Healthy
Conditions
Keywords
Rotigotine, Neupro, Japanese, Caucasian, Male, Female, Single dose, Pharmacokinetics
Brief summary
To investigate the Pharmacokinetics (PK) of transdermally delivered Rotigotine in Japanese and Caucasian Female and Male Healthy Subjects.
Interventions
Rotigotine transdermal patch, single-dose application over 24 hours 2 mg /24 hours (10 cm2)
Sponsors
Schwarz BioSciences GmbH
Alfred-Nobel-Str. 10
40789 Monheim am Rhein
UCB BIOSCIENCES GmbH
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
20 Years to 45 Years
Healthy volunteers
Yes
Inclusion criteria
* Subject is healthy according to assessments done at eligibility assessment (medical history, physical examination, blood pressure, heart rate, Electrocardiogram (ECG), hematology, clinical chemistry, urinalysis) * Subject is of normal body-weight as determined by a body mass index ranging between 18 to 28 kg / m² * Subject is Japanese or Caucasian. Japanese subjects are born in Japan and left Japan not more than 10 years ago. Both parents of the Japanese subjects are 100 % Japanese
Exclusion criteria
* Subjects (females) without medically adequate contraception (e.g. mechanical contraception (Intrauterine-Device IUD), sterilization, hysterectomy) or on lactation or pregnant women. Subjects with oral contraception or hormone replacement within 4 weeks prior to eligibility assessment * Subject has a history of chronic alcohol or drug abuse * Subject has a consumption of more than 20 g of alcohol / day (amount corresponds to 0.5 l of beer / day or 0.25 l of wine / day or 3 glasses (à 2 cl) of liquor / day * Subject has a clinically relevant allergy * Subject has a known or suspected drug hypersensitivity in particular, to any component of the trial medication * Subject has any clinically significant abnormality in physical examination * Subject has a heart rate at rest less than 50 beats per minute (bpm) or more than 100 bpm * Subject has systolic blood pressure lower than 100 mmHg or higher than 145 mmHg or diastolic blood pressure higher than 95 mmHg or lower than 60 mmHg * Subject has an atopic or eczematous dermatitis and / or an active skin disease or skin tumors * Subject has a history of significant skin hypersensitivity to adhesives or other transdermal products or recent unresolved contact dermatitis
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Area under the concentration-time curve (AUC) from zero up to the last measured concentration greater than the Lower Limit of Quantitation (LOQ) [AUC (0-t)] of unconjugated Rotigotine | From Baseline (0 hours Pre-Dose) up to 60 hours Post-Dose | Blood sampling at 0 hours (Pre-Dose), 1 hour, 2 hours, 4 hours, 8 hours, 12 hours, 16 hours, 24 hours, 25 hours, 26 hours, 28 hours, 30 hours, 33 hours, 36 hours, 48 hours, and 60 hours Post-Dose |
| Area under the concentration-time curve from zero up to the last measured concentration greater than the Lower Limit of Quantitation (LOQ) normalized [AUC (0-t)norm] of unconjugated Rotigotine | From Baseline (0 hours Pre-Dose) up to 60 hours Post-Dose | Blood sampling at 0 hours (Pre-Dose), 1 hour, 2 hours, 4 hours, 8 hours, 12 hours, 16 hours, 24 hours, 25 hours, 26 hours, 28 hours, 30 hours, 33 hours, 36 hours, 48 hours, and 60 hours Post-Dose |
| Maximum concentration in plasma [Cmax] of unconjugated Rotigotine | From Baseline (0 hours Pre-Dose) up to 60 hours Post-Dose | Blood sampling at 0 hours (Pre-Dose), 1 hour, 2 hours, 4 hours, 8 hours, 12 hours, 16 hours, 24 hours, 25 hours, 26 hours, 28 hours, 30 hours, 33 hours, 36 hours, 48 hours, and 60 hours Post-Dose |
| Maximum concentration in plasma normalized by body weight [Cmax,norm] of unconjugated Rotigotine | From Baseline (0 hours Pre-Dose) up to 60 hours Post-Dose | Blood sampling at 0 hours (Pre-Dose), 1 hour, 2 hours, 4 hours, 8 hours, 12 hours, 16 hours, 24 hours, 25 hours, 26 hours, 28 hours, 30 hours, 33 hours, 36 hours, 48 hours, and 60 hours Post-Dose |
| Area under the concentration-time curve from zero up to the last measured concentration greater than the Lower Limit of Quantitation (LOQ) [AUC (0-t)] of total Rotigotine | From Baseline (0 hours Pre-Dose) up to 60 hours Post-Dose | Blood sampling at 0 hours (Pre-Dose), 1 hour, 2 hours, 4 hours, 8 hours, 12 hours, 16 hours, 24 hours, 25 hours, 26 hours, 28 hours, 30 hours, 33 hours, 36 hours, 48 hours, and 60 hours Post-Dose |
| Maximum concentration in plasma [Cmax] of total Rotigotine | From Baseline (0 hours Pre-Dose) up to 60 hours Post-Dose | Blood sampling at 0 hours (Pre-Dose), 1 hour, 2 hours, 4 hours, 8 hours, 12 hours, 16 hours, 24 hours, 25 hours, 26 hours, 28 hours, 30 hours, 33 hours, 36 hours, 48 hours, and 60 hours Post-Dose |
| Maximum concentration in plasma normalized by body weight [Cmax,norm] of total Rotigotine | From Baseline (0 hours Pre-Dose) up to 60 hours Post-Dose | Blood sampling at 0 hours (Pre-Dose), 1 hour, 2 hours, 4 hours, 8 hours, 12 hours, 16 hours, 24 hours, 25 hours, 26 hours, 28 hours, 30 hours, 33 hours, 36 hours, 48 hours, and 60 hours Post-Dose |
| Area under the concentration-time curve from zero up to the last measured concentration greater than the Lower Limit of Quantitation (LOQ) [AUC (0-t)] of total Despropylrotigotine | From Baseline (0 hours Pre-Dose) up to 60 hours Post-Dose | Blood sampling at 0 hours (Pre-Dose), 1 hour, 2 hours, 4 hours, 8 hours, 12 hours, 16 hours, 24 hours, 25 hours, 26 hours, 28 hours, 30 hours, 33 hours, 36 hours, 48 hours, and 60 hours Post-Dose |
| Area under the concentration-time curve from zero up to the last measured concentration greater than the Lower Limit of Quantitation (LOQ) normalized by body weight [AUC (0-t)] of total Despropylrotigotine | From Baseline (0 hours Pre-Dose) up to 60 hours Post-Dose | Blood sampling at 0 hours (Pre-Dose), 1 hour, 2 hours, 4 hours, 8 hours, 12 hours, 16 hours, 24 hours, 25 hours, 26 hours, 28 hours, 30 hours, 33 hours, 36 hours, 48 hours, and 60 hours Post-Dose |
| Maximum concentration in plasma [Cmax] of total Despropylrotigotine | From Baseline (0 hours Pre-Dose) up to 60 hours Post-Dose | Blood sampling at 0 hours (Pre-Dose), 1 hour, 2 hours, 4 hours, 8 hours, 12 hours, 16 hours, 24 hours, 25 hours, 26 hours, 28 hours, 30 hours, 33 hours, 36 hours, 48 hours, and 60 hours Post-Dose |
