Please select the eligibility criteria that correspond to the clinical trial below.
Title: AXS-05-MDD-301: A Randomized, Double-Blind, Placebo-Controlled Trial of AXS-05 in Subjects With Major Depressive Disorder
Brief Summary: A Phase 3, randomized, double-blind, placebo-controlled, multicenter trial of AXS-05 in patients with major depressive disorder (MDD).


Options:
A: 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 screening.
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, 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) or the M.I.N.I International Neuropsychiatric Interview a short, structured psychiatric interview.
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 two "treatment courses" 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 Massachusetts General Hospital Antidepressant Treatment Response Questionnaire (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 Selective serotonin reuptake inhibitor (SSRI) or Serotonin-norepinephrine reuptake inhibitor (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 Hamilton Depression 17-item Scale (HAMD17) score of \>/=20 at both screening and baseline visits (Day -5/-14 and Day 0).
6. In good general health, as ascertained by medical history, physical examination (PE) (including measurement of supine and standing vital signs), clinical laboratory evaluations, and 12-lead electrocardiogram (ECG).
7. 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 is post-menopausal with her last menses at least one year prior to screening); or
   2. 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.
8. Body mass index between 18-35kg/m2.
9. 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.
10. 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 HAMD score of \<20 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 five years 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.

11. Considered at significant risk for suicide during the course of the study according to any of the following criteria:

12. 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.

13. Has dementia, delirium, amnestic, or any other cognitive disorder.

14. Has a clinically significant abnormality on the screening physical examination that might affect safety, study participation, or confound interpretation of study results.

15. Participation in any clinical trial with an investigational drug or device within the past month or concurrent to study participation.

16. Known history or current episode of:

a. QTcF (a measure of the time between the start of the Q wave and the end of the T wave in the heart's electrical cycle-Fridericia-corrected) ≥450 msec at screening (Visit 1) or randomization b. Syncopal event within the past year. c. Congestive heart failure (CHF) New York Heart Association Criteria \>Stage 2 d. Angina pectoris e. Heart rate \<50 or \>105 beats per minute at screening or randomization

17. Chronic lung disease.

18. 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.

19. 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.

   20. 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.)

   21. History of hyperthyroidism which was treated (medically or surgically) less than six months prior to screening.

   22. 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.

   23. History of positive screening urine test for drugs of abuse at screening: cocaine, amphetamines, barbiturates, opiates.

   24. Chronic use of opiates.
B: Inclusion Criteria:

* Female who is non-pregnant, nonlactating, using an acceptable method of birth control, or is not of child-bearing potential;
* be diagnosed with current major depressive disorder either mild or severe, as evidenced by a score of at least 9 but not more than 20 on the Quick Inventory of Depression Symptomatology - Clinician Rated (QIDS-C);
* be anti-depressant naïve;
* be able to refrain from all use of grapefruit containing products from the time of admission until the last assessment is performed at discharge;
* smokes less than or equal to 10 cigarettes or equivalent daily.

Exclusion Criteria:

* has any current and primary Axis I disorder other than major depressive disorder;
* has any history of bipolar I or II disorder, dysthymia, psychotic depression, psychotic disorders, posttraumatic stress disorder, borderline personality disorder, obsessive compulsive disorder, or eating disorder;
* the duration of the current depressive episode is longer than 2 years at screening;
* has any history of a significant suicide attempt, or poses a current risk of attempting suicide;
* is known to be human immunodeficiency virus (HIV) positive, or positive for hepatitis B surface antigen or hepatitis A antibodies or hepatitis C total antibodies;
* has any clinically significant concurrent endocrine, renal, respiratory, cardiovascular, hematological, immunological, cerebrovascular, neurological, malignancy, or any other concurrent medical condition, or has any history of diabetes mellitus;
* donation of blood within 60 days prior to the anticipated first dose of trial medication.
C: * INCLUSION CRITERIA:

Male or female subjects, 18-70 years of age.

Female subjects of childbearing potential must be using a medically accepted means of contraception.

Each subject must have a level of understanding sufficient to agree to all required tests and examinations.

Each subject must understand the nature of the study and must sign an informed consent document.

Subjects must fulfill the criteria bipolar I or II disorder, current episode depressed without psychotic features as defined in the Diagnostic and Statistical Manual (DSM-IV) based on clinical assessment and confirmed by the Structured Clinical Interview for DSM (SCID-P).

Subjects must have an initial score at Visit 1 and Visit 2 of at least 20 on the MADRS.

Current duration of depressive episode should be at least 4 weeks.

Subjects must have experienced, in the opinion of the investigator, at least one previous major depressive episode as defined in DSM-IV (not including the current major depressive episode).

EXCLUSION CRITERIA:

Presence of psychotic features.

Female subjects who are either pregnant or nursing.

Serious, unstable illnesses including hepatic, renal, gastroenterologic, respiratory, cardiovascular (including ischemic heart disease), endocrinologic, neurologic, immunologic, or hematologic disease.

Subjects with uncorrected hypothyroidism or hyperthyroidism.

Clinically significant abnormal laboratory tests.

Current or past blood dyscrasia.

Documented history of hypersensitivity or intolerance to riluzole.

DSM-IV substance abuse or dependence within the past 90 days. No alcohol or recreational drug use will be permitted during the study.

Treatment with an injectable depot neuroleptic within less than one dosing interval between depot neuroleptic injections prior to visit 2.

Treatment with a reversible monoamine oxidase inhibitor (MAOI), guanethidine, or guanadrel within 1 week or with fluoxetine within 5 weeks prior to Visit 2.

Treatment with any other concomitant medication with primarily central nervous system (CNS) activity, other than specified in Appendix A.

Treatment with clozapine or electroconvulsive therapy (ECT) within 4 weeks prior to Visit 2.

Current diagnosis of schizophrenia or other psychotic disorder as defined in the DSM-IV.

Current Axis I Anxiety Disorder that is clinically significant.

Judged clinically to be at serious suicidal risk.
D: Key Inclusion Criteria:

* Age 18 - 65
* Currently meets DSM-5 criteria for MDD
* Body Mass Index between 18 and 40 kg/m\^2, inclusive

Key Exclusion Criteria:

* Suicide risk
* History of treatment resistance in current depressive episode
* History of electroconvulsive therapy, vagus nerve stimulation, transcranial magnetic stimulation or any experimental central nervous system treatment during the current episode or in the past 6 months
* Pregnant, breastfeeding, or planning to become pregnant or breastfeed during the study

Answer: D