Healthy
Conditions
Brief summary
The purpose of this study is to look at how the body processes the commonly prescribed birth control pill, ethinylestradiol + norgestimate (EE/NGM), in healthy female participants and the effect of tirzepatide on how EE/NGM is processed by the body. Information about any side effects that may occur will also be collected. Screening is required within 28 days prior to the start of the study. For each participant, the study will last about 20 weeks, including screening.
Interventions
DRUGTirzepatide
Administered SC
DRUGEE/NGM
Combination oral contraceptive administered orally
Sponsors
Eli Lilly and Company
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
BASIC_SCIENCE
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
18 Years to 45 Years
Healthy volunteers
Yes
Inclusion criteria
* Overtly healthy females as determined by medical history, physical examination, and other screening procedures * Have a body mass index (BMI) equal to or above 18.5 kilograms per meter squared (kg/m²), at screening * Are not intending to start a family within 2 months after the study
Exclusion criteria
* Have known allergies to either tirzepatide or ethinylestradiol or norgestimate or related compounds * Have a medical condition or medical history that precludes the taking of combined oral contraceptives * Have a history or presence of pancreatitis (history of chronic pancreatitis or idiopathic acute pancreatitis), elevation in serum amylase or lipase or gastrointestinal (GI) disorder (eg, relevant esophageal reflux or gall bladder disease) or any GI disease which impacts gastric emptying (eg, gastric bypass surgery, pyloric stenosis, with the exception of appendectomy) or could be aggravated by glucagon-like peptide-1 (GLP-1) analogs or dipeptidyl peptidase IV (DPP-IV) inhibitors * Have used hormonal implants or received hormonal injections in the past 12 months * Unwilling to comply with smoking restrictions during the study * Is a known user of drugs of abuse
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Period 1 and Period 2, Pharmacokinetics (PK): Area Under the Concentration Versus Time Curve (AUC) Within 1 Dosing Interval (AUC[0-tau]) of Ethinylestradiol (EE) | Period 1 and Period 2: Predose, 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 16, 24, 48 hours postdose | Pharmacokinetics (PK): Area Under the Concentration Versus Time Curve (AUC) Within 1 Dosing Interval (AUC\[0-tau\]) of Ethinylestradiol (EE) |
| Period 1 and Period 2, PK: Maximum Concentration (Cmax) of EE | Predose, 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 16, 24, 48 hours postdose | PK: Cmax of EE |
| Period 1 and Period 2, PK: Area Under the Concentration Versus Time Curve (AUC) Within 1 Dosing Interval (AUC[0-tau]) of Norelgestromin (NGMN) | Predose, 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 16, 24, 48 hours postdose | PK: Area Under the Concentration Versus Time Curve (AUC) Within 1 Dosing Interval (AUC\[0-tau\]) of Norelgestromin (NGMN) |
| Period 1 and Period 2, PK: Cmax of Norelgestromin (NGMN) | Predose, 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 16, 24, 48 hours postdose | PK: Cmax of Norelgestromin (NGMN) |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Overall Study Lead In Period and Period 1:
Participants received a 28-day packet of a combination OC containing 21 days of tablets that consist of active ingredients (0.035 mg EE and 0.25 mg NGM) self-administered QD on Day 1 to Day 21, and 7 days of non-active tablets self-administer orally QD on Day 22 to Day 28 approximately the same time each day.
