Trial to Evaluate the Pharmacokinetics, Safety, and Tolerability of Rotigotine in Healthy Korean Subjects

Sponsor

UCB Pharma (Industry)

Overall Status

Completed

CT.gov ID

NCT01964573

Collaborator

(none)

Enrollment

Location

Arms

Duration (Months)

23.6

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The objective of this trial is to investigate the PK (Pharmacokinetic) of repeated-dose applications of the Rotigotine transdermal patch in healthy young male and female Korean subjects to be submitted to MFDS for new drug application approval.

Condition or Disease	Intervention/Treatment	Phase
Parkinson's Disease	Drug: Rotigotine Other: Placebo	Phase 1

Study Design

Study Type:

Interventional

Actual Enrollment :

48 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Double (Participant, Investigator)

Primary Purpose:

Basic Science

Official Title:

A Single-site, Randomized, Double-blind, Placebo-controlled, Repeated-dose Trial to Evaluate the Pharmacokinetics, Safety, and Tolerability of Rotigotine in 2 Different Dosages (2 mg / 24 Hours [10 cm2], 4 mg / 24 Hours [20 cm2]) in Healthy Korean Subjects

Study Start Date :

Dec 1, 2006

Actual Primary Completion Date :

Feb 1, 2007

Actual Study Completion Date :

Feb 1, 2007

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Rotigotine group	Drug: Rotigotine Day 1-3: 2 mg patch once daily Day 4-6: 4 mg patch once daily Other Names: Neupro
Placebo Comparator: Placebo group Placebo matched to rotigotine will be administered in the same way as within the Rotigotine group.	Other: Placebo Placebo patches matching with Rotigotine 2 mg patches and 4 mg patches. Frequency: Day 1-3: 2 mg patch once daily Day 4-6: 4 mg patch once daily

Arm

Intervention/Treatment

Experimental: Rotigotine group

Drug: Rotigotine

Day 1-3: 2 mg patch once daily Day 4-6: 4 mg patch once daily

Other Names:

Neupro

Placebo Comparator: Placebo group

Placebo matched to rotigotine will be administered in the same way as within the Rotigotine group.

Other: Placebo

Placebo patches matching with Rotigotine 2 mg patches and 4 mg patches. Frequency: Day 1-3: 2 mg patch once daily Day 4-6: 4 mg patch once daily

Outcome Measures

Primary Outcome Measures

Plasma concentrations of unconjugated Rotigotine [Day 3 and Day 6 predose, and 1, 2, 3, 4, 6, 8, 12, 16, 24 hours after patch application at Day 3 and 6 and 25, 26, 28, 30, 33 and 36, 48, 60, 72 hours after patch application on Day 6]
Plasma concentrations of total Rotigotine [Day 3 and Day 6 predose, and 1, 2, 3, 4, 6, 8, 12, 16, 24 hours after patch application at Day 3 and 6 and 25, 26, 28, 30, 33 and 36, 48, 60, 72 hours after patch application on Day 6]
Area under the plasma concentration-time curve from 0 to 24 hours at steady-state (AUC (0-24), ss) for unconjugated Rotigotine [Day 3 and Day 6 predose, and 1, 2, 3, 4, 6, 8, 12, 16, 24 hours after patch application at Day 3 and 6 and 25, 26, 28, 30, 33 and 36, 48, 60, 72 hours after patch application on Day 6]
Area under the plasma concentration-time curve from 0 to 24 hours at steady-state (AUC (0-24), ss) for total Rotigotine [Day 3 and Day 6 predose, and 1, 2, 3, 4, 6, 8, 12, 16, 24 hours after patch application at Day 3 and 6 and 25, 26, 28, 30, 33 and 36, 48, 60, 72 hours after patch application on Day 6]
Area under the plasma concentration-time curve from 0 to 24 hours at steady-state normalized by Body Weight (AUC (0-24), ss, norm (BW)) for unconjugated Rotigotine [Day 3 and Day 6 predose, and 1, 2, 3, 4, 6, 8, 12, 16, 24 hours after patch application at Day 3 and 6 and 25, 26, 28, 30, 33 and 36, 48, 60, 72 hours after patch application on Day 6]
Area under the plasma concentration-time curve from 0 to 24 hours at steady-state normalized by Body Weight (AUC (0-24), ss, norm (BW)) for total Rotigotine [Day 3 and Day 6 predose, and 1, 2, 3, 4, 6, 8, 12, 16, 24 hours after patch application at Day 3 and 6 and 25, 26, 28, 30, 33 and 36, 48, 60, 72 hours after patch application on Day 6]
Maximum plasma concentration (Cmax) for unconjugated Rotigotine [Day 3 and Day 6 predose, and 1, 2, 3, 4, 6, 8, 12, 16, 24 hours after patch application at Day 3 and 6 and 25, 26, 28, 30, 33 and 36, 48, 60, 72 hours after patch application on Day 6]
Maximum plasma concentration (Cmax) for total Rotigotine [Day 3 and Day 6 predose, and 1, 2, 3, 4, 6, 8, 12, 16, 24 hours after patch application at Day 3 and 6 and 25, 26, 28, 30, 33 and 36, 48, 60, 72 hours after patch application on Day 6]
Maximum plasma concentration normalized by Body Weight (Cmax, norm (BW)) for unconjugated Rotigotine [Day 3 and Day 6 predose, and 1, 2, 3, 4, 6, 8, 12, 16, 24 hours after patch application at Day 3 and 6 and 25, 26, 28, 30, 33 and 36, 48, 60, 72 hours after patch application on Day 6]
Maximum plasma concentration normalized by Body Weight (Cmax, norm (BW)) for total Rotigotine [Day 3 and Day 6 predose, and 1, 2, 3, 4, 6, 8, 12, 16, 24 hours after patch application at Day 3 and 6 and 25, 26, 28, 30, 33 and 36, 48, 60, 72 hours after patch application on Day 6]

Secondary Outcome Measures

Area under the plasma concentration-time curve from 0 to 24 hours at steady-state normalized by apparent-dose (AUC (0-24), ss, norm (apparent-dose)) of unconjugated Rotigotine [Day 3 and Day 6 predose, and 1, 2, 3, 4, 6, 8, 12, 16, 24 hours after patch application at Day 3 and 6 and 25, 26, 28, 30, 33 and 36, 48, 60, 72 hours after patch application on Day 6]
Area under the plasma concentration-time curve from 0 to 24 hours at steady-state normalized by apparent-dose (AUC (0-24), ss, norm (apparent-dose)) of total Rotigotine [Day 3 and Day 6 predose, and 1, 2, 3, 4, 6, 8, 12, 16, 24 hours after patch application at Day 3 and 6 and 25, 26, 28, 30, 33 and 36, 48, 60, 72 hours after patch application on Day 6]
Maximum plasma concentration normalized by apparent-dose (Cmax, norm (apparent-dose)) of unconjugated Rotigotine [Day 3 and Day 6 predose, and 1, 2, 3, 4, 6, 8, 12, 16, 24 hours after patch application at Day 3 and 6 and 25, 26, 28, 30, 33 and 36, 48, 60, 72 hours after patch application on Day 6]
Maximum plasma concentration normalized by apparent-dose (Cmax, norm (apparent-dose)) of total Rotigotine [Day 3 and Day 6 predose, and 1, 2, 3, 4, 6, 8, 12, 16, 24 hours after patch application at Day 3 and 6 and 25, 26, 28, 30, 33 and 36, 48, 60, 72 hours after patch application on Day 6]
Area under the plasma concentration-time curve from 0 to 24 hours at steady-state normalized by drug content (AUC (0-24), ss, norm (mgdc)) for unconjugated Rotigotine [Day 3 and Day 6 predose, and 1, 2, 3, 4, 6, 8, 12, 16, 24 hours after patch application at Day 3 and 6 and 25, 26, 28, 30, 33 and 36, 48, 60, 72 hours after patch application on Day 6]
Area under the plasma concentration-time curve from 0 to 24 hours at steady-state normalized by drug content (AUC (0-24), ss, norm (mgdc)) for total Rotigotine [Day 3 and Day 6 predose, and 1, 2, 3, 4, 6, 8, 12, 16, 24 hours after patch application at Day 3 and 6 and 25, 26, 28, 30, 33 and 36, 48, 60, 72 hours after patch application on Day 6]
Maximum plasma concentration normalized by drug content of patch (Cmax, norm (mgdc)) for unconjugated Rotigotine [Day 3 and Day 6 predose, and 1, 2, 3, 4, 6, 8, 12, 16, 24 hours after patch application at Day 3 and 6 and 25, 26, 28, 30, 33 and 36, 48, 60, 72 hours after patch application on Day 6]
Maximum plasma concentration normalized by drug content of patch (Cmax, norm (mgdc)) for total Rotigotine [Day 3 and Day 6 predose, and 1, 2, 3, 4, 6, 8, 12, 16, 24 hours after patch application at Day 3 and 6 and 25, 26, 28, 30, 33 and 36, 48, 60, 72 hours after patch application on Day 6]
Terminal half-life (t ½) for unconjugated Rotigotine [Day 3 and Day 6 predose, and 1, 2, 3, 4, 6, 8, 12, 16, 24 hours after patch application at Day 3 and 6 and 25, 26, 28, 30, 33 and 36, 48, 60, 72 hours after patch application on Day 6]
Terminal half-life (t ½) for total Rotigotine [Day 3 and Day 6 predose, and 1, 2, 3, 4, 6, 8, 12, 16, 24 hours after patch application at Day 3 and 6 and 25, 26, 28, 30, 33 and 36, 48, 60, 72 hours after patch application on Day 6]
Time to reach maximum plasma concentration during a dosing interval at steady-state (t max, ss) for unconjugated Rotigotine [Day 3 and Day 6 predose, and 1, 2, 3, 4, 6, 8, 12, 16, 24 hours after patch application at Day 3 and 6 and 25, 26, 28, 30, 33 and 36, 48, 60, 72 hours after patch application on Day 6]
Time to reach maximum plasma concentration during a dosing interval at steady-state (t max, ss) for total Rotigotine [Day 3 and Day 6 predose, and 1, 2, 3, 4, 6, 8, 12, 16, 24 hours after patch application at Day 3 and 6 and 25, 26, 28, 30, 33 and 36, 48, 60, 72 hours after patch application on Day 6]
Apparent total body clearance (CL/f) for unconjugated Rotigotine [Day 3 and Day 6 predose, and 1, 2, 3, 4, 6, 8, 12, 16, 24 hours after patch application at Day 3 and 6 and 25, 26, 28, 30, 33 and 36, 48, 60, 72 hours after patch application on Day 6]
