Trial Outcomes & Findings for A Study on the Effects of LY2409021 on the Electrical Impulses of the Heart (NCT NCT01460368)
NCT ID: NCT01460368
Last Updated: 2019-01-07
Results Overview
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.
Recruitment status
COMPLETED
Study phase
PHASE1
Target enrollment
67 participants
Primary outcome timeframe
Baseline, 2, 4, 6, 8, 12, and 24 hours
Results posted on
2019-01-07
Participant Flow
Participant milestones
| Measure |
Part A: LY2409021
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.
|
Part B: LY2409021, Placebo, Moxifloxacin
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.
|
Part B: Moxifloxacin, LY2409021, Placebo
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.
|
Part B: Placebo, Moxifloxacin, LY2409021
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.
|
Part B: Moxifloxacin, Placebo, LY2409021
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.
|
Part B: Placebo, LY2409021, Moxifloxacin
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.
|
Part B: LY2409021, Moxifloxacin, Placebo
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.
|
|---|---|---|---|---|---|---|---|
|
Part A
STARTED
|
7
|
0
|
0
|
0
|
0
|
0
|
0
|
|
Part A
Received at Least One Dose of Study Drug
|
7
|
0
|
0
|
0
|
0
|
0
|
0
|
|
Part A
COMPLETED
|
7
|
0
|
0
|
0
|
0
|
0
|
0
|
|
Part A
NOT COMPLETED
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
|
Part B: First Intervention (Period 1)
STARTED
|
0
|
10
|
10
|
10
|
10
|
10
|
10
|
|
Part B: First Intervention (Period 1)
Received at Least One Dose of Study Drug
|
0
|
10
|
10
|
10
|
10
|
10
|
10
|
|
Part B: First Intervention (Period 1)
COMPLETED
|
0
|
10
|
10
|
10
|
9
|
10
|
10
|
|
Part B: First Intervention (Period 1)
NOT COMPLETED
|
0
|
0
|
0
|
0
|
1
|
0
|
0
|
|
Part B: Washout (up to 15 Days)
STARTED
|
0
|
8
|
10
|
10
|
9
|
10
|
9
|
|
Part B: Washout (up to 15 Days)
COMPLETED
|
0
|
8
|
9
|
10
|
9
|
10
|
9
|
|
Part B: Washout (up to 15 Days)
NOT COMPLETED
|
0
|
0
|
1
|
0
|
0
|
0
|
0
|
|
Part B: Second Intervention (Period 2)
STARTED
|
0
|
10
|
10
|
10
|
9
|
10
|
10
|
|
Part B: Second Intervention (Period 2)
COMPLETED
|
0
|
8
|
10
|
10
|
9
|
10
|
9
|
|
Part B: Second Intervention (Period 2)
NOT COMPLETED
|
0
|
2
|
0
|
0
|
0
|
0
|
1
|
|
Part B: Third Interventions (Period 3)
STARTED
|
0
|
8
|
9
|
10
|
9
|
10
|
9
|
|
Part B: Third Interventions (Period 3)
COMPLETED
|
0
|
8
|
8
|
9
|
9
|
9
|
9
|
|
Part B: Third Interventions (Period 3)
NOT COMPLETED
|
0
|
0
|
1
|
1
|
0
|
1
|
0
|
Reasons for withdrawal
| Measure |
Part A: LY2409021
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.
|
Part B: LY2409021, Placebo, Moxifloxacin
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.
|
Part B: Moxifloxacin, LY2409021, Placebo
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.
|
Part B: Placebo, Moxifloxacin, LY2409021
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.
|
Part B: Moxifloxacin, Placebo, LY2409021
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.
|
Part B: Placebo, LY2409021, Moxifloxacin
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.
|
Part B: LY2409021, Moxifloxacin, Placebo
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.
|
|---|---|---|---|---|---|---|---|
|
Part B: First Intervention (Period 1)
Lost to Follow-up
|
0
|
0
|
0
|
0
|
1
|
0
|
0
|
|
Part B: Second Intervention (Period 2)
Withdrawal by Subject
|
0
|
1
|
0
|
0
|
0
|
0
|
1
|
|
Part B: Second Intervention (Period 2)
Lost to Follow-up
|
0
|
1
|
0
|
0
|
0
|
0
|
0
|
|
Part B: Washout (up to 15 Days)
Protocol Violation
|
0
|
0
|
1
|
0
|
0
|
0
|
0
|
|
Part B: Third Interventions (Period 3)
Withdrawal by Subject
|
0
|
0
|
1
|
1
|
0
|
1
|
0
|
Baseline Characteristics
A Study on the Effects of LY2409021 on the Electrical Impulses of the Heart
Baseline characteristics by cohort
| Measure |
Part A
n=7 Participants
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.
|
Part B
n=60 Participants
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
n=67 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
47.3 years
STANDARD_DEVIATION 7.7 • n=99 Participants
|
39.7 years
STANDARD_DEVIATION 12.8 • n=107 Participants
|
40.4 years
STANDARD_DEVIATION 12.5 • n=206 Participants
|
|
Sex: Female, Male
Female
|
0 Participants
n=99 Participants
|
14 Participants
n=107 Participants
|
14 Participants
n=206 Participants
|
|
Sex: Female, Male
Male
|
7 Participants
n=99 Participants
|
46 Participants
n=107 Participants
|
53 Participants
n=206 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
3 Participants
n=99 Participants
|
20 Participants
n=107 Participants
|
23 Participants
n=206 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
4 Participants
n=99 Participants
|
40 Participants
n=107 Participants
|
44 Participants
n=206 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
0 Participants
n=206 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=99 Participants
|
2 Participants
n=107 Participants
|
2 Participants
n=206 Participants
|
|
Race (NIH/OMB)
Asian
|
0 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
0 Participants
n=206 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
0 Participants
n=206 Participants
|
|
Race (NIH/OMB)
Black or African American
|
3 Participants
n=99 Participants
|
23 Participants
n=107 Participants
|
26 Participants
n=206 Participants
|
|
Race (NIH/OMB)
White
|
4 Participants
n=99 Participants
|
35 Participants
n=107 Participants
|
39 Participants
n=206 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
0 Participants
n=206 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
0 Participants
n=206 Participants
|
|
Region of Enrollment
United States
|
7 Participants
n=99 Participants
|
60 Participants
n=107 Participants
|
67 Participants
n=206 Participants
|
PRIMARY outcome
Timeframe: Baseline, 2, 4, 6, 8, 12, and 24 hoursPopulation: Participants who received at least 1 dose of LY2409021 or Placebo with evaluable Fridericia Correction Formula (QTcF) data.
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.
Outcome measures
| Measure |
Part B: LY2409021
n=58 Participants
300 milligrams (mg) LY2409021 administered orally as a single dose on Day 1 of the relevant treatment period.
|
Part B: Placebo
n=56 Participants
Placebo: Administered orally as a single dose on Day 1 of the relevant treatment period.
|
|---|---|---|
|
Part B: Mean Change From Baseline in 12-lead Electrocardiogram (ECG) Corrected QT Intervals (LY2409021)
2 hours postdose
|
-14.72 milliseconds
Interval -16.44 to -13.0
|
-15.35 milliseconds
Interval -17.1 to -13.59
|
|
Part B: Mean Change From Baseline in 12-lead Electrocardiogram (ECG) Corrected QT Intervals (LY2409021)
4 hours postdose
|
-5.43 milliseconds
Interval -7.15 to -3.72
|
-9.12 milliseconds
Interval -10.89 to -7.35
|
|
Part B: Mean Change From Baseline in 12-lead Electrocardiogram (ECG) Corrected QT Intervals (LY2409021)
6 hours postdose
|
6.13 milliseconds
Interval 4.4 to 7.85
|
-3.01 milliseconds
Interval -4.77 to -1.26
|
|
Part B: Mean Change From Baseline in 12-lead Electrocardiogram (ECG) Corrected QT Intervals (LY2409021)
8 hours postdose
|
7.80 milliseconds
Interval 6.09 to 9.51
|
-1.29 milliseconds
Interval -3.02 to 0.45
|
|
Part B: Mean Change From Baseline in 12-lead Electrocardiogram (ECG) Corrected QT Intervals (LY2409021)
12 hours postdose
|
-13.45 milliseconds
Interval -15.15 to -11.74
|
-13.30 milliseconds
Interval -15.05 to -11.55
|
|
Part B: Mean Change From Baseline in 12-lead Electrocardiogram (ECG) Corrected QT Intervals (LY2409021)
24 hours postdose
|
-1.32 milliseconds
Interval -3.04 to 0.4
|
-4.95 milliseconds
Interval -6.7 to -3.2
|
SECONDARY outcome
Timeframe: Baseline, 2 and 4 hoursPopulation: Participants who received at least 1 dose of Moxifloxacin or Placebo with evaluable QTcF data.
