A single centre, double blind, randomised , parallel group, ascending single and multiple dose, safety and tolerability, pharmacokinetic and pharmacodynamic study of oral ketamine in healthy volunteer and patients with a history of depression or anxiety cohorts.
This randomised controlled parallel group Phase I trial (n=48) evaluated the safety and efficacy of ketamine for depression anxiety.
This study will investigate the safety and tolerability of ketamine given to healthy volunteers and patients with a history of depression and anxiety. It will examine how the drug is absorbed and excreted from the body. The study will also examine what effects ketamine has on specific functions of the body.
Study Arms & Interventions
Experimental Arm
experimental
Interventions
Ketamine
Placebo
Participants
Inclusion Criteria
Subjects will be eligible for enrolment for Cohorts 1, 2, 3 and 5: on the basis of:
a) Provide written informed consent
b) Male or non-pregnant females
c) Aged 18 to 55 years on the day of consent
d) Body Mass Index greater than 18 and less than 30kg/m2 on day of consent
Locations
Unknown facility — Australia
e) Healthy individuals as determined by medical history, physical examination, ECG, vital signs and laboratory tests
f) HIV and Hepatitis B and C negative
g) Non-smoker (for at least 6 months prior to the date of consent).
h) Drug free as determined by urine drug testing
Subjects will be eligible for enrolment for Cohort 4 on the basis of:
a) Provide written informed consent
b) Male or non-pregnant females
c) Aged 18 to 60 years on the day of consent
d) Body Mass Index greater than 18 and less than 35 kg/m2 on day of consent
e) Healthy individuals as determined by medical history, physical examination, ECG, vital signs and laboratory tests
f) HIV and Hepatitis B and C negative
g) Previously Diagnosed DSM-5 Major Depressive Disorder (MDD) (n=6) or Generalized Anxiety Disorder (GAD) /Social Anxiety Disorder (SAD) (n=6)
h) An inadequate response, ie treatment was not successful, treatment with at least 2 prescribed antidepressants
i) MADRS score of at least 20 (MDD) or HAM-A score of 18 (GAD/SAD)
j) Psychotropic medication and/or psychotherapy regime is stable i.e no change to drugs or dose or visit schedule within previous four weeks
k) Previous positive response to off label SC injection ketamine use as determined by documentation of a 50% change in previous Hamilton Anxiety Scale (HAM-A) for MDD, Spielberger State Anxiety inventory (SSAI) plus Fear Questionnaire (FQ) for SAD
l) Drug free as determined by urine drug testing
Exclusion Criteria
Subjects will be excluded for Cohorts 1, 2, 3 and 5: on the basis of:
a) Evidence from medical history, physical or laboratory examinations of clinically significant neurologic, psychiatric, cardiac, respiratory, renal, hepatic, endocrine, gastrointestinal, immunological condition or any other diagnosed conditions that might interfere with the absorption, distribution, metabolism or excretion of the drug, interfere with the ability to accurately record study measurements or which may potentiate or predispose to undesired effects.
b) Participants receiving treatment with monoamine oxidase inhibitors, vasoconstriction agents, thyroxine or benzodiazepines.
c) Any clinically significant history of alcohol or drug abuse or dependency including ketamine or its excipients.
d) Any clinically significant illness in the 30 days prior to dosing day 1.
e) Any clinically significant infection or febrile illness in the five days prior to dosing day 1.
f) Clinically significant Abnormal ECG at the screening visit
g) Females who are pregnant or breastfeeding
h) Females who are not using effective contraception for the prevention of pregnancy ie prescribed hormonal contraceptives or other reliable methods
i) Participation in any drug study in the 60 days preceding dosing day 1
j) Participants who do not consent to their GP being contacted prior to the commencement of the study, if necessary, about their medical history or after the study about any adverse results or reactions
k) Participants who, in the opinion of the Investigator, do not understand the information and procedures of the study, or would not be compliant with them (in particular the study restrictions and risks involved).
l) Any participation for whom the Investigator believes, for any reason, inclusion would not be an acceptable risk
m) Subject with any clinically significant abnormality or abnormal laboratory test results found during medical screening
n) History of mental illness requiring medication or treatment by a physician
Subjects will be excluded for Cohort 4: on the basis of:
a) Evidence from medical history, physical or laboratory examinations of clinically significant neurologic, cardiac, respiratory, renal, hepatic, endocrine, gastrointestinal, immunological condition or any other diagnosed conditions that might interfere with the absorption, distribution, metabolism or excretion of the drug, interfere with the ability to accurately record study measurements or which may potentiate or predispose to undesired effects.
b) Participants receiving treatment with monoamine oxidase inhibitors, vasoconstriction agents, thyroxine or benzodiazepines.
c) Any clinically significant history of alcohol or drug abuse or dependency.
d) Any clinically significant illness in the 30 days prior to dosing day 1.
e) Any clinically significant infection or febrile illness in the five days prior to dosing day 1.
f) Clinically significant Abnormal ECG at the screening visit
g) Females who are pregnant or breastfeeding
h) Females who are not using effective contraception for the prevention of pregnancy ie prescribed hormonal contraceptives or other reliable methods
i) Participation in any drug study in the 60 days preceding dosing day 1
j) Participants who do not consent to their GP being contacted prior to the commencement of the study, if necessary, about their medical history or after the study about any adverse results or reactions
k) Participants who, in the opinion of the Investigator, do not understand the information and procedures of the study, or would not be compliant with them (in particular the study restrictions and risks involved).
l) Any participation for whom the Investigator believes, for any reason, inclusion would not be an acceptable risk
m) Subject with any clinically significant abnormality or abnormal laboratory test results found during medical screening
n) Past or current history of schizophrenia, bipolar disorder, or other psychotic disorder
o) History of abuse of ketamine or phencyclidine
p) Significant current risk of suicide as assessed by C-SSRS
q) Contraindication to the use of ketamine, e.g., any condition in which a significant elevation of blood pressure would be hazardous, such as decompensated heart failure, severe or poorly controlled hypertension (blood pressure systolic less than or equal to 160 or diastolic less than or equal to 90, tested on 2 or more occasions); within last 3 months, recent myocardial infarction, stroke, cerebral haemorrhage; myasthenia gravis.
r) History of neurogenerative disorder eg Alzheimers disease, vascular dementia, Parkinson's disease or evidence of mild cognitive impairment