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

This study has been terminated.
(Trial was Terminated prior to subjects receiving study drug; no trial results)
Sponsor:
Information provided by:
Eli Lilly and Company
ClinicalTrials.gov Identifier:
NCT01257178
First received: December 7, 2010
Last updated: June 2, 2011
Last verified: June 2011
  Purpose

The purpose of this study is to evaluate the impact of hepatic dysfunction on the pharmacokinetics and safety of LY2624803 and its major metabolite, LSN2797276.


Condition Intervention Phase
Insomnia
Drug: LY2624803
Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Pharmacokinetics Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Basic Science
Official Title: A Single Dose Pharmacokinetics Study of LY2624803 in Subjects With Hepatic Impairment

Further study details as provided by Eli Lilly and Company:

Primary Outcome Measures:
  • LY2624803 and the metabolite LSN2797276 Area under the Curve from time 0 to infinity [AUC(0-∞)] [ Time Frame: Predose through 120 hours post dose ] [ Designated as safety issue: No ]
  • LY2624803 and the metabolite LSN2797276, Maximum Concentration (Cmax) [ Time Frame: Predose through 120 hours post dose ] [ Designated as safety issue: No ]
  • LY2624803 and the metabolite LSN2797276, Time to maximum plasma concentration(tmax) [ Time Frame: Predose through 120 hours post dose ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • LY2624803 and the metabolite LSN2797276, Elimination half live (t1/2) [ Time Frame: Predose through 120 hours post dose ] [ Designated as safety issue: No ]
  • LY2624803 and the metabolite LSN2797276, AUC to the last quantifiable sample [AUC(0-tlast)] [ Time Frame: Predose through 120 hours post dose ] [ Designated as safety issue: No ]
  • LY2624803 and the metabolite LSN2797276, Apparent clearance (CL/F) [ Time Frame: Predose through 120 hours post dose ] [ Designated as safety issue: No ]
  • LY2624803 and the metabolite LSN2797276, Apparent volume of distribution (V/F) [ Time Frame: Predose through 120 hours post dose ] [ Designated as safety issue: No ]
  • LY2624803 and the metabolite LSN2797276, Parent to metabolite ratios (MR) of Cmax [ Time Frame: Predose through 120 hours post dose ] [ Designated as safety issue: No ]
  • LY2624803 and the metabolite LSN2797276, Parent to metabolite ratios (MR) of AUC [ Time Frame: Predose through 120 hours post dose ] [ Designated as safety issue: No ]

Enrollment: 0
Study Start Date: November 2010
Study Completion Date: November 2010
Primary Completion Date: November 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Normal hepatic function
6mg, oral, once on day 1
Drug: LY2624803
Administered orally
Experimental: Mild hepatic impairment
6 mg, oral, once on day 1
Drug: LY2624803
Administered orally
Experimental: Moderate hepatic impairment
6 mg, oral, once on day 1
Drug: LY2624803
Administered orally
Experimental: Severe hepatic impairment
6 mg, oral, once on day 1
Drug: LY2624803
Administered orally

  Eligibility

Ages Eligible for Study:   18 Years to 75 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01257178

Locations
Germany
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.
Mitte, Germany
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.
Muenchen, Germany
Hungary
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.
Debrecen, Hungary
Russian Federation
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.
Moscow, Russian Federation
Sponsors and Collaborators
Eli Lilly and Company
Investigators
Study Director: 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
  More Information

No publications provided

Responsible Party: Chief Medical Officer, Eli Lilly
ClinicalTrials.gov Identifier: NCT01257178     History of Changes
Other Study ID Numbers: 12809, I2K-MC-ZZBL
Study First Received: December 7, 2010
Last Updated: June 2, 2011
Health Authority: United States: Food and Drug Administration
Germany: Federal Institute for Drugs and Medical Devices
Russia: Ministry of Health of the Russian Federation
Hungary: National Institute of Pharmacy

ClinicalTrials.gov processed this record on September 18, 2014