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.
Outcome measures
| Measure |
Part B: LY2409021
n=56 Participants
300 milligrams (mg) LY2409021 administered orally as a single dose on Day 1 of the relevant treatment period.
|
Part B: Placebo
n=54 Participants
Placebo: Administered orally as a single dose on Day 1 of the relevant treatment period.
|
|---|---|---|
|
Part B: Mean Change From Baseline in 12-lead Electrocardiogram (ECG) Corrected QT Intervals (Moxifloxacin)
2 hours postdose
|
-7.39 milliseconds
Interval -9.13 to -5.64
|
-15.46 milliseconds
Interval -17.22 to -13.7
|
|
Part B: Mean Change From Baseline in 12-lead Electrocardiogram (ECG) Corrected QT Intervals (Moxifloxacin)
4 hours postdose
|
1.45 milliseconds
Interval -0.28 to 3.18
|
-9.11 milliseconds
Interval -10.88 to -7.34
|
Adverse Events
Part A: LY2409021
Serious events: 0 serious events
Other events: 1 other events
Deaths: 0 deaths
Part B: Placebo
Serious events: 0 serious events
Other events: 12 other events
Deaths: 0 deaths
Part B: Moxifloxacin
Serious events: 0 serious events
Other events: 11 other events
Deaths: 0 deaths
Part B: LY2409021
Serious events: 0 serious events
Other events: 9 other events
Deaths: 0 deaths
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
Part A: LY2409021
n=7 participants at risk
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.
|
Part B: Placebo
n=57 participants at risk
Administered orally as a single dose on Day 1 of the relevant treatment period.
|
Part B: Moxifloxacin
n=58 participants at risk
400 milligrams (mg) Moxifloxacin administered orally as a single dose on Day 1 of the relevant treatment period.
|
Part B: LY2409021
n=59 participants at risk
300 milligrams (mg) LY2409021 administered orally as a single dose on Day 1 of the relevant treatment period.
|
|---|---|---|---|---|
|
Eye disorders
Eyelid oedema
|
0.00%
0/7
|
0.00%
0/57
|
1.7%
1/58 • Number of events 1
|
0.00%
0/59
|
|
Gastrointestinal disorders
Abdominal pain
|
0.00%
0/7
|
1.8%
1/57 • Number of events 1
|
0.00%
0/58
|
1.7%
1/59 • Number of events 1
|
|
Gastrointestinal disorders
Abdominal pain lower
|
0.00%
0/7
|
1.8%
1/57 • Number of events 1
|
0.00%
0/58
|
0.00%
0/59
|
|
Gastrointestinal disorders
Abdominal pain upper
|
0.00%
0/7
|
0.00%
0/57
|
0.00%
0/58
|
1.7%
1/59 • Number of events 1
|
|
Gastrointestinal disorders
Diarrhoea
|
0.00%
0/7
|
0.00%
0/57
|
1.7%
1/58 • Number of events 1
|
0.00%
0/59
|
|
Gastrointestinal disorders
Dyspepsia
|
0.00%
0/7
|
0.00%
0/57
|
3.4%
2/58 • Number of events 2
|
0.00%
0/59
|
|
Gastrointestinal disorders
Nausea
|
0.00%
0/7
|
0.00%
0/57
|
0.00%
0/58
|
1.7%
1/59 • Number of events 1
|
|
Gastrointestinal disorders
Toothache
|
0.00%
0/7
|
1.8%
1/57 • Number of events 1
|
0.00%
0/58
|
0.00%
0/59
|
|
General disorders
Application site rash
|
0.00%
0/7
|
1.8%
1/57 • Number of events 1
|
1.7%
1/58 • Number of events 1
