Transdermal Patch CVD 2000: The Effect of Heat on Fentanyl Release From Fentanyl TDSs in Healthy Adults
Condition: Peer Review, Research
Intervention: Duragesic reference fentanyl TDS; Apotex generic fentanyl TDS; Mylan generic fentanyl TDS
Intervention description: 25 µg/hour; 25 µg/hour; 25 µg/hour
Intervention MeSH terms: Fentanyl
Phase: Phase 4
Study type: Interventional
Primary purpose: Health Services Research
Allocation: Non-Randomized
Intervention model: Crossover Assignment
Masking: None (Open Label)
Enrollment: 10.0
Sex: All
Minimum age: 18 Years
Maximum age: 45 Years
Healthy volunteers: Accepts Healthy Volunteers
Keywords: Bioequivalence; Therapeutic Equivalency

Summary:

      This is an Open-label, Non-Randomized, 3-way Crossover Bioequivalence Study to compare
      fentanyl release after heating of a brand name (Duragesic) and generic (Apotex and Mylan)
      fentanyl (transdermal delivery system)TDSs in healthy adults.
    

Eligibility criteria:

        Inclusion Criteria:

          -  1. Men or non-pregnant women of any ethnic background between the age of 18 and 45
             years old.

          -  2. Subjects must be non-smokers (must have refrained from the use of
             nicotine-containing substances, including tobacco products (e.g., cigarettes, cigars,
             chewing tobacco, gum, patch or electronic cigarettes) over the previous 2 months and
             are not currently using tobacco products.

          -  3. Provide written informed consent before initiation of any study procedures.

          -  4. Available for follow-up for the planned duration of the study.

          -  5. Able to communicate well with the investigators.

          -  6. Able to adhere to the study protocol schedule.

          -  7. Subjects who are within their ideal body weight (BMI>17 and ≤ 28).

          -  8. Demonstrate comprehension of the protocol procedures and knowledge of study by
             passing (>70% correct responses) a written examination containing 20 multiple choice
             and true false questions covering all aspects of the study including the purpose,
             procedures, risks and benefits.

          -  9. Subjects deemed to be healthy as judged by the Medically Accountable Investigator
             (MAI) and determined by medical history, physical examination, and medication history.

          -  10. Negative urine drug screening test.

          -  11. Have a normal blood pressure (systolic: 90-140 mmHg; diastolic: 50-90 mmHg) and
             heart rate (55-100 bpm).

          -  12. Have normal screening laboratories for WBC, Hgb, platelets, sodium, potassium,
             chloride, bicarbonate, BUN, creatinine, ALT, AST and total bilirubin.

          -  13. Have normal screening laboratories for urine protein and urine glucose.

          -  14. Female subjects must be of non-childbearing potential (as defined as surgically
             sterile [i.e. history of hysterectomy or tubal ligation] or postmenopausal for more
             than 1 year), or if of childbearing potential must be non-pregnant at the time of
             enrollment and on the morning of each procedure, and must agree to use hormonal or
             barrier birth control such as implants, injectables, combined oral contraceptives,
             some intrauterine devices (IUDs), sexual abstinence, or a vasectomized partner.

          -  15. Agrees not to participate in another clinical study during the study period.

          -  16. Agrees not to donate blood to a blood bank throughout participation in the study
             and for at least 3 months after last procedure day.

          -  17. Have a normal ECG.

        Exclusion Criteria:

          -  1. Women who are pregnant, lactating, breast feeding or have a positive serum
             pregnancy test at enrollment or on the morning of any procedure day.

          -  2. Smokers (current use or use over the previous 2 months of nicotine-containing
             substances, including tobacco products (e.g., cigarettes, cigars, chewing tobacco,
             gum, patch or electronic cigarettes).

          -  3. Participation in any ongoing investigational drug trial or clinical drug trial.

          -  4. Abnormal Vital signs, defined as:

               -  Hypertension (systolic blood pressure >140 mm Hg or diastolic blood pressure >90
                  mm Hg) at rest on 2 separate days)

               -  Heart rate <55 at rest on 2 separate days

               -  Respiratory rate >20

          -  5. Temperature > 38.0°C (100.4°F) or symptoms of an acute self-limited illness such as
             an upper respiratory infection or gastroenteritis within 7 days of application of the
             fentanyl TDS.

          -  6. History of chronic obstructive pulmonary disease.

          -  7. Active positive Hepatitis B, C, and HIV serologies.

          -  8. Positive urine drug screening test.

          -  9. Use of any prescription medication during the period 0 to 30 days or over-the
             counter medication (vitamin, herbal supplements and birth control medications not
             included) during the period 0 to 3 days before entry to the study.

          -  10. Donation or loss of greater than one pint of blood within 60 days of entry to the
             study.

          -  11. Any prior serious adverse reaction or hypersensitivity to fentanyl, naltrexone or
             naloxone or any of the inactive ingredients in the TDS (alcohol, ethylene vinyl
             acetate-copolymer membrane and hydroxyethyl cellulose, polyester, silicone adhesive,
             isopropyl myristate, octyldodecanol, polybutene, polyisobutene, dimethicone NF, or
             polyolefin).

          -  12. Have a diagnosis of schizophrenia or other major psychiatric diagnosis or mental
             illness (e.g. major depression).

          -  13. Received an experimental agent (vaccine, drug, biologic, device, blood product or
             medication) within 1 month before enrollment in this study or expects to receive an
             experimental agent during the study.

          -  14. Any condition that would, in the opinion of the Medically Accountable Investigator
             (MAI), place the subject at an unacceptable risk of injury or render the subject
             unable to meet the requirements of the protocol.

          -  15. Inability to communicate or co-operate with the investigators.

          -  16. History of consumption of alcohol within 24 hours prior to dose administration.

          -  17. Within 72 hours prior to dosing, use of antihistamines or use of topical drugs at
             TDS site.

          -  18. Subject has an obvious difference in skin color between arms or the presence of a
             skin condition, open sore, scar tissue, tattoo, or coloration that would interfere
             with placement of test articles, skin assessment, or reactions to drug.

          -  19. Use of monoamine oxidase inhibitors 21 days prior to study.

          -  20. Failure to pass opioid dependence challenge test on each procedure day before
             application of the fentanyl TDS. Each subject will be injected subcutaneously with
             naloxone HCl (0.8 mg injection) and will be observed for 45 minutes for signs and
             symptoms of opioid withdrawal.