Safety and Tolerability of Multiple Doses of ITI-214 in Healthy Adults and in Adults With Stable Schizophrenia

NCT01900522 | Terminated Phase 1

• 2 other identifiers: ITI-214_102U1111-1142-0234
• Study Type: interventional
• Target: 76
• Locations: 1 country
• Sites: 2

Brief Summary

The purpose of this study is to characterize the safety and tolerability profile of ITI-214 when administered as multiple doses of oral solution at escalating dose levels.

Conditions

Schizophrenia

Keywords

Drug therapy

Outcome Measures

Primary Outcomes (1)

• Percentage of participants who experience at least one treatment-emergent adverse event (TEAE)

  A treatment-emergent adverse event (TEAE) is defined as an adverse event with an onset that occurs after receiving study drug and within 30 days after receiving the last dose of study drug. A TEAE may also be a pre-treatment adverse event or a concurrent medical condition diagnosed prior to the date of first dose of study drug, which increases in intensity after the start of dosing.

  Day 1 to Day 44 (up to 24 hours postdose)

Secondary Outcomes (4)

• Tmax: Time to Reach the Maximum Plasma Concentration

  Days 1 and 14 (up to 24 hours postdose)

• Cmax: Maximum Observed Plasma Concentration

  Days 1 and 14 (up to 24 hours postdose)

• AUC(0-tlqc): Area Under the Plasma Concentration-Time Curve From Time 0 to the Time of the Last Quantifiable Concentration

  Days 1 and 14 (up to 24 hours postdose)

• AUC(0-24): Area Under the Plasma Concentration-Time Curve From Time 0 to 24 Hours Postdose

  Days 1 and 14 (up to 24 hours postdose)

Study Arms (2)

Multiple Rising Dose (MRD) Phase: Ascending ITI-214 Doses

EXPERIMENTAL

ITI-214 Doses (A, B, C, D, matching placebo), solution, orally, once daily for 14 days.

Drug: ITI-214 Dose A; Drug: ITI-214 Dose B; Drug: ITI-214 Dose C; Drug: ITI-214 Dose D (Elderly); Drug: Placebo

Neuroimaging Phase: ITI-214 Doses

EXPERIMENTAL

ITI-214 (E,F, G, H, matching Placebo) Oral solution, once daily for 7 days in 3 periods with placebo and two of the ITI-214 Doses (E, F, G and H) in a cross-over fashion with minimum 7 days washout between periods

Drug: ITI-214 Dose E; Drug: ITI-214 Dose F; Drug: ITI-214 Dose G; Drug: ITI-214 Dose H; Drug: Placebo

