A Randomized, Double-Blind, Placebo Controlled, Two-Period Cross-Over, Proof of Activity Study to Evaluate the Effects of TAK-041 on Motivational Anhedonia as Add-On to Antipsychotics in Participants With Stable Schizophrenia
Condition: Stable Schizophrenia
MeSH terms: Anhedonia; Schizophrenia
Intervention: TAK-041; Placebo; Second Generation Antipsychotics (SGA)
Intervention description: TAK-041 suspension; TAK-041 placebo-matching suspension; Second generation antipsychotics included risperidone, paliperidone, iloperidone, quetiapine, olanzapine, ziprasidone, asenapine and lurasidone.
Intervention MeSH terms: Antipsychotic Agents
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 23.0
Sex: All
Minimum age: 18 Years
Maximum age: 60 Years
Healthy volunteers: No
Keywords: Drug therapy

Summary:

      The purpose of the study is to determine whether motivation/reward deficits observed in
      schizophrenia are attenuated and whether cognitive impairment associated with schizophrenia
      is improved by add-on TAK-041 administration to antipsychotics in participants with stable
      schizophrenia.
    

Eligibility criteria:

        Inclusion Criteria:

          1. Is on a stable dose of antipsychotics for at least 2 months as documented by medical
             history and assessed by site staff (other than those on the excluded medication list).

          2. Meets schizophrenia criteria as defined by the Diagnostic and Statistical Manual of
             Mental Disorders (DSM-5) by the Mini International Neuropsychiatric Interview (MINI).

          3. Have Positive and Negative Syndrome Scale (PANSS) total score less than or equal to
             (<=) 90 and PANSS Negative Symptom Factor Score ([NSFS]; Sum of PANSS N1, N2, N3, N4,
             N6, G7, and G16) greater than or equal to (>=) 15 at screening and baseline (Day -1).

          4. Has stable Screening and baseline (Day-1) PANSS and NSFS total scores (less than [<]
             20 percent [%] change).

          5. Have had a structural brain magnetic resonance imaging (MRI) within the preceding year
             or during screening indicating no concerning structural brain abnormalities or other
             abnormalities that would interfere with interpretation of functional brain imaging
             results.

        Exclusion Criteria:

          1. Has a history of cancer (malignancy).

          2. Has a positive alcohol and/ or positive drug screen at Screening or Day -1.

          3. Is positive for hepatitis B surface antigen (HBsAg), hepatitis C (HCV) antibody, or
             human immunodeficiency virus (HIV) antibody/antigen (confirmatory testing is allowed;
             most sensitive test should take precedence).

          4. Had major surgery, or donated or lost 1 unit of blood (approximately 500 milliliters
             [mL]) within 4 weeks prior to the pretrial/Screening Visit.

          5. Has abnormal Screening or baseline laboratory values (>upper limit of normal [ULN] for
             the respective serum chemistries) of alanine aminotransferase (ALT), aspartate
             aminotransferase (AST), total bilirubin (TBILI), alkaline phosphatase (ALP),
             γ-glutamyl transferase (GGT) confirmed upon repeat testing, 5'-nucleotidase (Screening
             only), and/or abnormal urine osmolality, confirmed upon repeat testing.

          6. Meets DSM-5 criteria for substance use disorder or history of alcohol abuse within 1
             month prior to Screening Visit.

          7. Has a history of claustrophobia or inability to tolerate mock scanner environment
             during habituation/screening session.

          8. Fulfills any of the MRI contraindications on the site standard radiography screening
             document.

          9. Has a history in the last year from the randomization visit or is currently receiving
             treatment with clozapine.

         10. Has a current diagnosis of a significant psychiatric illness other than schizophrenia,
             per DSM-5 and is in an acute phase or episode.

         11. Has a risk of suicide according to the investigator's clinical judgment (example, per
             C-SSRS positive answers on questions 4 or 5 or has made a suicide attempt within 6
             months prior to screening visit).