Bioequivalence Study of Rotigotine Transdermal Patch With Two Different Formulations in Healthy Japanese Subjects

Single-site, Open-label, Randomized, Cross-over Study in Healthy Japanese Subjects to Evaluate the Bioequivalence of Single Dose Rotigotine Transdermal Patch (2 mg/24 h) Comparing 2 Different Formulations

To investigate and compare the drug amount delivered to the body after each single administration of Rotigotine patch with 2 different formulations in healthy Japanese subjects.

Study Overview

• Status: Completed
• Conditions: Healthy Volunteers
• Intervention / Treatment: Drug: Rotigotine PR 2.1.4; Drug: Rotigotine PR 2.2.1

• Study Type: Interventional
• Enrollment (Actual): 55
• Phase: Phase 1

Contacts and Locations

Study Locations

• Germany
  • Neuss, Germany
    • 1

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years to 55 years (ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Healthy Japanese male and female volunteers with the age between 20 and 55 years old

Exclusion Criteria:

• Subject has participated or is participating in any other clinical studies of investigational drug or another Investigational Medical Product (IMP) within the last 3 months
• Subject is not healthy (eg, taking any drug treatments, excessive amount of alcohol, cigarettes, having any medical or emotional/psychological problems, a drug/alcohol abuse, having abnormal safety parameters)
• Subject has a QTcB (QT interval corrected for Heart Rate [HR] using Bazett´s formula) interval of ≥ 430 ms (≥ 450 ms for females) or any other clinically relevant finding in Electrocardiogram (ECG) at the Eligibility Assessment (EA)
• Subject is having clinically relevant allergy or clinically relevant drug hypersensitivity to any components of the Investigational Medical Product (IMP), or/and having an atopic or eczematous Dermatitis, Psoriasis and/or active skin disease
• Subject has a recent history (within 2 years) of chronic alcohol or drug abuse and has a history of significant skin hypersensitivity to transdermal products, and of an atopic or eczematous Dermatitis, Psoriasis, and/or active skin disease and have a history of suicide attempt, Epilepsy and/or seizures
• Subject has made a blood donation or a comparable blood loss within the last 3 months prior to the Eligibility Assessment (EA)
• Subject is pregnant or nursing

Study Plan

How is the study designed?

Design Details

• Allocation: RANDOMIZED
• Interventional Model: CROSSOVER
• Masking: NONE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Treatment A - Treatment B; Treatment A: Test; drug product PR 2.2.1 Treatment B: Reference; drug product PR 2.1.4 Sequence of two single applications of Rotigotine transdermal patches (PR 2.2.1 first) for 24 hours separated by a Washout Period of 5 days.	Drug: Rotigotine PR 2.1.4; Treatment B: Rotigotine transdermal patch (2 mg/24 h [10 cm^2]). Reference; drug product PR 2.1.4. Single application of 1 patch for 24 hours.; Other Names: Neupro; Drug: Rotigotine PR 2.2.1; Treatment A: Rotigotine transdermal patch (2 mg/24 h [10 cm^2]). Test; drug product PR 2.2.1. Single application of 1 patch for 24 hours.; Other Names: Neupro
EXPERIMENTAL: Treatment B - Treatment A; Treatment B: Reference; drug product PR 2.1.4 Treatment A: Test; drug product PR 2.2.1 Sequence of two single applications of Rotigotine transdermal patches (PR 2.1.4 first) for 24 hours separated by a Washout Period of 5 days.	Drug: Rotigotine PR 2.1.4; Treatment B: Rotigotine transdermal patch (2 mg/24 h [10 cm^2]). Reference; drug product PR 2.1.4. Single application of 1 patch for 24 hours.; Other Names: Neupro; Drug: Rotigotine PR 2.2.1; Treatment A: Rotigotine transdermal patch (2 mg/24 h [10 cm^2]). Test; drug product PR 2.2.1. Single application of 1 patch for 24 hours.; Other Names: Neupro

