Bioequivalence of Two Transdermal Clonidine Administrations in Healthy Volunteers

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

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.

Study Overview

• Status: Completed
• Conditions: Healthy
• Intervention / Treatment: Drug: Intervention 1: Catapres-TTS-3; Drug: Intervention 2: Catapres-TTS-3; Drug: Catapres-TTS-1; Drug: Catapres-TTS-1

• Study Type: Interventional
• Enrollment (Actual): 56
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Texas
    • Austin, Texas, United States
      • 253.2486.1 Boehringer Ingelheim Investigational Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion criteria:

1. A complete medical history, including the physical examination, vital signs (BP, PR), 12-lead ECG, clinical laboratory tests
2. Age greater than or equal to 18 and Age less than or equal to 65 years
3. BMI greater than or equal to 18.5 and BMI less than or equal to 32.0 kg/m2 (Body Mass Index)
4. Signed and dated written informed consent prior to admission to the study

5. 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:

1. Any finding of the medical examination (including BP, PR and ECG) deviating from normal
2. 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
3. Any subject with orthostatic hypotension at baseline screening exam
4. Any laboratory value outside the reference range
5. Any evidence of a clinically relevant concomitant disease
6. Gastrointestinal, hepatic, renal, respiratory, cardiovascular, metabolic (including insulin-dependent diabetes), immunological or hormonal disorders
7. Diseases of the central nervous system (such as epilepsy) or psychiatric disorders (such as depression) or neurological disorders (such as neuropathy)
8. History of relevant orthostatic hypotension, fainting spells or blackouts
9. Chronic or relevant acute infections
10. History of relevant allergy/hypersensitivity
11. 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.
12. Use of drugs which might reasonably influence the results of the trial within 10 days prior to administration or during the trial
13. Participation in another trial with an investigational drug within two months prior to administration or during the trial
14. Any concomitant therapy
15. Smoker
16. History of alcohol abuse
17. History of drug abuse
18. Blood donation
19. Excessive physical activities (within one week prior to administration or during the trial)
20. Subjects should not swim during the treatment periods of the trial
21. 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
22. Pregnancy or planning to become pregnant within two months of study completion
23. Positive pregnancy test
24. A screening ECG that displays first-degree atrioventricular block (P-R interval > 0.20 seconds) or other conduction disturbance

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Double

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Catapres-TTS-3 crossover 1; 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; Catapres-TTS-3 Oppanol; Drug: Intervention 2: Catapres-TTS-3; Catapres-TTS-3 Vistanex
Experimental: Catapres-TTS-3 crossover 2; 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; Catapres-TTS-3 Oppanol; Drug: Intervention 2: Catapres-TTS-3; Catapres-TTS-3 Vistanex
Experimental: Catapres-TTS-1 crossover 1; subject to receive 0.1 mg/24 hr Catapres-TTS-1 with Oppanol (T2) and Vistanex (R2) simultaneously	Drug: Catapres-TTS-1; Catapres-TTS-1 Oppanol; Drug: Catapres-TTS-1; Catapres-TTS-1 Vistanex

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

Collaborators and Investigators

• Sponsor: Boehringer Ingelheim

Publications and helpful links

Helpful Links

• Related Info

Study record dates

Study Major Dates

• Study Start: March 1, 2014
• Primary Completion (Actual): June 1, 2014
• Study Completion (Actual): June 1, 2014

Study Registration Dates

• First Submitted: March 24, 2014
• First Submitted That Met QC Criteria: March 24, 2014
• First Posted (Estimate): March 26, 2014

Study Record Updates

• Last Update Posted (Estimate): July 16, 2015
• Last Update Submitted That Met QC Criteria: June 19, 2015
• Last Verified: June 1, 2015

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Antihypertensive Agents; Autonomic Agents; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Adrenergic alpha-2 Receptor Agonists; Adrenergic alpha-Agonists; Adrenergic Agonists; Sympatholytics; Clonidine
• Other Study ID Numbers: 253.2486