A Study of LY2189102 in Patients With Type 2 Diabetes

• Sponsor: Eli Lilly and Company (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00942188
• Collaborator: (none)
• Enrollment: 106
• Locations: 18
• Arms: 4
• Duration (Months): 17
• Patients Per Site: 5.9
• Patients Per Site Per Month: 0.3

Study Details

Study Description

Brief Summary

Study to evaluate the safety, tolerability and efficacy of LY2189102 in patients with type 2 diabetes.

Condition or Disease	Intervention/Treatment	Phase
Type 2 Diabetes	Drug: LY2189102; Drug: Placebo	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 106 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Triple (Participant, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: Phase 2 Randomized, Double-blind, Placebo Controlled, Parallel Design Study in Patients With Type 2 Diabetes Mellitus Who Are Stable on Diet and Exercise, With or Without Metformin Monotherapy.
• Study Start Date: Jun 1, 2009
• Actual Primary Completion Date: Nov 1, 2010
• Actual Study Completion Date: Nov 1, 2010

Arms and Interventions

Arm	Intervention/Treatment
Experimental: 0.6 milligrams (mg) LY2189102	Drug: LY2189102; Participants received 2 subcutaneous (SC) injections weekly for 12 weeks.
Experimental: 18 mg LY2189102	Drug: LY2189102; Participants received 2 subcutaneous (SC) injections weekly for 12 weeks.
Experimental: 180 mg LY2189102	Drug: LY2189102; Participants received 2 subcutaneous (SC) injections weekly for 12 weeks.
Placebo Comparator: Placebo 0.9% Sodium Chloride	Drug: Placebo; Participants received 2 SC injections weekly for 12 weeks.

Outcome Measures

Primary Outcome Measures

1. Change From Baseline in the Glycosylated Hemoglobin (HbA1c) at 12 Weeks [Baseline, 12 weeks]

   Change in HbA1c from baseline following 12 weeks of therapy (that is, HbA1c at week 12 minus HbA1c at baseline). The Least Squares (LS) Mean Value was based on an analysis of covariance (ANCOVA) model with treatment and site as class variables and baseline HbA1c as a continuous covariate.

Secondary Outcome Measures

1. Change From Baseline in Fasting Glucose at 12 Weeks [Baseline, 12 weeks]

   Change in fasting glucose following 12 weeks of therapy (that is, fasting glucose at week 12 minus fasting glucose at baseline). The Least Squares (LS) Mean Value was based on an analysis of covariance (ANCOVA) model with treatment and site as class variables and baseline value as a continuous covariate.

2. Change From Baseline in Insulin Sensitivity (Fasting Insulin) at 12 Weeks [Baseline, 12 weeks]

   Change in serum fasting insulin from baseline to endpoint (that is, serum insulin at week 12 minus serum insulin at week 0). The Least Squares (LS) Mean Value was based on an analysis of covariance (ANCOVA) model with treatment and site as class variables and baseline value as a continuous covariate.

3. Number of Participants With a Change From Baseline in Beta-Cell Function Measured by Glucose and Insulin Changes With the Mixed Meal Tolerance Test (MMTT) at 12 Weeks [Baseline, 12 weeks]

   The number of participants with a change from baseline in glucose and insulin at 2 hours after the MMTT was analyzed. The MMTT measures glucose and insulin before and after a standardized meal is eaten. Glucose and insulin levels were measured before the MMTT and 2 hours after the MMTT.

4. Change From Baseline in the Glycosylated Hemoglobin (HbA1c) at Week 10 and Week 12 [Baseline, week 10, week 12]

   The change from baseline in HbA1c at week 10 (that is HbA1c at week 10 minus HbA1c at baseline) and week 12 (that is, HbA1c at week 12 minus HbA1c at baseline). The Least Squares (LS) Mean Value was based on an analysis of covariance (ANCOVA) model with treatment and site as class variables and baseline value as a continuous covariate.

5. Pharmacokinetics (PK) Maximum Serum Concentration (Cmax) of LY2189102 at End of Dosing (12 Weeks) [Prior to and 1 and 3-4 days after the first dose, prior to every other dose, and 6 and 12 weeks after the last dose]

   The Cmax value measures the maximum serum concentration and is estimated for LY2189102. The values were generated as individual estimates from a population pharmacokinetics (PK) model. Placebo samples were not assayed for serum concentration of LY2189102 because the participants in the placebo treatment arm did not receive LY2189102 study drug.

6. PK: Area Under the Concentration Time Curve for Dosing Interval (Tau) at Steady State (AUCτ,SS) at End of Dosing (12 Weeks) [Prior to and 1 and 3-4 days after the first dose, prior to every other dose, and 6 and 12 weeks after the last dose]

   Individual estimates of AUCtau at end of dosing generated from a population pharmacokinetic (PK) model.

7. Pharmacokinetics Measured by Serum Concentration at End of Dosing (12 Weeks) [Prior to and 1 and 3-4 days after the first dose, prior to every other dose, and 6 and 12 weeks after the last dose]

   Pharmacokinetics Measured by Serum Concentration at End of Dosing.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 20 Years to 75 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Have Type 2 Diabetes and confirmed by fasting C-peptide levels greater than or equal to 0.8 nanograms per milliliter [ng/ml]), with duration of more than 3 months.

• Body mass index between 25 and 40 kilograms per square meter (kg/m2).

• Stable on diet and exercise alone, with or without metformin monotherapy (stable regimen or dose for at least 8 weeks).

• Drug-naïve or previous anti-diabetic pharmacotherapy use is allowed (for the latter, patient must have stopped taking pharmacotherapy greater than 12 weeks prior to screening and only if deemed appropriate by the investigator).

• Angiotensin converting enzyme inhibitors, angiotensin II receptor blockers, thiazide diuretics or calcium channel blockers are permitted for the treatment of hypertension or proteinuria.

• Glycated hemoglobin level between 7% and 10%.

• Baseline High-sensitivity C-reactive protein greater than or equal to 2 milligrams per liter (mg/L)

• Females of childbearing potential (not surgically sterilized and between menarche and 1 year post-menopause) must test negative for pregnancy at the time of enrollment based on a pregnancy test. Furthermore, sexually active female and male participants must agree to use 2 reliable methods of birth control during the study and for 3 months following the last dose of study drug.

• Reliable and willing to make themselves available for the duration of the study and are willing to follow study procedures.

Exclusion Criteria:

• Current use of anti-diabetic pharmacotherapy (except metformin, under conditions specified in Inclusion Criteria above).

• Current treatment with anti-inflammatory drugs, including corticosteroids and non-steroidal anti-inflammatory drugs (100 mg per day or less of aspirin allowed).

• Within 60 days of the initial dose of the study drug, have received treatment with a drug that has not received regulatory approval for any indication.

• Presence of autoantibodies to glutamic acid decarboxylase 65 or islet-cell autoantibody-2.

• Evidence of tuberculosis as documented by a specific assay, medical history, and chest x-ray. A specific assay, (for example, tuberculin testing) will be conducted unless it is medically inappropriate. Exceptions include patients with a history of a positive specific assay for TB who have been treated with isonicotinyl hydrazine (documented) for at least 6 months, or patients with a previous diagnosis of TB who have been appropriately treated and can provide documentation.

• Symptomatic herpes zoster within 3 months of randomization.

• Show evidence of hepatitis C and/or positive hepatitis B surface antigen.

• Show evidence of human immunodeficiency virus and/or positive test of antibodies to human immunodeficiency virus (HIV).

• Received live or attenuated vaccine(s) within the previous 3 months prior to randomization or will receive within 3 months from the end of study.

• Screening serum creatinine greater than 2.0 milligrams per deciliter (mg/dL).

• Serum aspartate aminotransferase or alanine aminotransaminase concentration greater than 2x the upper limit of normal.

• Known allergies to LY2189102 or excipients.

• Previously completed or withdrawn from this study or any other study investigating LY2189102.

• Have donated blood of greater than 500 mL within the preceding 30 days and intend to donate within 3 months from the end of study.

