Crossover Study to Evaluate the PK Effects of Two Different Wafer Administration Protocols.

An Open Label, Two-way Crossover Study to Evaluate the PK Effects of Two Different Wafer Administration Protocols in Healthy Volunteers Under Fasted Conditions.

The study will look at whether it is preferable to administer two wafers simultaneously or separately.

Study Overview

• Status: Completed
• Conditions: Pain
• Intervention / Treatment: Drug: Sublingual ketamine wafers

• Study Type: Interventional
• Enrollment (Actual): 10
• Phase: Phase 2

Contacts and Locations

Study Locations

• Australia
  • Western Australia
    • Nedlands, Western Australia, Australia, 6009
      • Linear Clinical Research

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Males or females aged 18-65 years.
• Good general health without clinically significant renal, hepatic, cardiac or respiratory disease, as determined by the Principal Investigator.
• Willing and able to give informed consent and agree to complete all study procedures.
• Have suitable venous access for blood sampling.

• Female participants are eligible only if all the following apply:

  1. Not pregnant (women of child bearing potential must have a negative serum pregnancy test at screening and negative urine pregnancy test at check-in for each inpatient period);
  2. Not lactating;
  3. Not planning to become pregnant during the study;
  4. Be surgically sterile (irreversible surgical sterilisation by hysterectomy, bilateral oophorectomy, or bilateral salpingectomy), or have undergone bilateral tubal ligation; or be at least two years post-menopausal; or is practicing double-barrier contraception or is using an insertable, injectable, transdermal, or combination oral contraceptive for greater than 2 months prior to screening visits and commits to the use of an acceptable form of highly effective birth control for the duration of the study and for 30 days after the last dose study drug administration.
• BMI within the range of 19-30 kg/m2 (inclusive).
• Deemed able to read and understand English in order to communicate with research staff and complete protocol required questionnaires and forms.

Exclusion Criteria:

• Has a laboratory value at the Screening Visit that is outside the normal range, unless it is judged by the Investigator as not clinically significant after appropriate evaluation. One repeat of initial laboratory testing is allowed.
• AST, ALT and ALP tests in excess of 1.5 times the upper limit of normal.
• Any gastrointestinal condition that could affect drug absorption.
• History of any clinically significant condition involving the bladder or urinary tract, including frequent urinary tract infections (e.g. > 2 per year), or current symptoms of bladder irritation such as frequent or urgent need to urinate or burning with urination.
• History (within the last six months) of or current clinically significant psychiatric disorder including anxiety, psychosis or depression.
• Current inflammatory or ulcerative disease of the oral cavity that could impair the absorption of sublingual medication.
• History of severe allergic or anaphylactic drug-related reactions.
• History of hypersensitivity to ketamine or any of the excipients of Wafermine™.
• 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 (or longer if the medication has a half-life long enough to potentially expose the healthy participant to any significant systemic exposure). Exception: Hormone replacement therapy and oral contraceptives in female participants is allowed.
• 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.
• Participation in another clinical trial of an investigational agent within 30 days of screening.
• Positive serology for hepatitis C virus (HCV), hepatitis B or human immunodeficiency virus (HIV).
• Clinically significant, as determined by the Investigator, abnormal ECG (12-lead) or vital signs at the screening visit or pre-dose on any treatment day.
• Known or suspected drug (including analgesic drugs or tranquilizers) or alcohol abuse or dependence, as defined by DSM-IV, and not in full remission, as judged by the Investigator, or history of alcohol abuse or excessive intake of alcohol, defined as regular weekly intake of >15 units for men and >10 units for women. (1 unit = 25 mL spirits, 125 mL wine, 250 mL beer or lager.)
• Positive results on the urine drug screen or breath alcohol test at screening and/or pre-dose. A positive result on the urinary drug screen at screening is allowed at the discretion of the Investigator provided the result can be reliably explained by recent medication and/or dietary history.
• Significant history of illicit drug use (as determined by the Investigator).
• Any alcohol use within 24 hours prior to each inpatient treatment period.
• Unwillingness or inability to comply with the requirements of this protocol, including the presence of any condition (physical, mental, or social) that is likely to affect the participant returning for subsequent visits on schedule.
• Blood donation (1 unit or more) within 1 month prior to the screening visit and until the end of study participation.
• Current or previous tobacco user (within 12 months prior to screening).
• Participants who routinely consume more than four standard caffeinated beverages per 24-hour period.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Treatment A: Simultaneous Administration; Sublingual ketamine 50mg (2 x 25mg wafers) administered simultaneously at T=0 minute.	Drug: Sublingual ketamine wafers; Two sublingual ketamine 25 mg wafers; Other Names: Wafermine
Experimental: Treatment B: Sequential Administration; Sublingual ketamine 50mg (2 x 25mg wafers) administered sequentially, one 25 mg wafer at T=0 minute and one 25 mg wafer at T=3 minutes.	Drug: Sublingual ketamine wafers; Two sublingual ketamine 25 mg wafers; Other Names: Wafermine

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Bioavailability	Plasma concentrations collected for 10 hours after simultaneous wafer administration and sequential wafer administration	10 hours

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of treatment related adverse events		From time of initial dose until 3 days after final dose.
Participant Acceptance	Participant will rate their experience by completing a questionnaire 20 minutes after each dose.	20 minutes
Administrator Acceptance	The person administering drug will rate their experience by completing a questionnaire 20 minutes after each dose.	20 minutes

Collaborators and Investigators

• Sponsor: iX Biopharma Ltd.
• Investigators: Principal Investigator: Sam Salman, MD, iX Biopharma

Study record dates

Study Major Dates

• Study Start: July 1, 2016
• Primary Completion (Actual): August 1, 2016
• Study Completion (Actual): August 1, 2016

Study Registration Dates

• First Submitted: August 2, 2016
• First Submitted That Met QC Criteria: August 2, 2016
• First Posted (Estimate): August 5, 2016

Study Record Updates

• Last Update Posted (Estimate): August 19, 2016
• Last Update Submitted That Met QC Criteria: August 17, 2016
• Last Verified: August 1, 2016

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Central Nervous System Depressants; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Anesthetics, Dissociative; Anesthetics, Intravenous; Anesthetics, General; Anesthetics; Excitatory Amino Acid Antagonists; Excitatory Amino Acid Agents; Ketamine
• Other Study ID Numbers: KET011

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO