Study to Evaluate the Pharmacokinetics, Safety, Tolerability of Repeated Dose Transdermal Rotigotine in Japanese and Caucasian Subjects

Parallel Group Trial to Evaluate the Pharmacokinetics and Safety/Tolerability of Repeated Dose Treatment With Rotigotine Continuous Delivery System (5 cm^2/2.25 mg, 10 cm^2/4.5 mg, 20 cm^2/9 mg) in Japanese and Caucasian Healthy Subjects

To investigate the repeated dose Pharmacokinetics (PK) of transdermally delivered Rotigotine in Japanese and Caucasian female and male healthy subjects.

Study Overview

• Status: Completed
• Conditions: Healthy
• Intervention / Treatment: Drug: Rotigotine transdermal patch 1mg / 24 hours; Drug: Rotigotine transdermal patch 2 mg / 24 hours; Drug: Rotigotine transdermal patch 4 mg / 24 hours

• Study Type: Interventional
• Enrollment (Actual): 26
• Phase: Phase 1

Contacts and Locations

Study Locations

• Germany
  • Neuss, Germany
    • 1

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years to 45 years (ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Subject is healthy according to assessments done at eligibility assessment (medical history, physical examination, blood pressure, heart rate, 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 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

Study Plan

How is the study designed?

Design Details

• Allocation: NON_RANDOMIZED
• Interventional Model: PARALLEL
• Masking: NONE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Rotigotine in Japanese subjects; Repeated-Dose application of 1,2, and 4 mg / 24 hours Rotigotine in healthy Japanese subjects; Transdermal patch over 24 hours	Drug: Rotigotine transdermal patch 1mg / 24 hours; Rotigotine transdermal patch, repeated dose application over 24 hours; 1 mg / 24 hours; Other Names: Neupro; Drug: Rotigotine transdermal patch 2 mg / 24 hours; Rotigotine transdermal patch, repeated dose application over 24 hours; 2 mg / 24 hours; Other Names: Neupro; Drug: Rotigotine transdermal patch 4 mg / 24 hours; Rotigotine transdermal patch, repeated dose application over 24 hours; 4 mg / 24 hours; Other Names: Neupro
EXPERIMENTAL: Rotigotine in Caucasian subjects; Multiple-Dose application of 1, 2, and 4 mg / 24 hours Rotigotine in healthy Caucasian subjects; Transdermal patch over 24 hours	Drug: Rotigotine transdermal patch 1mg / 24 hours; Rotigotine transdermal patch, repeated dose application over 24 hours; 1 mg / 24 hours; Other Names: Neupro; Drug: Rotigotine transdermal patch 2 mg / 24 hours; Rotigotine transdermal patch, repeated dose application over 24 hours; 2 mg / 24 hours; Other Names: Neupro; Drug: Rotigotine transdermal patch 4 mg / 24 hours; Rotigotine transdermal patch, repeated dose application over 24 hours; 4 mg / 24 hours; Other Names: Neupro

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Area under the concentration-time curve of unconjugated Rotigotine in steady-state within one dosing interval (AUCtau,ss)	Blood sampling at 0 hours (predose), 1 hour, 2 hours, 4 hours, 8 hours, 12 hours, 16 hours, and 24 hours
Area under the concentration-time curve of unconjugated Rotigotine in steady-state within one dosing interval normalized by Body Weight [AUCtau,ss,norm(BW)]	Blood sampling at 0 hours (predose), 1 hour, 2 hours, 4 hours, 8 hours, 12 hours, 16 hours, and 24 hours
Maximum concentration of unconjugated Rotigotine in plasma at steady-state (Cmax,ss)	Blood sampling at 0 hours (predose), 1 hour, 2 hours, 4 hours, 8 hours, 12 hours, 16 hours, and 24 hours
Maximum concentration of unconjugated Rotigotine in plasma at steady-state normalized by Body Weight [Cmax,ss,norm(BW)]	Blood sampling at 0 hours (predose), 1 hour, 2 hours, 4 hours, 8 hours, 12 hours, 16 hours, and 24 hours
Maximum concentration of unconjugated Rotigotine in plasma at steady-state normalized by apparent dose [Cmax,ss,norm(appd)]	Blood sampling at 0 hours (predose), 1 hour, 2 hours, 4 hours, 8 hours, 12 hours, 16 hours, and 24 hours
Maximum concentration of unconjugated Rotigotine in plasma at steady-state normalized by Body Weight and apparent dose [Cmax,ss,norm(BW,appd)]	Blood sampling at 0 hours (predose), 1 hour, 2 hours, 4 hours, 8 hours, 12 hours, 16 hours, and 24 hours
Area under the concentration-time curve of total Rotigotine in steady-state within one dosing interval (AUCtau,ss)	Blood sampling at 0 hours (predose), 1 hour, 2 hours, 4 hours, 8 hours, 12 hours, 16 hours, and 24 hours
Area under the concentration-time curve of total Rotigotine in steady-state within one dosing interval normalized by Body Weight [AUCtau,ss,norm(BW)]	Blood sampling at 0 hours (predose), 1 hour, 2 hours, 4 hours, 8 hours, 12 hours, 16 hours, and 24 hours
Maximum concentration of total Rotigotine in plasma at steady-state (Cmax,ss)	Blood sampling at 0 hours (predose), 1 hour, 2 hours, 4 hours, 8 hours, 12 hours, 16 hours, and 24 hours
Maximum concentration of total Rotigotine in plasma at steady-state normalized by Body Weight [Cmax,ss,norm(BW)]	Blood sampling at 0 hours (predose), 1 hour, 2 hours, 4 hours, 8 hours, 12 hours, 16 hours, and 24 hours
Maximum concentration of total Rotigotine in plasma at steady-state normalized by apparent dose [Cmax,ss,norm(appd)]	Blood sampling at 0 hours (predose), 1 hour, 2 hours, 4 hours, 8 hours, 12 hours, 16 hours, and 24 hours
Maximum concentration of total Rotigotine in plasma at steady-state normalized by Body Weight and apparent dose [Cmax,ss,norm(BW,appd)]	Blood sampling at 0 hours (predose), 1 hour, 2 hours, 4 hours, 8 hours, 12 hours, 16 hours, and 24 hours

