Bioequivalence of Two Transdermal Clonidine Administrations in Healthy Volunteers

Study Overview
=================
Brief Summary
-----------------
To establish the bioequivalence and adhesion properties of transdermal clonidine prepared with Oppanol® brands of polyisobutylene (PIB) vs. transdermal clonidine prepared with VistanexTM brands of polyisobutylene (PIB) in healthy male and female volunteers.

Official Title
-----------------
A Randomized, Double-blind Study Designed to Assess the Bioequivalence and Adhesion Properties of Transdermal Clonidine-VistanexTM Compared to Transdermal Clonidine-Oppanol® Following Transdermal Administration in Healthy Male and Female Volunteers

Conditions
-----------------
Healthy

Intervention / Treatment
-----------------
* Drug: Catapres-TTS-1
* Drug: Intervention 1: Catapres-TTS-3
* Drug: Intervention 1: Catapres-TTS-3
* Drug: Intervention 2: Catapres-TTS-3
* Drug: Catapres-TTS-1
* Drug: Intervention 2: Catapres-TTS-3


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion criteria: A complete medical history, including the physical examination, vital signs (BP, PR), 12-lead ECG, clinical laboratory tests Age greater than or equal to 18 and Age less than or equal to 65 years BMI greater than or equal to 18.5 and BMI less than or equal to 32.0 kg/m2 (Body Mass Index) Signed and dated written informed consent prior to admission to the study Male subjects, or females who meet any of the following criteria from at least 30 days before the first study drug administration and until 30 days after trial completion: Using adequate contraception, e.g. any of the following methods plus condom: implants, injectables, combined oral contraceptives, intrauterine device (IUD) Sexually abstinent Have a vasectomised sexual partner (vasectomy at least one year prior to enrolment) Surgically sterilised (including hysterectomy) Postmenopausal defined as at least one year of spontaneous amenorrhea Exclusion criteria: Any finding of the medical examination (including BP, PR and ECG) deviating from normal Repeated measurement of supine systolic blood pressure outside the range of 100-140 mm Hg or diastolic blood pressure outside the range of 60-90 mm Hg or pulse less than 55 bpm Any subject with orthostatic hypotension at baseline screening exam Any laboratory value outside the reference range Any evidence of a clinically relevant concomitant disease Gastrointestinal, hepatic, renal, respiratory, cardiovascular, metabolic (including insulin-dependent diabetes), immunological or hormonal disorders Diseases of the central nervous system (such as epilepsy) or psychiatric disorders (such as depression) or neurological disorders (such as neuropathy) History of relevant orthostatic hypotension, fainting spells or blackouts Chronic or relevant acute infections History of relevant allergy/hypersensitivity Intake of drugs with a long half-life (greater than 24 hours) within at least one month or less than 10 half-lives of the respective drug prior to administration or during the trial. Use of drugs which might reasonably influence the results of the trial within 10 days prior to administration or during the trial Participation in another trial with an investigational drug within two months prior to administration or during the trial Any concomitant therapy Smoker History of alcohol abuse History of drug abuse Blood donation Excessive physical activities (within one week prior to administration or during the trial) Subjects should not swim during the treatment periods of the trial Any condition of the skin, including eczema, psoriasis, or lymphedema, that involves the upper arm in the area that would be utilized for application of the treatments Pregnancy or planning to become pregnant within two months of study completion Positive pregnancy test A screening ECG that displays first-degree atrioventricular block (P-R interval > 0.20 seconds) or other conduction disturbance

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Catapres-TTS-3 crossover 1<br>subject to receive 0.3 mg/24 hr Catapres-TTS-3 Oppanol (T1) first, followed by Catapres-TTS-3 Vistanex (R1) | Drug: Intervention 1: Catapres-TTS-3<br>* Catapres-TTS-3 Oppanol<br>Drug: Intervention 2: Catapres-TTS-3<br>* Catapres-TTS-3 Vistanex<br>|
| Experimental: Catapres-TTS-3 crossover 2<br>subject to receive 0.3 mg/24 hr Catapres-TTS-3 Vistanex (R1) first, followed by Catapres-TTS-3 Oppanol (T1) | Drug: Intervention 1: Catapres-TTS-3<br>* Catapres-TTS-3 Oppanol<br>Drug: Intervention 2: Catapres-TTS-3<br>* Catapres-TTS-3 Vistanex<br>|
| Experimental: Catapres-TTS-1 crossover 1<br>subject to receive 0.1 mg/24 hr Catapres-TTS-1 with Oppanol (T2) and Vistanex (R2) simultaneously | Drug: Catapres-TTS-1<br>* Catapres-TTS-1 Oppanol<br>Drug: Catapres-TTS-1<br>* Catapres-TTS-1 Vistanex<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| AUC0-168 (Area Under the Concentration-time Curve of Clonidine in Plasma Over the Time Interval From 0 to 168 h) | AUC0-168 (area under the concentration-time curve of clonidine in plasma over the time interval from 0 to 168 h) The values for geometric mean and geometric coefficient of variation (gCV) are actually adjusted geometric means and adjusted intra-individual gCVs, respectively. | 1 hour (h) before patch administration and 12h, 24h, 48h, 72h, 96h, 120h, 144h, 168h after patch administration | 
| Cavg (Average of Measured Concentrations of Clonidine in Plasma on Days 5, 6, and 7) | Cavg (average of measured concentrations of clonidine in plasma on Days 5, 6, and 7) The values for geometric mean and gCV are actually adjusted geometric means and adjusted intra-individual gCVs, respectively. | 1 hour (h) before patch administration and 12h, 24h, 48h, 72h, 96h, 120h, 144h, 168h, 192h, 216h, 240h after patch administration | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| AUC0-inf(Area Under the Concentration-time Curve of Clonidine in Plasma Over the Time Interval From 0 to Infinity) | AUC 0-inf(area under the concentration-time curve of clonidine in plasma over the time interval from 0 to infinity) The values for geometric mean and gCV are actually adjusted geometric means and adjusted intra-individual gCVs, respectively. | 1 hour (h) before patch administration and 12h, 24h, 48h, 72h, 96h, 120h, 144h, 168h, 192h, 216h, 240h after patch administration | 
| Cmax (Maximum Concentration of Clonidine in Plasma) | Cmax (maximum concentration of clonidine in plasma) The values for geometric mean and gCV are actually adjusted geometric means and adjusted intra-individual gCVs, respectively. | 1 hour (h) before patch administration and 12h, 24h, 48h, 72h, 96h, 120h, 144h, 168h, 192h, 216h, 240h after patch administration |