Diabetes Mellitus, Type 2
Conditions
Brief summary
The main purpose of this study is to learn more about the safety and side effects of tirzepatide in Chinese participants with type 2 diabetes mellitus. The study will also measure how much tirzepatide gets into the bloodstream and how long it takes the body to remove it. The study will last about six or eight months for each participant.
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 type 2 diabetes mellitus (T2DM) controlled with diet and exercise alone or are stable on a single oral antihyperglycemic medication (OAM), metformin, acarbose, or sulphonylureas only (other types of OAM \[dipeptidyl peptidase IV inhibitors, sodium-glucose cotransporter-2 inhibitors, and thiazolidinediones\] are not allowed in this study), for at least 3 months * Have a body mass greater than or equal to (≥)23 kilograms per square meter (kg/m²), inclusive
Exclusion criteria
* Have type 1 diabetes mellitus * Have a history of severe hypoglycemia and/or hypoglycemia unawareness within the 6 months prior to Visit 1 * Have a history of heart block or PR interval greater than (\>)220 milliseconds (msec) or any abnormality in the 12-lead electrocardiogram (ECG) 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 a GI disease that impacts gastric emptying or could be aggravated by glucagon-like peptide-1 (GLP-1) analogs or dipeptidyl peptidase IV (DPP-IV) inhibitors * Have known allergies to tirzepatide, GLP-1 analogs, or related compounds or any components of the formulation
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 up to 43 Weeks | The number of participants with one or more SAEs is assessed as related to the study drug and is summarized cumulatively. A serious adverse event is defined as an event that results in death, initial or prolonged hospitalization, is life-threatening, leads to persistent or significant disability/incapacity, is associated with congenital anomaly/birth defect, or is considered significant by the investigator for any other reason. A summary of SAEs and other non-serious adverse events (AEs), regardless of causality, is 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 Hour Post-dose (AUC [0-168]) of Tirzepatide (Cohort 1) | Week 0 - (Pre-dose, 8, 24, 48, 72, 168 hours post-dose); Week 7 - (Pre-dose, 8, 24, 48, 72, 168 hours post-dose); Week 15 - (Pre-dose, 8, 24, 48, 72, 168 hours post-dose). | PK: AUC \[0-168\] of Tirzepatide. |
| PK: AUC [0-168] of Tirzepatide (Cohort 2) | Week 0 - (Pre-dose, 8, 24, 48, 72, 168 hours post-dose); Week 7 - (Pre-dose, 8, 24, 48, 72, 168 hours post-dose); Week 23 - (Pre-dose, 8, 24, 48, 72, 168 hours post-dose). | PK: AUC \[0-168\] of Tirzepatide. |
| PK: Maximum Concentration (Cmax) of Tirzepatide (Cohort 1) | Week 0 - (Pre-dose, 8, 24, 48, 72, 168 hours post-dose); Week 7 - (Pre-dose, 8, 24, 48, 72, 168 hours post-dose); Week 15 - (Pre-dose, 8, 24, 48, 72, 168 hours post-dose). | PK: Cmax of Tirzepatide. |
| PK: Cmax of Tirzepatide (Cohort 2) | Week 0 - (Pre-dose, 8, 24, 48, 72, 168 hours post-dose); Week 7 - (Pre-dose, 8, 24, 48, 72, 168 hours post-dose); Week 23 - (Pre-dose, 8, 24, 48, 72, 168 hours post-dose). | PK: Cmax of Tirzepatide. |
Countries
China
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Placebo Participants received placebo QW SC. | 4 |
| Cohort 1 (2.5 to 10 Milligram (mg) Tirzepatide) Participants in Cohort 1 received weekly SC doses of tirzepatide with titration regimen starting from 2.5 mg for Weeks 0 through 3 followed by 5 mg for Weeks 4 through 7, 7.5 mg for Weeks 8 through 11, and 10 mg for Weeks 12 through 15. | 10 |
| Cohort 2 (2.5 to 15 mg Tirzepatide) Participants in Cohort 2 received weekly SC doses of tirzepatide with titration regimen starting from 2.5 mg for Weeks 0 through 3 followed by 5 mg for Weeks 4 through 7, 7.5 mg for Weeks 8 through 11, 10 mg for Weeks 12 through 15, 12.5 mg for Weeks 16 through 19, and 15 mg for Weeks 20 through 23. | 10 |
| Total | 24 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Adverse Event | 1 | 0 | 0 |
| Overall Study | Protocol Violation | 0 | 1 | 0 |
Baseline characteristics
| Characteristic | Placebo | Total | Cohort 2 (2.5 to 15 mg Tirzepatide) | Cohort 1 (2.5 to 10 Milligram (mg) Tirzepatide) |
|---|---|---|---|---|
| Age, Continuous | 56.5 years STANDARD_DEVIATION 7.5 | 56.3 years STANDARD_DEVIATION 5.4 | 56.8 years STANDARD_DEVIATION 5.4 | 55.8 years STANDARD_DEVIATION 5.2 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 4 Participants | 24 Participants | 10 Participants | 10 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 4 Participants | 24 Participants | 10 Participants | 10 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 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 |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Region of Enrollment China | 4 Participants | 24 Participants | 10 Participants | 10 Participants |
| Sex: Female, Male Female | 1 Participants | 11 Participants | 4 Participants | 6 Participants |
| Sex: Female, Male Male | 3 Participants | 13 Participants | 6 Participants | 4 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 4 | 0 / 10 | 0 / 10 |
| other Total, other adverse events | 4 / 4 | 10 / 10 | 10 / 10 |
| serious Total, serious adverse events | 1 / 4 | 0 / 10 | 0 / 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 one or more SAEs is assessed as related to the study drug and is summarized cumulatively. A serious adverse event is defined as an event that results in death, initial or prolonged hospitalization, is life-threatening, leads to persistent or significant disability/incapacity, is associated with congenital anomaly/birth defect, or is considered significant by the investigator for any other reason. A summary of SAEs and other non-serious adverse events (AEs), regardless of causality, is reported in the Reported Adverse Events module.
