Diabetes Mellitus, Type 2
Conditions
Brief summary
The main purpose of this study is to determine the side effects related to LY3493269 in participants with type 2 diabetes. Blood tests will be performed to check concentrations of LY3493269 in the bloodstream. Each enrolled participant will receive LY3493269, dulaglutide, or placebo. The study will last up to approximately 16 weeks for each participant and may include up to 11 visits.
Interventions
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 70 Years
Healthy volunteers
No
Inclusion criteria
* Are male or female not of childbearing potential * Have a body mass index of 23 to 50 kilograms per square meter (kg/m²), inclusive, at screening * Have had a stable body weight (\<5% body weight change) for the 3 months prior to screening * Have not modified their diet or adopted any nutritional lifestyle modification in the 3 months prior to screening * Have type 2 diabetes mellitus (T2DM) controlled with diet and exercise alone or are on a stable dose of metformin for at least 3 months before screening. Patients with comorbid conditions commonly associated with diabetes (for example, hypertension, hypercholesterolemia, hypothyroidism) may be eligible for inclusion if conditions are assessed by the investigator to be well controlled and stable for at least 3 months prior to screening * Have an HbA1c of at least 7.0% and no more than 10.5% at screening * Have clinical laboratory test results within the normal range for the population or investigative site, or with abnormalities deemed not clinically significant by the investigator
Exclusion criteria
* Have type 1 diabetes mellitus or latent autoimmune diabetes in adults * Have uncontrolled diabetes, defined as an episode of ketoacidosis or hyperosmolar state requiring hospitalization in the 6 months prior to screening * Have a history of proliferative diabetic retinopathy, diabetic maculopathy, or severe nonproliferative diabetic retinopathy that requires acute treatment * Have had more than 1 episode of severe hypoglycemia, as defined by the American Diabetes Association criteria, within 6 months before screening or has a history of hypoglycemia unawareness or poor recognition of hypoglycemic symptoms. * Have a definitive diagnosis of autonomic neuropathy as evidenced by urinary retention, resting tachycardia, orthostatic hypotension, or diabetic diarrhea * Have a history of acute or chronic pancreatitis * Have a self or family history (first-degree relative) of multiple endocrine neoplasia type 2A or type 2B, thyroid C-cell hyperplasia, or medullary thyroid carcinoma * Have calcitonin levels of 20 picograms per millilitre (pg/mL) or more at screening
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With One or More Treatment-Emergent Adverse Event(s) (TEAEs) and Serious Adverse Event(s) (SAEs) Considered by the Investigator to be Related to Study Drug Administration | Baseline through final follow-up at Day 57 | TEAE is an untoward medical occurrence that emerges during a defined treatment period, having been absent pretreatment, or worsens relative to the pretreatment state, and does not necessarily have to have a causal relationship with this treatment. An SAE is defined as any untoward medical occurrence that, at any dose: 1. Results in death 2. Is life-threatening 3. Requires inpatient hospitalization or prolongation of existing hospitalization 4. Results in persistent disability/incapacity 5. Is a congenital anomaly/birth defect 6. Other situations: Based on medical or scientific judgement. A summary of SAEs, TEAEs and other non-serious adverse events (AEs), regardless of causality, will be reported in the Reported Adverse Events module |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Pharmacokinetics (PK): Area Under the Concentration Versus Time Curve From Time Zero to 168 Hours Postdose AUC(0-168) of LY3493269 | Predose, 6, 12, 24, 48, 72, 96 and 168 h postdose at Weeks 1 and 4. | Area Under the Concentration Versus Time Curve from Time Zero to 168 Hours Postdose AUC(0-168) of LY3493269 |
| PK: Maximum Observed Drug Concentration (Cmax) of LY3493269 | Predose, 6, 12, 24, 48, 72, 96 and 168 h postdose at Weeks 1 and 4. | Maximum Observed Drug Concentration (Cmax) of LY3493269 |
| Pharmacodynamics (PD):Change From Baseline to Day 29 in Fasting Plasma Glucose | Baseline, Day 29 | Pharmacodynamics (PD): Summary Statistics (Mean, Standard Deviation) of Change From Baseline to Day 29. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Placebo Participants received placebo subcutaneously (SC) once weekly (QW) for 4 weeks. | 7 |
| 1.5 mg Dulaglutide Participants received 1.5 mg dulaglutide SC QW for 4 weeks. | 8 |
| 0.3 mg LY3493269 Participants received 4 fixed dosed of 0.3 mg LY3493269 SC QW for 4 weeks. | 8 |
| 1 mg LY3493269 Participants received 4 fixed dosed of 1 mg LY3493269 SC QW for 4 weeks | 8 |
| 0.75/1.5/3 mg LY3493269 Participants received LY3493269 0.75 mg on week 1, 1.5 mg on week 2 and 3 mg on week 3 and 4 SC as weekly doses. | 11 |
| 1.5/3/4/5 mg LY3493269 Participants received LY3493269 1.5 mg on week 1, 3 mg on week 2, 4 mg on week 3 and 5 mg on week 4 as weekly doses. | 14 |
| Total | 56 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 |
|---|---|---|---|---|---|---|---|
| Overall Study | Withdrawal by Subject | 0 | 0 | 0 | 0 | 0 | 1 |
Baseline characteristics
| Characteristic | Placebo | 1.5 mg Dulaglutide | 0.3 mg LY3493269 | 1 mg LY3493269 | 0.75/1.5/3 mg LY3493269 | 1.5/3/4/5 mg LY3493269 | Total |
|---|---|---|---|---|---|---|---|
| Age, Continuous | 56.9 years STANDARD_DEVIATION 6.7 | 63.3 years STANDARD_DEVIATION 6.6 | 60.9 years STANDARD_DEVIATION 5.6 | 59.8 years STANDARD_DEVIATION 3.4 | 55.1 years STANDARD_DEVIATION 5.3 | 59.9 years STANDARD_DEVIATION 6.9 | 59.2 years STANDARD_DEVIATION 6.3 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 7 Participants | 4 Participants | 5 Participants | 8 Participants | 9 Participants | 13 Participants | 46 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 0 Participants | 4 Participants | 3 Participants | 0 Participants | 2 Participants | 1 Participants | 10 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 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 | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 1 Participants | 1 Participants | 0 Participants | 1 Participants | 1 Participants | 4 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 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 | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 7 Participants | 7 Participants | 5 Participants | 8 Participants | 10 Participants | 13 Participants | 50 Participants |
| Region of Enrollment United States | 7 Participants | 8 Participants | 8 Participants | 8 Participants | 11 Participants | 14 Participants | 56 Participants |
| Sex: Female, Male Female | 4 Participants | 3 Participants | 2 Participants | 4 Participants | 6 Participants | 6 Participants | 25 Participants |
| Sex: Female, Male Male | 3 Participants | 5 Participants | 6 Participants | 4 Participants | 5 Participants | 8 Participants | 31 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk |
|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 7 | 0 / 8 | 0 / 8 | 0 / 8 | 0 / 11 | 0 / 14 |
| other Total, other adverse events | 2 / 7 | 5 / 8 | 5 / 8 | 7 / 8 | 11 / 11 | 13 / 14 |
| serious Total, serious adverse events | 0 / 7 | 0 / 8 | 0 / 8 | 0 / 8 | 0 / 11 | 0 / 14 |
Outcome results
Primary
Number of Participants With One or More Treatment-Emergent Adverse Event(s) (TEAEs) and Serious Adverse Event(s) (SAEs) Considered by the Investigator to be Related to Study Drug Administration
TEAE is an untoward medical occurrence that emerges during a defined treatment period, having been absent pretreatment, or worsens relative to the pretreatment state, and does not necessarily have to have a causal relationship with this treatment. An SAE is defined as any untoward medical occurrence that, at any dose: 1. Results in death 2. Is life-threatening 3. Requires inpatient hospitalization or prolongation of existing hospitalization 4. Results in persistent disability/incapacity 5. Is a congenital anomaly/birth defect 6. Other situations: Based on medical or scientific judgement. A summary of SAEs, TEAEs and other non-serious adverse events (AEs), regardless of causality, will be reported in the Reported Adverse Events module
Time frame: Baseline through final follow-up at Day 57
Population: All participants who received at least one dose of study drug.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Placebo | Number of Participants With One or More Treatment-Emergent Adverse Event(s) (TEAEs) and Serious Adverse Event(s) (SAEs) Considered by the Investigator to be Related to Study Drug Administration | TEAEs Related to Study Drug Administration | 2 Participants |
| Placebo | Number of Participants With One or More Treatment-Emergent Adverse Event(s) (TEAEs) and Serious Adverse Event(s) (SAEs) Considered by the Investigator to be Related to Study Drug Administration | SAEs Related to Study Drug Administration | 0 Participants |
