Please select the eligibility criteria that correspond to the clinical trial below.
Title: A Multicentre, Double-blind, Randomised, Placebo - Controlled Phase II Study to Assess Efficacy, Safety and Pharmacokinetics of Inhaled Esketamine in Subject With Treatment-resistant Bipolar Depression
Brief Summary: The purpose of the study is to determine the efficacy, safety and pharmacokinetics of inhaled Esketamine in participants with treatment-resistant bipolar depression (TRBD). The study is to determine the efficacy and dose response of three Esketamine doses, compared with placebo.


Options:
A: Inclusion Criteria:

* Patients with a diagnosis of Major Depressive Disorder, currently depressed without psychotic features
* Females must be of non-childbearing potential.

Exclusion Criteria:

* Treatment with Clozapine or ECT within 3 months prior to study
* Current or past history of psychotic features or a diagnosis of schizophrenia or any other psychotic disorder as defined in the DSM-IV
B: Inclusion Criteria:

1. Age 18 to 65 years
2. A diagnosis of BD type I or II according to SCID-I interview;
3. Currently in a depressive or mixed episode, based on DSM-IV/ SCID-I criteria;
4. MADRAS \>20 at entry in the study;
5. No CURRENT liver, kidney, heart disease or ulcers or bleeding dyscrasia;
6. No HYSTORY of kidney dysfunction or cardiac problems;
7. ON therapeutic doses of a mood stabilizing drug (lithium, anticonvulsants, any atypical antipsychotics) or combinations for at least ONE month.
8. Allowed psychiatric co-morbid conditions, such as anxiety disorders, PTSD and substance use (as long as do NOT meet abuse or dependence criteria according to the SCID-I in the past 2 months).

Exclusion Criteria:

1. CANNOT be on any :

   Anti-inflammatory: NSAIDs: Aspirin (bufferin, bayer aspirin, ecotrin), diflunisal (dolobid, diflunisal),Salsalate (amigesic, salflex), Ibuprofen (motrin, advil), Naproxen (naprosyn,aleve, midol extended relief), Fenoprofen (nalfon), Ketoprofen (actron), dexketoprofen(ketron D), Flurbiprofen (ansaid), Oxaprozin (daypro), Loxoprofen (loxfen, loxonin), Indomethacin (indocin, indocin SR), Sulindac (clinoril), Etodolac (lodine), Ketorolac (toradol), diclofenac (voltaren, cataflam), Nabumetone (Relafen) Piroxicam (feldene), Meloxicam (mobic), Tenoxicam (mobiflex), Lornoxicam (xefo),mefenamic acid (ponstel), meclofenamic acid (meclofenamate sodium), celecoxib (celebrex) Anticoagulants: Coumadin (Warfarin), Heparin Anti-oxidant agents Fish oil NAC ( N-acetyl cysteine)
2. Pregnancy
3. CANNOT change the dose of the psychotropic medications during the trial

Women Able to Become Pregnant: Participation in this study may involve risks to an embryo, fetus, or unborn child. If the subject is a female and able to become pregnant, a urine pregnancy test will be performed which must be negative prior to enrolling into the study, and the subject must agree not to become pregnant during the study. Urine pregnancy tests will be performed at Screening visit and week 8. The study staff will review adequate birth control methods with the subject and will remind her that she should not become pregnant during the study. Appropriate methods of birth control include: hormonal contraceptives (such as birth control pills, patches, and implants), barrier methods (such as a condom and diaphragms and spermicidal foam or jelly, surgical (hysterectomy or tubal ligation) or intrauterine device (IUD). The subject will be instructed to notify the study doctor immediately if there is a chance that she has become pregnant.

Also, if the subject is breast-feeding an infant or plan on breast-feeding an infant, she must notify the study doctor. It is not known if this drug is excreted in human milk; therefore, breast-feeding is not permitted during the study.

