Clinical trial NCT01606436: A Study Measuring Effect of LY2140023 (Pomaglumetad Methionil) on Electrocardiographs in Participants With Schizophrenia
Official title: A Placebo- and Positive-Controlled Study of the Electrophysiological Effects on the QT Interval After a Supratherapeutic Dose of LY2140023 in Subjects With Schizophrenia
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Schizophrenic Disorders
Lead sponsor: Denovo Biopharma LLC
Sponsor class: INDUSTRY
First posted: 2012-05-25
Enrollment: 86
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: BASIC_SCIENCE

Brief summary: This study determined if a single dose of LY2140023 (pomaglumetad methionil) affects the electrical activity in the heart in participants with schizophrenia. This study also helped determine how a single high dose of LY2140023 is tolerated by participants.

Detailed description: The primary objective of this study was to determine that a single supratherapeutic dose of LY2140023 does not differ from placebo in the mean change from baseline in 12-lead electrocardiogram (ECG) QT interval measurements, such that the upper bound of the 2-sided 90% confidence interval (CI) for the greatest time-matched mean effect is \<10 ms in subjects with schizophrenia. The secondary objective was to further evaluate the tolerability of a supratherapeutic single dose of LY2140023 monohydrate.

Male or female subjects diagnosed with schizophrenia and aged between 18 and 65 years, inclusive, who had not been hospitalized for psychiatric illness for at least 12 weeks prior to Day 1 of the lead-in period, and who had a Clinical Global Impression - Severity scale score of \<4 were included in the study.

Eligibility criteria: Inclusion Criteria:

* Diagnosis of schizophrenia
* Female participants who are postmenopausal
* Not hospitalized for psychiatric illness for at least 12 weeks prior to Day 1 of the study and have a Clinical Global Impression Severity Scale score of \<4
* Willing and able to be hospitalized from Day 1 to the end of the study
* Can be washed out of their antipsychotic medication for the duration of the study
* Considered reliable, able to understand, and willing to perform all study procedures
* Understand the nature of the study and give written informed consent
* Clinical laboratory test results within normal reference range
* Venous access sufficient to allow blood sampling
* Clinically acceptable sitting blood pressure and heart rate

Exclusion Criteria:

* Currently enrolled in, have completed or have discontinued from a clinical trial involving an investigational drug within the last 30 days
* Known allergies to pomaglumetad methionil (LY2140023) or its active metabolite (LY404039), moxifloxacin, related compounds, or components
* Previously completed this study or prematurely discontinued from any study after having received at least 1 dose of pomaglumetad methionil (LY2140023)
* Received treatment with clozapine
* Received aripiprazole within 2 months prior to screening
* Taking either thioridazine or thiothixene
* Receiving treatment with depot antipsychotic medication within 12 weeks, prior to screening
* Taking any medications other than those that are specifically permitted in the protocol
* Asthma needing active beta 2 (B2) agonist within 14 days of the study
* Active suicidal ideation with some intent to act, without specific plan or with specific plan and intent or had suicidal behavior such as actual attempt, interrupted attempt, aborted attempt, preparatory act, or behavior within the past 3 months
* Substance dependence or substance abuse (except nicotine and caffeine) within the 6 months prior to admission
* Substance-induced psychosis within 7 days of admission (or at any time during the dosing period)
* History of 1 or more seizures (with exceptions)
* Screening electroencephalogram (EEG) with paroxysmal (epileptiform) activity
* Have had electroconvulsive therapy (ECT) within 3 months of Day 1 of the study or who are expected to have ECT at any time during the live phase of this study
* Parkinson's disease, dementia-related psychosis, or related disorders
* 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
* History of leukopenia or agranulocytosis
* Alanine aminotransferase/serum glutamic pyruvic transaminase (ALT/SGPT) or aspartate aminotransferase/serum glutamic oxaloacetic transaminase (AST/SGOT) values greater than 2 times the upper limit of normal (ULN) or total bilirubin values greater than 1.5 times the ULN of the performing laboratory at screening
* Abnormality in the 12-lead electrocardiogram (ECG) that increases the risks associated with participating in the study
* Premature ventricular contraction (PVC) associated with symptoms and/or any complex PVCs
* Heart rhythm disturbance by history or ECG at screening
* Personal or family history of long QT wave syndrome
* Family history of sudden unexplained death or cardiac death in a family member under 60 years of age
* Unexplained syncope within the last year
* Acute, serious, or unstable medical conditions
* Prolactin level of greater than 200 nanograms per milliliter (ng/mL) (200 micrograms per liter \[ug/L\] or 4228 milli-international units per liter \[mIU/L\]) at screening (with the exception of participants treated with risperidone) at screening
* 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
* Smoke greater than or equal to 40 cigarettes per day
* Movement disorder that could interfere with conducting 12-lead ECGs

Primary outcomes:
measure: Change From Baseline up to 12 Hours Postdose in QT Interval Corrected for Heart Rate (QTc)
timeFrame: Baseline, up to 12 hours postdose in each treatment period
Secondary outcomes:
Other outcomes:
Locations:
city: Garden Grove
country: United States
facility: 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.
state: California
city: San Diego
country: United States
facility: 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.
state: California
city: North Miami
country: United States
facility: 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.
state: Florida
city: Overland Park
country: United States
facility: 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.
state: Kansas
city: Rockville
country: United States
facility: 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.
state: Maryland
city: Saint Louis
country: United States
facility: 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.
state: Missouri
city: Philadelphia
country: United States
facility: 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.
state: Pennsylvania
city: Austin
country: United States
facility: 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.
state: Texas
Study officials:
affiliation: Eli Lilly and Company
name: 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)
role: STUDY_DIRECTOR
References: