MedPath

Study to Evaluate the Pharmacokinetics (PK), Safety, Tolerability of Single-Dose Transdermal Rotigotine in Japanese and Caucasian Healthy Male / Female Subjects

Phase 1
Completed
Conditions
Healthy
Interventions
Registration Number
NCT01761526
Lead Sponsor
UCB BIOSCIENCES GmbH
Brief Summary

To investigate the Pharmacokinetics (PK) of transdermally delivered Rotigotine in Japanese and Caucasian Female and Male Healthy Subjects.

Detailed Description

Not available

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
50
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
Read More
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
Read More

Study & Design

Study Type
INTERVENTIONAL
Study Design
SINGLE_GROUP
Arm && Interventions
GroupInterventionDescription
Rotigotine in Healthy JapaneseRotigotine transdermal patch* Rotigotine transdermal patch * Single dose application of 2 mg / 24 hours Rotigotine in Healthy Japanese subjects * Transdermal patch over 24 hours
Rotigotine in CaucasianRotigotine transdermal patch* Rotigotine transdermal patch * Single-Dose application of 2 mg / 24 hours Rotigotine in healthy Caucasian subjects * Transdermal patch over 24 hours
Primary Outcome Measures
NameTimeMethod
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 RotigotineFrom 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 RotigotineFrom 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 RotigotineFrom 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 RotigotineFrom 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 RotigotineFrom 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 RotigotineFrom 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 RotigotineFrom 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 DespropylrotigotineFrom 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 DesthienylethylrotigotineFrom 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 DespropylrotigotineFrom 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 DespropylrotigotineFrom 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 DespropylrotigotineFrom 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 DesthienylethylrotigotineFrom 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 DesthienylethylrotigotineFrom 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 DesthienylethylrotigotineFrom 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 Outcome Measures
NameTimeMethod
Terminal half-life [t1/2] of unconjugated RotigotineFrom 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 RotigotineFrom 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 RotigotineFrom 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

Renal Clearance [CLR] of unconjugated RotigotineFrom 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

Terminal half-life [t1/2] of total RotigotineFrom 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 RotigotineFrom 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 RotigotineFrom 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

Renal clearance [CLR] of total RotigotineFrom 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 DespropylrotigotineFrom 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 DespropylrotigotineFrom 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 DesthienylethylrotigotineFrom 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 DesthienylethylrotigotineFrom 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

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

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

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

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 DesthienylethylrotigotineFrom 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

Terminal half-life [t1/2] of total DespropylrotigotineFrom 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

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

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

Renal Clearance [CLR] of total DespropylrotigotineFrom 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 DesthienylethylrotigotineFrom 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

Trial Locations

Locations (1)

01

🇩🇪

Neuss, Germany

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