Healthy Volunteers
Conditions
Keywords
Rotigotine, Neupro®
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 sites.
Interventions
DRUGrotigotine transdermal patch (Neupro®)
Rotigotine 4.5 mg/10 cm\^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. |
| 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 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| AUC(0-∞) Norm (BW) | 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-∞) norm (BW) is the area under the plasma concentration- time curve from zero up to infinity 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(mg). |
| 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-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). |
| 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 (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). |
| AUC(0-∞) Norm (Apparent Dose) | 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-∞) norm (apparent dose) is the area under the plasma concentration- time curve from zero up to infinity normalized by apparent dose (mg). |
Countries
Germany
Participant flow
Recruitment details
A total of 40 healthy, male subjects has been randomized in order to complete the trial with at least 30 subjects eligible for the Pharmacokinetic Set (PKS). Baseline characteristics refer to the PKS.
Pre-assignment details
One subject that fulfilled predefined criteria for patch adhesiveness was excluded from the PKS.
Participants by arm
| Arm | Count |
|---|---|
| Sequence A-B (Test: PR 2.1.1 WCL - Reference: PR 2.1.1 AND) Treatment A (Rotigotine transdermal patch 4.5 mg/10 cm\^2 manufactured at LTS West Caldwell, USA) in first intervention period and Treatment B (Rotigotine transdermal patch 4.5 mg/10 cm\^2 manufactured at LTS Andernach, Germany) in second intervention period (after washout period of at least 5 days) | 20 |
| Sequence B-A (Reference: PR 2.1.1 AND - Test: PR 2.1.1 WCL) Treatment B (Rotigotine transdermal patch 4.5 mg/10 cm\^2 manufactured at LTS Andernach, Germany) in first intervention period and Treatment A (Rotigotine transdermal patch 4.5 mg/10 cm\^2 manufactured at LTS West Caldwell, USA) in second intervention period (after washout period of at least 5 days) | 18 |
| Total | 38 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| First Intervention- 24 Hours | Withdrawal by Subject | 0 | 1 |
Baseline characteristics
| Characteristic | Sequence A-B (Test: PR 2.1.1 WCL - Reference: PR 2.1.1 AND) | Sequence B-A (Reference: PR 2.1.1 AND - Test: PR 2.1.1 WCL) | Total |
|---|---|---|---|
| Age, Continuous | 37.0 years STANDARD_DEVIATION 11.7 | 32.8 years STANDARD_DEVIATION 7.2 | 35.0 years STANDARD_DEVIATION 9.9 |
| Body Mass Index (BMI) | 25.03 kilogram per square meter (kg/m^2) STANDARD_DEVIATION 2.16 | 25.87 kilogram per square meter (kg/m^2) STANDARD_DEVIATION 1.77 | 25.43 kilogram per square meter (kg/m^2) STANDARD_DEVIATION 2 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 20 Participants | 18 Participants | 38 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Height | 1.82 meter (m) STANDARD_DEVIATION 0.07 | 1.82 meter (m) STANDARD_DEVIATION 0.08 | 1.82 meter (m) STANDARD_DEVIATION 0.08 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 20 Participants | 18 Participants | 38 Participants |
| Sex: Female, Male Female | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Male | 20 Participants | 18 Participants | 38 Participants |
| Weight | 83.18 kilogram (kg) STANDARD_DEVIATION 9.62 | 85.33 kilogram (kg) STANDARD_DEVIATION 8.75 | 84.20 kilogram (kg) STANDARD_DEVIATION 9.16 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 5 / 39 | 6 / 40 |
| serious Total, serious adverse events | 0 / 39 | 0 / 40 |
Outcome results
Primary
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: PR 2.1.1 WCL) | AUC(0-∞) of Unconjugated Rotigotine | 4.51237 (ng/ mL)*h | Standard Deviation 1.80709 |
| Treatment B (Reference: PR 2.1.1 AND) | AUC(0-∞) of Unconjugated Rotigotine | 4.55159 (ng/ mL)*h | Standard Deviation 2.42524 |
Comparison: Bioequivalence testing by using the 90% Confidence Interval (CI).90% CI: [0.9714, 1.0899]ANOVA
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: PR 2.1.1 WCL) | AUC(0-tz) of Unconjugated Rotigotine | 4.3899 (ng/ mL)*h | Standard Deviation 1.7959 |
| Treatment B (Reference: PR 2.1.1 AND) | AUC(0-tz) of Unconjugated Rotigotine | 4.4255 (ng/ mL)*h | Standard Deviation 2.3969 |
