Schizophrenia MedDRA version: 20.0 Level: PT Classification code 10039626 Term: Schizophrenia System Organ Class: 10037175 - Psychiatric disorders
Conditions
Interventions
Product Name: TAK-831
Pharmaceutical Form: Tablet
INN or Proposed INN: TAK-831
Current Sponsor code: TAK-831
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 10-
Pha
Sponsors
Takeda Development Centre Europe Ltd.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Understand the study procedures and agree to participate by providing written informed consent. 2. Be willing and able to comply with all study procedures and restrictions (see Sections 7.3 and 7.4 for a summary of restrictions). 3. Be male or a female aged 18 to 50 years, inclusive, at the Screening Visit. 4. Have a body mass index (BMI) =18.5 and =33.0 (kg/m2) at the Screening Visit. 5. Had a structural brain MRI within the preceding year or during screening indicating no concerning structural brain abnormalities or that would interfere with interpretation of functional brain imaging results. 6. Be judged to be in good health by the investigator, based on clinical evaluations including laboratory safety tests, medical history, physical examination, 12-lead ECG, and vital sign measurements performed at the Screening Visit and prior to administration of the initial dose of study drug/invasive procedure. 7. Meet the following birth control requirements: – Is a male subject who is sterile or agrees to use an appropriate method of contraception, including a condom with spermicide, from study drug administration on the first day of the first dose until 5 half lives plus 90 days after the last dose of study drug administration. No restrictions are required for a vasectomized male subject provided the subject is at least 1 year post–bilateral vasectomy procedure prior to study drug administration on first day of the first dose. A male subject whose vasectomy procedure was performed less than 4 months prior to study drug administration on the first day of the first dose must follow the same restrictions as a nonvasectomized male. Appropriate documentation of surgical procedure should be provided. – Is a male subject who agrees to not donate sperm from study drug administration on the first day of the first dose until 5 half lives plus 90 days after the last dose of study drug administration. – Is a female subject with no childbearing potential, defined by at least 1 of the following criteria: a) Postmenopausal (defined as 12 months of spontaneous amenorrhea in females aged >45 years, 6 months of spontaneous amenorrhea in females aged >45 years with serum follicle-stimulating hormone [FSH] levels >40 mIU/mL). Appropriate documentation of FSH levels is required. b) Surgically sterile by hysterectomy and/or bilateral oophorectomy with appropriate documentation of surgical procedure. c) Had a tubal ligation with appropriate documentation of surgical procedure. d) Has a congenital condition resulting in no uterus. – Is a female subject with child-bearing potential must have the following criteria: a) A negative pregnancy test at Screening and Baseline. b) Agrees to use 2 forms of contraception methods. c) Is not breastfeeding. 8. With a current DSM-5 diagnosis of schizophrenia who are receiving stable antipsychotic therapy (no increase, no decrease >20% in dose in the preceding 2 months). 9. With stable screening and baseline PANSS total and NSFS scores (<20% change); PANSS total =90; NSFS =15. 10. Receiving stable antipsychotic medication at doses not to exceed risperidone 10 mg or its equivalent. 11. Able to swallow study drug in tablet form. 12. Should a patient require a caregiver to accompany him/her during the study, the caregiver should be available for the full duration of the study. 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 subje
Exclusion criteria
Exclusion criteria: 1. Has participated in another investigational study within 30 days prior to the prestudy (screening) visit or 450 ms (males) or >470 ms (females) confirmed with one repeat testing, at the Screening Visit or Check-in. 6. Has a positive alcohol or drug screen. 7. Has a positive pregnancy test or plan to become pregnant during the study (female subjects only). 8. Is positive for hepatitis B surface antigen (HBsAg), hepatitis C antibodies, or human immunodeficiency virus (HIV) (confirmatory testing is allowed; most sensitive test should take precedence). 9. Had major surgery, donated or lost 250 mL of blood within 4 weeks prior to the prestudy (screening) visit. 10. Use of disallowed concomitant medications. 11. Is unable to refrain from or anticipates the use of any medication (except those prescribed), including prescription and nonprescription drugs or herbal remedies beginning approximately 7 days prior to administration of the initial dose of study drug, throughout the study (including washout intervals between treatment periods), until the poststudy visit. There may be certain medications that are permitted, see Section 7.3. 12. Consumes >15 cigarettes/day or is unable to refrain from nicotine consumption for >5 hours 13. Unwilling or unable to comply with the requirements of the protocol, including inability to participate in magnetic resonance imaging (MRI) scanning. 14. Subject has a known hypersensitivity to any component of the formulation of TAK-831 15. If male, the subject intends to donate sperm during the course of this study or for 184 days (ie, 90 days after 5 half-lives) have elapsed since the last dose of study drug. 16. Subject has a history of significant skin reactions (hypersensitivity) to adhesives, metals or plastic. 17. The subject is considered by the investigator to be at imminent risk of suicide or injury to self, others, or property, or subjects who within the past year prior to Screening have attempted suicide. Subjects who have positive answers on item 4 or 5 on the C-SSRS (based on the past year) prior to randomization are excluded. 18. Ongoing disability, medical or neurological history, cognitive impairment or conditions that, in the opinion of the investigator, may interfere with study conduct or clinical assessments, including but not limited to: a) Panic attacks, depressive episode or other major psychiatric comorbid conditions within the preceding 6 months. b) Substance abuse or dependence (with the exception of nicotine dependence) within the preceding 12 months. c) Positive drug screen for disallowed substances. d) Evidence of extrapyramidal AEs as measured by a SAS score >6 e) Evidence of depressio
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To determine whether TAK-831 is superior to placebo in improving the average % of conditioned responses during the eyeblink conditioning (EBC) test.;Secondary Objective: To determine whether add-on TAK-831 can be discriminated from placebo during the Task Set Switching (TSS) paradigm as measured by the pattern of functional magnetic resonance imaging (fMRI) blood oxygen level-dependent activation. To determine whether add-on TAK- 831 compared to placebo increases ventral striatum activation as measured by fMRI BOLD during the monetary incentive delay task (MID). To determine whether add-on TAK-831 compared to placebo improves sensory processing as measured by event-related potentials (ERPs) mismatch negativity (MMN) and p300. To determine whether add-on TAK-831 compared to placebo improves the auditory steadystate response (ASSR) to 40 Hz stimulation. To determine whether addon TAK-831 compared to placebo increases cerebellar blood flow as measured by arterial spin labeling (ASL). To determine whether add-on TAK-831 compared to placebo improves the composite score of a neurocognitive test battery.;Primary end point(s): Average % of conditioned responses during the EBC test.;Timepoint(s) of evaluation of this end point: Day 8 | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): 1.Computed probability that the pattern of fMRI BOLD activation during the TSS paradigm came from a subject receiving add-on TAK- 831 treatment at that time. 2.fMRI BOLD signal in the ventral striatum during the anticipation period of reward trials vs the anticipation period of the neutral trials of the MID. 3.MMN amplitude at Fz (electroencephalogram [EEG]). 4.P300 amplitude at midline parietal electrode (Pz) (EEG). 5.ASSR at midline central electrode (Cz) (EEG). 6.Cerebellar blood flow (CBF) using ASL in cerebellar grey matter. 7.Cognitive battery composite score. 8.Plasma D-serine and L-serine levels, and plasma D-serine:total serine ratio. 9.TAK-831 plasma concentrations.;Timepoint(s) of evaluation of this end point: Day 8 | — |
Countries
United Kingdom
Contacts
Public ContactStudy Manager
Takeda Development Centre Europe Ltd
Outcome results
None listed