Diabetes Mellitus, Type 2
Conditions
Brief summary
The main purpose of this study was to evaluate the safety and tolerability of LY2405319. It was given as a daily injection under the skin to participants with type 2 diabetes mellitus (T2DM) for 28 days. This study determined how long the drug stays in the body and how it affects blood sugar levels. After screening, the study lasted about 2 months for each participant. Participants continued their prestudy regimen of diet and exercise alone or in combination with metformin.
Interventions
DRUGLY2405319
Administered SC
DRUGPlacebo
Administered SC
Sponsors
Eli Lilly and Company
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
BASIC_SCIENCE
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
* Have a diagnosis of T2DM. * Are on diet and exercise or diet, exercise, and metformin (stable dose of at least 1000 mg/day for at least 60 days) regimen. * Have a glycosylated hemoglobin A1c (HbA1c) value of 7.0% to 10.0%, inclusive, or are on metformin and an additional oral antidiabetic medication (OAM) with an HbA1c value of 6.5% to 9.5%, inclusive. * Participants on another OAM in addition to metformin therapy may be randomized if removed from treatment of the other OAM ≥14 days prior to study drug administration and fasting blood glucose is ≥145 mg per deciliter (mg/dL) and ≤270 mg/dL. * Are females not of child-bearing potential due to surgical sterilization or are postmenopausal. * Have a body mass index (BMI) ≥25 and ≤40. * Have clinical laboratory test results within normal reference range for the population.
Exclusion criteria
* Use insulin, thiazolidinediones (TZDs), dipeptidyl peptidase (DPP) IV inhibitors, or exenatide during the 3 months prior to screening. * Have had more than 1 episode of severe hypoglycemia requiring assistance of another person to administer a resuscitative action within 6 months prior to entry into the study or are currently diagnosed with having hypoglycemia unawareness. * Have had 2 or more emergency room visits or hospitalizations due to poor glucose control in the past 6 months. * Have any abnormality of the electrocardiogram (ECG) that will, in the opinion of the investigator, impair the ability to measure the QT (a corrected QC \[QTc\] \[Bazett's correction\] interval \>450 milliseconds \[msec\] for men and \>470 msec for women or a PR interval \>220 msec are specifically excluded) or have conduction abnormalities that may confound the QTc analysis. * Have a personal or family history of long QT syndrome, family history of sudden death, personal history of unexplained syncope within the last year; or use prescription or over-the-counter medications known to prolong the QT or QTc interval. * Have diastolic blood pressure (DBP) ≥95 millimeters of mercury (mm Hg) and/or systolic blood pressure (SBP) ≥160 mm Hg. * Have an active or untreated malignancy or have been in remission from a clinically significant malignancy for \<5 years. * Have a history of a transplanted organ. * Evidence of a significant active, uncontrolled endocrine or autoimmune abnormality, as judged by the investigator, at screening. * Have a history of human immunodeficiency virus (HIV). * Have a known allergy to yeast or yeast proteins, history of anaphylaxis with bronchospasm, or atopic dermatitis with chronic urticaria. * Have any other condition (including known drug or alcohol abuse or psychiatric disorder within the last 6 months) that may preclude the participant from following and completing the protocol. * Have a significant history of or current cardiovascular, respiratory, hepatic, renal, gastrointestinal, endocrine (including pancreatitis), 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. * Are women who are breastfeeding. * Have had a significant change in weight, defined as a gain or loss of at least 4 kilograms (kg) (9 pounds) in the 90 days prior to randomization. * Have taken in the 30 days prior to randomization, a medication, herbal product, or nutritional supplement that affects adipose mass or distribution or energy balance. * Are receiving chronic (\>2 weeks) systemic glucocorticoid therapy (excluding topical or inhaled preparations) or have received such therapy within 4 weeks immediately prior to second screening appointment. * Have current or recent (within the past 3 months) use of gemfibrozil or fenofibrate, niacin, ezetimibe, or bile acid binding resins (for example, cholestyramines). Stable statin therapy of ≥3 months will be allowed. * Are currently taking central nervous system (CNS) stimulant.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With One or More Serious Adverse Event(s) (SAEs) Considered by the Investigator to be Related to Study Drug Administration | Baseline through Day 56 | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 7 Point Self-monitored Blood Glucose (SMBG) | Baseline (Day -5, -4, or -3) and Week 4 (Days 24, 25, or 26) | 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. |
| Change From Baseline to Week 4 in Glucose Area Under the Curve (AUC) | Predose and 2 hours postdose (Baseline, Week 4) | 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. |
| Change From Baseline to Week 4 in Insulin Area Under the Curve (AUC) | Predose and 2 hours postdose (Baseline, Week 4) | 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. |
| Change From Baseline to Week 4 in C-peptide Area Under the Curve (AUC) | Predose and 2 hours postdose (Baseline, Week 4) | 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. |
| Change From Baseline to Day 28 in Fasting Lipid Profile | Baseline, Day 28 | 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. |
| Change From Baseline to Day 28 in Body Weight | Baseline, Day 28 | 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. |
| Change From Baseline to Day 28 in Adiponectin | Baseline, Day 28 | 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. |
| Change From Baseline to Day 28 in Fasting Glucose | Baseline, Day 28 | 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. |
| Pharmacokinetics: Area Under the Concentration Time Curve (AUC) of LY2405319 | Predose through Day 28 (48 hours postdose) | 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. |
| Pharmacokinetics: Maximum Concentration (Cmax) of LY2405319 | Predose through Day 28 (48 hours postdose) | 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. |
| The Number of Participants With Anti-LY2405319 Antibodies | Day 1 through Day 56 | The number of participants that tested positive for anti-LY2405319 antibodies is presented. |
| Change From Baseline to Day 28 in Eating Inventory for Cognitive Restraint of Eating, Disinhibition, and Hunger | Baseline, Day 28 | 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. |
| Change From Baseline to Day 28 in the Food Preference Questionnaire (FPQ) Score | Baseline, Day 28 | 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. |
| Change From Baseline to Day 28 in The Patient Health Questionnaire (PHQ-9) Score | Baseline, Day 28 | 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. |
| Change From Baseline to Day 28 in C-Reactive Protein | Baseline, Day 28 | 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. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| 3 mg LY2405319 3 mg LY2405319 injected SC once daily for 28 days. | 11 |
| 10 mg LY2405319 10 mg LY2405319 injected SC once daily for 28 days. | 10 |
| 20 mg LY2405319 20 mg LY2405319 injected SC once daily for 28 days. | 15 |
| Placebo Placebo-matching LY2405319 injected subcutaneously (SC) once daily for 28 days. | 10 |
| Total | 46 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 |
|---|---|---|---|---|---|---|
| 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
| Characteristic | 3 mg LY2405319 | Total | Placebo | 20 mg LY2405319 | 10 mg LY2405319 |
|---|---|---|---|---|---|
| Age, Continuous | 56.5 Years STANDARD_DEVIATION 7.3 | 57.7 Years STANDARD_DEVIATION 8.4 | 58.6 Years STANDARD_DEVIATION 6.3 | 56.9 Years STANDARD_DEVIATION 10.2 | 59.6 Years STANDARD_DEVIATION 9.2 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 11 Participants | 46 Participants | 10 Participants | 15 Participants | 10 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 1 Participants | 0 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 1 Participants | 0 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 11 Participants | 44 Participants | 10 Participants | 13 Participants | 10 Participants |
| Region of Enrollment United States | 11 participants | 46 participants | 10 participants | 15 participants | 10 participants |
| Sex: Female, Male Female | 4 Participants | 20 Participants | 6 Participants | 7 Participants | 3 Participants |
| Sex: Female, Male Male | 7 Participants | 26 Participants | 4 Participants | 8 Participants | 7 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 7 / 11 | 8 / 10 | 11 / 15 | 9 / 10 |
| serious Total, serious adverse events | 0 / 11 | 0 / 10 | 2 / 15 | 1 / 10 |
Outcome results
Primary
Number of Participants With One or More Serious Adverse Event(s) (SAEs) Considered by the Investigator to be Related to Study Drug Administration
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.
Time frame: Baseline through Day 56
Population: All participants who received at least 1 dose of study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| 3 mg LY2405319 | Number of Participants With One or More Serious Adverse Event(s) (SAEs) Considered by the Investigator to be Related to Study Drug Administration | 0 number of participants |
| 10 mg LY2405319 | Number of Participants With One or More Serious Adverse Event(s) (SAEs) Considered by the Investigator to be Related to Study Drug Administration | 0 number of participants |
| 20 mg LY2405319 | 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 |
| Placebo | Number of Participants With One or More Serious Adverse Event(s) (SAEs) Considered by the Investigator to be Related to Study Drug Administration | 0 number of participants |
Secondary
7 Point Self-monitored Blood Glucose (SMBG)
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.
Time frame: 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.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| 3 mg LY2405319 | 7 Point Self-monitored Blood Glucose (SMBG) | Baseline (Days -6, -5, or -4) | 178.01 mg/dL | Standard Error 5.95 |
| 3 mg LY2405319 | 7 Point Self-monitored Blood Glucose (SMBG) | Week 4 (Days 24, 25, or 26) | 171.03 mg/dL | Standard Error 6.1 |
| 10 mg LY2405319 | 7 Point Self-monitored Blood Glucose (SMBG) | Week 4 (Days 24, 25, or 26) | 167.95 mg/dL | Standard Error 8.09 |
| 10 mg LY2405319 | 7 Point Self-monitored Blood Glucose (SMBG) | Baseline (Days -6, -5, or -4) | 171.13 mg/dL | Standard Error 5.02 |
| 20 mg LY2405319 | 7 Point Self-monitored Blood Glucose (SMBG) | Week 4 (Days 24, 25, or 26) | 188.52 mg/dL | Standard Error 7.14 |
| 20 mg LY2405319 | 7 Point Self-monitored Blood Glucose (SMBG) | Baseline (Days -6, -5, or -4) | 183.97 mg/dL | Standard Error 4.19 |
| Placebo | 7 Point Self-monitored Blood Glucose (SMBG) | Week 4 (Days 24, 25, or 26) | 177.41 mg/dL | Standard Error 7.24 |
| Placebo | 7 Point Self-monitored Blood Glucose (SMBG) | Baseline (Days -6, -5, or -4) | 172.46 mg/dL | Standard Error 5.33 |
Secondary
Change From Baseline to Day 28 in Adiponectin
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.
Time frame: Baseline, Day 28
Population: All participants who received at least 1 dose of study drug with evaluable adiponectin data.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| 3 mg LY2405319 | Change From Baseline to Day 28 in Adiponectin | 1850.7 nanograms per milliliter (ng/mL) |
| 10 mg LY2405319 | Change From Baseline to Day 28 in Adiponectin | 2907.1 nanograms per milliliter (ng/mL) |
| 20 mg LY2405319 | Change From Baseline to Day 28 in Adiponectin | 5648.6 nanograms per milliliter (ng/mL) |
| Placebo | Change From Baseline to Day 28 in Adiponectin | 458.3 nanograms per milliliter (ng/mL) |
Secondary
Change From Baseline to Day 28 in Body Weight
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.
Time frame: Baseline, Day 28
Population: All participants who received at least 1 dose of study drug with evaluable body weight data.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| 3 mg LY2405319 | Change From Baseline to Day 28 in Body Weight | -0.7 kilograms (kg) |
| 10 mg LY2405319 | Change From Baseline to Day 28 in Body Weight | -1.8 kilograms (kg) |
| 20 mg LY2405319 | Change From Baseline to Day 28 in Body Weight | -1.5 kilograms (kg) |
| Placebo | Change From Baseline to Day 28 in Body Weight | -0.2 kilograms (kg) |
Secondary
Change From Baseline to Day 28 in C-Reactive Protein
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.
Time frame: Baseline, Day 28
Population: All participants who received at least 1 dose of study drug with evaluable C-reactive protein data.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| 3 mg LY2405319 | Change From Baseline to Day 28 in C-Reactive Protein | -0.6 milligrams per liter (mg/L) |
| 10 mg LY2405319 | Change From Baseline to Day 28 in C-Reactive Protein | 0.3 milligrams per liter (mg/L) |
| 20 mg LY2405319 | Change From Baseline to Day 28 in C-Reactive Protein | 0.0 milligrams per liter (mg/L) |
| Placebo | Change From Baseline to Day 28 in C-Reactive Protein | 0.4 milligrams per liter (mg/L) |
Secondary
Change From Baseline to Day 28 in Eating Inventory for Cognitive Restraint of Eating, Disinhibition, and Hunger
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.
Time frame: Baseline, Day 28
Population: All participants who received at least 1 dose of study drug with evaluable EI data.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) |
|---|---|---|---|
| 3 mg LY2405319 | Change From Baseline to Day 28 in Eating Inventory for Cognitive Restraint of Eating, Disinhibition, and Hunger | Cognitive restraint of eating | -1.10 units on a scale |
| 3 mg LY2405319 | Change From Baseline to Day 28 in Eating Inventory for Cognitive Restraint of Eating, Disinhibition, and Hunger | Hunger | 1.00 units on a scale |
| 3 mg LY2405319 | Change From Baseline to Day 28 in Eating Inventory for Cognitive Restraint of Eating, Disinhibition, and Hunger | Disinhibition | 0.34 units on a scale |
| 10 mg LY2405319 | Change From Baseline to Day 28 in Eating Inventory for Cognitive Restraint of Eating, Disinhibition, and Hunger | Cognitive restraint of eating | -0.35 units on a scale |
| 10 mg LY2405319 | Change From Baseline to Day 28 in Eating Inventory for Cognitive Restraint of Eating, Disinhibition, and Hunger | Hunger | 2.05 units on a scale |
| 10 mg LY2405319 | Change From Baseline to Day 28 in Eating Inventory for Cognitive Restraint of Eating, Disinhibition, and Hunger | Disinhibition | 0.04 units on a scale |
| 20 mg LY2405319 | Change From Baseline to Day 28 in Eating Inventory for Cognitive Restraint of Eating, Disinhibition, and Hunger | Disinhibition | -1.59 units on a scale |
| 20 mg LY2405319 | 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 |
| 20 mg LY2405319 | Change From Baseline to Day 28 in Eating Inventory for Cognitive Restraint of Eating, Disinhibition, and Hunger | Hunger | 0.53 units on a scale |
| Placebo | Change From Baseline to Day 28 in Eating Inventory for Cognitive Restraint of Eating, Disinhibition, and Hunger | Cognitive restraint of eating | -2.99 units on a scale |
| Placebo | Change From Baseline to Day 28 in Eating Inventory for Cognitive Restraint of Eating, Disinhibition, and Hunger | Hunger | 0.29 units on a scale |
| Placebo | Change From Baseline to Day 28 in Eating Inventory for Cognitive Restraint of Eating, Disinhibition, and Hunger | Disinhibition | 0.04 units on a scale |
Secondary
Change From Baseline to Day 28 in Fasting Glucose
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.
Time frame: Baseline, Day 28
Population: Participants who received at least 1 dose of study drug with evaluable blood glucose data.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| 3 mg LY2405319 | Change From Baseline to Day 28 in Fasting Glucose | -3.5 milligrams per deciliter (mg/dL) |
| 10 mg LY2405319 | Change From Baseline to Day 28 in Fasting Glucose | -6.7 milligrams per deciliter (mg/dL) |
| 20 mg LY2405319 | Change From Baseline to Day 28 in Fasting Glucose | -10.5 milligrams per deciliter (mg/dL) |
| Placebo | Change From Baseline to Day 28 in Fasting Glucose | 3.2 milligrams per deciliter (mg/dL) |
Secondary
Change From Baseline to Day 28 in Fasting Lipid Profile
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.
