Stable SchizophreniaPhase 2NCT03319953

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

A Phase 2 study testing TAK-041 and Second Generation Antipsychotics (SGA) in people with Stable Schizophrenia, run by Neurocrine Biosciences at 1 site in United Kingdom.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial 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. Read more about this study

Who is it for?: Ages 18 to 60 years
Conditions the study is for: Stable Schizophrenia
What is being tested?: TAK-041 and Second Generation Antipsychotics (SGA)
Type of treatment: Pill or oral medicine
Could I receive a placebo?: Yes, some participants may receive a placebo
How many people: 23 participants
Where: 1 siteUnited Kingdom
Study dates: 21 Dec 2017to 6 Nov 2019
Phase: Phase 2
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 to 60 years
All sexes
No healthy volunteers
Adult

Who may be able to join

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.

Who cannot join

Has a history of cancer (malignancy).
Has a positive alcohol and/ or positive drug screen at Screening or Day -1.
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.

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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).

Trial locations and contacts

1 site in 1 country.

United Kingdom1 site

Kings College London
London, SE58AF

Other trials in United Kingdom

About this study

Official title: 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

Read the detailed description

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.

Conditions: Stable Schizophrenia
Being tested: TAK-041, Placebo, Second Generation Antipsychotics (SGA)
Keywords: Drug therapy

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

TAK-041Drug
TAK-041 suspension
PlaceboDrug
TAK-041 placebo-matching suspension
Second Generation Antipsychotics (SGA)Drug
Second generation antipsychotics included risperidone, paliperidone, iloperidone, quetiapine, olanzapine, ziprasidone, asenapine and lurasidone.

Study groups in NCT03319953
Study group	Role	What they receive
Treatment Sequence 1: TAK-041 40 mg/Placebo + Antipsychotics	Experimental	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. Receives: Drug: TAK-041; Drug: Placebo; Drug: Second Generation Antipsychotics (SGA)
Treatment Sequence 2: Placebo/TAK-041 40 mg + Antipsychotics	Experimental	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. Receives: Drug: TAK-041; Drug: Placebo; Drug: Second Generation Antipsychotics (SGA)
Treatment Sequence 3: TAK-041 160 mg/Placebo + Antipsychotics	Experimental	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. Receives: Drug: TAK-041; Drug: Placebo; Drug: Second Generation Antipsychotics (SGA)
Treatment Sequence 4: Placebo/TAK-041 160 mg + Antipsychotics	Experimental	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. Receives: Drug: TAK-041; Drug: Placebo; Drug: Second Generation Antipsychotics (SGA)

What is being measured

The primary outcome is the main question the study is designed to answer.

Change From Baseline in the Brief Assessment of Cognition in Schizophrenia (BACS) Composite Score at Second Testing After TAK-041 Administration
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.
Measured: Baseline (Day -1) and Day 14
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
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.
Measured: Day 1

Secondary outcomes (5)

Percentage of Participants Who Experience at Least One Treatment Emergent Adverse Event (TEAE)
An Adverse Event (AE) is defined as any untoward medical occurrence in a clinical investigation participant administered a drug; it does not necessarily have to have a causal relationship with this treatment. A TEAE is defined as an adverse event with an onset that occurs after receiving study drug.
Measured: 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
Clinical Laboratory parameters included tests for chemistry, hematology and urinalysis. Markedly abnormal values during treatment period were categorized as: alanine aminotransferase (ALT)>3.0 U/L*upper limit of normal(ULN),albumin<25 g/L*lower limit of normal(LLN), alkaline phosphatase >3.0 U/L*ULN, aspartate aminotransferase >3.0 U/L*ULN, bilirubin >34.2 umol/L*ULN, calcium <1.75 mmol/L, >2.88 mmol/L, chloride <75 mmol/L, >126 mmol/L, creatinine >177umol/L, gamma glutamyl transferase >3 U/L*ULN, glucose <2.8 mmol/L, >19.4 mmol/L, potassium<3 mmol/L, >6 mmol/L, sodium <130 mmol/L, >150 mmol/L,Urea <130 mmol/L, erythrocytes <0.8*LLN >1.2*ULN, hematocrit <0.8*LLN, >1.2*ULN, hemoglobin <0.8 g/L*LLN, >1.2 g/L*ULN, leukocytes <0.5 (10^9/L)*LLN, >1.5 (10^9/L)*ULN, platelets <75(10^9/L), >600(10^9/L).
Measured: 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
Vital signs included oral body temperature measurement, supine and standing blood pressure, respiration rate, and pulse. Pulse and blood pressure were measured after 5 minutes supine and again at 1 and 3 minutes after standing. The markedly abnormal value (MAV) criteria for vital signs included systolic blood pressure < 85 mmHg, > 180 mmHg; diastolic blood pressure < 50 mmHg, > 110 mmHg; pulse < 50 beats/min, > 120 beats/min; temperature < 35.6 C > 37.7 C.
Measured: 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
The markedly abnormal value (MAV) criteria for 12-lead ECG parameters included ECG Mean Heart Rate < 50 beats/min, > 120 beats/min; PR Interval, Aggregate <= 80 msec, >= 200 msec; QRS Duration, Aggregate <= 80 msec, >= 180 msec; QTcB Interval, Aggregate <= 300 msec, >= 500 msec OR (>= 30 msec change from baseline and >= 450 msec); QTcF Interval, Aggregate <= 300 msec, >= 500 msec OR (>= 30 msec change from baseline and >= 450 msec).
Measured: 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)
Treatment-emergent suicidal ideation (SI) or suicidal behavior (SB) compared to baseline will be measured by an increase in suicidal ideation category (1-5 on the C-SSRS) or suicidal behavior category (6-10 on the C-SSRS) during treatment from the maximum suicidal ideation/behavior category at baseline, or any suicidal ideation/behavior during treatment if there is none at baseline. C-SSRS is used to assess whether participant experienced suicidal ideation (1: wish to be dead; 2: non-specific active suicidal thoughts; 3: active suicidal ideation with any methods (not plan) without intent to act; 4: active suicidal ideation with some intent to act, without specific plan; 5: active suicidal ideation with specific plan and intent) and suicidal behavior (6: actual attempt; 7: interrupted attempt; 8: aborted attempt; 9: preparatory acts or behavior; 10: suicidal behavior).
Measured: Baseline (Day -1) and Days 14, 35 and 77

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

21 Dec 20176 Nov 2019

First posted24 Oct 2017
Study start21 Dec 2017
Primary completion11 Sep 2019
Study completion6 Nov 2019

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Publications (1)Papers the sponsor has linked to this study.
Other trials for Stable SchizophreniaStudies of the same condition, open and under way.
More trials run by Neurocrine BiosciencesThe sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 2
Primary purpose: Treatment
Allocation: Randomised
Intervention model: Crossover
Masking: Quadruple blind
Who is masked: Participant, Care provider, Investigator, Outcomes assessor
Enrolment: 23 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT03319953
Sponsor's protocol ID: TAK-041-2001
Other IDs: U1111-1191-6915, 2017-001084-20, 17/YH/0195, 03319953, 2017
Status last verified: Mar 2021
First submitted: 20 Oct 2017
Last updated: 19 Mar 2021
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: No
FDA-regulated drug: No
FDA-regulated device: No
Individual data sharing: Yes: Takeda provides access to the de-identified individual participant data (IPD) for eligible studies to aid qualified researchers in addressing legitimate scientific objectives (Takeda's data sharing commitment is available on https://clinicaltrials.takeda.com/takedas-commitment?commitment=5). These IPDs will be provided in a secure research environment following approval of a data sharing request, and under the terms of a data sharing agreement

Publications

Hawkins PCT, Schwarz AJ, Stone JM, Pepper F, Gilleen J, Gijsen S, Mazibuko N, Arkilo D, Yin W, Wu J, Khudyakov P, Behrje R, Rosen L, Posener J, Mehta MA, Laurenza A. The GPR139 agonist TAK-041 produces time-dependent alterations to cerebral blood flow and reward system function in patients with schizophrenia: a randomised placebo-controlled trial. Psychopharmacology (Berl). 2026 Apr;243(4):819-829. doi: 10.1007/s00213-025-06884-x. Epub 2025 Aug 16.
PubMed 40817174

