Healthy VolunteersPhase 1NCT02748694

Phase 1 TAK-041 First-in-Human Safety, Tolerability, and Pharmacokinetics Study

A Phase 1 study testing TAK-041 in people with Healthy Volunteers and Schizophrenia, run by Neurocrine Biosciences at 1 site in United States.

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 this study is to evaluate the safety, tolerability, and pharmacokinetics (PK) of TAK-041: 1. Following oral single and multiple doses in healthy participants. 2. As add-on therapy to antipsychotics in stable schizophrenia participants. 3. Read more about this study

Who is it for?: Ages 18 to 55 yearsHealthy volunteers can take part
Conditions the study is for: Healthy Volunteers, Schizophrenia
What is being tested?: TAK-041
Type of treatment: Pill or oral medicine
Could I receive a placebo?: Yes, some participants may receive a placebo
How many people: 114 participants
Where: 1 siteUnited States
Study dates: 9 May 2016to 22 Sep 2019
Phase: Phase 1
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 55 years
All sexes
Healthy volunteers accepted
Adult

Who may be able to join

Healthy Participants and Participants with Schizophrenia:
In the opinion of the investigator, the participant is capable of understanding and complying with protocol requirements.
The participant signs and dates a written, informed consent form and any required privacy authorization prior to the initiation of any participant procedures including requesting that a participant fast for any laboratory evaluations.
The participant is willing to comply with study restrictions described in the protocol.
The participant is a healthy adult man or woman (of non-childbearing potential as described in the protocol)
The participant is aged 18 to 55 years, inclusive, at the time of informed consent.

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The participant weighs at least 45 kilogram (kg) (99 pound [lb]) with a body mass index from 18 to 32 kilogram per square meter (kg/m^2) for healthy participants and up to 40.5 kg/m^2 for participants with schizophrenia, inclusive at screening.
A male participant who is nonsterilized and sexually active with a female partner of childbearing potential agrees to use adequate contraception (as defined in the protocol)from signing of informed consent throughout the duration of the study and for 145 days have elapsed since the last dose of study drug.
Participants with schizophrenia only-:
Is on a stable dose of an antipsychotic medication for at least 2 months as documented by medical history and assessed by site staff.
Meets schizophrenia criteria as defined by the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) by the Mini International Neuropsychiatric Interview (MINI).
Has 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).

Who cannot join

Healthy Participants:
The participant has received any investigational compound within 30 days prior to the first dose of study drug, or due to the half-life of the investigational drug is likely to still have detectable plasma levels of that compound.
The participant is an immediate family member, study site employee, or is in a dependent relationship with a study site employee who is involved in the conduct of this study (example spouse, parent, child, sibling) or may consent under duress
The participant has a known hypersensitivity to any component of the formulation of TAK-041.
The participant has a positive urine/blood drug result for drugs of abuse (defined as any illicit drug use) at Screening or Check-in (Day -1).
The participant taken any excluded medication, supplements, or food products during the time periods listed in the protocol.

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The participant is lactose intolerant (Part3 only).
If female, the participant is of childbearing potential (example, premenopausal, not sterilized).
If male, the participant intends to donate sperm during the course of this study or for 145 days have elapsed since the last dose of study drug.
The participant has evidence of current active cardiovascular, central nervous system, hepatobiliary disease including history of biliary tree disorders, gallstones, endoscopic retrograde cholangio pancreatography (ERCP), and/or cholecystectomy, hematopoietic disease, renal dysfunction, metabolic or endocrine dysfunction, serious allergy, asthma, hypoxemia, hypertension, seizures, or allergic skin rash. There is any finding in the participant's medical history, physical examination, or safety laboratory test results (including elevated alkaline phosphatase (ALP), elevated bilirubin, elevated GGT, or elevated 5'-nucleotidase) that in the judgment of the principal investigator represents a reasonable suspicion of a disease that would contraindicate taking TAK-041, or that might interfere with the conduct of the study. This includes, but is not limited to, peptic ulcer disease, cholestasis, seizure disorders, and cardiac arrhythmias.
The participant has current or recent (within 6 months) gastrointestinal disease that would be expected to influence the absorption of drugs (that is, a history of malabsorption, esophageal reflux, peptic ulcer disease, erosive esophagitis, frequent [more than once per week] occurrence of heartburn, or any surgical intervention).
Had major surgery, or donated or lost 1 unit of blood (approximately 500 mL) within 4 weeks prior to Screening.
The participant has a history of cancer, except basal cell carcinoma that has been in remission for at least 5 years prior to Day 1. Participant has a positive test result for hepatitis B surface antigen (HBsAg), hepatitis C virus (HCV) antibody at Screening or a known history of human immunodeficiency virus (HIV) infection.
The participant has used nicotine-containing products (including but not limited to cigarettes, pipes, cigars, chewing tobacco, nicotine patch or nicotine gum) within 21 days prior to Check-in on Day -1. Cotinine test is positive at Screening or Day -1.
The participant has poor peripheral venous access.
Had a transfusion of any blood product within 30 days prior to Day 1.
Participant has a Screening or Check-in abnormal (clinically significant) electrocardiogram (ECG). Entry of any participant with an abnormal (not clinically significant) ECG must be approved, and documented by signature of the principal investigator or a medically qualified sub-investigator.
The participant has a sustained resting heart rate outside the range 40 to 100 beats per minute (bpm), confirmed on repeat testing within a maximum of 30 minutes, at Screening or Check-in.
The participant has a QT interval with Fridericia correction method (QTcF) >450 millisecond (ms) or PR outside the range 120 to 220 ms, confirmed on repeat testing within a maximum of 30 minutes, at the Screening Visit or Check-in.
The participant has abnormal Screening or Check-in laboratory values (> upper limit of normal [ULN] for the respective serum chemistries) of alanine transaminase (ALT), aspartate aminotransferase (AST), total bilirubin (TBILI), ALP, gamma-glutamyl transpeptidase (GGT), 5'nucleotidase (Screening only) and/or abnormal urine osmolality, confirmed upon repeat testing.
The participant has a clinically significant history of head injury or trauma associated with loss of consciousness for >15 minutes.
Is considered by the investigator to be at an imminent risk of suicide injury to self, other, property, or participants who within the past year prior to Screening have attempted suicide. Participants having positive answer on item 4 or 5 on Columbia Suicide Severity Rating Scale (C-SSRS) (based on the past year) prior to randomization are excluded.
The participant has a history of significant skin reactions (hypersensitivity) to adhesives, metals or plastic; this criterion applies only to participants participating in the study of the two wearable digital devices.
Participants with schizophrenia only:
Has an undetectable level of baseline antipsychotic medication at Screening.
Has a lifetime diagnosis of schizoaffective disorder; a lifetime diagnosis of bipolar disorder; or a lifetime diagnosis of obsessive compulsive disorder based on the Mini International Neuropsychiatric Interview (MINI) combined with the general psychiatric evaluation. As an exception, participants with a historical prior lifetime diagnosis of schizoaffective disorder may be enrolled in the study with sponsor or designee approval provided that the principal investigator can attest that the participant's overall history and current clinical presentation and history is most consistent with schizophrenia, not schizoaffective disorder.
Has a recent (within the last 6 months) diagnosis of panic disorder, depressive episode, or other comorbid psychiatric conditions requiring clinical attention based on the MINI for DSM-5 and the general psychiatric evaluation.
Has a history of drug abuse (defined as any illicit drug use) or a history of alcohol abuse (defined as 4 or more alcoholic beverages per day) within 1 year prior to the Screening Visit or is unwilling to agree to abstain from alcohol and drugs throughout the study.
Has a diagnosis of substance use disorder (with the exception of nicotine dependence) within the preceding 6 months based on the MINI for DSM-5 and the general psychiatric evaluation.
Has evidence or history of current clinically significant cardiovascular disease, including uncontrolled hypertension (standing or supine diastolic blood pressure >90 millimeter of mercury (mm Hg) and/or standing or supine systolic blood pressure >145 mm Hg, with or without treatment), symptomatic ischemic heart disease, uncompensated heart failure or recent (past 12 months) acute myocardial infarction or bypass surgery. Controlled essential hypertension, non-clinically significant sinus bradycardia and sinus tachycardia will not be considered significant medical illnesses and would not exclude a participant from the study. Other well-controlled medical illnesses may be permitted that do not increase hepatic risks or other safety risks to the participant's participation in the judgement of the investigator in consultation with the sponsor or designee.
Has evidence of clinically significant extrapyramidal symptoms as measured by a Simson-Angus Scale (SAS) score >6.
The participant has evidence of depression as measured by a Calgary Depression Score (CDSS) score >9.
Has received TAK-041 in a previous clinical study; or has previously or is currently participating in this study; has received treatment with other experimental therapies within the preceding 60 days or <5 half-lives prior to randomization, whichever is longer; has participated in 2 or more clinical studies within 12 months prior to Screening; or has participated in a clinical study for a psychiatric condition that is exclusionary per this protocol.

Trial locations and contacts

1 site in 1 country.

United States1 site

Parexel Early Phase Clinic Unit- Los Angeles
Glendale, California, 91206

Other trials in United States

About this study

Official title: A Randomized, Double -Blind, Placebo-Controlled, Phase 1, Ascending Oral Single and Multiple Dose Study to Evaluate the Safety, Tolerability, and Pharmacokinetics of TAK-041 in Healthy Subjects and Subjects With Stable Schizophrenia and a Randomized Open-Label, Single Dose, Parallel Design to Evaluate the Relative Bioavailability and Effect of Food on the Pharmacokinetics of TAK-041 Tablet Formulation in Healthy Subjects

The purpose of this study is to evaluate the safety, tolerability, and pharmacokinetics (PK) of TAK-041:

Following oral single and multiple doses in healthy participants.
As add-on therapy to antipsychotics in stable schizophrenia participants.
To determine the oral bioavailability of the TAK-041 tablet formulation compared to the oral suspension formulation in the fasted state.
To assess the effect of food on the PK of TAK-041 in healthy participants.

Read the detailed description

The drug being tested in this study is called TAK-041. TAK-041 is being tested to evaluate its safety, tolerability, and PK of single and multiple doses in healthy participants and as add-on therapy to antipsychotics in participants with stable schizophrenia. This study will also assess the oral bioavailability in healthy participants administered with tablet formulation compared to oral suspension formulation in fasted state, and effect of high-fat, high-calorie meal on the PK of single dose of TAK-041 tablet formulation.

The study will enroll approximately 114 participants. The study is composed of 4 parts. Part 1 (single-rising dose [SRD], alternating panel design and a sequential panel design), Part 2 (multiple-rising dose [MRD], sequential panel design), Part 3 (open label parallel design), and Part 4 (single dose cohort).

Part 1 consists of 5 cohorts, participants in Cohorts 1 and 2 will be randomly assigned (by chance, like flipping a coin) to treatment sequences of 2 periods and for Cohorts 3 to 5 participants will be assigned to a single dose sequential-panel:

TAK-041 5-160 mg
Placebo (inactive) - this is a similar formulation that looks like the study drug but has no active ingredient.

Part 2 consists of 4 cohorts, participants will be randomly assigned to one of the two treatments:

TAK-041
Placebo Dose levels for Part 2 cohort 1 will be based on emerging safety/tolerability and PK data from Part 1. The dose levels for Part 2 Cohorts 2 onwards will be based on emerging safety/tolerability and available PK data from Part 1 and from preceding cohorts in Part 2.

Part 3 consists of 2 cohorts, participants will be randomly assigned to one of the two treatments under fasted state or fed state:

TAK-041 40 mg tablet (Fasted state)
TAK-041 40 mg tablet (Fed state)

Part 4 consists of 1 cohort, participants will be randomly assigned to one of the two treatments:

TAK-041
Placebo The dose levels for Part 4 will be based upon the emerging safety/tolerability and PK data of same dose in healthy participants from Part 2.

This single center trial will be conducted in the United States. Participants will remain confined to the study site from check-in (Day -1) through Days 5 of each period in Part 1, on Days -2 to 3, Days 7 to 10, Days 14 to 17, Day 21 to 24 in Part 2, on Days 1 to 3 in Part 3, and on Days -2 to 3, Days 7 to 10, Days 14 to 17, Days 21 to 24 in Part 4. A final visit that completes the study will occur 12 to 16 days after the last safety and PK follow-up visit in Part 1, 2 and 4, and 18 days after dosing in Part 3.

Conditions: Healthy Volunteers, Schizophrenia
Being tested: TAK-041, TAK-041 Placebo
Keywords: Drug Therapy
Medical subject headings: Schizophrenia

What participants receive

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

TAK-041Drug
TAK-041 tablets or oral suspension.
TAK-041 PlaceboDrug
TAK-041 placebo-matching suspension or tablet.

Study groups in NCT02748694
Study group	Role	What they receive
Part 1 (SRD): Placebo Cohorts 1-5	Placebo comparator	TAK-041 placebo-matching suspension, orally, once on Day 1 in fasted healthy participants in the SRD period. Receives: Drug: TAK-041 Placebo
Part 1 (SRD): Cohort 1: TAK-041 5/20 mg	Experimental	TAK-041 5 mg, suspension, orally, once on Day 1 in fasted healthy participants in the SRD period. Participants also received 20 mg, suspension, orally, once on Day 8 in the SRD period. Receives: Drug: TAK-041
Part 1 (SRD): Cohort 2: TAK-041 10/40 mg	Experimental	TAK-041 10 mg, suspension, orally, once on Day 1 in fasted healthy participants in the SRD period. Participants also received 40 mg, suspension, orally, once on Day 8 in the SRD period. Receives: Drug: TAK-041
Part 1 (SRD): Cohort 3: TAK-041 80 mg	Experimental	TAK-041 80 mg, suspension, orally, once on Day 1 in fasted healthy participants in the SRD period. Receives: Drug: TAK-041
Part 1 (SRD): Cohort 4: TAK-041 120 mg	Experimental	TAK-041 120 mg, suspension, orally, once on Day 1 in fasted healthy participants in the SRD period. Receives: Drug: TAK-041
Part 1 (SRD): Cohort 5: TAK-041 160 mg	Experimental	TAK-041 160 mg, suspension, orally, once on Day 1 in fasted healthy participants in the SRD period. Receives: Drug: TAK-041
Part 2 (MRD): Placebo Cohorts 1-4	Placebo comparator	TAK-041 placebo-matching suspension, orally, once on Day 1 in fasted healthy participants in the multiple-rising dose (MRD) period. Receives: Drug: TAK-041 Placebo
Part 2 (MRD): Cohort 1: TAK-041 40/20 mg	Experimental	TAK-041 40 mg as loading dose, suspension, orally, once on Day 1 in fasted healthy participants followed by 20 mg (half the initial dose) as a maintenance dose on Days 8, 15 and 22 in the MRD period. Receives: Drug: TAK-041
Part 2 (MRD): Cohort 2: TAK-041 80/40 mg	Experimental	TAK-041 80 mg as loading dose, suspension, orally, once on Day 1 in fasted healthy participants followed by 40 mg (half the initial dose) as a maintenance dose on Days 8, 15 and 22 in the MRD period. Receives: Drug: TAK-041
Part 2 (MRD): Cohort 3: TAK-041 120/60 mg	Experimental	TAK-041 120 mg as loading dose, suspension, orally, once on Day 1 in fasted healthy participants followed by 60 mg (half the initial dose) as a maintenance dose on Days 8, 15 and 22 in the MRD period. Receives: Drug: TAK-041
Part 2 (MRD): Cohort 4: TAK-041 160/80 mg	Experimental	TAK-041 160 mg as loading dose, suspension, orally, once on Day 1 in fasted healthy participants followed by 80 mg (half the initial dose) as a maintenance dose on Days 8, 15 and 22 in the MRD period. Receives: Drug: TAK-041
Part 3: Relative Bioavailability (RBA)/Food Effect: Regimen A	Experimental	TAK-041 40 mg, tablet, orally, once on Day 1 in fasted state (Regimen A) in Cohort 1. Receives: Drug: TAK-041
Part 3: RBA/Food Effect: Regimen B	Experimental	TAK-041 40 mg, tablet, orally, once on Day 1 in fed state (Regimen B) in Cohort 2. Receives: Drug: TAK-041
Part 4: MRD: Placebo	Placebo comparator	TAK-041 placebo-matching, suspension, orally, on Days 1, 8, 15 and 22 in participants with schizophrenia Receives: Drug: TAK-041; Drug: TAK-041 Placebo
Part 4: MRD: TAK-041 160/80 mg	Experimental	TAK-041 160 mg as loading dose, suspension, orally, once on Day 1 followed by 80 mg (half the initial dose) as a maintenance dose on Days 8, 15 and 22 in participants with schizophrenia. Receives: Drug: TAK-041

What is being measured

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

Percentage of Participants Who Experienced at Least One Treatment-Emergent Adverse Event (TEAE)
An AE was defined as any untoward medical occurrence in a clinical investigation participant administered a drug or due to a study procedure; it did not necessarily have to have a causal relationship with this treatment. A TEAE was defined as an AE that occurred or worsened after receiving the first dose of study drug and within 6 weeks after the last dose of study drug. A TEAE may also have been a pre-treatment AE or a concurrent medical condition diagnosed before the date of first dose of study drug that increased in severity after the start of dosing.
Measured: From the first dose of study drug up to 42 days after the last dose of study drug (Up to 12 weeks)
Percentage of Participants Who Discontinued Study Drug Due to an Adverse Event (AE)
An AE was defined as any untoward medical occurrence in a clinical investigation participant administered a drug or due to a study procedure; it did not necessarily have to have a causal relationship with this treatment.
Measured: From the first dose of study drug up to 42 days after the last dose of study drug (Up to 12 weeks)
Percentage of Participants With Markedly Abnormal Value (MAV) Criteria for Safety Laboratory Tests At Least Once Post-dose
Clinical laboratory tests included serum chemistry, hematology and urinalysis. MAV criteria:Alanine aminotransferase(U/L) >3 x upper limit of normal(ULN);albumin<2.5g/dL,<25g/L;alkaline phosphatase (U/L)>3 x ULN; aspartate aminotransferase (U/L)>3 x ULN;bicarbonate<8.0 mmol/L; bilirubin>2.0mg/dL, >34.2 μmol/L;blood urea nitrogen>30 mg/dL,>10.7mmol/L;calcium<7.0 mg/dL,<1.75 mmol/L, >11.5 mg/dL,>2.88 mmol/L;chloride<75 mmol/L,>126 mmol/L;creatine kinase(U/L) >5 xULN; creatinine>2.0 mg/dL,>177μmol/L;direct bilirubin>2 x ULN;gamma glutamyl transferase (U/L)>3 x ULN;glucose<50 mg/dL,<2.8 mmol/L,>350 mg/dL,>19.4 mmol/L;potassium<3.0 mmol/L >6.0 mmol/L; protein(g/L)<0.8 x LLN >1.2 x ULN;sodium<130mmol/L >150mmol/L;erythrocytes(10^12erythrocytes/L) <0.8 x LLN,>1.2 x ULN;hematocrit(fraction of 1)<0.8 x LLN,>1.2xULN;hemoglobin(g/L)<0.8 x LLN>1.2 x ULN;leukocytes(10^9 leukocytes/L)<0.5 x LLN >1.5 x ULN;platelets(10^9 platelets/L)<75->600. Categories with at least one participant are reported.
Measured: From the first dose of study drug up to 42 days after the last dose of study drug (Up to 12 weeks)
Percentage of Participants With 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 was 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. Categories with data in at least one arm group are reported.
Measured: From the first dose of study drug up to 42 days after the last dose of study drug (Up to 12 weeks)
Percentage of Participants With Markedly Abnormal Criteria for 12-Lead Electrocardiogram (ECG) Parameters 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). Categories with data in at least one arm group are reported.
Measured: From the first dose of study drug up to 42 days after the last dose of study drug (Up to 12 weeks)
Part 2: Percentage of Participants Who Experienced Clinically Significant Abnormal Changes in Continuous 12-Lead Holter ECG Measurements at Least Once Post-Dose
The markedly abnormal value (MAV) criteria for continuous 12-lead Holter 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). Categories with data in at least one arm group are reported.
Measured: Part 2: from first dose up to Day 66
Part 3: Cmax: Maximum Observed Plasma Concentration for TAK-041 in RBA/Food Effect Participants [Day 1]
Measured: Part 3: Day 1 pre-dose and at multiple time points (up to 96 hours) post-dose
Part 3: AUC96: Area Under the Plasma Concentration-Time Curve From Time 0 to 96 Hours (AUC96) for TAK-041 in RBA/Food Effect Participants [Day 1]
Measured: Part 3: Day 1 pre-dose and at multiple time points (up to 96 hours) post-dose

Secondary outcomes (24)

Part 1: Cmax: Maximum Observed Plasma Concentration for TAK-041 in SRD Participants [Day 1]
Measured: Part 1: Day 1 pre-dose and at multiple time points post dose, up to 96 hours for Cohorts 1 and 2; up to 168 hours for Cohorts 3-5
Part 1: Cmax: Maximum Observed Plasma Concentration for TAK-041 in SRD Participants [Day 8], Cohorts 1 (20 mg) and 2 (40 mg) Only
Measured: Part 1: Pre-dose on Day 8 and at multiple timepoints (Up to 96 hours) post-dose
Parts 2 and 4: Cmax: Maximum Observed Plasma Concentration for TAK-041 in MRD Participants [Day 1]
Measured: Parts 2 and 4: Day 1 pre-dose and at multiple time points (up to 168 hours) post-dose
Part 1: Tmax: Time to Reach the Cmax for TAK-041 in SRD Participants [Day 1]
Measured: Part 1: Day 1 pre-dose and at multiple time points post dose, up to 96 hours for Cohorts 1 and 2; up to 168 hours for Cohorts 3-5
Part 1: Tmax: Time to Reach the Cmax for TAK-041 in SRD Participants [Day 8], Cohorts 1 (20 mg) and 2 (40 mg) Only
Measured: Part 1: Pre-dose on Day 8 and at multiple timepoints (Up to 96 hours) post-dose
Parts 2 and 4: Tmax: Time to Reach the Cmax for TAK-041 in MRD Participants [Day 1]
Measured: Parts 2 and 4: Day 1 pre-dose and at multiple time points (up to 168 hours) post-dose
Part 3: Tmax: Time to Reach the Cmax for TAK-041 in RBA/Food Effect Participants [Day 1]
Measured: Part 3: Day 1 pre-dose and at multiple time points (up to 96 hours) post-dose
Part 1: AUC24: Area Under the Plasma Concentration-Time Curve From Time 0 to 24 Hours for TAK-041 in SRD Participants [Day 1]
Measured: Part 1: Day 1 pre-dose and at multiple time points post dose, up to 96 hours for Cohorts 1 and 2; up to 168 hours for Cohorts 3-5
Part 1: AUC24: Area Under the Plasma Concentration-Time Curve From Time 0 to 24 Hours for TAK-041 in SRD Participants [Day 8], Cohorts 1 (20 mg) and 2 (40 mg) Only
Measured: Part 1: Pre-dose on Day 8 and at multiple timepoints (Up to 96 hours) post-dose
Parts 2 and 4: AUC24: Area Under the Plasma Concentration-Time Curve From Time 0 to 24 Hours for TAK-041 in MRD Participants [Day 1]
Measured: Parts 2 and 4: Day 1 pre-dose and at multiple time points (up to 168 hours) post-dose
Part 3: AUC24: Area Under the Plasma Concentration-Time Curve From Time 0 to 24 Hours for TAK-041 in RBA/Food Effect Participants [Day 1]
Measured: Part 3: Day 1 pre-dose and at multiple time points (up to 96 hours) post-dose
Part 1: AUC96: Area Under the Plasma Concentration-Time Curve From Time 0 to 96 Hours for TAK-041 in SRD Participants [Day 1]
Measured: Part 1: Day 1 pre-dose and at multiple time points post dose, up to 96 hours for Cohorts 1 and 2; up to 168 hours for Cohorts 3-5
Part 1: AUC96: Area Under the Plasma Concentration-Time Curve From Time 0 to 96 Hours for TAK-041 in SRD Participants [Day 8], Cohorts 1 (20 mg) and 2 (40 mg) Only
Measured: Part 1: Pre-dose on Day 8 and at multiple timepoints (Up to 96 hours) post-dose
Parts 2 and 4: AUC96: Area Under the Plasma Concentration-Time Curve From Time 0 to 96 Hours for TAK-041 in MRD Participants [Day 1]
Measured: Parts 2 and 4: Day 1 pre-dose and at multiple time points (up to 168 hours) post-dose
Part 1: AUCt: Area Under the Plasma Concentration-Time Curve From Time 0 to Time t for TAK-041 in SRD Participants [Day 1]
Measured: Part 1: Day 1 pre-dose and at multiple time points post dose, up to 96 hours for Cohorts 1 and 2; up to 168 hours for Cohorts 3-5
Part 1: AUCt: Area Under the Plasma Concentration-Time Curve From Time 0 to Time t for TAK-041 in SRD Participants [Day 8], Cohorts 1 (20 mg) and 2 (40 mg) Only
Measured: Part 1: Pre-dose on Day 8 and at multiple timepoints (Up to 96 hours) post-dose
Parts 2 and 4: AUCt: Area Under the Plasma Concentration-Time Curve From Time 0 to Time t for TAK-041 in MRD Participants [Day 1]
Measured: Parts 2 and 4: Day 1 pre-dose and at multiple time points (up to 168 hours) post-dose
Part 3: AUCt: Area Under the Plasma Concentration-Time Curve From Time 0 to Time t for TAK-041 in RBA/Food Effect Participants [Day 1]
Measured: Part 3: Day 1 pre-dose and at multiple time points (up to 96 hours) post-dose
Part 1: AUCinf: Area Under the Plasma Concentration-Time Curve From Time 0 to Infinity for TAK-041 in SRD Participants [Day 1]
Measured: Part 1: Day 1 pre-dose and at multiple time points post dose, up to 96 hours for Cohorts 1 and 2; up to 168 hours for Cohorts 3-5
Part 1: AUCinf: Area Under the Plasma Concentration-Time Curve From Time 0 to Infinity for TAK-041 in SRD Participants [Day 8], Cohorts 1 (20 mg) and 2 (40 mg) Only
Measured: Part 1: Pre-dose on Day 8 and at multiple timepoints (Up to 96 hours) post-dose
Parts 2 and 4: AUCtau: Area Under the Plasma Concentration-Time Curve From Time 0 to Time Tau Over the Dosing Interval for TAK-041 in MRD Participants [Day 1]
Measured: Parts 2 and 4: Day 1 pre-dose and at multiple time points (up to 168 hours) post-dose
Part 1: T1/2z: Terminal Disposition Phase Half-Life for TAK-041 in SRD Participants [Day 1]
Measured: Part 1: Day 1 pre-dose and at multiple time points post dose, up to 96 hours for Cohorts 1 and 2; up to 168 hours for Cohorts 3-5
Part 1: T1/2z: Terminal Disposition Phase Half-Life for TAK-041 in SRD Participants [Day 8], Cohorts 1 (20 mg) and 2 (40 mg) Only
Measured: Part 1: Pre-dose on Day 8 and at multiple timepoints (Up to 96 hours) post-dose
Parts 2 and 4: T1/2z: Terminal Disposition Phase Half-Life for TAK-041 in MRD Participants [Day 1]
Measured: Parts 2 and 4: Day 1 pre-dose and at multiple time points (up to 168 hours) post-dose

Timeline

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

9 May 201622 Sep 2019

First posted22 Apr 2016 (estimated)
Study start9 May 2016
Primary completion22 Sep 2019
Study completion22 Sep 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 Healthy VolunteersStudies 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 1
Primary purpose: Other
Allocation: Randomised
Intervention model: Parallel groups
Masking: Double blind
Who is masked: Participant, Investigator
Enrolment: 114 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT02748694
Sponsor's protocol ID: TAK-041-1001
Other IDs: U1111-1178-6559
Status last verified: Mar 2021
First submitted: 20 Apr 2016
Last updated: 19 Mar 2021
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: No
FDA-regulated drug: Yes
FDA-regulated device: No
Individual data sharing: Yes: Takeda makes patient-level, de-identified data sets and associated documents available for all interventional studies after applicable marketing approvals and commercial availability have been received (or program is completely terminated), an opportunity for the primary publication of the research and final report development has been allowed, and other criteria have been met as set forth in Takeda's Data Sharing Policy (see www.TakedaClinicalTrials.com for details). To obtain access, researchers must submit a legitimate academic research proposal for adjudication by an independent review panel, who will review the scientific merit of the research and the requestor's qualifications and conflict of interest that can result in potential bias. Once approved, qualified researchers who sign a data sharing agreement are provided access to these data in a secure research environment.

Publications

Yin W, Han D, Khudyakov P, Behrje R, Posener J, Laurenza A, Arkilo D. A phase 1 study to evaluate the safety, tolerability and pharmacokinetics of TAK-041 in healthy participants and patients with stable schizophrenia. Br J Clin Pharmacol. 2022 Aug;88(8):3872-3882. doi: 10.1111/bcp.15305. Epub 2022 Apr 17.
PubMed 35277995

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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, Phase 1, Ascending Oral Single and Multiple Dose Study to Evaluate the Safety, Tolerability, and Pharmacokinetics of TAK-041 in Healthy Subjects and Subjects With Stable Schizophrenia and a Randomized Open-Label, Single Dose, Parallel Design to Evaluate the Relative Bioavailability and Effect of Food on the Pharmacokinetics of TAK-041 Tablet Formulation in Healthy Subjects
ClinicalTrials.gov ID: NCT02748694
Acronym / sponsor ID: TAK-041-1001
Conditions: Healthy Volunteers, Schizophrenia
Keywords: Drug Therapy
Phase: Phase 1
Study type: Interventional
Recruitment status: Completed
Enrolment: 114 participants (actual)
Lead sponsor: Neurocrine BiosciencesIndustry (pharma, biotech, devices)
Collaborators: Takeda
Study start: 9 May 2016 (actual)
Primary completion: 22 Sep 2019 (actual)
Study completion: 22 Sep 2019 (actual)
First posted: 22 Apr 2016 (estimated)
Results: Posted 1 Mar 2021

Clinical summary

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

The purpose of this study is to evaluate the safety, tolerability, and pharmacokinetics (PK) of TAK-041:

Following oral single and multiple doses in healthy participants.
As add-on therapy to antipsychotics in stable schizophrenia participants.
To determine the oral bioavailability of the TAK-041 tablet formulation compared to the oral suspension formulation in the fasted state.
To assess the effect of food on the PK of TAK-041 in healthy participants.

