Clinical trial NCT01854216: Study to Evaluate the Pharmacokinetics, Safety, Tolerability of Repeated Dose Transdermal Rotigotine in Japanese and Caucasian Subjects
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy
Keywords: Rotigotine
Neupro
Japanese
Caucasian
Male
Female
Single dose
Pharmacokinetics
Lead sponsor: UCB Pharma
Sponsor class: INDUSTRY
First posted: 2013-05-15
Enrollment: 26
Sex: ALL
Minimum age (years): 20
Maximum age (years): 45
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL

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


Eligibility criteria: 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

Primary outcomes:
measure: Area under the concentration-time curve of unconjugated Rotigotine in steady-state within one dosing interval (AUCtau,ss)
timeFrame: Blood sampling at 0 hours (predose), 1 hour, 2 hours, 4 hours, 8 hours, 12 hours, 16 hours, and 24 hours
measure: Area under the concentration-time curve of unconjugated Rotigotine in steady-state within one dosing interval normalized by Body Weight [AUCtau,ss,norm(BW)]
timeFrame: Blood sampling at 0 hours (predose), 1 hour, 2 hours, 4 hours, 8 hours, 12 hours, 16 hours, and 24 hours
measure: Maximum concentration of unconjugated Rotigotine in plasma at steady-state (Cmax,ss)
timeFrame: Blood sampling at 0 hours (predose), 1 hour, 2 hours, 4 hours, 8 hours, 12 hours, 16 hours, and 24 hours
measure: Maximum concentration of unconjugated Rotigotine in plasma at steady-state normalized by Body Weight [Cmax,ss,norm(BW)]
timeFrame: Blood sampling at 0 hours (predose), 1 hour, 2 hours, 4 hours, 8 hours, 12 hours, 16 hours, and 24 hours
measure: Maximum concentration of unconjugated Rotigotine in plasma at steady-state normalized by apparent dose [Cmax,ss,norm(appd)]
timeFrame: Blood sampling at 0 hours (predose), 1 hour, 2 hours, 4 hours, 8 hours, 12 hours, 16 hours, and 24 hours
measure: Maximum concentration of unconjugated Rotigotine in plasma at steady-state normalized by Body Weight and apparent dose [Cmax,ss,norm(BW,appd)]
timeFrame: Blood sampling at 0 hours (predose), 1 hour, 2 hours, 4 hours, 8 hours, 12 hours, 16 hours, and 24 hours
measure: Area under the concentration-time curve of total Rotigotine in steady-state within one dosing interval (AUCtau,ss)
timeFrame: Blood sampling at 0 hours (predose), 1 hour, 2 hours, 4 hours, 8 hours, 12 hours, 16 hours, and 24 hours
measure: Area under the concentration-time curve of total Rotigotine in steady-state within one dosing interval normalized by Body Weight [AUCtau,ss,norm(BW)]
timeFrame: Blood sampling at 0 hours (predose), 1 hour, 2 hours, 4 hours, 8 hours, 12 hours, 16 hours, and 24 hours
measure: Maximum concentration of total Rotigotine in plasma at steady-state (Cmax,ss)
timeFrame: Blood sampling at 0 hours (predose), 1 hour, 2 hours, 4 hours, 8 hours, 12 hours, 16 hours, and 24 hours
measure: Maximum concentration of total Rotigotine in plasma at steady-state normalized by Body Weight [Cmax,ss,norm(BW)]
timeFrame: Blood sampling at 0 hours (predose), 1 hour, 2 hours, 4 hours, 8 hours, 12 hours, 16 hours, and 24 hours
measure: Maximum concentration of total Rotigotine in plasma at steady-state normalized by apparent dose [Cmax,ss,norm(appd)]
timeFrame: Blood sampling at 0 hours (predose), 1 hour, 2 hours, 4 hours, 8 hours, 12 hours, 16 hours, and 24 hours
measure: Maximum concentration of total Rotigotine in plasma at steady-state normalized by Body Weight and apparent dose [Cmax,ss,norm(BW,appd)]
timeFrame: Blood sampling at 0 hours (predose), 1 hour, 2 hours, 4 hours, 8 hours, 12 hours, 16 hours, and 24 hours
Secondary outcomes:
measure: Terminal half-life (t1/2) of unconjugated Rotigotine in steady-state
timeFrame: Blood sampling at 24 hours, 25 hours, 26 hours, 28 hours, 30 hours, 33 hours, 36 hours, 48 hours
measure: Time of maximum concentration (tmax) of unconjugated Rotigotine in steady-state (tmax,ss)
timeFrame: Blood sampling at 0 hours (predose), 1 hour, 2 hours, 4 hours, 8 hours, 12 hours, 16 hours, and 24 hours
measure: Apparent total body clearance of unconjugated Rotigotine normalized by Body Weight (CL/f/BW)
timeFrame: Blood sampling at 0 hours (predose), 1 hour, 2 hours, 4 hours, 8 hours, 12 hours, 16 hours, and 24 hours
measure: Apparent volume of distribution of unconjugated Rotigotine normalized by Body Weight (Vz/f/BW)
timeFrame: 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
measure: Terminal half-life (t1/2) of total Rotigotine in steady-state
timeFrame: Blood sampling at 24 hours, 25 hours, 26 hours, 28 hours, 30 hours, 33 hours, 36 hours, 48 hours
measure: Time of maximum concentration (tmax) of total Rotigotine in steady-state (tmax,ss)
timeFrame: Blood sampling at 0 hours (predose), 1 hour, 2 hours, 4 hours, 8 hours, 12 hours, 16 hours, and 24 hours
measure: Apparent total body clearance of total Rotigotine normalized by Body Weight (CL/f/BW)
timeFrame: Blood sampling at 0 hours (predose), 1 hour, 2 hours, 4 hours, 8 hours, 12 hours, 16 hours, and 24 hours
measure: Apparent volume of distribution of total Rotigotine normalized by Body Weight (Vz/f/BW)
timeFrame: 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
Other outcomes:
Locations:
city: Neuss
country: Germany
facility: 1
Study officials:
affiliation: +1 877 822 9493 (UCB)
name: UCB Clinical Trial Call Center
role: STUDY_DIRECTOR
References:
citation: 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.