Comparison: Bioequivalence testing by using the 90% Confidence Interval (CI).90% CI: [0.9693, 1.0951]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: PR 2.1.1 WCL) | Cmax of Unconjugated Rotigotine | 0.21103 ng/ mL | Standard Deviation 0.08827 |
| Treatment B (Reference: PR 2.1.1 AND) | Cmax of Unconjugated Rotigotine | 0.20386 ng/ mL | Standard Deviation 0.10194 |
Comparison: Bioequivalence testing by using the 90% Confidence Interval (CI).90% CI: [0.9903, 1.1284]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: PR 2.1.1 WCL) | Apparent Dose | 1.932 mg | Standard Deviation 0.398 |
| Treatment B (Reference: PR 2.1.1 AND) | Apparent Dose | 1.927 mg | Standard Deviation 0.489 |
Secondary
AUC(0-∞) Norm (Apparent Dose)
The AUC(0-∞) norm (apparent dose) is the area under the plasma concentration- time curve from zero up to infinity 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: PR 2.1.1 WCL) | AUC(0-∞) Norm (Apparent Dose) | 2.30523 (ng/ mL)*(h/ mg) | Standard Deviation 0.71105 |
| Treatment B (Reference: PR 2.1.1 AND) | AUC(0-∞) Norm (Apparent Dose) | 2.29747 (ng/ mL)*(h/ mg) | Standard Deviation 0.78191 |
Secondary
AUC(0-∞) Norm (BW)
The AUC(0-∞) norm (BW) is the area under the plasma concentration- time curve from zero up to infinity 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: PR 2.1.1 WCL) | AUC(0-∞) Norm (BW) | 375.224 (ng/ mL)*h*kg | Standard Deviation 141.465 |
| Treatment B (Reference: PR 2.1.1 AND) | AUC(0-∞) Norm (BW) | 378.003 (ng/ mL)*h*kg | Standard Deviation 191.344 |
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: PR 2.1.1 WCL) | AUC(0-tz) Norm (Apparent Dose) of Unconjugated Rotigotine | 2.23980 (ng/ mL)*(h/ mg) | Standard Deviation 0.71015 |
| Treatment B (Reference: PR 2.1.1 AND) | AUC(0-tz) Norm (Apparent Dose) of Unconjugated Rotigotine | 2.23035 (ng/ mL)*(h/ mg) | Standard Deviation 0.77992 |
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: PR 2.1.1 WCL) | AUC(0-tz) Norm (BW) of Unconjugated Rotigotine | 364.930 (ng/ mL)*h*kg | Standard Deviation 140.747 |
| Treatment B (Reference: PR 2.1.1 AND) | AUC(0-tz) Norm (BW) of Unconjugated Rotigotine | 367.452 (ng/ mL)*h*kg | Standard Deviation 189.279 |
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: PR 2.1.1 WCL) | CL/f of Unconjugated Rotigotine | 1185.98 L/h | Standard Deviation 574.45 |
| Treatment B (Reference: PR 2.1.1 AND) | CL/f of Unconjugated Rotigotine | 1227.56 L/h | Standard Deviation 541.82 |
Secondary
Cmax,Norm (Apparent Dose) of Unconjugated Rotigotine
The Cmax,norm (apparent dose) is the maximum plasma 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: PR 2.1.1 WCL) | Cmax,Norm (Apparent Dose) of Unconjugated Rotigotine | 0.108148 (ng/ mL)/ mg | Standard Deviation 0.037618 |
| Treatment B (Reference: PR 2.1.1 AND) | Cmax,Norm (Apparent Dose) of Unconjugated Rotigotine | 0.103965 (ng/ mL)/ mg | Standard Deviation 0.035474 |
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: PR 2.1.1 WCL) | Cmax,Norm (BW) of Unconjugated Rotigotine | 17.6070 (ng/ mL) * kg | Standard Deviation 7.2645 |
| Treatment B (Reference: PR 2.1.1 AND) | Cmax,Norm (BW) of Unconjugated Rotigotine | 16.9748 (ng/ mL) * kg | Standard Deviation 8.193 |
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: PR 2.1.1 WCL) | MRT of Unconjugated Rotigotine | 19.914 hour (h) | Standard Deviation 1.62 |
| Treatment B (Reference: PR 2.1.1 AND) | MRT of Unconjugated Rotigotine | 19.980 hour (h) | Standard Deviation 2.038 |
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: PR 2.1.1 WCL) | t1/2 of Unconjugated Rotigotine | 5.5408 hour (h) | Standard Deviation 1.0205 |
| Treatment B (Reference: PR 2.1.1 AND) | t1/2 of Unconjugated Rotigotine | 5.7878 hour (h) | Standard Deviation 1.1985 |
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: PR 2.1.1 WCL) | Tmax of Unconjugated Rotigotine | 16.00 hour (h) | Full Range 4.92 |
| Treatment B (Reference: PR 2.1.1 AND) | Tmax of Unconjugated Rotigotine | 16.00 hour (h) | Full Range 5.12 |
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: PR 2.1.1 WCL) | λz of Unconjugated Rotigotine | 0.129745 1/ hour (1/h) | Standard Deviation 0.026292 |
| Treatment B (Reference: PR 2.1.1 AND) | λz of Unconjugated Rotigotine | 0.125217 1/ hour (1/h) | Standard Deviation 0.027732 |