Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12616000600448
Ethics application status
Approved
Date submitted
6/05/2016
Date registered
10/05/2016
Date last updated
7/12/2020
Date data sharing statement initially provided
7/12/2020
Date results information initially provided
7/12/2020
Type of registration
Prospectively registered

Titles & IDs
Public title
Comparative assessment of the absorption of a generic formulation of buprenorphine transdermal patch against the innovator buprenorphine transdermal patch conducted under fasting conditions and at steady state with the inclusion of a naltrexone block in healthy male and female volunteers
Scientific title
A multiple dose, randomized, open label, bioequivalence study of a test formulation of buprenorphine transdermal patch in a 2 way crossover comparison against the innovator buprenorphine transdermal patch conducted under fasting conditions and at steady state with the inclusion of a naltrexone block in healthy male and female volunteers
Secondary ID [1] 289142 0
None
Universal Trial Number (UTN)
U1111-1181-0823
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Buprenorphine is a partial opioid agonist indicated for the management of moderate to severe pain. 298646 0
Condition category
Condition code
Anaesthesiology 298708 298708 0 0
Pain management

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Multiple dose, crossover study design whereby each participant receives the test formulation of buprenorphine (1 x 20 mcg/hr patch) on three occasions with the patch being replaced every 7 days, and the innovator formulation of buprenorphine (1 x 20 mcg/hr patch) on three occasions with the patch being replaced every 7 days with the inclusion of a naltrexone block given 12 hours prior to patch application, at application and every 24 hours up until removal of the last patch in each study period. Each naltrexone dose will be 50 mg. Each buprenorphine dosing will be seperated by a four week washout period. The intervention for this trial is the test formulation of buprenorphine .

Study Days 1 and 15 of each study period no water is allowed for 1 hour prior to dosing until 1 hour after dosing (except for the water consumed with the dose). Participants are required not to eat for 10 hours before receiving each dose on days 1 and 15 in each study period and to fast for approximately 4 hours after receiving each dose on days 1 and 15 of each study period. Bathroom visits will be supervised to ensure no unauthorised water or food intake and for personal safety. Participants will be confined at the Clinical Site for 12 hours prior to dosing to ensure compliance and will be monitored and for 24 hours after dosing.

Standard meals will be consumed at the Clinical Site with no additional food intake allowed. Alcohol breath testing will be performed upon each participant reporting to the Clinical Site 12 hours prior to dosing.

On study days 2-14 and 16-22 subjects will report to Zenith Technology for the provision of one blood sample.

Pre and post study laboratory tests will be completed to assess the health of participants along with HIV, Hepatitis and drugs of abuse testing.

Each buprenorphine patch will be applied to the upper arm with each consecutive patch applied to a different site. Investigators will examine every subject to ensure the patch has been applied correctly.

Each dose of naltrexone will be taken orally with 240 ml of water at ambient temperature. Medication must be swallowed whole and a mouth check will be conducted to ensure the medication has been taken as directed.
Intervention code [1] 294656 0
Treatment: Drugs
Comparator / control treatment
Multiple dose, crossover study design whereby each participant receives the test formulation of buprenorphine (1 x 20 mcg/hr patch) on three occasions and the innovator formulation of buprenorphine (1 x 20 mcg/hr patch) on three occasions with each dose separated by a four week washout period. The comparator/control for this trial is the innovator formulation of buprenorphine .
Control group
Active

Outcomes
Primary outcome [1] 298189 0
To compare the bioavailability of buprenorphine (as summarised by AUC0-t(ss), Cmax(ss) and Cmin(ss)). All plasma samples will be assayed for buprenorphine using one fully validated LC/MS/MS method. Validation will be conducted to comply with EU and FDA guidelines.
Timepoint [1] 298189 0
On day 1 in each study period at pre dose and at 12, 24, 72 and 120 hours post dose application.

On day 8 in each study period at pre dose and at 48 and 96 hours post dose application.

On day 15 in each study period the sampling intervals will be at 0, 6, 10, 12, 18, 24 36, 48, 60, 72, 84, 96, 108, 120, 132, 144, 156 and 168 hours post dosing.
Secondary outcome [1] 323439 0
All plasma samples will be assayed for buprenorphine to determine time to maximum peak concentration (Tmax) and the elimination half life (t1/2). Tmax will be the time where the maximum concentration occurred in the sample points. T1/2 = 0.693/Kel where kel is the terminal elimination rate constant.
Timepoint [1] 323439 0
On day 1 in each study period at pre dose and at 12, 24, 72 and 120 hours post dose application.

On day 8 in each study period at pre dose and at 48 and 96 hours post dose application.

