Trial Outcomes & Findings for A Study of LY2484595 on the Electrical Activity of the Heart (NCT NCT01537887)
NCT ID: NCT01537887
Last Updated: 2019-03-07
Results Overview
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.
Recruitment status
COMPLETED
Study phase
PHASE1
Target enrollment
72 participants
Primary outcome timeframe
Predose of Day 1, Day 10
Results posted on
2019-03-07
Participant Flow
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.
Participant milestones
| Measure |
Sequence 1
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
|
Sequence 2
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
|
Sequence 3
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
|
Sequence 4
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
|
Sequence 5
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
|
Sequence 6
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 1
STARTED
|
12
|
12
|
12
|
12
|
12
|
12
|
|
Period 1
Received at Least 1 Dose of Study Drug
|
12
|
12
|
11
|
12
|
12
|
12
|
|
Period 1
COMPLETED
|
12
|
12
|
11
|
12
|
11
|
11
|
|
Period 1
NOT COMPLETED
|
0
|
0
|
1
|
0
|
1
|
1
|
|
Period 2
STARTED
|
12
|
12
|
11
|
12
|
11
|
11
|
|
Period 2
COMPLETED
|
12
|
11
|
11
|
12
|
11
|
11
|
|
Period 2
NOT COMPLETED
|
0
|
1
|
0
|
0
|
0
|
0
|
|
Period 3
STARTED
|
12
|
11
|
11
|
12
|
11
|
11
|
|
Period 3
COMPLETED
|
12
|
10
|
10
|
12
|
11
|
11
|
|
Period 3
NOT COMPLETED
|
0
|
1
|
1
|
0
|
0
|
0
|
Reasons for withdrawal
| Measure |
Sequence 1
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
|
Sequence 2
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
|
Sequence 3
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
|
Sequence 4
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
|
Sequence 5
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
|
Sequence 6
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 1
Physician Decision
|
0
|
0
|
0
|
0
|
1
|
1
|
|
Period 1
Did not receive treatment
|
0
|
0
|
1
|
0
|
0
|
0
|
|
Period 2
Withdrawal by Subject
|
0
|
1
|
0
|
0
|
0
|
0
|
|
Period 3
Adverse Event
|
0
|
0
|
1
|
0
|
0
|
0
|
|
Period 3
Withdrawal by Subject
|
0
|
1
|
0
|
0
|
0
|
0
|
Baseline Characteristics
A Study of LY2484595 on the Electrical Activity of the Heart
Baseline characteristics by cohort
| Measure |
All Participants
n=71 Participants
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.
|
|---|---|
|
Age, Continuous
|
43.1 years
STANDARD_DEVIATION 13.3 • n=5 Participants
|
|
Sex: Female, Male
Female
|
19 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
52 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Black or African American
|
17 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
White
|
53 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
More than one race
|
1 Participants
n=5 Participants
|
|
Region of Enrollment
United States
|
71 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: Predose of Day 1, Day 10Population: All participants who received at least one dose of study drug and had both baseline and post-baseline ECG measurements on 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.
Outcome measures
| Measure |
Placebo
n=68 Participants
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.
|
LY2484595
n=69 Participants
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.
|
|---|---|---|
|
Change From Baseline to Day 10 in QT Interval Corrected for Heart Rate (QTc) for LY2484595 Versus Placebo
4-hour postdose on Day 10
|
-2.7 milliseconds (msec)
Standard Deviation 7.5
|
-4.6 milliseconds (msec)
Standard Deviation 8.5
|
|
Change From Baseline to Day 10 in QT Interval Corrected for Heart Rate (QTc) for LY2484595 Versus Placebo
6-hour postdose on Day 10
|
-2.0 milliseconds (msec)
Standard Deviation 7.7
|
-1.1 milliseconds (msec)
Standard Deviation 8.5
|
SECONDARY outcome
Timeframe: Predose, 1, 2, 3, 4, 6, 12, 24, 72, and 168 Hours PostdosePopulation: Participants who received at least one dose of LY2484595 and had pharmacokinetic data.
Outcome measures
| Measure |
Placebo
n=69 Participants
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.
|
LY2484595
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.
|
|---|---|---|
|
Pharmacokinetics: Maximum Drug Concentration (Cmax) of LY2484595 During One Dosing Interval at Steady State
|
5270 nanograms/milliliter (ng/mL)
Geometric Coefficient of Variation 65
|
—
|
SECONDARY outcome
Timeframe: Predose, 1, 2, 3, 4, 6, 12, 24, 72, and 168 Hours PostdosePopulation: Participants who received at least one dose of LY2484595 and had pharmacokinetic data.
