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CompletedNCT01241435Updated Oct 22, 2018Results posted

A Study of LY2216684 in Participants With Impaired Hepatic Function

A Phase 1 interventional study of LY2216684 in Depressive Disorder, Major, sponsored by Eli Lilly and Company. Completed at 3 sites in United States. Open to participants aged 18 Years to 65 Years, including healthy volunteers. Per ClinicalTrials.gov, last updated 2018-10-22.

Sponsored by Eli Lilly and Company · Phase 1, Interventional, and Treatment

Phase
Phase 1
Study type
Interventional
Enrollment
36
Allocation
Not applicable
Ages
18 Years to 65 Years
Sex
All
01

Study summary

The purpose of this study is to evaluate the effect of liver function on how much of the study drug (LY2216684) gets into the blood stream and how long it takes the body to get rid of it. Information about any side effects that may occur will also be collected.

The duration of participation in this study is approximately 12 days, not including the screening visit. This study requires 1 clinic confinement of 5 days/4 nights followed by 1 out-patient follow-up visit. A screening visit is required within 30 days prior to the start of the study. This research study will be an open-label study.

The study involves a single oral dose of 18 milligrams (mg) LY2216684 given as 2 tablets.

02

Conditions studied

  • Depressive Disorder, Major
03

In context

Depressive Disorder

4,845 studies on the registry are indexed under Depressive Disorder; 514 are open to participants now.

This study's enrollment of 36 is below the median of 80 across 3,999 interventional studies indexed under Depressive Disorder.

Browse Depressive Disorder studies →

Lead sponsor

Eli Lilly and Company is the lead sponsor of 2,048 studies on the registry; 140 are open to participants now.

Of its 521 completed or terminated interventional studies of FDA-regulated products, 341 (65%) have results posted.

Counted across the registry records on this site, refreshed daily.

04

Who can participate

Ages eligible
18 Years to 65 Years
Sexes eligible
All
Accepts healthy volunteers
Yes

Inclusion criteria

  • 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, who have used a reliable method of birth control for 6 weeks prior to administration of study drug, and who agree to use a reliable method of birth control during the study and for 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 follicle stimulating hormone [FSH] levels greater than or equal to 40 milli-internation units per milliliter [mIU/mL]).
  • Have a body mass index (BMI) of 17.0 to 35.0 kilograms per meters squared (kg/m\^2), inclusive, at screening.
  • Have acceptable blood pressure and pulse rate (sitting) as determined by the investigator.
  • Have venous access sufficient to allow blood sampling as per the protocol.
  • Are reliable and willing to make themselves available for the duration of the study and to follow study procedures.
  • Have given written informed consent approved by Lilly and the institutional review board (IRB) governing the site.

Control Participants (Participants with Normal Hepatic Function):

  • Are overtly healthy, as determined by medical history and physical examination.
  • Have clinical laboratory test results within normal reference ranges for the investigative site or results with acceptable deviations, which are judged to be not clinically significant by the investigator, at the time of screening.

Participants with Mild, Moderate, or Severe Hepatic Impairment:

  • Participants with stable liver disease (alcoholic liver disease, post-hepatitis, biliary cirrhosis, cryptogenic) classified as Child-Pugh score A, B, or C (Pugh et al. 1973).
  • Clinical laboratory test results with deviations that are judged by the investigator to be compatible with the hepatic impairment of the participant or of no additional clinical significance for this study.

Exclusion criteria

Exclusion Criteria:

All Participants:

  • 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 to LY2216684 or related compounds.
  • Are persons who have previously completed or withdrawn from this study or any other study investigating LY2216684 in the past 6 months from screening.
  • Have an electrocardiogram (ECG) reading considered clinically significant by the investigator or a history of significant cardiac dysrhythmia or conduction defect that, in the opinion of the investigator, increases the risks associated with participating in the study.
  • Show evidence of human immunodeficiency virus (HIV) and/or positive human HIV antibodies.
  • There is evidence or history of neurological disease such as transient ischemic attack, stroke, syncope episodes, encephalitis, or meningitis, except participants with liver disease-related encephalopathy may be allowed.
  • Presence of acute infection with fever.
  • Are women with a positive pregnancy test or women who are lactating.
  • Have lost 500 milliliters (mL) or more of blood in the 3 months prior to study entry.
  • Are participants who have an average weekly alcohol intake that exceeds 21 units per week, or are unwilling to adhere to restrictions during the study (1 unit = 12 ounces [oz] or 360 mL of beer, 5 oz or 150 mL of wine, or 1.5 oz or 45 mL of distilled spirits).
  • Are participants who are unwilling to adhere to study caffeine restrictions.
  • Are participants who are unwilling to abide by smoking restrictions while resident in the clinical research unit (CRU).
  • Have a documented or suspected history of glaucoma.

