A Study of Baricitinib and Birth Control Pills in Healthy Females

• Sponsor: Eli Lilly and Company (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01896726
• Collaborator: (none)
• Enrollment: 20
• Location: 1
• Arm: 1
• Duration (Months): 3
• Patients Per Site Per Month: 6.6

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Healthy Volunteers	Drug: Baricitinib; Drug: Microgynon	Phase 1

Study Design

• Study Type: Interventional
• Actual Enrollment: 20 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Basic Science
• Official Title: The Effects of Multiple Doses of Baricitinib on the Pharmacokinetics of a Single Dose of an Oral Contraceptive in Healthy Female Subjects
• Study Start Date: Jul 1, 2013
• Actual Primary Completion Date: Oct 1, 2013
• Actual Study Completion Date: Oct 1, 2013

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Baricitinib + Microgynon Microgynon [30 micrograms (µg) ethinyl estradiol and 150 µg levonorgestrel] administered orally, once daily (QD), on Days 1 and 29. Baricitinib, 10 milligrams (mg), administered orally QD on Days 23 through 30.	Drug: Baricitinib; Administered orally; Other Names: LY3009104 ; Drug: Microgynon; Administered orally

Outcome Measures

Primary Outcome Measures

1. 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]

2. 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]

3. 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]

4. 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]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 65 Years
• Sexes Eligible for Study: Female
• Accepts 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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Leeds	West Yorkshire	United Kingdom	LS2 9LH

Sponsors and Collaborators

• Eli Lilly and Company

Investigators

• Study Director: Call 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

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Eli Lilly and Company
• ClinicalTrials.gov Identifier: NCT01896726
• Other Study ID Numbers: 14601; I4V-MC-JAGD
• First Posted: Jul 11, 2013
• Last Update Posted: Jun 6, 2017
• Last Verified: May 1, 2017

• Additional relevant MeSH terms: Ethinyl estradiol, levonorgestrel drug combination; Ethinyl Estradiol-Norgestrel Combination

Study Results

Participant Flow

Pre-assignment Detail	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.

Arm/Group Title	Baricitinib + Microgynon
Arm/Group Description	Microgynon tablet [30 micrograms (µg) ethinyl estradiol and 150 µg levonorgestrel] administered orally, once daily (QD), on Days 1 and 29. 10 milligrams (mg) baricitinib tablet administered orally, QD, on Days 23 through 30.
Period Title: Treatment Period 1 (Days 1-22)
STARTED	20
Received Microgynon	20
COMPLETED	20
NOT COMPLETED	0
Period Title: Treatment Period 1 (Days 1-22)
STARTED	20
Received at Least 1 Dose of Baricitinib	20
Received Microgynon	18
COMPLETED	18
NOT COMPLETED	2

Baseline Characteristics

Arm/Group Title	Baricitinib + Microgynon
Arm/Group Description	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.
Overall Participants	20
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	44.1 (12.7)
Sex: Female, Male (Count of Participants)
Female	20 100%
Male	0 0%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	0 0%
Not Hispanic or Latino	20 100%
Unknown or Not Reported	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%
Asian	0 0%
Native Hawaiian or Other Pacific Islander	0 0%
Black or African American	3 15%
White	17 85%
More than one race	0 0%
Unknown or Not Reported	0 0%
Region of Enrollment (Count of Participants)
United Kingdom	20 100%

Outcome Measures

1. Primary Outcome

Title	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

Outcome Measure Data

Analysis Population Description

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/Group Title	Microgynon Alone	Baricitinib + Microgynon
Arm/Group Description	Microgynon tablet (30 µg ethinyl estradiol and 150 µg levonorgestrel) administered orally, QD, on Day 1	10 mg baricitinib tablet administered orally, QD, on Days 23 through 30 with coadministration of Microgynon tablet (30 µg ethinyl estradiol and 150 µg levonorgestrel) administered orally, QD, on Day 29.
Measure Participants	20	18
Geometric Mean (Geometric Coefficient of Variation) [picograms/milliliter (pg/mL)]	63.8 (23)	59.7 (24)