| Maximum concentration in plasma normalized by body weight [Cmax,norm] of total Despropylrotigotine | From Baseline (0 hours Pre-Dose) up to 60 hours Post-Dose | Blood sampling at 0 hours (Pre-Dose), 1 hour, 2 hours, 4 hours, 8 hours, 12 hours, 16 hours, 24 hours, 25 hours, 26 hours, 28 hours, 30 hours, 33 hours, 36 hours, 48 hours, and 60 hours Post-Dose |
| Area under the concentration-time curve from zero up to the last measured concentration greater than the Lower Limit of Quantitation (LOQ) [AUC (0-t)] of total Desthienylethylrotigotine | From Baseline (0 hours Pre-Dose) up to 60 hours Post-Dose | Blood sampling at 0 hours (Pre-Dose), 1 hour, 2 hours, 4 hours, 8 hours, 12 hours, 16 hours, 24 hours, 25 hours, 26 hours, 28 hours, 30 hours, 33 hours, 36 hours, 48 hours, and 60 hours Post-Dose |
| Area under the concentration-time curve from zero up to the last measured concentration greater than the Lower Limit of Quantitation (LOQ) normalized by body weight [AUC (0-t)] of total Desthienylethylrotigotine | From Baseline (0 hours Pre-Dose) up to 60 hours Post-Dose | Blood sampling at 0 hours (Pre-Dose), 1 hour, 2 hours, 4 hours, 8 hours, 12 hours, 16 hours, 24 hours, 25 hours, 26 hours, 28 hours, 30 hours, 33 hours, 36 hours, 48 hours, and 60 hours Post-Dose |
| Maximum concentration in plasma [Cmax] of total Desthienylethylrotigotine | From Baseline (0 hours Pre-Dose) up to 60 hours Post-Dose | Blood sampling at 0 hours (Pre-Dose), 1 hour, 2 hours, 4 hours, 8 hours, 12 hours, 16 hours, 24 hours, 25 hours, 26 hours, 28 hours, 30 hours, 33 hours, 36 hours, 48 hours, and 60 hours Post-Dose |
| Maximum concentration in plasma normalized by body weight [Cmax, norm] of total Desthienylethylrotigotine | From Baseline (0 hours Pre-Dose) up to 60 hours Post-Dose | Blood sampling at 0 hours (Pre-Dose), 1 hour, 2 hours, 4 hours, 8 hours, 12 hours, 16 hours, 24 hours, 25 hours, 26 hours, 28 hours, 30 hours, 33 hours, 36 hours, 48 hours, and 60 hours Post-Dose |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Renal clearance [CLR] of total Rotigotine | From Baseline (0 hours Pre-Dose) up to 60 hours Post-Dose | Blood sampling at 0 hours (Pre-Dose), 1 hour, 2 hours, 4 hours, 8 hours, 12 hours, 16 hours, 24 hours, 25 hours, 26 hours, 28 hours, 30 hours, 33 hours, 36 hours, 48 hours, and 60 hours Post-Dose |
| Terminal half-life [t1/2] of total Despropylrotigotine | From Baseline (0 hours Pre-Dose) up to 60 hours Post-Dose | Blood sampling at 0 hours (Pre-Dose), 1 hour, 2 hours, 4 hours, 8 hours, 12 hours, 16 hours, 24 hours, 25 hours, 26 hours, 28 hours, 30 hours, 33 hours, 36 hours, 48 hours, and 60 hours Post-Dose |
| Time of maximum concentration [tmax] of total Despropylrotigotine | From Baseline (0 hours Pre-Dose) up to 60 hours Post-Dose | Blood sampling at 0 hours (Pre-Dose), 1 hour, 2 hours, 4 hours, 8 hours, 12 hours, 16 hours, 24 hours, 25 hours, 26 hours, 28 hours, 30 hours, 33 hours, 36 hours, 48 hours, and 60 hours Post-Dose |
| Area under the concentration-time curve from zero to infinity [AUC (0-inf)] of total Despropylrotigotine | From Baseline (0 hours Pre-Dose) up to 60 hours Post-Dose | Blood sampling at 0 hours (Pre-Dose), 1 hour, 2 hours, 4 hours, 8 hours, 12 hours, 16 hours, 24 hours, 25 hours, 26 hours, 28 hours, 30 hours, 33 hours, 36 hours, 48 hours, and 60 hours Post-Dose |
