A Study of LY2484595 on the Electrical Activity of the Heart

• Sponsor: Eli Lilly and Company (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01537887
• Collaborator: (none)
• Enrollment: 72
• Locations: 2
• Arms: 3
• Duration (Months): 4
• Patients Per Site: 36
• Patients Per Site Per Month: 9.1

Study Details

Study Description

Brief Summary

The purpose of this study is to evaluate the effect on the electrical activity of the heart as measured by an electrocardiogram (ECG) after dosing with 10 days of LY2484595 compared to 10 days of placebo in relation to a single dose of moxifloxacin. Information about any side effects that occur will also be collected.

Condition or Disease	Intervention/Treatment	Phase
Healthy Volunteers	Drug: LY2484595; Drug: Placebo; Drug: Moxifloxacin	Phase 1

Study Design

• Study Type: Interventional
• Actual Enrollment: 72 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Basic Science
• Official Title: A Placebo- and Positive-Controlled Study of the Effect of LY2484595 on QT Interval in Healthy Subjects
• Study Start Date: Feb 1, 2012
• Actual Primary Completion Date: Jun 1, 2012
• Actual Study Completion Date: Jun 1, 2012

Arms and Interventions

Arm	Intervention/Treatment
Placebo Comparator: Placebo Administered orally once daily for 10 days during 1 of the 3 crossover periods, separated by at least a 14-day washout period.	Drug: Placebo; Administered orally once daily for 10 days.
Experimental: 1200 milligrams (mg) LY2484595 Administered orally once daily for 10 days during 1 of the 3 crossover periods, separated by at least a 14-day washout period.	Drug: LY2484595; Administered orally once daily for 10 days.
Active Comparator: 400 mg Moxifloxacin Positive control, unblinded treatment administered orally once during 1 of 3 crossover periods, separated by at least a 14-day washout period.	Drug: Moxifloxacin; Single dose administered orally.

Outcome Measures

Primary Outcome Measures

1. Change From Baseline to Day 10 in QT Interval Corrected for Heart Rate (QTc) for LY2484595 Versus Placebo [Predose of Day 1, Day 10]

   Data were collected using a 12-lead electrocardiogram (ECG). The QT interval is the time between the start of the Q wave and the end of the T wave in the cardiac electrical cycle and corrected for heart rate. Population-corrected QT interval (QTcP) formula: QTcP = QT / RR^ß, where ß is the population correction factor.

Secondary Outcome Measures

1. Pharmacokinetics: Maximum Drug Concentration (Cmax) of LY2484595 During One Dosing Interval at Steady State [Predose, 1, 2, 3, 4, 6, 12, 24, 72, and 168 Hours Postdose]

2. Pharmacokinetics: Area Under the Concentration Curve (AUC) of LY2484595 During One Dosing Interval at Steady State [Predose, 1, 2, 3, 4, 6, 12, 24, 72, and 168 Hours Postdose]

3. Percentage Change From Baseline to Day 11 in Fasting Lipids and Apolipoproteins [Baseline, Day 11]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 65 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Inclusion Criteria:

• Healthy males and females

• Body mass index (BMI) of 18.5 to 29 kilograms per square meter (kg/m²)

• Reliable and willing to be available for the duration of the study and are willing to follow study procedures

• Provided written informed consent

Exclusion Criteria:

• Known allergies to LY2484595 or moxifloxacin

• Personal or family history of long QT syndrome, heart failure, or low blood potassium (hypokalemia) a family history of sudden death, or unexplained syncope within the last year

• Positive findings on urinary drug screening

• Cigarette smokers

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.	Daytona Beach	Florida	United States	32117
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.	Evansville	Indiana	United States	47710

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: NCT01537887
• Other Study ID Numbers: 11947; I1V-MC-EIAK
• First Posted: Feb 23, 2012
• Last Update Posted: Mar 7, 2019
• Last Verified: Nov 1, 2018

• Additional relevant MeSH terms: Moxifloxacin; Evacetrapib

Study Results

Participant Flow

Pre-assignment Detail	Participants were randomized to 1 of 6 treatment sequences in a crossover design with 3 treatments; 1200 mg LY2484595, then placebo, then moxifloxacin. There was a washout period of ≥14 days between each dose. Participants were dosed 3 times during the entire study.

Arm/Group Title	Sequence 1	Sequence 2	Sequence 3	Sequence 4	Sequence 5	Sequence 6
Arm/Group Description	Placebo or 1200 milligrams (mg) LY2484595 administered orally twice daily for 10 days, or 400 mg moxifloxacin single oral dose on Day 1 during 1 of the 3 crossover periods. There was at least 14 days washout between consecutive dosing periods. Sequence 1 (ABC): LY248495, then placebo, then moxifloxacin	Placebo or 1200 mg LY2484595 administered orally twice daily for 10 days, or 400 mg moxifloxacin single oral dose on Day 1 during 1 of the 3 crossover periods. There was at least 14 days washout between consecutive dosing periods. Sequence 2 (BCA): placebo, then moxifloxacin, then LY2484595	Placebo or 1200 mg LY2484595 administered orally twice daily for 10 days, or 400 mg moxifloxacin single oral dose on Day 1 during 1 of the 3 crossover periods. There was at least 14 days washout between consecutive dosing periods. Sequence 3 (CAB): moxifloxacin, then LY2484595, placebo	Placebo or 1200 mg LY2484595 administered orally twice daily for 10 days, or 400 mg moxifloxacin single oral dose on Day 1 during 1 of the 3 crossover periods. There was at least 14 days washout between consecutive dosing periods. Sequence 4 (CBA): moxifloxacin, then placebo, then LY2484595	Placebo or 1200 mg LY2484595 administered orally twice daily for 10 days, or 400 mg moxifloxacin single oral dose on Day 1 during 1 of the 3 crossover periods. There was at least 14 days washout between consecutive dosing periods. Sequence 5 (ACB): LY2484595, then moxifloxacin, then placebo	Placebo or 1200 mg LY2484595 administered orally twice daily for 10 days, or 400 mg moxifloxacin single oral dose on Day 1 during 1 of the 3 crossover periods. There was at least 14 days washout between consecutive dosing periods. Sequence 6 (BAC): placebo, then LY2484595, then moxifloxacin
Period Title: Period 1
STARTED	12	12	12	12	12	12
Received at Least 1 Dose of Study Drug	12	12	11	12	12	12
COMPLETED	12	12	11	12	11	11
NOT COMPLETED	0	0	1	0	1	1
Period Title: Period 1
STARTED	12	12	11	12	11	11
COMPLETED	12	11	11	12	11	11
NOT COMPLETED	0	1	0	0	0	0
Period Title: Period 1
STARTED	12	11	11	12	11	11
COMPLETED	12	10	10	12	11	11
NOT COMPLETED	0	1	1	0	0	0

Baseline Characteristics

Arm/Group Title	All Participants
Arm/Group Description	Placebo or 1200 mg LY2484595 administered orally once daily for 10 days, or 400 mg moxifloxacin single oral dose on Day 1 during 1 of the 3 crossover periods. There was at least 14 days washout between consecutive dosing periods.
Overall Participants	71
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	43.1 (13.3)
Sex: Female, Male (Count of Participants)
Female	19 26.8%
Male	52 73.2%
Race/Ethnicity, Customized (Count of Participants)
Black or African American	17 23.9%
White	53 74.6%
More than one race	1 1.4%
Region of Enrollment (Count of Participants)
United States	71 100%

Outcome Measures

1. Primary Outcome

Title	Change From Baseline to Day 10 in QT Interval Corrected for Heart Rate (QTc) for LY2484595 Versus Placebo
Description	Data were collected using a 12-lead electrocardiogram (ECG). The QT interval is the time between the start of the Q wave and the end of the T wave in the cardiac electrical cycle and corrected for heart rate. Population-corrected QT interval (QTcP) formula: QTcP = QT / RR^ß, where ß is the population correction factor.
Time Frame	Predose of Day 1, Day 10

Outcome Measure Data

Analysis Population Description

All participants who received at least one dose of study drug and had both baseline and post-baseline ECG measurements on Day 10.

Arm/Group Title	Placebo	LY2484595
Arm/Group Description	Administered orally once daily for 10 days during 1 of the 3 crossover periods. There was at least 14 days washout between consecutive dosing periods.	1200 milligrams (mg) LY2484595 administered orally once daily for 10 days during 1 of the 3 crossover periods. There was at least 14 days washout between consecutive dosing periods.
Measure Participants	68	69
4-hour postdose on Day 10	-2.7 (7.5)	-4.6 (8.5)
6-hour postdose on Day 10	-2.0 (7.7)	-1.1 (8.5)

2. Secondary Outcome

Title	Pharmacokinetics: Maximum Drug Concentration (Cmax) of LY2484595 During One Dosing Interval at Steady State
Time Frame	Predose, 1, 2, 3, 4, 6, 12, 24, 72, and 168 Hours Postdose

Outcome Measure Data

Analysis Population Description

Participants who received at least one dose of LY2484595 and had pharmacokinetic data.

Arm/Group Title	LY2484595
Arm/Group Description	1200 milligrams (mg) LY2484595 administered orally once daily for 10 days during 1 of the 3 crossover periods. There was at least 14 days washout between consecutive dosing periods.
Measure Participants	69
Geometric Mean (Geometric Coefficient of Variation) [nanograms/milliliter (ng/mL)]	5270 (65)

3. Secondary Outcome

Title	Pharmacokinetics: Area Under the Concentration Curve (AUC) of LY2484595 During One Dosing Interval at Steady State
Time Frame	Predose, 1, 2, 3, 4, 6, 12, 24, 72, and 168 Hours Postdose

Outcome Measure Data

Analysis Population Description

Participants who received at least one dose of LY2484595 and had pharmacokinetic data.

Arm/Group Title	LY2484595
Arm/Group Description	1200 milligrams (mg) LY2484595 administered orally once daily for 10 days during 1 of the 3 crossover periods. There was at least 14 days washout between consecutive dosing periods.
Measure Participants	69
Geometric Mean (Geometric Coefficient of Variation) [nanograms*hour/milliliter (ng*h/mL)]	48300 (49)

4. Secondary Outcome

Title	Percentage Change From Baseline to Day 11 in Fasting Lipids and Apolipoproteins
Time Frame	Baseline, Day 11

Outcome Measure Data

Analysis Population Description

All participants who received at least one dose of study drug and had both baseline and post-baseline lipid or apolipoprotein (Apo) measurements on Day 11.

Arm/Group Title	Placebo	LY2484595
Arm/Group Description	Administered orally once daily for 10 days during 1 of the 3 crossover periods. There was at least 14 days washout between consecutive dosing periods.	1200 milligrams (mg) LY2484595 administered orally once daily for 10 days during 1 of the 3 crossover periods. There was at least 14 days washout between consecutive dosing periods.
Measure Participants	68	69
High-density lipoprotein cholesterol (HDL-C)	-8 (15)	112 (37)
Low-density lipoprotein cholesterol (LDL-C)	9 (17)	-35 (16)
Apo-A1	-9 (13)	32 (18)
Apo-B	8 (16)	-24 (18)

