Clinical trial NCT03785613: 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
Official title: Pilot Study to Investigate the Pharmacokinetic Characteristics of Two Buprenorphine Transdermal Patch Formulations as Compared to a Reference Patch
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Pain
Lead sponsor: Grünenthal GmbH
Sponsor class: INDUSTRY
First posted: 2018-12-24
Enrollment: 47
Sex: MALE
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Intervention model description: 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.
Primary purpose: TREATMENT

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.


Eligibility criteria: Inclusion Criteria:

* 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.

Exclusion Criteria:

* 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.
* Drinking of alcohol containing beverages within 48 hours before administration of investigational product(s).
* Blood donation or comparable blood loss (more than 100 milliliters) during the last 3 months.
* History of seizures or at risk (i.e., head trauma, epilepsy in family anamnesis, unclear loss of consciousness).
* Known or suspected of not being able to comply with the study protocol.
* Not able to communicate meaningfully with the investigator and staff.
* Smoking of more than 20 cigarettes per day or equivalent.
* History of any disorder of the respiratory center.
* Unhealthy skin according to examination by the study physician, not allowing proper patch administration.

Primary outcomes:
measure: Area under the concentration-time extrapolated to infinity (AUC)
timeFrame: 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
measure: Area under the concentration-time curve up the last quantifiable plasma concentration (AUC0-t)
timeFrame: 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
measure: Maximum plasma concentration (Cmax) of buprenorphine
timeFrame: 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:
measure: Time to attain maximum plasma concentration (tmax)
timeFrame: 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
measure: Lag-time observed from dosing to the time-point prior to the first quantifiable plasma concentration (tlag)
timeFrame: 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
measure: Terminal half-life (t1/2,z)
timeFrame: 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
measure: Assessment of skin adhesiveness
timeFrame: Day 1 to Day 5
measure: Assessment of skin irritation
timeFrame: At baseline, on Days 1-5 (immediately and 20 min following patch removal), on Days 8-10 (120 hours following patch application)
measure: Incidence of treatment emergent adverse events
timeFrame: From Day 1 (patch application) until Day 12 (Final examination)
Other outcomes:
Locations:
city: Allschwil
country: Switzerland
facility: Swiss Pharma Contract
Study officials:
affiliation: Grünenthal GmbH
name: Grünenthal Study Director
role: STUDY_DIRECTOR
References: