Diabetes Mellitus, Type 2, Obesity, Overweight
Conditions
Brief summary
The purpose of this study is to learn more about how tirzepatide affects stomach emptying in overweight/very overweight participants. Participants include those without diabetes and those with type 2 diabetes. The study will last about 13 weeks for each participant, including screening.
Interventions
DRUGTirzepatide
Tirzepatide administered SC.
DRUGAcetaminophen
Acetaminophen administered orally.
Sponsors
Eli Lilly and Company
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
BASIC_SCIENCE
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
* Have a body mass index (BMI) between 27 to 45 kilograms per meter squared (kg/m²), inclusive at screening * For nondiabetic subjects: as determined by medical history, physical examination, and safety assessments at screening * For participants with a confirmed type 2 diabetes diagnosis: The condition must be managed either by diet and exercise alone or on a stable dose of metformin for the past 3 months * Willing and agreeable to commit to the duration of the study and undergo study procedures as instructed by the clinic staff Key
Exclusion criteria
* Have undergone gastric bypass or bariatric surgery * Have received prescription drugs or over the counter drugs that promote weight loss in the past 6 months prior to screening * For participants with a confirmed type 2 diabetes diagnosis: Have experienced more than 1 episode of severe low blood sugar that require emergency treatment, hospitalization or third parties to administer rescue treatment, in the past 6 months * Have any lifetime history of a suicide attempt * Have other medical conditions or medical history that make participation in the study unsafe or which may interfere in the interpretation of the results of the study * Unwilling to comply with smoking and alcohol restrictions during the study
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Pharmacokinetics (PK): Area Under the Concentration Time Curve From Time Zero to Time T, Where T is the Last Time Point With a Measurable Concentration [ AUC(0-tlast)] of Acetaminophen | Pre-dose, 0.5, 0.75, 1, 2, 3, 4, 6, 9, 12, 24 and 36 hours post-dose on Day 1, Day 2 and Day 37 , Day 2 and Day 37 | Area Under the Concentration Time Curve From Time Zero to Time T, Where T is the Last Time Point With a Measurable Concentration \[ AUC(0-tlast)\] of Acetaminophen |
| PK: Maximum Observed Drug Concentration (Cmax) of Acetaminophen | Pre-dose, 0.5, 0.75, 1, 2, 3, 4, 6, 9, 12, 24 and 36 hours post-dose on Day 1, Day 2 and Day 37 , Day 2 and Day 37 | Maximum Observed Drug Concentration (cmax) of Acetaminophen |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| PK: Area Under the Concentration Versus Time Curve From Time Zero to Time T, Where T is the Last Time Point With a Measurable Concentration [ AUC(0-tlast)] of Acetaminophen at Steady State For T2DM | Pre-dose, 0.5, 0.75, 1, 2, 3, 4, 6, 9, 12, 24 and 36 hours post-dose on Day 1, Day 2 and Day 37 , Day 2 and Day 37 | Area Under the Concentration Versus Time Curve From Time Zero to Time T, Where T is the Last Time Point With a Measurable Concentration \[ AUC(0-tlast)\] of Acetaminophen at Steady State For T2DM |
| Hemoglobin A1c (HbA1c) Data by Diabetic Status | Predose on Day 29 and follow-up (Day 64) | Levels of Hemoglobin A1c (HbA1c) were assessed at predose on Day 29, and at follow-up (Day 64). |
| PK: Cmax of Acetaminophen at Steady State For T2DM | Pre-dose, 0.5, 0.75, 1, 2, 3, 4, 6, 9, 12, 24 and 36 hours post-dose on Day 1, Day 2 and Day 37 , Day 2 and Day 37 | PK: Cmax of Acetaminophen at Steady State T2DM |
| PK: Cmax of Acetaminophen at Steady State Non-diabetic | Pre-dose, 0.5, 0.75, 1, 2, 3, 4, 6, 9, 12, 24 and 36 hours post-dose on Day 1, Day 2 and Day 37 , Day 2 and Day 37 | PK: Cmax of Acetaminophen at Steady State Non-diabetic |
| PK: Area Under the Concentration Time Curve From Time Zero to Time T, Where T is the Last Time Point With a Measurable Concentration [ AUC(0-tlast)] of Acetaminophen at Steady State For Non-diabetic | Pre-dose, 0.5, 0.75, 1, 2, 3, 4, 6, 9, 12, 24 and 36 hours post-dose on Day 1, Day 2 and Day 37 , Day 2 and Day 37 | Area Under the Concentration Time Curve From Time Zero to Time T, Where T is the Last Time Point With a Measurable Concentration \[ AUC(0-tlast)\] of Acetaminophen at Steady State For Non-diabetic |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Non-Diabetic Participants received 5 mg tirzepatide on Day 1 and Day 8; 10 mg tirzepatide on Day 15, 22 and 29; 15 mg tirzepatide on Day 36 administered SC and 160 mg acetaminophen administered orally on Day -1, Day 2 and Day 37. | 18 |