Interventions

ITI-214 Dose A DRUG

ITI-214 Dose A Oral Solution

Multiple Rising Dose (MRD) Phase: Ascending ITI-214 Doses

ITI-214 Dose B DRUG

ITI-214 Oral Solution Dose B

Multiple Rising Dose (MRD) Phase: Ascending ITI-214 Doses

ITI-214 Dose C DRUG

ITI-214 Dose C Oral Solution

Multiple Rising Dose (MRD) Phase: Ascending ITI-214 Doses

ITI-214 Dose D (Elderly) DRUG

ITI-214 Dose D (Elderly) Oral Solution

Multiple Rising Dose (MRD) Phase: Ascending ITI-214 Doses

Placebo DRUG

ITI-214 Matching Placebo Oral Solution

Multiple Rising Dose (MRD) Phase: Ascending ITI-214 Doses

ITI-214 Dose E DRUG

ITI-214 Dose E Oral Solution

Neuroimaging Phase: ITI-214 Doses

ITI-214 Dose F DRUG

ITI-214 Dose F Oral Solution

Neuroimaging Phase: ITI-214 Doses

ITI-214 Dose G DRUG

ITI-214 Dose G Oral Solution

Neuroimaging Phase: ITI-214 Doses

ITI-214 Dose H DRUG

ITI-214 Dose H Oral Solution

Neuroimaging Phase: ITI-214 Doses

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Healthy Participants
• Is capable of understanding and complying with protocol requirements.
• The participant or; when applicable, the participant's legally acceptable representative signs and dates a written, informed consent form and any required privacy authorization prior to the initiation of any study procedures.
• Is a healthy man or woman, aged 18 to 55 years, inclusive (non-elderly) or aged ≥65 years (elderly), at the time of informed consent and first study medication dose.
• Weighs at least 50 kg and has a body mass index (BMI) between 18.0 and 35.0 kg/m\^2, inclusive at Screening.
• A male participant who is nonsterilized and sexually active with a female partner of childbearing potential agrees to use adequate contraception from signing of informed consent throughout the duration of the study and for 12 weeks after last dose.
• A female participant with no childbearing potential. The participant has been surgically sterilized (hysterectomy, bilateral oophorectomy or tubal ligation) or who are postmenopausal (defined as continuous amenorrhea of at least 2 years and follicle-stimulating hormone (FSH) \>40 IU/L.
• Participants with schizophrenia:
• Is capable of understanding and complying with protocol requirements.
• The participant or, when applicable, the participant's legally acceptable representative signs and dates a written, informed consent form and any required privacy authorization prior to the initiation of any study procedures.
• Is capable of consenting. A standard evaluation by a psychiatrist will be implemented to assess the participant's capacity to consent.
• Is a man or woman, aged 18 to 60 years (non-elderly), inclusive, or aged ≥65 years (elderly, if decided to enroll), at the time of informed consent and first study medication dose.
• Weighs at least 50 kg and has a body mass index (BMI) between 18.0 and 35.0 kg/m\^2, inclusive at Screening.
• Is diagnosed with schizophrenia criteria as defined by the Diagnostic \& Statistical Manual of Mental Disorders 4th Edition - Text Revision (DSM-IV-TR) and determined by the Structured Clinical Interview for DSM-IV Axis I Disorders (SCID-I), schizoaffective disorder, or schizophreniform disorder; on a stable dose of one and only one of the second generation antipsychotics (except olanzapine, clozapine, or quetiapine) for at least 2 months by medical history and assessed by site staff; Positive and Negative Syndrome Scale (PANSS) Conceptual Disorganization item score ≤ 4 and PANSS Hallucinatory Behavior or Unusual Thought Content item scores ≤ 4. For the MRD part, the subject is diagnosed with schizophrenia criteria as defined by the DSM-IV-TR and determined by the SCID-I, schizoaffective disorder, or schizophreniform disorder; on a stable dose of one and only one of the second generation antipsychotics (except clozapine) for at least 2 months by medical history and assessed by site staff; PANSS Conceptual Disorganization item score ≤ 4 and PANSS Hallucinatory Behavior or Unusual Thought Content item scores ≤ 4.
• A male participant who is nonsterilized and sexually active with a female partner of childbearing potential agrees to use adequate contraception from signing of informed consent throughout the duration of the study and for 12 weeks after last dose.

You may not qualify if:

• Healthy Participants
• Has received any investigational compound within 30 days prior to the first dose of study medication.
• Has received ITI-214 in a previous clinical study or as a therapeutic agent.
• Is an immediate family member, study site employee, or in a dependant relationship with a study site employee who is involved in the conduct of this study (eg, spouse, parent, child, sibling) or may consent under duress.
• Has uncontrolled, clinically significant neurologic, cardiovascular, pulmonary, hepatic, renal, metabolic, gastrointestinal, urologic, immunologic, endocrine disease, or psychiatric disorder, or other abnormality, which may impact the ability of the participant to participate or potentially confound the study results.
• Has a known hypersensitivity to any component of the formulation of ITI-214 or Listerine.
• Has a positive urine drug result for drugs of abuse at Screening or Check-in (Day -1).
• Has a history of drug abuse (defined as any illicit drug use) or a history of alcohol abuse within 1 year prior to the Screening visit or is unwilling to agree to abstain from alcohol and drugs throughout the study.
• Has taken any excluded medication, supplements, or food products.
• Is pregnant or lactating or intending to become pregnant before, during, or within 12 weeks after participating in this study; or intending to donate ova during such time period.
• If male, the participant 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 ITI-214, 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. Elderly participants may have been eligible for enrollment if approved by the investigator and Takeda medical monitor.
• Has mental retardation or medical condition that can cause cognitive impairment.
• Has current or recent (within 6 months) gastrointestinal disease that would be expected to influence the absorption of drugs (ie, a history of malabsorption, any surgical intervention known to impact absorption \[eg, bariatric surgery or bowel resection\], esophageal reflux, peptic ulcer disease, erosive esophagitis, or frequent \[more than once per week\] occurrence of heartburn).
• Has a history of cancer, except basal cell carcinoma which has not been in remission for at least 5 years prior to Check-in (Day -1)

Sponsors & Collaborators

• Takeda: lead
• Intra-Cellular Therapies, Inc.: collaborator

Study Sites (2)

Unknown Facility

Glendale, California, United States

Location

Unknown Facility

New York, New York, United States

Location

MeSH Terms

Conditions

Schizophrenia

Interventions

Aging

Condition Hierarchy (Ancestors)

Schizophrenia Spectrum and Other Psychotic Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Growth and Development; Physiological Phenomena

Study Officials

• Medical Director

  Takeda

  STUDY DIRECTOR

Study Design

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

Study Record Dates

• First Submitted: July 11, 2013
• First Posted: July 16, 2013
• Study Start: July 1, 2013
• Primary Completion: September 1, 2014
• Study Completion: December 1, 2014
• Last Updated: February 19, 2015

Record last verified: 2015-02

Locations

US (2)