Outcome measures
| Measure |
Placebo
n=69 Participants
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.
|
LY2484595
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.
|
|---|---|---|
|
Pharmacokinetics: Area Under the Concentration Curve (AUC) of LY2484595 During One Dosing Interval at Steady State
|
48300 nanograms*hour/milliliter (ng*h/mL)
Geometric Coefficient of Variation 49
|
—
|
SECONDARY outcome
Timeframe: Baseline, Day 11Population: 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.
Outcome measures
| Measure |
Placebo
n=68 Participants
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.
|
LY2484595
n=69 Participants
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.
|
|---|---|---|
|
Percentage Change From Baseline to Day 11 in Fasting Lipids and Apolipoproteins
High-density lipoprotein cholesterol (HDL-C)
|
-8 percentage change
Standard Deviation 15
|
112 percentage change
Standard Deviation 37
|
|
Percentage Change From Baseline to Day 11 in Fasting Lipids and Apolipoproteins
Low-density lipoprotein cholesterol (LDL-C)
|
9 percentage change
Standard Deviation 17
|
-35 percentage change
Standard Deviation 16
|
|
Percentage Change From Baseline to Day 11 in Fasting Lipids and Apolipoproteins
Apo-A1
|
-9 percentage change
Standard Deviation 13
|
32 percentage change
Standard Deviation 18
|
|
Percentage Change From Baseline to Day 11 in Fasting Lipids and Apolipoproteins
Apo-B
|
8 percentage change
Standard Deviation 16
|
-24 percentage change
Standard Deviation 18
|
Adverse Events
LY2484595
Serious events: 0 serious events
Other events: 33 other events
Deaths: 0 deaths
Placebo
Serious events: 1 serious events
Other events: 24 other events
Deaths: 0 deaths
Moxifloxacin
Serious events: 0 serious events
Other events: 11 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
LY2484595
n=70 participants at risk
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.
|
Placebo
n=69 participants at risk
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.
|
Moxifloxacin
n=69 participants at risk
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.
|
|---|---|---|---|
|
Vascular disorders
Deep vein thrombosis
|
0.00%
0/70
|
1.4%
1/69 • Number of events 1
|
0.00%
0/69
|
Other adverse events
| Measure |
LY2484595
n=70 participants at risk
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.
|
Placebo
n=69 participants at risk
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.
|
Moxifloxacin
n=69 participants at risk
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.
|
|---|---|---|---|
|
Ear and labyrinth disorders
Ear discomfort
|
1.4%
1/70 • Number of events 1
|
0.00%
0/69
|
0.00%
0/69
|
|
Ear and labyrinth disorders
Ear pruritus
|
1.4%
1/70 • Number of events 1
|
0.00%
0/69
|
0.00%
0/69
|
|
Eye disorders
Blepharospasm
|
1.4%
1/70 • Number of events 1
|
0.00%
0/69
|
0.00%
0/69
|
|
Eye disorders
Eyelid oedema
|
0.00%
0/70
|
0.00%
0/69
|
1.4%
1/69 • Number of events 1
|
|
Eye disorders
Ocular hyperaemia
|
0.00%
0/70
|
1.4%
1/69 • Number of events 2
|
1.4%
1/69 • Number of events 1
|
|
Gastrointestinal disorders
Abdominal discomfort
|
0.00%
0/70
|
1.4%
1/69 • Number of events 2
|
0.00%
0/69
|
|
Gastrointestinal disorders
Abdominal distension
|
1.4%
1/70 • Number of events 1
|
0.00%
0/69
|
0.00%
0/69
|
|
Gastrointestinal disorders
Abdominal pain
|
4.3%
