| Eligibility |
Inclusion Criteria:
- A subject will be eligible for inclusion only if all of the following criteria are
met:
1. Male or female, 18 to 70 years of age, inclusive, at screen.
2. Able to read, understand, and provide written, dated informed consent prior to
screening. Participants will be deemed likely to comply with study protocol and
communicate with study personnel about adverse events and other clinically
important information.
3. Diagnosed with Major Depressive Disorder (MDD), single or recurrent or Bipolar-II
Disorder and currently experiencing a Major Depressive Episode (MDE) of at least
eight weeks in duration, prior to screening, according to the criteria defined in
the Diagnosis and Statistical Manual of Mental Disorders, Fourth Edition, Text
Revision(DSM-IV-TR™). The diagnosis of MDD will be made by a site psychiatrist
and supported by the Structured Clinical Interview for DSM-IV-TR™ (SCID-I/P).
4. Has a history of TRD during the current MDE, as assessed by the investigator. TRD
is defined as failure to achieve a satisfactory response (e.g., less than 50%
improvement of depression symptoms), as perceived by the participant, to at least
one "treatment course" of a therapeutic dose of an antidepressant therapy of at
least 8 weeks duration. The adequacy of dose and duration of the antidepressant
therapy will be determined as per the MGH ATRQ criteria. Participants must
currently be on a stable (for at least 4 weeks) and adequate (according to the
MGH ATRQ) dose of ongoing SSRI or SNRI antidepressant therapy, of which total
duration must be at least 8 weeks. Participants may also have a history of
intolerance to at least 2 antidepressant medications. These patients with the
intolerance history will not be required to be currently taking an antidepressant
medication.
5. Meet the threshold on the total SSI score of >/=6 at both screening and baseline
visits.
6. Participants must qualify as "Moderately Treatment Refractory" using the Maudsley
staging method, which incorporates past treatments, severity of symptoms and
duration of presenting episode.
7. In good general health, as ascertained by medical history, physical examination
(PE) (including measurement of supine and standing vital signs), clinical
laboratory evaluations, and 3-lead electrocardiogram (ECG) if no evaluation
available from the last 6 months.
8. If female, a status of non-childbearing potential or use of an acceptable form of
birth control per the following specific criteria:
a. Non-childbearing potential (e.g., physiologically incapable of becoming
pregnant, i.e., permanently sterilized (status post hysterectomy, bilateral tubal
ligation), or is post-menopausal with her last menses at least one year prior to
screening); or b. Childbearing potential, and meets the following criteria: i.
Childbearing potential, including women using any form of hormonal birth control,
on hormone replacement therapy started prior to 12 months of amenorrhea, using an
intrauterine device (IUD), having a monogamous relationship with a partner who
has had a vasectomy, or is sexually abstinent.
ii. Negative urinary pregnancy test at screening, confirmed by a negative urinary
pregnancy test at randomization prior to receiving study treatment.
iii. Willing and able to continuously use one of the following methods of birth
control during the course of the study, defined as those which result in a low
failure rate (i.e., less than 1% per year) when used consistently and correctly:
implants, injectable or patch hormonal contraception, oral contraceptives, IUD,
double-barrier contraception, sexual abstinence. The form of birth control will
be documented at screening and baseline.
9. Body mass index between 17-40kg/m2.
10. Concurrent psychotherapy will be allowed if the type (e.g., supportive, cognitive
behavioral, insight-oriented, et al) and frequency (e.g., weekly or monthly) of
the therapy has been stable for at least three months prior to screening and if
the type and frequency of the therapy is expected to remain stable during the
course of the subject's participation in the study.
11. Concurrent hypnotic therapy (e.g., with zolpidem, zaleplon, melatonin, or
trazodone) will be allowed if the therapy has been stable for at least 4 weeks
prior to screening and if it is expected to remain stable during the course of
the subject's participation in the study.
Exclusion Criteria:
- A potential participant will NOT be eligible for participation in this study if any of
the following criteria are met:
1. Female of childbearing potential who is not willing to use one of the specified
forms of birth control during the study.
2. Female that is pregnant or breastfeeding.
3. Female with a positive pregnancy test at screening or baseline.
4. Total SSI score of <6 at the screen or baseline visits.
6. Current diagnosis of a Substance Use Disorder (Abuse or Dependence, as defined by
DSM-IV-TR™), with the exception of nicotine dependence, at screening or within six
months prior to screening.
7. Current diagnosis of Axis I disorders other than Dysthymic Disorder, Generalized
Anxiety Disorder, Social Anxiety Disorder, Panic Disorder, Agoraphobia, or Specific
Phobia (unless one of these is comorbid and clinically unstable, and/or the focus of
the participant's treatment for the past six months or more).
8. History of schizophrenia or schizoaffective disorders, or any history of psychotic
symptoms in the current or previous depressive episodes.
9. History of anorexia nervosa, bulimia nervosa, or eating disorder not otherwise
specified, within one year of screening.
10. Any Axis I or Axis II Disorder, which at screening is clinically predominant to
their MDD or has been predominant to their MDD at any time within six months prior to
screening. A diagnosis of borderline personality disorder is excluded.
11. In the judgment of the investigator, the subject is at significant risk for
suicidal behavior during the course of his/her participation in the study.
12. Has dementia, delirium, amnestic, or any other cognitive disorder.
13. Has a clinically significant abnormality on the screening physical examination
that might affect safety, study participation, or confound interpretation of study
results.
14. Participation in any clinical trial with an investigational drug or device within
the past month or concurrent to study participation.
15. Known history or current episode of:
1. QTcF (Fridericia-corrected) =450 msec at screening (Visit 1) or randomization
2. Syncopal event within the past year.
3. Congestive heart failure (CHF) New York Heart Association Criteria >Stage 2
4. Angina pectoris
5. Heart rate <50 or >105 beats per minute at screening or randomization
16. Chronic lung disease.
17. Lifetime history of surgical procedures involving the brain or meninges,
encephalitis, meningitis, degenerative central nervous system disorder (e.g.,
Alzheimer's or Parkinson's Disease), epilepsy, mental retardation, or any other
disease/procedure/accident/intervention associated with significant injury to or
malfunction of the central nervous system (CNS), or a history of significant head
trauma within the past two years.
18. Presents with any of the following lab abnormalities w/in the past 6 months:
1. Thyroid stimulating hormone (TSH) outside of the normal limits and clinically
significant as determined by the investigator. Free thyroxine (T4) levels may be
measured if TSH level is high. Subject will be excluded if T4 level is clinically
significant.
2. Any other clinically significant abnormal laboratory result at the time of the
screening exam.
19. History of hypothyroidism and has been on a stable dosage of thyroid
replacement medication for less than six months prior to screening.(Subjects on a
stable dosage of thyroid replacement medication for at least six months or more
prior to screening are eligible for enrollment.)
20. History of hyperthyroidism which was treated (medically or surgically) less
than six months prior to screening.
21. Any current or past history of any physical condition which in the
investigator's opinion might put the subject at risk or interfere with study
results interpretation.
22. History of positive screening urine test for drugs of abuse at screening:
cocaine, amphetamines, barbiturates, opiates.
23. Current (or chronic) use of opiates. History of Opioid Use Disorder.
24. Current use of lamotrigine and an inability to stop the medication prior to
receiving ketamine.
|