Adverse Events

Arm/Group Title	LY2484595		Placebo		Moxifloxacin
Arm/Group Description	1200 milligrams (mg) LY2484595 administered orally once daily for 10 days during 1 of the 3 crossover periods. There was at least 14 days washout between consecutive dosing periods.		Administered orally once daily for 10 days during 1 of the 3 crossover periods. There was at least 14 days washout between consecutive dosing periods.		400 mg Moxifloxacin: Positive control, unblinded treatment administered orally once during 1 of 3 crossover periods. There was at least 14 days washout between consecutive dosing periods.
All Cause Mortality
	LY2484595		Placebo		Moxifloxacin
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	LY2484595		Placebo		Moxifloxacin
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/70 (0%)		1/69 (1.4%)		0/69 (0%)
Vascular disorders
Deep vein thrombosis	0/70 (0%)	0	1/69 (1.4%)	1	0/69 (0%)	0
Other (Not Including Serious) Adverse Events
	LY2484595		Placebo		Moxifloxacin
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	33/70 (47.1%)		24/69 (34.8%)		11/69 (15.9%)
Ear and labyrinth disorders
Ear discomfort	1/70 (1.4%)	1	0/69 (0%)	0	0/69 (0%)	0
Ear pruritus	1/70 (1.4%)	1	0/69 (0%)	0	0/69 (0%)	0
Eye disorders
Blepharospasm	1/70 (1.4%)	1	0/69 (0%)	0	0/69 (0%)	0
Eyelid oedema	0/70 (0%)	0	0/69 (0%)	0	1/69 (1.4%)	1
Ocular hyperaemia	0/70 (0%)	0	1/69 (1.4%)	2	1/69 (1.4%)	1
Gastrointestinal disorders
Abdominal discomfort	0/70 (0%)	0	1/69 (1.4%)	2	0/69 (0%)	0
Abdominal distension	1/70 (1.4%)	1	0/69 (0%)	0	0/69 (0%)	0
Abdominal pain	3/70 (4.3%)	3	0/69 (0%)	0	0/69 (0%)	0
Abdominal pain upper	1/70 (1.4%)	1	1/69 (1.4%)	1	0/69 (0%)	0
Cheilitis	1/70 (1.4%)	1	0/69 (0%)	0	0/69 (0%)	0
Constipation	1/70 (1.4%)	1	3/69 (4.3%)	3	1/69 (1.4%)	1
Diarrhoea	14/70 (20%)	16	4/69 (5.8%)	4	0/69 (0%)	0
Dyspepsia	1/70 (1.4%)	1	0/69 (0%)	0	0/69 (0%)	0
Flatulence	2/70 (2.9%)	2	0/69 (0%)	0	0/69 (0%)	0
Gastrooesophageal reflux disease	1/70 (1.4%)	1	1/69 (1.4%)	1	0/69 (0%)	0
Nausea	6/70 (8.6%)	7	1/69 (1.4%)	1	2/69 (2.9%)	2
Vomiting	1/70 (1.4%)	1	0/69 (0%)	0	0/69 (0%)	0
General disorders
Application site dermatitis	2/70 (2.9%)	2	1/69 (1.4%)	1	0/69 (0%)	0
Application site irritation	1/70 (1.4%)	1	0/69 (0%)	0	0/69 (0%)	0
Application site pruritus	1/70 (1.4%)	1	0/69 (0%)	0	0/69 (0%)	0
Application site rash	0/70 (0%)	0	1/69 (1.4%)	1	0/69 (0%)	0
Chills	1/70 (1.4%)	1	0/69 (0%)	0	0/69 (0%)	0
Fatigue	1/70 (1.4%)	1	1/69 (1.4%)	1	0/69 (0%)	0
Feeling hot	1/70 (1.4%)	1	0/69 (0%)	0	0/69 (0%)	0
Non-cardiac chest pain	0/70 (0%)	0	1/69 (1.4%)	1	0/69 (0%)	0
Infections and infestations
Folliculitis	1/70 (1.4%)	1	0/69 (0%)	0	0/69 (0%)	0
Oral herpes	0/70 (0%)	0	1/69 (1.4%)	1	0/69 (0%)	0
Pharyngitis	1/70 (1.4%)	1	0/69 (0%)	0	0/69 (0%)	0
Streptococcal infection	0/70 (0%)	0	0/69 (0%)	0	1/69 (1.4%)	1
Injury, poisoning and procedural complications
Arthropod bite	1/70 (1.4%)	1	1/69 (1.4%)	1	0/69 (0%)	0
Excoriation	0/70 (0%)	0	1/69 (1.4%)	1	0/69 (0%)	0
Eye injury	0/70 (0%)	0	0/69 (0%)	0	1/69 (1.4%)	1
Hand fracture	1/70 (1.4%)	2	0/69 (0%)	0	0/69 (0%)	0
Laceration	1/70 (1.4%)	1	1/69 (1.4%)	1	1/69 (1.4%)	1
Investigations
Hepatic enzyme increased	1/70 (1.4%)	1	0/69 (0%)	0	0/69 (0%)	0
Metabolism and nutrition disorders
Decreased appetite	1/70 (1.4%)	1	1/69 (1.4%)	1	0/69 (0%)	0
Musculoskeletal and connective tissue disorders
Arthralgia	2/70 (2.9%)	2	1/69 (1.4%)	1	0/69 (0%)	0
Back pain	1/70 (1.4%)	1	1/69 (1.4%)	1	0/69 (0%)	0
Musculoskeletal discomfort	1/70 (1.4%)	1	0/69 (0%)	0	0/69 (0%)	0
Myalgia	1/70 (1.4%)	1	2/69 (2.9%)	2	0/69 (0%)	0
Neck pain	2/70 (2.9%)	2	0/69 (0%)	0	0/69 (0%)	0
Pain in extremity	1/70 (1.4%)	1	0/69 (0%)	0	1/69 (1.4%)	1
Nervous system disorders
Dysaesthesia	1/70 (1.4%)	1	0/69 (0%)	0	0/69 (0%)	0
Headache	5/70 (7.1%)	7	4/69 (5.8%)	4	2/69 (2.9%)	2
Paraesthesia	2/70 (2.9%)	2	0/69 (0%)	0	0/69 (0%)	0
Psychiatric disorders
Insomnia	1/70 (1.4%)	1	1/69 (1.4%)	1	1/69 (1.4%)	1
Renal and urinary disorders
Bladder dilatation	0/70 (0%)	0	1/69 (1.4%)	1	0/69 (0%)	0
Dysuria	1/70 (1.4%)	1	1/69 (1.4%)	1	0/69 (0%)	0
Urine odour abnormal	0/70 (0%)	0	1/69 (1.4%)	1	0/69 (0%)	0
Respiratory, thoracic and mediastinal disorders
Epistaxis	1/70 (1.4%)	1	0/69 (0%)	0	1/69 (1.4%)	1
Nasal congestion	3/70 (4.3%)	3	1/69 (1.4%)	1	0/69 (0%)	0
Rhinorrhoea	0/70 (0%)	0	1/69 (1.4%)	1	0/69 (0%)	0
Sinus congestion	1/70 (1.4%)	1	0/69 (0%)	0	0/69 (0%)	0
Sneezing	1/70 (1.4%)	1	1/69 (1.4%)	1	0/69 (0%)	0
Skin and subcutaneous tissue disorders
Acne	1/70 (1.4%)	1	0/69 (0%)	0	0/69 (0%)	0
Dermatitis	0/70 (0%)	0	2/69 (2.9%)	2	0/69 (0%)	0
Ecchymosis	0/70 (0%)	0	1/69 (1.4%)	1	0/69 (0%)	0
Hyperhidrosis	1/70 (1.4%)	1	0/69 (0%)	0	0/69 (0%)	0
Papule	1/70 (1.4%)	1	0/69 (0%)	0	0/69 (0%)	0
Pruritus	1/70 (1.4%)	1	1/69 (1.4%)	1	1/69 (1.4%)	1
Rash	1/70 (1.4%)	1	0/69 (0%)	0	0/69 (0%)	0
Rash papular	0/70 (0%)	0	1/69 (1.4%)	1	0/69 (0%)	0
Vascular disorders
Flushing	2/70 (2.9%)	2	0/69 (0%)	0	0/69 (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.