Clinical trial NCT03359785: A Study to Evaluate Multiple Oral Doses of Luvadaxistat in Adults With Schizophrenia
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Schizophrenia
Keywords: Drug therapy
Lead sponsor: Neurocrine Biosciences
Sponsor class: INDUSTRY
Collaborators: name: Takeda
First posted: 2017-12-02
Enrollment: 31
Sex: ALL
Minimum age (years): 18
Maximum age (years): 60
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

Brief summary: 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.

Detailed description: 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.

Eligibility criteria: Inclusion Criteria:

* 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.

Exclusion Criteria:

* 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.

Primary outcomes:
measure: Change From Baseline in Average Percent of Conditioned Responses During the Eye Blink Conditioning (EBC) Test at Day 8
timeFrame: Baseline, Day 8 of each treatment period
Secondary outcomes:
measure: Change From Baseline in the Mean Mismatch Negativity (MMN) at Day 8
timeFrame: Baseline, Day 8 of each treatment period
measure: Change From Baseline in the Mean P300 Amplitude at Day 8
timeFrame: Baseline, Day 8 of each treatment period
measure: Change From Baseline in the Mean Auditory Steady State Response (ASSR) at Day 8
timeFrame: Baseline, Day 8 of each treatment period
measure: Change From Baseline on the Brief Assessment of Cognition in Schizophrenia (BACS) Composite Score at Day 7
timeFrame: Baseline, Day 7 of each treatment period
measure: Change From Baseline in the Mean Plasma Concentrations of D-serine and L-serine at Day 8
timeFrame: Day 1 and at multiple time points (up to 6 hours) to Day 8 pre-dose
measure: Change From Baseline in the Mean Plasma D-serine to Total Serine Ratio at Day 8
timeFrame: Baseline and Day 8 of each treatment period
measure: Mean Plasma Concentration of Luvadaxistat
timeFrame: 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
Other outcomes:
Locations:
city: Gaithersburg
country: United States
facility: CBH Health, LLC
state: Maryland
Study officials:
References: