Type 2 Diabetes Mellitus
Conditions
Brief summary
The purposes of this study are to determine: * The safety of tirzepatide and any side effects that might be associated with it. * How much tirzepatide gets into the bloodstream and how long it takes the body to remove it. * How tirzepatide affects the levels of blood sugar. This study includes eight weekly doses of tirzepatide or placebo given as subcutaneous (SC) injections just under the skin. The study will last about 16 weeks (total), including screening and follow-up. This study is for research purposes only and is not intended to treat any medical conditions.
Interventions
DRUGTirzepatide
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
20 Years to 70 Years
Healthy volunteers
No
Inclusion criteria
* Have T2DM controlled with diet and exercise alone or are stable on a single oral antidiabetic medication (metformin or dipeptidyl peptidase \[DPP\]-IV inhibitors) * Have a body mass index of 20.0 to 35.0 kilograms per square meter, inclusive
Exclusion criteria
* Have known allergies to tirzepatide, glucagon-like peptide (GLP)-1 analogs, or related compounds * Have had more than 1 episode of severe hypoglycemia, as defined by the American Diabetes Association criteria, within 6 months before entry into the study or has a history of hypoglycemia unawareness or poor recognition of hypoglycemic symptoms * Have an abnormality in the 12-lead electrocardiogram at screening that, in the opinion of the investigator, increases the risks associated with participating in the study * Have a history or presence of pancreatitis or gastrointestinal (GI) disorder or any GI disease which impacts gastric emptying or could be aggravated by GLP-1 analogs or DPP-IV inhibitors
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 85 | Safety was assessed from time of consent through end of study (up to 85 days). Data presented are the number of participants who experienced 1 or more SAEs considered by the investigator to be related to study drug. A summary of SAEs and other non-serious AEs, regardless of causality is located in the Reported Adverse Events section of this record. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Pharmacokinetics (PK): Maximum Observed Concentration (Cmax) of Tirzepatide | Predose, 8, 24, 48, 72 and 168 hours post dose for Day 1 administration, and Predose, 8, 24, 48, and 168 hours post dose for Day 50 administration | Pharmacokinetics (PK): Maximum observed drug concentration (Cmax) of Tirzepatide in plasma. |
| PK: Area Under the Concentration Versus Time Curve (AUC) of Tirzepatide | Predose, 8, 24, 48, 72 and 168 hours post dose for Day 1 administration, and Predose, 8, 24, 48, and 168 hours post dose for Day 50 administration | Area under the concentration versus time curve from time zero to tau (τ) of Tirzepatide (AUC\[0- τ\]), where tau is dosing interval of (0-168 hours). |
| Pharmacodynamics (PD): Change From Baseline to 8 Weeks in Fasting Plasma Glucose | Baseline, Week 8 | Change from baseline to 8 weeks in Fasting Plasma Glucose was measured to investigate the PD effect of Tirzepatide after multiple SC doses administered to Japanese patients with T2DM |
Countries
Japan
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Placebo Participants received placebo administered into the subcutaneous (SC) tissue of the abdominal wall. | 9 |
| 2.5 mg/5 mg/10 mg Tirzepatide (Cohort 1) Participants received tirzepatide with titration regimen starting from 2.5 mg (milligrams) for Days 1 and 8 followed by 5 mg for Days 15 and 22, and 10 mg for Days 29, 36, 43, and 50 administered into the SC tissue of the abdominal wall. | 12 |
| 5 mg/10 mg/15 mg Tirzepatide (Cohort 2) Participants received tirzepatide with titration regimen starting from 5 mg for Days 1 and 8 followed by 10 mg for Days 15, 22, 29, and 36, and 15 mg for Days 43 and 50 administered into the SC tissue of the abdominal wall. | 16 |
| 5 mg Tirzepatide (Cohort 3) Participants received 5 mg tirzepatide administered into the SC tissue of the abdominal wall. | 11 |
| Total | 48 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Overall Study | Adverse Event | 0 | 0 | 1 | 0 |
| Overall Study | Withdrawal by Subject | 0 | 1 | 0 | 0 |
Baseline characteristics
| Characteristic | 5 mg Tirzepatide (Cohort 3) | Total | Placebo | 2.5 mg/5 mg/10 mg Tirzepatide (Cohort 1) | 5 mg/10 mg/15 mg Tirzepatide (Cohort 2) |
|---|---|---|---|---|---|
| Age, Continuous | 57.5 Years STANDARD_DEVIATION 7.9 | 57.4 Years STANDARD_DEVIATION 8.8 | 57.4 Years STANDARD_DEVIATION 11.6 | 56.9 Years STANDARD_DEVIATION 9.5 | 57.7 Years STANDARD_DEVIATION 8 |
| Body Mass Index (BMI) | 26.68 kg/m² STANDARD_DEVIATION 3.29 | 25.42 kg/m² STANDARD_DEVIATION 3.16 | 22.58 kg/m² STANDARD_DEVIATION 2.09 | 25.49 kg/m² STANDARD_DEVIATION 2.75 | 26.10 kg/m² STANDARD_DEVIATION 3.11 |
| 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 | 48 Participants | 9 Participants | 12 Participants | 16 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 | 11 Participants | 48 Participants | 9 Participants | 12 Participants | 16 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants | 0 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 | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Region of Enrollment Japan | 11 Participants | 48 Participants | 9 Participants | 12 Participants | 16 Participants |
| Sex: Female, Male Female | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 1 Participants |
| Sex: Female, Male Male | 11 Participants | 47 Participants | 9 Participants | 12 Participants | 15 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 | 0 / 9 | 0 / 12 | 0 / 16 | 0 / 11 |
| other Total, other adverse events | 4 / 9 | 11 / 12 | 15 / 16 | 6 / 11 |
| serious Total, serious adverse events | 0 / 9 | 0 / 12 | 0 / 16 | 0 / 11 |
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
Safety was assessed from time of consent through end of study (up to 85 days). Data presented are the number of participants who experienced 1 or more SAEs considered by the investigator to be related to study drug. A summary of SAEs and other non-serious AEs, regardless of causality is located in the Reported Adverse Events section of this record.
Time frame: Baseline through Day 85
Population: All randomized participants who received at least one dose of study drug.
| Arm | Measure | Value (COUNT_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 Participants |
| 2.5 mg/5 mg/10 mg Tirzepatide (Cohort 1) | Number of Participants With One or More Serious Adverse Event(s) (SAEs) Considered by the Investigator to be Related to Study Drug Administration | 0 Participants |
| 5 mg/10 mg/15 mg Tirzepatide (Cohort 2) | Number of Participants With One or More Serious Adverse Event(s) (SAEs) Considered by the Investigator to be Related to Study Drug Administration | 0 Participants |
| 5 mg Tirzepatide (Cohort 3) | Number of Participants With One or More Serious Adverse Event(s) (SAEs) Considered by the Investigator to be Related to Study Drug Administration | 0 Participants |
Secondary
Pharmacodynamics (PD): Change From Baseline to 8 Weeks in Fasting Plasma Glucose
Change from baseline to 8 weeks in Fasting Plasma Glucose was measured to investigate the PD effect of Tirzepatide after multiple SC doses administered to Japanese patients with T2DM
Time frame: Baseline, Week 8
Population: All randomized participants who received at least one dose of drug and have evaluable PK data.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Pharmacodynamics (PD): Change From Baseline to 8 Weeks in Fasting Plasma Glucose | -4.0 milligram per deciliter (mg/dL) | Standard Deviation 23.7 |
| 2.5 mg/5 mg/10 mg Tirzepatide (Cohort 1) | Pharmacodynamics (PD): Change From Baseline to 8 Weeks in Fasting Plasma Glucose | -77.5 milligram per deciliter (mg/dL) | Standard Deviation 24.2 |
| 5 mg/10 mg/15 mg Tirzepatide (Cohort 2) | Pharmacodynamics (PD): Change From Baseline to 8 Weeks in Fasting Plasma Glucose | -72.6 milligram per deciliter (mg/dL) | Standard Deviation 30.9 |
| 5 mg Tirzepatide (Cohort 3) | Pharmacodynamics (PD): Change From Baseline to 8 Weeks in Fasting Plasma Glucose | -51.7 milligram per deciliter (mg/dL) | Standard Deviation 28.9 |
Secondary
Pharmacokinetics (PK): Maximum Observed Concentration (Cmax) of Tirzepatide
Pharmacokinetics (PK): Maximum observed drug concentration (Cmax) of Tirzepatide in plasma.
