A Pharmacokinetic Study of the Coadministration of LY2216684 With Sertraline

December 13, 2018 updated by: Eli Lilly and Company

LY2216684 and Sertraline Pharmacokinetic Interaction Study in Healthy Subjects

LY2216684 is being studied as adjunctive treatment for major depressive disorder (MDD) in participants who are partial responders to selective serotonin reuptake inhibitors (SSRIs). Sertraline is a medication that is widely used to treat MDD and is a known substrate of cytochrome P450s (CYP450s), including CYP450 2D6 (CYP2D6), CYP450 2C19 (CYP2C19), CYPP450 3A4 (CYP3A4), and a modest inhibitor of CYP2D6. Based on the diversity of hepatic metabolic clearance pathways for LY2216684 and its elimination by the kidney, it is expected that CYP2D6 inhibition by sertraline will not result in a substantial change in the pharmacokinetic (PK) profile of LY2216684. LY2216684 is only known to be a moderate inhibitor of CYP2C19, so it is unlikely that coadministration of sertraline with LY2216684 will result in a clinically meaningful change in the PK of sertraline. This study is being conducted to test these hypotheses.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
20

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Florida
      • Daytona Beach, Florida, United States
        • 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.

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years to 65 years (Adult, Older Adult)

Accepts Healthy Volunteers

Yes

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • 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 and for 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).
  • Body mass index (BMI) up to 32.0 kilograms per square meter (kg/m^2).
  • 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 and pulse rate (supine position and standing) as determined by the investigator.
  • Are reliable and willing to be available for the duration of the study and willing to follow study procedures.
  • Provided written informed consent approved by Lilly and the institutional review board (IRB) governing the site.

Exclusion Criteria:

  • Are currently enrolled in, or discontinued within the last 30 days from, a clinical trial involving an investigational drug or device, or off-label use of a 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/intolerance to LY2216684, sertraline, 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.
  • Have a history or presence of the signs and/or symptoms of urinary retention or benign prostatic hypertrophy.
  • Show evidence of significant active neuropsychiatric disease or a history of suicidal thoughts or suicide attempt.
  • 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.
  • Are women with a positive pregnancy test or women who are lactating.
  • Intend to use over-the-counter or prescription medication within 14 days prior to dosing unless deemed acceptable by the investigator and sponsor's medical monitor.
  • Have donated blood of more than 500 milliliters (mL) within 4 weeks prior to screening.
  • Have an average weekly alcohol intake that exceeds 14 units per week or are unwilling to stop alcohol consumption 48 hours prior to check-in until the completion of the study (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.
  • Have used any tobacco-containing 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 enrollment.
  • Have consumed grapefruit or grapefruit-containing products 7 days prior to enrollment and during the study.
  • Have a documented or suspected history of glaucoma.
  • Participants determined to be unsuitable by the investigator for any reason.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: LY2216684/sertraline/LY2216684 + sertraline

Period 1: LY2216684 18 milligram (mg) oral (po) dose on Days 1-3.

Period 2: Sertraline 50 mg po dose on Day 4 followed by sertraline 100 mg po dose on Days 5-10.

Period 3: LY2216684 18 mg po dose + sertraline 100 mg po dose on Days 11-13.
Drug: LY2216684
po administration
Drug: Sertraline
po administration

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Pharmacokinetic (PK) Parameter: Area Under the Plasma Concentration-Time Curve Over a 24-Hour Dosing Interval (AUCτ) of LY2216684
Time Frame: 0, 1, 2, 3, 4, 6, 8, 12, 24 hours post-dose on Day 3 and Day 13
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 LY221684 was administered alone (Day 3) and when LY2216684 was coadministered with sertraline (Day 13). The Day 13-to-Day 3 ratio of the LY2216684 LS geometric mean of AUCτ and the associated 90% confidence interval (CI) of the ratio were calculated.
0, 1, 2, 3, 4, 6, 8, 12, 24 hours post-dose on Day 3 and Day 13
Pharmacokinetic (PK) Parameter: Maximum Plasma Concentration (Cmax) of LY2216684
Time Frame: 0, 1, 2, 3, 4, 6, 8, 12, 24 hours post-dose on Day 3 and Day 13
The Least Squares (LS) geometric mean Cmax of LY2216684 was determined when LY2216684 was administered alone (Day 3) and when LY2216684 was coadministered with sertraline (Day 13). The Day 13-to-Day 3 ratio of the LY2216684 LS geometric mean of Cmax and the associated 90% confidence interval (CI) of the ratio were calculated.
0, 1, 2, 3, 4, 6, 8, 12, 24 hours post-dose on Day 3 and Day 13
Pharmacokinetic (PK) Parameter: Time to Maximum Plasma Concentration (Tmax) of LY2216684
Time Frame: 0, 1, 2, 3, 4, 6, 8, 12, 24 hours post-dose on Day 3 and Day 13
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 sertraline (Day 13). The 90% confidence interval (CI) for the median of differences was calculated.
0, 1, 2, 3, 4, 6, 8, 12, 24 hours post-dose on Day 3 and Day 13
Pharmacokinetic (PK) Parameter: Area Under the Plasma Concentration-Time Curve Over a 24-Hour Dosing Interval (AUCτ) of Sertraline
Time Frame: 0, 1, 2, 3, 4, 6, 8, 12, 24 hours post-dose on Day 10 and Day 13
The Least Squares (LS) geometric mean AUCτ of sertraline was calculated based on the sertraline plasma concentration time curve from time 0 hour (hr) to time 24 hr (tau [τ]) when sertraline was administered alone (Day 10) and when sertraline was coadministered with LY2216684 (Day 13). The Day 13-to-Day 10 ratio of the sertraline LS geometric mean of AUCτ and the associated 90% confidence interval (CI) of the ratio were calculated.
0, 1, 2, 3, 4, 6, 8, 12, 24 hours post-dose on Day 10 and Day 13
Pharmacokinetic (PK) Parameter: Maximum Plasma Concentration (Cmax) of Sertraline
Time Frame: 0, 1, 2, 3, 4, 6, 8, 12, 24 hours post-dose on Day 10 and Day 13
The Least Squares (LS) geometric mean Cmax of sertraline was determined when sertraline was administered alone (Day 10) and when sertraline was coadministered with LY2216684 (Day 13). The Day 13-to-Day 10 ratio of the sertraline LS geometric mean of Cmax and the associated 90% confidence interval (CI) of the ratio were calculated.
0, 1, 2, 3, 4, 6, 8, 12, 24 hours post-dose on Day 10 and Day 13
Pharmacokinetic (PK) Parameter: Time to Maximum Plasma Concentration (Tmax) of Sertraline
Time Frame: 0, 1, 2, 3, 4, 6, 8, 12, 24 hours post-dose on Day 10 and Day 13
Tmax of sertraline was determined using the median of paired differences between the 2 treatment groups when sertraline was administered alone (Day 10) and when sertraline was coadministered with LY2216684 (Day 13). The 90% confidence interval (CI) for the median of differences was calculated.
0, 1, 2, 3, 4, 6, 8, 12, 24 hours post-dose on Day 10 and Day 13

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Eli Lilly and Company

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
November 1, 2010

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
January 1, 2011

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
January 1, 2011

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
November 29, 2010

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
November 29, 2010

First Posted (Estimate)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
December 1, 2010

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
January 4, 2019

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
December 13, 2018

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
December 1, 2018

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • 12611
  • H9P-EW-LNCT (Other Identifier: Eli Lilly and Company)

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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