A Study to Measure if There is Any Difference in How the Body Breaks Down or Inactivates Either Fluoxetine or LY2216684 When Both of These Medicines Are Given Together.

NCT01243957 | Completed Phase 1 Results

• 2 other identifiers: 12597H9P-EW-LNCH
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to measure if there is any difference in how the body breaks down or inactivates either fluoxetine or LY2216684 when both of these medicines are given together. This study will look at how fluoxetine might affect LY2216684 and how giving LY2216684 might affect fluoxetine in the body. The duration of study participation in this study is approximately 36 days not including the screening appointment. This study requires 1 research unit confinement of 29 days/28 nights followed by 1 outpatient appointment. A screening appointment is required within 30 days prior to the start of the study.

Conditions

Major Depressive Disorder

Outcome Measures

Primary Outcomes (3)

• Pharmacokinetic (PK) Parameter: Area Under the Plasma Concentration-Time Curve Over a 24-Hour Dosing Interval (AUCτ) of LY2216684

  The Least Squares (LS) geometric mean AUCτ of LY2216684 was calculated based on the LY2216684 plasma concentration time curve from time 0 hour (hr) to time 24 hr (tau \[τ\]) when LY2216684 was administered alone (Day 3) and when LY2216684 was coadministered with fluoxetine (Day 27). The Day 27-to-Day 3 ratio of the LY2216684 LS geometric mean of AUCτ and the associated 90% confidence interval (CI) of the ratio were calculated.

  Predose and 1, 2, 3, 4, 6, 8, 12, and 24 hours post-dose on Days 3 and 27

• Pharmacokinetic (PK) Parameter: Maximum Plasma Concentration (Cmax) of LY2216684

  The Least Squares (LS) geometric mean Cmax of LY2216684 was determined when LY2216684 was administered alone (Day 3) and when LY2216684 was coadministered with fluoxetine (Day 27). The Day 27-to-Day 3 ratio of the LY2216684 LS geometric mean of Cmax and the associated 90% confidence interval (CI) of the ratio were calculated.

  Predose and 1, 2, 3, 4, 6, 8, 12, and 24 hours post-dose on Days 3 and 27

• Pharmacokinetic (PK) Parameter: Time to Maximum Plasma Concentration (Tmax) of LY2216684

  Tmax of LY2216684 was determined using the median of paired differences between the 2 treatment groups when LY2216684 was administered alone (Day 3) and when LY2216684 was coadministered with fluoxetine (Day 27). The 90% confidence interval (CI) for the median of differences was calculated.

  Predose and 1, 2, 3, 4, 6, 8, 12, and 24 hours post-dose on Days 3 and 27

Secondary Outcomes (3)

• Pharmacokinetic (PK) Parameter: Area Under the Plasma Concentration Time-Curve Over a 24-Hour Dosing Interval (AUCτ) of Fluoxetine and Norfluoxetine

  Predose and 1, 2, 3, 4, 6, 8, 12, and 24 hours post-dose on Days 24 and 27

• Pharmacokinetic (PK) Parameter: Maximum Plasma Concentration (Cmax) of Fluoxetine and Norfluoxetine

  Predose and 1, 2, 3, 4, 6, 8, 12, and 24 hours post-dose on Days 24 and 27

• Pharmacokinetic (PK) Parameter: Time to Maximum Plasma Concentration (Tmax) of Fluoxetine and Norfluoxetine

  Predose and 1, 2, 3, 4, 6, 8, 12, and 24 hours post-dose on Days 24 and 27

Study Arms (1)

LY2216684 + fluoxetine

EXPERIMENTAL

LY2216684: 18 milligrams (mg) oral (po) once daily (QD) on Days 1, 2, and 3 and Days 25-27 Fluoxetine: 60 mg po QD for 7 days (Days 4-10) then 20 mg po QD for 17 days (Days 11-27)

Drug: LY2216684; Drug: Fluoxetine

Interventions

LY2216684 DRUG

LY2216684: 18 mg po QD on Days 1, 2, and 3 and Days 25-27

LY2216684 + fluoxetine

Fluoxetine DRUG

Fluoxetine: 60 mg po QD for 7 days (Days 4-10) then 20 mg po QD for 17 days (Days 11-27)

LY2216684 + fluoxetine

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Are overtly healthy as determined by medical history and physical examination.
• Male participants: Agree to use a reliable method of birth control during the study + 3 months following the last dose of study drug.
• Female participants: Are women of child-bearing potential who test negative for pregnancy at the time of enrollment, have used a reliable method of birth control for 6 weeks prior to administration of study drug, and agree to use a reliable method of birth control during the study + 1 month following the last dose of study drug; or are women not of child-bearing potential due to surgical sterilization (hysterectomy, bilateral oophorectomy, or tubal ligation) or menopause (at least 1 year without menses or 6 months without menses and a follicle stimulating hormone (FSH) level ≥40 mass International Units per milliliter (mIU/mL).
• Are between the ages of 18-65 years, inclusive.
• Are between the body mass index (BMI) of 18.5-32.0 kilograms per square meter (kg/m\^2), inclusive.
• Have screening 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 blood sampling according to the protocol.
• Have normal blood pressure (BP) and pulse rate (supine position and standing) as determined by the investigator.
• Are reliable and available for the duration of the study and are willing to follow study procedures.
• Provided written informed consent approved by Lilly and the institutional review board (IRB) governing the site.

You may not qualify if:

• Are investigator site personnel directly affiliated with this study or their immediate families. Immediate family is defined as a spouse, parent, child or sibling, whether biological or legally adopted.
• Are Lilly employees.
• Are currently enrolled in, or discontinued within the last 30 days from, a clinical trial involving an investigational drug or device other than the study drug 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 LY2216684, fluoxetine, or related compounds.
• Are persons who previously completed or discontinued from this study, or any other study investigating LY2216684 within 6 months prior to screening.
• Have a clinically significant abnormality in the 12-lead electrocardiogram (ECG) as determined by the investigator.
• Have significant history of or current cardiovascular (including dysrhythmias), 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 of seizure disorders.
• Have a history or presence of the signs and/or symptoms of hyponatremia.
• Have a history or presence of the signs and/or symptoms of hyperthyroidism as determined by an abnormal thyroid stimulating hormone (TSH) at screening.
• Show evidence of significant active neuropsychiatric disease or a history of suicidal thoughts or attempted suicide.
• Regularly use known drugs of abuse and/or show positive findings on urinary drug screening.
• Show evidence of human immunodeficiency virus (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.

Sponsors & Collaborators

• Eli Lilly and Company: lead

Study Sites (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

Evansville, Indiana, United States

Location

MeSH Terms

Conditions

Depressive Disorder, Major

Interventions

alpha-((5-fluoro-2-methoxyphenyl)methyl)-alpha-(tetrahydro-2H-pyran-4-yl)-2-morpholinemethanol; Fluoxetine

Condition Hierarchy (Ancestors)

Depressive Disorder; Mood Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Propylamines; Amines; Organic Chemicals

Results Point of Contact

• Title: Chief Medical Officer
• Organization: Eli Lilly and Company

800-545-5979

Study Officials

• 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 DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: GT60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 17, 2010
• First Posted: November 19, 2010
• Study Start: October 1, 2010
• Primary Completion: January 1, 2011
• Study Completion: January 1, 2011
• Last Updated: January 29, 2019
• Results First Posted: October 22, 2018

Record last verified: 2019-01

Locations

US (1)