Healthy
Conditions
Brief summary
This study has four parts. Each participant will enroll in one part. Part A: The purpose of Part A is to compare study drug tirzepatide solution formulation to a powder formulation mixed with water and given subcutaneously (SC) (just under the skin). Part A will measure how much of the study drug gets into the blood stream and how long it takes the body to get rid of it. Part B: The purpose of Part B is to evaluate the safety and tolerability of tirzepatide intravenous (IV) formulation when administered into a vein. Part C: The purpose of Part C is to evaluate the safety and tolerability of tirzepatide following multiple SC weekly doses of a solution. Part D: The purpose of Part D is to evaluate the safety and tolerability of tirzepatide following single IV bolus dose of lyophilized formulation. This study will last approximately 70 days for each part (Part A, Part B or Part D) and 92 days for Part C. This does not include screening. Screening is required within 28 days prior to the start of the study.
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)
Masking description
Part A, B and D are not blinded. Part C is blinded to Participant and Investigator
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
Yes
Inclusion criteria
* Overtly healthy males or females, as determined by medical history and physical examination * Male participants: agree to use an effective method of contraception for the duration of the study and for 3 months following the last dose of investigational product * Female participants: not of childbearing potential due to surgical sterilization (hysterectomy or bilateral oophorectomy or tubal ligation) or menopause. Women with an intact uterus are deemed postmenopausal if they are greater than or equal to (≥)45 years old and have not taken hormones or oral contraceptives within the last year and had cessation of menses for at least 1 year. Or, have had at least 6 months of amenorrhea with follicle-stimulating hormone levels consistent with a postmenopausal state * Have a body mass index of 18.5 to 32.0 kilograms per meter squared (kg/m²) inclusive
Exclusion criteria
* Currently enrolled in a clinical trial involving an investigational product or any other type of medical research judged not to be scientifically or medically compatible with this study * Received treatment with a drug that has not received regulatory approval for any indication within 30 days of screening * Have a history of heart block, or a pulse rate (PR) interval greater than (\>)200 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 significant history of or current cardiovascular (myocardial infarction, congestive heart failure, cerebrovascular accident, venous thromboembolism, etc.), respiratory, hepatic, renal, gastrointestinal (GI), endocrine, hematological (including history of thrombocytopenia), or neurological disorders capable of significantly altering the absorption, metabolism, or elimination of drugs, or of constituting a risk when taking the study medication, or interfering with the interpretation of data
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| PK Part B: Area Under the Concentration Versus Time Curve [AUC (0-∞)] of Tirzepatide | Part B: Predose, 0.08 hours (h), 0.16h, 0.5h, 1h, 2h, 4h, 8h, 12h, 24h, 36h, 48h, 72h, 96h, 120h, 144h, 168h, 336h, 816h-864h and >=70 days post dose | PK Part B: Area under the concentration versus time curve \[AUC (0-∞)\] of tirzepatide. |
| Pharmacokinetics (PK) Part A: Area Under the Concentration Versus Time Curve [AUC (0-∞)] of Tirzepatide | Part A: Predose, 8, 12, 24, 48, 72, 96, 120, 144, 168, 336, 480, 816-864 hours postdose | Pharmacokinetics (PK) Part A: Area under the concentration versus time curve \[AUC (0-∞)\] of tirzepatide. |
| PK Part A: Maximum Observed Drug Concentration (Cmax) of Tirzepatide | Part A: Predose, 8, 12, 24, 48, 72, 96, 120, 144, 168, 336, 480 and 816-864 hours postdose | PK Part A: Maximum observed plasma drug concentration (Cmax) of tirzepatide. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| PK Part C: Area Under the Concentration Versus Time Curve [AUC (0-τ)] of Tirzepatide | Part C: Predose, 8 hours (h) (day (D)1), 24h (D2), 48h (D3),72h (D4), predose (D8), predose (D15), 8h (D15), 24h (D16), 48h (D17), 72h (D18), predose (D22), 8h (D22), 24h (D23), 48h (D24), 72h (D25), D57 and >= D96 postdose | PK Part C: Area under the concentration versus time curve during one dosing interval (168 hours) \[AUC (0-τ)\] of tirzepatide. |
| PK Part C: Maximum Observed Drug Concentration (Cmax) of Tirzepatide | Part C: Predose, 8 hours (h) (day (D)1), 24h (D2), 48h (D3),72h (D4), predose (D8), predose (D15), 8h (D15), 24h (D16), 48h (D17), 72h (D18), predose (D22), 8h (D22), 24h (D23), 48h (D24), 72h (D25), D57 and >= D96 postdose | PK Part C: Maximum observed plasma drug concentration (Cmax) of tirzepatide. |
| PK Part D: Area Under the Concentration Versus Time Curve [AUC (0-∞)] of Tirzepatide | Part D: Predose, 0.08 hours (h), 0.16h, 0.5h, 1h, 2h, 4h, 8h, 12h, 24h, 36h, 48h, 72h, 96h, 120h, 144h, 168h, 336h, 816-864h and >= 70 days postdose | PK Part D: Area under the concentration versus time curve \[AUC (0-∞)\] of tirzepatide. |
Countries
United States
Participant flow
Recruitment details
4-part study, Part A (2-period, 2-treatment, crossover study with at least 35 days of washout period), Part B (fixed, single-arm treatment study), Part C (placebo-controlled, 4-week dose escalation study) and Part D (a fixed, single-arm treatment study).
Participants by arm
| Arm | Count |
|---|---|
| Sequence 1-Part A Participants received 5 milligrams (mg) of tirzepatide subcutaneous (SC) solution formulation in Period 1 and 5 mg of tirzepatide SC lyophilized formulation in Period 2. | 10 |
| Sequence 2-Part A Participants received 5 mg of tirzepatide SC lyophilized formulation in Period 1 and 5 mg of tirzepatide SC solution formulation in Period 2. | 10 |
| 0.5 mg Tirzepatide IV-Part B Participants received Intravenous (IV) infusion of a single 0.5 mg dose of tirzepatide solution formulation. | 8 |
| Placebo SC-Part C Participants received SC injection of placebo. | 4 |
| 5 mg/7.5 mg/ 10 mg Tirzepatide SC-Part C Participants received tirzepatide subcutaneous solution formulation at 5 mg on Days 1 (week 1) and 8 (Week 2), 7.5 mg on Day 15 (Week 3) and 10 mg on Day 22 (Week 4). | 12 |
| 0.5 mg Tirzepatide Bolus IV-Part D Participants received IV bolus of 0.5 mg tirzepatide lyophilized formulation. | 8 |
| Total | 52 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 |
|---|---|---|---|---|---|---|---|
| Period 1 | Adverse Event | 0 | 0 | 0 | 0 | 1 | 0 |
| Period 1 | Lost to Follow-up | 0 | 0 | 1 | 0 | 0 | 0 |
| Period 2 | Lost to Follow-up | 1 | 1 | 0 | 0 | 0 | 0 |
Baseline characteristics
| Characteristic | Total | Sequence 2-Part A | 0.5 mg Tirzepatide IV-Part B | Placebo SC-Part C | Sequence 1-Part A | 5 mg/7.5 mg/ 10 mg Tirzepatide SC-Part C | 0.5 mg Tirzepatide Bolus IV-Part D |
