Healthy Volunteers
Conditions
Brief summary
The main purpose of this study is to find out how the body absorbs and breaks down a common birth control pill called Microgynon when it is given with the study drug called baricitinib. Safety and the body's ability to tolerate baricitinib and Microgynon will also be studied. The study will last approximately 6 weeks for each participant.
Interventions
DRUGBaricitinib
Administered orally
DRUGMicrogynon
Administered orally
Sponsors
Eli Lilly and Company
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
BASIC_SCIENCE
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
18 Years to 65 Years
Healthy volunteers
Yes
Inclusion criteria
* Premenopausal females currently successfully using non-hormonal methods of contraception including tubular ligation, cervical vault cap, diaphragm, or non-hormonal coil with spermicide will be required in addition to use a second approved method of contraception for the duration of the study \[that is (i.e.), a male sexual partner who agrees to use a male condom with spermicide; a sterile sexual partner; or abstinence (participants reporting abstinence who become sexually active while on the study must agree to use other additional barrier methods of contraception)\]. The pregnancy test result must be negative at screening and at each check-in visit. Participants must have a regular menstrual cycle of approximately 28 days duration for at least 4 previous cycles prior to screening * Postmenopausal females, or women not of child-bearing potential due to surgical sterilization (at least 3 months after surgical hysterectomy, or at least 3 months after bilateral oophorectomy or bilateral tubal occlusion with or without hysterectomy) confirmed by medical history, or menopause. Menopausal women include women with spontaneous amenorrhea for at least 12 months or amenorrhea not induced by a medical condition such as anorexia nervosa and/or not taking medications during that time of amenorrhea \[example (e.g.), oral contraceptives (OCs), hormones, gonadotropin releasing hormone, anti-estrogens, selective estrogen receptor modulators, or chemotherapy\]. Postmenopausal status should be confirmed by a serum follicle-stimulating hormone level at screening greater than 40 international units per liter (IU/L) * Have a body mass index of 18 to 30 kilograms per square meter (kg/m\^2), inclusive
Exclusion criteria
* Have a positive pregnancy test or are lactating * Are currently enrolled in, have completed or discontinued within the last 90 days from a clinical trial involving a study drug; or are concurrently enrolled in any other type of medical research judged not to be scientifically or medically compatible with this study * Are persons who have previously completed or withdrawn from this study or any other study investigating baricitinib, and have previously received the study drug * Have known allergies to baricitinib or Microgynon (containing ethinyl estradiol and levonorgestrel) or related compounds * Have used or intend to use drugs or substances that are known to be inducers or inhibitors of cytochrome P450 3A (eg, St. John's wort, rifampin, ketoconazole) within 30 days prior to the first dose * Have taken OCs within 3 months, implanted contraceptives within 6 months, injectable contraceptives within 12 months, or topical controlled delivery contraceptives (patch) or hormonal coils within 3 months prior to the study * Have a history or presence of any thromboembolic disease, recurrent jaundice, acute or chronic liver disease, hormonally-induced migraines, undiagnosed vaginal bleeding, significant hyperlipidemia, and mammary, endometrial, or hepatic carcinoma (known or suspected) * Smokes more than 10 cigarettes per day
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Pharmacokinetics (PK): Maximum Concentration (Cmax) of Ethinyl Estradiol | Days 1 and 29: predose and 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, 14, 24 and 48 hours post dose |
| PK: Cmax of Levonorgestrel | Days 1 and 29: predose and 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, 14, 24 and 48 hours post dose |
| PK: Area Under the Concentration Versus Time Curve From Time Zero to Infinity [AUC(0-∞)] of Ethinyl Estradiol | Days 1 and 29: predose and 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, 14, 24 and 48 hours post dose |
| PK: AUC(0-∞) of Levonorgestrel | Days 1 and 29: predose and 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, 14, 24 and 48 hours post dose |
Countries
United Kingdom
Participant flow
Pre-assignment details
This was an open-label, fixed-sequence, 2-period study. Each participant received a single dose of Microgynon on Day 1 of Treatment Period 1. During Treatment Period 2, participants received baricitinib on Days 23 through 30 with coadministration of Microgynon on Day 29.