• Have had other recent or ongoing signs of infection (for example, fever, current treatment with antibiotics).

• Experienced a serious bacterial infection within 6 months of randomization.

• Have a serious medical illness including but not limited to any cardiovascular, hepatic, respiratory, hematological, endocrine, or neurological disease, or any clinically significant laboratory abnormality.

• Have had lymphoma, leukemia, or any non-breast malignancy within the past 5 years except for basal cell or squamous epithelial carcinomas of the skin that have been resected with no evidence of metastatic disease.

• Have had a previous reaction to other biologics that, in the opinion of the investigator, puts the patient at serious risk.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	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.	Mobile	Alabama	United States	36689
2	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.	Anaheim	California	United States	92801
3	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.	Chula Vista	California	United States	91911
4	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.	La Mesa	California	United States	91942
5	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.	Walnut Creek	California	United States	94598
6	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.	Washington	District of Columbia	United States	20003
7	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.	Miami Gardens	Florida	United States	33169
8	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.	Miami	Florida	United States	33169
9	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.	Boise	Idaho	United States	83702
10	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.	Baltimore	Maryland	United States	21287
11	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.	Dearborn	Michigan	United States	48126
12	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.	Philadelphia	Pennsylvania	United States	19107
13	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.	Arlington	Texas	United States	76014
14	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.	Dallas	Texas	United States	75230
15	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.	San Antonio	Texas	United States	78229
16	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.	Tomball	Texas	United States	77375
17	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.	Salt Lake City	Utah	United States	84107
18	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.	Richmond	Virginia	United States	23294

Sponsors and Collaborators

• Eli Lilly and Company

Investigators

• Study Director: 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), Eli Lilly and Company

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Eli Lilly and Company
• ClinicalTrials.gov Identifier: NCT00942188
• Other Study ID Numbers: 13286; H9C-MC-BBDK
• First Posted: Jul 20, 2009
• Last Update Posted: Sep 18, 2019
• Last Verified: Sep 1, 2019

• Individual Participant Data (IPD) Sharing Statement: Yes
• Plan to Share IPD: Yes
• Keywords provided by Eli Lilly and Company: Diabetes; Type 2 Diabetes
• Additional relevant MeSH terms: Diabetes Mellitus; Diabetes Mellitus, Type 2

Study Results

Participant Flow

Arm/Group Title	0.6 mg LY2189102	18 mg LY2189102	180 mg LY2189102	Placebo
Arm/Group Description	Participants received 2 subcutaneous (SC) injections weekly for 12 weeks.	Participants received 2 SC injections weekly for 12 weeks.	Participants received 2 SC injections weekly for 12 weeks.	Participants received 2 SC injections of 0.9% sodium chloride weekly for 12 weeks.
Period Title: Overall Study
STARTED	26	26	27	27
COMPLETED	22	16	18	23
NOT COMPLETED	4	10	9	4

Baseline Characteristics

Arm/Group Title	0.6 mg LY2189102	18 mg LY2189102	180 mg LY2189102	Placebo	Total
Arm/Group Description	Participants received 2 subcutaneous (SC) injections weekly for 12 weeks.	Participants received 2 SC injections weekly for 12 weeks.	Participants received 2 SC injections weekly for 12 weeks.	Participants received 2 SC injections of 0.9% sodium chloride weekly for 12 weeks.	Total of all reporting groups
Overall Participants	26	26	27	27	106
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	52.9 (6.75)	53.7 (10.74)	51.3 (9.17)	52.9 (9.41)	52.7 (9.05)
Sex: Female, Male (Count of Participants)
Female	15 57.7%	17 65.4%	15 55.6%	20 74.1%	67 63.2%
Male	11 42.3%	9 34.6%	12 44.4%	7 25.9%	39 36.8%
Race/Ethnicity, Customized (Count of Participants)
Caucasian	6 23.1%	12 46.2%	10 37%	10 37%	38 35.8%
African	3 11.5%	6 23.1%	3 11.1%	3 11.1%	15 14.2%
Hispanic	15 57.7%	7 26.9%	13 48.1%	14 51.9%	49 46.2%
East Asian	0 0%	1 3.8%	0 0%	0 0%	1 0.9%
Other	2 7.7%	0 0%	1 3.7%	0 0%	3 2.8%
Region of Enrollment (Count of Participants)
United States	26 100%	26 100%	27 100%	27 100%	106 100%
Percentage of Glycosylated Fraction of Hemoglobin (HbA1c) (percentage of glycosylated hemoglobin) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [percentage of glycosylated hemoglobin]	7.540 (0.5596)	7.950 (0.7002)	8.271 (0.9380)	7.824 (0.6557)	7.882 (0.7544)
Fasting Glucose (millimoles per liter (mmol/L)) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [millimoles per liter (mmol/L)]	8.152 (1.8154)	9.106 (2.2001)	10.300 (2.1440)	9.339 (1.7315)	9.208 (2.0688)
Fasting Insulin (microinternational units per milliliter) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [microinternational units per milliliter]	15.083 (12.0562)	15.034 (6.9383)	13.989 (14.4076)	15.120 (12.5253)	14.821 (11.7856)
High-sensitivity C-reactive Protein (hsCRP) (milligrams per liter (mg/L)) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [milligrams per liter (mg/L)]	6.214 (6.2179)	6.024 (4.4956)	7.183 (6.9691)	6.093 (4.5289)	6.373 (5.5685)
Body Mass Index (BMI) (kilograms per square meter (kg/m^2)) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [kilograms per square meter (kg/m^2)]	33.0 (3.73)	33.7 (3.72)	33.1 (4.02)	32.5 (4.62)	33.1 (4.01)
Number of Participants on Diet and Exercise Only (Count of Participants)
Diet and Exercise Only - Yes	5 19.2%	3 11.5%	4 14.8%	7 25.9%	19 17.9%
Diet and Exercise Only - No	21 80.8%	23 88.5%	23 85.2%	20 74.1%	87 82.1%
Number of Participants on Anti-diabetic Medications (Count of Participants)
Biguanides	20 76.9%	23 88.5%	22 81.5%	20 74.1%	85 80.2%
Glucagon-like Peptide (GLP) Analogs and Agonists	1 3.8%	0 0%	0 0%	0 0%	1 0.9%
DPP-4 Inhibitors	0 0%	0 0%	4 14.8%	0 0%	4 3.8%
Enhancers of Insulin Effects	0 0%	1 3.8%	0 0%	0 0%	1 0.9%
Sufonylureas	8 30.8%	7 26.9%	5 18.5%	6 22.2%	26 24.5%

Outcome Measures

1. Primary Outcome

Title	Change From Baseline in the Glycosylated Hemoglobin (HbA1c) at 12 Weeks
Description	Change in HbA1c from baseline following 12 weeks of therapy (that is, HbA1c at week 12 minus HbA1c at baseline). The Least Squares (LS) Mean Value was based on an analysis of covariance (ANCOVA) model with treatment and site as class variables and baseline HbA1c as a continuous covariate.
Time Frame	Baseline, 12 weeks

Outcome Measure Data

Analysis Population Description

Compliant set. All randomized participants receiving at least 11 doses of study drug were analyzed according to the treatment subjects were assigned.

Arm/Group Title	0.6 mg LY2189102	18 mg LY2189102	180 mg LY2189102	Placebo
Arm/Group Description	Participants received 2 subcutaneous (SC) injections weekly for 12 weeks.	Participants received 2 SC injections weekly for 12 weeks.	Participants received 2 SC injections weekly for 12 weeks.	Participants received 2 SC injections of 0.9% sodium chloride weekly for 12 weeks.
Measure Participants	21	16	19	23
Least Squares Mean (Standard Error) [percentage of glycosylated hemoglobin]	-0.457 (0.1454)	-0.561 (0.1530)	-0.428 (0.1379)	-0.183 (0.1315)

2. Secondary Outcome

Title	Change From Baseline in Fasting Glucose at 12 Weeks
Description	Change in fasting glucose following 12 weeks of therapy (that is, fasting glucose at week 12 minus fasting glucose at baseline). The Least Squares (LS) Mean Value was based on an analysis of covariance (ANCOVA) model with treatment and site as class variables and baseline value as a continuous covariate.
Time Frame	Baseline, 12 weeks

Outcome Measure Data

Analysis Population Description

Compliant set. All randomized participants receiving at least 11 doses of study drug were analyzed according to the treatment subjects were assigned.

