Inclusion Criteria:  Each subject must sign an informed consent form (ICF) indicating that he or she understands the purpose of and procedures required for the study and are willing to participate in the study. Participant must meet Diagnostic and Statistical Manual of Mental Disorders -5 Edition -Text Revised (DSM-5) diagnostic criteria for Major Depressive Disorder (MDD), without psychotic features, based upon clinical assessment, and confirmed by the Mini International Neuropsychiatric Interview (MINI). Participant must have had an inadequate response to at least 1 antidepressants in the current episode of depression assessed by the antidepressant treatment response questionnaire (ATRQ), and was taking another oral antidepressant 2 weeks before entering the screening period which will be assessed "non-response" by Montgomery Asberg Depression Rating Scale (MADRS) during the screening period, defined as MADRS total score reduced ≤25%. Comfortable with self-administration of intranasal medication and able to follow instructions provided. A woman of childbearing potential must have a negative serum (β-human chorionic gonadotropin [β-hCG]) at Screening and a negative urine pregnancy test prior to Period 1 randomization on Day 1.  Exclusion Criteria:  Subject has a current DSM-5 diagnosis of psychotic disorder, MDD with psychosis, bipolar, obsessive compulsive disorder (OCD), intellectual disability, Autism spectrum Disorder, borderline personality disorder, antisocial personality disorder, histrionic personality disorder, and narcissistic personality disorder. Subject has suicidal ideation with intent to act within the past 6 months based on the Columbia-Suicide Severity Rating Scale (C-SSRS), or has a history of suicidal behavior within the past year as assessed on the C-SSRS. Subject has uncontrolled hypertension (SBP > 140 mmHg or DBP > 90 mmHg) despite diet, exercise or a stable dose of a permitted anti-hypertensive treatment at Screening or Day 1 prior to Period 1 randomization; or any past history of hypertensive crisis. Subject had a history of severe pulmonary insufficiency or SpO2<93% at screening time or prior to dosing. Anatomical or medical conditions that may impede delivery or absorption of study medication. Subject is a woman who is pregnant, breast-feeding, or planning to become pregnant while enrolled in this study or within 12 weeks after the last dose of study drug. Hepatitis B surface antigen (HBsAg), hepatitis C antibody (HCVAb), syphilis antibody and human immunodeficiency virus (HIV) antibody tests positive. Subject has had major surgery, (e.g., requiring general anesthesia) within 12 weeks before screening, or has surgery planned during the time the subject is expected to participate in the study.