary
AUC(0-tz) of Unconjugated Rotigotine
The AUC(0-tz) is the area under the plasma concentration- time curve from zero up to the last analytically quantifiable concentration.
Time frame: Pharmacokinetic samples were taken predose, after 1, 2, 3, 4, 6, 8, 12, 16, 24 (before patch removal), 25, 26, 28, 30, 32, 36, 40 and 48 hours after patch application
Population: Pharmacokinetic Set (PKS)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Treatment A (Test: PR2.1.1) | AUC(0-tz) of Unconjugated Rotigotine | 3.0168 (ng/ mL)*h | Standard Deviation 1.4077 |
| Treatment B (Reference: PR1.0) | AUC(0-tz) of Unconjugated Rotigotine | 3.0635 (ng/ mL)*h | Standard Deviation 1.4309 |
Comparison: Bioequivalence testing by using the 90% Confidence Interval (CI).90% CI: [0.9103, 1.0688]ANOVA
Primary
Cmax of Unconjugated Rotigotine
The Cmax is the maximum plasma concentration.
Time frame: Pharmacokinetic samples were taken predose, after 1, 2, 3, 4, 6, 8, 12, 16, 24 (before patch removal), 25, 26, 28, 30, 32, 36, 40 and 48 hours after patch application.
Population: Pharmacokinetic Set (PKS)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Treatment A (Test: PR2.1.1) | Cmax of Unconjugated Rotigotine | 0.14418 ng/ mL | Standard Deviation 0.06211 |
| Treatment B (Reference: PR1.0) | Cmax of Unconjugated Rotigotine | 0.15155 ng/ mL | Standard Deviation 0.0654 |
Comparison: Bioequivalence testing by using the 90% Confidence Interval (CI).90% CI: [0.8861, 1.0367]ANOVA
Secondary
Apparent Dose
Apparent dose of unconjugated rotigotine in mg. The Apparent dose of unconjugated rotigotine was determined from the patches removed on Day 2.
Time frame: 48 hours
Population: Pharmacokinetic Set (PKS)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Treatment A (Test: PR2.1.1) | Apparent Dose | 1.676 mg | Standard Deviation 0.423 |
| Treatment B (Reference: PR1.0) | Apparent Dose | 1.890 mg | Standard Deviation 0.561 |
Secondary
AUC(0-∞) of Unconjugated Rotigotine
The AUC(0-∞) is the area under the plasma concentration- time curve from zero up to infinity.
Time frame: Pharmacokinetic samples were taken predose, after 1, 2, 3, 4, 6, 8, 12, 16, 24 (before patch removal), 25, 26, 28, 30, 32, 36, 40 and 48 hours after patch application.
Population: Pharmacokinetic Set (PKS)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Treatment A (Test: PR2.1.1) | AUC(0-∞) of Unconjugated Rotigotine | 3.12622 (ng/ mL)*h | Standard Deviation 1.41536 |
| Treatment B (Reference: PR1.0) | AUC(0-∞) of Unconjugated Rotigotine | 3.16403 (ng/ mL)*h | Standard Deviation 1.43028 |
Comparison: Bioequivalence testing by using the 90% Confidence Interval (CI).90% CI: [0.9179, 1.0671]ANOVA
Secondary
AUC(0-tz)Norm (Apparent Dose) of Unconjugated Rotigotine
The AUC(0-tz)Norm (Apparent dose) is the area under the plasma concentration- time curve from zero up to the last analytically quantifiable concentration normalized by apparent dose (mg).
Time frame: Pharmacokinetic samples were taken predose, after 1, 2, 3, 4, 6, 8, 12, 16, 24 (before patch removal), 25, 26, 28, 30, 32, 36, 40 and 48 hours after patch application.
Population: Pharmacokinetic Set (PKS)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Treatment A (Test: PR2.1.1) | AUC(0-tz)Norm (Apparent Dose) of Unconjugated Rotigotine | 1.78200 (ng/ mL)*(h/ mg) | Standard Deviation 0.71912 |
| Treatment B (Reference: PR1.0) | AUC(0-tz)Norm (Apparent Dose) of Unconjugated Rotigotine | 1.58900 (ng/ mL)*(h/ mg) | Standard Deviation 0.54806 |
Secondary
AUC(0-tz)Norm (BW) of Unconjugated Rotigotine
The AUC(0-tz)Norm (BW) is the area under the plasma concentration- time curve from zero up to the last analytically quantifiable concentration normalized by body weight (kg).
Time frame: Pharmacokinetic samples were taken predose, after 1, 2, 3, 4, 6, 8, 12, 16, 24 (before patch removal), 25, 26, 28, 30, 32, 36, 40 and 48 hours after patch application.
Population: Pharmacokinetic Set (PKS)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Treatment A (Test: PR2.1.1) | AUC(0-tz)Norm (BW) of Unconjugated Rotigotine | 239.241 (ng/ mL)*h*kg | Standard Deviation 112.475 |
| Treatment B (Reference: PR1.0) | AUC(0-tz)Norm (BW) of Unconjugated Rotigotine | 243.841 (ng/ mL)*h*kg | Standard Deviation 116.64 |
Secondary
CL/f of Unconjugated Rotigotine
The CL/f is the apparent total body clearance.