Detailed description

TAK-041 5-160 mg
Placebo (inactive) - this is a similar formulation that looks like the study drug but has no active ingredient.

Part 2 consists of 4 cohorts, participants will be randomly assigned to one of the two treatments:

TAK-041
Placebo Dose levels for Part 2 cohort 1 will be based on emerging safety/tolerability and PK data from Part 1. The dose levels for Part 2 Cohorts 2 onwards will be based on emerging safety/tolerability and available PK data from Part 1 and from preceding cohorts in Part 2.

Part 3 consists of 2 cohorts, participants will be randomly assigned to one of the two treatments under fasted state or fed state:

TAK-041 40 mg tablet (Fasted state)
TAK-041 40 mg tablet (Fed state)

Part 4 consists of 1 cohort, participants will be randomly assigned to one of the two treatments:

TAK-041
Placebo The dose levels for Part 4 will be based upon the emerging safety/tolerability and PK data of same dose in healthy participants from Part 2.

Study design

Primary purpose: Other
Allocation: Randomised
Intervention model: Parallel groups
Masking: Double blind (participant, investigator)
Number of arms: 15

Arm	Type	Receives
Part 1 (SRD): Placebo Cohorts 1-5	Placebo comparator	Drug: TAK-041 PlaceboTAK-041 placebo-matching suspension, orally, once on Day 1 in fasted healthy participants in the SRD period.
Part 1 (SRD): Cohort 1: TAK-041 5/20 mg	Experimental	Drug: TAK-041TAK-041 5 mg, suspension, orally, once on Day 1 in fasted healthy participants in the SRD period. Participants also received 20 mg, suspension, orally, once on Day 8 in the SRD period.
Part 1 (SRD): Cohort 2: TAK-041 10/40 mg	Experimental	Drug: TAK-041TAK-041 10 mg, suspension, orally, once on Day 1 in fasted healthy participants in the SRD period. Participants also received 40 mg, suspension, orally, once on Day 8 in the SRD period.
Part 1 (SRD): Cohort 3: TAK-041 80 mg	Experimental	Drug: TAK-041TAK-041 80 mg, suspension, orally, once on Day 1 in fasted healthy participants in the SRD period.
Part 1 (SRD): Cohort 4: TAK-041 120 mg	Experimental	Drug: TAK-041TAK-041 120 mg, suspension, orally, once on Day 1 in fasted healthy participants in the SRD period.
Part 1 (SRD): Cohort 5: TAK-041 160 mg	Experimental	Drug: TAK-041TAK-041 160 mg, suspension, orally, once on Day 1 in fasted healthy participants in the SRD period.
Part 2 (MRD): Placebo Cohorts 1-4	Placebo comparator	Drug: TAK-041 PlaceboTAK-041 placebo-matching suspension, orally, once on Day 1 in fasted healthy participants in the multiple-rising dose (MRD) period.
Part 2 (MRD): Cohort 1: TAK-041 40/20 mg	Experimental	Drug: TAK-041TAK-041 40 mg as loading dose, suspension, orally, once on Day 1 in fasted healthy participants followed by 20 mg (half the initial dose) as a maintenance dose on Days 8, 15 and 22 in the MRD period.
Part 2 (MRD): Cohort 2: TAK-041 80/40 mg	Experimental	Drug: TAK-041TAK-041 80 mg as loading dose, suspension, orally, once on Day 1 in fasted healthy participants followed by 40 mg (half the initial dose) as a maintenance dose on Days 8, 15 and 22 in the MRD period.
Part 2 (MRD): Cohort 3: TAK-041 120/60 mg	Experimental	Drug: TAK-041TAK-041 120 mg as loading dose, suspension, orally, once on Day 1 in fasted healthy participants followed by 60 mg (half the initial dose) as a maintenance dose on Days 8, 15 and 22 in the MRD period.
Part 2 (MRD): Cohort 4: TAK-041 160/80 mg	Experimental	Drug: TAK-041TAK-041 160 mg as loading dose, suspension, orally, once on Day 1 in fasted healthy participants followed by 80 mg (half the initial dose) as a maintenance dose on Days 8, 15 and 22 in the MRD period.
Part 3: Relative Bioavailability (RBA)/Food Effect: Regimen A	Experimental	Drug: TAK-041TAK-041 40 mg, tablet, orally, once on Day 1 in fasted state (Regimen A) in Cohort 1.
Part 3: RBA/Food Effect: Regimen B	Experimental	Drug: TAK-041TAK-041 40 mg, tablet, orally, once on Day 1 in fed state (Regimen B) in Cohort 2.
Part 4: MRD: Placebo	Placebo comparator	Drug: TAK-041, Drug: TAK-041 PlaceboTAK-041 placebo-matching, suspension, orally, on Days 1, 8, 15 and 22 in participants with schizophrenia
Part 4: MRD: TAK-041 160/80 mg	Experimental	Drug: TAK-041TAK-041 160 mg as loading dose, suspension, orally, once on Day 1 followed by 80 mg (half the initial dose) as a maintenance dose on Days 8, 15 and 22 in participants with schizophrenia.

Who may qualify

Ages: 18 to 55 years
Sex: All
Healthy volunteers: Accepted
Age groups: Adult

Key inclusion criteria (13 listed)

In the opinion of the investigator, the participant is capable of understanding and complying with protocol requirements.
The participant signs and dates a written, informed consent form and any required privacy authorization prior to the initiation of any participant procedures including requesting that a participant fast for any laboratory evaluations.
The participant is willing to comply with study restrictions described in the protocol.
The participant is a healthy adult man or woman (of non-childbearing potential as described in the protocol)
The participant is aged 18 to 55 years, inclusive, at the time of informed consent.

Key exclusion criteria (33 listed)

The participant has received any investigational compound within 30 days prior to the first dose of study drug, or due to the half-life of the investigational drug is likely to still have detectable plasma levels of that compound.
The participant is an immediate family member, study site employee, or is in a dependent relationship with a study site employee who is involved in the conduct of this study (example spouse, parent, child, sibling) or may consent under duress
The participant has a known hypersensitivity to any component of the formulation of TAK-041.
The participant has a positive urine/blood drug result for drugs of abuse (defined as any illicit drug use) at Screening or Check-in (Day -1).
The participant taken any excluded medication, supplements, or food products during the time periods listed in the protocol.

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 tablets or oral suspension.	Drug	Part 1 (SRD): Cohort 1: TAK-041 5/20 mg, Part 1 (SRD): Cohort 2: TAK-041 10/40 mg, Part 1 (SRD): Cohort 3: TAK-041 80 mg, Part 1 (SRD): Cohort 4: TAK-041 120 mg, Part 1 (SRD): Cohort 5: TAK-041 160 mg, Part 2 (MRD): Cohort 1: TAK-041 40/20 mg, Part 2 (MRD): Cohort 2: TAK-041 80/40 mg, Part 2 (MRD): Cohort 3: TAK-041 120/60 mg, Part 2 (MRD): Cohort 4: TAK-041 160/80 mg, Part 3: RBA/Food Effect: Regimen B, Part 3: Relative Bioavailability (RBA)/Food Effect: Regimen A, Part 4: MRD: Placebo, Part 4: MRD: TAK-041 160/80 mg
TAK-041 PlaceboTAK-041 placebo-matching suspension or tablet.	Drug	Part 1 (SRD): Placebo Cohorts 1-5, Part 2 (MRD): Placebo Cohorts 1-4, Part 4: MRD: Placebo

Primary outcome

Percentage of Participants Who Experienced at Least One Treatment-Emergent Adverse Event (TEAE)
Time frame: From the first dose of study drug up to 42 days after the last dose of study drug (Up to 12 weeks)
An AE was defined as any untoward medical occurrence in a clinical investigation participant administered a drug or due to a study procedure; it did not necessarily have to have a causal relationship with this treatment. A TEAE was defined as an AE that occurred or worsened after receiving the first dose of study drug and within 6 weeks after the last dose of study drug. A TEAE may also have been a pre-treatment AE or a concurrent medical condition diagnosed before the date of first dose of study drug that increased in severity after the start of dosing.
Percentage of Participants Who Discontinued Study Drug Due to an Adverse Event (AE)
Time frame: From the first dose of study drug up to 42 days after the last dose of study drug (Up to 12 weeks)
An AE was defined as any untoward medical occurrence in a clinical investigation participant administered a drug or due to a study procedure; it did not necessarily have to have a causal relationship with this treatment.
Percentage of Participants With Markedly Abnormal Value (MAV) Criteria for Safety Laboratory Tests At Least Once Post-dose
Time frame: From the first dose of study drug up to 42 days after the last dose of study drug (Up to 12 weeks)
Clinical laboratory tests included serum chemistry, hematology and urinalysis. MAV criteria:Alanine aminotransferase(U/L) >3 x upper limit of normal(ULN);albumin<2.5g/dL,<25g/L;alkaline phosphatase (U/L)>3 x ULN; aspartate aminotransferase (U/L)>3 x ULN;bicarbonate<8.0 mmol/L; bilirubin>2.0mg/dL, >34.2 μmol/L;blood urea nitrogen>30 mg/dL,>10.7mmol/L;calcium<7.0 mg/dL,<1.75 mmol/L, >11.5 mg/dL,>2.88 mmol/L;chloride<75 mmol/L,>126 mmol/L;creatine kinase(U/L) >5 xULN; creatinine>2.0 mg/dL,>177μmol/L;direct bilirubin>2 x ULN;gamma glutamyl transferase (U/L)>3 x ULN;glucose<50 mg/dL,<2.8 mmol/L,>350 mg/dL,>19.4 mmol/L;potassium<3.0 mmol/L >6.0 mmol/L; protein(g/L)<0.8 x LLN >1.2 x ULN;sodium<130mmol/L >150mmol/L;erythrocytes(10^12erythrocytes/L) <0.8 x LLN,>1.2 x ULN;hematocrit(fraction of 1)<0.8 x LLN,>1.2xULN;hemoglobin(g/L)<0.8 x LLN>1.2 x ULN;leukocytes(10^9 leukocytes/L)<0.5 x LLN >1.5 x ULN;platelets(10^9 platelets/L)<75->600. Categories with at least one participant are reported.
Percentage of Participants With Markedly Abnormal Criteria for Vital Sign Measurements at Least Once Post-dose
Time frame: From the first dose of study drug up to 42 days after the last dose of study drug (Up to 12 weeks)
Vital signs included oral body temperature measurement, supine and standing blood pressure, respiration rate, and pulse. Pulse and blood pressure was 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. Categories with data in at least one arm group are reported.
Percentage of Participants With Markedly Abnormal Criteria for 12-Lead Electrocardiogram (ECG) Parameters at Least Once Post-dose
Time frame: From the first dose of study drug up to 42 days after the last dose of study drug (Up to 12 weeks)
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). Categories with data in at least one arm group are reported.
Part 2: Percentage of Participants Who Experienced Clinically Significant Abnormal Changes in Continuous 12-Lead Holter ECG Measurements at Least Once Post-Dose
Time frame: Part 2: from first dose up to Day 66
The markedly abnormal value (MAV) criteria for continuous 12-lead Holter 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). Categories with data in at least one arm group are reported.
Part 3: Cmax: Maximum Observed Plasma Concentration for TAK-041 in RBA/Food Effect Participants [Day 1]
Time frame: Part 3: Day 1 pre-dose and at multiple time points (up to 96 hours) post-dose
Part 3: AUC96: Area Under the Plasma Concentration-Time Curve From Time 0 to 96 Hours (AUC96) for TAK-041 in RBA/Food Effect Participants [Day 1]
Time frame: Part 3: Day 1 pre-dose and at multiple time points (up to 96 hours) post-dose

24 secondary outcomes

Part 1: Cmax: Maximum Observed Plasma Concentration for TAK-041 in SRD Participants [Day 1]
Time frame: Part 1: Day 1 pre-dose and at multiple time points post dose, up to 96 hours for Cohorts 1 and 2; up to 168 hours for Cohorts 3-5
Part 1: Cmax: Maximum Observed Plasma Concentration for TAK-041 in SRD Participants [Day 8], Cohorts 1 (20 mg) and 2 (40 mg) Only
Time frame: Part 1: Pre-dose on Day 8 and at multiple timepoints (Up to 96 hours) post-dose
Parts 2 and 4: Cmax: Maximum Observed Plasma Concentration for TAK-041 in MRD Participants [Day 1]
Time frame: Parts 2 and 4: Day 1 pre-dose and at multiple time points (up to 168 hours) post-dose
Part 1: Tmax: Time to Reach the Cmax for TAK-041 in SRD Participants [Day 1]
Time frame: Part 1: Day 1 pre-dose and at multiple time points post dose, up to 96 hours for Cohorts 1 and 2; up to 168 hours for Cohorts 3-5
Part 1: Tmax: Time to Reach the Cmax for TAK-041 in SRD Participants [Day 8], Cohorts 1 (20 mg) and 2 (40 mg) Only
Time frame: Part 1: Pre-dose on Day 8 and at multiple timepoints (Up to 96 hours) post-dose
Parts 2 and 4: Tmax: Time to Reach the Cmax for TAK-041 in MRD Participants [Day 1]
Time frame: Parts 2 and 4: Day 1 pre-dose and at multiple time points (up to 168 hours) post-dose
Part 3: Tmax: Time to Reach the Cmax for TAK-041 in RBA/Food Effect Participants [Day 1]
Time frame: Part 3: Day 1 pre-dose and at multiple time points (up to 96 hours) post-dose
Part 1: AUC24: Area Under the Plasma Concentration-Time Curve From Time 0 to 24 Hours for TAK-041 in SRD Participants [Day 1]
Time frame: Part 1: Day 1 pre-dose and at multiple time points post dose, up to 96 hours for Cohorts 1 and 2; up to 168 hours for Cohorts 3-5
Part 1: AUC24: Area Under the Plasma Concentration-Time Curve From Time 0 to 24 Hours for TAK-041 in SRD Participants [Day 8], Cohorts 1 (20 mg) and 2 (40 mg) Only
Time frame: Part 1: Pre-dose on Day 8 and at multiple timepoints (Up to 96 hours) post-dose
Parts 2 and 4: AUC24: Area Under the Plasma Concentration-Time Curve From Time 0 to 24 Hours for TAK-041 in MRD Participants [Day 1]
Time frame: Parts 2 and 4: Day 1 pre-dose and at multiple time points (up to 168 hours) post-dose
Part 3: AUC24: Area Under the Plasma Concentration-Time Curve From Time 0 to 24 Hours for TAK-041 in RBA/Food Effect Participants [Day 1]
Time frame: Part 3: Day 1 pre-dose and at multiple time points (up to 96 hours) post-dose
Part 1: AUC96: Area Under the Plasma Concentration-Time Curve From Time 0 to 96 Hours for TAK-041 in SRD Participants [Day 1]
Time frame: Part 1: Day 1 pre-dose and at multiple time points post dose, up to 96 hours for Cohorts 1 and 2; up to 168 hours for Cohorts 3-5
Part 1: AUC96: Area Under the Plasma Concentration-Time Curve From Time 0 to 96 Hours for TAK-041 in SRD Participants [Day 8], Cohorts 1 (20 mg) and 2 (40 mg) Only
Time frame: Part 1: Pre-dose on Day 8 and at multiple timepoints (Up to 96 hours) post-dose
Parts 2 and 4: AUC96: Area Under the Plasma Concentration-Time Curve From Time 0 to 96 Hours for TAK-041 in MRD Participants [Day 1]
Time frame: Parts 2 and 4: Day 1 pre-dose and at multiple time points (up to 168 hours) post-dose
Part 1: AUCt: Area Under the Plasma Concentration-Time Curve From Time 0 to Time t for TAK-041 in SRD Participants [Day 1]
Time frame: Part 1: Day 1 pre-dose and at multiple time points post dose, up to 96 hours for Cohorts 1 and 2; up to 168 hours for Cohorts 3-5
Part 1: AUCt: Area Under the Plasma Concentration-Time Curve From Time 0 to Time t for TAK-041 in SRD Participants [Day 8], Cohorts 1 (20 mg) and 2 (40 mg) Only
Time frame: Part 1: Pre-dose on Day 8 and at multiple timepoints (Up to 96 hours) post-dose
Parts 2 and 4: AUCt: Area Under the Plasma Concentration-Time Curve From Time 0 to Time t for TAK-041 in MRD Participants [Day 1]
Time frame: Parts 2 and 4: Day 1 pre-dose and at multiple time points (up to 168 hours) post-dose
Part 3: AUCt: Area Under the Plasma Concentration-Time Curve From Time 0 to Time t for TAK-041 in RBA/Food Effect Participants [Day 1]
Time frame: Part 3: Day 1 pre-dose and at multiple time points (up to 96 hours) post-dose
Part 1: AUCinf: Area Under the Plasma Concentration-Time Curve From Time 0 to Infinity for TAK-041 in SRD Participants [Day 1]
Time frame: Part 1: Day 1 pre-dose and at multiple time points post dose, up to 96 hours for Cohorts 1 and 2; up to 168 hours for Cohorts 3-5
Part 1: AUCinf: Area Under the Plasma Concentration-Time Curve From Time 0 to Infinity for TAK-041 in SRD Participants [Day 8], Cohorts 1 (20 mg) and 2 (40 mg) Only
Time frame: Part 1: Pre-dose on Day 8 and at multiple timepoints (Up to 96 hours) post-dose
Parts 2 and 4: AUCtau: Area Under the Plasma Concentration-Time Curve From Time 0 to Time Tau Over the Dosing Interval for TAK-041 in MRD Participants [Day 1]
Time frame: Parts 2 and 4: Day 1 pre-dose and at multiple time points (up to 168 hours) post-dose
Part 1: T1/2z: Terminal Disposition Phase Half-Life for TAK-041 in SRD Participants [Day 1]
Time frame: Part 1: Day 1 pre-dose and at multiple time points post dose, up to 96 hours for Cohorts 1 and 2; up to 168 hours for Cohorts 3-5
Part 1: T1/2z: Terminal Disposition Phase Half-Life for TAK-041 in SRD Participants [Day 8], Cohorts 1 (20 mg) and 2 (40 mg) Only
Time frame: Part 1: Pre-dose on Day 8 and at multiple timepoints (Up to 96 hours) post-dose
Parts 2 and 4: T1/2z: Terminal Disposition Phase Half-Life for TAK-041 in MRD Participants [Day 1]
Time frame: Parts 2 and 4: Day 1 pre-dose and at multiple time points (up to 168 hours) post-dose

Results and safety

Results posted to the registry on 1 Mar 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
Part 1 (SRD): Placebo Cohorts 1-5	10	10
Part 1 (SRD): Cohort 1: TAK-041 5/20 mg	6	6
Part 1 (SRD): Cohort 2: TAK-041 10/40 mg	6	6
Part 1 (SRD): Cohort 3: TAK-041 80 mg	6	6
Part 1 (SRD): Cohort 4: TAK-041 120 mg	6	6
Part 1 (SRD): Cohort 5: TAK-041 160 mg	6	6
Part 2 (MRD): Placebo Cohorts 1-4	8	8
Part 2 (MRD): Cohort 1: TAK-041 40/20 mg	6	6
Part 2 (MRD): Cohort 2: TAK-041 80/40 mg	6	6
Part 2 (MRD): Cohort 3: TAK-041 120/60 mg	6	6
Part 2 (MRD): Cohort 4: TAK-041 160/80 mg	6	6
Part 3: Relative Bioavailability (RBA)/Food Effect: Regimen A	9	9
Part 3: RBA/Food Effect: Regimen B	9	9
Part 4: MRD: Placebo	8	8
Part 4: MRD: TAK-041 160/80 mg	16	14

Primary outcome: Percentage of Participants Who Experienced at Least One Treatment-Emergent Adverse Event (TEAE)

Time frame: From the first dose of study drug up to 42 days after the last dose of study drug (Up to 12 weeks). Number. Unit: percentage of participants

Measure	Part 1 (SRD): Placebo Cohorts 1-5 n = 10	Part 1 (SRD): Cohort 1: TAK-041 5 mg n = 6	Part 1 (SRD): Cohort 2: TAK-041 10 mg n = 6	Part 1 (SRD): Cohort 1: TAK-041 20 mg n = 6	Part 1 (SRD): Cohort 2: TAK-041 40 mg n = 6	Part 1 (SRD): Cohort 3: TAK-041 80 mg n = 6	Part 1 (SRD): Cohort 4: TAK-041 120 mg n = 6	Part 1 (SRD): Cohort 5: TAK-041 160 mg n = 6	Part 2 (MRD): Placebo Cohorts 1-4 n = 8	Part 2 (MRD): Cohort 1: TAK-041 40/20 mg n = 6	Part 2 (MRD): Cohort 2: TAK-041 80/40 mg n = 6	Part 2 (MRD): Cohort 3: TAK-041 120/60 mg n = 6	Part 2 (MRD): Cohort 4: TAK-041 160/80 mg n = 6	Part 3: Relative Bioavailability (RBA)/Food Effect: Regimen A n = 9	Part 3: RBA/Food Effect: Regimen B n = 9	Part 4: MRD: Placebo n = 8	Part 4: MRD: TAK-041 160/80 mg n = 16
Value	40.0	0	0	0	0	33.3	33.3	33.3	37.5	66.7	66.7	50.0	83.3	11.1	22.2	75.0	56.3

Population analysed: Safety Set included all participants who were enrolled and received at least 1 dose of study drug.

Primary outcome: Percentage of Participants Who Discontinued Study Drug Due to an Adverse Event (AE)

Time frame: From the first dose of study drug up to 42 days after the last dose of study drug (Up to 12 weeks). Number. Unit: percentage of participants

Measure	Part 1 (SRD): Placebo Cohorts 1-5 n = 10	Part 1 (SRD): Cohort 1: TAK-041 5 mg n = 6	Part 1 (SRD): Cohort 2: TAK-041 10 mg n = 6	Part 1 (SRD): Cohort 1: TAK-041 20 mg n = 6	Part 1 (SRD): Cohort 2: TAK-041 40 mg n = 6	Part 1 (SRD): Cohort 3: TAK-041 80 mg n = 6	Part 1 (SRD): Cohort 4: TAK-041 120 mg n = 6	Part 1 (SRD): Cohort 5: TAK-041 160 mg n = 6	Part 2 (MRD): Placebo Cohorts 1-4 n = 8	Part 2 (MRD): Cohort 1: TAK-041 40/20 mg n = 6	Part 2 (MRD): Cohort 2: TAK-041 80/40 mg n = 6	Part 2 (MRD): Cohort 3: TAK-041 120/60 mg n = 6	Part 2 (MRD): Cohort 4: TAK-041 160/80 mg n = 6	Part 3: Relative Bioavailability (RBA)/Food Effect: Regimen A n = 9	Part 3: RBA/Food Effect: Regimen B n = 9	Part 4: MRD: Placebo n = 8	Part 4: MRD: TAK-041 160/80 mg n = 16
Value	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0

Population analysed: Safety Set included all participants who were enrolled and received at least 1 dose of study drug.