|---|---|---|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 51 Participants | 10 Participants | 8 Participants | 4 Participants | 10 Participants | 11 Participants | 8 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 9 Participants | 1 Participants | 1 Participants | 1 Participants | 3 Participants | 1 Participants | 2 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 43 Participants | 9 Participants | 7 Participants | 3 Participants | 7 Participants | 11 Participants | 6 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 | 2 Participants | 1 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 29 Participants | 7 Participants | 3 Participants | 2 Participants | 5 Participants | 8 Participants | 4 Participants |
| Race (NIH/OMB) More than one race | 1 Participants | 0 Participants | 0 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 | 20 Participants | 2 Participants | 4 Participants | 2 Participants | 5 Participants | 4 Participants | 3 Participants |
| Region of Enrollment United States | 52 participants | 10 participants | 8 participants | 4 participants | 10 participants | 12 participants | 8 participants |
| Sex: Female, Male Female | 15 Participants | 2 Participants | 0 Participants | 0 Participants | 2 Participants | 7 Participants | 4 Participants |
| Sex: Female, Male Male | 37 Participants | 8 Participants | 8 Participants | 4 Participants | 8 Participants | 5 Participants | 4 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 | EG006 affected / at risk | EG007 affected / at risk | EG008 affected / at risk |
|---|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 20 | 0 / 20 | 0 / 8 | 0 / 4 | 0 / 12 | 0 / 12 | 0 / 12 | 0 / 11 | 0 / 8 |
| other Total, other adverse events | 9 / 20 | 5 / 20 | 1 / 8 | 1 / 4 | 4 / 12 | 2 / 12 | 6 / 12 | 4 / 11 | 3 / 8 |
| serious Total, serious adverse events | 0 / 20 | 0 / 20 | 0 / 8 | 0 / 4 | 0 / 12 | 0 / 12 | 0 / 12 | 0 / 11 | 0 / 8 |
Outcome results
Primary
Pharmacokinetics (PK) Part A: Area Under the Concentration Versus Time Curve [AUC (0-∞)] of Tirzepatide
Pharmacokinetics (PK) Part A: Area under the concentration versus time curve \[AUC (0-∞)\] of tirzepatide.
Time frame: Part A: Predose, 8, 12, 24, 48, 72, 96, 120, 144, 168, 336, 480, 816-864 hours postdose
Population: All randomized participants from Part A group, who received at least one dose of study drug and had evaluable PK data
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| 5 mg Tirzepatide SC (Lyophilized)-Part A | Pharmacokinetics (PK) Part A: Area Under the Concentration Versus Time Curve [AUC (0-∞)] of Tirzepatide | 113000 nanograms*hours per milliliter(ng*hr/mL) | Geometric Coefficient of Variation 19 |
| 5 mg Tirzepatide SC (Solution)-Part A | Pharmacokinetics (PK) Part A: Area Under the Concentration Versus Time Curve [AUC (0-∞)] of Tirzepatide | 109000 nanograms*hours per milliliter(ng*hr/mL) | Geometric Coefficient of Variation 17 |
Primary
PK Part A: Maximum Observed Drug Concentration (Cmax) of Tirzepatide
PK Part A: Maximum observed plasma drug concentration (Cmax) of tirzepatide.
Time frame: Part A: Predose, 8, 12, 24, 48, 72, 96, 120, 144, 168, 336, 480 and 816-864 hours postdose
Population: All randomized participants from Part A group, who received at least one dose of study drug and had evaluable PK data.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| 5 mg Tirzepatide SC (Lyophilized)-Part A | PK Part A: Maximum Observed Drug Concentration (Cmax) of Tirzepatide | 524 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 27 |
| 5 mg Tirzepatide SC (Solution)-Part A | PK Part A: Maximum Observed Drug Concentration (Cmax) of Tirzepatide | 575 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 22 |
Primary
PK Part B: Area Under the Concentration Versus Time Curve [AUC (0-∞)] of Tirzepatide
PK Part B: Area under the concentration versus time curve \[AUC (0-∞)\] of tirzepatide.
