Single-site, Open-label, Randomized, Cross-over Study in Healthy Chinese Subjects to Evaluate the Bioequivalence of Single-dose Rotigotine Transdermal Patch Comparing 2 Different Formulations

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

The primary objective of the study is to establish Bioequivalence (BE) of 2 different formulations of the 2 mg/24 hr (10 cm^2) Rotigotine transdermal patches in Chinese subjects.

Study Overview

• Status: Completed
• Conditions: Healthy
• Intervention / Treatment: Drug: Rotigotine PR2.2.1; Drug: Rotigotine PR2.1.1

Detailed Description

Bioequivalence will be concluded if the 90 % Confidence Intervals (CIs) for the ratio Treatment A/Treatment B are fully included in the acceptance range from 0.8-1.25 for AUC(0-t) and AUC, and within the acceptance range from 0.7 to 1.43 for Cmax.

• Study Type: Interventional
• Enrollment (Actual): 50
• Phase: Phase 1

Contacts and Locations

Study Locations

• China
  • Hong Kong, China
    • 1

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 40 years (Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: Male

Description

Inclusion Criteria:

• An Independent Ethics Committee (IEC) approved written Informed Consent form is signed and dated by the subject
• Subject is considered reliable and capable of adhering to the protocol, visit schedule, and patch application according to the judgment of the investigator
• Subject is willing and able to comply with all study requirements
• Subject is Chinese (with all 4 grandparents being of Chinese origin, as well), male, and aged between 18 and 40 years (inclusive)
• Subject is healthy (no clinically significant findings in any of the investigations at the Eligibility Assessment (EA))
• Subject has a body mass index between 19 kg/m² and 24 kg/m² (inclusive), and a body weight greater than or equal to 50 kg
• Subject agreed to practice a medically accepted method of contraception (eg, condom, spermicide) unless sexually abstinent for the duration of the study and up to 3 months after the final patch application

Exclusion Criteria:

• Subject has previously participated in this study or subject has previously been assigned to treatment in a Rotigotine study
• Subject has participated in another study of an Investigational Medicinal Product (IMP) (or a medical device) within the previous 3 months or is currently participating in another study of an IMP (or a medical device)
• Subject has a history of diagnosis, counseling, or treatment for chronic alcohol or drug abuse within the previous 2 years
• Subject has a known clinically significant allergy or known or suspected clinically significant drug hypersensitivity to any components of the IMP or comparable drugs that, in the opinion of the investigator, could jeopardize or would compromise the subject's ability to participate in this study
• Subject has lifetime history of suicide attempt
• Subject has a history of significant skin hypersensitivity to adhesives or other transdermal products or has recently unresolved contact dermatitis
• Subject has an medical or psychiatric condition that, in the opinion of the investigator, could jeopardize or would compromise the subject's ability to participate in this study
• Subject has a history or present condition of epilepsy and/or seizures
• Subject has a history or present condition of an atopic or eczematous dermatitis, psoriasis, and/or an active skin disease

