A Study of Safety and Tolerability in Subjects With Schizophrenia

NCT01354353 | Completed Phase 1 Results

• 2 other identifiers: 13565H8Y-MC-HBDB
• Study Type: interventional
• Target: 75
• Locations: 1 country
• Sites: 2

Brief Summary

This is an inpatient, open-label, multiple-dose, multicenter study to evaluate the safety and tolerability of LY2140023 given at doses expected to reflect multiples of the anticipated therapeutic exposure under clinical investigation. In the event of poor tolerability in Part A of this study Part B may be conducted to explore higher doses using titration. Participants in both Parts A and B will participate in a 9 day wash-out period of current medication (Study Days 1-9); participants coming into the study on aripiprazole will remain on their current therapy throughout.

Conditions

Schizophrenia

Outcome Measures

Primary Outcomes (1)

• Number of Participants With Clinically Significant Events (Physical Assessments and Clinical Lab Tests)

  Participants with at least 1 postdose (Day 10 through the end of study visit \[Day 21\]) treatment emergent adverse event (TEAE) were counted by dose cohort. A summary of serious and other non-serious adverse events regardless of causality is located in the Reported Adverse Events module.

  Baseline up to Day 21 for Part A

Secondary Outcomes (9)

• Part A: Pharmacokinetics, Maximum Concentration (Cmax)

  Pre-dose and post-dose on Day 10 and Day 16

• Part B: Pharmacokinetics, Maximum Concentration (Cmax)

  Pre-dose and post-dose on Days 12, 15, 18, 21, and 24

• Part A: Pharmacokinetics, Area Under the Concentration - Time Curve (AUC)

  Pre-dose and post-dose on Day 10 and Day 16

• Part B: Pharmacokinetics, Area Under the Concentration - Time Curve (AUC)

  Pre-dose and post-dose on Days 12, 15, 18, 21, and 24

• Percentage of Participants With Increased Severity From Baseline to Day 17 in Clinical Global Impression- Severity Scale (CGI-S)

  Baseline through Day 17 for Part A

Study Arms (7)

Aripiprazole

ACTIVE COMPARATOR

Part A: Continue current prescribed dosing regimen -- Study Day 1 to discharge (Study Day 21). Part B: Continue current prescribed dosing regimen (≤ 30 milligrams \[mg\]/day ) -- Study Day 1 to discharge (Study Day 23, 25 or 28 based on adaptive design)

Drug: Aripiprazole

Part A: 160 mg LY2140023

EXPERIMENTAL

Administered orally, twice daily (BID) for 6 days (Study Days 10-15) and as a single morning dose on the 7th day (Study Day 16)

Drug: LY2140023

Part A: 240 mg LY2140023

EXPERIMENTAL

Administered orally BID for 6 days (Study Days 10-15) and as a single morning dose on the 7th day (Study Day 16)

Drug: LY2140023

Part A: 320 mg LY2140023

EXPERIMENTAL

Administered orally BID for 6 days (Study Days 10-15) and as a single morning dose on the 7th day (Study Day 16)

Drug: LY2140023

Part A: 400 mg LY2140023

EXPERIMENTAL

Administered orally BID for 6 days (Study Days 10-15) and as a single morning dose on the 7th day (Study Day 16)

Drug: LY2140023

Part A: 480 mg LY2140023

EXPERIMENTAL

Administered orally BID for 6 days (Study Days 10-15) and as a single morning dose on the 7th day (Study Day 16)

Drug: LY2140023

Part B: LY2140023

EXPERIMENTAL

If doses up to or equal to 400 mg BID are not tolerated, Part B of the study may be started. The dose of LY2140023 will be titrated in the same participant from highest dose that was tolerated in Part A, with the intention to reach a dose of 480 mg LY2140023.

Drug: LY2140023

Interventions

LY2140023 DRUG

Administered orally

Also known as: pomaglumetad methionil

Part A: 160 mg LY2140023; Part A: 240 mg LY2140023; Part A: 320 mg LY2140023; Part A: 400 mg LY2140023; Part A: 480 mg LY2140023; Part B: LY2140023