Arm/Group Title	0.6 mg LY2189102	18 mg LY2189102	180 mg LY2189102	Placebo
Arm/Group Description	Participants received 2 subcutaneous (SC) injections weekly for 12 weeks.	Participants received 2 SC injections weekly for 12 weeks.	Participants received 2 SC injections weekly for 12 weeks.	Participants received 2 SC injections of 0.9% sodium chloride weekly for 12 weeks.
Measure Participants	20	15	19	23
Least Squares Mean (Standard Error) [millimole per liter (mmol/L)]	-0.873 (0.4802)	-1.270 (0.5299)	-0.629 (0.4591)	-0.019 (0.4404)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	0.6 mg LY2189102, Placebo
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.854
	Confidence Interval	(2-Sided) 95%; -1.94 to 0.23
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	18 mg LY2189102, Placebo
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-1.252
	Confidence Interval	(2-Sided) 95%; -2.48 to -0.03
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	180 mg LY2189102, Placebo
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.610
	Confidence Interval	(2-Sided) 95%; -1.76 to 0.54
	Parameter Dispersion	Type: Value:
	Estimation Comments

3. Secondary Outcome

Title	Change From Baseline in Insulin Sensitivity (Fasting Insulin) at 12 Weeks
Description	Change in serum fasting insulin from baseline to endpoint (that is, serum insulin at week 12 minus serum insulin at week 0). The Least Squares (LS) Mean Value was based on an analysis of covariance (ANCOVA) model with treatment and site as class variables and baseline value as a continuous covariate.
Time Frame	Baseline, 12 weeks

Outcome Measure Data

Analysis Population Description

Compliant set. All randomized participants receiving at least 11 doses of study drug were analyzed according to the treatment subjects were assigned.

Arm/Group Title	0.6 mg LY2189102	18 mg LY2189102	180 mg LY2189102	Placebo
Arm/Group Description	Participants received 2 subcutaneous (SC) injections weekly for 12 weeks.	Participants received 2 SC injections weekly for 12 weeks.	Participants received 2 SC injections weekly for 12 weeks.	Participants received 2 SC injections of 0.9% sodium chloride weekly for 12 weeks.
Measure Participants	20	15	19	21
Least Squares Mean (Standard Error) [microinternational Units per liter]	-1.589 (2.9549)	-0.918 (3.3206)	-0.229 (2.7836)	1.405 (2.8722)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	0.6 mg LY2189102, Placebo
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-2.995
	Confidence Interval	(2-Sided) 95%; -9.82 to 3.83
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	18 mg LY2189102, Placebo
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-2.324
	Confidence Interval	(2-Sided) 95%; -10.21 to 5.56
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	180 mg LY2189102, Placebo
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-1.635
	Confidence Interval	(2-Sided) 95%; -9.16 to 5.89
	Parameter Dispersion	Type: Value:
	Estimation Comments

4. Secondary Outcome

Title	Number of Participants With a Change From Baseline in Beta-Cell Function Measured by Glucose and Insulin Changes With the Mixed Meal Tolerance Test (MMTT) at 12 Weeks
Description	The number of participants with a change from baseline in glucose and insulin at 2 hours after the MMTT was analyzed. The MMTT measures glucose and insulin before and after a standardized meal is eaten. Glucose and insulin levels were measured before the MMTT and 2 hours after the MMTT.
Time Frame	Baseline, 12 weeks

Outcome Measure Data

Analysis Population Description

Full analysis set. All randomized participants who received at least 1 dose of the study drug according to the treatment they were assigned and for whom the data are considered sufficient and interpretable. Differences in Ns are due to either dropouts and no post-baseline measure or something occurred to the sample (for example, not taken, broke).

