A Study of Safety and Tolerability in Subjects With Schizophrenia

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Eli Lilly and Company
ClinicalTrials.gov Identifier:
NCT01354353
First received: May 13, 2011
Last updated: August 9, 2012
Last verified: August 2012
  Purpose

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. Subjects in both parts A and B will participate in a 9 day wash-out period of current medication (Study days 1-9); subjects coming into the study on aripiprazole will remain on their current therapy throughout.


Condition Intervention Phase
Schizophrenia
Drug: LY2140023
Drug: Aripiprazole
Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Official Title: Safety and Tolerability of Multiple Ascending Doses of LY2140023 in Subjects With Schizophrenia

Resource links provided by NLM:


Further study details as provided by Eli Lilly and Company:

Primary Outcome Measures:
  • Number of participants with clinically significant events (physical assessments and clinical lab tests) [ Time Frame: Baseline up to Day 21 for Part A; Baseline up to Day 29 for Part B ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Part A: Pharmacokinetics, maximum concentration (Cmax) [ Time Frame: Pre dose and post dose on day 10 and day 16 ] [ Designated as safety issue: No ]
  • Part B: Pharmacokinetics, maximum concentration (Cmax) [ Time Frame: Pre-dose and post-dose on days 12, 15, 18, 21,and 24 ] [ Designated as safety issue: No ]
  • Part A: Pharmacokinetics, area under the concentration - time curve (AUC) [ Time Frame: Pre-dose and post-dose on Day 10 and Day 16 ] [ Designated as safety issue: No ]
  • Part B: Pharmacokinetics, area under the concentration - time curve (AUC) [ Time Frame: Pre-dose and post dose on days 12, 15, 18, 21,and 24 ] [ Designated as safety issue: No ]
  • Change from baseline in Clinical Global Impression- Severity Scale (CGI-S) [ Time Frame: Baseline through Day 17 for Part A, Baseline through Day 25 for Part B ] [ Designated as safety issue: Yes ]
  • Change from baseline in Brief Psychiatric Rating Scale (BPRS) [ Time Frame: Baseline through Day 17 for Part A, Baseline through Day 25 for Part B ] [ Designated as safety issue: Yes ]
  • Change from baseline in Abnormal Involuntary Movement Scale (AIMS) [ Time Frame: Baseline through Day 17 for Part A, Baseline through Day 25 for Part B ] [ Designated as safety issue: Yes ]
  • Change from baseline through 21 days in Simpson-Angus Scale (SAS) [ Time Frame: Baseline through Day 17 for Part A, Baseline through Day 25 for Part B ] [ Designated as safety issue: Yes ]
  • Change from baseline through 21 days in Barnes Akathisia Scale (BAS) [ Time Frame: Baseline through Day 17 for Part A, Baseline through Day 25 for Part B ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 120
Study Start Date: May 2011
Study Completion Date: March 2012
Primary Completion Date: March 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Aripiprazole
Part A: Continue current prescribed dosing regimen -- Study Day 1 to discharge (Study Day 21). Part B: Continue current prescribed dosing regimen -- Study Day 1 to discharge (Study Day 23, 25 or 28 based on adaptive design)
Drug: Aripiprazole
Administered orally
Experimental: Part A: 160 mg LY2140023
Administered orally, twice daily for 6 days (Study Days 10-15) and as a single morning dose on the 7th day (Study Day 16)
Drug: LY2140023
Administered orally
Experimental: Part A: 240 mg LY2140023
Administered orally, twice daily for 6 days (Study Days 10-15) and as a single morning dose on the 7th day (Study Day 16)
Drug: LY2140023
Administered orally
Experimental: Part A: 320 mg LY2140023
Administered orally, twice daily for 6 days (Study Days 10-15) and as a single morning dose on the 7th day (Study Day 16)
Drug: LY2140023
Administered orally
Experimental: Part A: 400 mg LY2140023
Administered orally, twice daily for 6 days (Study Days 10-15) and as a single morning dose on the 7th day (Study Day 16)
Drug: LY2140023
Administered orally
Experimental: Part A: 480 mg LY2140023
Administered orally, twice daily for 6 days (Study Days 10-15) and as a single morning dose on the 7th day (Study Day 16)
Drug: LY2140023
Administered orally
Experimental: Part B: LY2140023
If doses up to or equal to 400 mg twice daily are not tolerated, Part B of the study may be started. The dose of LY2140023 will be titrated in the same subject from highest dose that was tolerated in Part A, with the intention to reach a dose of 480 mg LY2140023.
Drug: LY2140023
Administered orally

