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 Subjects With Stable Schizophrenia
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 23
- 试验地点
- 1
- 主要终点
- Change From Baseline in the Brief Assessment of Cognition in Schizophrenia (BACS) Composite Score at Second Testing After TAK-041 Administration
研究概览
简要总结
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.
详细描述
The drug being tested in this study is called TAK-041. TAK-041 is being tested to treat people who have stable schizophrenia. This study will look whether motivation/reward deficits observed in schizophrenia are attenuated and whether cognitive impairment associated with schizophrenia is improved in people who take TAK-041 in addition to standard care.
The study will enroll approximately 32 patients. Participants will be randomly assigned (by chance, like flipping a coin) in 1:1 ratio to one of the two treatment sequences -which will remain undisclosed to the patient and study doctor during the study (unless there is an urgent medical need) to receive either TAK-041 40 mg or Placebo first and then will be crossed over to receive the opposite Intervention.
All participants will be asked to take oral suspension on Day 1 of each Period. There will be a wash-out Period of 35 days between the dosing days in Period 1 and 2.
This single-center trial will be conducted in the United Kingdom. The overall time to participate in this study is approximately 126 to 154 days. Participants will make multiple visits to the clinic plus a final visit 77 days after receiving their last dose of drug for a follow-up assessment.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 60 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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).
- •Meets schizophrenia criteria as defined by the Diagnostic and Statistical Manual of Mental Disorders (DSM-5) by the Mini International Neuropsychiatric Interview (MINI).
- •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).
- •Has stable Screening and baseline (Day-1) PANSS and NSFS total scores (less than [<] 20 percent [%] change).
- •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.
排除标准
- •Has a history of cancer (malignancy).
- •Has a positive alcohol and/ or positive drug screen at Screening or Day -
- •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).
- •Had major surgery, or donated or lost 1 unit of blood (approximately 500 milliliters [mL]) within 4 weeks prior to the pretrial/Screening Visit.
- •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.
- •Meets DSM-5 criteria for substance use disorder or history of alcohol abuse within 1 month prior to Screening Visit.
- •Has a history of claustrophobia or inability to tolerate mock scanner environment during habituation/screening session.
- •Fulfills any of the MRI contraindications on the site standard radiography screening document.
- •Has a history in the last year from the randomization visit or is currently receiving treatment with clozapine.
- •Has a current diagnosis of a significant psychiatric illness other than schizophrenia, per DSM-5 and is in an acute phase or episode.
- •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).
研究组 & 干预措施
Treatment Sequence 1: TAK-041 40 mg/Placebo + Antipsychotics
TAK-041 40 milligram (mg), suspension, orally on Day 1 of Treatment Period 1, followed by 35 day Wash-out Period, followed by TAK-041 placebo-matching, suspension, orally on Day 1 of Treatment Period 2. All participants received a stable dose of antipsychotics as per standard of care throughout the duration of the Treatment Period.
干预措施: TAK-041 (Drug)
Treatment Sequence 1: TAK-041 40 mg/Placebo + Antipsychotics
TAK-041 40 milligram (mg), suspension, orally on Day 1 of Treatment Period 1, followed by 35 day Wash-out Period, followed by TAK-041 placebo-matching, suspension, orally on Day 1 of Treatment Period 2. All participants received a stable dose of antipsychotics as per standard of care throughout the duration of the Treatment Period.
干预措施: Placebo (Drug)
Treatment Sequence 1: TAK-041 40 mg/Placebo + Antipsychotics
TAK-041 40 milligram (mg), suspension, orally on Day 1 of Treatment Period 1, followed by 35 day Wash-out Period, followed by TAK-041 placebo-matching, suspension, orally on Day 1 of Treatment Period 2. All participants received a stable dose of antipsychotics as per standard of care throughout the duration of the Treatment Period.
干预措施: Second Generation Antipsychotics (SGA) (Drug)
Treatment Sequence 2: Placebo/TAK-041 40 mg + Antipsychotics
TAK-041 placebo-matching, suspension, orally on Day 1 of Treatment Period 1, followed by 35 days Wash-out Period, followed by TAK-041 40 mg, suspension, orally on Day 1 of Treatment Period 2. All participants received a stable dose of antipsychotics as per standard of care throughout the duration of the Treatment Period.
干预措施: TAK-041 (Drug)
Treatment Sequence 2: Placebo/TAK-041 40 mg + Antipsychotics
TAK-041 placebo-matching, suspension, orally on Day 1 of Treatment Period 1, followed by 35 days Wash-out Period, followed by TAK-041 40 mg, suspension, orally on Day 1 of Treatment Period 2. All participants received a stable dose of antipsychotics as per standard of care throughout the duration of the Treatment Period.
干预措施: Placebo (Drug)
Treatment Sequence 2: Placebo/TAK-041 40 mg + Antipsychotics
TAK-041 placebo-matching, suspension, orally on Day 1 of Treatment Period 1, followed by 35 days Wash-out Period, followed by TAK-041 40 mg, suspension, orally on Day 1 of Treatment Period 2. All participants received a stable dose of antipsychotics as per standard of care throughout the duration of the Treatment Period.