3/70 • Number of events 3
|
0.00%
0/69
|
0.00%
0/69
|
|
Gastrointestinal disorders
Abdominal pain upper
|
1.4%
1/70 • Number of events 1
|
1.4%
1/69 • Number of events 1
|
0.00%
0/69
|
|
Gastrointestinal disorders
Cheilitis
|
1.4%
1/70 • Number of events 1
|
0.00%
0/69
|
0.00%
0/69
|
|
Gastrointestinal disorders
Constipation
|
1.4%
1/70 • Number of events 1
|
4.3%
3/69 • Number of events 3
|
1.4%
1/69 • Number of events 1
|
|
Gastrointestinal disorders
Diarrhoea
|
20.0%
14/70 • Number of events 16
|
5.8%
4/69 • Number of events 4
|
0.00%
0/69
|
|
Gastrointestinal disorders
Dyspepsia
|
1.4%
1/70 • Number of events 1
|
0.00%
0/69
|
0.00%
0/69
|
|
Gastrointestinal disorders
Flatulence
|
2.9%
2/70 • Number of events 2
|
0.00%
0/69
|
0.00%
0/69
|
|
Gastrointestinal disorders
Gastrooesophageal reflux disease
|
1.4%
1/70 • Number of events 1
|
1.4%
1/69 • Number of events 1
|
0.00%
0/69
|
|
Gastrointestinal disorders
Nausea
|
8.6%
6/70 • Number of events 7
|
1.4%
1/69 • Number of events 1
|
2.9%
2/69 • Number of events 2
|
|
Gastrointestinal disorders
Vomiting
|
1.4%
1/70 • Number of events 1
|
0.00%
0/69
|
0.00%
0/69
|
|
General disorders
Application site dermatitis
|
2.9%
2/70 • Number of events 2
|
1.4%
1/69 • Number of events 1
|
0.00%
0/69
|
|
General disorders
Application site irritation
|
1.4%
1/70 • Number of events 1
|
0.00%
0/69
|
0.00%
0/69
|
|
General disorders
Application site pruritus
|
1.4%
1/70 • Number of events 1
|
0.00%
0/69
|
0.00%
0/69
|
|
General disorders
Application site rash
|
0.00%
0/70
|
1.4%
1/69 • Number of events 1
|
0.00%
0/69
|
|
General disorders
Chills
|
1.4%
1/70 • Number of events 1
|
0.00%
0/69
|
0.00%
0/69
|
|
General disorders
Fatigue
|
1.4%
1/70 • Number of events 1
|
1.4%
1/69 • Number of events 1
|
0.00%
0/69
|
|
General disorders
Feeling hot
|
1.4%
1/70 • Number of events 1
|
0.00%
0/69
|
0.00%
0/69
|
|
General disorders
Non-cardiac chest pain
|
0.00%
0/70
|
1.4%
1/69 • Number of events 1
|
0.00%
0/69
|
|
Infections and infestations
Folliculitis
|
1.4%
1/70 • Number of events 1
|
0.00%
0/69
|
0.00%
0/69
|
|
Infections and infestations
Oral herpes
|
0.00%
0/70
|
1.4%
1/69 • Number of events 1
|
0.00%
0/69
|
|
Infections and infestations
Pharyngitis
|
1.4%
1/70 • Number of events 1
|
0.00%
0/69
|
0.00%
0/69
|
|
Infections and infestations
Streptococcal infection
|
0.00%
0/70
|
0.00%
0/69
|
1.4%
1/69 • Number of events 1
|
|
Injury, poisoning and procedural complications
Arthropod bite
|
1.4%
1/70 • Number of events 1
|
1.4%
1/69 • Number of events 1
|
0.00%
0/69
|
|
Injury, poisoning and procedural complications
Excoriation
|
0.00%
0/70
|
1.4%
1/69 • Number of events 1
|
0.00%
0/69
|
|
Injury, poisoning and procedural complications
Eye injury
|
0.00%
0/70
|
0.00%
0/69
|
1.4%
1/69 • Number of events 1
|
|
Injury, poisoning and procedural complications
Hand fracture
|
1.4%
1/70 • Number of events 2
|
0.00%
0/69
|
0.00%
0/69
|
|
Injury, poisoning and procedural complications
Laceration
|
1.4%
1/70 • Number of events 1
|
1.4%
1/69 • Number of events 1
|
1.4%
1/69 • Number of events 1
|
|
Investigations
Hepatic enzyme increased
|
1.4%
1/70 • Number of events 1
|
0.00%
0/69
|
0.00%
0/69
|
|
Metabolism and nutrition disorders
Decreased appetite
|
1.4%
1/70 • Number of events 1
|
1.4%
1/69 • Number of events 1
|
0.00%
0/69
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
