A Phase 2 Randomized, Double-Blind, Placebo-Controlled, Cross-Over Study to Evaluate Pharmacodynamic Effects, Safety, Tolerability, and Pharmacokinetics of Multiple Oral Doses of TAK-831 in Adult Subjects With Schizophrenia
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 31
- 试验地点
- 1
- 主要终点
- Change From Baseline in Average Percent of Conditioned Responses During the Eye Blink Conditioning (EBC) Test at Day 8
研究概览
简要总结
The purpose of this study is to determine whether luvadaxistat is superior to placebo in improving cerebellar function as measured with the average percentage of conditioned responses during the eyeblink conditioning (EBC) test.
详细描述
The drug being tested in this study is called luvadaxistat. Luvadaxistat is being tested to treat people with schizophrenia.
Participants will be randomly assigned to one of the two treatment sequences which will remain undisclosed to the participant and study doctor during the study (unless there is an urgent medical need):
- Luvadaxistat 500 milligrams (mg) followed by matching placebo
- Matching placebo followed by luvadaxistat 50 mg
Participants will receive luvadaxistat 500 mg during the treatment period in which they are assigned to luvadaxistat. Following an interim analysis, there will be a study-wide decision about whether to treat the additional participants with luvadaxistat 500 mg during the active treatment period to or treat them with luvadaxistat 50 mg during this period. After the interim analysis, the participant and study doctor will not be aware of which luvadaxistat dose is being used.
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
- •Have a body mass index (BMI) greater than or equal to (>=) 18.5 and less than or equal to (<=) 40.0 (kilogram per square meter [kg/m^2]) at the Screening Visit.
- •With a current Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) diagnosis of schizophrenia who are receiving stable antipsychotic therapy (no increase, no decrease greater than [>] 20% in dose in the preceding 2 months).
- •Positive and Negative Syndrome Scale (PANSS) negative symptom factor score (NSFS) >= 15, stable screening and baseline PANSS NSFS (< 25% change).
- •PANSS total score <= 90; stable screening and baseline PANSS total score (less than [<] 20% change).
- •Receiving stable (no increase, no decrease > 25% in dose in the preceding 2 months)antipsychotic medication at doses not to exceed risperidone 6 mg or its equivalent. Concomitant treatment with a subtherapeutic dose of a second antipsychotic may be permitted with sponsor or designee approval if used as a hypnotic (maximum of quetiapine 300 mg or its equivalent once daily at bedtime) and participants does not show morning sedation as per the investigator opinion, but not if it is used for refractory positive psychosis symptoms. Under this exception, the total daily dose the second antipsychotic will not have to be included in the calculation of the 6 mg/day risperidone-equivalent limit.
排除标准
- •Has a history of cancer (malignancy) excluding treated basal cell carcinoma or treated stage 0 (in situ) cervical carcinoma.
- •Has a history of significant multiple and/or severe allergies (example [eg], food, drug, latex allergy) or has had an anaphylactic reaction or significant intolerability to prescription or nonprescription drugs or food.
- •Has a QT interval with Fridericia's correction method (QTcF) > 450 milliseconds [ms] (males) or > 470 ms (females) confirmed with one repeat testing, at the Screening Visit or Check-in.
- •Has a positive alcohol or drug screen for disallowed substances, including amphetamines, barbiturates, cocaine, marijuana, methadone, methamphetamine, 3,4-methylenedioxymethamphetamine, phencyclidine, or nonprescribed benzodiazepines or opiates.
- •Is positive for hepatitis B surface antigen (HBsAg), hepatitis C antibodies, or has HIV by history (confirmatory testing is allowed; most sensitive test should take precedence).
- •Had major surgery, donated or lost 250 milliliter [mL] of blood within 4 weeks prior to the prestudy (screening) visit.
- •Has a known hypersensitivity to any component of the formulation of luvadaxistat.
- •Has a history of significant skin reactions (hypersensitivity) to adhesives, metals or plastic.
- •Is considered by the investigator to be at imminent risk of suicide or injury to self, others, or property, or participants who within the past year prior to Screening have attempted suicide. Participants who have positive answers on item 4 or 5 on the Columbia Suicide Severity Rating Scale (C-SSRS) (based on the past year) prior to randomization are excluded.
