Study of LY2409021 in Participants With Type 1 Diabetes

• Sponsor: Eli Lilly and Company (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01640834
• Collaborator: (none)
• Enrollment: 20
• Location: 1
• Arms: 3
• Duration (Months): 2
• Patients Per Site Per Month: 9.8

Study Details

Study Description

Brief Summary

This study involves taking a single dose of 100 milligrams (mg) or 300 mg LY2409021 or placebo (an inactive medicine) taken as up to 3 capsules by mouth. The study will evaluate if this drug will reduce the amount of insulin a type 1 diabetic needs over 24 hours. This study includes a 7-day hospitalization period at the clinical research unit (CRU) and will involve screening within 30 days of the start of the study as well as telephone consultations within 5 days after discharge from the CRU.

Condition or Disease	Intervention/Treatment	Phase
Diabetes Mellitus, Type 1	Drug: LY2409021; Drug: Placebo; Drug: Glucagon	Phase 1

Study Design

• Study Type: Interventional
• Actual Enrollment: 20 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• Official Title: Pilot Study of the Effects of LY2409021 in Patients With Type 1 Diabetes Mellitus
• Study Start Date: Jul 1, 2012
• Actual Primary Completion Date: Sep 1, 2012
• Actual Study Completion Date: Sep 1, 2012

Arms and Interventions

Arm	Intervention/Treatment
Experimental: 100 mg LY2409021 LY2409021: 100 milligrams (mg), 1 capsule, administered as a single oral dose on Day 2. Placebo: 2 capsules, administered as a single oral dose on Day 2. Glucagon: 1 mg administered via intramuscular injection on Day 3.	Drug: LY2409021; Administered orally; Drug: Placebo; Administered orally; Drug: Glucagon; Administered via intramuscular injection
Experimental: 300 mg LY2409021 LY2409021: 300 milligrams (mg), 3 capsules (3 X 100-mg capsules), administered as a single oral dose on Day 2. Glucagon: 1 mg administered via intramuscular injection on Day 3.	Drug: LY2409021; Administered orally; Drug: Glucagon; Administered via intramuscular injection
Placebo Comparator: Placebo Placebo: 3 capsules administered as a single oral dose on Day 2. Glucagon: 1 milligram (mg) administered via intramuscular injection on Day 3.	Drug: Placebo; Administered orally; Drug: Glucagon; Administered via intramuscular injection

Outcome Measures

Primary Outcome Measures

1. Pharmacodynamics: Change From Baseline to Day 2 in 24-hour Insulin Dose [Baseline (Day 1), Day 2]

   The mean absolute change in total insulin dose over 24 hours (Day 2, 24-hour insulin dose - Day 1, 24-hour insulin dose) is reported.

Secondary Outcome Measures

1. Pharmacodynamics: Percentage Change From Baseline to Day 2 in 24-hour Insulin [Baseline (Day 1), Day 2]

   The percentage change in total insulin dose over 24 hours (Day 2, 24-hour insulin dose - Day 1, 24-hour insulin dose) is reported.

2. Pharmacokinetics: Maximum Concentration (Cmax) of LY2409021 [Predose (Day 2) through 120 hours postdose (Day 7)]

3. Pharmacokinetics: Area Under the Concentration Curve (AUC) of LY2409021 [Predose (Day 2) through 120 hours postdose (Day 7)]

   Exposure in terms of AUC of LY2409021 from time 0 extrapolated to infinity (AUCinf) is reported.

4. Pharmacodynamics: Change From Baseline in 24 Hour Insulin Dose During Drug Washout Period [Baseline (Day 1), Day 3 up to Day 6]

   Data were not captured, and, therefore, this outcome measure was not analyzed. Zero participants were included in the analysis.

5. Pharmacodynamics: Change From Baseline in 24 Hour Insulin Dose Needed to Maintain Euglycemia [Baseline (Day 1), Day 3 up to Day 6]

   Data were not captured, and, therefore, this outcome measure was not analyzed. Zero participants were included in the analysis.

6. Pharmacodynamics: Maximum Concentration (Cmax) of Glucose Concentration After 1 Milligram (mg) Glucagon Injection on Day 3 [Day 3]

   The Cmax of glucose following a single dose of glucagon (1 mg) administered via an intramuscular injection is reported.

7. Pharmacodynamics: Area Under the Glucose Concentration Curve After a Single Dose of Glucagon on Day 3 [Day 3]

   Area under the glucose concentration curve from time 0 through 2 hours after a single dose of glucagon (1 milligram) administered via an intramuscular injection is reported.

Eligibility Criteria

Criteria

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

Inclusion Criteria:

• Have had type 1 diabetes mellitus (T1DM) based on the World Health Organization classification for at least 1 year and have a daily insulin dose ≤1.5 international units (IU) per kilogram (kg) of body weight

• Have a glycated hemoglobin A1c (HbA1c) of no greater than 9.0% as measured at screening

• Have a body mass index (BMI) ≥19.0 and ≤35.0 kilograms per meter squared (kg/m^2)

• Have given written informed consent approved by Lilly

Exclusion Criteria:

• Received any oral or injectable medication intended for the treatment of diabetes mellitus other than insulins in the 3 months prior to screening

• Have had more than 1 episode of severe hypoglycemia within 3 months prior to entry into the study, or are currently diagnosed as having hypoglycemia unawareness

• Are pregnant or intend to become pregnant during the course of the study

• Women who are breastfeeding

• Have a history of stroke, myocardial infarction, heart failure, unstable angina, or a coronary revascularization procedure within 6 months of screening

• Have fasting triglycerides >500 milligrams per deciliter (mg/dL) (5.65 millimoles per liter [mmol/L])

• Have obvious clinical signs, symptoms, or laboratory evidence of liver disease (alanine transaminase [ALT] or aspartate transaminase [AST] greater than 2 times the upper limit of normal at screening)

• Have a history of renal transplantation or are currently receiving renal dialysis or have a screening creatinine >2.0 mg/dL (177 micromoles per liter [μmol/L])

• Have had any other disease, illness, or condition (including known diabetic autonomic neuropathy, drug or alcohol abuse, or psychiatric disorder) within the 6 months prior to screening that precludes the participant from following and completing the study or could increase their risk for hypoglycemia, according to the investigator's judgment

• Are currently enrolled in, have completed, or have discontinued within the last 30 days from a clinical trial involving an off-label use of an investigational drug or device, or are concurrently enrolled in any other type of medical research judged not to be scientifically or medically compatible with this study

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.	Neuss		Germany	41460

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: NCT01640834
• Other Study ID Numbers: 14576; I1R-MC-GLBR; 2011-006178-19
• First Posted: Jul 16, 2012
• Last Update Posted: Oct 29, 2018
• Last Verified: Mar 1, 2018

• Additional relevant MeSH terms: Diabetes Mellitus; Diabetes Mellitus, Type 1; Glucagon

Study Results

Participant Flow

Arm/Group Title	100 mg LY2409021	300 mg LY2409021	Placebo
Arm/Group Description	LY2409021: 100 milligrams (mg), 1 capsule, administered as a single oral dose on Day 2. Placebo: 2 capsules, administered as a single oral dose on Day 2. Glucagon: 1 mg administered via intramuscular injection on Day 3.	LY2409021: 300 milligrams (mg), 3 capsules (3 X 100-mg capsules), administered as a single oral dose on Day 2. Glucagon: 1 mg administered via intramuscular injection on Day 3.	Placebo: 3 capsules administered as a single oral dose on Day 2. Glucagon: 1 milligram (mg) administered via intramuscular injection on Day 3.
Period Title: Overall Study
STARTED	8	8	4
Received at Least 1 Dose of Study Drug	8	8	4
COMPLETED	8	8	4
NOT COMPLETED	0	0	0

Baseline Characteristics

Arm/Group Title	100 mg LY2409021	300 mg LY2409021	Placebo	Total
Arm/Group Description	LY2409021: 100 milligrams (mg), 1 capsule, administered as a single oral dose on Day 2. Placebo: 2 capsules, administered as a single oral dose on Day 2. Glucagon: 1 mg administered via intramuscular injection on Day 3.	LY2409021: 300 milligrams (mg), 3 capsules (3 X 100-mg capsules), administered as a single oral dose on Day 2. Glucagon: 1 mg administered via intramuscular injection on Day 3.	Placebo: 3 capsules administered as a single oral dose on Day 2. Glucagon: 1 milligram (mg) administered via intramuscular injection on Day 3.	Total of all reporting groups
Overall Participants	8	8	4	20
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	38.6 (12.8)	47.1 (5.7)	43.3 (10.6)	43.0 (10.3)
Sex: Female, Male (Count of Participants)
Female	0 0%	0 0%	0 0%	0 0%
Male	8 100%	8 100%	4 100%	20 100%
Race/Ethnicity, Customized (Count of Participants)
White	8 100%	8 100%	4 100%	20 100%
Region of Enrollment (Count of Participants)
Germany	8 100%	8 100%	4 100%	20 100%

Outcome Measures

1. Primary Outcome

Title	Pharmacodynamics: Change From Baseline to Day 2 in 24-hour Insulin Dose
Description	The mean absolute change in total insulin dose over 24 hours (Day 2, 24-hour insulin dose - Day 1, 24-hour insulin dose) is reported.
Time Frame	Baseline (Day 1), Day 2

Outcome Measure Data

Analysis Population Description

All participants who received a dose of LY2409021 or placebo and had evaluable 24-hour insulin data.

Arm/Group Title	100 mg LY2409021	300 mg LY2409021	Placebo
Arm/Group Description	LY2409021: 100 milligrams (mg), 1 capsule, administered as a single oral dose on Day 2. Placebo: 2 capsules, administered as a single oral dose on Day 2. Glucagon: 1 mg administered via intramuscular injection on Day 3.	LY2409021: 300 milligrams (mg), 3 capsules (3 X 100-mg capsules), administered as a single oral dose on Day 2. Glucagon: 1 mg administered via intramuscular injection on Day 3.	Placebo: 3 capsules administered as a single oral dose on Day 2. Glucagon: 1 milligram (mg) administered via intramuscular injection on Day 3.
Measure Participants	8	8	4
Mean (Standard Deviation) [insulin units]	1.85 (7.15)	0.80 (9.63)	7.69 (2.99)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	100 mg LY2409021
	Comments	The mean change on Day 2 from Day 1 in the 24-hour insulin dose for the placebo group was subtracted from each participant's change on Day 2 from Day 1 in the 24-hour insulin dose. This placebo adjusted 24-hour insulin dose was compared within the 100-mg LY2409021 dose group using a 1 sample t-test.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0542
	Comments
	Method	t-test, 1 sided
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	-5.84
	Confidence Interval	(2-Sided) 95%; -11.82 to 0.14
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	300 mg LY2409021
	Comments	The mean change on Day 2 from Day 1 in the 24-hour insulin dose for the placebo group was subtracted from each participant's change on Day 2 from Day 1 in the 24-hour insulin dose. This placebo adjusted 24-hour insulin dose was compared within the 300-mg LY2409021 dose group.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0826
	Comments
	Method	t-test, 1 sided
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	-6.89
	Confidence Interval	(2-Sided) 95%; -14.95 to 1.16
	Parameter Dispersion	Type: Value:
	Estimation Comments

2. Secondary Outcome

Title	Pharmacodynamics: Percentage Change From Baseline to Day 2 in 24-hour Insulin
Description	The percentage change in total insulin dose over 24 hours (Day 2, 24-hour insulin dose - Day 1, 24-hour insulin dose) is reported.
Time Frame	Baseline (Day 1), Day 2

Outcome Measure Data

Analysis Population Description

All participants who received a dose of LY2409021 or placebo and had evaluable 24-hour insulin data.

Arm/Group Title	100 mg LY2409021	300 mg LY2409021	Placebo
Arm/Group Description	LY2409021: 100 milligrams (mg), 1 capsule, administered as a single oral dose on Day 2. Placebo: 2 capsules, administered as a single oral dose on Day 2. Glucagon: 1 mg administered via intramuscular injection on Day 3.	LY2409021: 300 milligrams (mg), 3 capsules (3 X 100-mg capsules), administered as a single oral dose on Day 2. Glucagon: 1 mg administered via intramuscular injection on Day 3.	Placebo: 3 capsules administered as a single oral dose on Day 2. Glucagon: 1 milligram (mg) administered via intramuscular injection on Day 3.
Measure Participants	8	8	4
Mean (Standard Deviation) [percentage of insulin units]	5.71 (19.90)	3.12 (18.34)	22.75 (22.20)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	100 mg LY2409021
	Comments	Analysis was performed using the percent change in insulin dose, which takes into account absolute differences in individual insulin doses. The mean percent change on Day 2 from Day 1 in the 24-hour insulin dose for the placebo group was subtracted from each participant's percent change on Day 2 from Day 1 in the 24-hour insulin dose. This placebo adjusted 24-hour insulin dose was compared within the 100-mg LY2409021 dose group using a 1 sample t-test.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0460
	Comments
	Method	t-test, 1 sided
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	-17.0
	Confidence Interval	(2-Sided) 95%; -33.7 to -0.4
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	300 mg LY2409021
	Comments	Analysis was performed using the percent change in insulin dose, which takes into account absolute differences in individual insulin doses. The mean percent change on Day 2 from Day 1 in the 24-hour insulin dose for the placebo group was subtracted from each participant's percent change on Day 2 from Day 1 in the 24-hour insulin dose. This placebo adjusted 24-hour insulin dose was compared within the 300-mg LY2409021 dose group using a 1 sample t-test.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0192
	Comments
	Method	t-test, 1 sided
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	-19.6
	Confidence Interval	(2-Sided) 95%; -35.0 to -4.3
	Parameter Dispersion	Type: Value:
	Estimation Comments

3. Secondary Outcome

Title	Pharmacokinetics: Maximum Concentration (Cmax) of LY2409021
Time Frame	Predose (Day 2) through 120 hours postdose (Day 7)

Outcome Measure Data

Analysis Population Description

All participants who received a dose of LY2409021 and had evaluable pharmacokinetic data.

Arm/Group Title	100 mg LY2409021	300 mg LY2409021
Arm/Group Description	LY2409021: 100 milligrams (mg), 1 capsule, administered as a single oral dose on Day 2. Placebo: 2 capsules, administered as a single oral dose on Day 2. Glucagon: 1 mg administered via intramuscular injection on Day 3.	LY2409021: 300 milligrams (mg), 3 capsules (3 X 100-mg capsules), administered as a single oral dose on Day 2. Glucagon: 1 mg administered via intramuscular injection on Day 3.
Measure Participants	8	8
Geometric Mean (Geometric Coefficient of Variation) [nanograms per milliliter]	2620 (23)	6090 (23)

4. Secondary Outcome

Title	Pharmacokinetics: Area Under the Concentration Curve (AUC) of LY2409021
Description	Exposure in terms of AUC of LY2409021 from time 0 extrapolated to infinity (AUCinf) is reported.
Time Frame	Predose (Day 2) through 120 hours postdose (Day 7)

Outcome Measure Data

Analysis Population Description

All participants who received a dose of LY2409021 and had evaluable pharmacokinetic data.

Arm/Group Title	100 mg LY2409021	300 mg LY2409021
Arm/Group Description	LY2409021: 100 milligrams (mg), capsule, administered as a single oral dose on Day 2. Placebo: 2 capsules, administered as a single oral dose on Day 2. Glucagon: 1 mg administered via intramuscular injection on Day 3.	LY2409021: 300 milligrams (mg), capsules (3 X 100-mg capsules), administered as a single oral dose on Day 2. Glucagon: 1 mg administered via intramuscular injection on Day 3.
Measure Participants	8	8
Geometric Mean (Geometric Coefficient of Variation) [nanograms * hours per milliliter]	209000 (30)	506000 (22)

5. Secondary Outcome

Title	Pharmacodynamics: Change From Baseline in 24 Hour Insulin Dose During Drug Washout Period
Description	Data were not captured, and, therefore, this outcome measure was not analyzed. Zero participants were included in the analysis.
Time Frame	Baseline (Day 1), Day 3 up to Day 6

Outcome Measure Data

Analysis Population Description

This outcome measure was not analyzed.

Arm/Group Title	100 mg LY2409021	300 mg LY2409021	Placebo
Arm/Group Description	LY2409021: 100 milligrams (mg), 1 capsule, administered as a single oral dose on Day 2. Placebo: 2 capsules, administered as a single oral dose on Day 2. Glucagon: 1 mg administered via intramuscular injection on Day 3.	LY2409021: 300 milligrams (mg), 3 capsules (3 X 100-mg capsules), administered as a single oral dose on Day 2. Glucagon: 1 mg administered via intramuscular injection on Day 3.	Placebo: 3 capsules administered as a single oral dose on Day 2. Glucagon: 1 milligram (mg) administered via intramuscular injection on Day 3.
Measure Participants	0	0	0

6. Secondary Outcome

Title	Pharmacodynamics: Change From Baseline in 24 Hour Insulin Dose Needed to Maintain Euglycemia
Description	Data were not captured, and, therefore, this outcome measure was not analyzed. Zero participants were included in the analysis.
Time Frame	Baseline (Day 1), Day 3 up to Day 6

Outcome Measure Data

Analysis Population Description

This outcome measure was not analyzed.

Arm/Group Title	100 mg LY2409021	300 mg LY2409021	Placebo
Arm/Group Description	LY2409021: 100 milligrams (mg), 1 capsule, administered as a single oral dose on Day 2. Placebo: 2 capsules, administered as a single oral dose on Day 2. Glucagon: 1 mg administered via intramuscular injection on Day 3.	LY2409021: 300 milligrams (mg), 3 capsules (3 X 100-mg capsules), administered as a single oral dose on Day 2. Glucagon: 1 mg administered via intramuscular injection on Day 3.	Placebo: 3 capsules administered as a single oral dose on Day 2. Glucagon: 1 milligram (mg) administered via intramuscular injection on Day 3.
Measure Participants	0	0	0

7. Secondary Outcome

Title	Pharmacodynamics: Maximum Concentration (Cmax) of Glucose Concentration After 1 Milligram (mg) Glucagon Injection on Day 3
Description	The Cmax of glucose following a single dose of glucagon (1 mg) administered via an intramuscular injection is reported.
Time Frame	Day 3

Outcome Measure Data

Analysis Population Description

All participants who received a dose of LY2409021 or placebo and had evaluable post-glucagon injection glucose concentration data.

Arm/Group Title	100 mg LY2409021	300 mg LY2409021	Placebo
Arm/Group Description	LY2409021: 100 milligrams (mg), 1 capsule, administered as a single oral dose on Day 2. Placebo: 2 capsules, administered as a single oral dose on Day 2. Glucagon: 1 mg administered via intramuscular injection on Day 3.	LY2409021: 300 milligrams (mg), 3 capsules (3 X 100-mg capsules), administered as a single oral dose on Day 2. Glucagon: 1 mg administered via intramuscular injection on Day 3.	Placebo: 3 capsules administered as a single oral dose on Day 2. Glucagon: 1 milligram (mg) administered via intramuscular injection on Day 3.
Measure Participants	8	8	4
Geometric Mean (Geometric Coefficient of Variation) [milligrams per deciliter]	154.9 (19)	141.3 (19)	201.8 (11)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	100 mg LY2409021, Placebo
	Comments	Statistical analysis of the effect of LY2409021 treatment on peak glucose concentration after an intramuscular injection of glucagon (1 milligram).
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0187
	Comments
	Method	t-test, 2 sided
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	-46
	Confidence Interval	(2-Sided) 95%; -82 to -9
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	300 mg LY2409021, Placebo
	Comments	Statistical analysis of the effect of LY2409021 treatment on peak glucose concentration after an intramuscular injection of glucagon (1 milligram).
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0048
	Comments
	Method	t-test, 2 sided
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	-59
	Confidence Interval	(2-Sided) 95%; -96 to -23
	Parameter Dispersion	Type: Value:
	Estimation Comments

8. Secondary Outcome

Title	Pharmacodynamics: Area Under the Glucose Concentration Curve After a Single Dose of Glucagon on Day 3
Description	Area under the glucose concentration curve from time 0 through 2 hours after a single dose of glucagon (1 milligram) administered via an intramuscular injection is reported.
Time Frame	Day 3

Outcome Measure Data

Analysis Population Description

All participants who received a dose of LY2409021 or placebo and had evaluable post-glucagon injection glucose concentration data.

Arm/Group Title	100 mg LY2409021	300 mg LY2409021	Placebo
Arm/Group Description	LY2409021: 100 milligrams (mg), 1 capsule, administered as a single oral dose on Day 2. Placebo: 2 capsules, administered as a single oral dose on Day 2. Glucagon: 1 mg administered via intramuscular injection on Day 3.	LY2409021: 300 milligrams (mg), 3 capsules (3 X 100-mg capsules), administered as a single oral dose on Day 2. Glucagon: 1 mg administered via intramuscular injection on Day 3.	Placebo: 3 capsules administered as a single oral dose on Day 2. Glucagon: 1 milligram (mg) administered via intramuscular injection on Day 3.
Measure Participants	8	8	4
Geometric Mean (Geometric Coefficient of Variation) [milligrams * minutes per deciliter]	15534.3 (21)	14885.5 (16)	20189.7 (9)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	100 mg LY2409021, Placebo
	Comments	Statistical analysis of the effect of LY2409021 treatment on area under the glucose concentration curve from time 0 to 2 hours postdose following an intramuscular injection of glucagon (1 milligram).
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0278
	Comments
	Method	t-test, 2 sided
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	-4423
	Confidence Interval	(2-Sided) 95%; -8256 to -590
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	300 mg LY2409021, Placebo
	Comments	Statistical analysis of the effect of LY2409021 treatment on area under the glucose concentration curve from time 0 to 2 hours postdose following an intramuscular injection of glucagon (1 milligram).
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0046
	Comments
	Method	t-test, 2 sided
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	-5187
	Confidence Interval	(2-Sided) 95%; -8371 to -2004
	Parameter Dispersion	Type: Value:
	Estimation Comments

Adverse Events

Arm/Group Title	100 mg LY2409021		300 mg LY2409021		Placebo
Arm/Group Description	LY2409021: 100 milligrams (mg), 1 capsule, administered as a single oral dose on Day 2. Placebo: 2 capsules, administered as a single oral dose on Day 2. Glucagon: 1 mg administered via intramuscular injection on Day 3.		LY2409021: 300 milligrams (mg), 3 capsules (3 X 100-mg capsules), administered as a single oral dose on Day 2. Glucagon: 1 mg administered via intramuscular injection on Day 3.		Placebo: 3 capsules administered as a single oral dose on Day 2. Glucagon: 1 milligram (mg) administered via intramuscular injection on Day 3.
All Cause Mortality
	100 mg LY2409021		300 mg LY2409021		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	100 mg LY2409021		300 mg LY2409021		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/8 (0%)		0/8 (0%)		0/4 (0%)
Other (Not Including Serious) Adverse Events
	100 mg LY2409021		300 mg LY2409021		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	6/8 (75%)		6/8 (75%)		4/4 (100%)
Gastrointestinal disorders
Constipation	0/8 (0%)	0	1/8 (12.5%)	1	0/4 (0%)	0
Diarrhoea	0/8 (0%)	0	1/8 (12.5%)	1	0/4 (0%)	0
Toothache	0/8 (0%)	0	1/8 (12.5%)	1	0/4 (0%)	0
General disorders
Discomfort	0/8 (0%)	0	1/8 (12.5%)	1	0/4 (0%)	0
Metabolism and nutrition disorders
Hypoglycaemia	6/8 (75%)	19	6/8 (75%)	13	3/4 (75%)	6
Musculoskeletal and connective tissue disorders
Muscle spasms	1/8 (12.5%)	1	0/8 (0%)	0	0/4 (0%)	0
Pain in extremity	0/8 (0%)	0	0/8 (0%)	0	1/4 (25%)	1
Nervous system disorders
Headache	0/8 (0%)	0	1/8 (12.5%)	1	0/4 (0%)	0
Skin and subcutaneous tissue disorders
Hyperhidrosis	0/8 (0%)	0	1/8 (12.5%)	1	0/4 (0%)	0

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.