  Eligibility

Ages Eligible for Study:   18 Years to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Have a diagnosis of schizophrenic disorder
  • Female subjects 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 CGI-S 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 subject can be washed out of their Standard of Care(SOC)therapy (other than aripiprazole for the aripiprazole subjects) for the duration of the study without detrimental effect to the subject's mental health (Clinical Global Impression-Severity Scale(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

Subjects 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 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

Exclusion Criteria:

  • 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
  • Subjects with moderate to severe renal impairment as defined by creatinine clearance (CrCl) <60 ml/min
  • Have previously completed this study or have discontinued from any study investigating LY2140023 after having received at least 1 dose of LY2140023
  • Subjects for whom treatment with LY2140023 or aripiprazole as specified in this protocol, is relatively or absolutely clinically contraindicated
  • Subjects who have received treatment with clozapine
  • Subjects who have a diagnosis of schizophrenia who are taking either thioridazine or thiothixene
  • Subjects receiving treatment with depot antipsychotic medication within 12 weeks, prior to screening
  • Subjects who are taking any of medications that are specifically excluded
  • Subjects 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
  • Subjects 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
  • A diagnosis of Parkinson's disease, dementia-related psychosis, or related disorders
  • Subject with untreated hyperthyroidism or hypothyroidism needing a thyroid hormone supplement who have not been on a stable dose of medication for at least 2 months prior to screening
  • Have leukopenia or history of leukopenia during the subject's lifetime
  • Subjects with alanine aminotransferase (ALT/SGPT) or aspartate aminotransferase (AST/SGOT) values >2 times the upper limit of normal (ULN) of the performing laboratory, or total bilirubin values >1.5 times the ULN of the performing laboratory at screening
  • Subjects with corrected QT interval (Bazett's); QTcB) >450 msec (male) or >470 msec (female) at admission
  • Have acute, serious or unstable medical conditions, including (but not limited to) inadequately controlled diabetes (hemoglobin A1c(HgbAlc) >8%), severe hypertriglyceridemia (fasting triglycerides greater than or equal to 500 mg/dL or 5.65 mmol/L),hepatic insufficiency (specifically any degree of jaundice), recent cerebrovascular accidents, seizure disorders, serious acute systemic infection or immunology disease, unstable cardiovascular disorders (including ischemic heart disease), renal, gastroenterologic, respiratory, endocrinologic, neurologic, or hematologic diseases
  • Prolactin level of >200 ng/mL (200 ug/L, or 4228 mIU/L) at screening with the exception of subjects treated with risperidone. Subjects treated with risperidone are excluded if the prolactin level is >300 ng/mL (300 ug/L, or 6342 mIU/L) at screening)
  • Subjects with known medical history of Human Immunodeficiency Virus positive (HIV+) status
  • Test positive for (1) Hepatitis C virus antibody or (2) Hepatitis B surface antigen (HBsAg) with or without positive Hepatitis B core total antibody. Subjects with positive Hepatitis B core antibody test and negative HBsAg may be included in the study if ALT/SGPT and AST/SGOT levels are less than 2 times the upper limit of normal (ULN) and total bilirubin does not exceed the ULN of the central laboratory
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01354353

Locations
United States, California
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, United States, 92845
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, United States, 91206
Sponsors and Collaborators
Eli Lilly and Company
Investigators
Study Director: 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
  More Information

No publications provided

Responsible Party: Eli Lilly and Company
ClinicalTrials.gov Identifier: NCT01354353     History of Changes
Other Study ID Numbers: 13565, H8Y-MC-HBDB
Study First Received: May 13, 2011
Last Updated: August 9, 2012
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Schizophrenia
Schizophrenia and Disorders with Psychotic Features
Mental Disorders
Aripiprazole
Antipsychotic Agents
Tranquilizing Agents
Central Nervous System Depressants
Physiological Effects of Drugs
Pharmacologic Actions
Central Nervous System Agents
Therapeutic Uses
Psychotropic Drugs

ClinicalTrials.gov processed this record on July 28, 2014