Healthy, Obese, Obesity, Overweight
Conditions
Keywords
Pharmacokinetics
Brief summary
The main purpose of this study is to see how much of orforglipron (study drug) gets into the bloodstream and how long it takes the body to get rid of it when given as capsules compared to tablets in healthy overweight and obese participants. The safety and tolerability (side effects) of orforglipron when given as capsules and tablets will also be evaluated. The study will be conducted in two parts, with part A and B lasting up to approximately 25 and 22 weeks each respectively, including the screening period.
Interventions
DRUGOrforglipron
Administered orally
Sponsors
Eli Lilly and Company
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
BASIC_SCIENCE
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
Yes
Inclusion criteria
* Participants who are overtly healthy as determined by medical history and physical examination. * Have a stable body weight for one month prior to screening (less than or equal to 5 percent body weight gain or loss) and Body Mass Index (BMI) in range of 27 to 40 kilogram per meter square (kg/m²). * Participants must be reliable and willing to make themselves available for the duration of the study and are willing to follow study procedures. * Have venous access sufficient to allow for blood sampling.
Exclusion criteria
* Have hemoglobin A1c (HbA1c) level of 6.5 percent (%) or greater. * Have a history of current cardiovascular, respiratory, hepatic, renal, gastrointestinal, endocrine, hematological, or neurological disorders or other significant active, uncontrolled medical conditions. * Have significant history of or currently have major depressive disorder or psychiatric disorder within the last 2 years. * Obesity induced by other endocrine disorders, such as Cushing's syndrome or Prader-Willi syndrome. * Have known clinically significant gastric emptying abnormality. * Have undergone bariatric surgery (for example: Lap-Band, Gastric Bypass) * Have a known self or family history (first-degree relative) of multiple endocrine neoplasia type 2A or type 2B, thyroid C-cell hyperplasia, or any form of thyroid cancer. * Have an abnormal 12-lead electrocardiogram (ECG) at screening. * Have history of pancreatitis. * Judged by the study investigator to be at serious suicidal risk and have answered "Yes" to either question 4 or 5 on the Columbia-Suicide Severity Rating Scale \[C-SSRS\]). * Have difficulty swallowing capsules or tablets.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Part B: Pharmacokinetics (PK): Steady-state Area Under the Concentration Time Curve From Time Zero to the End of the Dosing Interval, Tau (AUC[0-tau]) of LY3502970 on Day 7 | Pre-dose, 0.5, 1, 2, 4, 6, 8, 12, 16 and 24 hours post-dose on Day 7 for each dosing treatment period (1 period=7 days) | PK: Area under the concentration versus time curve from time 0 to the end of the once daily dosing interval at steady state AUC\[0-tau\] on Day 7. |
| Part B: PK: Steady-state Maximum Observed Concentration (Cmax) of LY3502970 on Day 7 | Pre-dose, 0.5, 1, 2, 4, 6, 8, 12, 16 and 24 hours post-dose on Day 7 for each dosing treatment period (1 period=7 days) | PK: Maximum concentration of LY3502970 during a once daily dosing interval at steady state on Day 7. |
Countries
United States
Contacts
STUDY_DIRECTORCall 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 Mon - Fri 9 AM - 5 PM Eastern time (UTC/GMT - 5 hours, EST)
Eli Lilly and Company
Participant flow
Recruitment details
This study enrolled 533 participants across 4 mutually exclusive cohorts in 2 parts: Part A (pilot relative bioavailability; Cohorts 1A and 2A) and Part B (bioequivalence; Cohorts 1B and 2B). As per sponsor decision, for Part A tablet (Cohorts 1A and 2A), dose levels are presented as Dose Level 1 through Dose Level 18, where Dose Level 1 represents the lowest dose and Dose Level 18 represents the highest dose.
