PainPhase 1NCT03785613

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

A Phase 1 study testing Test Product T1: Buprenorphine patch (9 mg), Test Product T2: Buprenorphine patch (3.8 mg) and Reference Product R: Transtec patch (20 mg) in people with Pain, run by Grünenthal GmbH at 1 site in Switzerland.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial 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… Read more about this study

Who is it for?: Ages 18 to 55 years, men onlyHealthy volunteers can take part
Conditions the study is for: Pain
What is being tested?: Test Product T1: Buprenorphine patch (9 mg), Test Product T2: Buprenorphine patch (3.8 mg) and Reference Product R: Transtec patch (20 mg)
Could I receive a placebo?: Yes, some participants may receive a placebo
How many people: 47 participants
Where: 1 siteSwitzerland
Study dates: 7 Nov 2005to 14 Mar 2006
Phase: Phase 1
Are there results?: None posted in the registry

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 55 years
Men only
Healthy volunteers accepted
Adult

Who may be able to join

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.

Who cannot join

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.

Show all 23Show fewer

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.

Trial locations and contacts

1 site in 1 country.

Switzerland1 site

Swiss Pharma Contract
Allschwil, 4123

Other trials in Switzerland

About this study

Official title: Pilot Study to Investigate the Pharmacokinetic Characteristics of Two Buprenorphine Transdermal Patch Formulations as Compared to a Reference Patch

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
Being tested: Test Product T1: Buprenorphine patch (9 mg), Test Product T2: Buprenorphine patch (3.8 mg), Reference Product R: Transtec patch (20 mg), Matching placebo patch to T1, Matching placebo patch to T2
Medical subject headings: Pain

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

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 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.
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.
Matching placebo patch to T1Drug
Placebo patch to T1.
Matching placebo patch to T2Drug
Placebo patch to T2.
Matching placebo patch to RDrug
Placebo patch to R.

Study groups in NCT03785613
Study group	Role	What they receive
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. Receives: 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. Receives: 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. Receives: Drug: Reference Product R: Transtec patch (20 mg); Drug: Matching placebo patch to R

What is being measured

The primary outcome is the main question the study is designed to answer.

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:
Measured: 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:
Measured: 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:
Measured: 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)
Time of maximum concentration, time after administration at which Cmax occurs. Blood sampling for the determination of the plasma concentrations will be performed at the following time points:
Measured: 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)
Lag-time observed from dosing to the time-point prior to the first quantifiable plasma concentration. Blood sampling for the determination of the plasma concentrations will be performed at the following time points:
Measured: 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)
Apparent terminal elimination half-life. Blood sampling for the determination of the plasma concentrations will be performed at the following time points:
Measured: 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
Reading of skin adhesiveness of the patch will be performed for test/reference and placebo administration sites each on Days 1-5 (every 12 hours following patch application and at 96 hours following patch application immediately before patch removal).
Measured: Day 1 to Day 5
Assessment of skin irritation
Assessment of skin irritation will be performed (for test/reference and placebo patch each) at baseline, on Days 1-5 (immediately and 20 min following patch removal), and on Days 8-10 (120 hours following patch application).
Measured: At baseline, on Days 1-5 (immediately and 20 min following patch removal), on Days 8-10 (120 hours following patch application)
Incidence of treatment emergent adverse events
Number of adverse events and participants with adverse events.
Measured: From Day 1 (patch application) until Day 12 (Final examination)

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

7 Nov 200514 Mar 2006

First posted24 Dec 2018
Study start7 Nov 2005
Primary completion14 Mar 2006
Study completion14 Mar 2006

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Other trials for PainStudies of the same condition, open and under way.
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 1
Primary purpose: Treatment
Allocation: Randomised
Intervention model: Crossover
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.
Masking: None (open label)
Enrolment: 47 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT03785613
Sponsor's protocol ID: HP5303/05
Status last verified: Dec 2018
First submitted: 20 Dec 2018
Last updated: 24 Dec 2018
Results posted: No
Data monitoring committee: No
FDA-regulated drug: No
FDA-regulated device: No
Individual data sharing: No

