| Eligibility |
Inclusion Criteria:
A subject will be eligible for inclusion in this study only if all of the following
criteria apply:
1. 18 to 65 years of age, inclusive, at screening.
2. Able to understand and provide written and dated informed consent prior to screening.
Deemed likely to comply with study protocol and communicate AEs and other clinically
important information, and agree to be hospitalized to complete screening and initiate
experimental treatment.
3. Resides in a stable living situation, in the opinion of the investigator
4. Has an identified reliable informant, in the opinion of the investigator
5. Diagnosed with bipolar disorder (BD) according to the criteria defined in the DSM-5.
The diagnosis of BD will be made by a psychiatrist and supported by the MINI 7.0.2.
6. Suicidal ideation or behavior as evidenced by an answer of "Yes" to item 4 or item 5
on the C-SSRS.
7. A score of greater than or equal to 20 on the 10 items of the BISS that correspond
with MADRS (equivalent to MADRS (BDM) total score of 30).
8. In good general health, as ascertained by medical history, physical examination
(including measurement of seated vital signs), clinical laboratory evaluations, and
electrocardiogram
9. If female, a status of non-childbearing potential or use of an acceptable form of
birth control per the following specific criteria:
1. Non-childbearing potential (e.g., physiologically incapable of becoming pregnant,
i.e., permanently sterilized [status post hysterectomy, bilateral tubal
ligation], or post-menopausal with last menses at least one year prior to
screening); or
2. Childbearing potential, and meets the following criteria:
i. 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 sexually abstinent.
ii. Negative urinary pregnancy test at screening, confirmed by a second 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 pre-ketamine baseline.
10. Body mass index between 18-35kg/m2.
11. Concurrent psychotherapy will be allowed if the type and frequency of the therapy
(e.g., weekly or monthly) has been stable for at least three months prior to screening
and is expected to remain stable for the duration of the study.
12. Concurrent hypnotic therapy (e.g., with zolpidem, zaleplon, melatonin,
benzodiazepines, or trazodone) will be allowed if the therapy has been stable for at
least four weeks prior to screening and if it is expected to remain stable during the
course of the subject's participation in the study. Subjects can also continue
treatment with benzodiazepines used for anxiety if therapy has been stable for at
least four 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 subject will not be eligible for inclusion in this study if any of the following criteria
apply:
1. Female of childbearing potential who is not willing to use one of the specified forms
of birth control during the study.
2. Female who is pregnant or breastfeeding.
3. Female with a positive pregnancy test at screening or before oral dosing of
investigational product.
4. Current DSM-5 diagnosis of moderate or severe substance use disorder (except marijuana
or tobacco use disorder) within the 12 months prior to screening. Substance abuse
cannot be the precipitant of entry to treatment.
5. Subjects with a lifetime history of PCP/ketamine drug use, or failed use of ketamine
for depression.
6. History of schizophrenia or schizoaffective disorder, or any history of psychotic
symptoms when not in an acute bipolar mood episode.
7. History of anorexia nervosa, bulimia nervosa, or eating disorder NOS (OSFED) within
five years of screening.
8. Has dementia, delirium, amnestic, or any other cognitive disorder.
9. Any major psychiatric disorder, including a personality disorder, which is clinically
predominant to BD at screening, or has been the primary focus of treatment predominant
to BD at any time within six months prior to screening.
10. Current major psychiatric disorder, diagnosed at screening with the MINI 7.0.2, that
is the primary focus of treatment, with BD as the secondary focus of treatment, within
the past six months.
11. A clinically significant abnormality on the screening physical examination that might
affect safety or study participation, or that might confound interpretation of study
results according to the study clinician.
12. Current episode of:
1. Untreated hypertension, (Stage 1 or greater) as defined by a systolic blood
pressure =140 mmHg or diastolic blood pressure =90 mmHg at screening on two of
three measurements at least 15 minutes apart. If untreated due to missing
medication dose/s this is not exclusionary.
2. Hypertension, Stage 2, as defined by a systolic blood pressure =155 mmHg or
diastolic blood pressure =99 mmHg within 1.5 hours prior to ketamine infusion on
two of three measurements at least 15 minutes apart at the pre-ketamine
assessment (on Day 0 at Visit 1).
3. Recent myocardial infarction (within one year).
4. Syncopal event within the past year.
5. Congestive heart failure (CHF) New York Heart Association Criteria >Stage 2.
6. Angina pectoris.
7. Heart rate <50 or >105 beats per minute at screening, pre-ketamine infusion (Day
0) or at randomization (Day 1).
8. QTcF =450 msec at screening for men, = 470 msec for women, pre-ketamine infusion
(Day 0), or at randomization (Day 1), on two of three measurements at least 15
minutes apart.
13. History of hypertension, or on antihypertensives for the purpose of lowering blood
pressure, with either an increase in antihypertensive dose or increase in the number
of antihypertensive drugs used to treat hypertension over the last two months.
14. Chronic lung disease, excluding asthma.
15. Lifetime history of surgical procedures involving the brain or meninges, encephalitis,
meningitis, degenerative central nervous system (CNS) disorder (e.g., Alzheimer's or
Parkinson's Disease), epilepsy, mental retardation, or any other
disease/procedure/accident/intervention that, according to the screening clinician, is
deemed associated with significant injury to or malfunction of the CNS; or history of
significant head trauma within the past two years.
16. Presents with any of the following lab abnormalities:
a. Subjects with diabetes mellitus fulfilling any of the following criteria: i.
Unstable diabetes mellitus defined as glycosylated hemoglobin (HbA1c) >8.0 % at
screening.
ii. Admitted to hospital for treatment of diabetes mellitus or diabetes
mellitus-related illness in the past 12 weeks.
iii. Not under physician care for diabetes mellitus. iv. Has not been on the same dose
of oral hypoglycemic drug(s) and/or diet for the four weeks prior to screening. For
thiazolidinediones (glitazones) this period should not be less than eight weeks.
b. Any other clinically significant abnormal laboratory result (as determined by the
investigator and medical monitor) at the time of the screening.
17. 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.
18. Subjects on exclusionary concomitant psychotropic medications (see Appendix 1) as
defined in the study manual.
19. At randomization, subjects prescribed more than one agent in each category;
1. Approved antidepressants (e.g., SSRIs, SNRIs, TeCAs, fluoxetine), but not 5-HT-2a
antagonists (lurasidone, aripiprazole, olanzapine, quetiapine)
2. Mood stabilizers (e.g., lithium, carbamazepine, valproic acid)
20. Subjects with exclusionary laboratory values (see Table 2).
21. Known allergies to lurasidone or Latuda, cycloserine or Seromycin, or the excipients
mannitol, croscarmellose sodium, magnesium stearate, silicon dioxide, and/or HPMC
(hydroxypropylmethylcellulose).
22. Participation in any clinical trial with an investigational drug or device within the
past month or concurrent to study participation.
23. Study site personnel and/or persons employed by NeuroRx, Inc. or Target Health or by
the investigator or study site (i.e., permanent, temporary contract worker, or
designee responsible for the conduct of the study), or an immediate family member
(i.e., spouse or parent, child, or sibling [biological or legally adopted]) of such
persons.
|