Control Participants (Participants with Normal Hepatic Function):

  • Have significant active hematological disease, history of significant active bleeding, or coagulation disorder.
  • Use or intend to use over-the-counter (including vitamins/mineral supplements, herbal medicine) or prescription medications 14 days, prior to enrollment and during the study.
  • Have history or presence of cardiovascular, respiratory, 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.
  • Regularly use known drugs of abuse and/or show positive findings on urinary drug screening.
  • Evidence of hepatitis C and/or positive hepatitis C antibody.
  • Evidence of hepatitis B and/or positive hepatitis B surface antigen.
  • Show evidence of significant active neuropsychiatric disease.

Participants with Mild, Moderate, or Severe Hepatic Impairment:

  • Evidence of any significant active disease other than that responsible for or associated with liver impairment.
  • Have history or presence of cardiovascular, respiratory, renal, endocrine, hematological, or neurological disorders capable of significantly altering the absorption, metabolism, or elimination of drugs or of constituting a risk when taking the study medication or interfering with the interpretation of data.
  • Evidence of hepatorenal syndrome.
  • Spontaneous bacterial peritonitis within 6 months of study entry.
  • Variceal bleeding within 3 months of study entry.
  • Severe hyponatremia (sodium [Na] \<120 millimole per liter [mmol/L]).
  • Presence of hepatocellular carcinoma.
  • Severe encephalopathy.
  • Hemoglobin \<9.0 grams per deciliter (g/dL).
  • Platelet count \<50 x 10\^9 cells per liter (cells/L), values \<50 x 10\^9 cells/L may be permitted at the discretion of the investigator in consultation with the sponsor.
  • Concomitant use of any drug except those indicated for the treatment of liver disease or related complications.
  • Concomitant use of anticoagulants including warfarin.
  • Regular use of drugs of abuse and/or positive findings on urinary drug screening except those prescribed for related complications (such as, pain, insomnia, or anxiety) of liver disease.
  • The use of medication known to interfere with hepatic metabolism (such as, barbiturates or phenothiazines) or known to alter other major organs or systems within 30 days prior to study entry.
05

Study design

Phase
Phase 1
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrollment
36 participants (actual)

Study arms

  • Experimental
    LY2216684

    LY2216684: A single dose of 18 milligrams (mg) administered orally in participants with normal hepatic function, mild hepatic impairment (Child-Pugh A), moderate hepatic impairment (Child-Pugh B), or severe hepatic impairment (Child-Pugh C)

    Drug: LY2216684

Interventions

  • DrugLY2216684

    Administered orally

    Also known as: Edivoxetine

06

What researchers measure

Primary outcomes

  1. Pharmacokinetics: Area Under the Concentration Curve (AUC)

    The area under the plasma concentration versus time curve from 0 hours to infinity (AUC \[0-∞\]) for LY2216684 is presented.

    Time frame: Up to 72 hours after administration of study drug

  2. Pharmacokinetics: Maximum Concentration (Cmax)

    Time frame: Up to 72 hours after administration of study drug

  3. Pharmacokinetics: Time to Maximum Concentration (Tmax)

    Time frame: Up to 72 hours after administration of study drug

07

Results

Posted Oct 22, 2018

Participant flow

Participant flow — Overall Study
MilestoneNormal Hepatic FunctionMild Hepatic ImpairmentModerate Hepatic ImpairmentSevere Hepatic Impairment
Started12888
Received at least 1 dose of study drug12888
Completed12888
Not completed0000

Outcome measures

PrimaryPharmacokinetics: Area Under the Concentration Curve (AUC)

The area under the plasma concentration versus time curve from 0 hours to infinity (AUC \[0-∞\]) for LY2216684 is presented.

