Diabetes Mellitus, Type 2
Conditions
Brief summary
The primary purpose of this Study is to help answer the following research question(s). * How does LY2189265 affect gastric emptying (the speed at which food and drink leaves the stomach) in patients with Type 2 diabetes? * How does LY2189265 affect how the body handles metformin (a drug used to treat Type 2 diabetes)? * Is LY2189265 safe and are any side effects associated with it? The study will be participant-blind in Week 1, and participant- and investigator-blind from Week 2 through Week 5. Each participant will receive placebo on Week 1 and once-weekly doses of LY2189265 or Placebo on Weeks 2 to 5. Participants taking metformin for the treatment of Type 2 Diabetes Mellitus (T2DM) will continue taking metformin as part of the study.
Interventions
BIOLOGICALLY2189265
1.5 mg administered subcutaneously
DRUGPlacebo
Administered subcutaneously
Sponsors
Eli Lilly and Company
Study design
Allocation
RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
1. Are males or females, diagnosed with Type 2 Diabetes Mellitus for greater than or equal to 3 months prior to screening. 2. Male patients agree to use a reliable method of birth control during the study and for 3 months following the last dose of study drug. Female patients must be of non-child-bearing potential due to surgical sterilization or menopause. 3. Have a body mass index (BMI) between 18.5 and 40.0 kilogram/square meter (kg/m²), inclusive. 4. Have Type 2 Diabetes Mellitus controlled with diet and exercise alone or are stable on a single oral antidiabetic medication (e.g. metformin) prior to screening, and have been taking a stable dose for \>7 days prior to the first dosing occasion. 5. Have a fasting blood glucose value at screening \>126 milligram/deciliter (mg/dL) (7.0 \[millimoles/liter\] mmol/L) for patients on a controlled diet, and \>108 mg/dL (6.0 mmol/L) for patients on oral antidiabetic medication, with an upper limit of 180 mg/dL (approximately 9.9 mmol/L) in each case. 6. Have a hemoglobin A1c (HbA1c) (indicates what your average blood glucose level has been in the past 3 months) value at screening (or within 4 weeks prior to screening) of 6.5% to 9.5%. If HbA1c is between 6.1% and 6.5%, patients may participate in the study providing they are receiving permissible oral antidiabetic medication. 7. Have clinical laboratory test results within normal ranges as determined by the study doctor. 8. Can provide enough blood in order to undergo the blood sampling required for the study. 9. Are reliable and willing to make themselves available for the duration of the study and are willing to follow study procedures. 10. Have signed the consent form approved by Lilly and the Ethical Review Board (ERB) governing the site.
Exclusion criteria
11. Are currently enrolled in, or discontinued within the last 30 days from, a clinical trial involving an investigational drug or device, or are concurrently enrolled in any other type of medical research judged not to be scientifically or medically compatible with this study. 12. Have previously been exposed to, or have known allergies to glucagon-like-peptide-1 (GLP-1)-related compounds including LY2189265. 13. Are persons who have previously completed or withdrawn from this study or any other study investigating LY2189265 or have received glucagon-like peptides or incretin mimetics in the past 3 months. 14. Have taken certain Type 2 Diabetes medications within 30 days prior to screening. 15. Have an abnormality in the electrocardiogram (ECG) performed at screening. 16. Have poorly controlled high blood pressure (systolic blood pressure \>160 millimeters of mercury \[mmHg\] and/or diastolic blood pressure \>100 mmHg). 17. Have a history or presence of respiratory, liver, kidney, hormonal, blood, or neurological disorders which may put the patient at risk when taking the study medication; or may interfere with the interpretation of data. 18. Have a history or presence of cardiovascular disorder within the last year, or signs of congestive heart failure, or are expected to require coronary artery bypass surgery or angioplasty. 19. Have a history or presence of pancreatitis or certain gastrointestinal disorders. 20. Have been exposed to radiation from clinical trials and from diagnostic X-ray or are exposed routinely via your job worker. 21. Have any non-removable metal objects such as metal plates, screws etc. in their chest or abdominal area. 22. Have had acute diarrhea or constipation within 14 days of study screening. 23. Show evidence of significant active neuropsychiatric disease. 24. Regularly use known drugs of abuse and/or show positive findings on urinary drug screening. 25. Intend to start new medication during the study, including over-the-counter and herbal medication. 26. Have donated blood of more than 500 milliliter (mL) within the last month prior to screening. 27. Have an average weekly alcohol intake that exceeds the study centre's guidelines and are unwilling to adhere to the alcohol restrictions in place throughout the study. 28. Smoke more than 10 cigarettes (or equivalent in nicotine) per day, and are unwilling to stop smoking on the day of medication administration or are unable to abide by clinical research unit (CRU) restrictions on other inpatient days. 29. Are allergic to eggs or other components of the meals to be served. 30. Are patients who, in the opinion of the investigator, are in any way unsuitable to participate in the study.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Time Required for 50% of Radioactivity To Be Emptied From the Stomach by Scintigraphy | Days 3, 10,17, 24 and 31 | After at least 8 hours fasting, participants received a radiolabeled breakfast containing technetium-99m-tin colloid (99mTc-tin colloid). After which serial anterior and posterior scintigraphy images were taken. Data presented are the time required for 50% of radioactivity to be emptied from stomach. The results presented are Geometric Least Squares (LS) Mean. LS Mean values were controlled for weeks. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Area Under the Curve (AUC) of Metformin | Days 3, 17 and 31 | Metformin was used as a secondary marker in the study to correlate the effect of LY2189265 on gastric emptying to the pharmacokinetics (PK) (measured as AUC) of concomitant medications. Participants taking metformin for treatment of Type 2 Diabetes Mellitus (T2DM) underwent PK assessments for metformin in parallel to their scintigraphy assessments for gastric emptying. AUC of metformin was calculated during one dosing interval. |
| Maximum Concentration (Cmax) of Metformin | Days 3, 17 and 31 | Metformin was used as a secondary marker in the study to correlate the effect of LY2189265 on gastric emptying to the pharmacokinetics (PK) (measured as Cmax) of concomitant medications. Participants taking metformin for treatment of Type 2 Diabetes Mellitus (T2DM) underwent PK assessments for metformin in parallel to their scintigraphy assessments for gastric emptying. |
| Time to Maximum Concentration (Tmax) of Metformin | Days 3, 17 and 31 | Metformin was used as a secondary marker in the study to correlate the effect of LY2189265 on gastric emptying to the pharmacokinetics (PK) (measured as Tmax) of concomitant medications. Participants taking metformin for treatment of Type 2 Diabetes Mellitus (T2DM) underwent PK assessments for metformin in parallel to their scintigraphy assessments for gastric emptying. |
| Number of Participants With Clinically Significant Effects | Baseline through 5 weeks | Adverse events (AEs) were considered clinically significant effects. A summary of serious adverse events (SAEs) and other nonserious AEs are located in the Reported Adverse Event section. |
Countries
United Kingdom
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Placebo Participants received placebo on Week 1 and once-weekly doses of placebo on Weeks 2 to 5. | 13 |
| LY2189265 Participants received placebo on Week 1 and once-weekly doses of 1.5 milligram (mg) LY2189265 on Weeks 2 to 5. | 25 |
| Total | 38 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 0 | 2 |
| Overall Study | Not received study drug | 0 | 1 |
| Overall Study | Protocol Violation | 2 | 4 |
Baseline characteristics
| Characteristic | LY2189265 | Total | Placebo |
|---|---|---|---|
| Age, Continuous | 58.9 years STANDARD_DEVIATION 9.8 | 56.5 years STANDARD_DEVIATION 11.7 | 52.0 years STANDARD_DEVIATION 14 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 25 Participants | 38 Participants | 13 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants | 4 Participants | 3 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 24 Participants | 34 Participants | 10 Participants |
| Region of Enrollment United Kingdom | 25 participants | 38 participants | 13 participants |
| Sex: Female, Male Female | 5 Participants | 7 Participants | 2 Participants |
| Sex: Female, Male Male | 20 Participants | 31 Participants | 11 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 7 / 13 | 11 / 25 | 20 / 24 |
| serious Total, serious adverse events | 0 / 13 | 0 / 25 | 0 / 24 |
Outcome results
Primary
Time Required for 50% of Radioactivity To Be Emptied From the Stomach by Scintigraphy
After at least 8 hours fasting, participants received a radiolabeled breakfast containing technetium-99m-tin colloid (99mTc-tin colloid). After which serial anterior and posterior scintigraphy images were taken. Data presented are the time required for 50% of radioactivity to be emptied from stomach. The results presented are Geometric Least Squares (LS) Mean. LS Mean values were controlled for weeks.
