The Efficacy and Safety of a Selective Estrogen Receptor Beta Agonist (LY500307) for Negative Symptoms and Cognitive Impairment Associated With Schizophrenia

• Sponsor: Indiana University (Other)
• Overall Status: Terminated
• CT.gov ID: NCT01874756
• Collaborator: Eli Lilly and Company (Industry)
• Enrollment: 95
• Locations: 4
• Arms: 4
• Actual Duration (Months): 54
• Patients Per Site: 23.8
• Patients Per Site Per Month: 0.4

Study Details

Study Description

Brief Summary

The primary objectives of this application are to determine if the selective ERβ agonist LY500307, when added to antipsychotic medications, improves negative and/or cognitive symptoms in patients with schizophrenia. The specific hypotheses to be tested are to determine if LY500307 is safe and well tolerated in this population and whether it elicits a sufficient efficacy signal to be advanced for further testing in schizophrenia. A two-stage Phase 1b/Phase 2a adaptive ("drop the inferior dose") experimental design is ongoing that combines three studies (clinical dose optimization, cortical target engagement confirmation and efficacy and safety assessment) into a single clinical trial.

Stage 1 was conducted in year 1 and Stage 2 will be conducted in years 2 and 3. The goal of Stage 1 was to identify and advance the highest dose that did not demonstrate a safety signal and had target selectivity as determined by lack of TT suppression. This criteria was fulfilled at both doses, the larger of the two (75 mg/day dose) was advanced to Stage 2. Furthermore, there was no suggestion of ERα receptor activation (i.e., no pattern of TT decreases or feminization AEs) at either dose (25 mg/day and 75 mg/day). A third arm of 150 mg/day was added to Stage 2 for evaluation. Stage 2 results in the following three arms: placebo, 75 mg/day and 150 mg/day. The goals of Stage 2 are to further assess LY500307 doses for safety and target selectivity, confirm cortical target engagement and assess efficacy.

Primary Aim 1: To determine if LY500307 demonstrates cortical target engagement as assessed by fMRI/N-back in frontal-parietal regions. Secondary measures of target engagement are fMRI episodic memory, Pseudo-Continuous Arterial Spin Labeling, Mismatch Negativity/evoked response potentials, Auditory Steady State Response, Auditory P300 and Quantitative EEG (QEEG).

Primary Aim 2: To determine if LY500307 is superior to placebo for one or more of the primary efficacy endpoints: negative symptoms (Negative Symptom Assessment Scale - 16-item total score), working memory (the composite score for the Letter Number Sequencing and Spatial Span tests) and verbal memory (Hopkins Verbal Learning Test).

Primary Aim 3: To determine if LY500307 reduces total testosterone (TT) plasma concentrations, which is indicative of loss of selectivity for ERβ and engagement of ERα, using the following criteria: Decrease in TT plasma concentrations of 50% from baseline in 50% of subjects per arm treated for two consecutive post-randomization values with LY500307 in Stage 1 and Stage 2 of the trial.

Primary Aim 4: To assess the safety of LY500307 by determining if there are SAEs, AEs "probably related to study drug," QTc prolongation, TT suppression (50% reduction from baseline) and to evaluate for other safety signals.

Condition or Disease	Intervention/Treatment	Phase
Schizophrenia	Drug: LY500307 150mg; Drug: LY500307 75mg; Drug: Placebo; Drug: LY500307 25mg	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 95 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Triple (Participant, Care Provider, Investigator)
• Primary Purpose: Treatment
• Official Title: The Efficacy and Safety of a Selective Estrogen Receptor Beta Agonist (LY500307) for Negative Symptoms and Cognitive Impairment Associated With Schizophrenia
• Actual Study Start Date: Jun 1, 2013
• Actual Primary Completion Date: Dec 1, 2017
• Actual Study Completion Date: Dec 1, 2017

Arms and Interventions

Arm	Intervention/Treatment
Experimental: LY500307 150mg LY500307 150mg	Drug: LY500307 150mg; LY500307 150mg daily dose (6 capsules of 25mg) for 8 weeks
Placebo Comparator: placebo placebo 6 pills of inactive drug	Drug: Placebo; 6 placebo capsules daily for 8 weeks
Experimental: LY500307 75mg LY500307 75mg	Drug: LY500307 75mg; LY500307 75mg daily dose (3 capsules of 25mg and 3 capsules of placebo) for 8 weeks
Experimental: LY500307 25mg LY500307 25mg	Drug: LY500307 25mg; LY500307 25mg daily dose (1 capsules of 25mg and 5 capsules of placebo) for 8 weeks

Outcome Measures

Primary Outcome Measures

1. Negative Symptom Changes - Negative Symptom Assessment Scale - 16-item (NSA-16) Total Score [Baseline, week 2, week 4, week 6, week 8]

   The Negative Symptom Assessment Scale - 16-item (NSA-16) is used to help clinicians rate behaviors (not psychopathology) commonly associated with negative symptoms of schizophrenia. The scale rates subjects on 16 "anchors," is a semi-structured, clinical interview, and each item is rated from 1 to 6. The total score is the sum of the 16 specific items and ranges from 16 to 96; a higher score indicates greater severity of illness. In addition, there is a global rating that represents the overall assessment of a subject's negative symptoms. The rating should not be an average of any particular behavior, but a gestalt of everything observed in the interview.

2. Working Memory Composite Score Changes [Baseline, week 2, week 4, week 6, week 8]

   Working memory (composite score of the Wechsler Memory Scale-III: Spatial Span (WMS) and Letter Number Span (LNS) tests). WMS has 2 sections in which a subject recalls increasingly difficult sequences. The total raw score range for both sections is 0-32. The raw score is then converted to a tscore based on normative ranges by age and sex, ranging from 0-100. For both the raw and tscore a higher score reflects better performance. LNS consists of 24 increasingly difficult sequences of letters and numbers that a subject is to recall and repeat back in Numeric-Alpha sequential order. The total raw score range is 0-24. The raw score is then converted to a tscore based on normative ranges by age and sex, ranging from 0-100. For both the raw and tscore a higher score reflects better performance. The Working Memory composite score is calculated by summing the WMS and LNS tscores, ranging from 0-200, a higher tscore reflects better performance.

3. Verbal Learning Composite Score Changes [Baseline, week 2, week 4, week 6, week 8]

   Verbal learning (composite score of the Hopkins Verbal Learning Test-Revised (HVLT-R)). The HVLT-R has 3 trials in which a subject recalls has many words from a list of 12 as they can. The total number recalled for each trial is summed and the score range is between 0-36. The raw score is then converted to a tscore based on normative ranges by age and sex, ranging from 0-100. For both the raw and tscore a higher score reflects better performance. The verbal learning composite score is calculated by using the HVLT-R tscore, a higher tscore reflects better performance.

4. Number of Subjects With Total Testosterone Reduction [week 2, week 4, week 8]

   Number of subjects with total testosterone reduction, as defined as a decrease in total testosterone plasma concentrations of 50% from baseline for two consecutive post-randomization values

5. Number of Subjects With QTc Prolongation [Week 4, Week 8]

   Number of subjects with QTc prolongation, as defined as any subject with a change from baseline of 60 msec or greater during the active treatment phases

6. Cortical Target Engagement [Baseline, 8 weeks]

   To determine if LY500307 demonstrates cortical target engagement as assessed by changes in the N-back in frontal-parietal regions during the MRI.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 65 Years
• Sexes Eligible for Study: Male
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• 18 to 65 years of age at study entry

• Male

• DSM IV-TR diagnosis of schizophrenia as confirmed by Structured Clinical Interview for DSM-IV-TR (SCID)

• Outpatient or inpatient status

• Mild to moderate overall disease severity as defined by a CGI-S score of less than or equal to 4 (moderately ill) at randomization

• Moderate levels of negative symptoms as defined by a PANSS negative symptom sub-score greater than or equal to 11.

• Clinical stability as defined by:

1. No exacerbation of illness leading to an intensification of treatment in the opinion of the investigator within four weeks prior to randomization, and

2. No change in antipsychotic medication for at least four weeks prior to randomization

Exclusion Criteria:

• Subjects with current acute, serious, or unstable medical conditions, including, but not limited to: inadequately controlled diabetes, asthma, COPD, severe hypertriglyceridemia, recent cerebrovascular accidents, acute systemic infection or immunologic disease, unstable cardiovascular disorders, malnutrition, or hepatic, renal gastroenterologic, respiratory, endocrinologic, neurologic, hematologic, or infectious diseases

• Known or suspected history of prostate cancer, breast cancer, or other clinically significant neoplastic disease (other than squamous cell or basal cell carcinoma of skin)

• Known or suspected history of deep venous thrombosis, stroke, venous thromboembolism, pulmonary embolism, paresis or paralysis that may be thrombogenic in origin

• Subjects currently receiving testosterone replacement therapy or drugs that influence the hypothalamus-pituitary-gonadal axis.

• Subjects who have clinically significant extrapyramidal signs (EPS) as defined by a score of >20 on the Simpson-Angus Scale (SAS)

• Clinically significant electrocardiogram (ECG) abnormality, including, but not limited to, a corrected QT interval (Bazett's; QTcB) >450 msec. Repeat ECGs may be conducted at the discretion of the principal investigator.

• Subjects with known medical history of Human Immunodeficiency Virus positive (HIV+) status

• Subjects with an active seizure disorder

• Subjects with implanted pacemaker, medication pump, vagal stimulator, deep brain stimulator, TENS unit, ventriculoperitoneal shunt, or other contraindication to undergoing an MRI scan

• Known IQ less than 70 based on medical history

• Current DSM IV-TR diagnosis of substance dependence (excluding caffeine and nicotine)

• Subjects who 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 moderate to severe renal impairment as defined by creatinine clearance (CrCl) < 60 ml/min (measured by the Cockcroft-Gault equation) at screening. Repeat evaluation may be conducted at the discretion of the Principal Investigator.

• Subjects with hepatic impairment as defined by liver transaminases or total bilirubin

3 × upper limit of normal (ULN). Repeat evaluation may be conducted at the discretion of the Principal Investigator.

• Subjects considered a high risk for suicidal acts - active suicidal ideation as determined by clinical interview OR any suicide attempt in 30 days prior to screening

• Subjects who have participated in a clinical trial with any pharmacological treatment intervention for which they received study-related medication in the four weeks prior to randomization OR subjects currently receiving treatment (within 1 dosing interval plus four weeks) with an investigational depot formulation of an antipsychotic medication

• Subjects who demonstrate overtly aggressive behavior or who are deemed to pose a substantial risk of danger in the Investigator's opinion

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Indiana University Center for NeuroImaging	Indianapolis	Indiana	United States	46202
2	IU Biostatistics	Indianapolis	Indiana	United States	46202
3	Prevention and Recovery Center for Early Psychosis	Indianapolis	Indiana	United States	46202
4	Larue D Carter Memorial Hospital	Indianapolis	Indiana	United States	46222

Sponsors and Collaborators

• Indiana University
• Eli Lilly and Company

Investigators

• Principal Investigator: Alan Breier, MD, Indiana University

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - May 1, 2017

More Information

Additional Information:

• Indiana University Psychotic Disorders Program

Publications

None provided.

• Responsible Party: Alan Breier, Psychiatrist, Indiana University
• ClinicalTrials.gov Identifier: NCT01874756
• Other Study ID Numbers: 1303010802
• First Posted: Jun 11, 2013
• Last Update Posted: Jul 2, 2019
• Last Verified: Jun 1, 2019

• Keywords provided by Alan Breier, Psychiatrist, Indiana University: schizophrenia; Estrogen receptor agonist; cognitive impairment; negative symptoms
• Additional relevant MeSH terms: Schizophrenia; Cognitive Dysfunction

Study Results

Participant Flow

Arm/Group Title	Placebo	LY500307 25mg	LY500307 75mg	LY500307 150mg
Arm/Group Description	placebo 6 pills of inactive drug Placebo: 6 placebo capsules daily for 8 weeks	LY500307 25mg LY500307 25mg: LY500307 25mg daily dose (1 capsules of 25mg and 5 capsules of placebo) for 8 weeks	LY500307 75mg LY500307 75mg: LY500307 75mg daily dose (3 capsules of 25mg and 3 capsules of placebo) for 8 weeks	LY500307 150mg LY500307 150mg: LY500307 150mg daily dose (6 capsules of 25mg) for 8 weeks
Period Title: Overall Study
STARTED	29	10	29	27
COMPLETED	28	10	27	21
NOT COMPLETED	1	0	2	6

Baseline Characteristics

Arm/Group Title	Placebo	LY500307 25mg	LY500307 75mg	LY500307 150mg	Total
Arm/Group Description	placebo 6 pills of inactive drug Placebo: 6 placebo capsules daily for 8 weeks	LY500307 25mg LY500307 25mg: LY500307 25mg daily dose (1 capsules of 25mg and 5 capsules of placebo) for 8 weeks	LY500307 75mg LY500307 75mg: LY500307 75mg daily dose (3 capsules of 25mg and 3 capsules of placebo) for 8 weeks	LY500307 150mg LY500307 150mg: LY500307 150mg daily dose (6 capsules of 25mg) for 8 weeks	Total of all reporting groups
Overall Participants	29	10	29	25	93
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%	0 0%	0 0%
Between 18 and 65 years	29 100%	10 100%	29 100%	25 100%	93 100%
>=65 years	0 0%	0 0%	0 0%	0 0%	0 0%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	36.28 (12.27)	36.64 (12.58)	37.15 (13.67)	37.64 (10.21)	37.07 (12.18)
Sex: Female, Male (Count of Participants)
Female	0 0%	0 0%	0 0%	0 0%	0 0%
Male	29 100%	10 100%	29 100%	25 100%	93 100%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%	0 0%	0 0%
Asian	0 0%	0 0%	0 0%	0 0%	0 0%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%	0 0%	0 0%
Black or African American	17 58.6%	6 60%	17 58.6%	12 48%	52 55.9%
White	11 37.9%	2 20%	12 41.4%	13 52%	38 40.9%
More than one race	1 3.4%	2 20%	0 0%	0 0%	3 3.2%
Unknown or Not Reported	0 0%	0 0%	0 0%	0 0%	0 0%
Region of Enrollment (participants) [Number]
United States	29 100%	10 100%	29 100%	25 100%	93 100%

Outcome Measures

1. Primary Outcome

Title	Negative Symptom Changes - Negative Symptom Assessment Scale - 16-item (NSA-16) Total Score
Description	The Negative Symptom Assessment Scale - 16-item (NSA-16) is used to help clinicians rate behaviors (not psychopathology) commonly associated with negative symptoms of schizophrenia. The scale rates subjects on 16 "anchors," is a semi-structured, clinical interview, and each item is rated from 1 to 6. The total score is the sum of the 16 specific items and ranges from 16 to 96; a higher score indicates greater severity of illness. In addition, there is a global rating that represents the overall assessment of a subject's negative symptoms. The rating should not be an average of any particular behavior, but a gestalt of everything observed in the interview.
Time Frame	Baseline, week 2, week 4, week 6, week 8

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	LY500307 150mg	Placebo	LY500307 75mg	LY500307 25mg
Arm/Group Description	LY500307 150mg LY500307 150mg: LY500307 150mg daily dose (6 capsules of 25mg) for 8 weeks	placebo 6 pills of inactive drug Placebo: 6 placebo capsules daily for 8 weeks	LY500307 75mg LY500307 75mg: LY500307 75mg daily dose (3 capsules of 25mg and 3 capsules of placebo) for 8 weeks	LY500307 25mg LY500307 25mg: LY500307 25mg daily dose (1 capsules of 25mg and 5 capsules of placebo) for 8 weeks
Measure Participants	25	29	29	10
Baseline	42.52 (11.05)	45.34 (12.03)	45.93 (13.99)	46.10 (12.60)
Week 2	40.96 (12.82)	46.10 (14.68)	44.82 (11.62)	47.20 (14.69)
Week 4	41.35 (12.38)	48.21 (14.32)	45.30 (12.16)	45.80 (13.41)
Week 6	43.43 (15.36)	46.46 (15.64)	43.19 (11.18)	44.10 (15.74)
Week 8	42.90 (14.09)	47.79 (16.26)	44.12 (12.72)	44.50 (13.56)

2. Primary Outcome

Title	Working Memory Composite Score Changes
Description	Working memory (composite score of the Wechsler Memory Scale-III: Spatial Span (WMS) and Letter Number Span (LNS) tests). WMS has 2 sections in which a subject recalls increasingly difficult sequences. The total raw score range for both sections is 0-32. The raw score is then converted to a tscore based on normative ranges by age and sex, ranging from 0-100. For both the raw and tscore a higher score reflects better performance. LNS consists of 24 increasingly difficult sequences of letters and numbers that a subject is to recall and repeat back in Numeric-Alpha sequential order. The total raw score range is 0-24. The raw score is then converted to a tscore based on normative ranges by age and sex, ranging from 0-100. For both the raw and tscore a higher score reflects better performance. The Working Memory composite score is calculated by summing the WMS and LNS tscores, ranging from 0-200, a higher tscore reflects better performance.
Time Frame	Baseline, week 2, week 4, week 6, week 8