Time frame: Predose, 8, 24, 48, 72 and 168 hours post dose for Day 1 administration, and Predose, 8, 24, 48, and 168 hours post dose for Day 50 administration
Population: All randomized participants who received at least one dose of study drug and have evaluable PK data.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Pharmacokinetics (PK): Maximum Observed Concentration (Cmax) of Tirzepatide | Day 1 | 215 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 18 |
| Placebo | Pharmacokinetics (PK): Maximum Observed Concentration (Cmax) of Tirzepatide | Day 50 | 1520 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 15 |
| 2.5 mg/5 mg/10 mg Tirzepatide (Cohort 1) | Pharmacokinetics (PK): Maximum Observed Concentration (Cmax) of Tirzepatide | Day 50 | 2270 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 17 |
| 2.5 mg/5 mg/10 mg Tirzepatide (Cohort 1) | Pharmacokinetics (PK): Maximum Observed Concentration (Cmax) of Tirzepatide | Day 1 | 442 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 23 |
| 5 mg/10 mg/15 mg Tirzepatide (Cohort 2) | Pharmacokinetics (PK): Maximum Observed Concentration (Cmax) of Tirzepatide | Day 50 | 838 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 22 |
| 5 mg/10 mg/15 mg Tirzepatide (Cohort 2) | Pharmacokinetics (PK): Maximum Observed Concentration (Cmax) of Tirzepatide | Day 1 | 364 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 20 |
Secondary
PK: Area Under the Concentration Versus Time Curve (AUC) of Tirzepatide
Area under the concentration versus time curve from time zero to tau (τ) of Tirzepatide (AUC\[0- τ\]), where tau is dosing interval of (0-168 hours).
Time frame: Predose, 8, 24, 48, 72 and 168 hours post dose for Day 1 administration, and Predose, 8, 24, 48, and 168 hours post dose for Day 50 administration
Population: All randomized participants who received at least one dose of study drug and have evaluable PK data.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | PK: Area Under the Concentration Versus Time Curve (AUC) of Tirzepatide | Day 50 | 192000 nanograms * hours per mL (ng*hr/mL) | Geometric Coefficient of Variation 16 |
| Placebo | PK: Area Under the Concentration Versus Time Curve (AUC) of Tirzepatide | Day 1 | 26100 nanograms * hours per mL (ng*hr/mL) | Geometric Coefficient of Variation 27 |
| 2.5 mg/5 mg/10 mg Tirzepatide (Cohort 1) | PK: Area Under the Concentration Versus Time Curve (AUC) of Tirzepatide | Day 1 | 54400 nanograms * hours per mL (ng*hr/mL) | Geometric Coefficient of Variation 16 |
| 2.5 mg/5 mg/10 mg Tirzepatide (Cohort 1) | PK: Area Under the Concentration Versus Time Curve (AUC) of Tirzepatide | Day 50 | 285000 nanograms * hours per mL (ng*hr/mL) | Geometric Coefficient of Variation 15 |
| 5 mg/10 mg/15 mg Tirzepatide (Cohort 2) | PK: Area Under the Concentration Versus Time Curve (AUC) of Tirzepatide | Day 1 | 48800 nanograms * hours per mL (ng*hr/mL) | Geometric Coefficient of Variation 16 |
| 5 mg/10 mg/15 mg Tirzepatide (Cohort 2) | PK: Area Under the Concentration Versus Time Curve (AUC) of Tirzepatide | Day 50 | 104000 nanograms * hours per mL (ng*hr/mL) | Geometric Coefficient of Variation 19 |