Clinical trial NCT01377831: Study of Ketamine Administered Intravenously and by Sublingual Wafer
Official title: An Open Label, Two Way Crossover Study to Evaluate the Bioavailability and Clinical Tolerability of a Novel Sublingual Wafer Formulation of Ketamine in Healthy Male Volunteers
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Pain
Lead sponsor: iX Biopharma Ltd.
Sponsor class: OTHER
First posted: 2011-06-21
Enrollment: 8
Sex: MALE
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: 8 Healthy Male Volunteers

Brief summary: To determine the rate and extent of of absorption of racemic ketamine from sublingual wafer

Detailed description: 1. To determine the apparent rate of disintegration of the sublingual wafer
2. To determine the overall clinical tolerability of ketamine when administered as a single dose via the sublingual route. Tolerability will be assessed using a range of objective and subjective parameters as assessed using modified Likert and Bond and Lader scales.

Eligibility criteria: Inclusion Criteria:

1. Adult males aged 18-65 years.
2. Good general health without clinically significant renal, hepatic, cardiac or respiratory disease, as determined by the Principal Investigator.
3. Good general mental health as determined by scores on the Symptom Checklist-90-R (SCL-90-R®), a screening instrument which evaluates a broad range of psychological problems and symptoms of psychopathology.
4. Agree to and be capable of signing an Informed Consent Form.
5. Have suitable venous access for blood sampling.
6. BMI within the range of 19-30 kg/m2.

Exclusion Criteria:

1. Renal impairment as evidenced by estimated creatinine clearance (CrCl), measured by the Cockcroft-Gault method, of less than 90 mL/min.
2. Have 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.
3. A score of more than two standard deviations from the mean on any of the key nine scales in the SCL-90-R ®
4. Any medical condition that in the opinion of the Investigator may adversely impact on the participant's ability to complete the study, including but not limited to:

   * History of cerebral trauma or stroke
   * History of seizure or epilepsy
   * Hyperthyroidism
   * Recent clinically significant URTI (within two weeks of Day 1) or respiratory infection
   * History of Myocardial Infarction or clinically significant cardiac disease including cardiac arrhythmia.
   * Poorly controlled hypertension - as assessed by the Principal Investigator.
   * Clinically significant history of asthma requiring regular supportive or preventative therapy (childhood asthma that has resolved \>5 years previously may be suitable for inclusion at the discretion of the Investigator.
   * Glaucoma
5. Plasma AST, ALT and ALP tests in excess of 1.5 times the upper limit of normal.
6. History of severe allergic or anaphylactic drug-related reactions.
7. History of hypersensitivity to ketamine or any of its excipients.
8. Current (within the last six months) clinically significant psychiatric disorder including anxiety, psychosis or depression.
9. Concurrent use of other medication on a regular or daily basis including but not limited to, theophylline, benzodiazepines, thyroxine, sedatives or anti-anxiolytics.
10. Participation in another clinical trial of an investigational agent within 30 days of study entry.
11. Known history of past or present infection with hepatitis C virus (HCV), hepatitis B or human immunodeficiency virus (HIV).
12. Clinically significant abnormal ECG (12-lead) at the screening visit or prior to dosing on Day 1, as determined by the Investigator.
13. Participants who have a marked prolongation of the QT corrected (QTc) interval (i.e., repeated demonstration of a QTc \>430 msec for males) at screening or prior to dosing on Day 1 in either study period will not be allowed to continue in the study.
14. Significant history of illicit drug or alcohol use or abuse (as determined by the Principal Investigator).
15. Any alcohol use within 24 hours prior to dosing on Day 1 in each of the study periods.
16. 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 follow-up visits on schedule.
17. Blood donation (1 unit or more) within 1 month prior to the screening visit.
18. Current or previous tobacco user (within 12 months prior to Day 1) .
19. Planned surgical procedure requiring general anaesthesia during the study period and within two weeks of study completion

Primary outcomes:
measure: Bioavailability of a single 25 mg dose of sublingual (SL) ketamine
timeFrame: 24 hours post-dose for two dosing periods, which were separated by 7 days.
Secondary outcomes:
measure: General clinical tolerability and safety
timeFrame: 24 hours post-dose for two dosing periods, which were separated by 7 days.
measure: Rate of disintegration
timeFrame: 5 minutes post-dose
Other outcomes:
Locations:
city: Adelaide
country: Australia
facility: Pain and Anaesthesia Research Clinic (PARC), Royal Adelaide Hospital
state: South Australia
Study officials:
affiliation: Pain and Anaesthesia Research Clinic - PARC
name: Pual Rolan
role: PRINCIPAL_INVESTIGATOR
References: