Clinical Study in Healthy Men to Investigate the Uptake of Buprenorphine and Its Elimination From the Body After Dermal Application as Patches for 96 Hours and for 72 Hours

NCT03770234 | Completed Phase 1

• 1 other identifier: HP5303/04
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of the study was to investigate the pharmacokinetics (i.e. the uptake, distribution and elimination from the body) of dermally applied buprenorphine during and after different application periods, i.e., a 96-hour and a 72-hour application of the Transtec (Registered Trademark) patch (release rate 35 micrograms per hour \[µg/hour\]). In the Transtec summary of product characteristics (prescribing information for the physician), the wearing time per patch is restricted to three days (72 hours) after which the patch has to be replaced. However, market experience has shown that the Transtec patches are sometimes worn for a period longer than three days, i.e. they sometimes happen to be only replaced every four days. There was currently no data available as how to evaluate this longer wearing period.

Conditions

Pain; Pharmacokinetics

Outcome Measures

Primary Outcomes (2)

• Pharmacokinetic parameter: AUC48-72 for buprenorphine

  Partial area under the plasma concentration-time curve (from 48 hours after application until 72 hours after application).

  From 48 hours to 72 hours

• Pharmacokinetic parameter: AUC72-96 for buprenorphine

  Partial area under the plasma concentration-time curve (from 72 hours after application until 96 hours after application).

  From 72 hours to 96 hours

Secondary Outcomes (8)

• Pharmacokinetic parameter: Cmax for buprenorphine

  Before application and after 4, 8, 16, 24, 32, 40, 48, 56, 64, 72, 80, 88, 96, 104,112,120,132,144,156, and 168 hours

• Pharmacokinetic parameter: tmax for buprenorphine

  Before application and after 4, 8, 16, 24, 32, 40, 48, 56, 64, 72, 80, 88, 96, 104,112,120,132,144,156, and 168 hours

• Pharmacokinetic parameter: AUC0-t for buprenorphine

  Before application and after 4, 8, 16, 24, 32, 40, 48, 56, 64, 72, 80, 88, 96, 104,112,120,132,144,156, and 168 hours

• Pharmacokinetic parameter: t1/2z for buprenorphine

  Before application and after 4, 8, 16, 24, 32, 40, 48, 56, 64, 72, 80, 88, 96, 104,112,120,132,144,156, and 168 hours

• Pharmacokinetic parameter: AUC0-inf for buprenorphine

  Before application and after 4, 8, 16, 24, 32, 40, 48, 56, 64, 72, 80, 88, 96, 104,112,120,132,144,156, and 168 hours

Study Arms (2)

Treatment A: Transtec patch application for 96 hours

EXPERIMENTAL

Transtec 35 µg/hour transdermal patch wearing period of 96 hours, with application of patch on Study Day 1 and removal on Study Day 5.

Drug: Transtec 35 µg/hour transdermal patch

Treatment B: Transtec patch application for 72 hours

EXPERIMENTAL

Transtec 35 µg/hour transdermal patch wearing period of 72 hours, with application of patch on Study Day 1 and removal on Study Day 4.

Drug: Transtec 35 µg/hour transdermal patch

Interventions

Transtec 35 µg/hour transdermal patch DRUG

Transdermal patch containing 20 mg buprenorphine in an active surface area of 25 squared centimeters. Buprenorphine release rate 35 µg/hour.

Treatment A: Transtec patch application for 96 hours; Treatment B: Transtec patch application for 72 hours

Eligibility Criteria

• Age: 25 Years - 45 Years
• Sex: male
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Male Caucasian volunteers, aged 25-45 years.
• Body mass index (BMI) between 18 and 30 kilogram/squared meter (extremes included).
• Good physical and mental health status (no current acute illness) determined on the basis of the medical history and a general clinical examination.
• Systolic blood pressure between 90 millimeter mercury (mmHg) and 150 mmHg (extremes included).
• Diastolic blood pressure between 45 mmHg and 90 mmHg (extremes included).
• Pulse rate between 45 beats per minute (bpm) and 100 bpm (extremes included).
• Electrocardiogram (12 lead) considered as normal by the investigator.
• Results of laboratory tests within the normal ranges for the testing laboratory. The investigator may include a participant having values outside the accepted range if, in his/her opinion, these values are of no clinical relevance. The decision will be justified.
• The participant has been informed using the informed consent approved by the local ethics committee.
• The consent was obtained by participant's signature.

You may not qualify if:

• Diseases and functional disorders of the central nervous system (CNS), endocrinological system, gastrointestinal tract, hepatobiliary system, renal system, respiratory system or cardiovascular system including marked repolarization abnormality (e.g. suspicious or definite congenital long QT syndrome) or co-medication that is known to influence cardiac repolarization substantially.
• History of seizures or at risk (i.e. head trauma, epilepsy in family anamnesis, unclear loss of consciousness).
• Malignancy.
• History of orthostatic hypotension.
• Positive human immunodeficiency virus (HIV) 1/2-antibodies, hepatitis B surface (HBs) -antigen, hepatitis B core (HBc) -antibodies, hepatitis C virus (HCV) -antibody tests at the screening examination.
• Drug allergy.
• Bronchial asthma.
• Participation in another clinical study within three month prior to the start of this study (exception: characterization of metabolizer status).
• Blood donation (more than 100 milliliters) within three month prior to the start of this study.
• Use of any medication within four weeks prior to the start of the study (self-medication or prescription).
• Evidence of alcohol, medication or drug abuse.
• Positive Naloxone challenge test.
• Positive drug abuse screening test.
• Extremely unbalanced diet (in the opinion of the investigator).
• Excessive consumption of food or beverages containing caffeine or other xanthines (more than five cups of coffee or equivalent per day).

Sponsors & Collaborators

• Grünenthal GmbH: lead

Study Sites (1)

Institut für Klinische Pharmakologie Bobenheim

Grünstadt, 67269, Germany

Location

MeSH Terms

Conditions

Pain

Interventions

Transdermal Patch

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Equipment and Supplies

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: Each participant will apply Transtec 35 µg/hour transdermal patch, once for 96 hours (Treatment A) and once for 72 hours (Treatment B) in randomized order. Between removal of the first patch and application of the second patch, there will be a washout period of at least 10 days.

Study Record Dates

• First Submitted: December 7, 2018
• First Posted: December 10, 2018
• Study Start: April 5, 2004
• Primary Completion: May 26, 2004
• Study Completion: May 26, 2004
• Last Updated: December 10, 2018

Record last verified: 2018-12

Data Sharing

• IPD Sharing: Will not share

Locations

DE (1)