Clinical Pilot Study in Healthy Men to Characterize the Uptake of Buprenorphine Into and Its Elimination From the Body After Topical Application of Two New Forms of a Skin Patch in Comparison to a Reference Patch

NCT03785613 | Completed Phase 1

• 1 other identifier: HP5303/05
• Study Type: interventional
• Target: 47
• Locations: 1 country
• Sites: 1

Brief Summary

This study is intended to produce information on the pharmacokinetic characteristics (uptake into and elimination from the body) of two new patch formulations of the analgesic buprenorphine as compared to the reference patch Transtec (Registered Trademark) 35 micrograms per hour (μg/h) in order to assess the suitability of the test formulations for a later confirmatory bioequivalence study. In addition to a reduced buprenorphine load, the new patch formulations may potentially provide improved wearing properties. A placebo patch formulation of the respective test or reference patch will be applied simultaneously to explore the skin tolerability and skin adhesiveness of the patch formulations. Furthermore, the safety and tolerability of the treatments will be assessed.

Conditions

Pain

Outcome Measures

Primary Outcomes (3)

• Area under the concentration-time extrapolated to infinity (AUC)

  For the analysis of buprenorphine in human plasma a liquid chromatography-double quadrupole mass spectrometry (LC-MS/MS)-validated method will be used. AUC is calculated by summation of the partial areas AUC(0-t) and the residual area AUC(t-∞) represents the recalculated plasma concentration at the last sampling time point with a quantifiable concentration. Blood sampling for the determination of the plasma concentrations will be performed at the following time points:

  pre-dose, and after 4, 8, 12, 16, 24, 36, 48, 60, 72, 80, 88, 96, 104, 112, 120, 132, 144, 156, and 168 hours post-dose

• Area under the concentration-time curve up the last quantifiable plasma concentration (AUC0-t)

  Area under data from administration until the last sampling point (tz) with a quantifiable concentration, calculated by the linear/log trapezoidal method, i.e., the linear trapezoidal rule is applied up to Cmax and then the log trapezoidal rule is applied for the remainder of the curve. If multiple maxima are observed in the concentration-time curve, Cmax is assigned to the first maximum. Blood sampling for the determination of the plasma concentrations will be performed at the following time points:

  pre-dose, and after 4, 8, 12, 16, 24, 36, 48, 60, 72, 80, 88, 96, 104, 112, 120, 132, 144, 156, and 168 hours post-dose

• Maximum plasma concentration (Cmax) of buprenorphine

  Maximum plasma concentration, highest observed plasma concentration of the measured concentration-time profile. Blood sampling for the determination of the plasma concentrations will be performed at the following time points:

  pre-dose, and after 4, 8, 12, 16, 24, 36, 48, 60, 72, 80, 88, 96, 104, 112, 120, 132, 144, 156, and 168 hours post-dose

Secondary Outcomes (6)

• Time to attain maximum plasma concentration (tmax)

  pre-dose, and after 4, 8, 12, 16, 24, 36, 48, 60, 72, 80, 88, 96, 104, 112, 120, 132, 144, 156, and 168 hours post-dose

• Lag-time observed from dosing to the time-point prior to the first quantifiable plasma concentration (tlag)

  pre-dose, and after 4, 8, 12, 16, 24, 36, 48, 60, 72, 80, 88, 96, 104, 112, 120, 132, 144, 156, and 168 hours post-dose

• Terminal half-life (t1/2,z)

  pre-dose, and after 4, 8, 12, 16, 24, 36, 48, 60, 72, 80, 88, 96, 104, 112, 120, 132, 144, 156, and 168 hours post-dose

• Assessment of skin adhesiveness

  Day 1 to Day 5

• Assessment of skin irritation

  At baseline, on Days 1-5 (immediately and 20 min following patch removal), on Days 8-10 (120 hours following patch application)

Study Arms (3)

Test Product T1: Buprenorphine patch (9 mg)

EXPERIMENTAL

Buprenorphine transdermal patch formulation, containing 9 milligrams buprenorphine in an active surface area of 25 square centimeters. Single application of transdermal patch during 96 hours, on skin in the midclavicular line directly under the clavicle. Matching placebo patch to T1: simultaneous application for 96 hours on the upper back.

Drug: Test Product T1: Buprenorphine patch (9 mg); Drug: Matching placebo patch to T1

Test Product T2: Buprenorphine patch (3.8 mg)

EXPERIMENTAL

Buprenorphine transdermal patch formulation, containing 3.8 milligrams buprenorphine in an active surface area of 10 square centimeters. Single application of patch during 96 hours, on skin in the midclavicular line directly under the clavicle. Matching placebo patch to T2: simultaneous application for 96 hours on the upper back.

Drug: Test Product T2: Buprenorphine patch (3.8 mg); Drug: Matching placebo patch to T2

Reference Product R: Transtec patch (20 mg)

ACTIVE COMPARATOR

Transtec (Registered Trademark) transdermal patch containing 20 milligrams buprenorphine in an active surface area of 25 square centimeters. Single application of transdermal patch during 96 hours, on skin in the midclavicular line directly under the clavicle. Matching placebo patch to R: simultaneous application for 96 hours on the upper back.

Drug: Reference Product R: Transtec patch (20 mg); Drug: Matching placebo patch to R

Interventions

Test Product T1: Buprenorphine patch (9 mg) DRUG

Buprenorphine transdermal patch formulation, containing 9 milligrams buprenorphine in an active surface area of 25 square centimeters.

Test Product T1: Buprenorphine patch (9 mg)

Test Product T2: Buprenorphine patch (3.8 mg) DRUG

Buprenorphine transdermal patch formulation, containing 3.8 milligrams buprenorphine in an active surface area of 10 square centimeters.

Test Product T2: Buprenorphine patch (3.8 mg)

Reference Product R: Transtec patch (20 mg) DRUG

Transtec (Registered Trademark) transdermal patch containing 20 milligrams buprenorphine in an active surface area of 25 square centimeters, release rate 35 micrograms per hour.

Reference Product R: Transtec patch (20 mg)

Matching placebo patch to T1 DRUG

Placebo patch to T1.

Test Product T1: Buprenorphine patch (9 mg)

Matching placebo patch to T2 DRUG

Placebo patch to T2.

Test Product T2: Buprenorphine patch (3.8 mg)

Matching placebo patch to R DRUG

Placebo patch to R.

Reference Product R: Transtec patch (20 mg)

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: male
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Male Caucasian participants aged 18-55 years.
• Body mass index (BMI) between 18 and 30 kilograms per square meter inclusive.
• Participants must be in good health as determined by medical history, physical examination, 12-lead electrocardiogram, vital signs, and clinical laboratory parameters.
• Participants giving written informed consent to participate within this trial.

You may not qualify if:

• Resting pulse rate less than or equal to 45 or greater than or equal to 95 beats per minute (participant has rested in the sitting position for at least 3 minutes).
• Resting blood pressure (participant has rested in the sitting position for at least 3 minutes) systolic blood pressure less than or equal to 100 and greater than or equal to 140 millimeters mercury (mmHg), diastolic blood pressure less than or equal to 50 and greater than or equal to 95 mmHg.
• Positive human immunodeficiency virus (HIV) type 1/2 antibodies, hepatitis B surface (HBs) antigen, hepatitis B core (HBc) antibodies, hepatitis C virus (HCV) antibodies.
• History or presence of orthostatic hypotension.
• Participation in another clinical study in the last three months before starting this study (exception: characterization of metabolizer status).
• Positive drug of abuse screening (amphetamines, tetrahydrocannabinol \[THC\], cocaine, morphines, or positive breath alcohol) at screening or baseline.
• Diseases or condition known to interfere with the absorption, distribution, metabolism or excretion of drugs.
• Marked repolarization abnormality (e.g., suspicious or definite congenital long QT syndrome) or co-medication that is known to influence cardiac repolarization substantially.
• Bronchial asthma.
• Definite or suspected history of drug allergy or hypersensitivity, especially known sensitivity to buprenorphine, naltrexone or naloxone.
• Patch allergy.
• Participants who have received any prescribed and non-prescribed systemic or topical medication two weeks before and during the study with the exception of short term medication, e.g. paracetamol for the treatment of headache.
• History or suspicion of alcohol or drug abuse, e.g., use of barbiturates, amphetamines, ecstasy, meta-chlorophenylpiperazine (mCPP), cannabis, or narcotics.
• Not able to abstain from drinking of caffeine containing beverages (tea, coffee, chocolate, or cola).
• Consumption of any quinine containing beverages (bitter lemon, tonic water) or food within two weeks before and during the study.

Sponsors & Collaborators

• Grünenthal GmbH: lead

Study Sites (1)

Swiss Pharma Contract

Allschwil, 4123, Switzerland

Location

MeSH Terms

Conditions

Pain

Condition Hierarchy (Ancestors)

Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Study Officials

• Grünenthal Study Director

  Grünenthal GmbH

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: 3-way cross-over (three periods, three treatments and six sequence groups) with single application each. There will be a wash-out period between administrations, i.e., between removal of previous patch and application of new patch of at least 10 days.

Study Record Dates

• First Submitted: December 20, 2018
• First Posted: December 24, 2018
• Study Start: November 7, 2005
• Primary Completion: March 14, 2006
• Study Completion: March 14, 2006
• Last Updated: December 24, 2018

Record last verified: 2018-12

Data Sharing

• IPD Sharing: Will not share

Locations

CH (1)