Apparent total body clearance (CL/f) for total Rotigotine [Day 3 and Day 6 predose, and 1, 2, 3, 4, 6, 8, 12, 16, 24 hours after patch application at Day 3 and 6 and 25, 26, 28, 30, 33 and 36, 48, 60, 72 hours after patch application on Day 6]
Apparent total body clearance normalized by Body Weight (CL/f norm (BW)) for unconjugated Rotigotine [Day 3 and Day 6 predose, and 1, 2, 3, 4, 6, 8, 12, 16, 24 hours after patch application at Day 3 and 6 and 25, 26, 28, 30, 33 and 36, 48, 60, 72 hours after patch application on Day 6]
Apparent total body clearance normalized by Body Weight (CL/f norm (BW)) for total Rotigotine [Day 3 and Day 6 predose, and 1, 2, 3, 4, 6, 8, 12, 16, 24 hours after patch application at Day 3 and 6 and 25, 26, 28, 30, 33 and 36, 48, 60, 72 hours after patch application on Day 6]
Apparent total body clearance normalized by apparent-dose (CL/f norm (apparent-dose)) for unconjugated Rotigotine [Day 3 and Day 6 predose, and 1, 2, 3, 4, 6, 8, 12, 16, 24 hours after patch application at Day 3 and 6 and 25, 26, 28, 30, 33 and 36, 48, 60, 72 hours after patch application on Day 6]
Apparent total body clearance normalized by apparent-dose (CL/f norm (apparent-dose)) for total Rotigotine [Day 3 and Day 6 predose, and 1, 2, 3, 4, 6, 8, 12, 16, 24 hours after patch application at Day 3 and 6 and 25, 26, 28, 30, 33 and 36, 48, 60, 72 hours after patch application on Day 6]
Apparent volume of distribution (Vz/f) for unconjugated Rotigotine [Day 3 and Day 6 predose, and 1, 2, 3, 4, 6, 8, 12, 16, 24 hours after patch application at Day 3 and 6 and 25, 26, 28, 30, 33 and 36, 48, 60, 72 hours after patch application on Day 6]
Apparent volume of distribution (Vz/f) for total Rotigotine [Day 3 and Day 6 predose, and 1, 2, 3, 4, 6, 8, 12, 16, 24 hours after patch application at Day 3 and 6 and 25, 26, 28, 30, 33 and 36, 48, 60, 72 hours after patch application on Day 6]
Apparent volume of distribution normalized by Body Weight (Vz/f norm (BW)) for unconjugated Rotigotine [Day 3 and Day 6 predose, and 1, 2, 3, 4, 6, 8, 12, 16, 24 hours after patch application at Day 3 and 6 and 25, 26, 28, 30, 33 and 36, 48, 60, 72 hours after patch application on Day 6]
Apparent volume of distribution normalized by Body Weight (Vz/f norm (BW)) for total Rotigotine [Day 3 and Day 6 predose, and 1, 2, 3, 4, 6, 8, 12, 16, 24 hours after patch application at Day 3 and 6 and 25, 26, 28, 30, 33 and 36, 48, 60, 72 hours after patch application on Day 6]
Plasma concentration at steady-state directly before patch removal (C (24), ss) for total Despropyl Rotigotine [Directly before patch removal at Day 2 to Day 7]
Plasma concentration at steady-state directly before patch removal (C (24), ss) for total Desthienyl Rotigotine [Directly before patch removal at Day 2 to Day 7]
Plasma concentration at steady-state 30 hours after last patch application (C (30 h), ss) for total Despropyl Rotigotine [At day 7 at 30 hours after last patch application]
Plasma concentration at steady-state 30 hours after last patch application (C (30 h), ss) for total Desthienyl Rotigotine [At day 7 at 30 hours after last patch application]
Amount excreted into urine from 0 to 24 hours at steady-state (Ae (0-24), ss) for unconjungated Rotigotine [Day 3 and Day 6 from 0 to after 24 hours of patch application]
Amount excreted into urine from 0 to 24 hours at steady-state (Ae (0-24), ss) for total Rotigotine [Day 3 and Day 6 from 0 to after 24 hours of patch application]
Amount excreted into urine from 0 to 24 hours at steady-state (Ae (0-24), ss) for total Despropyl Rotigotine [Day 3 and Day 6 from 0 to after 24 hours of patch application]
Amount excreted into urine from 0 to 24 hours at steady-state (Ae (0-24), ss) for total Desthienyl Rotigotine [Day 3 and Day 6 from 0 to after 24 hours of patch application]
Renal Clearance (CLR) for unconjugated Rotigotine [Day 3 and Day 6 from 0 to after 24 hours of patch application]
Renal Clearance (CLR) for total Rotigotine [Day 3 and Day 6 from 0 to after 24 hours of patch application]