| T2DM Participants received 5 mg tirzepatide on Day 1 and Day 8; 10 mg tirzepatide on Day 15, 22 and 29; 15 mg tirzepatide on Day 36 administered SC and 160 mg acetaminophen administered orally on Day -1, Day 2 and Day 37. | 18 |
| Total | 36 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 3 | 3 |
Baseline characteristics
| Characteristic | Non-Diabetic | Total | T2DM |
|---|---|---|---|
| Age, Continuous | 43.9 years STANDARD_DEVIATION 10.8 | 50.1 years STANDARD_DEVIATION 10.5 | 56.2 years STANDARD_DEVIATION 5.5 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 18 Participants | 36 Participants | 18 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 0 Participants | 0 Participants | 0 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 | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 4 Participants | 6 Participants | 2 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 | 14 Participants | 30 Participants | 16 Participants |
| Region of Enrollment United States | 18 Participants | 36 Participants | 18 Participants |
| Sex: Female, Male Female | 10 Participants | 23 Participants | 13 Participants |
| Sex: Female, Male Male | 8 Participants | 13 Participants | 5 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 18 | 0 / 18 |
| other Total, other adverse events | 16 / 18 | 16 / 18 |
| serious Total, serious adverse events | 0 / 18 | 0 / 18 |
Outcome results
Primary
Pharmacokinetics (PK): Area Under the Concentration Time Curve From Time Zero to Time T, Where T is the Last Time Point With a Measurable Concentration [ AUC(0-tlast)] of Acetaminophen
Area Under the Concentration Time Curve From Time Zero to Time T, Where T is the Last Time Point With a Measurable Concentration \[ AUC(0-tlast)\] of Acetaminophen
Time frame: Pre-dose, 0.5, 0.75, 1, 2, 3, 4, 6, 9, 12, 24 and 36 hours post-dose on Day 1, Day 2 and Day 37 , Day 2 and Day 37
Population: All randomized participants who received at least one dose of acetaminophen and have evaluable acetaminophen PK data.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Reference:160 mg Acetaminophen (Day -1) | Pharmacokinetics (PK): Area Under the Concentration Time Curve From Time Zero to Time T, Where T is the Last Time Point With a Measurable Concentration [ AUC(0-tlast)] of Acetaminophen | 49384 nanograms*hours per milliliter (ng*h/mL) |
| Test: 5 mg Tirzepatide + 160 mg Acetaminophen (Day 2) | Pharmacokinetics (PK): Area Under the Concentration Time Curve From Time Zero to Time T, Where T is the Last Time Point With a Measurable Concentration [ AUC(0-tlast)] of Acetaminophen | 43523 nanograms*hours per milliliter (ng*h/mL) |
| Test: 15 mg Tirzepatide + 160 mg Acetaminophen (Day 37) | Pharmacokinetics (PK): Area Under the Concentration Time Curve From Time Zero to Time T, Where T is the Last Time Point With a Measurable Concentration [ AUC(0-tlast)] of Acetaminophen | 57049 nanograms*hours per milliliter (ng*h/mL) |
90% CI: [0.803, 0.967]Wilcoxon signed rank test
90% CI: [1.05, 1.28]Wilcoxon signed rank test
Primary
PK: Maximum Observed Drug Concentration (Cmax) of Acetaminophen
Maximum Observed Drug Concentration (cmax) of Acetaminophen
Time frame: Pre-dose, 0.5, 0.75, 1, 2, 3, 4, 6, 9, 12, 24 and 36 hours post-dose on Day 1, Day 2 and Day 37 , Day 2 and Day 37
Population: All randomized participants who received at least one dose of acetaminophen and have evaluable acetaminophen PK data.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Reference:160 mg Acetaminophen (Day -1) | PK: Maximum Observed Drug Concentration (Cmax) of Acetaminophen | 11925 nanograms per milliliter (ng/mL) |
| Test: 5 mg Tirzepatide + 160 mg Acetaminophen (Day 2) | PK: Maximum Observed Drug Concentration (Cmax) of Acetaminophen | 5314 nanograms per milliliter (ng/mL) |
| Test: 15 mg Tirzepatide + 160 mg Acetaminophen (Day 37) | PK: Maximum Observed Drug Concentration (Cmax) of Acetaminophen | 8099 nanograms per milliliter (ng/mL) |
90% CI: [0.39, 0.509]Wilcoxon signed rank test
90% CI: [0.589, 0.783]Wilcoxon signed rank test
Secondary
Hemoglobin A1c (HbA1c) Data by Diabetic Status
Levels of Hemoglobin A1c (HbA1c) were assessed at predose on Day 29, and at follow-up (Day 64).