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Maximum plasma concentration of unconjugated Rotigotine (Cmax)	The value of the maximum plasma concentration is directly obtained from the observed plasma concentration versus time curves.	Pharmacokinetic (PK) samples will be taken predose, 1 h, 2 h, 3 h, 4 h, 6 h, 8 h, 12 h, 16 h, 24 h (before patch removal in the morning of Day 2), 25 h, 26 h, 28 h, 30 h, 32 h, 36 h, 40 h and 48 h after Rotigotine administration
Area under the plasma concentration-time curve from zero up to the last analytically quantifiable concentration of unconjugated Rotigotine (AUC 0-t)		Pharmacokinetic (PK) samples will be taken predose, 1 h, 2 h, 3 h, 4 h, 6 h, 8 h, 12 h, 16 h, 24 h (before patch removal in the morning of Day 2), 25 h, 26 h, 28 h, 30 h, 32 h, 36 h, 40 h and 48 h after Rotigotine administration

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Area under the plasma concentration-time curve from zero up to infinity (AUC(0-∞))	The area under the curve extrapolated to infinity is calculated as the sum of AUC(0-t) and a residual part extrapolated to infinite time.	Pharmacokinetic (PK) samples will be taken predose, 1 h, 2 h, 3 h, 4 h, 6 h, 8 h, 12 h, 16 h, 24 h (before patch removal in the morning of Day 2), 25 h, 26 h, 28 h, 30 h, 32 h, 36 h, 40 h and 48 h after Rotigotine administration
Area under the plasma concentration-time curve from zero up to the last analytically quantifiable concentration normalized by apparent dose (mg) (AUC(0-t) norm (apparent dose))		Pharmacokinetic (PK) samples will be taken predose, 1 h, 2 h, 3 h, 4 h, 6 h, 8 h, 12 h, 16 h, 24 h (before patch removal in the morning of Day 2), 25 h, 26 h, 28 h, 30 h, 32 h, 36 h, 40 h and 48 h after Rotigotine administration
Area under the plasma concentration-time curve from zero up to the last analytically quantifiable concentration normalized by body weight (kg) (AUC(0-t) norm (BW))		Pharmacokinetic (PK) samples will be taken predose, 1 h, 2 h, 3 h, 4 h, 6 h, 8 h, 12 h, 16 h, 24 h (before patch removal in the morning of Day 2), 25 h, 26 h, 28 h, 30 h, 32 h, 36 h, 40 h and 48 h after Rotigotine administration
Area under the plasma concentration-time curve from zero up to infinity normalized by apparent dose (mg) (AUC(0-∞) norm (apparent dose))		Pharmacokinetic (PK) samples will be taken predose, 1 h, 2 h, 3 h, 4 h, 6 h, 8 h, 12 h, 16 h, 24 h (before patch removal in the morning of Day 2), 25 h, 26 h, 28 h, 30 h, 32 h, 36 h, 40 h and 48 h after Rotigotine administration
Area under the plasma concentration-time curve from zero up to infinity normalized by body weight (kg) (AUC(0-∞) norm (BW))		Pharmacokinetic (PK) samples will be taken predose, 1 h, 2 h, 3 h, 4 h, 6 h, 8 h, 12 h, 16 h, 24 h (before patch removal in the morning of Day 2), 25 h, 26 h, 28 h, 30 h, 32 h, 36 h, 40 h and 48 h after Rotigotine administration
Maximum plasma concentration normalized by apparent dose (Cmax,norm (apparent dose))		Pharmacokinetic (PK) samples will be taken predose, 1 h, 2 h, 3 h, 4 h, 6 h, 8 h, 12 h, 16 h, 24 h (before patch removal in the morning of Day 2), 25 h, 26 h, 28 h, 30 h, 32 h, 36 h, 40 h and 48 h after Rotigotine administration
Maximum plasma concentration normalized by body weight (Cmax,norm (BW))		Pharmacokinetic (PK) samples will be taken predose, 1 h, 2 h, 3 h, 4 h, 6 h, 8 h, 12 h, 16 h, 24 h (before patch removal in the morning of Day 2), 25 h, 26 h, 28 h, 30 h, 32 h, 36 h, 40 h and 48 h after Rotigotine administration
Time to reach a maximum plasma concentration of unconjugated Rotigotine after patch application (tmax)		Pharmacokinetic (PK) samples will be taken predose, 1 h, 2 h, 3 h, 4 h, 6 h, 8 h, 12 h, 16 h, 24 h (before patch removal in the morning of Day 2), 25 h, 26 h, 28 h, 30 h, 32 h, 36 h, 40 h and 48 h after Rotigotine administration
Mean residence time (MRT)		Pharmacokinetic (PK) samples will be taken predose, 1 h, 2 h, 3 h, 4 h, 6 h, 8 h, 12 h, 16 h, 24 h (before patch removal in the morning of Day 2), 25 h, 26 h, 28 h, 30 h, 32 h, 36 h, 40 h and 48 h after Rotigotine administration
Rate constant of elimination (λz)		Pharmacokinetic (PK) samples will be taken predose, 1 h, 2 h, 3 h, 4 h, 6 h, 8 h, 12 h, 16 h, 24 h (before patch removal in the morning of Day 2), 25 h, 26 h, 28 h, 30 h, 32 h, 36 h, 40 h and 48 h after Rotigotine administration
Terminal half-life (t1/2)		Pharmacokinetic (PK) samples will be taken predose, 1 h, 2 h, 3 h, 4 h, 6 h, 8 h, 12 h, 16 h, 24 h (before patch removal in the morning of Day 2), 25 h, 26 h, 28 h, 30 h, 32 h, 36 h, 40 h and 48 h after Rotigotine administration
Relative bioavailability calculated based on maximum plasma concentration (fCmax)		Pharmacokinetic (PK) samples will be taken predose, 1 h, 2 h, 3 h, 4 h, 6 h, 8 h, 12 h, 16 h, 24 h (before patch removal in the morning of Day 2), 25 h, 26 h, 28 h, 30 h, 32 h, 36 h, 40 h and 48 h after Rotigotine administration
Relative bioavailability calculated based on the area under the plasma concentration-time curve (fAUC)		Pharmacokinetic (PK) samples will be taken predose, 1 h, 2 h, 3 h, 4 h, 6 h, 8 h, 12 h, 16 h, 24 h (before patch removal in the morning of Day 2), 25 h, 26 h, 28 h, 30 h, 32 h, 36 h, 40 h and 48 h after Rotigotine administration
Apparent total body clearance (CL/f)		Pharmacokinetic (PK) samples will be taken predose, 1 h, 2 h, 3 h, 4 h, 6 h, 8 h, 12 h, 16 h, 24 h (before patch removal in the morning of Day 2), 25 h, 26 h, 28 h, 30 h, 32 h, 36 h, 40 h and 48 h after Rotigotine administration

Collaborators and Investigators

• Sponsor: UCB Pharma
• Collaborators: Otsuka Pharmaceutical Co., Ltd.

Study record dates

Study Major Dates

• Study Start: March 1, 2012
• Primary Completion (ACTUAL): July 1, 2012
• Study Completion (ACTUAL): July 1, 2012

Study Registration Dates

• First Submitted: March 26, 2012
• First Submitted That Met QC Criteria: March 26, 2012
• First Posted (ESTIMATE): March 28, 2012

Study Record Updates

• Last Update Posted (ESTIMATE): July 9, 2012
• Last Update Submitted That Met QC Criteria: July 5, 2012
• Last Verified: July 1, 2012

More Information

Terms related to this study

• Keywords: Bioequivalence; Rotigotine; Neupro®; Transdermal Patch
• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Dopamine Agonists; Dopamine Agents; Rotigotine
• Other Study ID Numbers: PD0002; 2011-004851-38 (EUDRACT_NUMBER)