| Total body clearance of total Despropylrotigotine normalized by body weight [CL/f/BW] | From Baseline (0 hours Pre-Dose) up to 60 hours Post-Dose | Blood sampling at 0 hours (Pre-Dose), 1 hour, 2 hours, 4 hours, 8 hours, 12 hours, 16 hours, 24 hours, 25 hours, 26 hours, 28 hours, 30 hours, 33 hours, 36 hours, 48 hours, and 60 hours Post-Dose |
| Apparent volume of distribution of total Despropylrotigotine normalized by body weight [Vz/f/BW] | From Baseline (0 hours Pre-Dose) up to 60 hours Post-Dose | Blood sampling at 0 hours (Pre-Dose), 1 hour, 2 hours, 4 hours, 8 hours, 12 hours, 16 hours, 24 hours, 25 hours, 26 hours, 28 hours, 30 hours, 33 hours, 36 hours, 48 hours, and 60 hours Post-Dose |
| Amount of total Despropylrotigotine excreted into urine [Ae] | From Baseline (0 hours Pre-Dose) up to 60 hours Post-Dose | Blood sampling at 0 hours (Pre-Dose), 1 hour, 2 hours, 4 hours, 8 hours, 12 hours, 16 hours, 24 hours, 25 hours, 26 hours, 28 hours, 30 hours, 33 hours, 36 hours, 48 hours, and 60 hours Post-Dose |
| Fraction of total Despropylrotigotine excreted into urine [fe (% of dose)] | From Baseline (0 hours Pre-Dose) up to 60 hours Post-Dose | Blood sampling at 0 hours (Pre-Dose), 1 hour, 2 hours, 4 hours, 8 hours, 12 hours, 16 hours, 24 hours, 25 hours, 26 hours, 28 hours, 30 hours, 33 hours, 36 hours, 48 hours, and 60 hours Post-Dose |
| Renal Clearance [CLR] of total Despropylrotigotine | From Baseline (0 hours Pre-Dose) up to 60 hours Post-Dose | Blood sampling at 0 hours (Pre-Dose), 1 hour, 2 hours, 4 hours, 8 hours, 12 hours, 16 hours, 24 hours, 25 hours, 26 hours, 28 hours, 30 hours, 33 hours, 36 hours, 48 hours, and 60 hours Post-Dose |
| Terminal half-life [t1/2] of total Desthienylethylrotigotine | From Baseline (0 hours Pre-Dose) up to 60 hours Post-Dose | Blood sampling at 0 hours (Pre-Dose), 1 hour, 2 hours, 4 hours, 8 hours, 12 hours, 16 hours, 24 hours, 25 hours, 26 hours, 28 hours, 30 hours, 33 hours, 36 hours, 48 hours, and 60 hours Post-Dose |
| Time of maximum concentration [tmax] of total Desthienylethylrotigotine | From Baseline (0 hours Pre-Dose) up to 60 hours Post-Dose | Blood sampling at 0 hours (Pre-Dose), 1 hour, 2 hours, 4 hours, 8 hours, 12 hours, 16 hours, 24 hours, 25 hours, 26 hours, 28 hours, 30 hours, 33 hours, 36 hours, 48 hours, and 60 hours Post-Dose |
| Area under the concentration-time curve from zero to infinity [AUC (0-inf)] of total Desthienylethylrotigotine | From Baseline (0 hours Pre-Dose) up to 60 hours Post-Dose | Blood sampling at 0 hours (Pre-Dose), 1 hour, 2 hours, 4 hours, 8 hours, 12 hours, 16 hours, 24 hours, 25 hours, 26 hours, 28 hours, 30 hours, 33 hours, 36 hours, 48 hours, and 60 hours Post-Dose |
| Total body clearance of total Desthienylethylrotigotine normalized by body weight [CL/f/BW] | From Baseline (0 hours Pre-Dose) up to 60 hours Post-Dose | Blood sampling at 0 hours (Pre-Dose), 1 hour, 2 hours, 4 hours, 8 hours, 12 hours, 16 hours, 24 hours, 25 hours, 26 hours, 28 hours, 30 hours, 33 hours, 36 hours, 48 hours, and 60 hours Post-Dose |
