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Trial registered on ANZCTR


Registration number
ACTRN12617000002381
Ethics application status
Approved
Date submitted
15/12/2016
Date registered
3/01/2017
Date last updated
12/05/2017
Type of registration
Prospectively registered

Titles & IDs
Public title
A study of two different formulations of buprenorphine in healthy volunteers.
Scientific title
An open label, two-­way crossover study to evaluate the absolute bioavailability of BnoX Trademark, a novel sublingual wafer formulation of buprenorphine, in healthy volunteers under fasted conditions.
Secondary ID [1] 290743 0
Nil known
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Pain 301323 0
Addiction 301325 0
Condition category
Condition code
Anaesthesiology 301079 301079 0 0
Pain management
Mental Health 301081 301081 0 0
Addiction

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Participants will complete two inpatient sessions, with admission the afternoon before dosing, followed by 48 hours of observation after dosing. Study staff will administer to participants a single dose of intravenous buprenorphine 300mcg during one inpatient session and a single dose of sublingual (under-the-tongue) buprenoprhine wafer 800 mcg during another session. Study staff will observe the oral cavity to ensure sublingual buprenorphine wafer is dissolved. To block the opioid effects of buprenorphine, 50 mg oral naltrexone will be administered 12 hours and 1 hour pre-dose and 12 hours post-dose. The two inpatient sessions will be separated by a minimum of 7 days. No food will be allowed for 10 hours prior to and four hours following dosing.
Intervention code [1] 296651 0
Treatment: Drugs
Comparator / control treatment
The comparator drug is intravenous buprenorphine 300mcg.
Control group
Active

Outcomes
Primary outcome [1] 300498 0
To determine the absolute bioavailability of BnoX Trademark sublingual buprenorphine wafer versus intravenous buprenorphine. Standard non-compartmental analysis methods will be used to obtain PK variables for buprenorphine and norbuprenorphine for both routes of administration. The bioavailability after sublingual dosing will be estimated by the ratio of dose adjusted area under the plasma concentration-time curve following intravenous and sublingual dosing.
Timepoint [1] 300498 0
A total of 16 blood samples will be collected per participant per occasion (pre-dose and at 10, 20, 30, 45 mins, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24 and 48h post dose).
Secondary outcome [1] 330168 0
To determine safety and tolerability of a single dose of BnoX (buprenorphine wafer) administered via sublingual route. The most common side effects of buprenoprhine are sedation, drowsiness and dizziness. Participants will be administered Naltrexone to block opioid effects. Safety and tolerability will be monitored by collection of electrocardiograms, vital signs, oxygen saturation, and adverse event monitoring.
Timepoint [1] 330168 0
Electrocardiogram at pre-dose, 1 hour, 24 and 48 hours after dosing. Vital signs (blood pressure, pulse, respirations and oxygen saturation reading) pre-dose and at 10, 20, 30, 45 minutes and 1, 1.5, 2, 2.5, 3, 4, 6, 8, and 12 hours. Continuous oxygen saturation monitoring starting prior to dosing and for the first hour after dosing. Adverse event probes will be conducted at 20 minutes and at 2, 4, 12, 24, and 48 hours.

