Trial Outcomes & Findings for A Study of LY2405319 in Participants With Type 2 Diabetes (NCT NCT01869959)
NCT ID: NCT01869959
Last Updated: 2017-03-20
Results Overview
The number of participants with 1 or more SAEs considered by the investigator to be related to study drug administration is reported. SAEs were classified using the Medical Dictionary for Regulatory Activities (MedDRA) 11.0. A summary of serious and other non-serious adverse events regardless of causality is located in the Reported Adverse Events module.
COMPLETED
PHASE1
47 participants
Baseline through Day 56
2017-03-20
Participant Flow
Participant milestones
| Measure |
3 mg LY2405319
3 milligrams (mg) LY2405319 injected SC once daily for 28 days.
|
10 mg LY2405319
10 mg LY2405319 injected SC once daily for 28 days.
|
20 mg LY2405319
20 mg LY2405319 injected SC once daily for 28 days.
|
Placebo
Placebo-matching LY2405319 injected subcutaneously (SC) once daily for 28 days.
|
All Randomized Participants
All participants randomized in the study.
|
|---|---|---|---|---|---|
|
Randomization Period
STARTED
|
0
|
0
|
0
|
0
|
47
|
|
Randomization Period
COMPLETED
|
0
|
0
|
0
|
0
|
46
|
|
Randomization Period
NOT COMPLETED
|
0
|
0
|
0
|
0
|
1
|
|
Treatment Period
STARTED
|
11
|
10
|
15
|
10
|
0
|
|
Treatment Period
Received at Least 1 Dose of Study Drug
|
11
|
10
|
15
|
10
|
0
|
|
Treatment Period
COMPLETED
|
10
|
8
|
12
|
8
|
0
|
|
Treatment Period
NOT COMPLETED
|
1
|
2
|
3
|
2
|
0
|
Reasons for withdrawal
| Measure |
3 mg LY2405319
3 milligrams (mg) LY2405319 injected SC once daily for 28 days.
|
10 mg LY2405319
10 mg LY2405319 injected SC once daily for 28 days.
|
20 mg LY2405319
20 mg LY2405319 injected SC once daily for 28 days.
|
Placebo
Placebo-matching LY2405319 injected subcutaneously (SC) once daily for 28 days.
|
All Randomized Participants
All participants randomized in the study.
|
|---|---|---|---|---|---|
|
Randomization Period
Physician Decision
|
0
|
0
|
0
|
0
|
1
|
|
Treatment Period
Adverse Event
|
1
|
0
|
3
|
1
|
0
|
|
Treatment Period
Sponsor decision
|
0
|
1
|
0
|
1
|
0
|
|
Treatment Period
Withdrawal by Subject
|
0
|
1
|
0
|
0
|
0
|
Baseline Characteristics
A Study of LY2405319 in Participants With Type 2 Diabetes
Baseline characteristics by cohort
| Measure |
3 mg LY2405319
n=11 Participants
3 mg LY2405319 injected SC once daily for 28 days.
|
10 mg LY2405319
n=10 Participants
10 mg LY2405319 injected SC once daily for 28 days.
|
20 mg LY2405319
n=15 Participants
20 mg LY2405319 injected SC once daily for 28 days.
|
Placebo
n=10 Participants
Placebo-matching LY2405319 injected subcutaneously (SC) once daily for 28 days.
|
Total
n=46 Participants
Total of all reporting groups
|
|---|---|---|---|---|---|
|
Age, Continuous
|
56.5 Years
STANDARD_DEVIATION 7.3 • n=5 Participants
|
59.6 Years
STANDARD_DEVIATION 9.2 • n=7 Participants
|
56.9 Years
STANDARD_DEVIATION 10.2 • n=5 Participants
|
58.6 Years
STANDARD_DEVIATION 6.3 • n=4 Participants
|
57.7 Years
STANDARD_DEVIATION 8.4 • n=21 Participants
|
|
Sex: Female, Male
Female
|
4 Participants
n=5 Participants
|
3 Participants
n=7 Participants
|
7 Participants
n=5 Participants
|
6 Participants
n=4 Participants
|
20 Participants
n=21 Participants
|
|
Sex: Female, Male
Male
|
7 Participants
n=5 Participants
|
7 Participants
n=7 Participants
|
8 Participants
n=5 Participants
|
4 Participants
n=4 Participants
|
26 Participants
n=21 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
11 Participants
n=5 Participants
|
10 Participants
n=7 Participants
|
15 Participants
n=5 Participants
|
10 Participants
n=4 Participants
|
46 Participants
n=21 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
|
Race (NIH/OMB)
Asian
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
1 Participants
n=21 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
|
Race (NIH/OMB)
Black or African American
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
1 Participants
n=21 Participants
|
|
Race (NIH/OMB)
White
|
11 Participants
n=5 Participants
|
10 Participants
n=7 Participants
|
13 Participants
n=5 Participants
|
10 Participants
n=4 Participants
|
44 Participants
n=21 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
|
Region of Enrollment
United States
|
11 participants
n=5 Participants
|
10 participants
n=7 Participants
|
15 participants
n=5 Participants
|
10 participants
n=4 Participants
|
46 participants
n=21 Participants
|
PRIMARY outcome
Timeframe: Baseline through Day 56Population: All participants who received at least 1 dose of study drug.
The number of participants with 1 or more SAEs considered by the investigator to be related to study drug administration is reported. SAEs were classified using the Medical Dictionary for Regulatory Activities (MedDRA) 11.0. A summary of serious and other non-serious adverse events regardless of causality is located in the Reported Adverse Events module.
Outcome measures
| Measure |
20 mg LY2405319
n=15 Participants
Participants received 20 mg LY2405319 injected SC once daily for 28 days.
|
Placebo
n=10 Participants
Participants received placebo-matching LY2405319 injected SC once daily for 28 days.
|
3 mg LY2405319
n=11 Participants
Participants received 3 mg LY2405319 injected SC once daily for 28 days.
|
10 mg LY2405319
n=10 Participants
Participants received 10 mg LY2405319 injected SC once daily for 28 days.
|
|---|---|---|---|---|
|
Number of Participants With One or More Serious Adverse Event(s) (SAEs) Considered by the Investigator to be Related to Study Drug Administration
|
1 number of participants
|
0 number of participants
|
0 number of participants
|
0 number of participants
|
SECONDARY outcome
Timeframe: Baseline, Day 28Population: Participants who received at least 1 dose of study drug with evaluable blood glucose data.
Change from baseline to Day 28 in fasting blood glucose is presented. The predose fasting blood glucose measurement on Day 1 served as the baseline value. LS means were calculated using a linear mixed effects model with treatment, day, and treatment times day as fixed effects; baseline as covariate; and participant as a random effect.
Outcome measures
| Measure |
20 mg LY2405319
n=13 Participants
Participants received 20 mg LY2405319 injected SC once daily for 28 days.
|
Placebo
n=8 Participants
Participants received placebo-matching LY2405319 injected SC once daily for 28 days.
|
3 mg LY2405319
n=10 Participants
Participants received 3 mg LY2405319 injected SC once daily for 28 days.
|
10 mg LY2405319
n=8 Participants
Participants received 10 mg LY2405319 injected SC once daily for 28 days.
|
|---|---|---|---|---|
|
Change From Baseline to Day 28 in Fasting Glucose
|
-10.5 milligrams per deciliter (mg/dL)
Interval -24.3 to 3.4
|
3.2 milligrams per deciliter (mg/dL)
Interval -14.1 to 20.4
|
-3.5 milligrams per deciliter (mg/dL)
Interval -19.2 to 12.2
|
-6.7 milligrams per deciliter (mg/dL)
Interval -24.4 to 11.0
|
SECONDARY outcome
Timeframe: Baseline (Day -5, -4, or -3) and Week 4 (Days 24, 25, or 26)Population: All participants who received at least 1 dose of study drug with evaluable 7-Point SMBG data.
The daily mean of the 7-point SMBG values is presented. Seven-point glucose profiles were measured by participants at baseline and at Week 4. The 7-point SMBG mean on Days -5, -4, or -3 served as the baseline value; the 7-point SMBG mean on Days 24, 25, or 26 served as the Week 4 value. Blood glucose was measured before and 2 hours after each meal and at bedtime.
Outcome measures
| Measure |
20 mg LY2405319
n=15 Participants
Participants received 20 mg LY2405319 injected SC once daily for 28 days.
|
Placebo
n=10 Participants
Participants received placebo-matching LY2405319 injected SC once daily for 28 days.
|
3 mg LY2405319
n=11 Participants
Participants received 3 mg LY2405319 injected SC once daily for 28 days.
|
10 mg LY2405319
n=10 Participants
Participants received 10 mg LY2405319 injected SC once daily for 28 days.
|
|---|---|---|---|---|
|
7 Point Self-monitored Blood Glucose (SMBG)
Week 4 (Days 24, 25, or 26)
|
188.52 mg/dL
Standard Error 7.14
|
177.41 mg/dL
Standard Error 7.24
|
171.03 mg/dL
Standard Error 6.10
|
167.95 mg/dL
Standard Error 8.09
|
|
7 Point Self-monitored Blood Glucose (SMBG)
Baseline (Days -6, -5, or -4)
|
183.97 mg/dL
Standard Error 4.19
|
172.46 mg/dL
Standard Error 5.33
|
178.01 mg/dL
Standard Error 5.95
|
171.13 mg/dL
Standard Error 5.02
|
SECONDARY outcome
Timeframe: Predose and 2 hours postdose (Baseline, Week 4)Population: All participants who received at least 1 dose of study drug with evaluable glucose AUC data.
Change from baseline to Week 4 in glucose AUC during an oral glucose tolerance test (OGTT) is presented. Blood samples were obtained prior to the glucose bolus to 2 hours after administration of the glucose bolus. The AUC measurement on Day -1 served as the baseline value. LS means were calculated using an analysis of covariance model with treatment as fixed effect and baseline as covariate.
Outcome measures
| Measure |
20 mg LY2405319
n=11 Participants
Participants received 20 mg LY2405319 injected SC once daily for 28 days.
|
Placebo
n=8 Participants
Participants received placebo-matching LY2405319 injected SC once daily for 28 days.
|
3 mg LY2405319
n=10 Participants
Participants received 3 mg LY2405319 injected SC once daily for 28 days.
|
10 mg LY2405319
n=8 Participants
Participants received 10 mg LY2405319 injected SC once daily for 28 days.
|
|---|---|---|---|---|
|
Change From Baseline to Week 4 in Glucose Area Under the Curve (AUC)
|
-3.22 milligrams*hr per deciliter (mg*hr/dL)
Interval -51.94 to 45.49
|
-28.13 milligrams*hr per deciliter (mg*hr/dL)
Interval -83.13 to 26.87
|
12.89 milligrams*hr per deciliter (mg*hr/dL)
Interval -36.21 to 61.98
|
-8.46 milligrams*hr per deciliter (mg*hr/dL)
Interval -66.69 to 49.76
|
SECONDARY outcome
Timeframe: Predose and 2 hours postdose (Baseline, Week 4)Population: All participants who received at least 1 dose of study drug with evaluable insulin (AUC) data.