Time frame: Baseline up to 43 Weeks
Population: All participants who received at least one dose of study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Number of Participants With One or More Serious Adverse Event(s) (SAEs) Considered by the Investigator to be Related to Study Drug Administration. | 1 participants |
| Cohort 1 (2.5 to 10 Milligram (mg) Tirzepatide) | 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 |
| Cohort 2 (2.5 to 15 mg Tirzepatide) | 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
Pharmacokinetics (PK): Area Under the Concentration Versus Time Curve From Time Zero to 168 Hour Post-dose (AUC [0-168]) of Tirzepatide (Cohort 1)
PK: AUC \[0-168\] of Tirzepatide.
Time frame: Week 0 - (Pre-dose, 8, 24, 48, 72, 168 hours post-dose); Week 7 - (Pre-dose, 8, 24, 48, 72, 168 hours post-dose); Week 15 - (Pre-dose, 8, 24, 48, 72, 168 hours post-dose).
Population: All participants who received at least one dose of tirzepatide and had evaluable PK data in Cohort 1.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Pharmacokinetics (PK): Area Under the Concentration Versus Time Curve From Time Zero to 168 Hour Post-dose (AUC [0-168]) of Tirzepatide (Cohort 1) | Week 0 | 35100 nanogram hour per milliliter (ng*h/mL) | Geometric Coefficient of Variation 14 |
| Placebo | Pharmacokinetics (PK): Area Under the Concentration Versus Time Curve From Time Zero to 168 Hour Post-dose (AUC [0-168]) of Tirzepatide (Cohort 1) | Week 7 | 125000 nanogram hour per milliliter (ng*h/mL) | Geometric Coefficient of Variation 16 |
| Placebo | Pharmacokinetics (PK): Area Under the Concentration Versus Time Curve From Time Zero to 168 Hour Post-dose (AUC [0-168]) of Tirzepatide (Cohort 1) | Week 15 | 263000 nanogram hour per milliliter (ng*h/mL) | Geometric Coefficient of Variation 17 |
Secondary
PK: AUC [0-168] of Tirzepatide (Cohort 2)
PK: AUC \[0-168\] of Tirzepatide.
Time frame: Week 0 - (Pre-dose, 8, 24, 48, 72, 168 hours post-dose); Week 7 - (Pre-dose, 8, 24, 48, 72, 168 hours post-dose); Week 23 - (Pre-dose, 8, 24, 48, 72, 168 hours post-dose).
Population: All participants who received at least one dose of tirzepatide and had evaluable PK data in Cohort 2.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | PK: AUC [0-168] of Tirzepatide (Cohort 2) | Week 0 | 30900 nanogram hour per milliliter (ng*h/mL) | Geometric Coefficient of Variation 14 |
| Placebo | PK: AUC [0-168] of Tirzepatide (Cohort 2) | Week 7 | 110000 nanogram hour per milliliter (ng*h/mL) | Geometric Coefficient of Variation 16 |
| Placebo | PK: AUC [0-168] of Tirzepatide (Cohort 2) | Week 23 | 357000 nanogram hour per milliliter (ng*h/mL) | Geometric Coefficient of Variation 16 |
Secondary
PK: Cmax of Tirzepatide (Cohort 2)
PK: Cmax of Tirzepatide.
Time frame: Week 0 - (Pre-dose, 8, 24, 48, 72, 168 hours post-dose); Week 7 - (Pre-dose, 8, 24, 48, 72, 168 hours post-dose); Week 23 - (Pre-dose, 8, 24, 48, 72, 168 hours post-dose).
Population: All participants who received at least one dose of tirzepatide and had evaluable PK data in Cohort 2.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | PK: Cmax of Tirzepatide (Cohort 2) | Week 0 | 257 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 17 |
| Placebo | PK: Cmax of Tirzepatide (Cohort 2) | Week 7 | 915 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 18 |
| Placebo | PK: Cmax of Tirzepatide (Cohort 2) | Week 23 | 2930 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 20 |
Secondary
PK: Maximum Concentration (Cmax) of Tirzepatide (Cohort 1)
PK: Cmax of Tirzepatide.
Time frame: Week 0 - (Pre-dose, 8, 24, 48, 72, 168 hours post-dose); Week 7 - (Pre-dose, 8, 24, 48, 72, 168 hours post-dose); Week 15 - (Pre-dose, 8, 24, 48, 72, 168 hours post-dose).
Population: All participants who received at least one dose of tirzepatide and had evaluable PK data in Cohort 1.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | PK: Maximum Concentration (Cmax) of Tirzepatide (Cohort 1) | Week 0 | 306 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 28 |
| Placebo | PK: Maximum Concentration (Cmax) of Tirzepatide (Cohort 1) | Week 7 | 1030 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 13 |
| Placebo | PK: Maximum Concentration (Cmax) of Tirzepatide (Cohort 1) | Week 15 | 2200 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 16 |