Time frame: Days 3, 10,17, 24 and 31
Population: All randomized participants who received study drug, a radiolabeled breakfast, and had scintigraphy images taken. Those who violated protocol were excluded.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| Placebo | Time Required for 50% of Radioactivity To Be Emptied From the Stomach by Scintigraphy | Day 10 | 1.41 hours |
| Placebo | Time Required for 50% of Radioactivity To Be Emptied From the Stomach by Scintigraphy | Day 24 (n=9, 14) | 1.47 hours |
| Placebo | Time Required for 50% of Radioactivity To Be Emptied From the Stomach by Scintigraphy | Day 17 (n=9, 14) | 1.60 hours |
| Placebo | Time Required for 50% of Radioactivity To Be Emptied From the Stomach by Scintigraphy | Day 31 (n=10, 13) | 1.46 hours |
| Placebo | Time Required for 50% of Radioactivity To Be Emptied From the Stomach by Scintigraphy | Day 3 | 1.44 hours |
| LY2189265 | Time Required for 50% of Radioactivity To Be Emptied From the Stomach by Scintigraphy | Day 31 (n=10, 13) | 3.15 hours |
| LY2189265 | Time Required for 50% of Radioactivity To Be Emptied From the Stomach by Scintigraphy | Day 3 | 1.72 hours |
| LY2189265 | Time Required for 50% of Radioactivity To Be Emptied From the Stomach by Scintigraphy | Day 10 | 3.77 hours |
| LY2189265 | Time Required for 50% of Radioactivity To Be Emptied From the Stomach by Scintigraphy | Day 17 (n=9, 14) | 3.32 hours |
| LY2189265 | Time Required for 50% of Radioactivity To Be Emptied From the Stomach by Scintigraphy | Day 24 (n=9, 14) | 3.28 hours |
90% CI: [1.83, 2.62]Mixed Linear effects model analyses
90% CI: [1.61, 2.33]Mixed Linear effects model analyses
90% CI: [1.59, 2.29]Mixed Linear effects model analyses
90% CI: [1.52, 2.22]Mixed Linear effects model analyses
Secondary
Area Under the Curve (AUC) of Metformin
Metformin was used as a secondary marker in the study to correlate the effect of LY2189265 on gastric emptying to the pharmacokinetics (PK) (measured as AUC) of concomitant medications. Participants taking metformin for treatment of Type 2 Diabetes Mellitus (T2DM) underwent PK assessments for metformin in parallel to their scintigraphy assessments for gastric emptying. AUC of metformin was calculated during one dosing interval.
Time frame: Days 3, 17 and 31
Population: All randomized participants who received both study drug and immediate release metformin, and had PK data. Those who violated protocol were excluded.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Area Under the Curve (AUC) of Metformin | Day 17 | 14600 nanograms*hour/milliliter (ng*h/mL) | Geometric Coefficient of Variation 47 |
| Placebo | Area Under the Curve (AUC) of Metformin | Day 31 (n=6, 11) | 14600 nanograms*hour/milliliter (ng*h/mL) | Geometric Coefficient of Variation 47 |
| Placebo | Area Under the Curve (AUC) of Metformin | Day 3 | 13600 nanograms*hour/milliliter (ng*h/mL) | Geometric Coefficient of Variation 49 |
| LY2189265 | Area Under the Curve (AUC) of Metformin | Day 17 | 15300 nanograms*hour/milliliter (ng*h/mL) | Geometric Coefficient of Variation 43 |
| LY2189265 | Area Under the Curve (AUC) of Metformin | Day 31 (n=6, 11) | 15800 nanograms*hour/milliliter (ng*h/mL) | Geometric Coefficient of Variation 43 |
| LY2189265 | Area Under the Curve (AUC) of Metformin | Day 3 | 13700 nanograms*hour/milliliter (ng*h/mL) | Geometric Coefficient of Variation 40 |
Secondary
Maximum Concentration (Cmax) of Metformin
Metformin was used as a secondary marker in the study to correlate the effect of LY2189265 on gastric emptying to the pharmacokinetics (PK) (measured as Cmax) of concomitant medications. Participants taking metformin for treatment of Type 2 Diabetes Mellitus (T2DM) underwent PK assessments for metformin in parallel to their scintigraphy assessments for gastric emptying.