Change from baseline to Week 4 in insulin AUC during an OGTT is presented. Blood samples were obtained prior to the glucose bolus to 2 hours after administration of the glucose bolus. The AUC measurement on Day -1 served as the baseline value. LS means were calculated using an analysis of covariance model with treatment as fixed effect and baseline as covariate.
Outcome measures
| Measure |
20 mg LY2405319
n=12 Participants
Participants received 20 mg LY2405319 injected SC once daily for 28 days.
|
Placebo
n=8 Participants
Participants received placebo-matching LY2405319 injected SC once daily for 28 days.
|
3 mg LY2405319
n=10 Participants
Participants received 3 mg LY2405319 injected SC once daily for 28 days.
|
10 mg LY2405319
n=7 Participants
Participants received 10 mg LY2405319 injected SC once daily for 28 days.
|
|---|---|---|---|---|
|
Change From Baseline to Week 4 in Insulin Area Under the Curve (AUC)
|
-15.66 micro International units*hour/mL
Interval -25.11 to -6.21
|
-17.98 micro International units*hour/mL
Interval -29.54 to -6.42
|
-10.07 micro International units*hour/mL
Interval -20.4 to 0.26
|
-10.37 micro International units*hour/mL
Interval -23.11 to 2.36
|
SECONDARY outcome
Timeframe: Predose and 2 hours postdose (Baseline, Week 4)Population: All participants who received at least 1 dose of study drug with evaluable C-peptide AUC data.
Change from baseline to Week 4 in C-peptide AUC during an OGTT is presented. Blood samples were obtained prior to the glucose bolus to 2 hours after administration of the glucose bolus. The AUC measurement on Day -1 served as the baseline value. LS means were calculated using an analysis of covariance model with treatment as a fixed effect and baseline as covariate.
Outcome measures
| Measure |
20 mg LY2405319
n=12 Participants
Participants received 20 mg LY2405319 injected SC once daily for 28 days.
|
Placebo
n=8 Participants
Participants received placebo-matching LY2405319 injected SC once daily for 28 days.
|
3 mg LY2405319
n=10 Participants
Participants received 3 mg LY2405319 injected SC once daily for 28 days.
|
10 mg LY2405319
n=8 Participants
Participants received 10 mg LY2405319 injected SC once daily for 28 days.
|
|---|---|---|---|---|
|
Change From Baseline to Week 4 in C-peptide Area Under the Curve (AUC)
|
-1.39 nanograms*hours/milliliter (ng*hr/mL)
Interval -2.27 to -0.51
|
-1.59 nanograms*hours/milliliter (ng*hr/mL)
Interval -2.66 to -0.51
|
-0.61 nanograms*hours/milliliter (ng*hr/mL)
Interval -1.58 to 0.36
|
0.07 nanograms*hours/milliliter (ng*hr/mL)
Interval -1.03 to 1.17
|
SECONDARY outcome
Timeframe: Baseline, Day 28Population: All participants who received at least 1 dose of study drug with evaluable fasting lipid (ie, cholesterol, LDL-C, HDL-C, and triglyceride) data.
Change from baseline to Day 28 in fasting lipids, including cholesterol, low density lipoprotein cholesterol (LDL-C), high density lipoprotein cholesterol (HDL-C), and triglycerides is presented. The predose measurement for each variable on Day 1 served as the baseline value. LS means were calculated using a linear mixed effects model with treatment, day, and treatment times day as fixed effects; baseline as covariate; and participant as a random effect.
Outcome measures
| Measure |
20 mg LY2405319
n=13 Participants
Participants received 20 mg LY2405319 injected SC once daily for 28 days.
|
Placebo
n=8 Participants
Participants received placebo-matching LY2405319 injected SC once daily for 28 days.
|
3 mg LY2405319
n=10 Participants
Participants received 3 mg LY2405319 injected SC once daily for 28 days.
|
10 mg LY2405319
n=8 Participants
Participants received 10 mg LY2405319 injected SC once daily for 28 days.
|
|---|---|---|---|---|
|
Change From Baseline to Day 28 in Fasting Lipid Profile
Cholesterol (n=10, n=8, n=13, n=8)
|
-31.4 milligrams per deciliter (mg/dL)
Interval -40.7 to -22.0
|
-1.3 milligrams per deciliter (mg/dL)
Interval -13.0 to 10.4
|
3.9 milligrams per deciliter (mg/dL)
Interval -6.8 to 14.6
|
-32.5 milligrams per deciliter (mg/dL)
Interval -44.5 to -20.6
|
|
Change From Baseline to Day 28 in Fasting Lipid Profile
LDL-C (n=10, n=8, n=13, n=7)
|
-24.2 milligrams per deciliter (mg/dL)
Interval -33.3 to -15.1
|
-0.8 milligrams per deciliter (mg/dL)
Interval -13.1 to 11.5
|
-0.1 milligrams per deciliter (mg/dL)
Interval -10.5 to 10.3
|
-26.8 milligrams per deciliter (mg/dL)
Interval -38.6 to -14.9
|
|
Change From Baseline to Day 28 in Fasting Lipid Profile
HDL-C (n=10, n=8, n=13, n=8)
|
9.1 milligrams per deciliter (mg/dL)
Interval 6.0 to 12.1
|
-0.8 milligrams per deciliter (mg/dL)
Interval -4.7 to 3.1
|
10.6 milligrams per deciliter (mg/dL)
Interval 7.1 to 14.0
|
10.2 milligrams per deciliter (mg/dL)
Interval 6.3 to 14.1
|
|
Change From Baseline to Day 28 in Fasting Lipid Profile
Triglycerides (n=10, n=8, n=13, n=8)
|
-84.4 milligrams per deciliter (mg/dL)
Interval -105.0 to -63.8
|
6.8 milligrams per deciliter (mg/dL)
Interval -21.2 to 34.9
|
-38.5 milligrams per deciliter (mg/dL)
Interval -62.9 to -14.1
|
-81.0 milligrams per deciliter (mg/dL)
Interval -107.3 to -54.8
|
SECONDARY outcome
Timeframe: Baseline, Day 28Population: All participants who received at least 1 dose of study drug with evaluable body weight data.
Change from baseline to Day 28 in body weight is presented. The predose body weight measurement on Day 1 served as the baseline value. LS means were calculated using a linear mixed effects model with treatment, day, time, and treatment times time, treatment times day, and treatment times day times time were fixed effects; baseline as covariate; and participant as a random effect.
Outcome measures
| Measure |
20 mg LY2405319
n=13 Participants
Participants received 20 mg LY2405319 injected SC once daily for 28 days.
|
Placebo
n=8 Participants
Participants received placebo-matching LY2405319 injected SC once daily for 28 days.
|
3 mg LY2405319
n=10 Participants
Participants received 3 mg LY2405319 injected SC once daily for 28 days.
|
10 mg LY2405319
n=8 Participants
Participants received 10 mg LY2405319 injected SC once daily for 28 days.
|
|---|---|---|---|---|
|
Change From Baseline to Day 28 in Body Weight
|
-1.5 kilograms (kg)
Interval -2.3 to -0.7
|
-0.2 kilograms (kg)
Interval -1.3 to 0.8
|
-0.7 kilograms (kg)
Interval -1.6 to 0.3
|
-1.8 kilograms (kg)
Interval -2.9 to -0.6
|
SECONDARY outcome
Timeframe: Baseline, Day 28Population: All participants who received at least 1 dose of study drug with evaluable adiponectin data.
Change from baseline to Day 28 in adiponectin is presented. The predose adiponectin measurement on Day 1 served as the baseline value. LS means were calculated using a linear mixed effects model with treatment, day, treatment times day as fixed effects, baseline as covariate, and participant as random effect.
Outcome measures
| Measure |
20 mg LY2405319
n=12 Participants
Participants received 20 mg LY2405319 injected SC once daily for 28 days.
|
Placebo
n=8 Participants
Participants received placebo-matching LY2405319 injected SC once daily for 28 days.
|
3 mg LY2405319
n=10 Participants
Participants received 3 mg LY2405319 injected SC once daily for 28 days.
|
10 mg LY2405319
n=8 Participants
Participants received 10 mg LY2405319 injected SC once daily for 28 days.
|
|---|---|---|---|---|
|
Change From Baseline to Day 28 in Adiponectin
|
5648.6 nanograms per milliliter (ng/mL)
Interval 4345.2 to 6952.1
|
458.3 nanograms per milliliter (ng/mL)
Interval -1165.1 to 2081.6
|
1850.7 nanograms per milliliter (ng/mL)
Interval 405.1 to 3296.3
|
2907.1 nanograms per milliliter (ng/mL)
Interval 1289.1 to 4525.1
|
SECONDARY outcome
Timeframe: Baseline, Day 28Population: All participants who received at least 1 dose of study drug with evaluable C-reactive protein data.
Change from baseline to Day 28 in C-reactive protein is presented. The predose C-reactive protein measurement on Day 1 served as the baseline value. LS means were calculated using a linear mixed effects model with treatment, day, and treatment times day as fixed effects; baseline as covariate; and participant as random effect.
Outcome measures
| Measure |
20 mg LY2405319
n=13 Participants
Participants received 20 mg LY2405319 injected SC once daily for 28 days.
|
Placebo
n=8 Participants
Participants received placebo-matching LY2405319 injected SC once daily for 28 days.
|
3 mg LY2405319
n=10 Participants
Participants received 3 mg LY2405319 injected SC once daily for 28 days.
|
10 mg LY2405319
n=8 Participants
Participants received 10 mg LY2405319 injected SC once daily for 28 days.
|
|---|---|---|---|---|
|
Change From Baseline to Day 28 in C-Reactive Protein
|
0.0 milligrams per liter (mg/L)
Interval -1.6 to 1.7
|
0.4 milligrams per liter (mg/L)
Interval -1.8 to 2.5
|
-0.6 milligrams per liter (mg/L)
Interval -2.5 to 1.3
|
0.3 milligrams per liter (mg/L)
Interval -1.8 to 2.4
|
SECONDARY outcome
Timeframe: Predose through Day 28 (48 hours postdose)Population: All participants who received at least 1 dose of study drug with evaluable AUC of LY2405319 data.
AUC for LY2405319 is presented. Data represent AUC for 1 dosing interval at steady state. Blood samples were collected predose and at 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 24, and 48 hours postdose on Day 28.
Outcome measures
| Measure |
20 mg LY2405319
n=15 Participants
Participants received 20 mg LY2405319 injected SC once daily for 28 days.
|
Placebo
Participants received placebo-matching LY2405319 injected SC once daily for 28 days.
|
3 mg LY2405319
n=11 Participants
Participants received 3 mg LY2405319 injected SC once daily for 28 days.
|
10 mg LY2405319
n=10 Participants
Participants received 10 mg LY2405319 injected SC once daily for 28 days.
|
|---|---|---|---|---|
|
Pharmacokinetics: Area Under the Concentration Time Curve (AUC) of LY2405319
|
3410 nanograms*hours/milliliter (ng*hr/mL)
Geometric Coefficient of Variation 35.1
|
—
|
409 nanograms*hours/milliliter (ng*hr/mL)
Geometric Coefficient of Variation 26.0
|
1520 nanograms*hours/milliliter (ng*hr/mL)
Geometric Coefficient of Variation 38.9
|
SECONDARY outcome
Timeframe: Predose through Day 28 (48 hours postdose)Population: All participants who received at least 1 dose of study drug with evaluable Cmax of LY2405319 data.
Cmax of LY2405319 is presented. Blood samples were collected predose and at 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 24, and 48 hours postdose on Day 28.
Outcome measures
| Measure |
20 mg LY2405319
n=12 Participants
Participants received 20 mg LY2405319 injected SC once daily for 28 days.
|
Placebo
Participants received placebo-matching LY2405319 injected SC once daily for 28 days.
|
3 mg LY2405319
n=10 Participants
Participants received 3 mg LY2405319 injected SC once daily for 28 days.
|
10 mg LY2405319
n=8 Participants
Participants received 10 mg LY2405319 injected SC once daily for 28 days.
|
|---|---|---|---|---|
|
Pharmacokinetics: Maximum Concentration (Cmax) of LY2405319
|
247 nanograms per milliliter (ng/mL)
Geometric Coefficient of Variation 58.8
|
—
|
39.9 nanograms per milliliter (ng/mL)
Geometric Coefficient of Variation 34.7
|
105 nanograms per milliliter (ng/mL)
Geometric Coefficient of Variation 62.9
|
SECONDARY outcome
Timeframe: Day 1 through Day 56Population: All participants who received at least 1 dose of study drug with evaluable anti-LY2405319 antibody data.
The number of participants that tested positive for anti-LY2405319 antibodies is presented.
Outcome measures
| Measure |
20 mg LY2405319
n=15 Participants
Participants received 20 mg LY2405319 injected SC once daily for 28 days.
|
Placebo
n=10 Participants
Participants received placebo-matching LY2405319 injected SC once daily for 28 days.
|
3 mg LY2405319
n=11 Participants
Participants received 3 mg LY2405319 injected SC once daily for 28 days.
|
10 mg LY2405319
n=10 Participants
Participants received 10 mg LY2405319 injected SC once daily for 28 days.
|
|---|---|---|---|---|
|
The Number of Participants With Anti-LY2405319 Antibodies
|
13 number of participants
|
2 number of participants
|
6 number of participants
|
8 number of participants
|
SECONDARY outcome
Timeframe: Baseline, Day 28Population: All participants who received at least 1 dose of study drug with evaluable EI data.
Change from baseline to Day 28 in Eating Inventory (EI) subscales are presented. The EI is a 51-item inventory that measures dietary restraint (the cognitive intention to restrict energy intake; scores range from 0 to 21), disinhibition (the tendency to episodically overeat, often in response to external cues; scores range from 0 to 16), and perceived hunger (scores range from 0 to 14). A low score indicates a low exhibition of behavior and a high score indicates a high exhibition of behavior. The measurement for each variable obtained on Day -2 served as the baseline value. LS means were calculated using an analysis of covariance model with treatment, day, and treatment times day as fixed effects, and baseline as covariate.
Outcome measures
| Measure |
20 mg LY2405319
n=12 Participants
Participants received 20 mg LY2405319 injected SC once daily for 28 days.
|
Placebo
n=8 Participants
Participants received placebo-matching LY2405319 injected SC once daily for 28 days.
|
3 mg LY2405319
n=10 Participants
Participants received 3 mg LY2405319 injected SC once daily for 28 days.
|
10 mg LY2405319
n=8 Participants
Participants received 10 mg LY2405319 injected SC once daily for 28 days.
|
|---|---|---|---|---|
|
Change From Baseline to Day 28 in Eating Inventory for Cognitive Restraint of Eating, Disinhibition, and Hunger
Hunger
|
0.53 units on a scale
Interval -0.65 to 1.7
|
0.29 units on a scale
Interval -1.16 to 1.73
|
1.00 units on a scale
Interval -0.32 to 2.32
|
2.05 units on a scale
Interval 0.59 to 3.5
|
|
Change From Baseline to Day 28 in Eating Inventory for Cognitive Restraint of Eating, Disinhibition, and Hunger
Cognitive restraint of eating
|
-0.27 units on a scale
Interval -1.71 to 1.17
|
-2.99 units on a scale
Interval -4.73 to -1.25
|
-1.10 units on a scale
Interval -2.68 to 0.48
|
-0.35 units on a scale
Interval -2.09 to 1.39
|
|
Change From Baseline to Day 28 in Eating Inventory for Cognitive Restraint of Eating, Disinhibition, and Hunger
Disinhibition
|
-1.59 units on a scale
Interval -2.47 to -0.7
|
0.04 units on a scale
Interval -1.06 to 1.14
|
0.34 units on a scale
Interval -0.67 to 1.34
|
0.04 units on a scale
Interval -1.06 to 1.15
|
SECONDARY outcome
Timeframe: Baseline, Day 28Population: All participants who received at least 1 dose of study drug with evaluable FPQ data.
The table below represents the change from baseline in FPQ total score. The FPQ was administered to assess overall preference for foods of different macronutrient contents utilizing a macronutrient self-selection paradigm. Participants rated their preference on a range from 1 to 9 with 1 (dislike extremely) to 9 (like extremely) for a battery of 72 commonly consumed foods with fat content varying significantly in sugar, complex carbohydrates, and protein. The total score was calculated by averaging preference scores of 72 items. A low mean score of 1 to 9 scale indicate a low preference for the foods listed and a high mean score indicate a high preference for the foods listed. The FPQ measurement on Day -2 served as the baseline value. LS means were calculated using an analysis of covariance model with treatment, day, and treatment times day as fixed effects, and baseline as covariate.
Outcome measures
| Measure |
20 mg LY2405319
n=12 Participants
Participants received 20 mg LY2405319 injected SC once daily for 28 days.
|
Placebo
n=8 Participants
Participants received placebo-matching LY2405319 injected SC once daily for 28 days.
|
3 mg LY2405319
n=10 Participants
Participants received 3 mg LY2405319 injected SC once daily for 28 days.
|
10 mg LY2405319
n=8 Participants
Participants received 10 mg LY2405319 injected SC once daily for 28 days.
|
|---|---|---|---|---|
|
Change From Baseline to Day 28 in the Food Preference Questionnaire (FPQ) Score
|
-0.77 units on a scale
Interval -1.3 to -0.24
|
0.74 units on a scale
Interval 0.09 to 1.4
|
-0.06 units on a scale
Interval -0.73 to 0.61
|
-0.43 units on a scale
Interval -1.15 to 0.29
|
SECONDARY outcome
Timeframe: Baseline, Day 28Population: All participants who received at least 1 dose of study drug with evaluable PHQ-9 data.
Change from baseline to Day 28 in the PHQ-9 total score is presented. Participants were asked to score the severity of depressive symptoms over the last 2 weeks. Items were scored 0 (not at all), 1 (several days), 2 (half of the days), or 3 (nearly every day). The total PHQ-9 score is the sum of the score for each item and range from 0 to 27. A score of 0 means low depression severity and a score of 27 means high depression severity. Depression severity will be given a quality rating based on the total PHQ-9 score, as follows: None (0-4); Mild (5-9); Moderate (10-14); Moderately severe (15-19); and Severe (20-27). The PHQ-9 measurement obtained on Day -2 served as the baseline value. LS means were calculated using an analysis of covariance model with treatment, day, and treatment times day as fixed effects, and baseline as covariate.
Outcome measures
| Measure |
20 mg LY2405319
n=12 Participants
Participants received 20 mg LY2405319 injected SC once daily for 28 days.
|
Placebo
n=8 Participants
Participants received placebo-matching LY2405319 injected SC once daily for 28 days.
|
3 mg LY2405319
n=10 Participants
Participants received 3 mg LY2405319 injected SC once daily for 28 days.
|
10 mg LY2405319
n=8 Participants
Participants received 10 mg LY2405319 injected SC once daily for 28 days.
|
|---|---|---|---|---|
|
Change From Baseline to Day 28 in The Patient Health Questionnaire (PHQ-9) Score
|
1.82 units on a scale
Interval 0.08 to 3.56
|
2.57 units on a scale
Interval 0.43 to 4.71
|
1.26 units on a scale
Interval -0.71 to 3.24
|
-0.50 units on a scale
Interval -2.83 to 1.82
|
Adverse Events
3 mg LY2405319
10 mg LY2405319
20 mg LY2405319
Placebo
Serious adverse events
| Measure |
3 mg LY2405319
n=11 participants at risk
Participants received 3 mg LY2405319 injected SC once daily for 28 days.
|
10 mg LY2405319
n=10 participants at risk
Participants received 10 mg LY2405319 injected SC once daily for 28 days.
|
20 mg LY2405319
n=15 participants at risk
Participants received 20 mg LY2405319 injected SC once daily for 28 days.
|
Placebo
n=10 participants at risk
Participants received placebo-matching LY2405319 injected SC once daily for 28 days.
|
|---|---|---|---|---|
|
Eye disorders
Optic ischaemic neuropathy
|
0.00%
0/11
|
0.00%
0/10
|
6.7%
1/15 • Number of events 1
|
0.00%
0/10
|
|
Hepatobiliary disorders
Cholecystitis acute
|
0.00%
0/11
|
0.00%
0/10
|
0.00%
0/15
|
10.0%
1/10 • Number of events 1
|
|
Immune system disorders
Hypersensitivity
|
0.00%
0/11
|
0.00%
0/10
|
6.7%
1/15 • Number of events 1
|
0.00%
0/10
|
Other adverse events
| Measure |
3 mg LY2405319
n=11 participants at risk
Participants received 3 mg LY2405319 injected SC once daily for 28 days.
|
10 mg LY2405319
n=10 participants at risk
Participants received 10 mg LY2405319 injected SC once daily for 28 days.
|
20 mg LY2405319
n=15 participants at risk
Participants received 20 mg LY2405319 injected SC once daily for 28 days.
|
Placebo
n=10 participants at risk
Participants received placebo-matching LY2405319 injected SC once daily for 28 days.
|
|---|---|---|---|---|
|
Cardiac disorders
Palpitations
|
0.00%
0/11
|
0.00%
0/10
|
0.00%
0/15
|
10.0%
1/10 • Number of events 1
|
|
Ear and labyrinth disorders
Ear pain
|
0.00%
0/11
|
0.00%
0/10
|
0.00%
0/15
|
10.0%
1/10 • Number of events 1
|
|
Eye disorders
Vision blurred
|
0.00%
0/11
|
0.00%
0/10
|
6.7%
1/15 • Number of events 1
|
10.0%
1/10 • Number of events 1
|
|
Gastrointestinal disorders
Abdominal distension
|
9.1%
1/11 • Number of events 1
|
0.00%
0/10
|
6.7%
1/15 • Number of events 1
|
0.00%
0/10
|
|
Gastrointestinal disorders
Abdominal pain
|
0.00%
0/11
|
0.00%
0/10
|
13.3%
2/15 • Number of events 2
|
20.0%
2/10 • Number of events 2
|
|
Gastrointestinal disorders
Abdominal pain upper
|
18.2%
2/11 • Number of events 2
|
0.00%
0/10
|
0.00%
0/15
|
0.00%
0/10
|
|
Gastrointestinal disorders
Constipation
|
9.1%
1/11 • Number of events 2
|
0.00%
0/10
|
0.00%
0/15
|
10.0%
1/10 • Number of events 1
|
|
Gastrointestinal disorders
Diarrhoea
|
9.1%
1/11 • Number of events 1
|
10.0%
1/10 • Number of events 1
|
6.7%
1/15 • Number of events 1
|
0.00%
0/10
|
|
Gastrointestinal disorders
Dry mouth
|
0.00%
0/11
|
0.00%
0/10
|
0.00%
0/15
|
10.0%
1/10 • Number of events 1
|
|
Gastrointestinal disorders
Haematochezia
|
0.00%
0/11
|
10.0%
1/10 • Number of events 1
|
0.00%
0/15
|
0.00%
0/10
|
|
Gastrointestinal disorders
Nausea
|
9.1%
1/11 • Number of events 1
|
10.0%
1/10 • Number of events 1
|
13.3%
2/15 • Number of events 4
|
20.0%
2/10 • Number of events 2
|
|
Gastrointestinal disorders
Vomiting
|
0.00%
0/11
|
0.00%
0/10
|
13.3%
2/15 • Number of events 3
|
20.0%
2/10 • Number of events 2
|
|
General disorders
Application site rash
|
0.00%
0/11
|
0.00%
0/10
|
6.7%
1/15 • Number of events 1
|
0.00%
0/10
|
|
General disorders
Fatigue
|
0.00%
0/11
|
10.0%
1/10 • Number of events 1
|
0.00%
0/15
|
10.0%
1/10 • Number of events 1
|
|
General disorders
Influenza like illness
|
9.1%
1/11 • Number of events 1
|
0.00%
0/10
|
0.00%
0/15
|
10.0%
1/10 • Number of events 1
|
|
General disorders
Injection site bruising
|
0.00%
0/11
|
0.00%
0/10
|
6.7%
1/15 • Number of events 1
|
0.00%
0/10
|
|
General disorders
Injection site erythema
|
9.1%
1/11 • Number of events 3
|
60.0%
6/10 • Number of events 39
|
46.7%
7/15 • Number of events 46
|
20.0%
2/10 • Number of events 2
|
|
General disorders
Injection site haemorrhage
|
0.00%
0/11
|
50.0%
5/10 • Number of events 7
|
40.0%
6/15 • Number of events 11
|
30.0%
3/10 • Number of events 6
|
|
General disorders
Injection site induration
|
0.00%
0/11
|
10.0%
1/10 • Number of events 1
|
0.00%
0/15
|
20.0%
2/10 • Number of events 2
|
|
General disorders
Injection site inflammation
|
0.00%
0/11
|
0.00%
0/10
|
13.3%
2/15 • Number of events 3
|
0.00%
0/10
|
|
General disorders
Injection site irritation
|
9.1%
1/11 • Number of events 1
|
10.0%
1/10 • Number of events 1
|
0.00%
0/15
|
0.00%
0/10
|
|
General disorders
Injection site pain
|
0.00%
0/11
|
10.0%
1/10 • Number of events 1
|
0.00%
0/15
|
0.00%
0/10
|
|
General disorders
Injection site pruritus
|
0.00%
0/11
|
10.0%
1/10 • Number of events 4
|
0.00%
0/15
|
0.00%
0/10
|
|
General disorders
Injection site reaction
|
0.00%
0/11
|
30.0%
3/10 • Number of events 6
|
6.7%
1/15 • Number of events 2
|
0.00%
0/10
|
|
General disorders
Injection site swelling
|
0.00%
0/11
|
0.00%
0/10
|
0.00%
0/15
|
20.0%
