Phase 1
Completed N=75
A Study of Safety and Tolerability in Subjects With Schizophrenia
Source: ClinicalTrials.gov NCT01354353 ↗Enrolled (actual)
75
Serious AEs
2.9%
Results posted
Sep 2021
Primary outcomePrimary: Number of Participants With Clinically Significant Events (Physical Assessments and Clinical Lab Tests) — 5; 6; 9; 11 participants
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.
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Number of Participants With Clinically Significant Events (Physical Assessments and Clinical Lab Tests) |
5; 6; 9; 11; 11; 11 | — |
| SECONDARY Part A: Pharmacokinetics, Maximum Concentration (Cmax) |
496; 1170; 1410; 1830; 2630; 799 | — |
| SECONDARY Part B: Pharmacokinetics, Maximum Concentration (Cmax) |
— | — |
| SECONDARY Part A: Pharmacokinetics, Area Under the Concentration - Time Curve (AUC) |
2800; 6290; 8100; 10600; 14700; 4370 | — |
| SECONDARY Part B: Pharmacokinetics, Area Under the Concentration - Time Curve (AUC) |
— | — |
| SECONDARY Percentage of Participants With Increased Severity From Baseline to Day 17 in Clinical Global Impression- Severity Scale (CGI-S) |
0; 0; 0; 9.1; 0; 0 | — |
| SECONDARY Percentage of Participants With Worsening Symptoms From Baseline to Day 17 in Brief Psychiatric Rating Scale (BPRS) |
12.5; 0; 0; 0; 0; 0 | — |
| SECONDARY Percentage of Participants With Worsening Severity From Baseline to Day 17 in Extrapyramidal Symptoms as Measured by the Abnormal Involuntary Movement Scale (AIMS) |
0; 0; 0; 9.1; 0; 0 | — |
| SECONDARY Percentage of Participants With Increasing Impairment From Baseline to Day 17 in Extrapyramidal Symptoms as Measured by the Simpson-Angus Scale (SAS) |
6.3; 0; 0; 0; 0; 0 | — |
| SECONDARY Percentage of Participants With Worsening Symptoms From Baseline to Day 17 in Extrapyramidal Symptoms as Measured by the Barnes Akathisia Scale (BAS) |
0; 0; 10.0; 0; 0; 0 | — |
Eligibility Criteria
Inclusion Criteria
- 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 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
- Participants with corrected QT interval (Bazett's); QTcB >450 milliseconds (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 [HgbA1c] >8%), severe hypertriglyceridemia (fasting triglycerides greater than or equal to 500 milligrams/deciliter (mg/dL) or 5.65 micromoles/liter [umol/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 nanograms/milliliter (ng/mL) (200 micrograms/liter [ug/L], or 4228 milli international units/liter [mIU/L]) at screening with the exception of participants treated with risperidone. Participants treated with risperidone are excluded if the prolactin level is >300 ng/mL (300 ug/L, or 6342 mIU/L) at screening
- Participants 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. Participants 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 ULN and total bilirubin does not exceed the ULN of the central laboratory
Data sourced from ClinicalTrials.gov (NCT01354353). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication. Informational only — not medical advice.