Participants by arm
| Arm | Count |
|---|---|
| Baricitinib + Microgynon Microgynon tablet (30 µg ethinyl estradiol and 150 µg levonorgestrel) administered orally, QD, on Days 1 and 29. 10 mg baricitinib tablet administered orally, QD, on Days 23 through 30. | 20 |
| Total | 20 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Treatment Period 2 (Days 23-31) | Adverse Event | 1 |
| Treatment Period 2 (Days 23-31) | Lost to Follow-up | 1 |
Baseline characteristics
| Characteristic | Baricitinib + Microgynon |
|---|---|
| Age, Continuous | 44.1 years STANDARD_DEVIATION 12.7 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 20 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 3 Participants |
| Race (NIH/OMB) More than one race | 0 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 | 17 Participants |
| Region of Enrollment United Kingdom | 20 Participants |
| Sex: Female, Male Female | 20 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 | — / — | — / — | — / — |
| other Total, other adverse events | 3 / 20 | 4 / 20 | 4 / 18 |
| serious Total, serious adverse events | 0 / 20 | 0 / 20 | 1 / 18 |
Outcome results
Primary
Pharmacokinetics (PK): Maximum Concentration (Cmax) of Ethinyl Estradiol
Time frame: Days 1 and 29: predose and 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, 14, 24 and 48 hours post dose
Population: All enrolled participants who received study drug (Microgynon in Period 1 and at least 1 dose of baricitinib and Microgynon in Period 2) and had PK data to calculate Cmax of ethinyl estradiol.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Microgynon Alone | Pharmacokinetics (PK): Maximum Concentration (Cmax) of Ethinyl Estradiol | 63.8 picograms/milliliter (pg/mL) | Geometric Coefficient of Variation 23 |
| Baricitinib + Microgynon | Pharmacokinetics (PK): Maximum Concentration (Cmax) of Ethinyl Estradiol | 59.7 picograms/milliliter (pg/mL) | Geometric Coefficient of Variation 24 |
Primary
PK: Area Under the Concentration Versus Time Curve From Time Zero to Infinity [AUC(0-∞)] of Ethinyl Estradiol
Time frame: Days 1 and 29: predose and 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, 14, 24 and 48 hours post dose
Population: All enrolled participants who received study drug (Microgynon in Period 1 and at least 1 dose of baricitinib and Microgynon in Period 2) and had PK data to calculate AUC(0-∞) of ethinyl estradiol.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Microgynon Alone | PK: Area Under the Concentration Versus Time Curve From Time Zero to Infinity [AUC(0-∞)] of Ethinyl Estradiol | 694 picograms*hour/milliliter (pg*hr/mL) | Geometric Coefficient of Variation 24 |
| Baricitinib + Microgynon | PK: Area Under the Concentration Versus Time Curve From Time Zero to Infinity [AUC(0-∞)] of Ethinyl Estradiol | 697 picograms*hour/milliliter (pg*hr/mL) | Geometric Coefficient of Variation 25 |
Primary
PK: AUC(0-∞) of Levonorgestrel
Time frame: Days 1 and 29: predose and 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, 14, 24 and 48 hours post dose
Population: All enrolled participants who received study drug (Microgynon in Period 1 and at least 1 dose of baricitinib and Microgynon in Period 2) and had PK data to calculate AUC(0-∞) of levonorgestrel.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Microgynon Alone | PK: AUC(0-∞) of Levonorgestrel | 48200 pg*hr/mL | Geometric Coefficient of Variation 58 |
| Baricitinib + Microgynon | PK: AUC(0-∞) of Levonorgestrel | 42400 pg*hr/mL | Geometric Coefficient of Variation 45 |
Primary
PK: Cmax of Levonorgestrel
Time frame: Days 1 and 29: predose and 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, 14, 24 and 48 hours post dose
Population: All enrolled participants who received study drug (Microgynon in Period 1 and at least 1 dose of baricitinib and Microgynon in Period 2) and had PK data to calculate Cmax of levonorgestrel.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Microgynon Alone | PK: Cmax of Levonorgestrel | 3390 pg/mL | Geometric Coefficient of Variation 34 |
| Baricitinib + Microgynon | PK: Cmax of Levonorgestrel | 3340 pg/mL | Geometric Coefficient of Variation 26 |