干预措施: Second Generation Antipsychotics (SGA) (Drug)
Treatment Sequence 3: TAK-041 160 mg/Placebo + Antipsychotics
TAK-041 160 mg, suspension, orally on Day 1 of Treatment Period 1, followed by 35 days Wash-out Period, followed by TAK-041 placebo-matching, suspension, orally on Day 1 of Treatment Period 2. All participants received stable dose of antipsychotics as per standard of care throughout the duration of the Treatment Period.
干预措施: TAK-041 (Drug)
Treatment Sequence 3: TAK-041 160 mg/Placebo + Antipsychotics
TAK-041 160 mg, suspension, orally on Day 1 of Treatment Period 1, followed by 35 days Wash-out Period, followed by TAK-041 placebo-matching, suspension, orally on Day 1 of Treatment Period 2. All participants received stable dose of antipsychotics as per standard of care throughout the duration of the Treatment Period.
干预措施: Placebo (Drug)
Treatment Sequence 3: TAK-041 160 mg/Placebo + Antipsychotics
TAK-041 160 mg, suspension, orally on Day 1 of Treatment Period 1, followed by 35 days Wash-out Period, followed by TAK-041 placebo-matching, suspension, orally on Day 1 of Treatment Period 2. All participants received stable dose of antipsychotics as per standard of care throughout the duration of the Treatment Period.
干预措施: Second Generation Antipsychotics (SGA) (Drug)
Treatment Sequence 4: Placebo/TAK-041 160 mg + Antipsychotics
TAK-041 placebo-matching, suspension, orally on Day 1 of Treatment Period 1, followed by 35 days Wash-out Period, followed by TAK-041 160 mg, suspension, orally on Day 1 of Treatment Period 2. All participants received stable dose of antipsychotics as per standard of care throughout the duration of the Treatment Period.
干预措施: TAK-041 (Drug)
Treatment Sequence 4: Placebo/TAK-041 160 mg + Antipsychotics
TAK-041 placebo-matching, suspension, orally on Day 1 of Treatment Period 1, followed by 35 days Wash-out Period, followed by TAK-041 160 mg, suspension, orally on Day 1 of Treatment Period 2. All participants received stable dose of antipsychotics as per standard of care throughout the duration of the Treatment Period.
干预措施: Placebo (Drug)
Treatment Sequence 4: Placebo/TAK-041 160 mg + Antipsychotics
TAK-041 placebo-matching, suspension, orally on Day 1 of Treatment Period 1, followed by 35 days Wash-out Period, followed by TAK-041 160 mg, suspension, orally on Day 1 of Treatment Period 2. All participants received stable dose of antipsychotics as per standard of care throughout the duration of the Treatment Period.
干预措施: Second Generation Antipsychotics (SGA) (Drug)
结局指标
主要结局
Change From Baseline in the Brief Assessment of Cognition in Schizophrenia (BACS) Composite Score at Second Testing After TAK-041 Administration
时间窗: Baseline (Day -1) and Day 14
BACS is a reliable and sensitive measure of cognitive function in schizophrenia. The BACS consists of items across six subtests: Verbal Memory, Digit Sequencing, Token Motor, Verbal Fluency, Symbol Coding, and Tower of London. The subtest scale scores were used to compute a composite BACS t-score of 50 (20) is the mean (standard deviation) of a relevant index population. Higher values indicate better performance. Bayesian normal linear model was used for analysis.
Blood-Oxygen-Level-Dependent (BOLD) Signal in the Average Ventral Striatum (VS) Region of Interest (ROI) Activation in the Monetary Incentive Delay (MID) Reward Task at First Testing After TAK-041 Administration
时间窗: Day 1
Blood-oxygen-level-dependent imaging, or BOLD-contrast imaging, is a method used in functional magnetic resonance imaging (fMRI) to observe different areas of the brain or other organs, which are found to be active at any given time. The MID task is a reward anticipation paradigm that robustly engages the VS, a key area associated with coding incentive reward. Dysfunctional processing of reward information is associated with motivational impairments in schizophrenia. Motivational impairment is a key aspect of negative symptoms, and has been associated with reduced activity in the VS. Any change in BOLD signal that comes in fMRI is reported.
次要结局
- Percentage of Participants Who Experience at Least One Treatment Emergent Adverse Event (TEAE)(From the first dose of study drug up to 77 days after last dose of study drug (Up to Day 154))
- Percentage of Participants Who Meet the Markedly Abnormal Criteria for Safety Electrocardiogram (ECG) at Least Once Post Dose(From the first dose of study drug up to 77 days after last dose of study drug (Up to Day 154))
- Percentage of Participants Who Meet the Markedly Abnormal Criteria for Safety Laboratory Tests at Least Once Post Dose(From the first dose of study drug up to 77 days after last dose of study drug (Up to Day 154))
- Percentage of Participants Who Meet the Markedly Abnormal Criteria for Vital Sign Measurements At Least Once Post Dose(From the first dose of study drug up to 77 days after last dose of study drug (Up to Day 154))
- Number of Participants With Suicidal Ideation or Suicidal Behavior as Measured Using Columbia-Suicide Severity Rating Scale (C-SSRS)(Baseline (Day -1) and Days 14, 35 and 77)