A Study of LY2140023 in Hepatically-Impaired Participants

NCT01475136 | Completed Phase 1 Results

• 3 other identifiers: 12677H8Y-MC-HBCH2011-003033-34
• Study Type: interventional
• Target: 37
• Locations: 2 countries
• Sites: 2

Brief Summary

This study will explore how liver impairment affects blood levels of LY2140023 (a prodrug) and its active metabolite (LY404039).

Conditions

Hepatic Insufficiency

Outcome Measures

Primary Outcomes (3)

• Pharmacokinetics: Area Under the Concentration Time Curve (AUC) of LY2140023 and LY404039

  LY404039 is the active metabolite of LY2140023. AUC from zero to infinity AUC(0-∞) is presented.

  Predose and 0.5, 1, 2, 3, 4, 6, 9, 12, 16, 24, 36, and 48 hours postdose

• Pharmacokinetics: Maximum Observed Drug Concentration (Cmax) of LY2140023 and LY404039

  LY404039 is the active metabolite of LY2140023.

  Predose and 0.5, 1, 2, 3, 4, 6, 9, 12, 16, 24, 36, and 48 hours postdose

• Pharmacokinetics: Time of Maximal Concentration (Tmax) of LY2140023 and LY404039

  LY404039 is the active metabolite of LY2140023.

  Predose and 0.5, 1, 2, 3, 4, 6, 9, 12, 16, 24, 36, and 48 hours postdose

Study Arms (1)

LY2140023

EXPERIMENTAL

A single oral dose of 80 milligrams (mg) LY2140023 administered on Day 1.

Drug: LY2140023

Interventions

LY2140023 DRUG

LY2140023

Eligibility Criteria

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

You may qualify if:

• Male participants agree to use a reliable method of birth control during the study and for 3 months following the last dose of LY2140023
• Female participants of child-bearing potential who test negative for pregnancy at screening and agree to use a reliable method of birth control for the duration of the study and for at least 3 months after the last dose of LY2140023
• Female participants who are postmenopausal. Postmenopausal is defined as no menses for at least 1 year, or a plasma follicle stimulating hormone (FSH) value of greater than 40 units per liter (IU/L), unless the participant is taking hormone replacement therapy
• Have a body mass index (BMI) between 19 and 40 kilograms per square meter (kg/m\^2), inclusive at the time of screening
• Have clinical laboratory test results within the 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 sitting blood pressure and heart rate compatible with their disease state, as determined by the investigator
• Have venous access sufficient to allow for blood sampling as per the protocol
• 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 ethical review board (ERB) governing the site
• Control participants that have normal hepatic function, as determined by medical history and physical examination
• Hepatically-impaired participants that have stable hepatic impairment (for example, alcoholic, posthepatitis, biliary cirrhosis, or cryptogenic) classified as Child-Pugh class A, B, or C (mild, moderate, or severe impairment) who are considered acceptable for participation in the study by the investigator

You may not qualify if:

• Are currently enrolled in, have completed or discontinued within the last 90 days from last dosing of 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 LY2140023, LY404039, related compounds, or any components of the formulation
• Have previously discontinued after receiving at least 1 dose of LY2140023 or completed this study or any other study investigating LY2140023 and or LY404039
• 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, renal, gastrointestinal, endocrine, hematological, or neurological disorders capable of significantly altering the absorption (except cholecystectomy), metabolism, or elimination of drugs; of constituting a risk when taking the study medication; or of interfering with the interpretation of data
• Have evidence of significant active neuropsychiatric disease (for example, manic depressive illness, schizophrenia, or depression)
• Participants who answer 'yes' to either Question 4 (Active Suicidal Ideation with Some Intent to Act, Without Specific Plan) or Question 5 (Active Suicidal Ideation with Specific Plan and Intent) on the "Suicidal Ideation" portion of the Columbia Suicide Severity Rating Scale (C-SSRS), or answer "yes" to any of the suicide-related behaviors (actual attempt, interrupted attempt, aborted attempt, preparatory act, or behavior) on the "Suicidal Behavior" portion of the C-SSRS; and the ideation or behavior occurred within the past 3 months
• Have increased risk of seizures based on a history of:
• One or more seizures (except for a single simple febrile seizure \[lacking focality and lasting less than 15 minutes, not associated with a central nervous system (CNS) infection or severe metabolic disturbance\] as a child between ages 6 months to 5 years)
• Head trauma with loss of consciousness or a post-concussive syndrome within 1 year or lifetime history of head trauma with persistent neurological deficit (focal or diffuse)
• CNS infection, uncontrolled migraine or transient ischemic attack (TIA) within 1 year; stroke with persistent neurological deficit (focal or diffuse). Uncontrolled migraine is defined as migraine attacks that produce headache lasting up to 72 hours and are often accompanied by associated symptoms (nausea, photophobia, and phonophobia) that impair well-being and disrupt social functioning. TIA is defined as "mini-stroke" caused by temporary disturbance of blood supply to an area of the brain, which results in a sudden, brief decrease in brain function
• CNS infection with persistent neurological deficit (focal or diffuse)
• Brain surgery
• Electroencephalogram (EEG) with paroxysmal (epileptiform) activity (isolated spikes waves, repetitive bursts of sharp waves, paroxysmal activity, frank seizures, spike-wave complexes, sharp-slow wave complexes, or as locally defined)
• Brain structural lesion, including developmental abnormalities, as determined by examination or imaging studies (does not include hydrocephalus unless treated by shunt or resulting in neurological deficits)

Sponsors & Collaborators

• Denovo Biopharma LLC: lead

Study Sites (2)

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.

Munich, 81241, Germany

Location

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.

Balatonfüred, 8230, Hungary

Location

MeSH Terms

Conditions

Hepatic Insufficiency

Interventions

LY 2140023

Condition Hierarchy (Ancestors)

Liver Diseases; Digestive System Diseases

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: BASIC SCIENCE
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 16, 2011
• First Posted: November 21, 2011
• Study Start: November 1, 2011
• Primary Completion: December 1, 2012
• Study Completion: December 1, 2012
• Last Updated: September 22, 2021
• Results First Posted: September 22, 2021

Record last verified: 2013-01

Locations

DE (1); HU (1)