Primary outcome: Percentage of Participants With Markedly Abnormal Value (MAV) Criteria for Safety Laboratory Tests At Least Once Post-dose

Time frame: From the first dose of study drug up to 42 days after the last dose of study drug (Up to 12 weeks). Number. Unit: percentage of participants

Measure	Part 1 (SRD): Placebo Cohorts 1-5 n = 10	Part 1 (SRD): Cohort 1: TAK-041 5 mg n = 6	Part 1 (SRD): Cohort 2: TAK-041 10 mg n = 6	Part 1 (SRD): Cohort 1: TAK-041 20 mg n = 6	Part 1 (SRD): Cohort 2: TAK-041 40 mg n = 6	Part 1 (SRD): Cohort 3: TAK-041 80 mg n = 6	Part 1 (SRD): Cohort 4: TAK-041 120 mg n = 6	Part 1 (SRD): Cohort 5: TAK-041 160 mg n = 6	Part 2 (MRD): Placebo Cohorts 1-4 n = 8	Part 2 (MRD): Cohort 1: TAK-041 40/20 mg n = 6	Part 2 (MRD): Cohort 2: TAK-041 80/40 mg n = 6	Part 2 (MRD): Cohort 3: TAK-041 120/60 mg n = 6	Part 2 (MRD): Cohort 4: TAK-041 160/80 mg n = 6	Part 3: Relative Bioavailability (RBA)/Food Effect: Regimen A n = 9	Part 3: RBA/Food Effect: Regimen B n = 9	Part 4: MRD: Placebo n = 8	Part 4: MRD: TAK-041 160/80 mg n = 16
Creatine Kinase, > 5 x ULN	0	0	0	0	0	0	0	16.7	12.5	0	0	0	0	0	11.1	0	12.5
Glucose < 50 mg/dL, < 2.8 mmol/L	0	0	0	0	0	0	16.7	0	0	0	0	0	0	0	0	0	0
Aspartate Aminotransferase, > 3 x ULN

Primary outcome: Percentage of Participants With Markedly Abnormal Criteria for Vital Sign Measurements at Least Once Post-dose

Time frame: From the first dose of study drug up to 42 days after the last dose of study drug (Up to 12 weeks). Number. Unit: percentage of participants

Measure	Part 1 (SRD): Placebo Cohorts 1-5 n = 10	Part 1 (SRD): Cohort 1: TAK-041 5 mg n = 6	Part 1 (SRD): Cohort 2: TAK-041 10 mg n = 6	Part 1 (SRD): Cohort 1: TAK-041 20 mg n = 6	Part 1 (SRD): Cohort 2: TAK-041 40 mg n = 6	Part 1 (SRD): Cohort 3: TAK-041 80 mg n = 6	Part 1 (SRD): Cohort 4: TAK-041 120 mg n = 6	Part 1 (SRD): Cohort 5: TAK-041 160 mg n = 6	Part 2 (MRD): Placebo Cohorts 1-4 n = 8	Part 2 (MRD): Cohort 1: TAK-041 40/20 mg n = 6	Part 2 (MRD): Cohort 2: TAK-041 80/40 mg n = 6	Part 2 (MRD): Cohort 3: TAK-041 120/60 mg n = 6	Part 2 (MRD): Cohort 4: TAK-041 160/80 mg n = 6	Part 3: Relative Bioavailability (RBA)/Food Effect: Regimen A n = 9	Part 3: RBA/Food Effect: Regimen B n = 9	Part 4: MRD: Placebo n = 8	Part 4: MRD: TAK-041 160/80 mg n = 16
Systolic Blood Pressure, Standing, < 85 mmHg	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	12.5	0
Systolic Blood Pressure, Supine, < 85 mmHg	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Systolic Blood Pressure, 5 min Supine, < 85 mmHg

24 secondary outcomes are reported in the full results.

Adverse events

Time frame: From the first dose of study drug up to 42 days after the last dose of study drug (Up to 12 weeks). Other adverse events reported at 0% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Part 1 (SRD): Placebo Cohorts 1-5	0 of 10 (0%)	4 of 10 (40%)	0 of 10
Part 1 (SRD): Cohort 1: TAK-041 5 mg	0 of 6 (0%)	0 of 6 (0%)	0 of 6
Part 1 (SRD): Cohort 2: TAK-041 10 mg	0 of 6 (0%)	0 of 6 (0%)	0 of 6
Part 1 (SRD): Cohort 1: TAK-041 20 mg	0 of 6 (0%)	0 of 6 (0%)	0 of 6
Part 1 (SRD): Cohort 2: TAK-041 40 mg	0 of 6 (0%)	0 of 6 (0%)	0 of 6
Part 1 (SRD): Cohort 3: TAK-041 80 mg	0 of 6 (0%)	2 of 6 (33.3%)	0 of 6
Part 1 (SRD): Cohort 4: TAK-041 120 mg	0 of 6 (0%)	2 of 6 (33.3%)	0 of 6
Part 1 (SRD): Cohort 5: TAK-041 160 mg	0 of 8 (0%)	2 of 6 (33.3%)	0 of 6
Part 2 (MRD): Placebo Cohorts 1-4	0 of 6 (0%)	3 of 8 (37.5%)	0 of 8
Part 2 (MRD): Cohort 1: TAK-041 40/20 mg	0 of 6 (0%)	4 of 6 (66.7%)	0 of 6
Part 2 (MRD): Cohort 2: TAK-041 80/40 mg	0 of 6 (0%)	4 of 6 (66.7%)	0 of 6
Part 2 (MRD): Cohort 3: TAK-041 120/60 mg	0 of 6 (0%)	3 of 6 (50%)	0 of 6
Part 2 (MRD): Cohort 4: TAK-041 160/80 mg	0 of 6 (0%)	5 of 6 (83.3%)	0 of 6
Part 3: Relative Bioavailability (RBA)/Food Effect: Regimen A	0 of 9 (0%)	1 of 9 (11.1%)	0 of 9
Part 3: RBA/Food Effect: Regimen B	0 of 9 (0%)	2 of 9 (22.2%)	0 of 9
Part 4: MRD: Placebo	0 of 8 (0%)	6 of 8 (75%)	0 of 8
Part 4: MRD: TAK-041 160/80 mg	0 of 16 (0%)	9 of 16 (56.3%)	0 of 16

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 35277995Yin W, Han D, Khudyakov P, Behrje R, Posener J, Laurenza A, Arkilo D. A phase 1 study to evaluate the safety, tolerability and pharmacokinetics of TAK-041 in healthy participants and patients with stable schizophrenia. Br J Clin Pharmacol. 2022 Aug;88(8):3872-3882. doi: 10.1111/bcp.15305. Epub 2022 Apr 17.
Individual participant dataSharing planned: Yes. Takeda makes patient-level, de-identified data sets and associated documents available for all interventional studies after applicable marketing approvals and commercial availability have been received (or program is completely terminated), an opportunity for the primary publication of the research and final report development has been allowed, and other criteria have been met as set forth in Takeda's Data Sharing Policy (see www.TakedaClinicalTrials.com for details). To obtain access, researchers must submit a legitimate academic research proposal for adjudication by an independent review panel, who will review the scientific merit of the research and the requestor's qualifications and conflict of interest that can result in potential bias. Once approved, qualified researchers who sign a data sharing agreement are provided access to these data in a secure research environment.

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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 1 study testing TAK-041 in people with Healthy Volunteers and Schizophrenia, run by Neurocrine Biosciences at 1 site in United States.

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 13 inclusion and 33 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 States. 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. Some participants in this study may receive a placebo. 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 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

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 1 Mar 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?

Percentage of Participants Who Experienced at Least One Treatment-Emergent Adverse Event (TEAE) (time frame: From the first dose of study drug up to 42 days after the last dose of study drug (Up to 12 weeks)). The study lists 8 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 NCT02748694, 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.