Patients can be on any mood stabilizing agents or combinations, as well as on other psychotropic medications at study entry, and the doses of those medications cannot be changed during the trial. They cannot be on any anti-inflammatory or anti-oxidant agents or anticoagulant at the point they are enrolled. If patients decompensate significantly, and/or become acutely suicidal, participation on the trial will be terminated.
C: Inclusion Criteria:

1. Gender: female or male,
2. Age: 18 - 65 years old, inclusive, on the day of Screening,
3. Participant must meet Diagnostic and Statistical Manual of Mental Disorders, fifth edition (DSM-5) diagnostic criteria for depressive episode in Bipolar Disorder (BD) type I or II, without psychotic features, confirmed by the Mini International Neuropsychiatric Interview (MINI),
4. Participant must have in Montgomery-Asberg Depression Rating Scale (MADRS) total score of \>= 24 at Screening and predose on Day 1,
5. Participant is treatment resistant in the current episode of depression, defined as having an inadequate response to at least 2 adequate mood stabilizing treatment regimens administered for the sufficient duration and dose and administered in the current episode of depression,
6. Participant in the last mood stabilizing treatment regimen is to be administered at least one of the medication listed in the protocol,
7. Participant's last mood stabilizing treatment regimen is to be without antidepressant drugs from the class: SSRI, SNRI, TCA, MAOI or NaSSA,
8. Participant must be on stable mood stabilizing treatment regimen (listed in the protocol), remain non-responsive to it and continue the treatment from Screening to at least the duration of the double-blind treatment phase,
9. Participant's other drugs taken as a standard treatment for bipolar disorder, but not for depressive episode treatment, are to be allowed and may be continued through the study and it's administration is up to Investigator discretion,
10. Participant agrees to be hospitalized voluntarily for a period of 12 h before first administration and until the end of treatment phase on Day 14,
11. Participant must be medically stable on the basis of clinical laboratory tests, physical examination, vital signs, 12-lead ECG,
12. Participant agrees to blood sample collection for DNA analysis,
13. Participant of childbearing potential willing to use acceptable forms of contraception.

Exclusion Criteria:

1. Participant has a current DSM-5 diagnosis, according to MINI, of any other than BD disorder,
2. Participant has a BD with a rapid-cycling course (≥ 4 episodes per year),
3. Participant has in Young Mania Rating Scale (YMRS) total score of greater than 12 at Screening and every other assessment,
4. Participant has suicidal ideation in MADRS 'suicidal thoughts' subscale score greater or equal to 2 and/or in C-SSRS score greater or equal to 4 at Screening and/or has a history of suicidal thoughts within 6 months prior to Screening and/or history of suicidal attempt within 1 year prior to Screening,
5. Participant has a history or current signs and symptoms of chronic obstructive pulmonary disease (COPD), asthma, liver or renal insufficiency, significant cardiac, vascular, pulmonary, gastrointestinal, endocrine, hematologic, neurologic, rheumatologic or metabolic disturbances that are uncontrolled with medication change during last three months before Screening and/or that could influence the present general health condition at the Investigator's discretion,
6. Participant has uncontrolled hypertension,
7. Upper respiratory tract and/or chest infection and/or inflammation within 2 weeks preceding the first administration and during the treatment phase,
8. Participant took part in other clinical trial within 90 days preceding the Screening,
9. Known allergy or hypersensitivity, intolerance or contraindication to Esketamine/ketamine or its derivatives and/or to any study product excipients,
10. Blood drawn within 30 days prior to inclusion to the study,
11. History of drug, alcohol, chemical, sedatives or sleeping medications abuse or dependence (except nicotine or caffeine) within 2 years prior to Screening,
12. Lifetime abuse or dependence on ketamine or phencyclidine,
13. Positive results from pregnancy test for female participants,
14. Lactation in female participants,
15. Positive drug screen (except benzodiazepines evaluation during follow-up) or alcohol breath test.
D: Inclusion Criteria:

* Signed informed consent before any study-related procedures start.
* The patient is previously diagnosed with Major Depressive Disorder (MDD) and currently taking an antidepressant for at least 6 weeks.
* Patient has a history of poor response to 1 or more antidepressants (in addition to the antidepressant the patient is taking at enrollment) after exposure at adequate doses or maximum tolerated doses for ≥4 weeks.

Exclusion Criteria:

* Patient has a lifetime history of schizophrenia, bipolar, psychosis or psychotic depression.
* Patient has a lifetime history of failure to ECT therapy.
* Patient is pregnant or breast feeding.
* Length of current episode of depression exceeds ≥2 years.

Answer: C