On day 15 in each study period the sampling intervals will be at 0, 6, 10, 12, 18, 24 36, 48, 60, 72, 84, 96, 108, 120, 132, 144, 156 and 168 hours post dosing.

Eligibility
Key inclusion criteria
Healthy male and non-pregnant females
Aged between 18 and 55
Non-smoker
BMI between 18.5 and 30 inclusive
Normal, healthy individuals as determined by medical history, physical examination, ECG, blood pressure and laboratory tests
Able to provide written informed consent
Minimum age
18 Years
Maximum age
55 Years
Sex
Both males and females
Can healthy volunteers participate?
Yes
Key exclusion criteria
Any history of recent recurrent attacks of bronchitis, asthma, migraine headaches
Concomitant drug therapy of any kind
Sensitivity to buprenorphine or any other similar class of medicines, or the excipients of buprenorphine
Sensitivity to naltrexone or any other similar class of medicines, or the excipients of naltrexone
History of any conditions that might interfere with the absorption, distribution, metabolism or excretion of the drug
Females who are pregnant and/or are breastfeeding
Smoker (anyone who has smoked in the last 6 months)
History of alcohol or drug abuse or dependency
Participation in a drug study within 60 days of the start of the study or donated blood in the 60 days preceding the study.
Volunteers for whom the Clinical Investigator believes, for any reason, that participation would not be an acceptable risk

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
All formulations will be labelled as Formulation A and B. The identification of each treatment will only be known to the Managing Director and the Section Head - Trials and Regulatory Affairs.

Each participant will be identified by a 3 digit screening number and a 2 digit subject number. The screening number will be issued once the participant has given written consent to participate in the study and the two digit subject number (randomisation number) after acceptance into the study
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Randomisation list will be prepared using a computer program for a balanced two-way crossover design
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Crossover
Other design features
Phase
Phase 1
Type of endpoint/s
Bio-equivalence
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
13/05/2016
Actual
21/06/2016
Date of last participant enrolment
Anticipated
29/07/2016
Actual
1/08/2016
Date of last data collection
Anticipated
12/09/2016
Actual
26/09/2016
Sample size
Target
32
Accrual to date
Final
36
Recruitment outside Australia
Country [1] 7856 0
New Zealand
State/province [1] 7856 0
Otago

Funding & Sponsors
Funding source category [1] 293510 0
Commercial sector/Industry
Name [1] 293510 0
Juno Pharmaceuticals Pty Ltd
Country [1] 293510 0
Australia
Primary sponsor type
Commercial sector/Industry
Name
Zenith Technology Corp Ltd
Address
PO Box 1777
Dunedin 9054
Country
New Zealand
Secondary sponsor category [1] 292336 0
None
Name [1] 292336 0
Address [1] 292336 0
Country [1] 292336 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 294954 0
Northern B Health and Disability Ethics Committee
Ethics committee address [1] 294954 0
Ministry of Health
1 the Terrace
PO Box 5013
Wellington 6145
Ethics committee country [1] 294954 0
New Zealand
Date submitted for ethics approval [1] 294954 0
22/03/2016
Approval date [1] 294954 0
11/05/2016
Ethics approval number [1] 294954 0
16/NTB/61

Summary
Brief summary
The objective of this study is to evaluate the bioequivalence of the test (new) formulation of 1 x 20 mcg/hr against the reference formulation (innovator brand of 1 x 20 mcg/hr buprenorphine transdermal patch) following oral administration of a multiple dose of 20 mcg/hr with the inclusion of a naltrexone block in healthy male and female subjects under fasting conditions and at steady state.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 65626 0
Dr Noelyn Hung
Address 65626 0
Zenith Technology Corporation Limited
156 Frederick Street (PO Box 1777)
Dunedin 9016
Country 65626 0
New Zealand
Phone 65626 0
+6434779669
Fax 65626 0
+6434779605
Email 65626 0
[email protected]
Contact person for public queries
Name 65627 0
Mrs Linda Folland
Address 65627 0
Zenith Technology Corporation Limited
156 Frederick Street (PO Box 1777)
Dunedin 9016
Country 65627 0
New Zealand
Phone 65627 0
+6434779669
Fax 65627 0
+6434779605
Email 65627 0
[email protected]
Contact person for scientific queries
Name 65628 0
Dr Tak Hung
Address 65628 0
Zenith Technology Corporation Limited
156 Frederick Street (PO Box 1777)
Dunedin 9016
Country 65628 0
New Zealand
Phone 65628 0
+6434779669
Fax 65628 0
+6434779605
Email 65628 0
[email protected]

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment
All data will be compiled into a final report that is the property of the sponsor company. All participant data will be provided in summary format and result of the study only will be reported


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

Documents added manually
No documents have been uploaded by study researchers.

Documents added automatically
No additional documents have been identified.