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    Summary
    EudraCT Number:2017-002232-16
    Sponsor's Protocol Code Number:TAK-653-2001
    National Competent Authority:UK - MHRA
    Clinical Trial Type:EEA CTA
    Trial Status:Prematurely Ended
    Date on which this record was first entered in the EudraCT database:2017-09-14
    Trial results View results
    Index
    A. PROTOCOL INFORMATION
    B. SPONSOR INFORMATION
    C. APPLICANT IDENTIFICATION
    D. IMP IDENTIFICATION
    D.8 INFORMATION ON PLACEBO
    E. GENERAL INFORMATION ON THE TRIAL
    F. POPULATION OF TRIAL SUBJECTS
    G. INVESTIGATOR NETWORKS TO BE INVOLVED IN THE TRIAL
    N. REVIEW BY THE COMPETENT AUTHORITY OR ETHICS COMMITTEE IN THE COUNTRY CONCERNED
    P. END OF TRIAL
    Expand All   Collapse All
    A. Protocol Information
    A.1Member State ConcernedUK - MHRA
    A.2EudraCT number2017-002232-16
    A.3Full title of the trial
    A Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Efficacy and Safety of TAK-653 in the Treatment of Subjects with Treatment-Resistant Depression
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    A Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Efficacy and Safety of TAK-653 in the Treatment of Subjects with Treatment-Resistant Depression
    A.3.2Name or abbreviated title of the trial where available
    Efficacy and Safety of TAK-653 in Treatment-Resistant Depression
    A.4.1Sponsor's protocol code numberTAK-653-2001
    A.5.4Other Identifiers
    Name:INDNumber:134,863
    A.7Trial is part of a Paediatric Investigation Plan No
    A.8EMA Decision number of Paediatric Investigation Plan
    B. Sponsor Information
    B.Sponsor: 1
    B.1.1Name of SponsorMillennium Pharmaceuticals, Inc, a wholly owned subsidiary of Takeda Pharmaceutical Company, Ltd
    B.1.3.4CountryUnited States
    B.3.1 and B.3.2Status of the sponsorCommercial
    B.4 Source(s) of Monetary or Material Support for the clinical trial:
    B.4.1Name of organisation providing supportMillennium Pharmaceuticals, Inc, a wholly owned subsidiary of Takeda Pharmaceutical Company, Ltd
    B.4.2CountryUnited States
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisationMillennium Pharmaceuticals, Inc.
    B.5.2Functional name of contact pointTheresa Walls
    B.5.3 Address:
    B.5.3.1Street Address35 Landsdowne St.
    B.5.3.2Town/ cityCambridge
    B.5.3.3Post codeMA 02139
    B.5.3.4CountryUnited States
    B.5.6E-mailclinicaloperations@takeda.com
    D. IMP Identification
    D.IMP: 1
    D.1.2 and D.1.3IMP RoleTest
    D.2 Status of the IMP to be used in the clinical trial
    D.2.1IMP to be used in the trial has a marketing authorisation No
    D.2.5The IMP has been designated in this indication as an orphan drug in the Community No
    D.2.5.1Orphan drug designation number
    D.3 Description of the IMP
    D.3.1Product nameTAK-653
    D.3.2Product code TAK-653
    D.3.4Pharmaceutical form Tablet
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPOral use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNTBD
    D.3.9.1CAS number 1358751-06-0
    D.3.9.2Current sponsor codeTAK-653
    D.3.9.3Other descriptive nameTAK-653
    D.3.9.4EV Substance CodeSUB177200
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number1
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNTBD
    D.3.9.1CAS number 1358751-06-0
    D.3.9.2Current sponsor codeTAK-653
    D.3.9.3Other descriptive nameTAK-653
    D.3.9.4EV Substance CodeSUB177200
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number5
    D.3.11 The IMP contains an:
    D.3.11.1Active substance of chemical origin Yes