Time frame: Predose on Day 29 and follow-up (Day 64)
Population: All participants who received at least one dose of acetaminophen or tirzepatide, whether or not they completed all protocol requirements
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Reference:160 mg Acetaminophen (Day -1) | Hemoglobin A1c (HbA1c) Data by Diabetic Status | Day 29 ± 1 | 5.37 Percentage of HbA1c | Standard Deviation 0.45 |
| Reference:160 mg Acetaminophen (Day -1) | Hemoglobin A1c (HbA1c) Data by Diabetic Status | Day 64 ± 1 (Follow-Up) | 5.29 Percentage of HbA1c | Standard Deviation 0.45 |
| Test: 5 mg Tirzepatide + 160 mg Acetaminophen (Day 2) | Hemoglobin A1c (HbA1c) Data by Diabetic Status | Day 29 ± 1 | 7.27 Percentage of HbA1c | Standard Deviation 0.79 |
| Test: 5 mg Tirzepatide + 160 mg Acetaminophen (Day 2) | Hemoglobin A1c (HbA1c) Data by Diabetic Status | Day 64 ± 1 (Follow-Up) | 6.87 Percentage of HbA1c | Standard Deviation 0.75 |
Secondary
PK: Area Under the Concentration Time Curve From Time Zero to Time T, Where T is the Last Time Point With a Measurable Concentration [ AUC(0-tlast)] of Acetaminophen at Steady State For Non-diabetic
Area Under the Concentration Time Curve From Time Zero to Time T, Where T is the Last Time Point With a Measurable Concentration \[ AUC(0-tlast)\] of Acetaminophen at Steady State For Non-diabetic
Time frame: Pre-dose, 0.5, 0.75, 1, 2, 3, 4, 6, 9, 12, 24 and 36 hours post-dose on Day 1, Day 2 and Day 37 , Day 2 and Day 37
Population: All participants who received at least one dose of acetaminophen and have evaluable acetaminophen PK data.
| Arm | Measure | Value (GEOMETRIC_LEAST_SQUARES_MEAN) |
|---|---|---|
| Reference:160 mg Acetaminophen (Day -1) | PK: Area Under the Concentration Time Curve From Time Zero to Time T, Where T is the Last Time Point With a Measurable Concentration [ AUC(0-tlast)] of Acetaminophen at Steady State For Non-diabetic | 44350 nanograms*hours per milliliter (ng*h/mL) |
| Test: 5 mg Tirzepatide + 160 mg Acetaminophen (Day 2) | PK: Area Under the Concentration Time Curve From Time Zero to Time T, Where T is the Last Time Point With a Measurable Concentration [ AUC(0-tlast)] of Acetaminophen at Steady State For Non-diabetic | 39389 nanograms*hours per milliliter (ng*h/mL) |
| Test: 15 mg Tirzepatide + 160 mg Acetaminophen (Day 37) | PK: Area Under the Concentration Time Curve From Time Zero to Time T, Where T is the Last Time Point With a Measurable Concentration [ AUC(0-tlast)] of Acetaminophen at Steady State For Non-diabetic | 54735 nanograms*hours per milliliter (ng*h/mL) |
90% CI: [0.778, 1.01]
90% CI: [1.07, 1.42]
Secondary
PK: Area Under the Concentration Versus Time Curve From Time Zero to Time T, Where T is the Last Time Point With a Measurable Concentration [ AUC(0-tlast)] of Acetaminophen at Steady State For T2DM
Area Under the Concentration Versus Time Curve From Time Zero to Time T, Where T is the Last Time Point With a Measurable Concentration \[ AUC(0-tlast)\] of Acetaminophen at Steady State For T2DM
Time frame: Pre-dose, 0.5, 0.75, 1, 2, 3, 4, 6, 9, 12, 24 and 36 hours post-dose on Day 1, Day 2 and Day 37 , Day 2 and Day 37
Population: All participants who received at least one dose of acetaminophen and have evaluable acetaminophen PK data.