| 1.5 mg Dulaglutide | Number of Participants With One or More Treatment-Emergent Adverse Event(s) (TEAEs) and Serious Adverse Event(s) (SAEs) Considered by the Investigator to be Related to Study Drug Administration | SAEs Related to Study Drug Administration | 0 Participants |
| 1.5 mg Dulaglutide | Number of Participants With One or More Treatment-Emergent Adverse Event(s) (TEAEs) and Serious Adverse Event(s) (SAEs) Considered by the Investigator to be Related to Study Drug Administration | TEAEs Related to Study Drug Administration | 5 Participants |
| 0.3 mg LY3493269 | Number of Participants With One or More Treatment-Emergent Adverse Event(s) (TEAEs) and Serious Adverse Event(s) (SAEs) Considered by the Investigator to be Related to Study Drug Administration | SAEs Related to Study Drug Administration | 0 Participants |
| 0.3 mg LY3493269 | Number of Participants With One or More Treatment-Emergent Adverse Event(s) (TEAEs) and Serious Adverse Event(s) (SAEs) Considered by the Investigator to be Related to Study Drug Administration | TEAEs Related to Study Drug Administration | 3 Participants |
| 1 mg LY3493269 | Number of Participants With One or More Treatment-Emergent Adverse Event(s) (TEAEs) and Serious Adverse Event(s) (SAEs) Considered by the Investigator to be Related to Study Drug Administration | SAEs Related to Study Drug Administration | 0 Participants |
| 1 mg LY3493269 | Number of Participants With One or More Treatment-Emergent Adverse Event(s) (TEAEs) and Serious Adverse Event(s) (SAEs) Considered by the Investigator to be Related to Study Drug Administration | TEAEs Related to Study Drug Administration | 7 Participants |
| 0.75/1.5/3 mg LY3493269 | Number of Participants With One or More Treatment-Emergent Adverse Event(s) (TEAEs) and Serious Adverse Event(s) (SAEs) Considered by the Investigator to be Related to Study Drug Administration | SAEs Related to Study Drug Administration | 0 Participants |
| 0.75/1.5/3 mg LY3493269 | Number of Participants With One or More Treatment-Emergent Adverse Event(s) (TEAEs) and Serious Adverse Event(s) (SAEs) Considered by the Investigator to be Related to Study Drug Administration | TEAEs Related to Study Drug Administration | 10 Participants |
| 1.5/3/4/5 mg LY3493269 | Number of Participants With One or More Treatment-Emergent Adverse Event(s) (TEAEs) and Serious Adverse Event(s) (SAEs) Considered by the Investigator to be Related to Study Drug Administration | TEAEs Related to Study Drug Administration | 13 Participants |
| 1.5/3/4/5 mg LY3493269 | Number of Participants With One or More Treatment-Emergent Adverse Event(s) (TEAEs) and Serious Adverse Event(s) (SAEs) Considered by the Investigator to be Related to Study Drug Administration | SAEs Related to Study Drug Administration | 0 Participants |
Secondary
Pharmacodynamics (PD):Change From Baseline to Day 29 in Fasting Plasma Glucose
Pharmacodynamics (PD): Summary Statistics (Mean, Standard Deviation) of Change From Baseline to Day 29.
Time frame: Baseline, Day 29
Population: All participants who received at least one dose of study drug and had evaluable fasting plasma glucose data.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Pharmacodynamics (PD):Change From Baseline to Day 29 in Fasting Plasma Glucose | -1.07 millimoles per litre (mmol/L) | Standard Deviation 2.34 |
| 1.5 mg Dulaglutide | Pharmacodynamics (PD):Change From Baseline to Day 29 in Fasting Plasma Glucose | -4.11 millimoles per litre (mmol/L) | Standard Deviation 2.82 |
| 0.3 mg LY3493269 | Pharmacodynamics (PD):Change From Baseline to Day 29 in Fasting Plasma Glucose | -2.20 millimoles per litre (mmol/L) | Standard Deviation 1.47 |
| 1 mg LY3493269 | Pharmacodynamics (PD):Change From Baseline to Day 29 in Fasting Plasma Glucose | -4.83 millimoles per litre (mmol/L) | Standard Deviation 2.75 |
| 0.75/1.5/3 mg LY3493269 | Pharmacodynamics (PD):Change From Baseline to Day 29 in Fasting Plasma Glucose | -3.61 millimoles per litre (mmol/L) | Standard Deviation 3.29 |
| 1.5/3/4/5 mg LY3493269 | Pharmacodynamics (PD):Change From Baseline to Day 29 in Fasting Plasma Glucose | -3.98 millimoles per litre (mmol/L) | Standard Deviation 3.11 |
Secondary
Pharmacokinetics (PK): Area Under the Concentration Versus Time Curve From Time Zero to 168 Hours Postdose AUC(0-168) of LY3493269
Area Under the Concentration Versus Time Curve from Time Zero to 168 Hours Postdose AUC(0-168) of LY3493269
Time frame: Predose, 6, 12, 24, 48, 72, 96 and 168 h postdose at Weeks 1 and 4.
