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Trial registered on ANZCTR


Registration number
ACTRN12614000444684
Ethics application status
Approved
Date submitted
19/04/2014
Date registered
30/04/2014
Date last updated
17/12/2014
Type of registration
Prospectively registered

Titles & IDs
Public title
Evaluation of the Pharmacokinetics of Sublingual IPX237 in Healthy Volunteers
Scientific title
IPX237-B14-01: Evaluation of the Pharmacokinetics of Sublingual IPX237 in Healthy Volunteers
Secondary ID [1] 284465 0
None
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Depression 291694 0
Condition category
Condition code
Mental Health 292075 292075 0 0
Depression

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Single-center, open-label, randomized, single-dose, 4-sequence, 4-treatment crossover study with at least 5 days of washout between dosing in each treatment period.
Subjects will be randomized to one of four sequences to receive the following investigational treatments under fasted condition:
Treatment A: IPX237-L0003 sublingual paste (0.42 mL)90 mg, retained under the tongue for 2 minutes.
Treatment B: IPX237-L0003 sublingual paste (0.42 mL) 90mg, no restriction on retention or swallowing.
Treatment C: IPX237-L0002 sublingual paste (0.42 mL)45mg, retained under the tongue for 2 minutes.
Treatment D: 15 mg esketamine (free base equivalent), preservative-free, infused IV over 40 minutes.
The sublingual paste must be placed under the tongue using the prefilled applicator. Proper administration of the sublingual drug products should be confirmed by a mouth check. Subjects must not expectorate, drink, or rinse the mouth for at least 1 hour postdose.
The subject should be evaluated at 32 hours postdose to determine that they are medically stable. The subject should be driven home by a responsible adult.
Intervention code [1] 289221 0
Treatment: Drugs
Comparator / control treatment
Treatment D: 15 mg esketamine (free base equivalent)
Control group
Active

Outcomes
Primary outcome [1] 291950 0
Pharmacokinetics
Timepoint [1] 291950 0
During each treatment period, blood samples will be collected for measurement of esketamine and (S)-norketamine in plasma at the following times: within 60 minutes predose, and postdose at 10, 20, 30, 40, and 50 minutes and 1, 1.5, 2, 3, 4, 6, 8, 12, and 24 hours.
Secondary outcome [1] 307908 0
Safety
Timepoint [1] 307908 0
12-lead electrocardiograms (ECG), clinical laboratory tests, vital signs, adverse events (AEs), and concomitant medications will be evaluated over the course of the study. Physical examinations will be performed at Screening and at Study Exit. Single ECG will be evaluated at Screening, predose, and at 45 minutes, and 8 hours postdose. Vital signs will be measured in each period as specified.

Eligibility
Key inclusion criteria
Healthy volunteers between the ages of 18 and 55 years of age inclusive, weighing at least 60 kg with BMI of 18.0 kg/m2 to 29.5 kg/m2 (inclusive) at the time of informed consent.
Minimum age
18 Years
Maximum age
55 Years
Gender
Both males and females
Can healthy volunteers participate?
Yes
Key exclusion criteria
Presence of a clinically significant disorder, including acute or chronic infections or a malignant neoplasm and/or involving disease in one or more of these organ systems: cardiovascular, respiratory, renal, gastrointestinal, immunologic, musculoskeletal, hematologic, dermatologic, hepatic, reproductive, endocrine, or neurologic/psychiatric, as determined by clinical investigators.
History of psychosis in self or family.
History of or clinical signs of glaucoma.
History of or clinical signs of any form of epilepsy or seizures

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
Phase 1
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)
SA
Recruitment hospital [1] 2351 0
The Royal Adelaide Hospital - Adelaide

Funding & Sponsors
Funding source category [1] 289109 0
Commercial sector/Industry
Name [1] 289109 0
Impax Laboratories, Inc
Address [1] 289109 0
30831 Huntwood Avenue Hayward, CA 94544
Country [1] 289109 0
United States of America
Primary sponsor type
Commercial sector/Industry
Name
Impax Pharmaceuticals,A Division of Impax Laboratories, Inc.
Address
31047 Genstar Road Hayward, CA 94544
Country
United States of America
Secondary sponsor category [1] 287775 0
None
Name [1] 287775 0
Address [1] 287775 0
Country [1] 287775 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 290896 0
Bellberry Human Research Ethics Committee
Ethics committee address [1] 290896 0
71 Anzac Highway Ashford, SA 5035
Ethics committee country [1] 290896 0
Australia
Date submitted for ethics approval [1] 290896 0
14/05/2014
Approval date [1] 290896 0
06/06/2014
Ethics approval number [1] 290896 0

Summary
Brief summary
To characterize the pharmacokinetics (PK), safety, and tolerability of sublingually administered esketamine hydrochloride from IPX237 at two dose strengths, and to evaluate the effect of formulation retention in the sublingual space.
Trial website
Trial related presentations / publications
N/A
Public notes

Contacts
Principal investigator
Name 47854 0
Prof Guy Ludbrook
Address 47854 0
CMAX, a division of IDT Australia Limited Level 5 East Wing Royal Adelaide Hospital North Terrace Adelaide, SA 5000
Country 47854 0
Australia
Phone 47854 0
+61 8 8222 5422
Fax 47854 0
Email 47854 0
guy.ludbrook@adelaide.edu.au
Contact person for public queries
Name 47855 0
Mr Teo Franic
Address 47855 0
Level 5 East Wing Royal Adelaide Hospital North Terrace Adelaide SA 5000
Country 47855 0
Australia
Phone 47855 0
61 8 8222 3923
Fax 47855 0
Email 47855 0
Teo.franic@cmax.com.au
Contact person for scientific queries
Name 47856 0
Prof Guy Ludbrook
Address 47856 0
CMAX, a division of IDT Australia Limited Level 5 East Wing Royal Adelaide Hospital North Terrace Adelaide, SA 5000
Country 47856 0
Australia
Phone 47856 0
+61 8 8222 5422
Fax 47856 0
Email 47856 0
guy.ludbrook@adelaide.edu.au

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