Pre-assignment details
Part A: Cohorts 1A and 2A (each N=52) followed a 4-sequence crossover (12 and 18 periods); Cohort 2A included home (Periods 1-6) and inpatient dosing (Periods 7-18). Part B: Cohorts 1B (N=216; 9 periods) and 2B (N=213; 15 periods) followed a 3-sequence crossover; Cohort 2B included home (Periods 1-6) and inpatient dosing (Periods 7-15).
Baseline characteristics
| Characteristic | — |
|---|---|
| Age, Continuous | 42.8 Years STANDARD_DEVIATION 10.28 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 142 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 390 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 7 Participants |
| Race (NIH/OMB) Asian | 9 Participants |
| Race (NIH/OMB) Black or African American | 21 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 3 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 1 Participants |
| Race (NIH/OMB) White | 284 Participants |
| Region of Enrollment United States | 216 Participants |
| Sex: Female, Male Female | 214 Participants |
| Sex: Female, Male Male | 30 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 | EG009 affected / at risk | EG010 affected / at risk | EG011 affected / at risk | EG012 affected / at risk | EG013 affected / at risk | EG014 affected / at risk | EG015 affected / at risk | EG016 affected / at risk | EG017 affected / at risk | EG018 affected / at risk | EG019 affected / at risk | EG020 affected / at risk | EG021 affected / at risk | EG022 affected / at risk | EG023 affected / at risk | EG024 affected / at risk | EG025 affected / at risk | EG026 affected / at risk | EG027 affected / at risk | EG028 affected / at risk | EG029 affected / at risk | EG030 affected / at risk | EG031 affected / at risk | EG032 affected / at risk | EG033 affected / at risk | EG034 affected / at risk | EG035 affected / at risk | EG036 affected / at risk | EG037 affected / at risk |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 52 | 0 / 52 | 0 / 52 | 0 / 52 | 0 / 47 | 0 / 51 | 0 / 48 | 0 / 51 | 0 / 46 | 0 / 46 | 0 / 47 | 0 / 46 | 0 / 52 | 0 / 50 | 0 / 50 | 0 / 50 | 0 / 50 | 0 / 50 | 0 / 49 | 0 / 49 | 0 / 50 | 0 / 45 | 0 / 45 | 0 / 45 | 0 / 45 | 0 / 215 | 0 / 213 | 0 / 210 | 0 / 210 | 0 / 203 | 0 / 203 | 0 / 213 | 0 / 186 | 0 / 186 | 0 / 181 | 0 / 180 | 0 / 176 | 0 / 176 |
| other Total, other adverse events | 6 / 52 | 8 / 52 | 7 / 52 | 9 / 52 | 6 / 47 | 9 / 51 | 10 / 48 | 13 / 51 | 7 / 46 | 6 / 46 | 7 / 47 | 10 / 46 | 11 / 52 | 7 / 50 | 16 / 50 | 11 / 50 | 8 / 50 | 13 / 50 | 10 / 49 | 13 / 49 | 10 / 50 | 9 / 45 | 9 / 45 | 9 / 45 | 9 / 45 | 92 / 215 | 49 / 213 | 96 / 210 | 57 / 210 | 80 / 203 | 51 / 203 | 111 / 213 | 97 / 186 | 61 / 186 | 85 / 181 | 56 / 180 | 66 / 176 | 35 / 176 |
| serious Total, serious adverse events | 0 / 52 | 0 / 52 | 0 / 52 | 0 / 52 | 0 / 47 | 0 / 51 | 0 / 48 | 0 / 51 | 0 / 46 | 0 / 46 | 0 / 47 | 0 / 46 | 0 / 52 | 0 / 50 | 0 / 50 | 0 / 50 | 0 / 50 | 0 / 50 | 1 / 49 | 0 / 49 | 0 / 50 | 0 / 45 | 0 / 45 | 0 / 45 | 0 / 45 | 0 / 215 | 0 / 213 | 0 / 210 | 0 / 210 | 1 / 203 | 1 / 203 | 0 / 213 | 0 / 186 | 0 / 186 | 0 / 181 | 0 / 180 | 1 / 176 | 0 / 176 |
Outcome results
None listed