Study at a glance

From the registry record, last updated by the sponsor on 19 Mar 2021. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: 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
ClinicalTrials.gov ID: NCT03319953
Acronym / sponsor ID: TAK-041-2001
Conditions: Stable Schizophrenia
Keywords: Drug therapy
Phase: Phase 2
Study type: Interventional
Recruitment status: Completed
Enrolment: 23 participants (actual)
Lead sponsor: Neurocrine BiosciencesIndustry (pharma, biotech, devices)
Collaborators: Takeda
Study start: 21 Dec 2017 (actual)
Primary completion: 11 Sep 2019 (actual)
Study completion: 6 Nov 2019 (actual)
First posted: 24 Oct 2017 (actual)
Results: Posted 9 Feb 2021

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Detailed description

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.

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Crossover
Masking: Quadruple blind (participant, care provider, investigator, outcomes assessor)
Number of arms: 4

Arm	Type	Receives
Treatment Sequence 1: TAK-041 40 mg/Placebo + Antipsychotics	Experimental	Drug: TAK-041, Drug: Placebo, Drug: Second Generation Antipsychotics (SGA)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.
Treatment Sequence 2: Placebo/TAK-041 40 mg + Antipsychotics	Experimental	Drug: TAK-041, Drug: Placebo, Drug: Second Generation Antipsychotics (SGA)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.
Treatment Sequence 3: TAK-041 160 mg/Placebo + Antipsychotics	Experimental	Drug: TAK-041, Drug: Placebo, Drug: Second Generation Antipsychotics (SGA)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.
Treatment Sequence 4: Placebo/TAK-041 160 mg + Antipsychotics	Experimental	Drug: TAK-041, Drug: Placebo, Drug: Second Generation Antipsychotics (SGA)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.

Who may qualify

Ages: 18 to 60 years
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult

Key inclusion criteria (5 listed)

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.

Key exclusion criteria (11 listed)

Has a history of cancer (malignancy).
Has a positive alcohol and/ or positive drug screen at Screening or Day -1.
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.

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
TAK-041TAK-041 suspension	Drug	Treatment Sequence 1: TAK-041 40 mg/Placebo + Antipsychotics, Treatment Sequence 2: Placebo/TAK-041 40 mg + Antipsychotics, Treatment Sequence 3: TAK-041 160 mg/Placebo + Antipsychotics, Treatment Sequence 4: Placebo/TAK-041 160 mg + Antipsychotics
PlaceboTAK-041 placebo-matching suspension	Drug	Treatment Sequence 1: TAK-041 40 mg/Placebo + Antipsychotics, Treatment Sequence 2: Placebo/TAK-041 40 mg + Antipsychotics, Treatment Sequence 3: TAK-041 160 mg/Placebo + Antipsychotics, Treatment Sequence 4: Placebo/TAK-041 160 mg + Antipsychotics
Second Generation Antipsychotics (SGA)Second generation antipsychotics included risperidone, paliperidone, iloperidone, quetiapine, olanzapine, ziprasidone, asenapine and lurasidone.	Drug	Treatment Sequence 1: TAK-041 40 mg/Placebo + Antipsychotics, Treatment Sequence 2: Placebo/TAK-041 40 mg + Antipsychotics, Treatment Sequence 3: TAK-041 160 mg/Placebo + Antipsychotics, Treatment Sequence 4: Placebo/TAK-041 160 mg + Antipsychotics

Primary outcome

Change From Baseline in the Brief Assessment of Cognition in Schizophrenia (BACS) Composite Score at Second Testing After TAK-041 Administration
Time frame: 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
Time frame: 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.

