Safety, Tolerability and Pharmacokinetic Study of Multiple Rising Doses of TAK- 063 in Participants With Stable Schizophrenia and Healthy Participants

NCT01879722 | Completed Phase 1 Results

• 2 other identifiers: TAK-063_104U1111-1139-5355
• Study Type: interventional
• Target: 77
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to characterize the safety and tolerability of TAK-063 when administered as multiple oral doses at escalating dose levels in participants with stable schizophrenia and in healthy Japanese participants.

Conditions

Schizophrenia

Keywords

Drug therapy

Outcome Measures

Primary Outcomes (4)

• Percentage of Participants Who Experience at Least One Treatment-Emergent Adverse Event (TEAE) After 7 Days of Dosing

  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. An AE can therefore be any unfavorable and unintended sign (eg, a clinically significant abnormal laboratory finding), symptom, or disease temporally associated with the use of a drug, whether or not it is considered related to the drug. A treatment-emergent adverse event (TEAE) is defined as an adverse event with an onset that occurs after receiving study drug.

  Day 1 to Day 14

• Percentage of Participants With Markedly Abnormal Safety Laboratory Tests

  The percentage of participants with any markedly abnormal standard safety laboratory values, including hematology, serum chemistries, and urinalysis, during the treatment period.

  Day 1 to Day 8

• Percentage of Participants With Markedly Abnormal Vital Sign Measurements

  The percentage of participants who meet markedly abnormal criteria for vital signs, including oral body temperature, respiration rate, pulse, and resting blood pressure and after standing

  Day 1 to Day 8

• Percentage of Participants With Markedly Abnormal Values of 12-Lead Electrocardiogram (ECG) Parameters

  The percentage of participants who meet markedly abnormal criteria specified by the protocol and statistical analysis plan during the treatment period.

  Day 1 to Day 8

Secondary Outcomes (12)

• Cmax: Maximum Observed Plasma Concentration for TAK-063 and TAK-063 Metabolite M-I

  Days 1 and 7 pre-dose and multiple time-points post-dose (Up to 24 hours)

• Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for TAK-063 and TAK-063 Metabolite M-I

  Days 1 and 7 pre-dose and multiple time-points post-dose (Up to 24 hours)

• AUC(0-tlqc): Area Under the Plasma Concentration-Time Curve From Time 0 to the Time of the Last Quantifiable Concentration for TAK-063 and TAK-063 Metabolite M-I

  Days 1 and 7 pre-dose and multiple time-points post-dose (Up to 24 hours)

• AUC(0-24): Area Under the Plasma Concentration-Time Curve From Time 0 to 24 Hours Postdose for TAK-063 and TAK-063 Metabolite M-I

  Days 1 and 7 pre-dose and multiple time-points post-dose (Up to 24 hours)

• CL/F: Oral Clearance of TAK-063

  Days 1 and 7 pre-dose and multiple time-points post-dose (Up to 24 hours)

Study Arms (6)

TAK-063 3 mg

EXPERIMENTAL

TAK-063 3 mg, tablets, orally, once daily for 7 days.

Drug: TAK-063

TAK-063 10 mg

EXPERIMENTAL

TAK-063 10 mg, tablets, orally, once daily for 7 days.

Drug: TAK-063

TAK-063 20 mg

EXPERIMENTAL

TAK-063 20 mg, tablets, orally, once daily for 7 days.

Drug: TAK-063

TAK-063 30 mg

EXPERIMENTAL

TAK-063 30 mg, tablets, orally, once daily for 7 days.

Drug: TAK-063

TAK-063 100 mg

EXPERIMENTAL

TAK-063 100 mg, tablets, orally, once daily for 7 days.

Drug: TAK-063

Placebo

PLACEBO COMPARATOR

Placebo matching TAK-063, tablets, orally, once daily for 7 days.

Drug: TAK-063 Placebo

Interventions

TAK-063 DRUG

TAK-063 tablets

TAK-063 10 mg; TAK-063 100 mg; TAK-063 20 mg; TAK-063 3 mg; TAK-063 30 mg

TAK-063 Placebo DRUG

TAK-063 placebo-matching tablets

Placebo

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Healthy Participants:
• Aged 20-55 years, inclusive, at the time of informed consent and first study medication dose.
• Is a healthy adult male or female of Japanese descent (born to Japanese parents and grandparents and has lived outside of Japan for less than 5 years).
• Weighs at least 45 kg and has a body mass index (BMI) between 18.0 and 28.0 kg/m\^2, inclusive, at Screening.
• Participants with Stable Schizophrenia:
• Is aged 18 to 55 years, inclusive, at the time of informed consent and first study medication dose.
• Is an adult male or female with a diagnosis of schizophrenia or schizoaffective disorder.
• Weighs at least 45 kg and has a BMI between 18.0 and 35.0 kg/m\^2, inclusive at Screening.
• Has been receiving a stable dose of antipsychotic monotherapy for at least 1 month prior to Screening.
• Has not had an acute exacerbation of psychosis or been hospitalization for the treatment of schizophrenia or schizoaffective disorder for at least 3 months prior to Screening.

You may not qualify if:

• All Participants:
• Has uncontrolled, clinically significant neurologic, cardiovascular, pulmonary, hepatic, renal, metabolic, gastrointestinal, or endocrine disease or other abnormality (other than the disease being studied), which may impact the ability of the participant to participate or potentially confound the study results.
• If female, the participant is pregnant or lactating or intending to become pregnant, or intending to donate ova, before, during the course of the study or within 12 weeks after last dose.
• Intends to donate sperm during the course of this study or for 12 weeks after last dose.
• Has evidence of current cardiovascular, central nervous system, hepatic, 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 tests giving reasonable suspicion of a disease that would contraindicate taking TAK-063, or a similar drug in the same class, or that might interfere with the conduct of the study. This includes, but is not limited to, peptic ulcer disease, seizure disorders, and cardiac arrhythmias.
• Healthy Participants:
• Has a history or treatment of Axis I/II mental disorders according to Diagnostic and Statistical Manual of Mental Disorders, 4th Edition (DSM-IV) such as depression, anxiety disorders, bipolar disorder, attention deficit hyperactivity disorder (ADHD), autism spectrum disorders, anorexia nervosa, bulimia nervosa or schizophrenia within the past 3 years.
• Has used nicotine-containing products (including but not limited to cigarettes, pipes, cigars, chewing tobacco, nicotine patch or nicotine gum) within 28 days prior to Check-in Day -1. Cotinine test is positive at Screening or Check-in (Day -1).
• Participants with Stable Schizophrenia:
• Has a history of a primary DSM-IV axis I diagnosis other than schizophrenia or schizoaffective disorder.
• Has not discontinued antipsychotic or other psychotropic medications or is unable to discontinue antipsychotic or other psychotropic medications at Day -7 (or five half-lives prior to Day -1).
• Is taking a concomitant medication for a medical condition at a stable dose or regimen for less than two months or is taking a concomitant medication for a medical condition for less than two months and for which the discontinuation for the study period is not medically permissible.

Sponsors & Collaborators

• Takeda: lead

Study Sites (1)

Unknown Facility

Glendale, California, United States

Location

Related Publications (1)

• Goldsmith P, Affinito J, McCue M, Tsai M, Roepcke S, Xie J, Gertsik L, Macek TA. A Randomized Multiple Dose Pharmacokinetic Study of a Novel PDE10A Inhibitor TAK-063 in Subjects with Stable Schizophrenia and Japanese Subjects and Modeling of Exposure Relationships to Adverse Events. Drugs R D. 2017 Dec;17(4):631-643. doi: 10.1007/s40268-017-0214-8.

  PMID: 29103081 DERIVED

MeSH Terms

Conditions

Schizophrenia

Interventions

1-(2-fluoro-4-(1H-pyrazol-1-yl)phenyl)-5-methoxy-3-(1-phenyl-1H-pyrazol-5-yl)pyridazin-4(1H)-one

Condition Hierarchy (Ancestors)

Schizophrenia Spectrum and Other Psychotic Disorders; Mental Disorders

Results Point of Contact

• Title: Medical Director, Clinical Science
• Organization: Takeda (Note: This product was divested to Axsome in 2026)

clinicaltrialregistry@tpna.com

+1-877-825-3327

Study Officials

• Medical Director

  Takeda Global Research & Development Center, Inc. (Note: This product was divested to Axsome in 2026)

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 13, 2013
• First Posted: June 18, 2013
• Study Start: June 1, 2013
• Primary Completion: June 1, 2014
• Study Completion: June 1, 2014
• Last Updated: May 8, 2026
• Results First Posted: October 28, 2016

Record last verified: 2026-04

Locations

US (1)