A Study on the Effects of LY2409021 on the Electrical Impulses of the Heart

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.

ClinicalTrials.gov Identifier: NCT01460368

Recruitment Status : Completed

First Posted : October 26, 2011

Results First Posted : October 18, 2018

Last Update Posted : January 7, 2019

Sponsor:

Information provided by (Responsible Party):

Eli Lilly and Company

Study Type	Interventional
Study Design	Allocation: Randomized; Intervention Model: Crossover Assignment; Masking: Double (Participant, Investigator); Primary Purpose: Basic Science
Condition	Diabetes Mellitus, Type 2
Interventions	Drug: LY2409021 Drug: Placebo Drug: Moxifloxacin
Enrollment	67

Participant Flow

Recruitment Details
Pre-assignment Details


Arm/Group Title	Part A: LY2409021	Part B: LY2409021, Placebo, Moxifloxacin	Part B: Moxifloxacin, LY2409021, Placebo	Part B: Placebo, Moxifloxacin, LY2409021	Part B: Moxifloxacin, Placebo, LY2409021	Part B: Placebo, LY2409021, Moxifloxacin	Part B: LY2409021, Moxifloxacin, Placebo
Arm/Group Description	Participants received 2 standard me...	Period 1: 300 milligrams (mg) LY240...	Period 1: 400 milligrams (mg) Moxif...	Period 1: Placebo administered oral...	Period 1: 400 milligrams (mg) Moxif...	Period 1: Placebo administered oral...	Period 1: 300 milligrams (mg) LY240...
Arm/Group Description	Participants received 2 standard meals; one alone without LY2409021, and one along with a single dose of 300 milligrams (mg) LY2409021 administered orally to determine the effects of a meal on electrocardiogram (ECG) activity. Participants enrolled in Part A were not allowed to participate in Part B.	Period 1: 300 milligrams (mg) LY2409021 administered orally as a single dose on Day 1. Period 2: Placebo administered orally as a single dose on Day 1. Period 3: 400 milligrams (mg) Moxifloxacin administered orally as a single dose on Day 1.	Period 1: 400 milligrams (mg) Moxifloxacin administered orally as a single dose on Day 1. Period 2: 300 milligrams (mg) LY2409021 administered orally as a single dose on Day 1. Period 3: Placebo administered orally as a single dose on Day 1.	Period 1: Placebo administered orally as a single dose on Day 1. Period 2: 400 milligrams (mg) Moxifloxacin administered orally as a single dose on Day 1. Period 3: 300 milligrams (mg) LY2409021 administered orally as a single dose on Day 1.	Period 1: 400 milligrams (mg) Moxifloxacin administered orally as a single dose on Day 1. Period 2: Placebo administered orally as a single dose on Day 1. Period 3: 300 milligrams (mg) LY2409021 administered orally as a single dose on Day 1.	Period 1: Placebo administered orally as a single dose on Day 1. Period 2: 300 milligrams (mg) LY2409021 administered orally as a single dose on Day 1. Period 3: 400 milligrams (mg) Moxifloxacin administered orally as a single dose on Day 1.	Period 1: 300 milligrams (mg) LY2409021 administered orally as a single dose on Day 1. Period 2: 400 milligrams (mg) Moxifloxacin administered orally as a single dose on Day 1. Period 3: Placebo administered orally as a single dose on Day 1.
Period Title: Part A
Started	7	0	0	0	0	0	0
Received at Least One Dose of Study Drug	7	0	0	0	0	0	0
Completed	7	0	0	0	0	0	0
Not Completed	0	0	0	0	0	0	0
Period Title: Part B: First Intervention (Period 1)
Started	0	10	10	10	10	10	10
Received at Least One Dose of Study Drug	0	10	10	10	10	10	10
Completed	0	10	10	10	9	10	10
Not Completed	0	0	0	0	1	0	0
Reason Not Completed
Lost to Follow-up	0	0	0	0	1	0	0
Period Title: Part B: Washout (up to 15 Days)
Started	0	10	10	10	9	10	10
Completed	0	10	10	10	9	10	10
Not Completed	0	0	0	0	0	0	0
Period Title: Part B: Second Intervention (Period 2)
Started	0	10	10	10	9	10	10
Completed	0	8	10	10	9	10	9
Not Completed	0	2	0	0	0	0	1
Reason Not Completed
Withdrawal by Subject	0	1	0	0	0	0	1
Lost to Follow-up	0	1	0	0	0	0	0
Period Title: Part B: Washout (up to 15 Days)
Started	0	8	10	10	9	10	9
Completed	0	8	9	10	9	10	9
Not Completed	0	0	1	0	0	0	0
Reason Not Completed
Protocol Violation	0	0	1	0	0	0	0
Period Title: Part B: Third Interventions (Period 3)
Started	0	8	9	10	9	10	9
Completed	0	8	8	9	9	9	9
Not Completed	0	0	1	1	0	1	0
Reason Not Completed
Withdrawal by Subject	0	0	1	1	0	1	0

Baseline Characteristics

Arm/Group Title		Part A	Part B	Total
Arm/Group Description		A single dose of 300 milligrams (mg...	Participants received a single dose...	Total of all reporting groups
Arm/Group Description		A single dose of 300 milligrams (mg) LY2409021 administered orally on Day 1. Participants enrolled in Part A were not allowed to participate in Part B.	Participants received a single dose of either 300 milligrams (mg) LY2409021, 400 mg Moxifloxacin, or Placebo on Day 1 in 1 of 3 Study Periods so that after the completion of the 3 study periods, each participant received a single dose of each drug.	Total of all reporting groups
Overall Number of Baseline Participants		7	60	67
Baseline Analysis Population Description		...
Baseline Analysis Population Description		All participants who received at least 1 dose of study drug (Part A or Part B).
Age, Continuous Mean (Standard Deviation) Unit of measure: Years
	Number Analyzed	7 participants	60 participants	67 participants
		47.3 (7.7)	39.7 (12.8)	40.4 (12.5)
Sex: Female, Male Measure Type: Count of Participants Unit of measure: Participants
	Number Analyzed	7 participants	60 participants	67 participants
	Female	0	14	14
	Male	7	46	53
Ethnicity (NIH/OMB) Measure Type: Count of Participants Unit of measure: Participants
	Number Analyzed	7 participants	60 participants	67 participants
	Hispanic or Latino	3	20	23
	Not Hispanic or Latino	4	40	44
	Unknown or Not Reported	0	0	0
Race (NIH/OMB) Measure Type: Count of Participants Unit of measure: Participants
	Number Analyzed	7 participants	60 participants	67 participants
	American Indian or Alaska Native	0	2	2
	Asian	0	0	0
	Native Hawaiian or Other Pacific Islander	0	0	0
	Black or African American	3	23	26
	White	4	35	39
	More than one race	0	0	0
	Unknown or Not Reported	0	0	0
Region of Enrollment Measure Type: Count of Participants Unit of measure: Participants
United States	Number Analyzed	7 participants	60 participants	67 participants
United States		7	60	67

Outcome Measures

1.Primary Outcome


Title	Part B: Mean Change From Baseline in 12-lead Electrocardiogram (ECG) Corrected QT Intervals (LY2409021)
Description	The QT interval is a measure of the time between the start of the Q wa...
Description	The QT interval is a measure of the time between the start of the Q wave and the end of the T wave and was calculated from electrocardiogram (ECG) data using Fridericia's formula: QTc = QT/RR^0.33. Corrected QT (QTc) is the QT interval corrected for heart rate and RR, which is the interval between two R waves. Least Squares (LS) means were calculated using mixed effects model with fixed effects for treatment, time, period, sequence, and the time-by-treatment interaction, random effects for participant, the participant-by-treatment interaction, and participant-by-time interaction.
Time Frame	Baseline, 2, 4, 6, 8, 12, and 24 hours

Outcome Measure Data

Analysis Population Description

Participants who received at least 1 dose of LY2409021 or Placebo with evaluable Fridericia Correction Formula (QTcF) data.


Arm/Group Title		Part B: LY2409021	Part B: Placebo
Arm/Group Description:		300 milligrams (mg) LY2409021 admin...	Placebo: Administered orally as a s...
Arm/Group Description:		300 milligrams (mg) LY2409021 administered orally as a single dose on Day 1 of the relevant treatment period.	Placebo: Administered orally as a single dose on Day 1 of the relevant treatment period.
Overall Number of Participants Analyzed		58	56
Least Squares Mean (90% Confidence Interval) Unit of Measure: milliseconds
2 hours postdose	Number Analyzed	57 participants	54 participants
2 hours postdose		-14.72 (-16.44 to -13.00)	-15.35 (-17.10 to -13.59)
4 hours postdose	Number Analyzed	57 participants	53 participants
4 hours postdose		-5.43 (-7.15 to -3.72)	-9.12 (-10.89 to -7.35)
6 hours postdose	Number Analyzed	56 participants	54 participants
6 hours postdose		6.13 (4.40 to 7.85)	-3.01 (-4.77 to -1.26)
8 hours postdose	Number Analyzed	58 participants	56 participants
8 hours postdose		7.80 (6.09 to 9.51)	-1.29 (-3.02 to 0.45)
12 hours postdose	Number Analyzed	58 participants	55 participants
12 hours postdose		-13.45 (-15.15 to -11.74)	-13.30 (-15.05 to -11.55)
24 hours postdose	Number Analyzed	57 participants	55 participants
24 hours postdose		-1.32 (-3.04 to 0.40)	-4.95 (-6.70 to -3.20)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Part B: LY2409021, Part B: Placebo
	Comments	[Not Specified]
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]

Method of Estimation	Estimation Parameter	Least Squares Mean Difference
	Estimated Value	0.63
	Confidence Interval	(2-Sided) 90% -1.38 to 2.63
	Estimation Comments	Treatment comparison at 2 hours.

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Part B: LY2409021, Part B: Placebo
	Comments	[Not Specified]
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]

Method of Estimation	Estimation Parameter	Least Squares Means Difference
	Estimated Value	3.69
	Confidence Interval	(2-Sided) 90% 1.67 to 5.71
	Estimation Comments	Treatment comparison at 4 hours.

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Part B: LY2409021, Part B: Placebo
	Comments	[Not Specified]
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]

Method of Estimation	Estimation Parameter	Least Squares Means Difference
	Estimated Value	9.14
	Confidence Interval	(2-Sided) 90% 7.12 to 11.16
	Estimation Comments	Treatment comparison at 6 hours.

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Part B: LY2409021, Part B: Placebo
	Comments	[Not Specified]
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]

Method of Estimation	Estimation Parameter	Least Squares Means Difference
	Estimated Value	9.08
	Confidence Interval	(2-Sided) 90% 7.10 to 11.07
	Estimation Comments	Treatment comparison at 8 hours.

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	Part B: LY2409021, Part B: Placebo
	Comments	[Not Specified]
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]

Method of Estimation	Estimation Parameter	Least Squares Means Difference
	Estimated Value	-0.15
	Confidence Interval	(2-Sided) 90% -2.14 to 1.85
	Estimation Comments	Treatment comparison at 12 hours.

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	Part B: LY2409021, Part B: Placebo
	Comments	[Not Specified]
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]

Method of Estimation	Estimation Parameter	Least Squares Means Difference
	Estimated Value	3.63
	Confidence Interval	(2-Sided) 90% 1.63 to 5.63
	Estimation Comments	Treatment comparison at 24 hours.

2.Secondary Outcome


Title	Part B: Mean Change From Baseline in 12-lead Electrocardiogram (ECG) Corrected QT Intervals (Moxifloxacin)
Description	The QT interval is a measure of the time between the start of the Q wa...
Description	The QT interval is a measure of the time between the start of the Q wave and the end of the T wave and was calculated from electrocardiogram (ECG) data using Fridericia's formula: QTc = QT/RR^0.33. Corrected QT (QTc) is the QT interval corrected for heart rate and RR, which is the interval between two R waves. Least Squares (LS) means were calculated using mixed effects model with fixed effects for treatment, time, period, sequence, and the time-by-treatment interaction, random effects for participant, the participant-by-treatment interaction, and participant-by-time interaction.
Time Frame	Baseline, 2 and 4 hours

Outcome Measure Data

Analysis Population Description

Participants who received at least 1 dose of Moxifloxacin or Placebo with evaluable QTcF data.


Arm/Group Title		Part B: Moxifloxacin	Part B: Placebo
Arm/Group Description:		400 milligrams (mg) Moxifloxacin ad...	Placebo: Administered orally as a s...
Arm/Group Description:		400 milligrams (mg) Moxifloxacin administered orally as a single dose on Day 1 of the relevant treatment period.	Placebo: Administered orally as a single dose on Day 1 of the relevant treatment period.
Overall Number of Participants Analyzed		56	54
Least Squares Mean (90% Confidence Interval) Unit of Measure: milliseconds
2 hours postdose	Number Analyzed	55 participants	54 participants
2 hours postdose		-7.39 (-9.13 to -5.64)	-15.46 (-17.22 to -13.70)
4 hours postdose	Number Analyzed	56 participants	53 participants
4 hours postdose		1.45 (-0.28 to 3.18)	-9.11 (-10.88 to -7.34)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Part B: Moxifloxacin, Part B: Placebo
	Comments	[Not Specified]
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]

Method of Estimation	Estimation Parameter	Least Squares Mean Difference
	Estimated Value	8.07
	Confidence Interval	(2-Sided) 90% 5.21 to 10.94
	Estimation Comments	Treatment comparison at 2 hours.

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Part B: Moxifloxacin, Part B: Placebo
	Comments	[Not Specified]
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]

Method of Estimation	Estimation Parameter	Least Squares Mean Difference
	Estimated Value	10.56
	Confidence Interval	(2-Sided) 90% 7.69 to 13.43
	Estimation Comments	Treatment comparison at 4 hours.

Adverse Events

Time Frame	[Not Specified]
Adverse Event Reporting Description	[Not Specified]

Arm/Group Title	Part A: LY2409021		Part B: Placebo		Part B: Moxifloxacin		Part B: LY2409021
Arm/Group Description	A single dose of 300 milligrams (mg...		Administered orally as a single dos...		400 milligrams (mg) Moxifloxacin ad...		300 milligrams (mg) LY2409021 admin...
Arm/Group Description	A single dose of 300 milligrams (mg) LY2409021 administered orally on Day 1. Participants enrolled in Part A were not allowed to participate in Part B.		Administered orally as a single dose on Day 1 of the relevant treatment period.		400 milligrams (mg) Moxifloxacin administered orally as a single dose on Day 1 of the relevant treatment period.		300 milligrams (mg) LY2409021 administered orally as a single dose on Day 1 of the relevant treatment period.
All-Cause Mortality
	Part A: LY2409021		Part B: Placebo		Part B: Moxifloxacin		Part B: LY2409021
	Affected / at Risk (%)		Affected / at Risk (%)		Affected / at Risk (%)		Affected / at Risk (%)
Total	--/--		--/--		--/--		--/--
Serious Adverse Events Serious Adverse Events
	Part A: LY2409021		Part B: Placebo		Part B: Moxifloxacin		Part B: LY2409021
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/7 (0.00%)		0/57 (0.00%)		0/58 (0.00%)		0/59 (0.00%)
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	1%
	Part A: LY2409021		Part B: Placebo		Part B: Moxifloxacin		Part B: LY2409021
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/7 (14.29%)		12/57 (21.05%)		11/58 (18.97%)		9/59 (15.25%)
Eye disorders
Eyelid oedema ^† 1	0/7 (0.00%)	0	0/57 (0.00%)	0	1/58 (1.72%)	1	0/59 (0.00%)	0
Gastrointestinal disorders
Abdominal pain ^† 1	0/7 (0.00%)	0	1/57 (1.75%)	1	0/58 (0.00%)	0	1/59 (1.69%)	1
Abdominal pain lower ^† 1	0/7 (0.00%)	0	1/57 (1.75%)	1	0/58 (0.00%)	0	0/59 (0.00%)	0
Abdominal pain upper ^† 1	0/7 (0.00%)	0	0/57 (0.00%)	0	0/58 (0.00%)	0	1/59 (1.69%)	1
Diarrhoea ^† 1	0/7 (0.00%)	0	0/57 (0.00%)	0	1/58 (1.72%)	1	0/59 (0.00%)	0
Dyspepsia ^† 1	0/7 (0.00%)	0	0/57 (0.00%)	0	2/58 (3.45%)	2	0/59 (0.00%)	0
Nausea ^† 1	0/7 (0.00%)	0	0/57 (0.00%)	0	0/58 (0.00%)	0	1/59 (1.69%)	1
Toothache ^† 1	0/7 (0.00%)	0	1/57 (1.75%)	1	0/58 (0.00%)	0	0/59 (0.00%)	0
General disorders
Application site rash ^† 1	0/7 (0.00%)	0	1/57 (1.75%)	1	1/58 (1.72%)	1	0/59 (0.00%)	0
Application site reaction ^† 1	0/7 (0.00%)	0	0/57 (0.00%)	0	1/58 (1.72%)	1	1/59 (1.69%)	1
Vessel puncture site pain ^† 1	0/7 (0.00%)	0	1/57 (1.75%)	1	0/58 (0.00%)	0	0/59 (0.00%)	0
Infections and infestations
Influenza ^† 1	0/7 (0.00%)	0	0/57 (0.00%)	0	0/58 (0.00%)	0	1/59 (1.69%)	1
Upper respiratory tract infection ^† 1	0/7 (0.00%)	0	1/57 (1.75%)	1	3/58 (5.17%)	3	0/59 (0.00%)	0
Injury, poisoning and procedural complications
Excoriation ^† 1	0/7 (0.00%)	0	1/57 (1.75%)	1	0/58 (0.00%)	0	0/59 (0.00%)	0
Joint sprain ^† 1	0/7 (0.00%)	0	1/57 (1.75%)	1	0/58 (0.00%)	0	0/59 (0.00%)	0
Investigations
Cardiac murmur ^† 1	1/7 (14.29%)	1	0/57 (0.00%)	0	0/58 (0.00%)	0	0/59 (0.00%)	0
Musculoskeletal and connective tissue disorders
Arthralgia ^† 1	0/7 (0.00%)	0	0/57 (0.00%)	0	0/58 (0.00%)	0	1/59 (1.69%)	1
Back pain ^† 1	0/7 (0.00%)	0	1/57 (1.75%)	1	2/58 (3.45%)	2	1/59 (1.69%)	1
Muscle spasms ^† 1	0/7 (0.00%)	0	0/57 (0.00%)	0	1/58 (1.72%)	2	0/59 (0.00%)	0
Neck pain ^† 1	0/7 (0.00%)	0	0/57 (0.00%)	0	0/58 (0.00%)	0	1/59 (1.69%)	1
Pain in extremity ^† 1	0/7 (0.00%)	0	1/57 (1.75%)	1	0/58 (0.00%)	0	0/59 (0.00%)	0
Nervous system disorders
Dizziness ^† 1	0/7 (0.00%)	0	0/57 (0.00%)	0	1/58 (1.72%)	1	0/59 (0.00%)	0
Headache ^† 1	0/7 (0.00%)	0	3/57 (5.26%)	3	1/58 (1.72%)	1	1/59 (1.69%)	1
Tremor ^† 1	0/7 (0.00%)	0	0/57 (0.00%)	0	0/58 (0.00%)	0	1/59 (1.69%)	1
Psychiatric disorders
Abnormal dreams ^† 1	0/7 (0.00%)	0	0/57 (0.00%)	0	0/58 (0.00%)	0	2/59 (3.39%)	2
Anxiety ^† 1	0/7 (0.00%)	0	0/57 (0.00%)	0	0/58 (0.00%)	0	1/59 (1.69%)	1
Renal and urinary disorders
Pollakiuria ^† 1	0/7 (0.00%)	0	0/57 (0.00%)	0	1/58 (1.72%)	1	0/59 (0.00%)	0
Skin and subcutaneous tissue disorders
Drug eruption ^† 1	0/7 (0.00%)	0	1/57 (1.75%)	1	0/58 (0.00%)	0	0/59 (0.00%)	0
Hangnail ^† 1	0/7 (0.00%)	0	0/57 (0.00%)	0	1/58 (1.72%)	1	0/59 (0.00%)	0
Hyperhidrosis ^† 1	0/7 (0.00%)	0	0/57 (0.00%)	0	0/58 (0.00%)	0	1/59 (1.69%)	1
† Indicates events were collected by systematic assessment 1 Term from vocabulary, MedDRA 14.0

Limitations and Caveats

[Not Specified]

More Information

Certain Agreements

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

There IS 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.

Results Point of Contact

Layout table for Results Point of Contact information

Name/Title:	Chief Medical Officer
Organization:	Eli Lilly and Company
Phone:	800-545-5979

Layout table for additonal information

Responsible Party:	Eli Lilly and Company
ClinicalTrials.gov Identifier:	NCT01460368
Other Study ID Numbers:	14149 I1R-FW-GLBP ( Other Identifier: Eli Lilly and Company )
First Submitted:	October 7, 2011
First Posted:	October 26, 2011
Results First Submitted:	March 24, 2018
Results First Posted:	October 18, 2018
Last Update Posted:	January 7, 2019

To Top