Population: All participants who received at least one dose of LY3493269 and had evaluable PK data.
| Arm | Measure | Group | Value (GEOMETRIC_LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Pharmacokinetics (PK): Area Under the Concentration Versus Time Curve From Time Zero to 168 Hours Postdose AUC(0-168) of LY3493269 | Week 1 | 4220 nanogram*hour per milliliter (ng*h/mL) | Geometric Coefficient of Variation 27 |
| Placebo | Pharmacokinetics (PK): Area Under the Concentration Versus Time Curve From Time Zero to 168 Hours Postdose AUC(0-168) of LY3493269 | Week 4 | 10600 nanogram*hour per milliliter (ng*h/mL) | Geometric Coefficient of Variation 21 |
| 1.5 mg Dulaglutide | Pharmacokinetics (PK): Area Under the Concentration Versus Time Curve From Time Zero to 168 Hours Postdose AUC(0-168) of LY3493269 | Week 4 | 38500 nanogram*hour per milliliter (ng*h/mL) | Geometric Coefficient of Variation 25 |
| 1.5 mg Dulaglutide | Pharmacokinetics (PK): Area Under the Concentration Versus Time Curve From Time Zero to 168 Hours Postdose AUC(0-168) of LY3493269 | Week 1 | 18500 nanogram*hour per milliliter (ng*h/mL) | Geometric Coefficient of Variation 40 |
| 0.3 mg LY3493269 | Pharmacokinetics (PK): Area Under the Concentration Versus Time Curve From Time Zero to 168 Hours Postdose AUC(0-168) of LY3493269 | Week 1 | 10200 nanogram*hour per milliliter (ng*h/mL) | Geometric Coefficient of Variation 30 |
| 0.3 mg LY3493269 | Pharmacokinetics (PK): Area Under the Concentration Versus Time Curve From Time Zero to 168 Hours Postdose AUC(0-168) of LY3493269 | Week 4 | 105000 nanogram*hour per milliliter (ng*h/mL) | Geometric Coefficient of Variation 27 |
| 1 mg LY3493269 | Pharmacokinetics (PK): Area Under the Concentration Versus Time Curve From Time Zero to 168 Hours Postdose AUC(0-168) of LY3493269 | Week 1 | 22800 nanogram*hour per milliliter (ng*h/mL) | Geometric Coefficient of Variation 25 |
| 1 mg LY3493269 | Pharmacokinetics (PK): Area Under the Concentration Versus Time Curve From Time Zero to 168 Hours Postdose AUC(0-168) of LY3493269 | Week 4 | 123000 nanogram*hour per milliliter (ng*h/mL) | Geometric Coefficient of Variation 22 |
Secondary
PK: Maximum Observed Drug Concentration (Cmax) of LY3493269
Maximum Observed Drug Concentration (Cmax) of LY3493269
Time frame: Predose, 6, 12, 24, 48, 72, 96 and 168 h postdose at Weeks 1 and 4.
Population: All participants who received at least one dose of LY3493269 and had evaluable PK data.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | PK: Maximum Observed Drug Concentration (Cmax) of LY3493269 | Week 1 | 31.2 nanogram per milliliter (ng/mL) | Geometric Coefficient of Variation 31 |
| Placebo | PK: Maximum Observed Drug Concentration (Cmax) of LY3493269 | Week 4 | 80.3 nanogram per milliliter (ng/mL) | Geometric Coefficient of Variation 22 |
| 1.5 mg Dulaglutide | PK: Maximum Observed Drug Concentration (Cmax) of LY3493269 | Week 4 | 287 nanogram per milliliter (ng/mL) | Geometric Coefficient of Variation 26 |
| 1.5 mg Dulaglutide | PK: Maximum Observed Drug Concentration (Cmax) of LY3493269 | Week 1 | 153 nanogram per milliliter (ng/mL) | Geometric Coefficient of Variation 51 |
| 0.3 mg LY3493269 | PK: Maximum Observed Drug Concentration (Cmax) of LY3493269 | Week 1 | 73.6 nanogram per milliliter (ng/mL) | Geometric Coefficient of Variation 32 |
| 0.3 mg LY3493269 | PK: Maximum Observed Drug Concentration (Cmax) of LY3493269 | Week 4 | 818 nanogram per milliliter (ng/mL) | Geometric Coefficient of Variation 28 |
| 1 mg LY3493269 | PK: Maximum Observed Drug Concentration (Cmax) of LY3493269 | Week 1 | 165 nanogram per milliliter (ng/mL) | Geometric Coefficient of Variation 34 |
| 1 mg LY3493269 | PK: Maximum Observed Drug Concentration (Cmax) of LY3493269 | Week 4 | 920 nanogram per milliliter (ng/mL) | Geometric Coefficient of Variation 28 |