Clinical trial NCT01241435: A Study of LY2216684 in Participants With Impaired Hepatic Function
Official title: The Effect of Impaired Hepatic Function on the Pharmacokinetics of LY2216684
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Depressive Disorder, Major
Lead sponsor: Eli Lilly and Company
Sponsor class: INDUSTRY
First posted: 2010-11-16
Enrollment: 36
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief 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.


Eligibility criteria: 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:

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.

Primary outcomes:
measure: Pharmacokinetics: Area Under the Concentration Curve (AUC)
timeFrame: Up to 72 hours after administration of study drug
measure: Pharmacokinetics: Maximum Concentration (Cmax)
timeFrame: Up to 72 hours after administration of study drug
measure: Pharmacokinetics: Time to Maximum Concentration (Tmax)
timeFrame: Up to 72 hours after administration of study drug
Secondary outcomes:
Other outcomes:
Locations:
city: Miami
country: United States
facility: 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.
state: Florida
city: Orlando
country: United States
facility: 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.
state: Florida
city: San Antonio
country: United States
facility: 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.
state: Texas
Study officials:
affiliation: Eli Lilly and Company
name: 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)
role: STUDY_DIRECTOR
References: