Peer Review, ResearchPhase 4NCT02531971
Fentanyl Patch Pharmacokinetics in Healthy Adults
A Phase 4 study testing Intravenous fentanyl citrate, Duragesic® and Mylan generic fentanyl in people with Peer Review, Research, run by University of Maryland, Baltimore at 1 site in United States.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 to 45 yearsHealthy volunteers can take part
- Conditions the study is for
- Peer Review, Research
- What is being tested?
- Intravenous fentanyl citrate, Duragesic® and Mylan generic fentanyl
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 24 participants
- Where
- 1 siteUnited States
- Study dates
- 14 Jan 2016to 16 Oct 2018
- Phase
- Phase 4
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 45 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- 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
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- 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
- 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)
- 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
Who cannot join
- 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
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- 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)
- Medical history of personal drug or alcohol addiction or abuse
- 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
- Inability to communicate or cooperate with the investigators
- 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
- 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.
- 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
Trial locations and contacts
1 site in 1 country.
United States1 site
General Clinical Research Center
Baltimore, Maryland, 21201
About this study
Official title: Absolute Bioavailability/ Pharmacokinetic and Residual Drug Analysis of Duragesic ® Transdermal System and Generic Fentanyl Transdermal System in Healthy Adults
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.
Read the detailed description
Transdermal drug delivery systems (TDDS) available in the form of patches are convenient, attractive, and easy to use systems. Fentanyl patches are very popular TDDS available on the United States market today. Accurate determination of the rate and extent of drug release and absorption is crucial to ensure the safety of individuals using these and other types of patches. Delivery rate can be determined early in the development process by using in vitro skin flux permeation studies, and later in humans by accurately quantifying residual drug from patches post-wear and in pharmacokinetic studies. In this proposal, we will employ two types of evaluation to determine the rate and extent of drug release and absorption from RLD (reference listed drug) Duragesic ® TDDS (transdermal drug delivery system) and Generic Fentanyl TDDS, namely residual drug analysis post-wear and pharmacokinetic analysis in healthy adult volunteers. In addition, we will compare the plasma drug concentrations following patch and intravenous administration of Fentanyl, in order to determine the absolute bioavailability of these patches. We will conduct residual drug analysis of TDDS following in vivo wear using highly sensitive validated quantification methods. Positive outcome of this project will identify appropriate methods to determine the rate and extent of drug release and absorption from TDDS, and will help regulatory agencies in the development of Guidances for Industry regarding the characterization of drug release and absorption kinetics to ensure the safety of individuals utilizing these types of products
- Conditions
- Peer Review, Research
- Being tested
- Intravenous fentanyl citrate, Duragesic®, Mylan generic fentanyl
- Keywords
- Bioequivalence, Therapeutic Equivalency
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Intravenous fentanyl citrateDrug
100 micrograms (2 millilitres) via intravenous injection
Duragesic®Drug
Also called Duragesic® fentanyl skin patch
TDDS dosage is 25 micrograms/hour (worn for 72 h)
Mylan generic fentanylDrug
Also called Mylan generic fentanyl skin patch
TDDS dosage is 25 micrograms/hour (worn for 72 h)
| Study group | Role | What they receive |
|---|---|---|
| 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 Receives: 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 Receives: Drug: Intravenous fentanyl citrate; Drug: Duragesic®; Drug: Mylan generic fentanyl |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: 10 procedure days for Duragesic and Mylan arms each
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 Aug 2015 (estimated)
- Study start14 Jan 2016
- Primary completion16 Oct 2018
- Study completion16 Oct 2018
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Peer Review, ResearchStudies of the same condition, open and under way.
