Parkinson's Disease
Conditions
Keywords
Parkinson's Disease, Rotigotine, Pharmacokinetics, Healthy subjects
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.
Interventions
DRUGRotigotine
Day 1-3: 2 mg patch once daily Day 4-6: 4 mg patch once daily
OTHERPlacebo
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
Sponsors
UCB Pharma
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
BASIC_SCIENCE
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
19 Years to 45 Years
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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| 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
| Measure | Time frame |
|---|---|
| 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 |
| 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 |
| 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 |
| 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 |
| 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 |
Countries
South Korea
Outcome results
None listed