Healthy
Conditions
Brief summary
The purpose of this study is to determine the effect of quinidine on the levels of orforglipron in the blood stream and how long it takes the body to eliminate it, when administered orally in healthy participants. The study will last up to approximately 8 weeks including screening.
Interventions
DRUGOrforglipron
Administered orally
DRUGMidazolam
Administered orally
DRUGQuinidine
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
21 Years to 70 Years
Healthy volunteers
Yes
Inclusion criteria
* Are overtly healthy as determined by medical evaluation including medical history, physical examination, laboratory tests, and electrocardiogram (ECG) * Have a hemoglobin level of: * at least 11.4 grams per deciliter (g/dL) for individuals assigned female at birth (AFAB), and * at least 12.5 g/dL for individuals assigned male at birth (AMAB) * Have a body weight equal to or greater than 45 kilograms (kg), and a body mass index within the range of 18.5 to 35.0 kilogram per square meter (kg/m²) at screening
Exclusion criteria
* Have significant history of or current cardiovascular, respiratory, hepatic, renal, gastrointestinal (GI), endocrine, hematological, psychological, or neurological disorders capable of significantly altering the absorption, metabolism, or elimination of drugs; of constituting risk when taking orforglipron, midazolam, or quinidine; or interfering with the interpretation of data * Have a 12 lead electrocardiogram (ECG) abnormality, including known prolongation of QT/QTc interval, significant bradycardia, significant heart blocks or a history of any risk factors for ventricular arrhythmia, heart failure, hypokalemia or hypomagnesemia, or other factors that, in the opinion of the investigator, increases the risks associated with participating in the study * Have an abnormal blood pressure or pulse rate, deemed to be clinically significant by the investigator * Have a history of benign ethnic neutropenia * Have a GI disease or disorder, such as relevant esophageal reflux or gall bladder disease, which could be aggravated by glucagon-like peptide-1 (GLP-1) analogs or impacts gastric emptying, for example gastric bypass surgery or pyloric stenosis, except for appendectomy * Have a history or presence of pancreatitis, including chronic pancreatitis or idiopathic acute pancreatitis * Have known allergies to: * quinidine * midazolam * orforglipron * related compounds, or * any components of the formulation
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Pharmacokinetics (PK): Area Under the Concentration Versus Time Curve From Time Zero to Infinity (AUC0-inf) of Orforglipron | Predose, 0.5, 1, 2, 4, 6, 8, 12, 16, 24, 48, 72, 96 hours post orforglipron dose on days 1, 8 | PK: AUC0-inf of Orforglipron. |
| PK: Maximum Observed Concentration (Cmax) of Orforglipron | Predose, 0.5, 1, 2, 4, 6, 8, 12, 16, 24, 48, 72, 96 hours post orforglipron dose on days 1, 8 | PK: Cmax of Orforglipron. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| PK: Area Under the Concentration Versus Time Curve From Time Zero to Infinity (AUC0-inf) of Midazolam | Predose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24 hours post midazolam dose on days -1, 7 | PK: AUC0-inf of Midazolam. |
| PK: Maximum Concentration (Cmax) of Midazolam | Predose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24 hours post midazolam dose on days -1, 7 | PK: Cmax of Midazolam. |
| PK: Area Under the Concentration Versus Time Curve From Time Zero to Infinity (AUC0-inf) of 1-Hydroxymidazolam | Predose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24 hours post midazolam dose on days -1, 7 | PK: AUC0-inf of 1-Hydroxymidazolam (metabolite of Midazolam). |
| PK: Maximum Concentration (Cmax) of 1-Hydroxymidazolam | Predose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24 hours post midazolam dose on days -1, 7 | PK: Cmax of 1-Hydroxymidazolam (metabolite of Midazolam). |
Countries
United States
Contacts
STUDY_DIRECTORContact Lilly at 1-800-LillyRx (1-800-545-5979)
Eli Lilly and Company
Baseline characteristics
| Characteristic | — |
|---|---|
| Age, Continuous | 35.3 years STANDARD_DEVIATION 9.3 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 4 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 23 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants |
| Race (NIH/OMB) Black or African American | 3 Participants |
| Race (NIH/OMB) More than one race | 1 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 22 Participants |
| Region of Enrollment United States | 27 Participants |
| Sex: Female, Male Female | 13 Participants |
| Sex: Female, Male Male | 14 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 |
|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 27 | 0 / 27 | 0 / 27 | 0 / 27 | 0 / 27 |
| other Total, other adverse events | 4 / 27 | 7 / 27 | 6 / 27 | 1 / 27 | 7 / 27 |
| serious Total, serious adverse events | 0 / 27 | 0 / 27 | 0 / 27 | 0 / 27 | 0 / 27 |
Outcome results
None listed