MedDRA version: 20.0 Level: PT Classification code 10057840 Term: Major depression System Organ Class: 10037175 - Psychiatric disorders
Conditions
Interventions
Product Name: TAK-653
Product Code: TAK-653
Pharmaceutical Form: Tablet
INN or Proposed INN: TBD
CAS Number: 1358751-06-0
Sponsors
Millennium Pharmaceuticals, Inc, a wholly owned subsidiary of Takeda Pharmaceutical Company, Ltd
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Subject eligibility is determined according to the following criteria prior to entry into the study: 1. The subject signs and dates a written informed consent form. 2. The subject is male or female and aged 18 to 65 years, inclusive, at the time of informed consent. 3. The subject, if male, weighs more than or equal to 50 kg (110 lbs) and, if female, weighs more than or equal to 45 kg (99 lbs). 4. The subject has a body mass index (BMI) between 18.5 and 35.0 kg/m2, inclusive. 5. The subject has a primary diagnosis of MDD, without psychotic features, according to Diagnostic and Statistical Manual of Mental Disorders, 5th Edition (DSM 5) criteria, as assessed by a board-certified psychiatrist. MDD should be the principal diagnosis and the condition that best accounts for the clinical presentation. Subjects with a secondary diagnosis of generalized anxiety disorder or social anxiety disorder may be included if, in the principal investigator’s judgment, such diagnosis will not interfere with participation in the study or with outcome assessments. The diagnostic assessment must include a face-to-face evaluation of the subject using the Mini International Neuropsychiatric Interview (MINI). 6. The subject has MDD that is resistant to treatment (ie, TRD), defined as failure to respond to at least 2, but not more than 5, adequate trials of pharmacological treatment in the current episode, as determined using the MGH ATRQ. 7. The subject qualifies as a candidate for receiving ketamine infusions as a treatment for their depression, in the opinion of the investigator. 8. The subject is naïve to ketamine treatment. 9. The subject has a HAMD-17 total score of =22 at Screening (Visit 1). 10. The subject is on stable pharmacological treatment for depression (=50% change in dose) during the last 6 weeks prior to Randomization (Visit 4). Subjects who are not currently taking pharmacological treatment for depression may be eligible, with the approval of the medical monitor. 11. The subject is euthyroid. An abnormally high or low thyroid-stimulating hormone level may be corroborated by T3 and T4 levels in addition to a comprehensive history and physical examination to rule out a thyroid disorder. Subjects maintained on thyroid medication must be euthyroid for a period of =6 months prior to Screening (Visit 1). 12. A male subject who is nonsterilized and sexually active with a female partner of childbearing potential agrees to use barrier method of contraception (eg, condom with or without spermicide) from signing of informed consent throughout the duration of the study and for 100 days after the last dose of study drug. The female partner of a male subject should also be advised to use a highly effective method of contraception. 13. A female subject of childbearing potential who is sexually active with a nonsterilized male partner agrees to use a highly effective method of contraception from signing of informed consent throughout the duration of the study and for 40 days after the last dose of study drug. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 80
Exclusion criteria
Exclusion criteria: Any subject who meets any of the following criteria will not qualify for entry into the study: 1. The subject is found to be a match in the subject registry database with a subject who has participated in another study within the last 30 days (or at any time for an excluded medical or psychiatric condition). 2. The subject has received any investigational compound within 90 days prior to the first dose of study drug. 3. The subject is an immediate family member, study site employee, or is in a dependent relationship with a study site employee who is involved in conduct of this study (eg, spouse, parent, child, sibling) or may consent under duress. 4. The subject has any active or unstable medical condition or an abnormality that may affect safety, increase risk of seizure, or lower the seizure threshold, or may put them at risk due to their participation in this study, as judged by the investigator. 5. The subject or any immediate family member has a seizure disorder or a history of seizure disorder, except febrile convulsions. 6. The subject is currently diagnosed with a personality disorder, dementia, eating disorder, schizophrenia, schizoaffective disorder, or bipolar disorder. 7. The subject has a history of neurological abnormalities that is judged by the medical monitor to preclude the subject’s participation in the study; or brain injury including traumatic injury, perinatal encephalopathy, and postnatal brain damage, blood-brain barrier abnormality, and cavernous angioma. 8. The subject has a history of cerebral arteriosclerosis. 9. The subject is currently diagnosed with glaucoma. 10. The subject is at an imminent risk of suicide per the C-SSRS (score of 5) or per the investigator’s clinical judgment. 11. The subject has a history of cancer, except basal cell carcinoma that has been in remission for =5 years prior to Screening (Visit 1). 12. The subject has known gastrointestinal (GI) disease or GI procedure that could interfere with the oral absorption or tolerance of TAK-653, including difficulty swallowing tablets. 13. The subject has an abnormal and clinically-significant ECG at Screening (Visit 1). 14. The subject has abnormal Screening (Visit 1) clinical laboratory values that, in the opinion of the investigator, suggest a clinically-significant underlying disease. Subjects with liver function test (LFT) results that meet any of the discontinuation or withdrawal criteria must be excluded (see Section 7.4). 15. The subject has uncontrolled hypertension or a systolic blood pressure of >150 mm Hg or diastolic blood pressure >95 mm Hg at Screening (Visit 1). 16. The subject has a positive urine test result for drugs of abuse (defined as any illicit drug use) at Screening (Visit 1) or Day 1 (Visit 4). 17. The subject has a blood alcohol content of =0.06% at Screening (Visit 1), prior to ketamine infusion (Day -5 or Day -1), or Day 1 (Visit 4). 18. The subject is currently diagnosed with abuse of or dependence on alcohol or other drugs (except nicotine). The subject will be allowed to enroll if his/her drug and alcohol abuse/dependence is in full (complete, not partial) sustained (>1 year) remission.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To evaluate the efficacy of TAK-653 compared with placebo in maintaining the effect of ketamine treatment on depressive symptoms; Primary end point(s): Cohort 1 (ketamine responders): Time to relapse of depressive symptoms after treatment with study drug, as measured by Montgomery Åsberg Depression Rating Scale (MADRS) total score. ;Timepoint(s) of evaluation of this end point: time from the date of randomization until day 57 / early termination; Secondary Objective: To evaluate the overall effect of TAK-653 on subjects' illness. To evaluate the effect of TAK-653 on subjects' self-report of overall depressive symptom severity. To evaluate the safety and tolerability of TAK-653 in subjects with treatment-resistant depression (TRD). | — |
Secondary
| Measure | Time frame |
|---|---|
| Timepoint(s) of evaluation of this end point: a, b and c) At end of each week of treatment with study drug d and f) from the date of randomization until day 57 e) from the date of randomization until early termination ; Secondary end point(s): Cohort 1 (ketamine responders): a) Change from Baseline in MADRS total score at the end of each week of treatment with study drug. b) Change from Baseline in Clinical Global Impression–Severity Scale (CGI-S) score at the end of each week of treatment with study drug. c) Change from Baseline in Quick Inventory of Depressive Symptomatology–16 item (QIDS-SR16) total score at the end of each week of treatment with study drug. d) Percentage of subjects with TEAEs after treatment with study drug. e) Percentage of subjects with TEAEs that led to study drug discontinuation after treatment. f) Percentage of subjects with markedly abnormal values (MAVs) for vital signs, clinical laboratory tests, or ECG parameters after treatment with study drug. | — |
Countries
Belgium, Canada, Germany, United Kingdom, United States
Contacts
Public ContactTheresa Walls
Millennium Pharmaceuticals, Inc.
Outcome results
None listed