Eligibility
Key inclusion criteria
1. Good general health without clinically significant renal, hepatic, cardiac or respiratory disease, as determined by the Principal Investigator.
2. Have suitable venous access for blood sampling.
3. Female participants must not be pregnant or lactating and must be using a reliable form of birth control.
4. BMI within the range of 19-30 kg/m2 (inclusive).
5. Deemed able to read and understand English in order to communicate with research staff and complete protocol required questionnaires and forms.
Minimum age
18 Years
Maximum age
65 Years
Gender
Both males and females
Can healthy volunteers participate?
Yes
Key exclusion criteria
1. Has a laboratory value at the Screening Visit that is outside the normal range (including positive serology for Hepatitis B, C or HIV).
2. Any gastrointestinal condition which could affect drug absorption.
3. History (within the last six months) of or current clinically significant psychiatric disorder including anxiety, psychosis or depression.
4. Current inflammatory or ulcerative disease of the oral cavity that could impair the absorption of sublingual medication.
5. History of severe allergic or anaphylactic drug-related reactions.
6. History of hypersensitivity to buprenorphine or naltrexone or any of the excipients of the sublingual wafer.
7. Intake of any prescribed or Over-The-Counter (OTC)/non-prescribed drugs, vitamins/supplements, or herbal medicines, within 2 weeks of administration of investigational product/reference listed product (or longer if the medication has a half-life long enough to potentially expose the healthy participant to any significant systemic exposure).
8. Use of drugs with enzyme-inducing properties (such as rifampicin and St John’s Wort) within 3 weeks or 5 half-lives, whichever is greater, prior to treatment period 1 and throughout the study, or any drug known to be a strong inhibitor of CYP3A4 within 5 half-lives of treatment period 1 and throughout the study.
9. Participation in another clinical trial of an investigational agent within 30 days of study entry.
10. Clinically significant, as determined by the Investigator, abnormal ECG (12-lead) or vital signs at the screening visit or pre-dose (Day 1).
11. Known or suspected drug (including analgesic drugs or tranquilizers) or alcohol abuse or dependence.
12. Positive results on the urine drug screen or breath alcohol test at screening and/or pre-dose.
13. Any alcohol use within 24 hours prior to Day -1 in each of the inpatient treatment periods.

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)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Who is / are masked / blinded?



Intervention assignment
Other design features
Phase
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
WA

Funding & Sponsors
Funding source category [1] 295183 0
Commercial sector/Industry
Name [1] 295183 0
iX Biopharma Ltd.
Address [1] 295183 0
24 Augusta Street
Willetton, WA 6155
Australia
Country [1] 295183 0
Australia
Primary sponsor type
Commercial sector/Industry
Name
iX Biopharma Pty Ltd
Address
24 Augusta Street
Willetton, WA 6155
Australia
Country
Australia
Secondary sponsor category [1] 294010 0
None
Name [1] 294010 0
Nil known
Address [1] 294010 0
None
Country [1] 294010 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 296535 0
Bellberry Limited
Ethics committee address [1] 296535 0
129 Glen Osmond Rd.
Eastwood, SA 5063
Ethics committee country [1] 296535 0
Australia
Date submitted for ethics approval [1] 296535 0
Approval date [1] 296535 0
21/11/2016
Ethics approval number [1] 296535 0
2016-10-756

Summary
Brief summary
The sponsor has developed a wafer formulation of buprenorphine to be administered under the tongue. The buprenorphine wafer will be compared to intravenous buprenorphine (marketed in Australia as Temgesic). Healthy volunteers may participate in the study. Participants will complete two inpatient sessions, with admission the afternoon before dosing, followed by 48 hours of observation after dosing. Participants will receive a single dose of intravenous buprenorphine 300mcg during one inpatient session and a single dose of sublingual (under-the-tongue) buprenoprhine wafer 800 mcg during another session. Naltrexone is given to block opioid effects. The two inpatient sessions will be separated by a minimum of 7 days. No food will be allowed for 10 hours prior to and four hours following dosing.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 71154 0
Prof Stephan A. Schug
Address 71154 0
Linear Clinical Research Ltd
1st Floor, B Block, QEII Medical Centre
Hospital Avenue, Nedlands
WA 6009
Country 71154 0
Australia
Phone 71154 0
+61 (08) 6382 5100
Fax 71154 0
Email 71154 0
Stephan.schug@uwa.edu.au
Contact person for public queries
Name 71155 0
Ms Blagica Dimoski
Address 71155 0
Linear Clinical Research Ltd
1st Floor, B Block, QEII Medical Centre
Hospital Avenue, Nedlands
WA 6009
Country 71155 0
Australia
Phone 71155 0
+61 (08) 6382 5100
Fax 71155 0
Email 71155 0
enquiries@linear.org.au
Contact person for scientific queries
Name 71156 0
Dr Janakan Krishnarajah
Address 71156 0
iX Biopharma Pty Ltd
24 Augusta Street
Willetton, WA 6155


Country 71156 0
Australia
Phone 71156 0
+61 412 999 004
Fax 71156 0
Email 71156 0
j.krishnarajah@ixbiopharma.com

No information has been provided regarding IPD availability
Summary results
Have study results been published in a peer-reviewed journal?
Other publications
Have study results been made publicly available in another format?
Results – basic reporting
Results – plain English summary