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	LY500307 150mg	Placebo	LY500307 75mg	LY500307 25mg
Arm/Group Description	LY500307 150mg LY500307 150mg: LY500307 150mg daily dose (6 capsules of 25mg) for 8 weeks	placebo 6 pills of inactive drug Placebo: 6 placebo capsules daily for 8 weeks	LY500307 75mg LY500307 75mg: LY500307 75mg daily dose (3 capsules of 25mg and 3 capsules of placebo) for 8 weeks	LY500307 25mg LY500307 25mg: LY500307 25mg daily dose (1 capsules of 25mg and 5 capsules of placebo) for 8 weeks
Measure Participants	25	29	29	10
Baseline	34.76 (12.03)	33.21 (11.86)	34.79 (10.90)	35.70 (14.88)
Week 2	35.70 (10.68)	36.41 (12.55)	36.89 (8.94)	36.50 (13.09)
Week 4	35.30 (13.08)	35.93 (12.14)	37.54 (8.66)	35.90 (13.49)
Week 6	37.13 (11.43)	36.00 (10.99)	38.54 (9.63)	37.20 (13.37)
Week 8	37.86 (11.24)	38.04 (13.08)	37.48 (9.18)	38.00 (12.27)

3. Primary Outcome

Title	Verbal Learning Composite Score Changes
Description	Verbal learning (composite score of the Hopkins Verbal Learning Test-Revised (HVLT-R)). The HVLT-R has 3 trials in which a subject recalls has many words from a list of 12 as they can. The total number recalled for each trial is summed and the score range is between 0-36. The raw score is then converted to a tscore based on normative ranges by age and sex, ranging from 0-100. For both the raw and tscore a higher score reflects better performance. The verbal learning composite score is calculated by using the HVLT-R tscore, a higher tscore reflects better performance.
Time Frame	Baseline, week 2, week 4, week 6, week 8

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	LY500307 150mg	Placebo	LY500307 75mg	LY500307 25mg
Arm/Group Description	LY500307 150mg LY500307 150mg: LY500307 150mg daily dose (6 capsules of 25mg) for 8 weeks	placebo 6 pills of inactive drug Placebo: 6 placebo capsules daily for 8 weeks	LY500307 75mg LY500307 75mg: LY500307 75mg daily dose (3 capsules of 25mg and 3 capsules of placebo) for 8 weeks	LY500307 25mg LY500307 25mg: LY500307 25mg daily dose (1 capsules of 25mg and 5 capsules of placebo) for 8 weeks
Measure Participants	25	29	29	10
Baseline	33.36 (6.60)	33.93 (5.98)	34.50 (7.39)	32.30 (6.63)
Week 2	34.17 (6.97)	35.41 (8.73)	37.11 (8.22)	34.20 (4.87)
Week 4	33.96 (7.04)	35.11 (7.43)	37.42 (8.26)	34.60 (5.52)
Week 6	33.74 (6.78)	34.44 (7.84)	34.62 (7.13)	33.40 (6.28)
Week 8	34.67 (5.63)	35.54 (7.57)	37.12 (7.76)	37.30 (6.17)

4. Primary Outcome

Title	Number of Subjects With Total Testosterone Reduction
Description	Number of subjects with total testosterone reduction, as defined as a decrease in total testosterone plasma concentrations of 50% from baseline for two consecutive post-randomization values
Time Frame	week 2, week 4, week 8

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	LY500307 150mg	Placebo	LY500307 75mg	LY500307 25mg
Arm/Group Description	LY500307 150mg LY500307 150mg: LY500307 150mg daily dose (6 capsules of 25mg) for 8 weeks	placebo 6 pills of inactive drug Placebo: 6 placebo capsules daily for 8 weeks	LY500307 75mg LY500307 75mg: LY500307 75mg daily dose (3 capsules of 25mg and 3 capsules of placebo) for 8 weeks	LY500307 25mg LY500307 25mg: LY500307 25mg daily dose (1 capsules of 25mg and 5 capsules of placebo) for 8 weeks
Measure Participants	25	29	29	10
Week 2	0 0%	0 0%	0 0%	0 0%
Week 4	0 0%	0 0%	0 0%	0 0%
Week 8	0 0%	0 0%	0 0%	0 0%

5. Primary Outcome

Title	Number of Subjects With QTc Prolongation
Description	Number of subjects with QTc prolongation, as defined as any subject with a change from baseline of 60 msec or greater during the active treatment phases
Time Frame	Week 4, Week 8

