Fentanyl Patch Pharmacokinetics in Healthy Adults
Condition: Peer Review, Research
Intervention: Intravenous fentanyl citrate; Duragesic®; Mylan generic fentanyl
Intervention description: 100 micrograms (2 millilitres) via intravenous injection; TDDS dosage is 25 micrograms/hour (worn for 72 h); TDDS dosage is 25 micrograms/hour (worn for 72 h)
Intervention MeSH terms: Fentanyl
Phase: Phase 4
Study type: Interventional
Primary purpose: Other
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: None (Open Label)
Enrollment: 24.0
Sex: All
Minimum age: 18 Years
Maximum age: 45 Years
Healthy volunteers: Accepts Healthy Volunteers
Keywords: Bioequivalence; Therapeutic Equivalency

Summary:

      The study to be performed will utilize already FDA-approved marketed products in healthy
      adults for the purpose to generate data for establishing rate of drug delivery comparisons
      between RLD (reference listed drug) Duragesic ® TDDS (transdermal drug delivery system) and
      Generic Fentanyl TDDS in healthy adults and to ensure safety of individuals utilizing these
      types of products.
    

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, study restrictions and examination
             schedule

          7. Subjects who are within their ideal body weight (BMI between >17 and ≤28 kg/m2)

          8. Subjects deemed to be healthy as judged by the Medically Accountable Investigator
             (MAI) and determined by medical history, physical examination and medication history

          9. Subjects have no history of the following: ongoing acute or intermittent pain,
             postoperative pain, respiratory compromise, acute or severe asthma, or constipation
             (less than 1 bowel movement every 2 days)

         10. Negative urine drug screening test at the time of screening

         11. Have normal screening laboratories for white blood cells (WBC), hemoglobin (Hgb),
             platelets, sodium, potassium, chloride, bicarbonate, blood urea nitrogen (BUN),
             creatinine, ALT (liver function), AST (liver function) and bilirubin

         12. Have normal screening laboratories for urine protein and urine glucose

         13. 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 [no bleeding for 12 consecutive months], or if of childbearing potential
             must be non-pregnant at the time of enrollment and on the morning of the first day of
             each study session, 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 parter

         14. Agrees not to participate in another clinical study/trial during the study period or
             to participate in an investigational drug study for at least one month after last
             study session

         15. Agrees not to donate blood to a blood bank throughout participation in the study and
             for at least 3 months after last study day

         16. Have a normal ECG; must not have the following to be acceptable: pathologic Q wave
             abnormalities, significant ST-T wave changes, left ventricular hypertrophy, right
             bundle branch block, left bundle branch block. (sinus rhythm is between 55-100 beats
             per minute)

         17. Have normal vital signs:

               -  Temperature 35-37.9°C (95-100.3°F)

               -  Systolic blood pressure 90-140 mmHg

               -  Diastolic blood pressure 60-90 mmHg

               -  Heart rate 55-100 beats per minute

               -  Respiration rate 12-18 breaths per minute

        Exclusion Criteria:

          1. Women who are pregnant, lactating or breast feeding or have a positive serum pregnancy
             test at enrollment or positive urine pregnancy test on the morning of the first day of
             any study session

          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/study or clinical drug
             trial/study

          4. History of chronic obstructive pulmonary disease or cor pulmonale, or substantially
             decreased respiratory reserve, hypoxia, hypercapnia or pre-existing respiratory
             depression

          5. Active positive Hepatitis B, C and HIV serologies

          6. Positive urine drug screening test

          7. Use of any prescription medication during the session 0 to 30 days or over-the counter
             medication e.g. antihistamines or topical corticosteroids (vitamin, herbal supplements
             and birth control medications not included) during the session 0 to 3 days before
             entry to the study

          8. Use of medications or treatments that would significantly influence or exaggerate
             responses to the test product or that would alter inflammatory or immune response to
             the product or agents deemed to be immunosuppressive as determined by physician
             investigator with 72 hours prior to dosing (e.g. antihistamines, systemic or topical
             corticosteroids (within 3 weeks prior to dosing), cyclosporine, tacrolimus, cytotoxic
             drugs, immune globulin, Bacillus Calmette-Guerin (BCG), monoclonal antibodies,
             radiation therapy)

          9. Use of monoamine oxidase inhibitors 21 days prior to study

         10. Current use of mixed agonist/antagonist (such as pentazocine, nalbuphine or
             butorphanol) and partial agonist (buprenorphine) analgesics

         11. Current use of anticholinergics or other medications with anticholinergic activity

         12. Consumption of beverages containing alcohol, grapefruit juice, Seville oranges, or
             quinine (e.g. tonic water) or foods containing poppy seeds in the last 72 hours.

         13. Donation or loss of greater than one pint of blood within 60 days of entry to the
             study

         14. Any prior serious adverse reaction or hypersensitivity to fentanyl, morphine, codeine,
             hydrocodone, hydromorphone, oxycodone, oxymorphone, naltrexone or naloxone or any of
             the inactive ingredients in the TDDS (polyester/ethyl vinyl acetate, polyacrylate
             adhesive, silicone adhesive, dimethicone NF, or polyolefin)

         15. Have a diagnosis of schizophrenia or other major psychiatric diagnosis or mental
             illness (e.g. major depression)

         16. Medical history of personal drug or alcohol addiction or abuse

         17. Any condition that would, in the opinion of the MAI, place the subject at an
             unacceptable risk of injury or render the subject unable to meet the requirements of
             the protocol

         18. Inability to communicate or cooperate with the investigators

         19. Subject has an obvious difference in skin color between arms or the presence of a skin
             condition, excessive hair at the application site (upper arm), sunburn, raised moles
             and scars, open sore, scar tissue, tattoo, or coloration that would interfere with
             placement of test articles, skin assessment, or reactions to drug

         20. Failure to pass opioid dependence challenge test on the first day study day of any
             study session (i.e., before taking the first dose of naltrexone hydrochloride). Each
             subject will be injected subcutaneously with naloxone hydrochloride (0.8 mg injection)
             and will be observed for 45 minutes for signs and symptoms of opioid withdrawal.

         21. Within 4 weeks prior to dosing, use of medications or treatments that would
             significantly influence or exaggerate responses to the test product or that would
             alter inflammatory or immune response to the product or agents deemed to be
             immunosuppressive as determined by physician investigator