Secondary Outcome Measures

Outcome Measure	Time Frame
Terminal half-life (t1/2) of unconjugated Rotigotine in steady-state	Blood sampling at 24 hours, 25 hours, 26 hours, 28 hours, 30 hours, 33 hours, 36 hours, 48 hours
Time of maximum concentration (tmax) of unconjugated Rotigotine in steady-state (tmax,ss)	Blood sampling at 0 hours (predose), 1 hour, 2 hours, 4 hours, 8 hours, 12 hours, 16 hours, and 24 hours
Apparent total body clearance of unconjugated Rotigotine normalized by Body Weight (CL/f/BW)	Blood sampling at 0 hours (predose), 1 hour, 2 hours, 4 hours, 8 hours, 12 hours, 16 hours, and 24 hours
Apparent volume of distribution of unconjugated Rotigotine normalized by Body Weight (Vz/f/BW)	Blood sampling at 0 hours (predose), 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
Terminal half-life (t1/2) of total Rotigotine in steady-state	Blood sampling at 24 hours, 25 hours, 26 hours, 28 hours, 30 hours, 33 hours, 36 hours, 48 hours
Time of maximum concentration (tmax) of total Rotigotine in steady-state (tmax,ss)	Blood sampling at 0 hours (predose), 1 hour, 2 hours, 4 hours, 8 hours, 12 hours, 16 hours, and 24 hours
Apparent total body clearance of total Rotigotine normalized by Body Weight (CL/f/BW)	Blood sampling at 0 hours (predose), 1 hour, 2 hours, 4 hours, 8 hours, 12 hours, 16 hours, and 24 hours
Apparent volume of distribution of total Rotigotine normalized by Body Weight (Vz/f/BW)	Blood sampling at 0 hours (predose), 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

Collaborators and Investigators

• Sponsor: UCB BIOSCIENCES GmbH

Publications and helpful links

General Publications

• Cawello W, Kim SR, Braun M, Elshoff JP, Masahiro T, Ikeda J, Funaki T. Pharmacokinetics, safety, and tolerability of rotigotine transdermal system in healthy Japanese and Caucasian subjects following multiple-dose administration. Eur J Drug Metab Pharmacokinet. 2016 Aug;41(4):353-62. doi: 10.1007/s13318-015-0273-6. Epub 2015 Mar 13.

Study record dates

Study Major Dates

• Study Start: December 1, 2002
• Primary Completion (ACTUAL): March 1, 2003
• Study Completion (ACTUAL): March 1, 2003

Study Registration Dates

• First Submitted: May 10, 2013
• First Submitted That Met QC Criteria: May 10, 2013
• First Posted (ESTIMATE): May 15, 2013

Study Record Updates

• Last Update Posted (ESTIMATE): October 20, 2014
• Last Update Submitted That Met QC Criteria: October 17, 2014
• Last Verified: May 1, 2013

More Information

Terms related to this study

• Keywords: Pharmacokinetics; Japanese; Female; Male; Rotigotine; Neupro; Single dose; Caucasian
• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Dopamine Agonists; Dopamine Agents; Rotigotine
• Other Study ID Numbers: SP0718