Time frame: Baseline, Day 28
Population: All participants who received at least 1 dose of study drug with evaluable fasting lipid (ie, cholesterol, LDL-C, HDL-C, and triglyceride) data.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) |
|---|---|---|---|
| 3 mg LY2405319 | Change From Baseline to Day 28 in Fasting Lipid Profile | Cholesterol (n=10, n=8, n=13, n=8) | 3.9 milligrams per deciliter (mg/dL) |
| 3 mg LY2405319 | Change From Baseline to Day 28 in Fasting Lipid Profile | LDL-C (n=10, n=8, n=13, n=7) | -0.1 milligrams per deciliter (mg/dL) |
| 3 mg LY2405319 | Change From Baseline to Day 28 in Fasting Lipid Profile | HDL-C (n=10, n=8, n=13, n=8) | 10.6 milligrams per deciliter (mg/dL) |
| 3 mg LY2405319 | Change From Baseline to Day 28 in Fasting Lipid Profile | Triglycerides (n=10, n=8, n=13, n=8) | -38.5 milligrams per deciliter (mg/dL) |
| 10 mg LY2405319 | Change From Baseline to Day 28 in Fasting Lipid Profile | Triglycerides (n=10, n=8, n=13, n=8) | -81.0 milligrams per deciliter (mg/dL) |
| 10 mg LY2405319 | Change From Baseline to Day 28 in Fasting Lipid Profile | HDL-C (n=10, n=8, n=13, n=8) | 10.2 milligrams per deciliter (mg/dL) |
| 10 mg LY2405319 | Change From Baseline to Day 28 in Fasting Lipid Profile | LDL-C (n=10, n=8, n=13, n=7) | -26.8 milligrams per deciliter (mg/dL) |
| 10 mg LY2405319 | Change From Baseline to Day 28 in Fasting Lipid Profile | Cholesterol (n=10, n=8, n=13, n=8) | -32.5 milligrams per deciliter (mg/dL) |
| 20 mg LY2405319 | 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) |
| 20 mg LY2405319 | 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) |
| 20 mg LY2405319 | 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) |
| 20 mg LY2405319 | 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) |
| Placebo | Change From Baseline to Day 28 in Fasting Lipid Profile | LDL-C (n=10, n=8, n=13, n=7) | -0.8 milligrams per deciliter (mg/dL) |
| Placebo | Change From Baseline to Day 28 in Fasting Lipid Profile | Cholesterol (n=10, n=8, n=13, n=8) | -1.3 milligrams per deciliter (mg/dL) |
| Placebo | Change From Baseline to Day 28 in Fasting Lipid Profile | Triglycerides (n=10, n=8, n=13, n=8) | 6.8 milligrams per deciliter (mg/dL) |
| Placebo | Change From Baseline to Day 28 in Fasting Lipid Profile | HDL-C (n=10, n=8, n=13, n=8) | -0.8 milligrams per deciliter (mg/dL) |
Secondary
Change From Baseline to Day 28 in the Food Preference Questionnaire (FPQ) Score
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.
Time frame: Baseline, Day 28
Population: All participants who received at least 1 dose of study drug with evaluable FPQ data.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| 3 mg LY2405319 | Change From Baseline to Day 28 in the Food Preference Questionnaire (FPQ) Score | -0.06 units on a scale |
| 10 mg LY2405319 | Change From Baseline to Day 28 in the Food Preference Questionnaire (FPQ) Score | -0.43 units on a scale |
| 20 mg LY2405319 | Change From Baseline to Day 28 in the Food Preference Questionnaire (FPQ) Score | -0.77 units on a scale |
| Placebo | Change From Baseline to Day 28 in the Food Preference Questionnaire (FPQ) Score | 0.74 units on a scale |
Secondary
Change From Baseline to Day 28 in The Patient Health Questionnaire (PHQ-9) Score
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.
Time frame: Baseline, Day 28
Population: All participants who received at least 1 dose of study drug with evaluable PHQ-9 data.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| 3 mg LY2405319 | Change From Baseline to Day 28 in The Patient Health Questionnaire (PHQ-9) Score | 1.26 units on a scale |
| 10 mg LY2405319 | Change From Baseline to Day 28 in The Patient Health Questionnaire (PHQ-9) Score | -0.50 units on a scale |
| 20 mg LY2405319 | Change From Baseline to Day 28 in The Patient Health Questionnaire (PHQ-9) Score | 1.82 units on a scale |
| Placebo | Change From Baseline to Day 28 in The Patient Health Questionnaire (PHQ-9) Score | 2.57 units on a scale |
Secondary
Change From Baseline to Week 4 in C-peptide Area Under the Curve (AUC)
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.
Time frame: 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.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| 3 mg LY2405319 | Change From Baseline to Week 4 in C-peptide Area Under the Curve (AUC) | -0.61 nanograms*hours/milliliter (ng*hr/mL) |
| 10 mg LY2405319 | Change From Baseline to Week 4 in C-peptide Area Under the Curve (AUC) | 0.07 nanograms*hours/milliliter (ng*hr/mL) |
| 20 mg LY2405319 | Change From Baseline to Week 4 in C-peptide Area Under the Curve (AUC) | -1.39 nanograms*hours/milliliter (ng*hr/mL) |
| Placebo | Change From Baseline to Week 4 in C-peptide Area Under the Curve (AUC) | -1.59 nanograms*hours/milliliter (ng*hr/mL) |
Secondary
Change From Baseline to Week 4 in Glucose Area Under the Curve (AUC)
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.
Time frame: 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.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| 3 mg LY2405319 | Change From Baseline to Week 4 in Glucose Area Under the Curve (AUC) | 12.89 milligrams*hr per deciliter (mg*hr/dL) |
| 10 mg LY2405319 | Change From Baseline to Week 4 in Glucose Area Under the Curve (AUC) | -8.46 milligrams*hr per deciliter (mg*hr/dL) |
| 20 mg LY2405319 | Change From Baseline to Week 4 in Glucose Area Under the Curve (AUC) | -3.22 milligrams*hr per deciliter (mg*hr/dL) |
| Placebo | Change From Baseline to Week 4 in Glucose Area Under the Curve (AUC) | -28.13 milligrams*hr per deciliter (mg*hr/dL) |
Secondary
Change From Baseline to Week 4 in Insulin Area Under the Curve (AUC)
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.
Time frame: 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.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| 3 mg LY2405319 | Change From Baseline to Week 4 in Insulin Area Under the Curve (AUC) | -10.07 micro International units*hour/mL |
| 10 mg LY2405319 | Change From Baseline to Week 4 in Insulin Area Under the Curve (AUC) | -10.37 micro International units*hour/mL |
| 20 mg LY2405319 | Change From Baseline to Week 4 in Insulin Area Under the Curve (AUC) | -15.66 micro International units*hour/mL |
| Placebo | Change From Baseline to Week 4 in Insulin Area Under the Curve (AUC) | -17.98 micro International units*hour/mL |
Secondary
Pharmacokinetics: Area Under the Concentration Time Curve (AUC) of LY2405319
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.
Time frame: 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.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| 3 mg LY2405319 | Pharmacokinetics: Area Under the Concentration Time Curve (AUC) of LY2405319 | 409 nanograms*hours/milliliter (ng*hr/mL) | Geometric Coefficient of Variation 26 |
| 10 mg LY2405319 | Pharmacokinetics: Area Under the Concentration Time Curve (AUC) of LY2405319 | 1520 nanograms*hours/milliliter (ng*hr/mL) | Geometric Coefficient of Variation 38.9 |
| 20 mg LY2405319 | Pharmacokinetics: Area Under the Concentration Time Curve (AUC) of LY2405319 | 3410 nanograms*hours/milliliter (ng*hr/mL) | Geometric Coefficient of Variation 35.1 |
Secondary
Pharmacokinetics: Maximum Concentration (Cmax) of LY2405319
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.
Time frame: 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.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| 3 mg LY2405319 | Pharmacokinetics: Maximum Concentration (Cmax) of LY2405319 | 39.9 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 34.7 |
| 10 mg LY2405319 | Pharmacokinetics: Maximum Concentration (Cmax) of LY2405319 | 105 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 62.9 |
| 20 mg LY2405319 | Pharmacokinetics: Maximum Concentration (Cmax) of LY2405319 | 247 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 58.8 |
Secondary
The Number of Participants With Anti-LY2405319 Antibodies
The number of participants that tested positive for anti-LY2405319 antibodies is presented.
Time frame: Day 1 through Day 56
Population: All participants who received at least 1 dose of study drug with evaluable anti-LY2405319 antibody data.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| 3 mg LY2405319 | The Number of Participants With Anti-LY2405319 Antibodies | 6 number of participants |
| 10 mg LY2405319 | The Number of Participants With Anti-LY2405319 Antibodies | 8 number of participants |
| 20 mg LY2405319 | The Number of Participants With Anti-LY2405319 Antibodies | 13 number of participants |
| Placebo | The Number of Participants With Anti-LY2405319 Antibodies | 2 number of participants |