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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
UCB, Inc.
ClinicalTrials.gov Identifier:
NCT01964573
First received: October 14, 2013
Last updated: October 16, 2013
Last verified: October 2013
  Purpose

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 Intervention Phase
Parkinson's Disease
Drug: Rotigotine
Other: Placebo
Phase 1

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Pharmacokinetics Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, 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

Resource links provided by NLM:


Further study details as provided by UCB, Inc.:

Primary Outcome Measures:
  • Plasma concentrations of unconjugated Rotigotine [ Time Frame: 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 ] [ Designated as safety issue: No ]
  • Plasma concentrations of total Rotigotine [ Time Frame: 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 ] [ Designated as safety issue: No ]
  • Area under the plasma concentration-time curve from 0 to 24 hours at steady-state (AUC (0-24), ss) for unconjugated Rotigotine [ Time Frame: 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 ] [ Designated as safety issue: No ]
  • Area under the plasma concentration-time curve from 0 to 24 hours at steady-state (AUC (0-24), ss) for total Rotigotine [ Time Frame: 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 ] [ Designated as safety issue: No ]
  • 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 [ Time Frame: 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 ] [ Designated as safety issue: No ]
  • 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 [ Time Frame: 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 ] [ Designated as safety issue: No ]
  • Maximum plasma concentration (Cmax) for unconjugated Rotigotine [ Time Frame: 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 ] [ Designated as safety issue: No ]
  • Maximum plasma concentration (Cmax) for total Rotigotine [ Time Frame: 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 ] [ Designated as safety issue: No ]
  • Maximum plasma concentration normalized by Body Weight (Cmax, norm (BW)) for unconjugated Rotigotine [ Time Frame: 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 ] [ Designated as safety issue: No ]
  • Maximum plasma concentration normalized by Body Weight (Cmax, norm (BW)) for total Rotigotine [ Time Frame: 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 ] [ Designated as safety issue: No ]