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Treatment A - B; Single application of the test transdermal patch (Treatment A, Rotigotine PR2.2.1) for 24 hours, followed by a Wash-Out Period of 7 days and a single application of the reference transdermal patch (Treatment B, Rotigotine PR2.1.1) for 24 hours.	Drug: Rotigotine PR2.2.1; Treatment A: Rotigotine Transdermal patch 2 mg/24 hr (10 cm^2) Test drug product PR2.2.1. Single application of 1 patch for 24 hours.; Drug: Rotigotine PR2.1.1; Treatment B: Rotigotine Transdermal patch 2 mg/24 hr (10 cm^2) Reference drug product PR2.1.1. Single application of 1 patch for 24 hours.
Active Comparator: Treatment B - A; Single application of the reference transdermal patch (Treatment B, Rotigotine PR2.1.1) for 24 hours, followed by a Wash-Out Period of 7 days and a single application of the test transdermal patch (Treatment A, Rotigotine PR2.2.1) for 24 hours.	Drug: Rotigotine PR2.2.1; Treatment A: Rotigotine Transdermal patch 2 mg/24 hr (10 cm^2) Test drug product PR2.2.1. Single application of 1 patch for 24 hours.; Drug: Rotigotine PR2.1.1; Treatment B: Rotigotine Transdermal patch 2 mg/24 hr (10 cm^2) Reference drug product PR2.1.1. Single application of 1 patch for 24 hours.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Area under the plasma concentration-time curve from zero up to the last analytically quantifiable concentration (AUC(0-t))	Blood samples will be taken predose, and at 1 hr, 2 hr, 3 hr, 4 hr, 6 hr, 8 hr, 12 hr, 16 hr, 24 hr (immediately prior to patch removal in the morning of Day 2), 25 hr, 26 hr, 28 hr, 30 hr, 32 hr, 36 hr, 40 hr, and 48 hr after patch application.
Area under the plasma concentration-time curve from zero up to Infinity (AUC)	Blood samples will be taken predose, and at 1 hr, 2 hr, 3 hr, 4 hr, 6 hr, 8 hr, 12 hr, 16 hr, 24 hr (immediately prior to patch removal in the morning of Day 2), 25 hr, 26 hr, 28 hr, 30 hr, 32 hr, 36 hr, 40 hr, and 48 hr after patch application
The maximum plasma concentration of unconjugated Rotigotine (Cmax)	Blood samples will be taken predose, and at 1 hr, 2 hr, 3 hr, 4 hr, 6 hr, 8 hr, 12 hr, 16 hr, 24 hr (immediately prior to patch removal in the morning of Day 2), 25 hr, 26 hr, 28 hr, 30 hr, 32 hr, 36 hr, 40 hr, and 48 hr after patch application