|
0.00%
0/59
|
|
General disorders
Application site reaction
|
0.00%
0/7
|
0.00%
0/57
|
1.7%
1/58 • Number of events 1
|
1.7%
1/59 • Number of events 1
|
|
General disorders
Vessel puncture site pain
|
0.00%
0/7
|
1.8%
1/57 • Number of events 1
|
0.00%
0/58
|
0.00%
0/59
|
|
Infections and infestations
Influenza
|
0.00%
0/7
|
0.00%
0/57
|
0.00%
0/58
|
1.7%
1/59 • Number of events 1
|
|
Infections and infestations
Upper respiratory tract infection
|
0.00%
0/7
|
1.8%
1/57 • Number of events 1
|
5.2%
3/58 • Number of events 3
|
0.00%
0/59
|
|
Injury, poisoning and procedural complications
Excoriation
|
0.00%
0/7
|
1.8%
1/57 • Number of events 1
|
0.00%
0/58
|
0.00%
0/59
|
|
Injury, poisoning and procedural complications
Joint sprain
|
0.00%
0/7
|
1.8%
1/57 • Number of events 1
|
0.00%
0/58
|
0.00%
0/59
|
|
Investigations
Cardiac murmur
|
14.3%
1/7 • Number of events 1
|
0.00%
0/57
|
0.00%
0/58
|
0.00%
0/59
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
0.00%
0/7
|
0.00%
0/57
|
0.00%
0/58
|
1.7%
1/59 • Number of events 1
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
0.00%
0/7
|
1.8%
1/57 • Number of events 1
|
3.4%
2/58 • Number of events 2
|
1.7%
1/59 • Number of events 1
|
|
Musculoskeletal and connective tissue disorders
Muscle spasms
|
0.00%
0/7
|
0.00%
0/57
|
1.7%
1/58 • Number of events 2
|
0.00%
0/59
|
|
Musculoskeletal and connective tissue disorders
Neck pain
|
0.00%
0/7
|
0.00%
0/57
|
0.00%
0/58
|
1.7%
1/59 • Number of events 1
|
|
Musculoskeletal and connective tissue disorders
Pain in extremity
|
0.00%
0/7
|
1.8%
1/57 • Number of events 1
|
0.00%
0/58
|
0.00%
0/59
|
|
Nervous system disorders
Dizziness
|
0.00%
0/7
|
0.00%
0/57
|
1.7%
1/58 • Number of events 1
|
0.00%
0/59
|
|
Nervous system disorders
Headache
|
0.00%
0/7
|
5.3%
3/57 • Number of events 3
|
1.7%
1/58 • Number of events 1
|
1.7%
1/59 • Number of events 1
|
|
Nervous system disorders
Tremor
|
0.00%
0/7
|
0.00%
0/57
|
0.00%
0/58
|
1.7%
1/59 • Number of events 1
|
|
Psychiatric disorders
Abnormal dreams
|
0.00%
0/7
|
0.00%
0/57
|
0.00%
0/58
|
3.4%
2/59 • Number of events 2
|
|
Psychiatric disorders
Anxiety
|
0.00%
0/7
|
0.00%
0/57
|
0.00%
0/58
|
1.7%
1/59 • Number of events 1
|
|
Renal and urinary disorders
Pollakiuria
|
0.00%
0/7
|
0.00%
0/57
|
1.7%
1/58 • Number of events 1
|
0.00%
0/59
|
|
Skin and subcutaneous tissue disorders
Drug eruption
|
0.00%
0/7
|
1.8%
1/57 • Number of events 1
|
0.00%
0/58
|
0.00%
0/59
|
|
Skin and subcutaneous tissue disorders
Hangnail
|
0.00%
0/7
|
0.00%
0/57
|
1.7%
1/58 • Number of events 1
|
0.00%
0/59
|
|
Skin and subcutaneous tissue disorders
Hyperhidrosis
|
0.00%
0/7
|
0.00%
0/57
|
0.00%
0/58
|
1.7%
1/59 • Number of events 1
|
Additional Information
Chief Medical Officer
Eli Lilly and Company
Phone: 800-545-5979
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place
Restriction type: GT60