A Study of LY2216684 in Healthy Females

• ClinicalTrials.gov Identifier: NCT01373931
• Recruitment Status: Completed
• First Posted: June 15, 2011
• Results First Posted: October 23, 2018
• Last Update Posted: October 23, 2018
• Sponsor: Eli Lilly and Company
• Information provided by (Responsible Party): Eli Lilly and Company

Study Description

Brief Summary:

This study involves a single dose of 18 milligrams (mg) LY2216684 taken as 1 or 2 tablets by mouth. The study will evaluate effect of LY2216684 on the pharmacokinetics of an oral contraceptive Ortho Cyclen®. This study will run approximately 93 days.

Condition or disease	Intervention/treatment	Phase
Depressive Disorder, Major	Drug: LY2216684; Drug: Ortho Cyclen; Drug: Placebo	Phase 1

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 20 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Masking: Single (Participant)
• Primary Purpose: Treatment
• Official Title: Effect of LY2216684 on Oral Contraceptive Pharmacokinetics in Healthy Female Subjects
• Study Start Date: June 2011
• Actual Primary Completion Date: December 2011
• Actual Study Completion Date: December 2011

Arms and Interventions

Arm	Intervention/treatment
Experimental: OC + LY2216684 First, Then OC + Placebo; 28-day lead-in period of Ortho Cyclen (OC; 28-day packet), followed by randomization to OC administered orally once daily for 28 days + 18 milligrams (mg) of LY2216684 administered concomitantly orally once daily for 21 days, followed by OC administered orally once daily for 28 days + placebo administered concomitantly orally once daily for 21 days.	Drug: LY2216684; Administered orally; Drug: Ortho Cyclen; 35 micrograms (mcg) ethinyl estradiol and 250 mcg norgestimate administered orally; Drug: Placebo; Administered orally
Experimental: OC + Placebo First, Then OC + LY2216684; 28-day lead-in period of OC (28-day packet), followed by randomization to OC administered orally once daily for 28 days + placebo administered concomitantly orally once daily for 21 days, followed by OC administered orally once daily for 28 days + 18 mg of LY2216684 administered concomitantly orally once daily for 21 days.	Drug: LY2216684; Administered orally; Drug: Ortho Cyclen; 35 micrograms (mcg) ethinyl estradiol and 250 mcg norgestimate administered orally; Drug: Placebo; Administered orally

Outcome Measures

Primary Outcome Measures :

1. Pharmacokinetics: Maximum Plasma Concentration (Cmax) of Ethinyl Estradiol and Norelgestromin [ Time Frame: Predose up to 24 hours post dose on Day 21 ]
   The results presented are Geometric Least Squares (LS) mean. LS mean values were adjusted for treatment, sequence, period and participant.
2. Pharmacokinetics: Time to Maximum Plasma Concentration (Tmax) of Ethinyl Estradiol and Norelgestromin [ Time Frame: Predose up to 24 hours post dose on Day 21 ]
3. Area Under the Concentration-Time Curve Over a Dosing Interval (AUCτ) of Ethinyl Estradiol and Norelgestromin [ Time Frame: Predose up to 24 hours post dose on Day 21 ]
   The results presented are Geometric Least Squares (LS) mean. LS mean values were adjusted for treatment, sequence, period and participant.

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 45 Years (Adult)
• Sexes Eligible for Study: Female
• Accepts Healthy Volunteers: Yes

Criteria

Inclusion Criteria:

• Are overtly healthy females, as determined by medical history and physical examination
• As it is possible that LY2216684 may cause the oral contraceptive tablet to be less effective than usual, participants will be required in addition to use double barrier methods of contraception from the Screening until 2 months after the post study follow-up. Additional barrier methods of contraception may include the following: a non-hormonal intrauterine device with spermicide; female condom with spermicide; contraceptive sponge with spermicide; diaphragm with spermicide; cervical cap with spermicide; 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
• Have a body weight of >50 kilograms (kg)
• Have clinical laboratory test results within normal reference range for the population or investigator site, or results with acceptable deviations that are judged to be not clinically significant by the investigator
• Have venous access sufficient to allow for blood sampling as per the protocol
• Have normal blood pressure and pulse rate (sitting position) as determined by the investigator
• Are reliable and willing to make themselves available for the duration of the study and are willing to follow study procedures
• Have given written informed consent approved by Lilly and the institutional review board (IRB) governing the site