Arm/Group Title	0.6 mg LY2189102	18 mg LY2189102	180 mg LY2189102	Placebo
Arm/Group Description	Participants received 2 subcutaneous (SC) injections weekly for 12 weeks.	Participants received 2 SC injections weekly for 12 weeks.	Participants received 2 SC injections weekly for 12 weeks.	Participants received 2 SC injections of 0.9% sodium chloride weekly for 12 weeks.
Measure Participants	22	17	18	24
Glucose at 2 hours	22 84.6%	17 65.4%	18 66.7%	24 88.9%
Insulin at 2 hours	22 84.6%	17 65.4%	18 66.7%	24 88.9%

5. Secondary Outcome

Title	Change From Baseline in the Glycosylated Hemoglobin (HbA1c) at Week 10 and Week 12
Description	The change from baseline in HbA1c at week 10 (that is HbA1c at week 10 minus HbA1c at baseline) and week 12 (that is, HbA1c at week 12 minus HbA1c at baseline). The Least Squares (LS) Mean Value was based on an analysis of covariance (ANCOVA) model with treatment and site as class variables and baseline value as a continuous covariate.
Time Frame	Baseline, week 10, week 12

Outcome Measure Data

Analysis Population Description

Compliant set. All randomized participants receiving at least 11 doses of study drug were analyzed according to the treatment subjects were assigned.

Arm/Group Title	0.6 mg LY2189102	18 mg LY2189102	180 mg LY2189102	Placebo
Arm/Group Description	Participants received 2 subcutaneous (SC) injections weekly for 12 weeks.	Participants received 2 SC injections weekly for 12 weeks.	Participants received 2 SC injections weekly for 12 weeks.	Participants received 2 SC injections of 0.9% sodium chloride weekly for 12 weeks.
Measure Participants	21	16	19	23
HbA1c at Week 10	-0.456 (0.1459)	-0.555 (0.1541)	-0.413 (0.1412)	-0.186 (0.1322)
HbA1c at Week 12	-0.459 (0.1560)	-0.588 (0.1712)	-0.413 (0.1455)	-0.192 (0.1410)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	0.6 mg LY2189102, Placebo
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.270
	Confidence Interval	(2-Sided) 95%; -0.59 to 0.05
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	18 mg LY2189102, Placebo
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.369
	Confidence Interval	(2-Sided) 95%; -0.74 to 0.00
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	180 mg LY2189102, Placebo
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.227
	Confidence Interval	(2-Sided) 95%; -0.59 to 0.13
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	0.6 mg LY2189102, Placebo
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.267
	Confidence Interval	(2-Sided) 95%; -0.61 to 0.08
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	18 mg LY2189102, Placebo
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.396
	Confidence Interval	(2-Sided) 95%; -0.79 to 0.00
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	180 mg LY2189102, Placebo
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.221
	Confidence Interval	(2-Sided) 95%; -0.59 to 0.15
	Parameter Dispersion	Type: Value:
	Estimation Comments

6. Secondary Outcome

Title	Pharmacokinetics (PK) Maximum Serum Concentration (Cmax) of LY2189102 at End of Dosing (12 Weeks)
Description	The Cmax value measures the maximum serum concentration and is estimated for LY2189102. The values were generated as individual estimates from a population pharmacokinetics (PK) model. Placebo samples were not assayed for serum concentration of LY2189102 because the participants in the placebo treatment arm did not receive LY2189102 study drug.
Time Frame	Prior to and 1 and 3-4 days after the first dose, prior to every other dose, and 6 and 12 weeks after the last dose

Outcome Measure Data

Analysis Population Description

Full Analysis Set: All randomized participants who received at least 1 dose of the study drug according to the treatment they were assigned and for whom the data are considered sufficient and interpretable. Differences in Ns are due to either dropouts and no post-baseline measure or something occurred to the sample (for example, not taken, broke).

