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

• 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: Eli Lilly and Company
• Information provided by (Responsible Party): Eli Lilly and Company

Tracking Information

• First Submitted Date: October 7, 2011
• First Posted Date: October 26, 2011
• Results First Submitted Date: March 24, 2018
• Results First Posted Date: October 18, 2018
• Last Update Posted Date: January 7, 2019
• Study Start Date: October 2011
• Actual Primary Completion Date: March 2012 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: March 24, 2018)

Part B: Mean Change From Baseline in 12-lead Electrocardiogram (ECG) Corrected QT Intervals (LY2409021) [ Time Frame: Baseline, 2, 4, 6, 8, 12, and 24 hours ]

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.

• Original Primary Outcome Measures (submitted: October 24, 2011): Part B: Mean Change in 12-lead electrocardiogram (ECG) corrected QT intervals of LY2409021 compared to placebo [ Time Frame: baseline, up to 24 hours post dose ]

Current Secondary Outcome Measures (submitted: March 24, 2018)

Part B: Mean Change From Baseline in 12-lead Electrocardiogram (ECG) Corrected QT Intervals (Moxifloxacin) [ Time Frame: Baseline, 2 and 4 hours ]

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.

• Original Secondary Outcome Measures: Not Provided
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: A Study on the Effects of LY2409021 on the Electrical Impulses of the Heart
• Official Title: A Placebo- and Positive-Controlled Study of the Electrophysiological Effects of a Supratherapeutic Dose of LY2409021 in Healthy Subjects

Brief Summary

Part A: The purpose of Part A of the study is to look at the electrocardiogram (ECG) effects due to blood sugar changes after a meal compared to when LY2409021 is also given with a meal.

Part B: The purpose of Part B is to evaluate the effect of LY2409021, when given at a dose level much higher than what would normally be given, on the electrical activity of the heart as measured by ECG in relation to placebo and moxifloxacin.

• Detailed Description: This is a 2 part study. Part A is a single-dose study to compare the effects of a meal on glucose, insulin and QT in healthy participants with and without LY2409021. Part B of this study is a randomized, 3-period, crossover design, in which participants and investigators are blinded to placebo and LY2409021, and will assess the electrophysiological effects of a single supratherapeutic dose of LY2409021 compared to a positive control (moxifloxacin) and placebo.
• Study Type: Interventional
• Study Phase: Phase 1
• Study Design: Allocation: Randomized; Intervention Model: Crossover Assignment; Masking: Double (Participant, Investigator); Primary Purpose: Basic Science
• Condition: Diabetes Mellitus, Type 2

Intervention

• Drug: LY2409021
  Administered orally
• Drug: Placebo
  Administered orally
• Drug: Moxifloxacin
  Administered orally

Study Arms

• Experimental: Part A: LY2409021
  Participants will receive 2 standard meals; one alone without LY2409021, and one along with a single dose of 300 milligrams (mg) LY2409021 administered orally. Participants enrolled in Part A will not be allowed to participate in Part B.
  Intervention: Drug: LY2409021
• Experimental: Part B: LY2409021
  300 milligrams (mg) LY2409021 administered orally as a single dose on Day 1 of the relevant treatment period. The treatment and washout period was a total of 15 days in length.
  Intervention: Drug: LY2409021
• Placebo Comparator: Part B: Placebo
  Administered orally as a single dose on Day 1 of the relevant treatment period. The treatment and washout period was a total of 15 days in length.
  Intervention: Drug: Placebo
• Active Comparator: Part B: Moxifloxacin
  400 milligrams (mg) Moxifloxacin administered orally as a single dose on Day 1 of the relevant treatment period. The treatment and washout period was a total of 15 days in length.
  Intervention: Drug: Moxifloxacin