Time frame: Pharmacokinetic samples were taken predose, after 1, 2, 3, 4, 6, 8, 12, 16, 24 (before patch removal), 25, 26, 28, 30, 32, 36, 40 and 48 hours after patch application.
Population: Pharmacokinetic Set (PKS)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Treatment A (Test: PR2.1.1) | CL/f of Unconjugated Rotigotine | 1825.38 L/ h | Standard Deviation 1058.21 |
| Treatment B (Reference: PR1.0) | CL/f of Unconjugated Rotigotine | 1822.13 L/ h | Standard Deviation 1060.42 |
Secondary
Cmax,Norm (Apparent Dose) of Unconjugated Rotigotine
The Cmax,Norm (Apparent dose) is the maximum plasma concentration normalized by apparent dose.
Time frame: Pharmacokinetic samples were taken predose, after 1, 2, 3, 4, 6, 8, 12, 16, 24 (before patch removal), 25, 26, 28, 30, 32, 36, 40 and 48 hours after patch application.
Population: Pharmacokinetic Set (PKS)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Treatment A (Test: PR2.1.1) | Cmax,Norm (Apparent Dose) of Unconjugated Rotigotine | 0.085822 (ng/ mL) / mg | Standard Deviation 0.032789 |
| Treatment B (Reference: PR1.0) | Cmax,Norm (Apparent Dose) of Unconjugated Rotigotine | 0.079619 (ng/ mL) / mg | Standard Deviation 0.027178 |
Secondary
Cmax,Norm (BW) of Unconjugated Rotigotine
The Cmax,Norm (BW) is the maximum plasma concentration normalized by body weight (kg).
Time frame: Pharmacokinetic samples were taken predose, after 1, 2, 3, 4, 6, 8, 12, 16, 24 (before patch removal), 25, 26, 28, 30, 32, 36, 40 and 48 hours after patch application.
Population: Pharmacokinetic Set (PKS)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Treatment A (Test: PR2.1.1) | Cmax,Norm (BW) of Unconjugated Rotigotine | 11.4391 (ng/ mL)*kg | Standard Deviation 4.9667 |
| Treatment B (Reference: PR1.0) | Cmax,Norm (BW) of Unconjugated Rotigotine | 12.0441 (ng/ mL)*kg | Standard Deviation 5.3133 |
Secondary
MRT of Unconjugated Rotigotine
The MRT is the mean residence time.
Time frame: Pharmacokinetic samples were taken predose, after 1, 2, 3, 4, 6, 8, 12, 16, 24(before patch removal), 25, 26, 28, 30, 32, 36, 40 and 48 hours after patch application.
Population: Pharmacokinetic Set (PKS)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Treatment A (Test: PR2.1.1) | MRT of Unconjugated Rotigotine | 19.012 hour (h) | Standard Deviation 1.809 |
| Treatment B (Reference: PR1.0) | MRT of Unconjugated Rotigotine | 18.882 hour (h) | Standard Deviation 1.802 |
Secondary
t1/2 of Unconjugated Rotigotine
The t1/2 is the terminal half- life.
Time frame: Pharmacokinetic samples were taken predose, after 1, 2, 3, 4, 6, 8, 12, 16, 24 (before patch removal), 25, 26, 28, 30, 32, 36, 40 and 48 hours after patch application.
Population: Pharmacokinetic Set (PKS)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Treatment A (Test: PR2.1.1) | t1/2 of Unconjugated Rotigotine | 4.7665 hour (h) | Standard Deviation 1.1499 |
| Treatment B (Reference: PR1.0) | t1/2 of Unconjugated Rotigotine | 4.7128 hour (h) | Standard Deviation 0.8088 |
Secondary
Tmax of Unconjugated Rotigotine
The Tmax is the time to reach a maximum plasma concentration after patch application.
Time frame: Pharmacokinetic samples were taken predose, after 1, 2, 3, 4, 6, 8, 12, 16, 24 (before patch removal), 25, 26, 28, 30, 32, 36, 40 and 48 hours after patch application.
Population: Pharmacokinetic Set (PKS)
| Arm | Measure | Value (MEDIAN) | Dispersion |
|---|---|---|---|
| Treatment A (Test: PR2.1.1) | Tmax of Unconjugated Rotigotine | 16.00 hour (h) | Full Range 6.18 |
| Treatment B (Reference: PR1.0) | Tmax of Unconjugated Rotigotine | 16.00 hour (h) | Full Range 5.26 |
Secondary
λz of Unconjugated Rotigotine
The λz is the rate constant of elimination.
Time frame: Pharmacokinetic samples were taken predose, after 1, 2, 3, 4, 6, 8, 12, 16, 24 (before patch removal), 25, 26, 28, 30, 32, 36, 40 and 48 hours after patch application.
Population: Pharmacokinetic Set (PKS)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Treatment A (Test: PR2.1.1) | λz of Unconjugated Rotigotine | 0.153848 1/ hour (1/h) | Standard Deviation 0.037525 |
| Treatment B (Reference: PR1.0) | λz of Unconjugated Rotigotine | 0.151239 1/ hour (1/h) | Standard Deviation 0.025301 |