A Study to Assess the Relative Bioavailability of 4 Formulations of Fentanyl Transdermal System Compared Against DUROGESIC Fentanyl Transdermal Patch After Single Application in Healthy Volunteers

Study Overview
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Brief Summary
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The purpose of this study is to evaluate the pharmacokinetics and relative bioavailability of 4 new formulations of fentanyl transdermal patch in healthy participants after a single application for 72 hours.

Detailed Description
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This is an open-label (all people know the identity of the intervention), randomized (the study drug is assigned by chance), 4-way crossover (participants will receive different interventions sequentially during the trial) study. The study will assess the pharmacokinetics (how the drug is absorbed in the body, distributed within the body, and how it is removed from the body over time) and relative bioavailability (the extent to which a drug or other substance becomes available to the body) of 4 new formulations of fentanyl transdermal patch, TDS-Concept 1 50 µg/h, TDS-Concept 2 50 µg/h, TDS-Concept 3 50 µg/h and TDS-Concept 4 100 µg/h compared with DUROGESIC fentanyl 50 µg/h in healthy participants after a single application. All participants will be randomly assigned to 1 of 8 possible treatment sequences. During the 4 single-application treatment periods, each transdermal patch will be worn, on a different application site on the lateral side of the upper arm, continuously for 72 hours. The treatment periods will be separated by a washout period (period when receiving no treatment) of at least 8 and no more than 14 days. The total study length is from 64 days to a maximum of 82 days.

Official Title
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An Open-Label, Randomized, 4-Way Crossover Study to Assess the Relative Bioavailability of 4 New Formulations of Fentanyl Transdermal System Compared Against DUROGESIC Fentanyl Transdermal Patch After Single Application in Healthy Subjects

Conditions
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Healthy

Intervention / Treatment
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* Drug: Treatment A: DUROGESIC (8.4 mg fentanyl)
* Drug: Treatment B: Transdermal System-Concept 1 (6.2 mg fentanyl)
* Drug: Treatment C: Transdermal System-Concept 2 (6.2 mg fentanyl)
* Drug: Treatment D: Transdermal System-Concept 3 (7.1 mg fentanyl)
* Drug: Treatment E: Transdermal System-Concept 4 (11.0 mg fentanyl)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Body mass index (BMI; weight [kg]/height2 [m]2) between 18 and 30 kg/m2 (inclusive), and body weight not less than 50 kg Participants must utilize a medically acceptable method of contraception throughout the entire study period including the washout period and for 3 months (men) or 1 week (women) after the study is completed Men must not donate sperm from the first drug administration until 3 months after completion of the study Each participant will receive a test for opioid dependency. Only those participants that pass this challenge test will be allowed to continue in this study Non-smoker Exclusion Criteria: History of or current clinically significant medical illness, disease or condition that the investigator considers should exclude the subject or that could interfere with the interpretation of the study results Clinically significant abnormal laboratorial values Clinically significant abnormal physical examination, vital signs or electrocardiogram (ECG) Use of any prescription or nonprescription medication (including vitamins and herbal supplements), except for paracetamol, oral contraceptives and hormonal replacement therapy within 14 days before the first dose of the study drug is scheduled History of, or a reason to believe a participant has a history of drug or alcohol abuse within the past 5 years