Time frame: Days 3, 17 and 31
Population: All randomized participants who received both study drug and immediate release metformin, and had pharmacokinetic (PK) data. Those who violated protocol were excluded.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Maximum Concentration (Cmax) of Metformin | Day 3 | 1610 nanograms/milliliter (ng/mL) | Geometric Coefficient of Variation 48 |
| Placebo | Maximum Concentration (Cmax) of Metformin | Day 17 | 1690 nanograms/milliliter (ng/mL) | Geometric Coefficient of Variation 48 |
| Placebo | Maximum Concentration (Cmax) of Metformin | Day 31 (n=6, 11) | 1770 nanograms/milliliter (ng/mL) | Geometric Coefficient of Variation 46 |
| LY2189265 | Maximum Concentration (Cmax) of Metformin | Day 3 | 1690 nanograms/milliliter (ng/mL) | Geometric Coefficient of Variation 47 |
| LY2189265 | Maximum Concentration (Cmax) of Metformin | Day 17 | 1500 nanograms/milliliter (ng/mL) | Geometric Coefficient of Variation 53 |
| LY2189265 | Maximum Concentration (Cmax) of Metformin | Day 31 (n=6, 11) | 1680 nanograms/milliliter (ng/mL) | Geometric Coefficient of Variation 44 |
Secondary
Number of Participants With Clinically Significant Effects
Adverse events (AEs) were considered clinically significant effects. A summary of serious adverse events (SAEs) and other nonserious AEs are located in the Reported Adverse Event section.
Time frame: Baseline through 5 weeks
Population: All enrolled participants who received at least one dose of study drug.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo | Number of Participants With Clinically Significant Effects | SAEs | 0 participants |
| Placebo | Number of Participants With Clinically Significant Effects | Other nonserious AEs | 7 participants |
| LY2189265 | Number of Participants With Clinically Significant Effects | SAEs | 0 participants |
| LY2189265 | Number of Participants With Clinically Significant Effects | Other nonserious AEs | 11 participants |
| LY2189265 | Number of Participants With Clinically Significant Effects | SAEs | 0 participants |
| LY2189265 | Number of Participants With Clinically Significant Effects | Other nonserious AEs | 20 participants |
Secondary
Time to Maximum Concentration (Tmax) of Metformin
Metformin was used as a secondary marker in the study to correlate the effect of LY2189265 on gastric emptying to the pharmacokinetics (PK) (measured as Tmax) of concomitant medications. Participants taking metformin for treatment of Type 2 Diabetes Mellitus (T2DM) underwent PK assessments for metformin in parallel to their scintigraphy assessments for gastric emptying.
Time frame: Days 3, 17 and 31
Population: All randomized participants who received both study drug and immediate release metformin, and had pharmacokinetic (PK) data. Those who violated protocol were excluded.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Placebo | Time to Maximum Concentration (Tmax) of Metformin | Day 3 | 1.00 hour |
| Placebo | Time to Maximum Concentration (Tmax) of Metformin | Day 17 | 2.02 hour |
| Placebo | Time to Maximum Concentration (Tmax) of Metformin | Day 31 (n=6, 11) | 1.53 hour |
| LY2189265 | Time to Maximum Concentration (Tmax) of Metformin | Day 3 | 2.02 hour |
| LY2189265 | Time to Maximum Concentration (Tmax) of Metformin | Day 17 | 2.05 hour |
| LY2189265 | Time to Maximum Concentration (Tmax) of Metformin | Day 31 (n=6, 11) | 2.02 hour |