研究组 & 干预措施
Luvadaxistat 500 mg, then Placebo
Participants first received luvadaxistat 500 mg orally once daily (QD) for 8 days during treatment period 1. After a washout of 14 to 21 days, participants then received matching placebo orally QD for 8 days during treatment period 2.
干预措施: Luvadaxistat (Drug)
Luvadaxistat 500 mg, then Placebo
Participants first received luvadaxistat 500 mg orally once daily (QD) for 8 days during treatment period 1. After a washout of 14 to 21 days, participants then received matching placebo orally QD for 8 days during treatment period 2.
干预措施: Matching Placebo (Drug)
Placebo, then Luvadaxistat 500 mg
Participants first received matching placebo orally QD for 8 days during treatment period 1. After a washout of 14 to 21 days, participants then received luvadaxistat 500 mg orally QD for 8 days during treatment period 2.
干预措施: Luvadaxistat (Drug)
Placebo, then Luvadaxistat 500 mg
Participants first received matching placebo orally QD for 8 days during treatment period 1. After a washout of 14 to 21 days, participants then received luvadaxistat 500 mg orally QD for 8 days during treatment period 2.
干预措施: Matching Placebo (Drug)
Luvadaxistat 50 mg, then Placebo
Participants first received luvadaxistat 50 mg orally QD for 8 days during treatment period 1. After a washout of 14 to 21 days, participants then received matching placebo orally QD for 8 days during treatment period 2.
干预措施: Luvadaxistat (Drug)
Luvadaxistat 50 mg, then Placebo
Participants first received luvadaxistat 50 mg orally QD for 8 days during treatment period 1. After a washout of 14 to 21 days, participants then received matching placebo orally QD for 8 days during treatment period 2.
干预措施: Matching Placebo (Drug)
Placebo, then Luvadaxistat 50 mg
Participants first received matching placebo orally QD for 8 days during treatment period 1. After a washout of 14 to 21 days, participants then received luvadaxistat 50 mg orally QD for 8 days during treatment period 2.
干预措施: Luvadaxistat (Drug)
Placebo, then Luvadaxistat 50 mg
Participants first received matching placebo orally QD for 8 days during treatment period 1. After a washout of 14 to 21 days, participants then received luvadaxistat 50 mg orally QD for 8 days during treatment period 2.
干预措施: Matching Placebo (Drug)
结局指标
主要结局
Change From Baseline in Average Percent of Conditioned Responses During the Eye Blink Conditioning (EBC) Test at Day 8
时间窗: Baseline, Day 8 of each treatment period
EBC is a method used to investigate cerebellar-dependent learning. In EBC, a conditioned stimulus, a tone precedes but co-terminates with an unconditioned stimulus, an airpuff to the eyelid. Learning is demonstrated when an eyeblink (the conditioned response) occurs prior to the onset of the unconditioned stimulus. The percentage can range from 0% (no conditioned learning has occurred) to 100% (all responses are conditioned). Results are reported as least squares (LS) means at Day 8, determined using an analysis of variance (ANOVA).
次要结局
- Change From Baseline in the Mean P300 Amplitude at Day 8(Baseline, Day 8 of each treatment period)
- Change From Baseline in the Mean Plasma D-serine to Total Serine Ratio at Day 8(Baseline and Day 8 of each treatment period)
- Change From Baseline in the Mean Mismatch Negativity (MMN) at Day 8(Baseline, Day 8 of each treatment period)
- Change From Baseline on the Brief Assessment of Cognition in Schizophrenia (BACS) Composite Score at Day 7(Baseline, Day 7 of each treatment period)
- Change From Baseline in the Mean Plasma Concentrations of D-serine and L-serine at Day 8(Day 1 and at multiple time points (up to 6 hours) to Day 8 pre-dose)
- Change From Baseline in the Mean Auditory Steady State Response (ASSR) at Day 8(Baseline, Day 8 of each treatment period)
- Mean Plasma Concentration of Luvadaxistat(Day 1 0.25 to 2 hours and 3 to 6 hours post-dose, Day 7 pre-dose, 0.25 to 2 hours and 3 to 6 hours post-dose, and Day 8 pre-dose)