Arm/Group Title	0.6 mg LY2189102	18 mg LY2189102	180 mg LY2189102
Arm/Group Description	Participants received 2 subcutaneous (SC) injections weekly for 12 weeks.	Participants received 2 SC injections weekly for 12 weeks.	Participants received 2 SC injections weekly for 12 weeks.
Measure Participants	18	15	19
Mean (Standard Deviation) [nanograms per milliliter (ng/mL)]	269.39 (88.23)	6094.67 (2153.00)	39994.74 (17880.45)

7. Secondary Outcome

Title	PK: Area Under the Concentration Time Curve for Dosing Interval (Tau) at Steady State (AUCτ,SS) at End of Dosing (12 Weeks)
Description	Individual estimates of AUCtau at end of dosing generated from a population pharmacokinetic (PK) model.
Time Frame	Prior to and 1 and 3-4 days after the first dose, prior to every other dose, and 6 and 12 weeks after the last dose

Outcome Measure Data

Analysis Population Description

Compliant set. All randomized participants receiving at least 11 doses of study drug were analyzed according to the treatment subjects were assigned. Placebo samples were not assayed for serum concentration of LY2189102 because the participants in the placebo treatment arm did not receive LY2189102 study drug.

Arm/Group Title	0.6 mg LY2189102	18 mg LY2189102	180 mg LY2189102
Arm/Group Description	Participants received 2 subcutaneous (SC) injections weekly for 12 weeks.	Participants received 2 SC injections weekly for 12 weeks.	Participants received 2 SC injections weekly for 12 weeks.
Measure Participants	18	15	19
Mean (Standard Deviation) [nanogram*hour per milliliter (ng*h/mL)]	45777.78 (14933.09)	986533.33 (340965.83)	6555789.47 (2934693.46)

8. Secondary Outcome

Title	Pharmacokinetics Measured by Serum Concentration at End of Dosing (12 Weeks)
Description	Pharmacokinetics Measured by Serum Concentration at End of Dosing.
Time Frame	Prior to and 1 and 3-4 days after the first dose, prior to every other dose, and 6 and 12 weeks after the last dose

Outcome Measure Data

Analysis Population Description

All participants who received at least one dose of study drug and had evaluable PK data. Placebo samples were not assayed for serum concentration of LY2189102 because the participants in the placebo treatment arm did not receive LY2189102 study drug.

Arm/Group Title	0.6 mg LY2189102	18 mg LY2189102	180 mg LY2189102
Arm/Group Description	Participants received 2 subcutaneous (SC) injections weekly for 12 weeks.	Participants received 2 SC injections weekly for 12 weeks.	Participants received 2 SC injections weekly for 12 weeks.
Measure Participants	18	15	19
Mean (Standard Deviation) [nanograms per milliliter (ng/mL)]	252.83 (83.28)	5532.00 (1991.28)	35815.79 (15961.46)