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	LY500307 150mg	Placebo	LY500307 75mg	LY500307 25mg
Arm/Group Description	LY500307 150mg LY500307 150mg: LY500307 150mg daily dose (6 capsules of 25mg) for 8 weeks	placebo 6 pills of inactive drug Placebo: 6 placebo capsules daily for 8 weeks	LY500307 75mg LY500307 75mg: LY500307 75mg daily dose (3 capsules of 25mg and 3 capsules of placebo) for 8 weeks	LY500307 25mg LY500307 25mg: LY500307 25mg daily dose (1 capsules of 25mg and 5 capsules of placebo) for 8 weeks
Measure Participants	25	29	29	10
Week 4	0 0%	0 0%	0 0%	0 0%
Week 8	0 0%	0 0%	0 0%	0 0%

6. Primary Outcome

Title	Cortical Target Engagement
Description	To determine if LY500307 demonstrates cortical target engagement as assessed by changes in the N-back in frontal-parietal regions during the MRI.
Time Frame	Baseline, 8 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	LY500307 150mg	Placebo	LY500307 75mg	LY500307 25mg
Arm/Group Description	LY500307 150mg LY500307 150mg: LY500307 150mg daily dose (6 capsules of 25mg) for 8 weeks	placebo 6 pills of inactive drug Placebo: 6 placebo capsules daily for 8 weeks	LY500307 75mg LY500307 75mg: LY500307 75mg daily dose (3 capsules of 25mg and 3 capsules of placebo) for 8 weeks	LY500307 25mg LY500307 25mg: LY500307 25mg daily dose (1 capsules of 25mg and 5 capsules of placebo) for 8 weeks
Measure Participants	25	29	29	10
Baseline	0.15 (0.22)	0.16 (0.22)	0.27 (0.21)	0.21 (0.20)
Week 8	0.26 (0.21)	0.22 (0.22)	0.31 (0.26)	0.30 (0.22)

Adverse Events

Time Frame	Adverse event data was collected over the 8 week time period that subjects were enrolled in the study.
Arm/Group Title	Placebo		LY500307 25mg		LY500307 75mg		LY500307 150mg
Arm/Group Description	placebo 6 pills of inactive drug Placebo: 6 placebo capsules daily for 8 weeks		LY500307 25mg LY500307 25mg: LY500307 25mg daily dose (1 capsules of 25mg and 5 capsules of placebo) for 8 weeks		LY500307 75mg LY500307 75mg: LY500307 75mg daily dose (3 capsules of 25mg and 3 capsules of placebo) for 8 weeks		LY500307 150mg LY500307 150mg: LY500307 150mg daily dose (6 capsules of 25mg) for 8 weeks
All Cause Mortality
	Placebo		LY500307 25mg		LY500307 75mg		LY500307 150mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/29 (0%)		0/10 (0%)		0/29 (0%)		0/27 (0%)
Serious Adverse Events
	Placebo		LY500307 25mg		LY500307 75mg		LY500307 150mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/29 (3.4%)		0/10 (0%)		0/29 (0%)		1/25 (4%)
Blood and lymphatic system disorders
Hematemesis	1/29 (3.4%)	1	0/10 (0%)	0	0/29 (0%)	0	0/25 (0%)	0
Psychiatric disorders
Suicidal ideation	0/29 (0%)	0	0/10 (0%)	0	0/29 (0%)	0	1/25 (4%)	1
Other (Not Including Serious) Adverse Events
	Placebo		LY500307 25mg		LY500307 75mg		LY500307 150mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	4/29 (13.8%)		1/10 (10%)		3/29 (10.3%)		7/25 (28%)
Gastrointestinal disorders
Vomiting	0/29 (0%)	0	0/10 (0%)	0	2/29 (6.9%)	2	0/25 (0%)	0
Diarrhea	0/29 (0%)	0	0/10 (0%)	0	0/29 (0%)	0	2/25 (8%)	2
Infections and infestations
Upper Respiratory Infection	2/29 (6.9%)	2	0/10 (0%)	0	1/29 (3.4%)	1	0/25 (0%)	0
Psychiatric disorders
Suicidal Ideation	2/29 (6.9%)	2	0/10 (0%)	0	0/29 (0%)	0	0/25 (0%)	0
Psychotic Exacerbation	0/29 (0%)	0	0/10 (0%)	0	0/29 (0%)	0	2/25 (8%)	2
Renal and urinary disorders
Increased Urinary Frequency	0/29 (0%)	0	1/10 (10%)	1	0/29 (0%)	0	2/25 (8%)	2
Reproductive system and breast disorders
Erectile Dysfunction	0/29 (0%)	0	0/10 (0%)	0	0/29 (0%)	0	2/25 (8%)	2

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.