2.9%
2/70 • Number of events 2
|
1.4%
1/69 • Number of events 1
|
0.00%
0/69
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
1.4%
1/70 • Number of events 1
|
1.4%
1/69 • Number of events 1
|
0.00%
0/69
|
|
Musculoskeletal and connective tissue disorders
Musculoskeletal discomfort
|
1.4%
1/70 • Number of events 1
|
0.00%
0/69
|
0.00%
0/69
|
|
Musculoskeletal and connective tissue disorders
Myalgia
|
1.4%
1/70 • Number of events 1
|
2.9%
2/69 • Number of events 2
|
0.00%
0/69
|
|
Musculoskeletal and connective tissue disorders
Neck pain
|
2.9%
2/70 • Number of events 2
|
0.00%
0/69
|
0.00%
0/69
|
|
Musculoskeletal and connective tissue disorders
Pain in extremity
|
1.4%
1/70 • Number of events 1
|
0.00%
0/69
|
1.4%
1/69 • Number of events 1
|
|
Nervous system disorders
Dysaesthesia
|
1.4%
1/70 • Number of events 1
|
0.00%
0/69
|
0.00%
0/69
|
|
Nervous system disorders
Headache
|
7.1%
5/70 • Number of events 7
|
5.8%
4/69 • Number of events 4
|
2.9%
2/69 • Number of events 2
|
|
Nervous system disorders
Paraesthesia
|
2.9%
2/70 • Number of events 2
|
0.00%
0/69
|
0.00%
0/69
|
|
Psychiatric disorders
Insomnia
|
1.4%
1/70 • Number of events 1
|
1.4%
1/69 • Number of events 1
|
1.4%
1/69 • Number of events 1
|
|
Renal and urinary disorders
Bladder dilatation
|
0.00%
0/70
|
1.4%
1/69 • Number of events 1
|
0.00%
0/69
|
|
Renal and urinary disorders
Dysuria
|
1.4%
1/70 • Number of events 1
|
1.4%
1/69 • Number of events 1
|
0.00%
0/69
|
|
Renal and urinary disorders
Urine odour abnormal
|
0.00%
0/70
|
1.4%
1/69 • Number of events 1
|
0.00%
0/69
|
|
Respiratory, thoracic and mediastinal disorders
Epistaxis
|
1.4%
1/70 • Number of events 1
|
0.00%
0/69
|
1.4%
1/69 • Number of events 1
|
|
Respiratory, thoracic and mediastinal disorders
Nasal congestion
|
4.3%
3/70 • Number of events 3
|
1.4%
1/69 • Number of events 1
|
0.00%
0/69
|
|
Respiratory, thoracic and mediastinal disorders
Rhinorrhoea
|
0.00%
0/70
|
1.4%
1/69 • Number of events 1
|
0.00%
0/69
|
|
Respiratory, thoracic and mediastinal disorders
Sinus congestion
|
1.4%
1/70 • Number of events 1
|
0.00%
0/69
|
0.00%
0/69
|
|
Respiratory, thoracic and mediastinal disorders
Sneezing
|
1.4%
1/70 • Number of events 1
|
1.4%
1/69 • Number of events 1
|
0.00%
0/69
|
|
Skin and subcutaneous tissue disorders
Acne
|
1.4%
1/70 • Number of events 1
|
0.00%
0/69
|
0.00%
0/69
|
|
Skin and subcutaneous tissue disorders
Dermatitis
|
0.00%
0/70
|
2.9%
2/69 • Number of events 2
|
0.00%
0/69
|
|
Skin and subcutaneous tissue disorders
Ecchymosis
|
0.00%
0/70
|
1.4%
1/69 • Number of events 1
|
0.00%
0/69
|
|
Skin and subcutaneous tissue disorders
Hyperhidrosis
|
1.4%
1/70 • Number of events 1
|
0.00%
0/69
|
0.00%
0/69
|
|
Skin and subcutaneous tissue disorders
Papule
|
1.4%
1/70 • Number of events 1
|
0.00%
0/69
|
0.00%
0/69
|
|
Skin and subcutaneous tissue disorders
Pruritus
|
1.4%
1/70 • Number of events 1
|
1.4%
1/69 • Number of events 1
|
1.4%
1/69 • Number of events 1
|
|
Skin and subcutaneous tissue disorders
Rash
|
1.4%
1/70 • Number of events 1
|
0.00%
0/69
|
0.00%
0/69
|
|
Skin and subcutaneous tissue disorders
Rash papular
|
0.00%
0/70
|
1.4%
1/69 • Number of events 1
|
0.00%
0/69
|
|
Vascular disorders
Flushing
|
2.9%
2/70 • Number of events 2
|
0.00%
0/69
|
0.00%
0/69
|
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