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

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Study at a glance

From the registry record, last updated by the sponsor on 24 Dec 2018. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: Pilot Study to Investigate the Pharmacokinetic Characteristics of Two Buprenorphine Transdermal Patch Formulations as Compared to a Reference Patch
ClinicalTrials.gov ID: NCT03785613
Acronym / sponsor ID: HP5303/05
Conditions: Pain
Phase: Phase 1
Study type: Interventional
Recruitment status: Completed
Enrolment: 47 participants (actual)
Lead sponsor: Grünenthal GmbHIndustry (pharma, biotech, devices)
Study start: 7 Nov 2005 (actual)
Primary completion: 14 Mar 2006 (actual)
Study completion: 14 Mar 2006 (actual)
First posted: 24 Dec 2018 (actual)
Results: Not posted in the source record

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Crossover
Masking: None (open label)
Number of arms: 3
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.

Arm	Type	Receives
Test Product T1: Buprenorphine patch (9 mg)	Experimental	Drug: Test Product T1: Buprenorphine patch (9 mg), Drug: Matching placebo patch to T1Buprenorphine 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.
Test Product T2: Buprenorphine patch (3.8 mg)	Experimental	Drug: Test Product T2: Buprenorphine patch (3.8 mg), Drug: Matching placebo patch to T2Buprenorphine 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.
Reference Product R: Transtec patch (20 mg)	Active comparator	Drug: Reference Product R: Transtec patch (20 mg), Drug: Matching placebo patch to RTranstec (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.

Who may qualify

Ages: 18 to 55 years
Sex: Male only
Healthy volunteers: Accepted
Age groups: Adult

Key inclusion criteria (4 listed)

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.

Key exclusion criteria (23 listed)

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).

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
Test Product T1: Buprenorphine patch (9 mg)Buprenorphine transdermal patch formulation, containing 9 milligrams buprenorphine in an active surface area of 25 square centimeters.	Drug	Test Product T1: Buprenorphine patch (9 mg)
Test Product T2: Buprenorphine patch (3.8 mg)Buprenorphine transdermal patch formulation, containing 3.8 milligrams buprenorphine in an active surface area of 10 square centimeters.	Drug	Test Product T2: Buprenorphine patch (3.8 mg)
Reference Product R: Transtec patch (20 mg)Transtec (Registered Trademark) transdermal patch containing 20 milligrams buprenorphine in an active surface area of 25 square centimeters, release rate 35 micrograms per hour.	Drug	Reference Product R: Transtec patch (20 mg)
Matching placebo patch to T1Placebo patch to T1.	Drug	Test Product T1: Buprenorphine patch (9 mg)
Matching placebo patch to T2Placebo patch to T2.	Drug	Test Product T2: Buprenorphine patch (3.8 mg)
Matching placebo patch to RPlacebo patch to R.	Drug	Reference Product R: Transtec patch (20 mg)

Primary outcome

Area under the concentration-time extrapolated to infinity (AUC)
Time frame: 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
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:
Area under the concentration-time curve up the last quantifiable plasma concentration (AUC0-t)
Time frame: 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 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:
Maximum plasma concentration (Cmax) of buprenorphine
Time frame: 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, 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:

6 secondary outcomes

Time to attain maximum plasma concentration (tmax)
Time frame: 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)
Time frame: 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)
Time frame: 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
Time frame: Day 1 to Day 5
Assessment of skin irritation
Time frame: At baseline, on Days 1-5 (immediately and 20 min following patch removal), on Days 8-10 (120 hours following patch application)
Incidence of treatment emergent adverse events
Time frame: From Day 1 (patch application) until Day 12 (Final examination)

Results and safety

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 24 Dec 2018.
Individual participant dataSharing planned: No

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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.

Grünenthal Study Director study director

Grünenthal GmbH

1 site in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

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 4 inclusion and 23 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 24 Dec 2018. 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 Switzerland. 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 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

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 concentration-time extrapolated to infinity (AUC) (time frame: 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). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03785613.

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 24 Dec 2018.