Exclusion Criteria:

• Are currently enrolled in, have completed or discontinued within the last 30 days from, a clinical trial involving an investigational product other than the investigational product used in this study, or are concurrently enrolled in any other type of medical research judged not to be scientifically or medically compatible with this study
• Have known allergies to Ortho Cyclen, LY2216684, or related compounds
• Are participants who have previously completed or withdrawn from this study or any other study investigating LY2216684 within 6 months prior to Screening
• Have an abnormality in the 12-lead electrocardiogram (ECG) that, in the opinion of the investigator, increases the risks associated with participating in the study
• Have a history or presence of cardiovascular, respiratory, hepatic, renal, gastrointestinal, endocrine, hematological, or neurological disorders capable of significantly altering the absorption, metabolism, or elimination of drugs; of constituting a risk when taking the study medication; or of interfering with the interpretation of data
• Have a history or show evidence of significant active neuropsychiatric disease or have a history or suicide attempt or ideation
• Regular use of known drugs of abuse and/or show positive findings on urinary drug screening
• Show evidence of human immunodeficiency virus infection (HIV) and/or positive human HIV antibodies
• Show evidence of hepatitis C and/or positive hepatitis C antibody
• Show evidence of hepatitis B and/or positive hepatitis B surface antigen
• Are women with a positive pregnancy test or women who are lactating
• Intend to use over-the-counter or prescription medication (other than the acceptable oral contraceptive allowed in this study and influenza vaccinations) within 14 days prior to dosing unless deemed acceptable by the investigator and sponsor's medical monitor
• Have donated blood of more than 500 milliliter (mL) prior to lead-in phase Check-in (Day -1)
• Have an average weekly alcohol intake that exceeds 14 units per week, or are unwilling to stop alcohol consumption for 48 hours prior to each Check-in to the clinical research unit (CRU) [1 unit = 12 ounces (oz) or 360 mL of beer; 5 oz or 150 mL of wine; 1.5 oz or 45 mL of distilled spirits]
• Consume 5 or more cups of coffee (or other beverages of comparable caffeine content) per day, on a habitual basis, or any participants unwilling to adhere to study caffeine restrictions
• Use of any tobacco- or nicotine-containing products (including but not limited to cigarettes, pipes, cigars, chewing tobacco, nicotine patches, nicotine lozenges, or nicotine gum) within 6 months prior to the lead-in phase Check-in (Day -1) and during the study
• Have consumed grapefruit, starfruit, pomegranates, or products containing those items 7 days prior to enrollment or are unwilling to avoid them during the study
• Have a documented or suspected history of glaucoma
• Participants that have taken injectable contraceptives within 12 months of enrollment to this study or topical controlled delivery contraceptives (patch) for 3 months prior to enrollment into this study
• The history or presence of any contraindications to the combined oral contraceptive tablet including thrombosis and the history of any thromboembolic disease, recurrent jaundice, acute or chronic liver disease, migraines, undiagnosed vaginal bleeding, significant hyperlipidemia, and mammary, endometrial, or hepatic carcinoma (known or suspected)
• Participants determined to be unsuitable by the investigator for any reason

Contacts and Locations

Locations

United States, Wisconsin

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.

Madison, Wisconsin, United States

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

More Information

• Responsible Party: Eli Lilly and Company
• ClinicalTrials.gov Identifier: NCT01373931
• Other Study ID Numbers: 12615; H9P-EW-LNCX ( Other Identifier: Eli Lilly and Company )
• First Posted: June 15, 2011
• Results First Posted: October 23, 2018
• Last Update Posted: October 23, 2018
• Last Verified: March 2018

Additional relevant MeSH terms:

Depressive Disorder; Depressive Disorder, Major; Mood Disorders; Mental Disorders; Moxifloxacin; Norgestimate, ethinyl estradiol drug combination; Anti-Bacterial Agents; Anti-Infective Agents; Topoisomerase II Inhibitors; Topoisomerase Inhibitors; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Contraceptive Agents, Hormonal; Contraceptive Agents; Reproductive Control Agents; Physiological Effects of Drugs; Contraceptives, Oral, Combined; Contraceptives, Oral; Contraceptive Agents, Female