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 [ Time Frame: 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 ] [ Designated as safety issue: No ]
  • 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 [ Time Frame: 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 ] [ Designated as safety issue: No ]
  • Maximum plasma concentration normalized by apparent-dose (Cmax, norm (apparent-dose)) of unconjugated Rotigotine [ Time Frame: 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 ] [ Designated as safety issue: No ]
  • Maximum plasma concentration normalized by apparent-dose (Cmax, norm (apparent-dose)) of total Rotigotine [ Time Frame: 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 ] [ Designated as safety issue: No ]
  • 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 [ Time Frame: 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 ] [ Designated as safety issue: No ]
  • 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 [ Time Frame: 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 ] [ Designated as safety issue: No ]
  • Maximum plasma concentration normalized by drug content of patch (Cmax, norm (mgdc)) for unconjugated Rotigotine [ Time Frame: 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 ] [ Designated as safety issue: No ]
  • Maximum plasma concentration normalized by drug content of patch (Cmax, norm (mgdc)) for total Rotigotine [ Time Frame: 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 ] [ Designated as safety issue: No ]
  • Terminal half-life (t ½) for unconjugated Rotigotine [ Time Frame: 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 ] [ Designated as safety issue: No ]
  • Terminal half-life (t ½) for total Rotigotine [ Time Frame: 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 ] [ Designated as safety issue: No ]
  • Time to reach maximum plasma concentration during a dosing interval at steady-state (t max, ss) for unconjugated Rotigotine [ Time Frame: 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 ] [ Designated as safety issue: No ]
  • Time to reach maximum plasma concentration during a dosing interval at steady-state (t max, ss) for total Rotigotine [ Time Frame: 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 ] [ Designated as safety issue: No ]
  • Apparent total body clearance (CL/f) for unconjugated Rotigotine [ Time Frame: 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 ] [ Designated as safety issue: No ]
  • Apparent total body clearance (CL/f) for total Rotigotine [ Time Frame: 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 ] [ Designated as safety issue: No ]
  • Apparent total body clearance normalized by Body Weight (CL/f norm (BW)) for unconjugated Rotigotine [ Time Frame: 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 ] [ Designated as safety issue: No ]
  • Apparent total body clearance normalized by Body Weight (CL/f norm (BW)) for total Rotigotine [ Time Frame: 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 ] [ Designated as safety issue: No ]
  • Apparent total body clearance normalized by apparent-dose (CL/f norm (apparent-dose)) for unconjugated Rotigotine [ Time Frame: 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 ] [ Designated as safety issue: No ]
  • Apparent total body clearance normalized by apparent-dose (CL/f norm (apparent-dose)) for total Rotigotine [ Time Frame: 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 ] [ Designated as safety issue: No ]
  • Apparent volume of distribution (Vz/f) for unconjugated Rotigotine [ Time Frame: 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 ] [ Designated as safety issue: No ]
  • Apparent volume of distribution (Vz/f) for total Rotigotine [ Time Frame: 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 ] [ Designated as safety issue: No ]
  • Apparent volume of distribution normalized by Body Weight (Vz/f norm (BW)) for unconjugated Rotigotine [ Time Frame: 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 ] [ Designated as safety issue: No ]
  • Apparent volume of distribution normalized by Body Weight (Vz/f norm (BW)) for total Rotigotine [ Time Frame: 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 ] [ Designated as safety issue: No ]
  • Plasma concentration at steady-state directly before patch removal (C (24), ss) for total Despropyl Rotigotine [ Time Frame: Directly before patch removal at Day 2 to Day 7 ] [ Designated as safety issue: No ]
  • Plasma concentration at steady-state directly before patch removal (C (24), ss) for total Desthienyl Rotigotine [ Time Frame: Directly before patch removal at Day 2 to Day 7 ] [ Designated as safety issue: No ]
  • Plasma concentration at steady-state 30 hours after last patch application (C (30 h), ss) for total Despropyl Rotigotine [ Time Frame: At day 7 at 30 hours after last patch application ] [ Designated as safety issue: No ]
  • Plasma concentration at steady-state 30 hours after last patch application (C (30 h), ss) for total Desthienyl Rotigotine [ Time Frame: At day 7 at 30 hours after last patch application ] [ Designated as safety issue: No ]
  • Amount excreted into urine from 0 to 24 hours at steady-state (Ae (0-24), ss) for unconjungated Rotigotine [ Time Frame: Day 3 and Day 6 from 0 to after 24 hours of patch application ] [ Designated as safety issue: No ]
  • Amount excreted into urine from 0 to 24 hours at steady-state (Ae (0-24), ss) for total Rotigotine [ Time Frame: Day 3 and Day 6 from 0 to after 24 hours of patch application ] [ Designated as safety issue: No ]
  • Amount excreted into urine from 0 to 24 hours at steady-state (Ae (0-24), ss) for total Despropyl Rotigotine [ Time Frame: Day 3 and Day 6 from 0 to after 24 hours of patch application ] [ Designated as safety issue: No ]
  • Amount excreted into urine from 0 to 24 hours at steady-state (Ae (0-24), ss) for total Desthienyl Rotigotine [ Time Frame: Day 3 and Day 6 from 0 to after 24 hours of patch application ] [ Designated as safety issue: No ]
  • Renal Clearance (CLR) for unconjugated Rotigotine [ Time Frame: Day 3 and Day 6 from 0 to after 24 hours of patch application ] [ Designated as safety issue: No ]
  • Renal Clearance (CLR) for total Rotigotine [ Time Frame: Day 3 and Day 6 from 0 to after 24 hours of patch application ] [ Designated as safety issue: No ]

Enrollment: 48
Study Start Date: December 2006
Study Completion Date: February 2007
Primary Completion Date: February 2007 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Rotigotine group Drug: Rotigotine

Day 1-3: 2 mg patch once daily

Day 4-6: 4 mg patch once daily

Other Name: 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


  Eligibility

Ages Eligible for Study:   19 Years to 45 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01964573

Locations
Korea, Republic of
Seoul, Korea, Republic of
Sponsors and Collaborators
UCB, Inc.
Investigators
Study Director: UCB, Inc. +1 877 822 9493
  More Information

No publications provided

Responsible Party: UCB, Inc.
ClinicalTrials.gov Identifier: NCT01964573     History of Changes
Other Study ID Numbers: SP885
Study First Received: October 14, 2013
Last Updated: October 16, 2013
Health Authority: Korea: Food and Drug Administration

Keywords provided by UCB, Inc.:
Parkinson's Disease
Rotigotine
Pharmacokinetics
Healthy subjects

Additional relevant MeSH terms:
Parkinson Disease
Parkinsonian Disorders
Basal Ganglia Diseases
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Movement Disorders
Neurodegenerative Diseases
N 0437
Dopamine Agonists
Dopamine Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on August 20, 2014