Pharmacokinetic Characterization of the Active, Separated System With PK Controller (Fentanyl Iontophoretic Transdermal System, 40 Mcg Fentanyl Per Activation).

NCT01750060 | Completed Phase 1

• 1 other identifier: PK2011-001
• Study Type: interventional
• Target: 54
• Locations: 1 country
• Sites: 1

Brief Summary

"This study is a single-center, randomized, open-label, 3-period, 5-treatment, 6-sequence design. A total of 54 eligible subjects will receive three total treatments; one with intravenous (IV) infusion and two with the Study System. Each subject will be randomly assigned to receive a treatment sequence consisting of Treatment A (IV fentanyl citrate), Study System Treatment B (170 mcAmp), and one of three additional Study System treatments (140 mcAmp or 200 mcAmp or 230 mcAmp) "

Conditions

Pain, Postoperative

Outcome Measures

Primary Outcomes (5)

• Measure area under the fentanyl concentration-time curve (AUC)

  Measure area under the fentanyl concentration-time curve (AUC), one of the five key pharmacokinetic (PK) parameters for the Active, Separated System with PK Controller in the study population.

  The two-hour period for hours 23-24 for all treatment groups.

• Measure maximum fentanyl concentration (Cmax)

  Measure maximum fentanyl concentration (Cmax), one of the five key pharmacokinetic (PK) parameters for the Active, Separated System with PK Controller in the study population.

  The two-hour period for hours 23-24 for all treatment groups.

• Measure time to Cmax (tmax)

  Measure time to Cmax (tmax), one of the five key pharmacokinetic (PK) parameters for the Active, Separated System with PK Controller in the study population.

  The two-hour period for hours 23-24 for all treatment groups.

• Measure terminal half-life (t½)

  Measure terminal half-life (t½), one of the five key pharmacokinetic (PK) parameters for the Active, Separated System with PK Controller in the study population.

  The two-hour period for hours 23-24 for all treatment groups.

• Measure the amount of fentanyl absorbed

  Measure the amount of fentanyl absorbed, one of the five key pharmacokinetic (PK) parameters for the Active, Separated System with PK Controller in the study population.

  The two-hour period for hours 23-24 for all treatment groups.

Study Arms (5)

Fentanyl citrate IV infusion & Naltrexone

ACTIVE COMPARATOR

Fentanyl citrate (equivalent to 80 mcg fentanyl)administered over 20 minutes by IV infusion every hour through 23.33 hours. Naltrexone (50 mg) will be administered orally (PO) every 12 hours, beginning 14 hours before the start of fentanyl treatment and ending approximately 11 hours after completion of treatment regimen to antagonize the clinical opioid effects of fentanyl.

Drug: Fentanyl; Drug: Naltrexone

Fentanyl Study System (170 mcAmps) & Naltrexone

EXPERIMENTAL

Two consecutive 40 mcg fentanyl doses each delivered over 10 minutes by the Study System (170 mcAmps) every hour through 23.33 hours. Naltrexone (50 mg) will be administered orally (PO) every 12 hours, beginning 14 hours before the start of fentanyl treatment and ending approximately 11 hours after completion of treatment regimen to antagonize the clinical opioid effects of fentanyl.

Drug: Fentanyl; Drug: Naltrexone

Fentanyl, Study System (140 mcAmp) & Naltrexone

EXPERIMENTAL

Two consecutive 35 mcg fentanyl doses, each delivered over 10 minutes by the Study System (140 mcAmp) every hour through 23.33 hours. Naltrexone (50 mg) will be administered orally (PO) every 12 hours, beginning 14 hours before the start of fentanyl treatment and ending approximately 11 hours after completion of treatment regimen to antagonize the clinical opioid effects of fentanyl.

Drug: Fentanyl; Drug: Naltrexone

Fentanyl, Study System (200 mcAmp) & Naltrexone

EXPERIMENTAL

Two consecutive 50 mcg fentanyl doses, each delivered over 10 minutes by the Study System (200 mcAmp) every hour through 23.33 hours. Naltrexone (50 mg) will be administered orally (PO) every 12 hours, beginning 14 hours before the start of fentanyl treatment and ending approximately 11 hours after completion of treatment regimen to antagonize the clinical opioid effects of fentanyl.

Drug: Fentanyl; Drug: Naltrexone

Fentanyl, Study System (230 mcAmp) & Naltrexone

EXPERIMENTAL

Two consecutive 54 mcg fentanyl doses, each delivered over 10 minutes by the Study System (230 mcAmp) every hour through 23.33 hours. Naltrexone (50 mg) will be administered orally (PO) every 12 hours, beginning 14 hours before the start of fentanyl treatment and ending approximately 11 hours after completion of treatment regimen to antagonize the clinical opioid effects of fentanyl.

Drug: Fentanyl; Drug: Naltrexone

Interventions

Fentanyl DRUG

Fentanyl Study System (170 mcAmps) & Naltrexone; Fentanyl citrate IV infusion & Naltrexone; Fentanyl, Study System (140 mcAmp) & Naltrexone; Fentanyl, Study System (200 mcAmp) & Naltrexone; Fentanyl, Study System (230 mcAmp) & Naltrexone

Naltrexone DRUG

Fentanyl Study System (170 mcAmps) & Naltrexone; Fentanyl citrate IV infusion & Naltrexone; Fentanyl, Study System (140 mcAmp) & Naltrexone; Fentanyl, Study System (200 mcAmp) & Naltrexone; Fentanyl, Study System (230 mcAmp) & Naltrexone

Eligibility Criteria

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

You may qualify if:

• Subjects must provide written informed consent to participate in the study and document their understanding that they are free to withdraw from the study at any time.
• Subjects must be healthy volunteers with no clinically relevant abnormalities, as determined by medical history, physical examination, blood chemistry, complete blood count, routine urinalysis (a microscopic urine analysis will be performed at the Investigator's discretion if the macroscopic analysis is abnormal), and electrocardiogram (ECG). Prior medical history, physical examination, and physical and laboratory findings will be reviewed and repeated as deemed appropriate by the supervising physician.
• Subjects must be male or female volunteers, between ages 18 to 45 years, inclusive.
• Subjects must have a Body Mass Index (BMI = weight \[kg\]/height2 \[m2\] of 18 to 28 kg/m2, inclusive.
• Subjects must have an average blood pressure from three separate readings in the range of 100 to 139 mm Hg systolic (inclusive) and 50 and 89 mm Hg diastolic (inclusive) after sitting for 5 minutes before and between readings.
• Subjects must have negative urine drug test results (for drugs of abuse) in each urine sample collected at the time of fentanyl dosing in each treatment period. Each urine sample will be tested for the presence of cannabinoids, amphetamines, barbiturates, benzodiazepines, cocaine, and opiates.
• Subjects must have a negative alcohol test within the 24 hours before the start of fentanyl dosing in each treatment period.
• Subjects must provide consent to use a medically acceptable method of contraception throughout the entire duration of the study and for one week after the study is completed. Medically acceptable methods of contraception that may be used by the subject and/or female partner include birth control pills, diaphragm with spermicide, intrauterine device (IUD), condom with spermicide, vaginal spermicidal suppository, surgical sterilization (6 months post-surgery), post-menopausal (not experienced a menstrual period for a minimum of 2 years), and progestin implant or injection (used consistently for the 3 months prior to study dosing).

You may not qualify if:

• Subjects who are pregnant or plan to become pregnant during the time of their participation in this study
• Subjects with clinically significant medical problems that, in the opinion of the supervising principal investigator, place the subject at undue risk of AEs. These conditions can include, but are not limited to, dermatologic, psychiatric, respiratory, cardiovascular, hepatic, renal, gastrointestinal, hematological, genitourinary, gynecologic, neurologic, or endocrine or other organ abnormality or pathology.
• Subjects with evidence of orthostatic hypotension (e.g., supine-to-standing blood pressure decrease of ≥ 20 mm Hg systolic or ≥ 10 mm Hg diastolic AND ≥ 20 beats per minute (bpm) increase in heart rate after standing for 3 minutes) or with any reported symptoms of lightheadedness, dizziness, or fainting upon standing.
• Subjects with resting heart rate \< 50 or \> 100 beats per minute.
• Subjects with a history of chronic obstructive pulmonary disease (COPD) or any other lung disease (e.g., sleep apnea,asthma) that could cause CO2 retention beyond normal.
• Subjects with oxygen saturation \< 97% on room air.
• Subjects with active systemic skin disease or with active local skin disease, such as but not limited to, sunburn, psoriasis, or atopic dermatitis, which would preclude application of the Study System to the upper outer arm.
• Subjects with a history of significant dermatologic cancers (e.g., melanoma or squamous cell carcinoma). Basal cell carcinomas that were superficial and do not involve the arms are acceptable.
• Subjects with localized skin pigmentation (e.g., tattoos, sunburn, scars, branding, etc.) or open sores, body piercing, active skin lesions on the upper arms that could interfere with the ability to assess skin site reactions.
• Subjects with excessive body hair at the intended application site and who refuse hair clipping at the application site
• Subjects with a known allergy or hypersensitivity to fentanyl or other opioids, naltrexone, naloxone, cetylpyridinium chloride, skin adhesives, tapes, or other transdermal systems
• Subjects who have reported using:
• prescription medication (except for sex-hormone replacement or birth control) within 14 days prior to Day 0 of the first treatment period
• over-the-counter (OTC) medication (except for multivitamin supplements or acetaminophen \< 2 g/day) within 3 days prior to Day 0 of the first treatment period
• alcohol, grapefruit juice, Seville oranges (e.g., marmalade), caffeine, or xanthine-containing products within 48 hours prior to dosing in each fentanyl treatment group

Sponsors & Collaborators

• Incline Therapeutics, Inc.: lead

Study Sites (1)

PRACS Institute, Ltd.

Fargo, North Dakota, 58104, United States

Location

MeSH Terms

Conditions

Pain, Postoperative

Interventions

Fentanyl; Naltrexone

Condition Hierarchy (Ancestors)

Postoperative Complications; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Pain; Neurologic Manifestations; Signs and Symptoms

Intervention Hierarchy (Ancestors)

Piperidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Naloxone; Morphinans; Opiate Alkaloids; Alkaloids; Heterocyclic Compounds, Bridged-Ring; Heterocyclic Compounds, 4 or More Rings; Heterocyclic Compounds, Fused-Ring; Phenanthrenes; Polycyclic Aromatic Hydrocarbons; Polycyclic Compounds

Study Officials

• Robert I. Cooper, M.D.

  PRACS Institute, Ltd.

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 10, 2012
• First Posted: December 17, 2012
• Study Start: December 1, 2012
• Primary Completion: March 1, 2013
• Study Completion: March 1, 2013
• Last Updated: April 19, 2013

Record last verified: 2013-04

Locations

US (1)