Aripiprazole DRUG

Administered orally

Also known as: Abilify

Aripiprazole

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Have a diagnosis of schizophrenic disorder
• Female participants who test negative for pregnancy at screening and agree to use a reliable method of birth control for the duration of the study and for at least 3 months after the last LY2140023 dose or are postmenopausal
• Not have been hospitalized for psychiatric illness for at least 12 weeks prior to Day 1 of washout period and have a Clinical Global Impression -Severity (CGI-S) scale score of \<4
• Be willing and able as determined by the investigator to be hospitalized from the beginning of the washout period to the end of the study
• In the opinion of the investigator, the participant can be washed out of their Standard of Care (SOC) therapy (other than aripiprazole for the aripiprazole participants) for the duration of the study without detrimental effect to the participant's mental health (CGI-S \<4 after completion of the washout period)
• Be considered reliable, have a level of understanding sufficient to perform all tests and examinations required by the protocol, and be willing to perform all study procedures
• Be able to understand the nature of the study and have given their own informed consent
• Have clinical laboratory test results within normal reference range for the population or investigator site, or results with acceptable deviations that are judged to be not clinically significant by the investigator
• Have venous access sufficient to allow blood sampling
• Clinically acceptable sitting blood pressure and pulse rate, as determined by the investigator
• Participants on Aripiprazole prior to study entry must:
• On a stable dose of aripiprazole within the approved range in product labeling (less than or equal to 30 milligrams \[mg\]/day) for at least 60 days prior to Day 1 and with no anticipation of changes to dose, regimen (except as required for this study) or treatment within the next 1 month

You may not qualify if:

• Currently enrolled in, or discontinued within the 30 days prior to screening from, a clinical trial involving an investigational drug or concurrently enrolled in any other type of medical research judged not to be scientifically or medically compatible with this study
• Have known allergies to LY2140023, LY404039, aripiprazole, or related compounds
• Participants with moderate to severe renal impairment as defined by creatinine clearance (CrCl) \<60 milliliters (mL)/minute (min)
• Have previously completed this study or have discontinued from any study investigating LY2140023 after having received at least 1 dose of LY2140023
• Participants for whom treatment with LY2140023 or aripiprazole as specified in this protocol, is relatively or absolutely clinically contraindicated
• Participants who have received treatment with clozapine
• Participants who have a diagnosis of schizophrenia who are taking either thioridazine or thiothixene
• Participants receiving treatment with depot antipsychotic medication within 12 weeks, prior to screening
• Participants who are taking any of medications that are specifically excluded
• Participants who have answered 'yes' to either Question 4 (Active Suicidal Ideation with Some Intent to Act, Without Specific Plan) or Question 5 (Active Suicidal Ideation with Specific Plan and Intent) on the "Suicidal Ideation" portion of the Columbia suicide severity rating scale (C-SSRS), or answer "yes" to any of the suicide-related behaviors (actual attempt, interrupted attempt, aborted attempt, preparatory act or behavior) on the "Suicidal Behavior" portion of the C-SSRS; and the ideation or behavior occurred within the past 3 months
• Diagnostic and Statistical Manual of Mental Disorders-Fourth Edition (Text Revision) (DSM-IV-TR) diagnosis of substance dependence or substance abuse (except nicotine and caffeine) within the 6 months prior to admission
• Diagnosis of substance-induced psychosis by DSM-IV-TR criteria within 7 days of admission (or at any time during the dosing period)
• Have a history of one or more seizures except for either of the following 2 situations: a single simple febrile seizure between ages 6 months and 5 years or a single seizure with an identifiable etiology, which has been completely resolved
• Have a screening electroencephalogram (EEG) with paroxysmal (epileptiform) activity, for example, one that demonstrates 3 or more focal sharp or spike waves, any sharp and slow wave complex, or any epileptiform discharge that is rhythmic, sustained, or generalized, or as locally defined
• Participants who have had electroconvulsive therapy (ECT) within 3 months of observation period or who are expected to have ECT at any time during the live phase of this study

Sponsors & Collaborators

• Denovo Biopharma LLC: lead

Study Sites (2)

For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.

Garden Grove, California, 92845, United States

Location

For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.

Glendale, California, 91206, United States

Location

MeSH Terms

Conditions

Schizophrenia

Interventions

LY 2140023; pomaglumetad methionil; Aripiprazole

Condition Hierarchy (Ancestors)

Schizophrenia Spectrum and Other Psychotic Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Piperazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Quinolones; Quinolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Limitations and Caveats

No analyses were performed and results were not calculated for Part B of this study because the study was stopped prior to Part B being initiated.

Results Point of Contact

• Title: Chief Medical Officer
• Organization: Eli Lilly and Company

800-545-5979

Study Officials

• Call 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 Mon - Fri 9 AM - 5 PM Eastern time (UTC/GMT - 5 hours, EST)

  Eli Lilly and Company

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: GT60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: OTHER
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 13, 2011
• First Posted: May 16, 2011
• Study Start: May 1, 2011
• Primary Completion: March 1, 2012
• Study Completion: March 1, 2012
• Last Updated: September 14, 2022
• Results First Posted: September 14, 2021

Record last verified: 2022-08

Locations

US (2)