| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
|
| MedDRA Classification |
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 12.1 |
| E.1.2 | Level | LLT |
| E.1.2 | Classification code | 10039626 |
| E.1.2 | Term | Schizophrenia |
|
| E.1.3 | Condition being studied is a rare disease | No |
| E.2 Objective of the trial |
| E.2.1 | Main objective of the trial |
| 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. |
|
| E.2.2 | Secondary objectives of the trial |
The main secondary objectives are as follows, please refer to the Protocol Section 6.2 for further details.
•To test the hypothesis that the proportion of patients with potentially clinically significant weight gain, will be statistically significantly less for LY2140023 than for aripiprazole after 24 weeks of double-blind treatment.
•To evaluate the safety and tolerability of LY2140023 compared with aripiprazole
•To evaluate the efficacy of LY2140023 compared with aripiprazole
•To evaluate the efficacy of LY2140023 compared with aripiprazole within a prospectively defined genetic subgroup
•To assess whether LY2140023 demonstrates improvement compared with aripiprazole on health outcomes, including quality of life and functioning
•To further evaluate efficacy, safety, and tolerability of LY2140023 through assessment of all efficacy and safety measures at the end of the 28-week open-label phase.
|
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal 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, anti-estrogens, 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.
|
|
| E.4 | Principal exclusion criteria |
[12] Have any other current Axis I psychiatric diagnoses (as defined in DSM-IV-TR) in addition to schizophrenia.
[15] Patients who have a history of an inadequate clinical response, in the opinion of the investigator, to antipsychotic treatment for schizophrenia.
[16] Patients who require concomitant treatment with any other medication with primary central nervous system activity, other than those allowed as specified in Section 9.8 and Attachment 3, or with any other medication specifically excluded in Attachment 3.
[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 or Question 5 (on the "Suicidal Ideation" portion of the C–SSRS, or answer "yes" to any of the suicide-related behaviors on the "Suicidal Behavior" portion of the C–SSRS; and the ideation or behavior occurred within the past month.
[19] DSM-IV-TR diagnosis of substance dependence or substance abuse (except nicotine and caffeine) within the 6 months prior to Visit 1.
[20] Diagnosis of substance-induced psychosis by DSM-IV-TR criteria 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 either of the following 2 situations:
• A single simple febrile seizure between ages 6 months and 5 years (a single simple febrile seizure is defined as lacking focality and lasting less than 15 minutes, not associated with a central nervous system (CNS) infection or severe metabolic disturbance)
• A single seizure with an identifiable etiology, which has been completely resolved.
Note: The site must contact the sponsor or its representatives prior to entering a patient who has experienced any seizure.
[30] Patients with acute, serious, or unstable medical conditions,
[32] Patients with a corrected QT interval (Bazett’s; QTcB) >450 msec (male) or >470 msec (female) at Visit 1 (based on the central vendor’s ECG overread).
[34] Patients with moderate to severe renal impairment |
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
| Change from baseline in body weight during the double-blind treatment phase |
|
| E.6 and E.7 Scope of the trial |
| E.6 | Scope of the trial |
| E.6.1 | Diagnosis | No |
| E.6.2 | Prophylaxis | No |
| E.6.3 | Therapy | Yes |
| E.6.4 | Safety | Yes |
| E.6.5 | Efficacy | No |
| E.6.6 | Pharmacokinetic | No |
| E.6.7 | Pharmacodynamic | No |
| E.6.8 | Bioequivalence | No |
| E.6.9 | Dose response | No |
| E.6.10 | Pharmacogenetic | No |
| E.6.11 | Pharmacogenomic | No |
| E.6.12 | Pharmacoeconomic | No |
| E.6.13 | Others | No |
| E.7 | Trial type and phase |
| E.7.1 | Human pharmacology (Phase I) | No |
| E.7.1.1 | First administration to humans | No |
| E.7.1.2 | Bioequivalence study | No |
| E.7.1.3 | Other | Yes |
| E.7.1.3.1 | Other trial type description |
|
| E.7.2 | Therapeutic exploratory (Phase II) | No |
| E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
| E.7.4 | Therapeutic use (Phase IV) | No |
| E.8 Design of the trial |
| E.8.1 | Controlled | Yes |
| E.8.1.1 | Randomised | Yes |
| E.8.1.2 | Open | No |
| E.8.1.3 | Single blind | No |
| E.8.1.4 | Double blind | Yes |
| E.8.1.5 | Parallel group | Yes |
| E.8.1.6 | Cross over | No |
| E.8.1.7 | Other | No |
| E.8.2 | Comparator of controlled trial |
| E.8.2.1 | Other medicinal product(s) | Yes |
| E.8.2.2 | Placebo | No |
| E.8.2.3 | Other | No |
| E.8.3 |
The trial involves single site in the Member State concerned
| No |
| E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
| E.8.4.1 | Number of sites anticipated in Member State concerned | 3 |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 25 |
| E.8.6 Trial involving sites outside the EEA |
| E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
| E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
| E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
|
| E.8.7 | Trial has a data monitoring committee | Yes |
| E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
|
| last visit of the last subject. |
|
| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | 0 |
| E.8.9.1 | In the Member State concerned months | 18 |
| E.8.9.1 | In the Member State concerned days | 0 |
| E.8.9.2 | In all countries concerned by the trial years | 0 |
| E.8.9.2 | In all countries concerned by the trial months | 20 |
| E.8.9.2 | In all countries concerned by the trial days | 0 |
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