2/10 • Number of events 2
|
|
General disorders
Injection site urticaria
|
0.00%
0/11
|
0.00%
0/10
|
6.7%
1/15 • Number of events 1
|
10.0%
1/10 • Number of events 1
|
|
General disorders
Injection site warmth
|
0.00%
0/11
|
10.0%
1/10 • Number of events 1
|
0.00%
0/15
|
0.00%
0/10
|
|
General disorders
Oedema peripheral
|
9.1%
1/11 • Number of events 2
|
0.00%
0/10
|
0.00%
0/15
|
0.00%
0/10
|
|
General disorders
Pain
|
0.00%
0/11
|
0.00%
0/10
|
6.7%
1/15 • Number of events 1
|
0.00%
0/10
|
|
General disorders
Pyrexia
|
0.00%
0/11
|
0.00%
0/10
|
0.00%
0/15
|
10.0%
1/10 • Number of events 1
|
|
Infections and infestations
Tooth abscess
|
0.00%
0/11
|
0.00%
0/10
|
6.7%
1/15 • Number of events 1
|
0.00%
0/10
|
|
Infections and infestations
Viral upper respiratory tract infection
|
9.1%
1/11 • Number of events 1
|
0.00%
0/10
|
0.00%
0/15
|
0.00%
0/10
|
|
Injury, poisoning and procedural complications
Arthropod bite
|
0.00%
0/11
|
0.00%
0/10
|
6.7%
1/15 • Number of events 1
|
0.00%
0/10
|
|
Injury, poisoning and procedural complications
Scratch
|
0.00%
0/11
|
10.0%
1/10 • Number of events 1
|
0.00%
0/15
|
0.00%
0/10
|
|
Investigations
Blood calcium increased
|
9.1%
1/11 • Number of events 1
|
0.00%
0/10
|
0.00%
0/15
|
0.00%
0/10
|
|
Investigations
Blood creatine phosphokinase increased
|
0.00%
0/11
|
0.00%
0/10
|
6.7%
1/15 • Number of events 1
|
0.00%
0/10
|
|
Investigations
Hepatic enzyme increased
|
9.1%
1/11 • Number of events 1
|
0.00%
0/10
|
0.00%
0/15
|
0.00%
0/10
|
|
Metabolism and nutrition disorders
Decreased appetite
|
0.00%
0/11
|
0.00%
0/10
|
6.7%
1/15 • Number of events 1
|
10.0%
1/10 • Number of events 1
|
|
Metabolism and nutrition disorders
Hyperglycaemia
|
0.00%
0/11
|
0.00%
0/10
|
13.3%
2/15 • Number of events 2
|
0.00%
0/10
|
|
Metabolism and nutrition disorders
Hypoglycaemia
|
9.1%
1/11 • Number of events 1
|
20.0%
2/10 • Number of events 3
|
6.7%
1/15 • Number of events 1
|
10.0%
1/10 • Number of events 2
|
|
Metabolism and nutrition disorders
Increased appetite
|
9.1%
1/11 • Number of events 1
|
0.00%
0/10
|
6.7%
1/15 • Number of events 1
|
0.00%
0/10
|
|
Musculoskeletal and connective tissue disorders
Muscle spasms
|
0.00%
0/11
|
0.00%
0/10
|
0.00%
0/15
|
20.0%
2/10 • Number of events 2
|
|
Nervous system disorders
Dizziness
|
9.1%
1/11 • Number of events 1
|
0.00%
0/10
|
6.7%
1/15 • Number of events 1
|
0.00%
0/10
|
|
Nervous system disorders
Dysaesthesia
|
0.00%
0/11
|
0.00%
0/10
|
0.00%
0/15
|
10.0%
1/10 • Number of events 1
|
|
Nervous system disorders
Headache
|
9.1%
1/11 • Number of events 1
|
0.00%
0/10
|
6.7%
1/15 • Number of events 1
|
40.0%
4/10 • Number of events 4
|
|
Nervous system disorders
Somnolence
|
0.00%
0/11
|
0.00%
0/10
|
0.00%
0/15
|
10.0%
1/10 • Number of events 1
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
9.1%
1/11 • Number of events 1
|
0.00%
0/10
|
0.00%
0/15
|
0.00%
0/10
|
|
Skin and subcutaneous tissue disorders
Acne
|
9.1%
1/11 • Number of events 1
|
0.00%
0/10
|
0.00%
0/15
|
0.00%
0/10
|
|
Skin and subcutaneous tissue disorders
Dermatitis contact
|
9.1%
1/11 • Number of events 2
|
40.0%
4/10 • Number of events 7
|
20.0%
3/15 • Number of events 4
|
0.00%
0/10
|
|
Skin and subcutaneous tissue disorders
Pruritus
|
0.00%
0/11
|
0.00%
0/10
|
6.7%
1/15 • Number of events 1
|
0.00%
0/10
|
|
Skin and subcutaneous tissue disorders
Rash
|
0.00%
0/11
|
0.00%
0/10
|
6.7%
1/15 • Number of events 1
|
0.00%
0/10
|
|
Vascular disorders
Orthostatic hypotension
|
0.00%
0/11
|
10.0%
1/10 • Number of events 1
|
0.00%
0/15
|
0.00%
0/10
|
Additional Information
Chief Medical Officer
Eli Lilly and Company
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place
Restriction type: GT60