Fentanyl Patch Pharmacokinetics in Healthy Adults

NCT02531971 | Completed Phase 4 Results FDA Drug

• 1 other identifier: HP-00063835
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Peer Review, Research

Keywords

Bioequivalence; Therapeutic Equivalency

Outcome Measures

Primary Outcomes (1)

• Area Under the Curve (AUC 0-∞ ) ng∙h/mL

  drug concentration in serum vs. time; reflects the actual body exposure to drug after administration of a dose of the drug

  10 procedure days for Duragesic and Mylan arms each

Study Arms (2)

Fentanyl citrate (36 h), Duragesic (192 h), Mylan (192 h)

ACTIVE COMPARATOR

Volunteers received a single-dose of 100 µg fentanyl citrate infusion (Study Session I) and blood samples obtained 0-36 h, washout at least one week, then wore a Duragesic® fentanyl TDDS (25 µg/h) for 72 h (Study Session II) and blood samples obtained 0-192 h, washout at least one week, then wore a Mylan fentanyl TDDS (25 µg/h) for 72 h (Study Session III) and blood samples obtained 0-192 h

Drug: Intravenous fentanyl citrate; Drug: Duragesic®; Drug: Mylan generic fentanyl

Fentanyl citrate (36 h), Mylan (192 h), Duragesic (192 h)

ACTIVE COMPARATOR

Volunteers received a single-dose of 100 µg fentanyl citrate infusion (Study Session I) and blood samples obtained 0-36 h, washout at least one week, then wore a Mylan fentanyl TDDS (25 µg/h) for 72 h (Study Session II) and blood samples obtained 0-192 h, washout at least one week, then wore a Duragesic® fentanyl TDDS (25 µg/h) for 72 h (Study Session III) and blood samples obtained for 0-192 h

Drug: Intravenous fentanyl citrate; Drug: Duragesic®; Drug: Mylan generic fentanyl

Interventions

Intravenous fentanyl citrate DRUG

100 micrograms (2 millilitres) via intravenous injection

Fentanyl citrate (36 h), Duragesic (192 h), Mylan (192 h); Fentanyl citrate (36 h), Mylan (192 h), Duragesic (192 h)

Duragesic® DRUG

TDDS dosage is 25 micrograms/hour (worn for 72 h)

Also known as: Duragesic® fentanyl skin patch

Fentanyl citrate (36 h), Duragesic (192 h), Mylan (192 h); Fentanyl citrate (36 h), Mylan (192 h), Duragesic (192 h)

Mylan generic fentanyl DRUG

TDDS dosage is 25 micrograms/hour (worn for 72 h)

Also known as: Mylan generic fentanyl skin patch

Fentanyl citrate (36 h), Duragesic (192 h), Mylan (192 h); Fentanyl citrate (36 h), Mylan (192 h), Duragesic (192 h)

Eligibility Criteria

• Age: 18 Years - 45 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Men or non-pregnant women of any ethnic background between the age of 18 and 45 years old
• 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
• Provide written informed consent before initiation of any study procedures
• Available for follow-up for the planned duration of the study
• Able to communicate well with the investigators
• Able to adhere to the study protocol schedule, study restrictions and examination schedule
• Subjects who are within their ideal body weight (BMI between \>17 and ≤28 kg/m2)
• Subjects deemed to be healthy as judged by the Medically Accountable Investigator (MAI) and determined by medical history, physical examination and medication history
• 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)
• Negative urine drug screening test at the time of screening
• 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
• Have normal screening laboratories for urine protein and urine glucose
• 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
• 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
• Agrees not to donate blood to a blood bank throughout participation in the study and for at least 3 months after last study day

You may not qualify if:

• 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
• 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)
• Participation in any ongoing investigational drug trial/study or clinical drug trial/study
• History of chronic obstructive pulmonary disease or cor pulmonale, or substantially decreased respiratory reserve, hypoxia, hypercapnia or pre-existing respiratory depression
• Active positive Hepatitis B, C and HIV serologies
• Positive urine drug screening test
• 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
• 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)
• Use of monoamine oxidase inhibitors 21 days prior to study
• Current use of mixed agonist/antagonist (such as pentazocine, nalbuphine or butorphanol) and partial agonist (buprenorphine) analgesics
• Current use of anticholinergics or other medications with anticholinergic activity
• 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.
• Donation or loss of greater than one pint of blood within 60 days of entry to the study
• 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)
• Have a diagnosis of schizophrenia or other major psychiatric diagnosis or mental illness (e.g. major depression)

Sponsors & Collaborators

• University of Maryland, Baltimore: lead
• Food and Drug Administration (FDA): collaborator

Study Sites (1)

General Clinical Research Center

Baltimore, Maryland, 21201, United States

Location

MeSH Terms

Interventions

Fentanyl

Intervention Hierarchy (Ancestors)

Piperidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Results Point of Contact

• Title: Dr. Audra Stinchcomb
• Organization: University of Maryland, Baltimore

astinchc@rx.umaryland.edu

410-706-2646

Study Officials

• Audra Stinchcomb, PhD

  University of Maryland, School of Pharmacy

  PRINCIPAL INVESTIGATOR

• Hazem Hassan, PhD

  Univerisity of Maryland, School of Pharmacy

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: OTHER
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: August 19, 2015
• First Posted: August 25, 2015
• Study Start: January 14, 2016
• Primary Completion: October 16, 2018
• Study Completion: October 16, 2018
• Last Updated: March 26, 2020
• Results First Posted: March 26, 2020

Record last verified: 2020-03

Locations

US (1)