Efficacy and Safety of TAK-653 in Treatment-Resistant Depression

NCT03312894 | Withdrawn Phase 2 FDA Drug

• 5 other identifiers: TAK-653-20012017-002232-16U1111-1200-881717/SC/0606FAGG/R&D/LFT
• Study Type: interventional
• Target: N/A
• Locations: 0 countries
• Sites: N/A

Brief Summary

The purpose of this study is to evaluate the efficacy of TAK-653 compared with placebo in maintaining the effect of ketamine treatment on depressive symptoms.

Conditions

Treatment-Resistant Depression

Keywords

Drug therapy

Outcome Measures

Primary Outcomes (1)

• Cohort 1: Time to Relapse of Depressive Symptoms Postdose as Measured by Montgomery Åsberg Depression Rating Scale (MADRS) Total Score

  The MADRS is a 10-item clinician rated scale to measure overall severity of depressive symptoms. Items are rated on scale of 0 to 6, for a total score range of 0 (low severity of depressive symptoms) to 60 (high severity of depressive symptoms).

  Baseline up to Day 57

Secondary Outcomes (8)

• Cohort 1: Change from Baseline in MADRS Total Score at the End of Each Week of Treatment

  Baseline and weekly up to Day 57

• Cohort 1: Change from Baseline in Clinical Global Impression-Severity Scale (CGI-S) Score at the End of Each Week of Treatment

  Baseline and weekly up to Day 57

• Cohort 1: Change From Baseline in Quick Inventory of Depressive Symptomatology-16 Item (QIDS-SR16) Total Score at the End of Each Week of Treatment

  Baseline and weekly up to Day 57

• Cohort 1: Percentage of Participants with Treatment-Emergent Adverse Events (TEAEs)

  Baseline up to Day 78

• Cohort 1: Percentage of Participants with Treatment-Emergent Adverse Events (TEAEs) that Led to Study Drug Discontinuation

  Baseline up to Day 78

Study Arms (4)

Cohort 1 (Ketamine Responders): TAK-653 6 mg

EXPERIMENTAL

TAK-653 tablets plus TAK-653 placebo-matching tablets, orally, once daily on Days 1 and 2; followed by TAK-653 tablets, orally, once daily on Days 3 and 4; followed by TAK-653 tablets plus TAK-653 placebo-matching tablets, orally, once daily on Days 5 to 7; followed by TAK-653 tablets, orally, once daily on Days 8 to 56.

Drug: TAK-653; Drug: Placebo

Cohort 1 (Ketamine Responders): Placebo

PLACEBO COMPARATOR

TAK-653 placebo-matching tablets, orally, once daily up to Day 56

Drug: Placebo

Cohort 2 (Ketamine Nonresponders): TAK-653 6 mg

EXPERIMENTAL

TAK-653 tablets plus TAK-653 placebo-matching tablets, orally, once daily on Days 1 and 2; followed by TAK-653 tablets, orally, once daily on Days 3 and 4; followed by TAK-653 tablets plus TAK-653 placebo-matching tablets, orally, once daily on Days 5 to 7; followed by TAK-653 tablets, orally, once daily on Days 8 to 56.

Drug: TAK-653; Drug: Placebo

Cohort 2 (Ketamine Nonresponders): Placebo

PLACEBO COMPARATOR

TAK-653 Placebo-matching tablets, orally, once daily up to Day 56

Drug: Placebo

Interventions

TAK-653 DRUG

TAK-653 tablets

Cohort 1 (Ketamine Responders): TAK-653 6 mg; Cohort 2 (Ketamine Nonresponders): TAK-653 6 mg

Placebo DRUG

Placebo-matching tablets

Cohort 1 (Ketamine Responders): Placebo; Cohort 1 (Ketamine Responders): TAK-653 6 mg; Cohort 2 (Ketamine Nonresponders): Placebo; Cohort 2 (Ketamine Nonresponders): TAK-653 6 mg

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Has a primary diagnosis of major depressive disorder (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. Participants 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 participant using the Mini International Neuropsychiatric Interview (MINI).
• Has MDD that is resistant to treatment (i.e., 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 Massachusetts General Hospital - Antidepressant Treatment Response Questionnaire (MGH ATRQ).
• Qualifies as a candidate for receiving ketamine infusions as a treatment for their depression, in the opinion of the investigator.
• Is naive to ketamine treatment.
• Has a Hamilton Depression Rating Scale-17 (HAMD-17) total score of ≥22 at Screening.
• Is on stable pharmacological treatment for depression (≤50% change in dose) during the last 6 weeks prior to Randomization. Participants who are not currently taking pharmacological treatment for depression may be eligible, with the approval of the medical monitor.

You may not qualify if:

• The participant or any immediate family member has a seizure disorder or a history of seizure disorder, except febrile convulsions.
• Is currently diagnosed with a personality disorder, dementia, eating disorder, schizophrenia, schizoaffective disorder, or bipolar disorder.
• Has a history of neurological abnormalities that is judged by the medical monitor to preclude the participant's participation in the study; or brain injury including traumatic injury, perinatal encephalopathy, and postnatal brain damage, blood-brain barrier abnormality, and cavernous angioma.
• Has a history of cerebral arteriosclerosis.
• Is currently diagnosed with glaucoma.
• Is at an imminent risk of suicide per the Columbia - Suicide Severity Rating Scale (C-SSRS) (score of 5) or per the investigator's clinical judgment.
• Has uncontrolled hypertension or a systolic blood pressure of \>150 millimeter of mercury (mm Hg) or diastolic blood pressure \>95 mm Hg at Screening.
• Has a positive urine test result for drugs of abuse (defined as any illicit drug use) at Screening or Day 1.
• Has a blood alcohol content of ≥0.06% at Screening, prior to ketamine infusion (Day -5 or Day -1), or Day 1.
• Is currently diagnosed with abuse of or dependence on alcohol or other drugs (except nicotine). The participant will be allowed to enroll if his/her drug and alcohol abuse/dependence is in full (complete, not partial) sustained (\>1 year) remission.
• Has any contraindication to the administration of ketamine.

Sponsors & Collaborators

• Millennium Pharmaceuticals, Inc.: lead

MeSH Terms

Conditions

Depressive Disorder, Treatment-Resistant

Condition Hierarchy (Ancestors)

Depressive Disorder; Mood Disorders; Mental Disorders

Study Officials

• Medical Director

  Takeda

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 13, 2017
• First Posted: October 18, 2017
• Study Start: February 15, 2018
• Primary Completion: February 28, 2019
• Study Completion: September 30, 2019
• Last Updated: February 22, 2018

Record last verified: 2018-02