| Terminal half-life [t1/2] of unconjugated Rotigotine | From Baseline (0 hours Pre-Dose) up to 60 hours Post-Dose | Blood sampling at 0 hours (Pre-Dose), 1 hour, 2 hours, 4 hours, 8 hours, 12 hours, 16 hours, 24 hours, 25 hours, 26 hours, 28 hours, 30 hours, 33 hours, 36 hours, 48 hours, and 60 hours Post-Dose |
| Amount of total Desthienylethylrotigotine excreted into urine [Ae] | From Baseline (0 hours Pre-Dose) up to 60 hours Post-Dose | Blood sampling at 0 hours (Pre-Dose), 1 hour, 2 hours, 4 hours, 8 hours, 12 hours, 16 hours, 24 hours, 25 hours, 26 hours, 28 hours, 30 hours, 33 hours, 36 hours, 48 hours, and 60 hours Post-Dose |
| Fraction of total Desthienylethylrotigotine excreted into urine [fe (%of dose)] | From Baseline (0 hours Pre-Dose) up to 60 hours Post-Dose | Blood sampling at 0 hours (Pre-Dose), 1 hour, 2 hours, 4 hours, 8 hours, 12 hours, 16 hours, 24 hours, 25 hours, 26 hours, 28 hours, 30 hours, 33 hours, 36 hours, 48 hours, and 60 hours Post-Dose |
| Renal clearance [CLR] of total Desthienylethylrotigotine | From Baseline (0 hours Pre-Dose) up to 60 hours Post-Dose | Blood sampling at 0 hours (Pre-Dose), 1 hour, 2 hours, 4 hours, 8 hours, 12 hours, 16 hours, 24 hours, 25 hours, 26 hours, 28 hours, 30 hours, 33 hours, 36 hours, 48 hours, and 60 hours Post-Dose |
| Apparent volume of distribution of total Desthienylethylrotigotine normalized by body weight [Vz/f/BW] | From Baseline (0 hours Pre-Dose) up to 60 hours Post-Dose | Blood sampling at 0 hours (Pre-Dose), 1 hour, 2 hours, 4 hours, 8 hours, 12 hours, 16 hours, 24 hours, 25 hours, 26 hours, 28 hours, 30 hours, 33 hours, 36 hours, 48 hours, and 60 hours Post-Dose |
| Time of maximum concentration [tmax] of unconjugated Rotigotine | From Baseline (0 hours Pre-Dose) up to 60 hours Post-Dose | Blood sampling at 0 hours (Pre-Dose), 1 hour, 2 hours, 4 hours, 8 hours, 12 hours, 16 hours, 24 hours, 25 hours, 26 hours, 28 hours, 30 hours, 33 hours, 36 hours, 48 hours, and 60 hours Post-Dose |
| Area under the concentration-time curve from zero to infinity [AUC (0-inf)] of unconjugated Rotigotine | From Baseline (0 hours Pre-Dose) up to 60 hours Post-Dose | Blood sampling at 0 hours (Pre-Dose), 1 hour, 2 hours, 4 hours, 8 hours, 12 hours, 16 hours, 24 hours, 25 hours, 26 hours, 28 hours, 30 hours, 33 hours, 36 hours, 48 hours, and 60 hours Post-Dose |
| Total body clearance (CL) of unconjugated Rotigotine normalized by body weight (BW) [CL/f/BW] | From Baseline (0 hours Pre-Dose) up to 60 hours Post-Dose | Blood sampling at 0 hours (Pre-Dose), 1 hour, 2 hours, 4 hours, 8 hours, 12 hours, 16 hours, 24 hours, 25 hours, 26 hours, 28 hours, 30 hours, 33 hours, 36 hours, 48 hours, and 60 hours Post-Dose |
| Apparent volume of distribution of unconjugated Rotigotine normalized by body weight [Vz/f/BW] | From Baseline (0 hours Pre-Dose) up to 60 hours Post-Dose | Blood sampling at 0 hours (Pre-Dose), 1 hour, 2 hours, 4 hours, 8 hours, 12 hours, 16 hours, 24 hours, 25 hours, 26 hours, 28 hours, 30 hours, 33 hours, 36 hours, 48 hours, and 60 hours Post-Dose |