5 secondary outcomes

Percentage of Participants Who Experience at Least One Treatment Emergent Adverse Event (TEAE)
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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)
Time frame: Baseline (Day -1) and Days 14, 35 and 77

Results and safety

Results posted to the registry on 9 Feb 2021, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Treatment Sequence 1: TAK-041 40 mg/Placebo + Antipsychotics	3	3
Treatment Sequence 2: Placebo/TAK-041 40 mg + Antipsychotics	4	4
Treatment Sequence 3: TAK-041 160 mg/Placebo + Antipsychotics	9	9
Treatment Sequence 4: Placebo/TAK-041 160 mg + Antipsychotics	7	7

Primary outcome: Change From Baseline in the Brief Assessment of Cognition in Schizophrenia (BACS) Composite Score at Second Testing After TAK-041 Administration

Time frame: Baseline (Day -1) and Day 14. Mean (Standard Deviation). Unit: t-scale

Measure	Placebo n = 21	TAK-041 40 mg n = 7	TAK-041 160 mg n = 15
Baseline	29.72 (12.867)	27.35 (12.753)	27.89 (8.214)
Day 14	2.28 (6.963)	5.35 (6.944)	1.31 (5.618)

Placebo vs TAK-041 40 mg: p = 0.2079, Bayesian Normal Linear Model
Placebo vs TAK-041 160 mg: p = 0.0633, Bayesian Normal Linear Model

Population analysed: Pharmacodynamic (PD) Analysis Set included all participants who received at least 1 dose of study drug and had at least 1 evaluable primary or exploratory PD measurement. Number analyzed is the number of participants with data available for analyses.

Primary outcome: 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

Time frame: Day 1. Mean (Standard Deviation). Unit: BOLD signal

Measure	Placebo n = 20	TAK-041 40 mg n = 6	TAK-041 160 mg n = 13
Value	0.23 (0.396)	0.23 (0.202)	0.03 (0.458)

Placebo vs TAK-041 40 mg: p = 0.1706, Bayesian Normal Linear Model
Placebo vs TAK-041 160 mg: p = 0.0373, Bayesian Normal Linear Model

Population analysed: PD Analysis Set included all participants who received at least 1 dose of study drug and had at least 1 evaluable primary or exploratory PD measurement. Overall number of participants analyzed is the number of participants with data available for analyses.

5 secondary outcomes are reported in the full results.

Adverse events

Time frame: From the first dose of study drug up to 77 days after last dose of study drug (Up to Day 154). Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Placebo	0 of 21 (0%)	12 of 21 (57.1%)	0 of 21
TAK-041 40 mg	0 of 7 (0%)	5 of 7 (71.4%)	0 of 7
TAK-041 160 mg	0 of 15 (0%)	8 of 15 (53.3%)	0 of 15

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 19 Mar 2021.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Derived from this study: PubMed 40817174Hawkins PCT, Schwarz AJ, Stone JM, Pepper F, Gilleen J, Gijsen S, Mazibuko N, Arkilo D, Yin W, Wu J, Khudyakov P, Behrje R, Rosen L, Posener J, Mehta MA, Laurenza A. The GPR139 agonist TAK-041 produces time-dependent alterations to cerebral blood flow and reward system function in patients with schizophrenia: a randomised placebo-controlled trial. Psychopharmacology (Berl). 2026 Apr;243(4):819-829. doi: 10.1007/s00213-025-06884-x. Epub 2025 Aug 16.
Individual participant dataSharing planned: Yes. Takeda provides access to the de-identified individual participant data (IPD) for eligible studies to aid qualified researchers in addressing legitimate scientific objectives (Takeda's data sharing commitment is available on https://clinicaltrials.takeda.com/takedas-commitment?commitment=5). These IPDs will be provided in a secure research environment following approval of a data sharing request, and under the terms of a data sharing agreement

Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Medical Director Clinical Science study director

Takeda

1 site in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing TAK-041 and Second Generation Antipsychotics (SGA) in people with Stable Schizophrenia, run by Neurocrine Biosciences at 1 site in United Kingdom.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 5 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 19 Mar 2021. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 9 Feb 2021). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Change From Baseline in the Brief Assessment of Cognition in Schizophrenia (BACS) Composite Score at Second Testing After TAK-041 Administration (time frame: Baseline (Day -1) and Day 14). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03319953, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 19 Mar 2021; AzTrials last refreshed its copy on 28 Oct 2026.