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Pharmacokinetics of GS-4997 in Adults With Normal and Impaired Hepatic Function

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ClinicalTrials.gov Identifier: NCT02509624
Recruitment Status : Completed
First Posted : July 28, 2015
Last Update Posted : December 22, 2015
Sponsor:
Information provided by (Responsible Party):
Gilead Sciences

Brief Summary:
This study will evaluate the pharmacokinetics (PK), safety, and tolerability of GS-4997 in adults with impaired hepatic function relative to matched, healthy controls. Each participant in the control group will be matched to a participant with impaired hepatic function by age (± 10 years), gender, and body mass index (± 20%).

Condition or disease Intervention/treatment Phase
Diabetic Kidney Disease Drug: GS-4997 Phase 1

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 60 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase 1, Open-Label, Parallel-Group, Single Dose Study to Evaluate the Pharmacokinetics of GS-4997 in Subjects With Normal and Impaired Hepatic Function
Study Start Date : August 2015
Actual Primary Completion Date : December 2015
Actual Study Completion Date : December 2015

Arm Intervention/treatment
Experimental: Mild hepatic impairment (Class A)
Participants with mild hepatic impairment and matched healthy controls will receive a single dose of GS-4997 on Day 1.
Drug: GS-4997
GS-4997 6 mg tablet administered orally in a fed state

Experimental: Moderate hepatic impairment (Class B)
Participants with moderate hepatic impairment and matched healthy controls will receive a single dose of GS-4997 on Day 1.
Drug: GS-4997
GS-4997 6 mg tablet administered orally in a fed state

Experimental: Severe hepatic impairment (Class C)
Participants with severe hepatic impairment and matched healthy controls will receive a single dose of GS-4997 on Day 1.
Drug: GS-4997
GS-4997 6 mg tablet administered orally in a fed state




Primary Outcome Measures :
  1. Area under the concentration-time curve (AUC) for GS-4997 and its metabolite GS-607509 [ Time Frame: Predose and 1, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, 72, 96, and 120 hours postdose ]
    AUC is defined as the concentration of drug over time.

  2. Maximum observed plasma concentration (Cmax) of GS-4997 and its metabolite GS-607509 [ Time Frame: Predose and 1, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, 72, 96, and 120 hours postdose ]

Secondary Outcome Measures :
  1. Incidence of adverse events [ Time Frame: Up to 31 days ]
    The percentage of participants experiencing any adverse event will be summarized.

  2. Incidence of laboratory abnormalities [ Time Frame: Up to 31 days ]
    The percentage of participants experiencing any clinically significant laboratory abnormality will be summarized.



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

All individuals:

  • Body mass index (BMI) from 18 to 40 kg/m^2, inclusive
  • Creatinine clearance (CrCl) ≥ 60 mL/min (using the Cockcroft-Gault method) based on serum creatinine and body weight

Individuals with impaired hepatic function:

  • Aside from hepatic insufficiency, must be sufficiently healthy for study participation based upon screening evaluations.
  • Must have diagnosis of chronic (> 6 months), stable hepatic impairment with no clinically significant change in hepatic status within the 3 months (90 days) prior to study drug administration (Day 1).
  • Individuals with severe hepatic impairment must have a score on the Child-Pugh-Turcotte scale of 10-15 at screening.
  • Individuals with moderate hepatic impairment must have a score on the Child-Pugh-Turcotte scale of 7-9 at screening.
  • Individuals with mild hepatic impairment must have a score on the Child-Pugh-Turcotte scale of 5-6 at screening.

Healthy individuals (matched control):

  • Must be in good health based upon screening evaluations.

Exclusion Criteria:

All individuals:

  • Pregnant or lactating females
  • Have received any investigational compound or device within 30 days prior to study dosing
  • Current alcohol or substance abuse
  • A positive test result for human immunodeficiency virus (HIV-1/2) antibody
  • Have poor venous access that limits phlebotomy
  • Have been treated with systemic steroids, anti-HIV agents, immunosuppressant therapies, or chemotherapeutic agents within 3 months prior to screening or expected to receive these agents during the study (eg, corticosteroids, immunoglobulins, and other immune- or cytokine-based therapies) that would be contraindicated for other exclusion criteria.
  • Significant serious skin disease, such as but not limited to rash, food allergy, eczema, psoriasis, or urticaria
  • Significant drug sensitivity or drug allergy (such as anaphylaxis or hepatoxicity)
  • Unstable cardiac disease, including history of myocardial infarction within 1 year of screening, recurrent episodes of ventricular tachycardia despite appropriate medical therapy, decompensated congestive heart failure, or dilated cardiomyopathy with left ventricular ejection fraction < 40%), or a family history of Long QT Syndrome, or unexplained death in an otherwise healthy individual between the ages of 1 and 30 years.
  • Syncope, palpitations, or unexplained dizziness
  • Implanted defibrillator or pacemaker.
  • Severe peptic ulcer disease, severe gastroesophageal reflux disease, or other severe gastric acid hypersecretory conditions.
  • Medical or surgical treatment that permanently alters gastric absorption (eg, gastric or intestinal surgery). A history of cholecystectomy is not exclusionary.
  • History of prior allogeneic bone marrow progenitor cell or solid organ transplantation.
  • Currently registered on an organ transplantation list.
  • History of bleeding from esophageal varices within 90 days prior to Admission (Day -1).
  • Use of strong CYP3A4 inhibitors (eg, indinavir, nelfinavir, ritonavir, clarithromycin, itraconazole, ketoconazole, nefazodone, saquinavir, suboxone, telithromycin, atazanavir) and strong CYP3A4 inducers (eg, carbamazepine, rifampin, phenytoin and St. John's wort), within 28 days prior to study drug administration (Day 1).
  • Consumption of grapefruit juice, grapefruits, and Seville orange juice within 2 weeks prior to study drug administration (Day 1).
  • Recent significant changes in the use of nicotine or nicotine containing products

Individuals with impaired hepatic function:

  • Aside from hepatic insufficiency, serious or active medical or psychiatric illness that, in the opinion of the investigator, would interfere with treatment, assessment, or compliance with the protocol.
  • Chronic hepatitis B virus (HBV) infection, defined as a positive test for hepatitis B surface antigen (HBsAg), unless the patient has been treated with a nucleos(t)ide analog (eg, tenofovir or entecavir) for at least 6 months and the HBV DNA by polymerase chain reaction (PCR) assay has been persistently undetectable for at least 6 months.
  • Positive test for drugs of abuse, including alcohol at screening or on Day -1/check-in, with the exception of opioids and tetrahydrocannabinol (THC, marijuana) under prescription and investigator verification for pain management. Individuals who screen positive for benzodiazepines may be allowed if prescribed under the care of a physician and after review by investigator and Sponsor.
  • Requires paracentesis > 1 time per month.
  • Individuals with hepatic impairment with co-morbid diseases not associated with hepatic impairment requiring medication(s) must be taking the medication(s) without a change in dose for > 3 months prior to screening.
  • Changes in concomitant medications or dosage used to treat symptoms of hepatic impairment or associated co-morbid conditions that could lead to clinically significant changes in medical conditions during the course of the study that would affect the ability to interpret potential drug-drug interactions within 28 days prior to dosing.

Healthy individuals (matched control):

  • A positive test result for hepatitis C virus (HCV) antibody, hepatitis B surface antigen (HBsAg), or hepatitis B core antibody (anti-HBc)
  • Positive test for drugs of abuse, including alcohol at screening or on Day -1/check-in.
  • Have any serious or active medical or psychiatric illness (including depression) which, in the opinion of the investigator, would interfere with treatment, assessment, or compliance with the protocol.
  • History of liver disease.
  • Have taken any prescription medications or over-the-counter medications including herbal products within 28 days of commencing study drug dosing with the exception of vitamins, acetaminophen, ibuprofen, and hormonal contraceptive medications.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02509624


Locations
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United States, Colorado
Denver, Colorado, United States
United States, Florida
Miami, Florida, United States
Orlando, Florida, United States
United States, Minnesota
Minneapolis, Minnesota, United States
United States, Texas
San Antonio, Texas, United States
New Zealand
Grafton, Auckland, New Zealand
Sponsors and Collaborators
Gilead Sciences
Investigators
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Study Director: Thomas O'Riordan, MD Gilead Sciences

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Responsible Party: Gilead Sciences
ClinicalTrials.gov Identifier: NCT02509624     History of Changes
Other Study ID Numbers: GS-US-223-1018
First Posted: July 28, 2015    Key Record Dates
Last Update Posted: December 22, 2015
Last Verified: December 2015

Additional relevant MeSH terms:
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Kidney Diseases
Diabetic Nephropathies
Urologic Diseases
Diabetes Complications
Diabetes Mellitus
Endocrine System Diseases