| Arm | Measure | Value (GEOMETRIC_LEAST_SQUARES_MEAN) |
|---|---|---|
| Reference:160 mg Acetaminophen (Day -1) | PK: Area Under the Concentration Versus Time Curve From Time Zero to Time T, Where T is the Last Time Point With a Measurable Concentration [ AUC(0-tlast)] of Acetaminophen at Steady State For T2DM | 54989 nanograms*hours per milliliter (ng*h/mL) |
| Test: 5 mg Tirzepatide + 160 mg Acetaminophen (Day 2) | PK: Area Under the Concentration Versus Time Curve From Time Zero to Time T, Where T is the Last Time Point With a Measurable Concentration [ AUC(0-tlast)] of Acetaminophen at Steady State For T2DM | 48090 nanograms*hours per milliliter (ng*h/mL) |
| Test: 15 mg Tirzepatide + 160 mg Acetaminophen (Day 37) | PK: Area Under the Concentration Versus Time Curve From Time Zero to Time T, Where T is the Last Time Point With a Measurable Concentration [ AUC(0-tlast)] of Acetaminophen at Steady State For T2DM | 59440 nanograms*hours per milliliter (ng*h/mL) |
90% CI: [0.766, 0.999]
90% CI: [0.938, 1.25]
Secondary
PK: Cmax of Acetaminophen at Steady State For T2DM
PK: Cmax of Acetaminophen at Steady State T2DM
Time frame: Pre-dose, 0.5, 0.75, 1, 2, 3, 4, 6, 9, 12, 24 and 36 hours post-dose on Day 1, Day 2 and Day 37 , Day 2 and Day 37
Population: All participants who received at least one dose of acetaminophen and have evaluable acetaminophen PK data.
| Arm | Measure | Value (GEOMETRIC_LEAST_SQUARES_MEAN) |
|---|---|---|
| Reference:160 mg Acetaminophen (Day -1) | PK: Cmax of Acetaminophen at Steady State For T2DM | 13868 nanograms per milliliter (ng/mL) |
| Test: 5 mg Tirzepatide + 160 mg Acetaminophen (Day 2) | PK: Cmax of Acetaminophen at Steady State For T2DM | 6078 nanograms per milliliter (ng/mL) |
| Test: 15 mg Tirzepatide + 160 mg Acetaminophen (Day 37) | PK: Cmax of Acetaminophen at Steady State For T2DM | 7954 nanograms per milliliter (ng/mL) |
90% CI: [0.364, 0.527]
90% CI: [0.471, 0.698]
Secondary
PK: Cmax of Acetaminophen at Steady State Non-diabetic
PK: Cmax of Acetaminophen at Steady State Non-diabetic
Time frame: Pre-dose, 0.5, 0.75, 1, 2, 3, 4, 6, 9, 12, 24 and 36 hours post-dose on Day 1, Day 2 and Day 37 , Day 2 and Day 37
Population: All participants who received at least one dose of acetaminophen and have evaluable acetaminophen PK data.
| Arm | Measure | Value (GEOMETRIC_LEAST_SQUARES_MEAN) |
|---|---|---|
| Reference:160 mg Acetaminophen (Day -1) | PK: Cmax of Acetaminophen at Steady State Non-diabetic | 10255 nanograms per milliliter (ng/mL) |
| Test: 5 mg Tirzepatide + 160 mg Acetaminophen (Day 2) | PK: Cmax of Acetaminophen at Steady State Non-diabetic | 4646 nanograms per milliliter (ng/mL) |
| Test: 15 mg Tirzepatide + 160 mg Acetaminophen (Day 37) | PK: Cmax of Acetaminophen at Steady State Non-diabetic | 8245 nanograms per milliliter (ng/mL) |
90% CI: [0.376, 0.545]
90% CI: [0.66, 0.979]