Time frame:
Up to 72 hours after administration of study drug
Reported as:
Geometric mean · hours times nanograms/milliliter
Pharmacokinetics: Area Under the Concentration Curve (AUC)
hours times nanograms/milliliterNormal Hepatic FunctionMild Hepatic ImpairmentModerate Hepatic ImpairmentSevere Hepatic Impairment
Pharmacokinetics: Area Under the Concentration Curve (AUC)601 ± 32742 ± 52961 ± 451020 ± 16
PrimaryPharmacokinetics: Maximum Concentration (Cmax)
Time frame:
Up to 72 hours after administration of study drug
Reported as:
Geometric mean · nanograms/milliliter
Pharmacokinetics: Maximum Concentration (Cmax)
nanograms/milliliterNormal Hepatic FunctionMild Hepatic ImpairmentModerate Hepatic ImpairmentSevere Hepatic Impairment
Pharmacokinetics: Maximum Concentration (Cmax)46.8 ± 2739.6 ± 2841.9 ± 3334.7 ± 15
PrimaryPharmacokinetics: Time to Maximum Concentration (Tmax)
Time frame:
Up to 72 hours after administration of study drug
Reported as:
Median · hours
Pharmacokinetics: Time to Maximum Concentration (Tmax)
hoursNormal Hepatic FunctionMild Hepatic ImpairmentModerate Hepatic ImpairmentSevere Hepatic Impairment
Pharmacokinetics: Time to Maximum Concentration (Tmax)3.00 (1.00 to 5.00)3.50 (2.00 to 6.00)3.50 (1.00 to 5.00)3.50 (2.00 to 5.00)

Adverse events

Non-serious events are listed at a 5% frequency threshold.

Adverse event summary by group
GroupDeathsSeriousOther
Normal Hepatic Function—0/12 (0%)6/12 (50%)
Mild Hepatic Impairment—0/8 (0%)3/8 (37.5%)
Moderate Hepatic Impairment—0/8 (0%)6/8 (75%)
Severe Hepatic Impairment—0/8 (0%)5/8 (62.5%)
Most frequent other events
Showing 10 of 25
Most frequent other events
EventNormal Hepatic FunctionMild Hepatic ImpairmentModerate Hepatic ImpairmentSevere Hepatic Impairment
PalpitationsCardiac disorders0/120/80/82/8
TinnitusEar and labyrinth disorders0/120/81/82/8
ConstipationGastrointestinal disorders0/120/80/82/8
DizzinessNervous system disorders3/120/81/82/8
HeadacheNervous system disorders0/121/81/82/8
NauseaGastrointestinal disorders2/120/81/80/8
BlepharitisEye disorders0/120/81/80/8
Vision blurredEye disorders0/120/80/81/8
Abdominal discomfortGastrointestinal disorders0/121/80/80/8
Dry mouthGastrointestinal disorders0/120/80/81/8

Baseline characteristics

Participants who received at least one dose of study drug.

Age, Continuous
Age, Continuous(years)Normal Hepatic FunctionMild Hepatic ImpairmentModerate Hepatic ImpairmentSevere Hepatic ImpairmentTotal
Mean49.5 ± 6.355.0 ± 4.954.5 ± 5.651.4 ± 6.952.3 ± 6.2
Sex: Female, Male
Sex: Female, Male(Participants)Normal Hepatic FunctionMild Hepatic ImpairmentModerate Hepatic ImpairmentSevere Hepatic ImpairmentTotal
Female432110
Male856726
Race/Ethnicity, Customized
Race/Ethnicity, Customized(Participants)Normal Hepatic FunctionMild Hepatic ImpairmentModerate Hepatic ImpairmentSevere Hepatic ImpairmentTotal
White1088834
Black/African American10001
Multiple10001
Region of Enrollment
Region of Enrollment(Participants)Normal Hepatic FunctionMild Hepatic ImpairmentModerate Hepatic ImpairmentSevere Hepatic ImpairmentTotal
United States1288836
08

Study locations

3 sites
  • 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.
    Miami, Florida 33014, 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.
    Orlando, Florida 32809, 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.
    San Antonio, Texas 78215, United States
09

Updates

Tracking since Sep 25, 2026
No changes since tracking began. The registry record was last updated on Oct 22, 2018, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
10

Registry details

Key details

Study ID
NCT01241435
Lead sponsor
Eli Lilly and Company
Responsible party
Sponsor
First posted
Nov 16, 2010
Start date
Oct 2010
Primary completion
Apr 2011
Completion
Apr 2011
Results posted
Oct 22, 2018
Last update
Oct 22, 2018

Study contacts

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)
study director · Eli Lilly and Company

Oversight

Data monitoring committee
No
View the source record on ClinicalTrials.gov ↗

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