    D.3.11.2Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP) No
    The IMP is a:
    D.3.11.3Advanced Therapy IMP (ATIMP) No
    D.3.11.3.1Somatic cell therapy medicinal product No
    D.3.11.3.2Gene therapy medical product No
    D.3.11.3.3Tissue Engineered Product No
    D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) No
    D.3.11.3.5Committee on Advanced therapies (CAT) has issued a classification for this product No
    D.3.11.4Combination product that includes a device, but does not involve an Advanced Therapy No
    D.3.11.5Radiopharmaceutical medicinal product No
    D.3.11.6Immunological medicinal product (such as vaccine, allergen, immune serum) No
    D.3.11.7Plasma derived medicinal product No
    D.3.11.8Extractive medicinal product No
    D.3.11.9Recombinant medicinal product No
    D.3.11.10Medicinal product containing genetically modified organisms No
    D.3.11.11Herbal medicinal product No
    D.3.11.12Homeopathic medicinal product No
    D.3.11.13Another type of medicinal product No
    D.8 Information on Placebo
    D.8 Placebo: 1
    D.8.1Is a Placebo used in this Trial?Yes
    D.8.3Pharmaceutical form of the placeboTablet
    D.8.4Route of administration of the placeboOral use
    E. General Information on the Trial
    E.1 Medical condition or disease under investigation
    E.1.1Medical condition(s) being investigated
    E.1.1.1Medical condition in easily understood language
    Treatment Resistant Depression
    E.1.1.2Therapeutic area Psychiatry and Psychology [F] - Mental Disorders [F03]
    MedDRA Classification
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 20.0
    E.1.2Level PT
    E.1.2Classification code 10057840
    E.1.2Term Major depression
    E.1.2System Organ Class 10037175 - Psychiatric disorders
    E.1.3Condition being studied is a rare disease No
    E.2 Objective of the trial
    E.2.1Main objective of the trial
    To evaluate the efficacy of TAK-653 compared with placebo in maintaining the effect of ketamine treatment on depressive symptoms
    E.2.2Secondary objectives of the trial
    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).
    E.2.3Trial contains a sub-study No
    E.3Principal 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.
    E.4Principal 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.
    19. The subject has a positive test result for hepatitis B surface antigen (HBsAg) or hepatitis C virus antibody (anti-HCV), or is known to be human immunodeficiency virus (HIV) positive, at Screening (Visit 1).
    20. The subject has a known hypersensitivity to any component of the formulation of TAK-653.
    21. The subject has any contraindication to the administration of ketamine.
    22. The subject has taken any excluded medication or food product or received any excluded procedure during the time periods listed in Section 7.3.
    23. The subject has poor peripheral venous access.
    24. If female, the subject is pregnant or lactating or intending to become pregnant before participating in this study, during the study, and within 40 days after last dose of the study drug; or intending to donate ova during such time period.
    25. If male, the subject intends to donate sperm during the course of this study or within 100 days after the last dose of study drug.
    E.5 End points
    E.5.1Primary 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.
    E.5.1.1Timepoint(s) of evaluation of this end point
    time from the date of randomization until day 57 / early termination
    E.5.2Secondary 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.
    E.5.2.1Timepoint(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
    E.6 and E.7 Scope of the trial
    E.6Scope of the trial
    E.6.1Diagnosis No
    E.6.2Prophylaxis No
    E.6.3Therapy No
    E.6.4Safety Yes
    E.6.5Efficacy Yes
    E.6.6Pharmacokinetic Yes
    E.6.7Pharmacodynamic No
    E.6.8Bioequivalence No
    E.6.9Dose response No
    E.6.10Pharmacogenetic No
    E.6.11Pharmacogenomic Yes
    E.6.12Pharmacoeconomic No
    E.6.13Others No
    E.7Trial type and phase
    E.7.1Human pharmacology (Phase I) No
    E.7.1.1First administration to humans No
    E.7.1.2Bioequivalence study No
    E.7.1.3Other No
    E.7.1.3.1Other trial type description
    E.7.2Therapeutic exploratory (Phase II) Yes
    E.7.3Therapeutic confirmatory (Phase III) No
    E.7.4Therapeutic use (Phase IV) No
    E.8 Design of the trial
    E.8.1Controlled Yes
    E.8.1.1Randomised Yes
    E.8.1.2Open No
    E.8.1.3Single blind No
    E.8.1.4Double blind Yes
    E.8.1.5Parallel group No
    E.8.1.6Cross over No
    E.8.1.7Other No
    E.8.2 Comparator of controlled trial
    E.8.2.1Other medicinal product(s) No
    E.8.2.2Placebo Yes
    E.8.2.3Other No
    E.8.2.4Number of treatment arms in the trial2
    E.8.3 The trial involves single site in the Member State concerned No
    E.8.4 The trial involves multiple sites in the Member State concerned Yes
    E.8.4.1Number of sites anticipated in Member State concerned4
    E.8.5The trial involves multiple Member States Yes
    E.8.5.1Number of sites anticipated in the EEA15
    E.8.6 Trial involving sites outside the EEA
    E.8.6.1Trial being conducted both within and outside the EEA Yes
    E.8.6.2Trial being conducted completely outside of the EEA No
    E.8.6.3If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned
    Belgium
    Canada
    Germany
    United Kingdom
    United States
    E.8.7Trial has a data monitoring committee No
    E.8.8 Definition of the end of the trial and justification where it is not the last visit of the last subject undergoing the trial
    The end of the study is defined as the date the last subject completes the Follow-up Phone Call (Day 78).
    E.8.9 Initial estimate of the duration of the trial
    E.8.9.1In the Member State concerned years0
    E.8.9.1In the Member State concerned months10
    E.8.9.1In the Member State concerned days15
    E.8.9.2In all countries concerned by the trial years1
    E.8.9.2In all countries concerned by the trial months2
    E.8.9.2In all countries concerned by the trial days14
    F. Population of Trial Subjects
    F.1 Age Range
    F.1.1Trial has subjects under 18 No
    F.1.1.1In Utero No
    F.1.1.2Preterm newborn infants (up to gestational age < 37 weeks) No
    F.1.1.3Newborns (0-27 days) No
    F.1.1.4Infants and toddlers (28 days-23 months) No
    F.1.1.5Children (2-11years) No
    F.1.1.6Adolescents (12-17 years) No
    F.1.2Adults (18-64 years) Yes
    F.1.2.1Number of subjects for this age range: 80
    F.1.3Elderly (>=65 years) Yes
    F.1.3.1Number of subjects for this age range: 10
    F.2 Gender
    F.2.1Female Yes
    F.2.2Male Yes
    F.3 Group of trial subjects
    F.3.1Healthy volunteers No
    F.3.2Patients Yes
    F.3.3Specific vulnerable populations Yes
    F.3.3.1Women of childbearing potential not using contraception No
    F.3.3.2Women of child-bearing potential using contraception Yes
    F.3.3.3Pregnant women No
    F.3.3.4Nursing women No
    F.3.3.5Emergency situation No
    F.3.3.6Subjects incapable of giving consent personally No
    F.3.3.7Others No
    F.4 Planned number of subjects to be included
    F.4.1In the member state10
    F.4.2 For a multinational trial
    F.4.2.1In the EEA 30
    F.4.2.2In the whole clinical trial 90
    F.5 Plans for treatment or care after the subject has ended the participation in the trial (if it is different from the expected normal treatment of that condition)
    None
    G. Investigator Networks to be involved in the Trial
    N. Review by the Competent Authority or Ethics Committee in the country concerned
    N.Competent Authority Decision Authorised
    N.Date of Competent Authority Decision2017-10-12
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2017-12-15
    P. End of Trial
    P.End of Trial StatusPrematurely Ended
    P.Date of the global end of the trial2018-02-01
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