Time frame: Part B: Predose, 0.08 hours (h), 0.16h, 0.5h, 1h, 2h, 4h, 8h, 12h, 24h, 36h, 48h, 72h, 96h, 120h, 144h, 168h, 336h, 816h-864h and >=70 days post dose
Population: All randomized participants from Part B group, who received at least one dose of study drug and had evaluable PK data.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| 5 mg Tirzepatide SC (Lyophilized)-Part A | PK Part B: Area Under the Concentration Versus Time Curve [AUC (0-∞)] of Tirzepatide | 6680 ng*hr/mL | Geometric Coefficient of Variation 26 |
Secondary
PK Part C: Area Under the Concentration Versus Time Curve [AUC (0-τ)] of Tirzepatide
PK Part C: Area under the concentration versus time curve during one dosing interval (168 hours) \[AUC (0-τ)\] of tirzepatide.
Time frame: Part C: Predose, 8 hours (h) (day (D)1), 24h (D2), 48h (D3),72h (D4), predose (D8), predose (D15), 8h (D15), 24h (D16), 48h (D17), 72h (D18), predose (D22), 8h (D22), 24h (D23), 48h (D24), 72h (D25), D57 and >= D96 postdose
Population: All randomized participants from Part C group, who received at least one dose of study drug and had evaluable PK data. As per planned analysis, for 10 mg Tirzepatide SC-Part C arm, no PK samples were collected at 168 hour post dose (after the fourth dose. i.e. following dose at Week 4). Hence, no data was collected to calculate AUC (0-τ) for 10 mg Tirzepatide SC-Part C arm.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| 5 mg Tirzepatide SC (Lyophilized)-Part A | PK Part C: Area Under the Concentration Versus Time Curve [AUC (0-τ)] of Tirzepatide | 68900 ng*hr/mL | Geometric Coefficient of Variation 19 |
| 5 mg Tirzepatide SC (Solution)-Part A | PK Part C: Area Under the Concentration Versus Time Curve [AUC (0-τ)] of Tirzepatide | 149000 ng*hr/mL | Geometric Coefficient of Variation 26 |
Secondary
PK Part C: Maximum Observed Drug Concentration (Cmax) of Tirzepatide
PK Part C: Maximum observed plasma drug concentration (Cmax) of tirzepatide.
Time frame: Part C: Predose, 8 hours (h) (day (D)1), 24h (D2), 48h (D3),72h (D4), predose (D8), predose (D15), 8h (D15), 24h (D16), 48h (D17), 72h (D18), predose (D22), 8h (D22), 24h (D23), 48h (D24), 72h (D25), D57 and >= D96 postdose
Population: All randomized participants participants from Part C group, who received at least one dose of study drug and had evaluable PK data.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| 5 mg Tirzepatide SC (Lyophilized)-Part A | PK Part C: Maximum Observed Drug Concentration (Cmax) of Tirzepatide | 663 ng/mL | Geometric Coefficient of Variation 23 |
| 5 mg Tirzepatide SC (Solution)-Part A | PK Part C: Maximum Observed Drug Concentration (Cmax) of Tirzepatide | 1270 ng/mL | Geometric Coefficient of Variation 24 |
| 10 mg Tirzepatide SC-Part C | PK Part C: Maximum Observed Drug Concentration (Cmax) of Tirzepatide | 1900 ng/mL | Geometric Coefficient of Variation 24 |
Secondary
PK Part D: Area Under the Concentration Versus Time Curve [AUC (0-∞)] of Tirzepatide
PK Part D: Area under the concentration versus time curve \[AUC (0-∞)\] of tirzepatide.
Time frame: Part D: Predose, 0.08 hours (h), 0.16h, 0.5h, 1h, 2h, 4h, 8h, 12h, 24h, 36h, 48h, 72h, 96h, 120h, 144h, 168h, 336h, 816-864h and >= 70 days postdose
Population: All randomized participants from Part D group, who received at least one dose of study drug and had evaluable PK data.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| 5 mg Tirzepatide SC (Lyophilized)-Part A | PK Part D: Area Under the Concentration Versus Time Curve [AUC (0-∞)] of Tirzepatide | 14000 ng*hr/mL | Geometric Coefficient of Variation 16 |