A Phase 3, Multicenter, Double-Blind Comparison of LY2140023 and Aripiprazole in Patients with Schizophrenia Followed by Open-Label Treatment with LY2140023

• Register: EUCTR
• Last refreshed on: 8 October 2021
• Main ID: EUCTR2010-023550-36-ES
• Date of registration: 03/11/2011
• Prospective Registration: No
• Primary sponsor: Lilly S.A.
• Public title: A Phase 3, Multicenter, Double-Blind Comparison of LY2140023 and Aripiprazole in Patients with Schizophrenia Followed by Open-Label Treatment with LY2140023
• Scientific title: A Phase 3, Multicenter, Double-Blind Comparison of LY2140023 and Aripiprazole in Patients with DSM-IV-TR Schizophrenia Followed by Open-Label Treatment with LY2140023 - HBDE
• Date of first enrolment: 19/05/2011
• Target sample size: 670
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2010-023550-36
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes; Randomised: yes; Open: no; Single blind: no; Double blind: yes; Parallel group: yes; Cross over: no; Other: no; If controlled, specify comparator, Other Medicinial Product: yes; Placebo: no; Other: no; Number of treatment arms in the trial: 2
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): no Therapeutic confirmatory - (Phase III): yes Therapeutic use (Phase IV): no

Countries of recruitment

Austria, Belgium, France, Germany, Poland, Puerto Rico, Romania, Spain, Sweden, United States

Contacts

• Name: Clinica Operations
• Affiliation: Lilly S.A

• Name: Clinica Operations
• Affiliation: Lilly S.A

Key inclusion & exclusion criteria

Inclusion criteria:
[1] Patients are male or female, 18 to 65 years of age (inclusive) at study entry, with a diagnosis of schizophrenia as defined in the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision (DSM-IV-TR; APA 2000) (Disorganized, 295.10; Catatonic, 295.20; Paranoid 295.30; or Undifferentiated, 295.90) and confirmed by the Structured Clinical Interview for DSM-IV-TR (SCID).
[2] Female patients of childbearing potential must test negative for pregnancy at Visit 1 and agree to use a single, effective, medically acceptable method of
birth control, specifically: an oral contraceptive combined pill; an implantable contraceptive; an injectable contraceptive; a contraceptive patch (for women <198 pounds or 90 Kg); or an intrauterine device/system. The double-barrier method, as defined by two physical barriers such as a condom, diaphragm, or cervical occlusive cap, coupled with an additional barrier such as spermicidal foam, gel, film, cream or suppository, is also an acceptable method of birth control. Patients having undergone a hysterectomy or bilateral oophorectomy or other form of female sterilization, or patients having been medically confirmed to be post-menopausal, would not require any method of contraception. Menopausal women include women in either of the following categories:
[a] Spontaneous amenorrhea for at least 12 months, not induced by a
medical condition such as anorexia nervosa and not taking medications
during the amenorrhea that induced the amenorrhea (for example, oral
contraceptives, hormones, gonadotropin releasing hormone, antiestrogens, selective estrogen receptor modulators (SERMs), or
chemotherapy). or [b] Spontaneous amenorrhea for 6 to 12 months and a follicle-stimulating hormone (FSH) level greater than 40mIU/mL.
[3] In the opinion of the investigator, at Visit 1, patients must require initiation of or modification to current antipsychotic treatment as outpatients.
[4] Patients must be considered reliable and have a level of understanding
sufficient to perform all tests and examinations required by the protocol, and be willing to perform all study procedures.
[5] Patients must be able to understand the nature of the study and have given their own informed consent.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 670
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range

Exclusion criteria:
[6] Are currently enrolled in, or discontinued within the last 60 days from, a clinical trial involving an investigational product or nonapproved use of a drug or device, or concurrently enrolled in any other type of medical research
[7] Are investigator site personnel directly affiliated with this study and/or their immediate families
[8] Lilly employees.
[9] on treatment with aripiprazole in the past 2 months or aripiprazole nonresponders.
[10] Patients for whom treatment with LY2140023 or aripiprazole is relatively or absolutely clinically contraindicated.
[11] Are hospitalized within 2 weeks of Visit 1 or have been hospitalized for anexacerbation of symptoms of schizophrenia with a discharge date in the past 2months
[12] Have any other current Axis I psychiatric diagnoses
[13] Have previously completed or withdrawn from this study, or any other study investigating LY2140023 or any predecessor molecules with glutamatergic activity
[14] Patients who have received an adequate treatment trial with clozapine at doses greater than 200 mg daily within 12 months prior to Visit 1, or who have received any clozapine at all during the month before Visit 1
[15] Patients who have a history of an inadequate clinical response to antipsychotic treatment for schizophrenia
[16] Patients who require concomitant treatment with any other medication with primary central nervous system activity
[17] Patients who have received treatment with any depot formulation of an antipsychotic medication within 1 dosing interval, minimum of 4 weeks prior to Visit 1.
[18] Patients 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 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 month.
[19] diagnosis of substance dependence or abuse
[20] Diagnosis of substance-induced psychosis within 7 days of Visit 1 (or at any time during the study).
[21] Female patients who are pregnant, nursing, or who intend to become pregnant within 30 days of completing the study.
[22] Have known, uncorrected, narrow-angle glaucoma.
[23] Have a history of one or more seizures except for: 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.
[24] Patients who have had ECT within 3 months of Visit 1 or who will have ECT at any time during the study.
[25] Patients with untreated hyper- or hypothyroidism
[26] Have leukopenia or a history of leukopenia without a clear and resolved etiology, or known history of agranulocytosis during the patient?s lifetime.
[27] Patients with known medical history of Human Immunodeficiency Virus positive (HIV+) status.
[28] Test positive for (1) Hepatitis C virus antibody or (2) Hepatitis B surface antigen (HBsAg) with or without positive Hepatitis B core total antibody. Patients 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
[29] Patients with ALT/SGPT or AST/SGOT values >2 times ULN of the p

Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Schizophrenia
MedDRA version: 14.0 Level: PT Classification code 10039626 Term: Schizophrenia System Organ Class: 10037175 - Psychiatric disorders

Therapeutic area: Psychiatry and Psychology [F] - Mental Disorders [F03]

Intervention(s)

Product Name: LY2140023
Product Code: LY2140023
Pharmaceutical Form: Tablet
INN or Proposed INN: LY2140023
CAS Number: 635318-55-7
Current Sponsor code: LY2140023
Other descriptive name: N/A
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 40-
Pharmaceutical form of the placebo: Tablet
Route of administration of the placebo: Oral use

Product Name: LY2140023
Product Code: LY2140023
Pharmaceutical Form: Tablet
INN or Proposed INN: LY2140023
CAS Number: 635318-55-7
Current Sponsor code: LY2140023
Other descriptive name: N/A
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 80-
Pharmaceutical form of the placebo: Tablet
Route of administration of the placebo: Oral use

Product Name: LY2140023
Product Code: LY2140023
Pharmaceutical Form: Tablet
INN or Proposed INN: LY2140023
CAS Number: 635318-55-7
Current Sponsor code: LY2140023
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 20-
Pharmaceutical form of the placebo: Tablet
Route of administration of the placebo: Oral use

Trade Name: ABILIFY 10 mg comprimidos
Pharmaceutical Form: Capsule
INN or Proposed INN: ARIPIPRAZOL
CAS Number: 129722-12-9
Current Sponsor code: Abilify
Other descriptive name: ARIPIPRAZOLE
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 10-
Pharmaceutical form of the placebo: Capsule
Route of administration of the placebo: Oral use

Trade Name: ABILIFY 15 mg comprimidos
Pharmaceutical Form: Capsule
INN or Proposed INN: ARIPIPRAZOL
CAS Number: 129722-12-9
Current Sponsor code: Abilify
Other descriptive name: ARIPIPRAZOLE
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 15-
Pharmaceutical form of the placebo: Capsule
Route of admini

Primary Outcome(s)

Main Objective: The primary objective of this study is to test the hypothesis that mean weight gain, as assessed by change from baseline, will be statistically significantly less for flexibly dosed LY2140023 (20, 40, or 80 mg BID) than for flexibly dosed aripiprazole (10, 15, or 30 mg/day) in patients with
schizophrenia after 24 weeks of double-blind treatment.

Secondary Objective: LY2140023 vs aripiprazole after 24 w double-blind treatment:
To test hypothesis proportion patients potentially clinically significant weight gain will be statistically significantly less for LY than aripiprazole
To evaluate safety and tolerability based on rates and time to discontinuation due to lack of tolerability defined as discontinuation due AE?s
To evaluate safety and tolerability respect changes from baseline in EPS.
To evaluate efficacy based on: Change from baseline in PANS; CGI-S; and NSA-16 scales; Incidence of response defined as a 30% decrease from baseline for PANSS
To evaluate efficacy w/in prospectively defined subpopulation measured by change from baseline on PANSS and other efficacy measures
To assess whether LY demonstrates improvement vs aripiprazole on health outcomes quality of life and functioning
To further evaluate efficacy safety and tolerability of LY through assessment of all efficacy and safety measures at end of 28-w open-label phase

Timepoint(s) of evaluation of this end point: 24 weeks of double-blind treatment

Primary end point(s): Weight will be measured at every visit to the nearest 0.1 kg. Patients should be weighed wearing light clothing, after evacuation of bladder contents and bowel contents when possible. Weight should be measured at a consistent time of day if possible, and on the same scale for every assessment.

Secondary Outcome(s)

Secondary end point(s): The following efficacy measures will be collected at the times shown in the Study Schedule:
Positive and Negative Syndrome Scale (PANSS)
Clinical Global Impression-Severity (CGI-S)
16-Item Negative Symptom Assessment (NSA-16)

Timepoint(s) of evaluation of this end point: 24 weeks of double-blind treatment

Secondary ID(s)

2010-023550-36-AT

H8Y-MC-HBDE

Source(s) of Monetary Support

Lilly S.A.

Ethics review

Status: Approved
Approval date: 14/04/2011
Contact:

Results

• Results available: Yes
• Date Posted: 27/01/2018
• Date Completed: 12/10/2012
• URL: https://www.clinicaltrialsregister.eu/ctr-search/trial/2010-023550-36/results