Eligibility Criteria

Criteria

Ages Eligible for Study:

19 Years to 45 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Yes

Inclusion Criteria:

Subject is male or female and aged between 19 and 45 years of age (inclusive)
Subject is healthy (no clinically relevant findings in any of the investigations of the pre-examination) as judged by the investigator
Subject is of normal body weight as determined by a Body Mass Index (BMI) between 18 and 28 kg / m²
Subject is Korean (both parents are pure Korean)

Exclusion Criteria:

Subject has had a history of drug or alcohol abuse within the last 2 years
Subject has had a history of transient ischemic attack or stroke within the last 12 months
Subject has a history or current condition of Epilepsy and / or seizures
Subject has a history of significant skin hypersensitivity to adhesives or other transdermal products or recently unsolved Contact Dermatitis
Subject has a history or present condition of an Atopic or Eczematous Dermatitis, Psoriasis, and / or an active skin disease
Female subject is pregnant or lactating
Subject has any medical or psychiatric condition that, in the opinion of the investigator, could jeopardize or would compromise the subject's ability to participate in this trial
Subject has a QTcB (according to Bazett´s formula) interval of ≥ 450 ms for female or ≥ 430 ms for male or any other clinically relevant Electrocardiogram (ECG) finding
Subject has any clinically relevant abnormality in the physical examination, or any clinically relevant deviation from the normal range in the clinical chemistry, hematology, or urinalysis
Subject has a relevant hepatic dysfunction (total Bilirubin > 2 mg /dL or Alanine Aminotransferase [ALT] or Aspartate Aminotransferase [AST] greater than 2 times the upper limit of the normal reference range)
Subject has a positive test for Human Immunodeficiency Virus antibodies (HIV)-1/2Ab, Hepatitis B surface Antigen (HBsAg) or Hepatitis C Virus Antibody (HCV-Ab)
Subject has a positive test for alcohol or drugs
Subject consumes more than 150 g of alcohol / week
Subject has made a blood donation or had a comparable blood loss (> 400 ml) within the last 3 months
Subject smokes more than 5 cigarettes per day or has done so within previous 6 months
Subject has a clinically relevant allergy
Subject is taking any medication (excluding oral hormonal contraceptive) currently or within 2 weeks prior to the first day of dosing (with the exception of Acetaminophen [up to 1000 mg per day per os] which may have been taken up to 48 hours prior to commencement of dosing)
Female subject is currently taking an oral hormonal contraceptive but less than 2 months
Subject has a symptomatic orthostatic hypotension with a decrease of Blood Pressure (BP) from supine to standing position of ≥ 20 mmHg in systolic BP or of ≥ 10 mmHg in diastolic BP after 1 and / or 3 minutes
Subject has a pulse rate at rest less than 45 beats per minute or more than 100 beats per minute (measured in supine position)
Subject has a systolic Blood Pressure (BP) lower than 100 mmHg or higher than 150 mmHg or diastolic BP higher than 95 mmHg (measured in supine position)
Subject has a current or a history of clinically relevant motor disturbance, impairment of memory, sleep disturbance or neurodegenerative disease (e.g. , Alzheimer Dementia, Diffuse, Lewy Body Dementia, Amyotrophic Lateral Sclerosis [ALS], Multiple Sclerosis)
Subject has taken herbal medicine therapy within the last 2 weeks
Subject consumes more than 3 cups (more than 450 ml) of caffeinated beverages per day within the last 2 weeks