2. Primary Outcome

Title	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

Outcome Measure Data

Analysis Population Description

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/Group Title	Microgynon Alone	Baricitinib + Microgynon
Arm/Group Description	Microgynon tablet (30 µg ethinyl estradiol and 150 µg levonorgestrel) administered orally, QD, on Day 1	10 mg baricitinib tablet administered orally, QD, on Days 23 through 30 with coadministration of Microgynon tablet (30 µg ethinyl estradiol and 150 µg levonorgestrel) administered orally, QD, on Day 29.
Measure Participants	20	18
Geometric Mean (Geometric Coefficient of Variation) [pg/mL]	3390 (34)	3340 (26)

3. Primary Outcome

Title	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

Outcome Measure Data

Analysis Population Description

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/Group Title	Microgynon Alone	Baricitinib + Microgynon
Arm/Group Description	Microgynon tablet (30 µg ethinyl estradiol and 150 µg levonorgestrel) administered orally, QD, on Day 1	10 mg baricitinib tablet administered orally, QD, on Days 23 through 30 with coadministration of Microgynon tablet (30 µg ethinyl estradiol and 150 µg levonorgestrel) administered orally, QD, on Day 29.
Measure Participants	20	18
Geometric Mean (Geometric Coefficient of Variation) [picograms*hour/milliliter (pg*hr/mL)]	694 (24)	697 (25)

4. Primary Outcome

Title	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

Outcome Measure Data

Analysis Population Description

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/Group Title	Microgynon Alone	Baricitinib + Microgynon
Arm/Group Description	Microgynon tablet (30 µg ethinyl estradiol and 150 µg levonorgestrel) administered orally, QD, on Day 1	10 mg baricitinib tablet administered orally, QD, on Days 23 through 30 with coadministration of Microgynon tablet (30 µg ethinyl estradiol and 150 µg levonorgestrel) administered orally, QD, on Day 29.
Measure Participants	20	18
Geometric Mean (Geometric Coefficient of Variation) [pg*hr/mL]	48200 (58)	42400 (45)

Adverse Events

Time Frame	Baseline through study completion (up to Day 40).
Arm/Group Title	Microgynon Alone		Baricitinib		Baricitinib + Microgynon
Arm/Group Description	Microgynon tablet (30 µg ethinyl estradiol and 150 µg levonorgestrel) administered orally, QD, on Day 1. Adverse events are reported from baseline through predose on Day 23.		10 mg baricitinib tablet administered orally, QD, on Days 23 through 28. Adverse events are reported from postdose on Day 23 through predose on Day 29.		10 mg baricitinib tablet administered orally, QD, on Days 29 through 30 with coadministration of Microgynon tablet (30 µg ethinyl estradiol and 150 µg levonorgestrel) administered orally, QD, on Day 29. Adverse events are reported from postdose on Day 29 up to Day 40.
All Cause Mortality
	Microgynon Alone		Baricitinib		Baricitinib + Microgynon
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	Microgynon Alone		Baricitinib		Baricitinib + Microgynon
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/20 (0%)		0/20 (0%)		1/18 (5.6%)
Injury, poisoning and procedural complications
Maternal exposure during pregnancy	0/20 (0%)	0	0/20 (0%)	0	1/18 (5.6%)	1
Other (Not Including Serious) Adverse Events
	Microgynon Alone		Baricitinib		Baricitinib + Microgynon
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	3/20 (15%)		4/20 (20%)		4/18 (22.2%)
Gastrointestinal disorders
Diarrhoea	0/20 (0%)	0	0/20 (0%)	0	1/18 (5.6%)	1
Flatulence	0/20 (0%)	0	0/20 (0%)	0	1/18 (5.6%)	1
Infections and infestations
Vulvovaginal candidiasis	0/20 (0%)	0	0/20 (0%)	0	1/18 (5.6%)	1
Metabolism and nutrition disorders
Decreased appetite	0/20 (0%)	0	1/20 (5%)	1	1/18 (5.6%)	1
Musculoskeletal and connective tissue disorders
Back pain	1/20 (5%)	1	2/20 (10%)	2	0/18 (0%)	0
Nervous system disorders
Headache	2/20 (10%)	2	1/20 (5%)	1	0/18 (0%)	0

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.