| Amounts of unconjugated Rotigotine excreted in urine [Ae] | From Baseline (0 hours Pre-Dose) up to 60 hours Post-Dose | Blood sampling at 0 hours (Pre-Dose), 1 hour, 2 hours, 4 hours, 8 hours, 12 hours, 16 hours, 24 hours, 25 hours, 26 hours, 28 hours, 30 hours, 33 hours, 36 hours, 48 hours, and 60 hours Post-Dose |
| Fraction of unconjugated Rotigotine excreted into urine [fe (% of dose)] | From Baseline (0 hours Pre-Dose) up to 60 hours Post-Dose | Blood sampling at 0 hours (Pre-Dose), 1 hour, 2 hours, 4 hours, 8 hours, 12 hours, 16 hours, 24 hours, 25 hours, 26 hours, 28 hours, 30 hours, 33 hours, 36 hours, 48 hours, and 60 hours Post-Dose |
| Renal Clearance [CLR] of unconjugated Rotigotine | From Baseline (0 hours Pre-Dose) up to 60 hours Post-Dose | Blood sampling at 0 hours (Pre-Dose), 1 hour, 2 hours, 4 hours, 8 hours, 12 hours, 16 hours, 24 hours, 25 hours, 26 hours, 28 hours, 30 hours, 33 hours, 36 hours, 48 hours, and 60 hours Post-Dose |
| Terminal half-life [t1/2] of total Rotigotine | From Baseline (0 hours Pre-Dose) up to 60 hours Post-Dose | Blood sampling at 0 hours (Pre-Dose), 1 hour, 2 hours, 4 hours, 8 hours, 12 hours, 16 hours, 24 hours, 25 hours, 26 hours, 28 hours, 30 hours, 33 hours, 36 hours, 48 hours, and 60 hours Post-Dose |
| Time of maximum concentration [tmax] of total Rotigotine | From Baseline (0 hours Pre-Dose) up to 60 hours Post-Dose | Blood sampling at 0 hours (Pre-Dose), 1 hour, 2 hours, 4 hours, 8 hours, 12 hours, 16 hours, 24 hours, 25 hours, 26 hours, 28 hours, 30 hours, 33 hours, 36 hours, 48 hours, and 60 hours Post-Dose |
| Area under the concentration-time curve from zero to infinity [AUC (0-inf)] of total Rotigotine | From Baseline (0 hours Pre-Dose) up to 60 hours Post-Dose | Blood sampling at 0 hours (Pre-Dose), 1 hour, 2 hours, 4 hours, 8 hours, 12 hours, 16 hours, 24 hours, 25 hours, 26 hours, 28 hours, 30 hours, 33 hours, 36 hours, 48 hours, and 60 hours Post-Dose |
| Total body clearance of total Rotigotine normalized by body weight [CL/f/BW] | From Baseline (0 hours Pre-Dose) up to 60 hours Post-Dose | Blood sampling at 0 hours (Pre-Dose), 1 hour, 2 hours, 4 hours, 8 hours, 12 hours, 16 hours, 24 hours, 25 hours, 26 hours, 28 hours, 30 hours, 33 hours, 36 hours, 48 hours, and 60 hours Post-Dose |
| Apparent volume of distribution normalized of total Rotigotine by body weight [Vz/f/BW] | From Baseline (0 hours Pre-Dose) up to 60 hours Post-Dose | Blood sampling at 0 hours (Pre-Dose), 1 hour, 2 hours, 4 hours, 8 hours, 12 hours, 16 hours, 24 hours, 25 hours, 26 hours, 28 hours, 30 hours, 33 hours, 36 hours, 48 hours, and 60 hours Post-Dose |
| Amount of total Rotigotine excreted into urine [Ae] | From Baseline (0 hours Pre-Dose) up to 60 hours Post-Dose | Blood sampling at 0 hours (Pre-Dose), 1 hour, 2 hours, 4 hours, 8 hours, 12 hours, 16 hours, 24 hours, 25 hours, 26 hours, 28 hours, 30 hours, 33 hours, 36 hours, 48 hours, and 60 hours Post-Dose |
| Fraction of total Rotigotine excreted into urine [fe (% of dose)] | From Baseline (0 hours Pre-Dose) up to 60 hours Post-Dose | Blood sampling at 0 hours (Pre-Dose), 1 hour, 2 hours, 4 hours, 8 hours, 12 hours, 16 hours, 24 hours, 25 hours, 26 hours, 28 hours, 30 hours, 33 hours, 36 hours, 48 hours, and 60 hours Post-Dose |
Countries
Germany
Outcome results
None listed