Period 2:
Participants received a 28-day packet of a combination OC containing 21 days of tablets that consist of active ingredients (0.035 mg EE and 0.25 mg NGM) self-administered orally QD on Day 1 to Day 21, and 7 days of non-active tablets self-administer orally QD on Day 22 to Day 28 approximately the same time each day and a single dose 5 mg tirzepatide administered SC. | 40 |
| Total | 40 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Lead In Period | Adverse Event | 1 |
| Lead In Period | Protocol Violation | 1 |
| Period 1 | Physician Decision | 1 |
| Period 2 | Adverse Event | 5 |
| Period 2 | Dosing Termination by Sponsor | 4 |
Baseline characteristics
| Characteristic | Overall Study |
|---|---|
| Age, Continuous | 33.6 years STANDARD_DEVIATION 7.6 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 23 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 17 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 | 18 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 | 20 Participants |
| Region of Enrollment United States | 40 Participants |
| Sex: Female, Male Female | 40 Participants |
| Sex: Female, Male Male | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 40 | 0 / 38 | 0 / 28 |
| other Total, other adverse events | 9 / 40 | 10 / 38 | 18 / 28 |
| serious Total, serious adverse events | 0 / 40 | 0 / 38 | 0 / 28 |
Outcome results
Primary
Period 1 and Period 2, Pharmacokinetics (PK): Area Under the Concentration Versus Time Curve (AUC) Within 1 Dosing Interval (AUC[0-tau]) of Ethinylestradiol (EE)
Pharmacokinetics (PK): Area Under the Concentration Versus Time Curve (AUC) Within 1 Dosing Interval (AUC\[0-tau\]) of Ethinylestradiol (EE)
Time frame: Period 1 and Period 2: Predose, 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 16, 24, 48 hours postdose
Population: Period 1 and Period 2: All participants who received at least one dose of oral contraceptive or tirzepatide and had evaluable PK data.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| OC (0.035 mg EE and 0.25 mg NGM) | Period 1 and Period 2, Pharmacokinetics (PK): Area Under the Concentration Versus Time Curve (AUC) Within 1 Dosing Interval (AUC[0-tau]) of Ethinylestradiol (EE) | 966 picogram hour per milliliter (pg*h/mL) | Geometric Coefficient of Variation 40 |
| OC (0.035 mg EE and 0.25 mg NGM) + 5 mg Tirzepatide | Period 1 and Period 2, Pharmacokinetics (PK): Area Under the Concentration Versus Time Curve (AUC) Within 1 Dosing Interval (AUC[0-tau]) of Ethinylestradiol (EE) | 811 picogram hour per milliliter (pg*h/mL) | Geometric Coefficient of Variation 41 |
Primary
Period 1 and Period 2, PK: Area Under the Concentration Versus Time Curve (AUC) Within 1 Dosing Interval (AUC[0-tau]) of Norelgestromin (NGMN)
PK: Area Under the Concentration Versus Time Curve (AUC) Within 1 Dosing Interval (AUC\[0-tau\]) of Norelgestromin (NGMN)
Time frame: Predose, 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 16, 24, 48 hours postdose
Population: Period 1 and Period 2: All participants who received at least one dose of oral contraceptive or tirzepatide and had evaluable PK data.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| OC (0.035 mg EE and 0.25 mg NGM) | Period 1 and Period 2, PK: Area Under the Concentration Versus Time Curve (AUC) Within 1 Dosing Interval (AUC[0-tau]) of Norelgestromin (NGMN) | 19900 pg*h/mL | Geometric Coefficient of Variation 27 |
| OC (0.035 mg EE and 0.25 mg NGM) + 5 mg Tirzepatide | Period 1 and Period 2, PK: Area Under the Concentration Versus Time Curve (AUC) Within 1 Dosing Interval (AUC[0-tau]) of Norelgestromin (NGMN) | 14600 pg*h/mL | Geometric Coefficient of Variation 67 |
Primary
Period 1 and Period 2, PK: Cmax of Norelgestromin (NGMN)
PK: Cmax of Norelgestromin (NGMN)
Time frame: Predose, 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 16, 24, 48 hours postdose
Population: Period 1 and Period 2: All participants who received at least one dose of oral contraceptive or tirzepatide and had evaluable PK data.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| OC (0.035 mg EE and 0.25 mg NGM) | Period 1 and Period 2, PK: Cmax of Norelgestromin (NGMN) | 2070 pg/mL | Geometric Coefficient of Variation 27 |
| OC (0.035 mg EE and 0.25 mg NGM) + 5 mg Tirzepatide | Period 1 and Period 2, PK: Cmax of Norelgestromin (NGMN) | 892 pg/mL | Geometric Coefficient of Variation 74 |
Primary
Period 1 and Period 2, PK: Maximum Concentration (Cmax) of EE
PK: Cmax of EE
Time frame: Predose, 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 16, 24, 48 hours postdose
Population: Period 1 and Period 2: All participants who received at least one dose of oral contraceptive or tirzepatide and had evaluable PK data.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| OC (0.035 mg EE and 0.25 mg NGM) | Period 1 and Period 2, PK: Maximum Concentration (Cmax) of EE | 119 picogram per milliliter pg/mL | Geometric Coefficient of Variation 33 |
| OC (0.035 mg EE and 0.25 mg NGM) + 5 mg Tirzepatide | Period 1 and Period 2, PK: Maximum Concentration (Cmax) of EE | 49.6 picogram per milliliter pg/mL | Geometric Coefficient of Variation 63 |