Secondary Outcome Measures

Outcome Measure	Time Frame
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))	Blood samples will be taken predose, and at 1 hr, 2 hr, 3 hr, 4 hr, 6 hr, 8 hr, 12 hr, 16 hr, 24 hr (immediately prior to patch removal in the morning of Day 2), 25 hr, 26 hr, 28 hr, 30 hr, 32 hr, 36 hr, 40 hr, and 48 hr after patch application
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))	Blood samples will be taken predose, and at 1 hr, 2 hr, 3 hr, 4 hr, 6 hr, 8 hr, 12 hr, 16 hr, 24 hr (immediately prior to patch removal in the morning of Day 2), 25 hr, 26 hr, 28 hr, 30 hr, 32 hr, 36 hr, 40 hr, and 48 hr after patch application
Area under the plasma concentration-time curve from zero up to infinity normalized by apparent dose (mg) (AUCnorm (apparent dose))	Blood samples will be taken predose, and at 1 hr, 2 hr, 3 hr, 4 hr, 6 hr, 8 hr, 12 hr, 16 hr, 24 hr (immediately prior to patch removal in the morning of Day 2), 25 hr, 26 hr, 28 hr, 30 hr, 32 hr, 36 hr, 40 hr, and 48 hr after patch application
Area under the plasma concentration-time curve from zero up to infinity normalized by body weight (kg) (AUCnorm (BW))	Blood samples will be taken predose, and at 1 hr, 2 hr, 3 hr, 4 hr, 6 hr, 8 hr, 12 hr, 16 hr, 24 hr (immediately prior to patch removal in the morning of Day 2), 25 hr, 26 hr, 28 hr, 30 hr, 32 hr, 36 hr, 40 hr, and 48 hr after patch application
Maximum plasma concentration of unconjugated Rotigotine normalized by apparent dose (Cmax, norm (apparent dose))	Blood samples will be taken predose, and at 1 hr, 2 hr, 3 hr, 4 hr, 6 hr, 8 hr, 12 hr, 16 hr, 24 hr (immediately prior to patch removal in the morning of Day 2), 25 hr, 26 hr, 28 hr, 30 hr, 32 hr, 36 hr, 40 hr, and 48 hr after patch application
Maximum plasma concentration of unconjugated Rotigotine normalized by body weight (Cmax, norm (BW))	Blood samples will be taken predose, and at 1 hr, 2 hr, 3 hr, 4 hr, 6 hr, 8 hr, 12 hr, 16 hr, 24 hr (immediately prior to patch removal in the morning of Day 2), 25 hr, 26 hr, 28 hr, 30 hr, 32 hr, 36 hr, 40 hr, and 48 hr after patch application
Time to reach a maximum plasma concentration of unconjugated Rotigotine after patch application (tmax)	Blood samples will be taken predose, and at 1 hr, 2 hr, 3 hr, 4 hr, 6 hr, 8 hr, 12 hr, 16 hr, 24 hr (immediately prior to patch removal in the morning of Day 2), 25 hr, 26 hr, 28 hr, 30 hr, 32 hr, 36 hr, 40 hr, and 48 hr after patch application
Mean residence time (MRT)	Blood samples will be taken predose, and at 1 hr, 2 hr, 3 hr, 4 hr, 6 hr, 8 hr, 12 hr, 16 hr, 24 hr (immediately prior to patch removal in the morning of Day 2), 25 hr, 26 hr, 28 hr, 30 hr, 32 hr, 36 hr, 40 hr, and 48 hr after patch application
Rate constant of elimination (λz)	Blood samples will be taken predose, and at 1 hr, 2 hr, 3 hr, 4 hr, 6 hr, 8 hr, 12 hr, 16 hr, 24 hr (immediately prior to patch removal in the morning of Day 2), 25 hr, 26 hr, 28 hr, 30 hr, 32 hr, 36 hr, 40 hr, and 48 hr after patch application
Terminal half-life (t1/2)	Blood samples will be taken predose, and at 1 hr, 2 hr, 3 hr, 4 hr, 6 hr, 8 hr, 12 hr, 16 hr, 24 hr (immediately prior to patch removal in the morning of Day 2), 25 hr, 26 hr, 28 hr, 30 hr, 32 hr, 36 hr, 40 hr, and 48 hr after patch application
Relative bioavailability calculated based on Cmax (fCmax)	Blood samples will be taken predose, and at 1 hr, 2 hr, 3 hr, 4 hr, 6 hr, 8 hr, 12 hr, 16 hr, 24 hr (immediately prior to patch removal in the morning of Day 2), 25 hr, 26 hr, 28 hr, 30 hr, 32 hr, 36 hr, 40 hr, and 48 hr after patch application
Relative bioavailability calculated based on AUC (fAUC)	Blood samples will be taken predose, and at 1 hr, 2 hr, 3 hr, 4 hr, 6 hr, 8 hr, 12 hr, 16 hr, 24 hr (immediately prior to patch removal in the morning of Day 2), 25 hr, 26 hr, 28 hr, 30 hr, 32 hr, 36 hr, 40 hr, and 48 hr after patch application
Apparent total body clearance (CL/f)	Blood samples will be taken predose, and at 1 hr, 2 hr, 3 hr, 4 hr, 6 hr, 8 hr, 12 hr, 16 hr, 24 hr (immediately prior to patch removal in the morning of Day 2), 25 hr, 26 hr, 28 hr, 30 hr, 32 hr, 36 hr, 40 hr, and 48 hr after patch application

Collaborators and Investigators

• Sponsor: UCB Pharma SA

Publications and helpful links

General Publications

• Liu Y, Tomlinson B, Guo J, Asgharnejad M, Bauer L, Surmann E, Guo X, Elshoff JP. Pharmacokinetics, Tolerability, and Bioequivalence of Two Formulations of Rotigotine in Healthy Chinese Subjects. Clin Ther. 2018 Jul;40(7):1108-1121.e8. doi: 10.1016/j.clinthera.2018.05.009.

Study record dates

Study Major Dates

• Study Start: February 1, 2014
• Primary Completion (Actual): July 1, 2014
• Study Completion (Actual): July 1, 2014

Study Registration Dates

• First Submitted: February 20, 2014
• First Submitted That Met QC Criteria: February 20, 2014
• First Posted (Estimate): February 25, 2014

Study Record Updates

• Last Update Posted (Estimate): July 29, 2014
• Last Update Submitted That Met QC Criteria: July 28, 2014
• Last Verified: July 1, 2014

More Information

Terms related to this study

• Keywords: Bioequivalence; Rotigotine; 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: PD0011