Adverse Events

Arm/Group Title	0.6 mg LY2189102		18 mg LY2189102		180 mg LY2189102		Placebo
Arm/Group Description	Participants received 2 subcutaneous (SC) injections weekly for 12 weeks.		Participants received 2 SC injections weekly for 12 weeks.		Participants received 2 SC injections weekly for 12 weeks.		Participants received 2 SC injections of 0.9% sodium chloride weekly for 12 weeks.
All Cause Mortality
	0.6 mg LY2189102		18 mg LY2189102		180 mg LY2189102		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	0.6 mg LY2189102		18 mg LY2189102		180 mg LY2189102		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/26 (3.8%)		1/26 (3.8%)		0/27 (0%)		0/27 (0%)
General disorders
Chest pain	0/26 (0%)	0	1/26 (3.8%)	1	0/27 (0%)	0	0/27 (0%)	0
Nervous system disorders
Migraine	1/26 (3.8%)	1	0/26 (0%)	0	0/27 (0%)	0	0/27 (0%)	0
Respiratory, thoracic and mediastinal disorders
Asthma	0/26 (0%)	0	1/26 (3.8%)	1	0/27 (0%)	0	0/27 (0%)	0
Status asthmaticus	0/26 (0%)	0	1/26 (3.8%)	1	0/27 (0%)	0	0/27 (0%)	0
Other (Not Including Serious) Adverse Events
	0.6 mg LY2189102		18 mg LY2189102		180 mg LY2189102		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	19/26 (73.1%)		19/26 (73.1%)		23/27 (85.2%)		20/27 (74.1%)
Cardiac disorders
Cardiac disorder	0/26 (0%)	0	0/26 (0%)	0	2/27 (7.4%)	2	0/27 (0%)	0
Palpitations	2/26 (7.7%)	2	1/26 (3.8%)	1	0/27 (0%)	0	0/27 (0%)	0
Gastrointestinal disorders
Abdominal pain	0/26 (0%)	0	1/26 (3.8%)	1	2/27 (7.4%)	2	1/27 (3.7%)	1
Abdominal tenderness	0/26 (0%)	0	2/26 (7.7%)	2	0/27 (0%)	0	1/27 (3.7%)	1
Constipation	0/26 (0%)	0	2/26 (7.7%)	2	0/27 (0%)	0	0/27 (0%)	0
Diarrhoea	2/26 (7.7%)	3	3/26 (11.5%)	3	2/27 (7.4%)	2	3/27 (11.1%)	3
Flatulence	2/26 (7.7%)	2	0/26 (0%)	0	0/27 (0%)	0	0/27 (0%)	0
Nausea	2/26 (7.7%)	2	2/26 (7.7%)	2	1/27 (3.7%)	1	3/27 (11.1%)	3
Vomiting	1/26 (3.8%)	1	1/26 (3.8%)	1	0/27 (0%)	0	3/27 (11.1%)	3
General disorders
Injection site haematoma	0/26 (0%)	0	4/26 (15.4%)	4	0/27 (0%)	0	1/27 (3.7%)	1
Injection site irritation	0/26 (0%)	0	3/26 (11.5%)	3	1/27 (3.7%)	1	0/27 (0%)	0
Injection site pain	0/26 (0%)	0	2/26 (7.7%)	2	2/27 (7.4%)	2	0/27 (0%)	0
Oedema peripheral	1/26 (3.8%)	1	2/26 (7.7%)	2	1/27 (3.7%)	1	2/27 (7.4%)	3
Pyrexia	0/26 (0%)	0	0/26 (0%)	0	1/27 (3.7%)	1	2/27 (7.4%)	2
Infections and infestations
Nasopharyngitis	5/26 (19.2%)	5	3/26 (11.5%)	3	0/27 (0%)	0	1/27 (3.7%)	1
Sinusitis	1/26 (3.8%)	1	2/26 (7.7%)	2	0/27 (0%)	0	1/27 (3.7%)	1
Injury, poisoning and procedural complications
Muscle strain	2/26 (7.7%)	2	0/26 (0%)	0	0/27 (0%)	0	0/27 (0%)	0
Musculoskeletal and connective tissue disorders
Arthralgia	1/26 (3.8%)	2	3/26 (11.5%)	3	3/27 (11.1%)	4	1/27 (3.7%)	2
Musculoskeletal chest pain	1/26 (3.8%)	1	0/26 (0%)	0	0/27 (0%)	0	2/27 (7.4%)	2
Pain in extremity	1/26 (3.8%)	2	2/26 (7.7%)	2	1/27 (3.7%)	1	1/27 (3.7%)	1
Nervous system disorders
Dizziness	2/26 (7.7%)	2	0/26 (0%)	0	0/27 (0%)	0	1/27 (3.7%)	1
Headache	1/26 (3.8%)	1	4/26 (15.4%)	4	3/27 (11.1%)	3	2/27 (7.4%)	2
Paraesthesia	0/26 (0%)	0	0/26 (0%)	0	2/27 (7.4%)	2	0/27 (0%)	0
Respiratory, thoracic and mediastinal disorders
Cough	0/26 (0%)	0	2/26 (7.7%)	2	1/27 (3.7%)	1	2/27 (7.4%)	2
Pulmonary congestion	0/26 (0%)	0	0/26 (0%)	0	2/27 (7.4%)	2	0/27 (0%)	0
Vascular disorders
Hypertension	2/26 (7.7%)	2	2/26 (7.7%)	2	2/27 (7.4%)	2	1/27 (3.7%)	1

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.