- More trials run by University of Maryland, BaltimoreThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Other
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Enrolment
- 24 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Maryland, Baltimore
- Sponsor type
- University, hospital or other
- Collaborators
- Food and Drug Administration (FDA)
- Responsible party
- Principal investigator, Audra Stinchcomb, University of Maryland, Baltimore
- Investigators
- Audra Stinchcomb, PhD, Principal investigator, University of Maryland, School of PharmacyHazem Hassan, PhD, Principal investigator, Univerisity of Maryland, School of Pharmacy
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02531971
- Sponsor's protocol ID
- HP-00063835
- Status last verified
- Mar 2020
- First submitted
- 19 Aug 2015
- Last updated
- 26 Mar 2020
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 26 Mar 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Absolute Bioavailability/ Pharmacokinetic and Residual Drug Analysis of Duragesic ® Transdermal System and Generic Fentanyl Transdermal System in Healthy Adults
- ClinicalTrials.gov ID
- NCT02531971
- Acronym / sponsor ID
- HP-00063835
- Conditions
- Peer Review, Research
- Keywords
- Bioequivalence, Therapeutic Equivalency
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 24 participants (actual)
- Lead sponsor
- University of Maryland, BaltimoreUniversity, hospital or other
- Collaborators
- Food and Drug Administration (FDA)
- Study start
- 14 Jan 2016 (actual)
- Primary completion
- 16 Oct 2018 (actual)
- Study completion
- 16 Oct 2018 (actual)
- First posted
- 25 Aug 2015 (estimated)
- Results
- Posted 26 Mar 2020
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
Transdermal drug delivery systems (TDDS) available in the form of patches are convenient, attractive, and easy to use systems. Fentanyl patches are very popular TDDS available on the United States market today. Accurate determination of the rate and extent of drug release and absorption is crucial to ensure the safety of individuals using these and other types of patches. Delivery rate can be determined early in the development process by using in vitro skin flux permeation studies, and later in humans by accurately quantifying residual drug from patches post-wear and in pharmacokinetic studies. In this proposal, we will employ two types of evaluation to determine the rate and extent of drug release and absorption from RLD (reference listed drug) Duragesic ® TDDS (transdermal drug delivery system) and Generic Fentanyl TDDS, namely residual drug analysis post-wear and pharmacokinetic analysis in healthy adult volunteers. In addition, we will compare the plasma drug concentrations following patch and intravenous administration of Fentanyl, in order to determine the absolute bioavailability of these patches. We will conduct residual drug analysis of TDDS following in vivo wear using highly sensitive validated quantification methods. Positive outcome of this project will identify appropriate methods to determine the rate and extent of drug release and absorption from TDDS, and will help regulatory agencies in the development of Guidances for Industry regarding the characterization of drug release and absorption kinetics to ensure the safety of individuals utilizing these types of products
Study design
- Primary purpose
- Other
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Fentanyl citrate (36 h), Duragesic (192 h), Mylan (192 h) | Active comparator | Drug: Intravenous fentanyl citrate, Drug: Duragesic®, Drug: Mylan generic fentanylVolunteers 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 |
| Fentanyl citrate (36 h), Mylan (192 h), Duragesic (192 h) | Active comparator | Drug: Intravenous fentanyl citrate, Drug: Duragesic®, Drug: Mylan generic fentanylVolunteers 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 |
Who may qualify
- Ages
- 18 to 45 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (22 listed)
- 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
Key exclusion criteria (21 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Intravenous fentanyl citrate100 micrograms (2 millilitres) via intravenous injection | Drug | Fentanyl citrate (36 h), Duragesic (192 h), Mylan (192 h), Fentanyl citrate (36 h), Mylan (192 h), Duragesic (192 h) |
| Duragesic®Also: Duragesic® fentanyl skin patchTDDS dosage is 25 micrograms/hour (worn for 72 h) | Drug | Fentanyl citrate (36 h), Duragesic (192 h), Mylan (192 h), Fentanyl citrate (36 h), Mylan (192 h), Duragesic (192 h) |
| Mylan generic fentanylAlso: Mylan generic fentanyl skin patchTDDS dosage is 25 micrograms/hour (worn for 72 h) | Drug | Fentanyl citrate (36 h), Duragesic (192 h), Mylan (192 h), Fentanyl citrate (36 h), Mylan (192 h), Duragesic (192 h) |
Primary outcome
Area Under the Curve (AUC 0-∞ ) ng∙h/mL
Time frame: 10 procedure days for Duragesic and Mylan arms each
drug concentration in serum vs. time; reflects the actual body exposure to drug after administration of a dose of the drug
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 26 Mar 2020.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Audra Stinchcomb, PhD principal investigator
University of Maryland, School of Pharmacy
Hazem Hassan, PhD principal investigator
Univerisity of Maryland, School of Pharmacy
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Intravenous fentanyl citrate, Duragesic® and Mylan generic fentanyl in people with Peer Review, Research, run by University of Maryland, Baltimore at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 22 inclusion and 21 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 26 Mar 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 26 Mar 2020). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Area Under the Curve (AUC 0-∞ ) ng∙h/mL (time frame: 10 procedure days for Duragesic and Mylan arms each). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 26 Mar 2020.