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 55 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Treatment sequence 1 (AEBD)<br> | Drug: Treatment A: DUROGESIC (8.4 mg fentanyl)<br>* One DUROGESIC transdermal patch containing 8.4 mg of fentanyl applied on the skin for 72 hours.<br>Drug: Treatment B: Transdermal System-Concept 1 (6.2 mg fentanyl)<br>* One transdermal system-concept 1 patch containing approximately 6.2 mg of fentanyl applied on the skin for 72 hours.<br>Drug: Treatment D: Transdermal System-Concept 3 (7.1 mg fentanyl)<br>* One transdermal system-concept 3 patch containing approximately 7.1 mg of fentanyl applied on the skin for 72 hours.<br>Drug: Treatment E: Transdermal System-Concept 4 (11.0 mg fentanyl)<br>* One transdermal system-concept 4 patch containing approximately 11.0 mg of fentanyl applied on the skin for 72 hours.<br>|
| Experimental: Treatment sequence 2 (BACE)<br> | Drug: Treatment A: DUROGESIC (8.4 mg fentanyl)<br>* One DUROGESIC transdermal patch containing 8.4 mg of fentanyl applied on the skin for 72 hours.<br>Drug: Treatment B: Transdermal System-Concept 1 (6.2 mg fentanyl)<br>* One transdermal system-concept 1 patch containing approximately 6.2 mg of fentanyl applied on the skin for 72 hours.<br>Drug: Treatment C: Transdermal System-Concept 2 (6.2 mg fentanyl)<br>* One transdermal system-concept 2 patch containing approximately 6.2 mg of fentanyl applied on the skin for 72 hours.<br>Drug: Treatment E: Transdermal System-Concept 4 (11.0 mg fentanyl)<br>* One transdermal system-concept 4 patch containing approximately 11.0 mg of fentanyl applied on the skin for 72 hours.<br>|
| Experimental: Treatment sequence 3 (CBDA)<br> | Drug: Treatment A: DUROGESIC (8.4 mg fentanyl)<br>* One DUROGESIC transdermal patch containing 8.4 mg of fentanyl applied on the skin for 72 hours.<br>Drug: Treatment B: Transdermal System-Concept 1 (6.2 mg fentanyl)<br>* One transdermal system-concept 1 patch containing approximately 6.2 mg of fentanyl applied on the skin for 72 hours.<br>Drug: Treatment C: Transdermal System-Concept 2 (6.2 mg fentanyl)<br>* One transdermal system-concept 2 patch containing approximately 6.2 mg of fentanyl applied on the skin for 72 hours.<br>Drug: Treatment D: Transdermal System-Concept 3 (7.1 mg fentanyl)<br>* One transdermal system-concept 3 patch containing approximately 7.1 mg of fentanyl applied on the skin for 72 hours.<br>|
| Experimental: Treatment sequence 4 (EDAC)<br> | Drug: Treatment A: DUROGESIC (8.4 mg fentanyl)<br>* One DUROGESIC transdermal patch containing 8.4 mg of fentanyl applied on the skin for 72 hours.<br>Drug: Treatment C: Transdermal System-Concept 2 (6.2 mg fentanyl)<br>* One transdermal system-concept 2 patch containing approximately 6.2 mg of fentanyl applied on the skin for 72 hours.<br>Drug: Treatment D: Transdermal System-Concept 3 (7.1 mg fentanyl)<br>* One transdermal system-concept 3 patch containing approximately 7.1 mg of fentanyl applied on the skin for 72 hours.<br>Drug: Treatment E: Transdermal System-Concept 4 (11.0 mg fentanyl)<br>* One transdermal system-concept 4 patch containing approximately 11.0 mg of fentanyl applied on the skin for 72 hours.<br>|
| Experimental: Treatment sequence 5 (DECA)<br> | Drug: Treatment A: DUROGESIC (8.4 mg fentanyl)<br>* One DUROGESIC transdermal patch containing 8.4 mg of fentanyl applied on the skin for 72 hours.<br>Drug: Treatment C: Transdermal System-Concept 2 (6.2 mg fentanyl)<br>* One transdermal system-concept 2 patch containing approximately 6.2 mg of fentanyl applied on the skin for 72 hours.<br>Drug: Treatment D: Transdermal System-Concept 3 (7.1 mg fentanyl)<br>* One transdermal system-concept 3 patch containing approximately 7.1 mg of fentanyl applied on the skin for 72 hours.<br>Drug: Treatment E: Transdermal System-Concept 4 (11.0 mg fentanyl)<br>* One transdermal system-concept 4 patch containing approximately 11.0 mg of fentanyl applied on the skin for 72 hours.<br>|
| Experimental: Treatment sequence 6 (EADB)<br> | Drug: Treatment A: DUROGESIC (8.4 mg fentanyl)<br>* One DUROGESIC transdermal patch containing 8.4 mg of fentanyl applied on the skin for 72 hours.<br>Drug: Treatment B: Transdermal System-Concept 1 (6.2 mg fentanyl)<br>* One transdermal system-concept 1 patch containing approximately 6.2 mg of fentanyl applied on the skin for 72 hours.<br>Drug: Treatment D: Transdermal System-Concept 3 (7.1 mg fentanyl)<br>* One transdermal system-concept 3 patch containing approximately 7.1 mg of fentanyl applied on the skin for 72 hours.<br>Drug: Treatment E: Transdermal System-Concept 4 (11.0 mg fentanyl)<br>* One transdermal system-concept 4 patch containing approximately 11.0 mg of fentanyl applied on the skin for 72 hours.<br>|
| Experimental: Treatment sequence 7 (ABEC)<br> | Drug: Treatment A: DUROGESIC (8.4 mg fentanyl)<br>* One DUROGESIC transdermal patch containing 8.4 mg of fentanyl applied on the skin for 72 hours.<br>Drug: Treatment B: Transdermal System-Concept 1 (6.2 mg fentanyl)<br>* One transdermal system-concept 1 patch containing approximately 6.2 mg of fentanyl applied on the skin for 72 hours.<br>Drug: Treatment C: Transdermal System-Concept 2 (6.2 mg fentanyl)<br>* One transdermal system-concept 2 patch containing approximately 6.2 mg of fentanyl applied on the skin for 72 hours.<br>Drug: Treatment E: Transdermal System-Concept 4 (11.0 mg fentanyl)<br>* One transdermal system-concept 4 patch containing approximately 11.0 mg of fentanyl applied on the skin for 72 hours.<br>|
| Experimental: Treatment sequence 8 (BCAD)<br> | Drug: Treatment A: DUROGESIC (8.4 mg fentanyl)<br>* One DUROGESIC transdermal patch containing 8.4 mg of fentanyl applied on the skin for 72 hours.<br>Drug: Treatment B: Transdermal System-Concept 1 (6.2 mg fentanyl)<br>* One transdermal system-concept 1 patch containing approximately 6.2 mg of fentanyl applied on the skin for 72 hours.<br>Drug: Treatment C: Transdermal System-Concept 2 (6.2 mg fentanyl)<br>* One transdermal system-concept 2 patch containing approximately 6.2 mg of fentanyl applied on the skin for 72 hours.<br>Drug: Treatment D: Transdermal System-Concept 3 (7.1 mg fentanyl)<br>* One transdermal system-concept 3 patch containing approximately 7.1 mg of fentanyl applied on the skin for 72 hours.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Fentanyl serum concentrations |  | Up to 120 hours after applying the transdermal patch | 
| Determination of residual fentanyl content in the worn patchs | The fentanyl content in the patchs following their removal at the end of 72 hours | At the end of 72 hours after applying the transdermal patch | 
| The skin adherence score of the patches | The patch adherence will be scored from 0 to 4, where 0: >= 90% of the area adhered and no edges unattached; 1: >= 75% to < 90% adhered; 2: >= 50% and < 75% adhered; 3: > 0% and < 50% adhered, but not detached; 4: 0% adhered - patch detached. | Up to 72 hours after applying the transdermal patch | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The incidence of adverse events |  | Approximately 82 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Healthy, Fentanyl, Transdermal patch, DUROGESIC