A Study to Evaluate the Pharmacokinetics of LY2624803 in Subjects With Hepatic Impairment

• Register: ClinicalTrials.gov
• Last refreshed on: 19 February 2015
• Main ID: NCT01257178
• Date of registration: 07/12/2010
• Prospective Registration: No
• Primary sponsor: Eli Lilly and Company
• Public title: A Study to Evaluate the Pharmacokinetics of LY2624803 in Subjects With Hepatic Impairment
• Scientific title: A Single Dose Pharmacokinetics Study of LY2624803 in Subjects With Hepatic Impairment
• Date of first enrolment: November 2010
• Target sample size: 0
• Recruitment status: Terminated
• URL: http://clinicaltrials.gov/show/NCT01257178
• Study type: Interventional
• Study design: Allocation: Non-Randomized, Endpoint Classification: Pharmacokinetics Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Basic Science
• Phase: Phase 1

Countries of recruitment

Germany, Hungary, Russian Federation

Contacts

• 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)
• Affiliation: Eli Lilly and Company

Key inclusion & exclusion criteria

Inclusion Criteria:

All Subjects

- Sexually active male and female subjects and their partners must agree to use 2
methods of contraception such as condom or occlusive cap (diaphragm or cervical/vault
caps) together with spermicidal foam/gel/film/cream/suppository, from the time the
subject enters the study until 3 months after the final dosing occasion, unless the
male subject or partner has been sterilized (with confirmed azoospermia).

- Have a BMI between 18.5 and 35.0 kg/m2, inclusive.

- Have a body weight >50 kg.

- Have normal sitting blood pressure and heart rate compatible with their disease
state, 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 are willing to follow study procedures.

- Have given written informed consent approved by Lilly and the Ethical Review Board
governing the site.

Control Subjects

- Are males or females and with normal hepatic function, as determined by medical
history and physical examination.

- Have clinical laboratory test results within normal reference range for the
investigator site, or results with minor deviations not considered to be clinically
significant by the investigator.

Hepatic Impaired Subjects

•Have stable hepatic impairment (alcoholic, posthepatitis, biliary cirrhosis, cryptogenic)
classified as Child-Pugh class A, B, or C (mild, moderate, and severe impairment) who are
considered acceptable for participation in the study by the investigator.

Exclusion Criteria:

All Subjects

- Are currently enrolled in, or discontinued within the last 90 days from the last
dosing occasion in a clinical trial involving an investigational drug or device, 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 LY2624803 or related compounds.

- Have previously discontinued from this study or any other study investigating
LY2624803.

- Have an abnormality in the 12-lead ECG that, in the opinion of the investigator,
increases the risk associated with participating in the study.

- 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 HIV antibodies.

- Have donated blood of more than 500 mL within the last 3 months prior to the
screening visit.

- Use drugs or herbal remedies that are known inhibitors or inducers of CYP3A4 or
inhibitors of CYP2D6 enzyme pathways, unless in the opinion of the sponsor and
investigator the medication will not compromise safety.

- Are liver transplant subjects or have taken immunosuppressants following any organ
transplant.

- Have shown signs of variceal bleeding during the last 2 weeks prior to screening.

- Show evidence of irritable bowel syndrome or chronic diarrhea.

- Have an average weekly alcohol intake that exceeds 28 units per week (males) and 21
units per week (females), and are subjects unwilling to stop alcohol consumption for
the duration of the study (1 unit = 12 oz or 360 mL of beer; 5 oz or 150 mL of wine;
1.5 oz or 45 mL of distilled spirits).

- Are unable to swallow whole capsules.

- Are on total parenteral nutrition (TPN).

- Take anticoagulants for therapeutic use.

- Have a history of breast cancer.

- Exhibit any other condition, which, in the opinion of the investigator would preclude
participation in the study.

Control Subjects

- Have any medically significant history of neurologic disease, cancer, or cardiac,
respiratory, metabolic, hepatic, renal, gastrointestinal (except appendectomy),
dermatological, venereal, hematological disorder or disease.

- Have creatinine clearance (CrCl) <80 mL/min, as calculated by Cockcroft-Gault
equation.

- Show evidence of significant active neuropsychiatric disease in the opinion of the
investigator.

- Show evidence of hepatitis B and/or positive hepatitis B surface antigen (HBsAg).

- Show evidence of hepatitis C and/or positive hepatitis C antibody.

Mild Hepatic Impaired Subjects (Child-Pugh A)

- Show evidence of any significant active disease other than that responsible for or
associated with hepatic impairment.

- Show evidence of active renal disease with creatinine clearance <70 mL/min as
calculated by Cockcroft-Gault equation.

- Have severe ascites.

Moderate and Severe Hepatic Impaired Subjects (Child-Pugh B and C)

- Show evidence of any significant active disease other than that responsible for or
associated with moderate or severe hepatic impairment.

- Show evidence of hepatorenal syndrome as shown by creatinine clearance <50 mL/min, as
calculated by the Cockcroft-Gault equation.

- Have shown signs of spontaneous bacterial peritonitis within 6 months prior to
dosing.

- Have severe hyponatremia.

- Have hepatic encephalopathy (grade 2 to 4 encephalopathy).

- Show signs of hepatocellular carcinoma.

- Have a portal shunt.

- Show, in the opinion of the investigator, evidence of significant active
neuropsychiatric disease other than grade 1 hepatic encephalopathy.

- Have severe ascites.

- Have hemoglobin concentrations <9.0 g/dL.

- Have a platelet count of <50 x 109 cells/L, unless, after consultation with the
sponsor, they are considered as acceptable for participation in the study.

- Have total serum bilirubin concentrations >15 mg/dL (>257 µmol/L).

- Take medications known to interfere with hepatic metabolism (for example
barbiturates, phenothiazines) or known to alter other major organ systems.



Age minimum: 18 Years
Age maximum: 75 Years
Gender: Both

Health Condition(s) or Problem(s) studied

Insomnia

Intervention(s)

Drug: LY2624803

Primary Outcome(s)

LY2624803 and the metabolite LSN2797276 Area under the Curve from time 0 to infinity [AUC(0-8)] [Time Frame: Predose through 120 hours post dose]

LY2624803 and the metabolite LSN2797276, Time to maximum plasma concentration(tmax) [Time Frame: Predose through 120 hours post dose]

LY2624803 and the metabolite LSN2797276, Maximum Concentration (Cmax) [Time Frame: Predose through 120 hours post dose]

Secondary Outcome(s)

LY2624803 and the metabolite LSN2797276, Parent to metabolite ratios (MR) of AUC [Time Frame: Predose through 120 hours post dose]

LY2624803 and the metabolite LSN2797276, AUC to the last quantifiable sample [AUC(0-tlast)] [Time Frame: Predose through 120 hours post dose]

LY2624803 and the metabolite LSN2797276, Apparent volume of distribution (V/F) [Time Frame: Predose through 120 hours post dose]

LY2624803 and the metabolite LSN2797276, Apparent clearance (CL/F) [Time Frame: Predose through 120 hours post dose]

LY2624803 and the metabolite LSN2797276, Elimination half live (t1/2) [Time Frame: Predose through 120 hours post dose]

LY2624803 and the metabolite LSN2797276, Parent to metabolite ratios (MR) of Cmax [Time Frame: Predose through 120 hours post dose]

Secondary ID(s)

12809

I2K-MC-ZZBL

Source(s) of Monetary Support

Please refer to primary and secondary sponsors