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: March 24, 2018): 67
• Original Estimated Enrollment (submitted: October 24, 2011): 68
• Actual Study Completion Date: March 2012
• Actual Primary Completion Date: March 2012 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• are overtly healthy males or females, as determined by medical history and physical examination
• female participants: women not of child-bearing potential due to surgical sterilization (hysterectomy alone or at least 6 weeks postsurgical bilateral oophorectomy with or without hysterectomy or tubal ligation) confirmed by medical history, or menopause Women with an intact uterus are deemed postmenopausal if they are >=45 years old, have not taken hormones or oral contraceptives within the last year, had cessation of menses for at least 1 year, or have had 6 to 12 months of amenorrhea with follicle-stimulating hormone levels consistent with postmenopausal state
• have a body mass index (BMI) of 18.5 to 32 kilograms per meter squared (kg/m^2), inclusive, at screening
• have a fasting blood glucose between 54 to 110 milligrams per deciliter (mg/dL) (3.0 to 6.1 millimoles per liter [mmol/L])
• have a clinically normal screening electrocardiogram (ECG) with a measurable QT interval as judged by central reader, which allows accurate measurements of QT interval
• have clinical laboratory test results within normal reference range for the population or investigator site, or results with acceptable deviations that are judged to be not clinically significant by the investigator
• have venous access sufficient to allow for blood sampling
• are reliable and willing to make themselves available for the duration of the study and are willing to follow study procedures
• have normal blood pressure and pulse rate (supine) at screening, or with minor deviations judged to be acceptable by the investigator
• have given written informed consent approved by Lilly and the ethical review board (ERB) governing the site
• serum magnesium and potassium equal to or above the lower limit of normal

Exclusion Criteria:

• are currently enrolled in or have completed or discontinued within the last 30 days (from screening) from a clinical trial involving an investigational product; or are concurrently enrolled in any other type of medical research judged not to be scientifically or medically compatible with this study
• have known allergies to LY2409021, related compounds or any components of the formulations, or to moxifloxacin
• are persons who have previously received the investigational product in this study, have completed or withdrawn from this study or any other study investigating LY2409021
• personal or family history of long QT syndrome
• family history of sudden unexplained death or cardiac death in a family member under 60 years of age
• personal history of unexplained syncope within the last year
• have a history or presence of cardiovascular, respiratory, hepatic, renal, gastrointestinal, endocrine, hematological, or neurological disorders capable of significantly altering the absorption, metabolism, or elimination of drugs; of constituting a risk when taking the study medication; or of interfering with the interpretation of data
• regularly use known drugs of abuse and/or show positive findings on urinary drug screening
• show evidence of human immunodeficiency virus (HIV) infection and/or positive human HIV antibodies
• show evidence of hepatitis C and/or positive hepatitis C antibody
• show evidence of hepatitis B and/or positive hepatitis B surface antigen
• are women with a positive pregnancy test or women who are lactating
• intend to use over-the-counter (including mineral supplements and herbal medicine) or prescription medication within 7 days prior to dosing
• have donated blood of more than 500 milliliters (mL) within the last month
• have an average weekly alcohol intake that exceeds 21 units per week (males) and 14 units per week (females) (1 unit = 12 ounces [oz] or 360 mL of beer; 5 oz or 150 mL of wine; 1.5 oz or 45 mL of distilled spirits), or are unwilling to comply with alcohol restrictions during the study (that is, refrain from alcohol consumption from 24 hours prior to dosing until the completion of each treatment period and to consume no more than 2 units of alcohol per day between treatment periods)
• are participants who smoke more than 10 cigarettes per day and/or are unable to abide by the study restrictions for smoking/tobacco use (that is, refrain from smoking for approximately 2 hours prior to each ECG timepoint or for a total of approximately 12 hours)
• are participants who are unable to abide by the study restrictions for caffeine/xanthine use (that is, refrain from consuming caffeine/xanthine containing drinks and foods [such as coffee, tea, cola, and chocolate] on days on which ECGs are performed, and maintain consistent consumption habits on all other days of the study)

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years to 65 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT01460368
• Other Study ID Numbers: 14149; I1R-FW-GLBP ( Other Identifier: Eli Lilly and Company )
• Has Data Monitoring Committee: No
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Responsible Party: Eli Lilly and Company
• Study Sponsor: Eli Lilly and Company
• Collaborators: Not Provided

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

• PRS Account: Eli Lilly and Company
• Verification Date: December 2018