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Trial registered on ANZCTR


Registration number
ACTRN12617000140358
Ethics application status
Approved
Date submitted
21/01/2017
Date registered
25/01/2017
Date last updated
17/05/2017
Type of registration
Prospectively registered

Titles & IDs
Public title
A study to compare a two novel ketamine wafer formulations to intravenous ketamine in healthy adult volunteers.
Scientific title
An open label, three-way crossover study to evaluate the absolute bioavailability of two formulations of Wafermine Trademark, a novel sublingual wafer formulation of ketamine, in healthy volunteers under fasted conditions.
Secondary ID [1] 290755 0
Nil known
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Pain 301345 0
Condition category
Condition code
Anaesthesiology 301104 301104 0 0
Pain management

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Participants will complete three inpatient periods, each period separated by a minimum of 3 days. Participants will be admitted the afternoon before and will remain inpatient until 24 hours after each study medication dose. Two formulations of Wafermine Trademark sublingual ketamine wafers will be tested, Formulation A and Formulation B. The wafers contain identical pharmaceutical contents. The difference between the wafers is the freeze-drying method of manufacture. During one session, a single dose of Wafermine Trademark (ketamine wafer) Formulation A 25 mg will be administered under the tongue. During another session, a single dose of Wafermine Trademark (ketamine wafer) Formulation B 25 mg will be administered under the tongue. During another session, Ketalar Registered Trademark (intravenous ketamine) 10 mg will be administered over 5 minutes. No food or drink except water is allowed for at least 10 hours before the study medication dose. Water is restricted 1 hour before and after dosing.
Intervention code [1] 296660 0
Treatment: Drugs
Comparator / control treatment
The comparator is a single intravenous dose of United States Ketalar Registered Trademark 10 mg.
Control group
Active

Outcomes
Primary outcome [1] 300513 0
To determine the absolute bioavailability of two formulations of Wafermine Trademark versus intravenous Ketalar Registered Trademark (US). The bioavailability after sublingual dosing will be estimated by the ratio of dose adjusted Area under the plasma concentration-time curve from time zero to infinity and observed maximum plasma concentration. The pharmacokinetic analysis will be based on plasma concentrations of racemic ketamine and norketamine.
Timepoint [1] 300513 0
A total of 17 blood samples will be collected per participant per occasion (pre-dose and at 5, 10, 20, 30, 40, 50 mins and 1, 1.25, 1.5, 2, 3, 4, 6, 10, 14 and 24 hours post dose).
Secondary outcome [1] 330170 0
To determine safety and tolerability of a single dose of two formulations of Wafermine Trademark (ketamine wafer) administered via sublingual route. The most common adverse effects of ketamine are nausea and dizziness.
Timepoint [1] 330170 0
Safety and tolerability assessments include:
1. Adverse event probes at 30 minutes, 1, 2, 4, 10 and 24 hours, and in a follow-up phone call 3 days after the last dose of study medication.
2. Vital signs collected pre-dose and at 15 and 30 minutes, then at 1, 1.5, 2, 4, 6, 10 and 24 hours.
3. Continuous oxygen saturation monitoring starting prior to dosing and for the first two hours after dosing (oxygen saturation readings recorded at 30, 60, 90 and 120 minutes).
4. Modified Wilson Sedation Score pre-dose and at 15 and 30 minutes, then at 1, 1.5, 2, 4, 6, 10 and 24 hours;
5. Oral Symptom Questionnaire at pre-dose, 20 minutes, 1 and 24 hours.
6. Sublingual assessments at pre-dose, 20 minutes, 1 and 24 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. Females must be non-pregnant, non-lactating, and using an acceptable form of birth control.
4. BMI within the range of 19.0-30.0 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 abnormal, clinically significant laboratory value at the Screening Visit (including positive serology results for Hepatitis B or C or HIV). .
2. Any gastrointestinal condition, which could affect drug absorption.
3. History of clinically significant condition involving the bladder or urinary tract, including frequent urinary tract infections (e.g. greater than 2 per year), or current symptoms of bladder irritation such as frequent or urgent need to urinate or burning with urination.
4. History (within the last six months) of or current clinically significant psychiatric disorder including anxiety, psychosis or depression.
5. Current inflammatory or ulcerative disease of the oral cavity that could impair the absorption of sublingual medication.
6. History of severe allergic or anaphylactic drug-related reactions.
7. History of hypersensitivity to ketamine or any of the excipients of Wafermine Trademark.
8. Intake of any Over-The-Counter (OTC)/non-prescribed drugs including vitamins, minerals, supplements or herbal medicines within 1 week of Period 1 study drug administration, or intake of prescribed drugs within 2 weeks of Period 1 study drug administration. 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, 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. Drug (including analgesic drugs or tranquilizers) or alcohol abuse or dependence.

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] 295184 0
Commercial sector/Industry
Name [1] 295184 0
iX Biopharma Ltd.
Address [1] 295184 0
24 Augusta Street
Willetton, WA 6155
Country [1] 295184 0
Australia
Primary sponsor type
Commercial sector/Industry
Name
iX Biopharma Ltd.
Address
24 Augusta Street
Willetton, WA 6155

Country
Australia
Secondary sponsor category [1] 294011 0
None
Name [1] 294011 0
Nil known
Address [1] 294011 0
Nil known
Country [1] 294011 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 296536 0
Bellberry Limited
Ethics committee address [1] 296536 0
129 Glen Osmond Rd.
Eastwood, SA 5063
Ethics committee country [1] 296536 0
Australia
Date submitted for ethics approval [1] 296536 0
18/01/2017
Approval date [1] 296536 0
08/02/2017
Ethics approval number [1] 296536 0
2017-01-047

Summary
Brief summary
Participants will be admitted to the research clinical for three separate inpatient periods, each period separated by a minimum of 3 days. Participants will check in the afternoon before planned dosing and will stay inpatient for 24 hours after study medication for each inpatient period. In one period, a single dose of intravenous ketamine 10 mg will be administered and in the two other periods a single 25 mg ketamine wafer (two different formulations) will be administered under the tongue. No food or drink except water is allowed starting 10 hours before each study medication dose and for 4 hours after dosing. Water is restricted 1 hour before and after dosing.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 71182 0
Prof Stephan A. Schug
Address 71182 0
Linear Clinical Research Ltd
1st Floor, B Block, QEII Medical Centre
Hospital Avenue, Nedlands
WA 6009
Country 71182 0
Australia
Phone 71182 0
+61 (08) 6382 5100
Fax 71182 0
Email 71182 0
enquiries@linear.org.au
Contact person for public queries
Name 71183 0
Mr Simon Scott
Address 71183 0
Linear Clinical Research Ltd
1st Floor, B Block, QEII Medical Centre
Hospital Avenue, Nedlands
WA 6009
Country 71183 0
Australia
Phone 71183 0
+61 (08) 6382 5100
Fax 71183 0
Email 71183 0
enquiries@linear.org.au
Contact person for scientific queries
Name 71184 0
Dr Janakan Krishnarajah
Address 71184 0
iX Biopharma Pty Ltd
24 Augusta Street
Willetton, WA 6155


Country 71184 0
Australia
Phone 71184 0
+61 412 999 004
Fax 71184 0
Email 71184 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