Evaluate the Pharmacokinetics of GS-9876 in Subjects with Impaired Renal Functio
- Conditions
- Inflammatory DiseasesInflammatory and Immune System - Other inflammatory or immune system disordersInflammatory and Immune System - Rheumatoid arthritisInflammatory and Immune System - Autoimmune diseases
- Registration Number
- ACTRN12616001548426
- Lead Sponsor
- Gilead Sciences, Inc
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Recruiting
- Sex
- All
- Target Recruitment
- 60
All Subjects:
1) Have the ability to understand and sign a written informed consent form (ICF), which must be obtained prior to initiation of study procedures
2) Be between 18 through 75 years of age, inclusive at screening
3) Must be able to comply with the smoking restrictions at the study site.
4) Have a calculated body mass index (BMI) of >=18 kg/m2 and <=36 kg/m2 at screening
5) Females of childbearing potential must have a negative serum pregnancy test at screening and clinic admission (Day -1).
6) Female subjects must refrain from egg donation and in vitro fertilization during treatment and until at least 36 days after the last dose of study drug.
7) Male subjects and female subjects of childbearing potential who engage in heterosexual intercourse must agree to use protocol specified method(s) of contraception.
8) Male subjects must refrain from sperm donation from clinic admission (eg, Day -1),
throughout the study period, and continuing for at least 90 days following the last dose of study drug
9) Subjects have not donated blood within 56 days of study entry or plasma within 7 days of study entry and must refrain from blood donation from clinic admission, throughout the study period, and continuing for at least 30 days following the last dose of study drug.
10) Have either a normal 12-lead ECG or one with abnormalities that are considered clinically insignificant by the investigator in consultation with the sponsor
11) Must be willing and able to comply with all study requirements
12) Must, in the opinion of the investigator, be in good health based upon medical history and physical examination, including vital signs
13) Subjects must have the following laboratory parameters at screening:
a) Hemoglobin >=8.0 g/dL (International System of Units [SI]: <80 g/L)
b) White blood cells >=3.0 x 10^3 cells/mm3 (SI: <3.0 x 10^9 cells/L)
c) Neutrophils >=1.5 x 10^3 cells/mm3 (SI: <1.5 x 10^9 cells/L)
d) Lymphocytes >=0.5 x 10^3 cells/mm3 (SI: <0.5 x 10^9 cells/L)
e) Platelets >=100 x 10^3 cells/mm3 (SI: <100 x 10^9 cells/L)
f) Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) <1.5 x ULN
g) Total bilirubin level <2 x ULN
Subjects with Renal Impairment:
1) Must have diagnosis of chronic (>6 months), stable renal impairment with no clinically
significant change in renal function status within 90 days prior to study drug administration (Day 1).
2) Have a creatinine clearance (CLcr) =<90 mL/min (using the Cockcroft-Gault method
based on serum creatinine and actual body weight as measured at screening, ie,
Male: (140 – Age [years]) x (Weight [kg]) / 72 x (Serum Creatinine [mg/dL]) = CLcr (mL/min)
Female: (140 – Age [years]) x (Weight [kg]) / 72 x (Serum Creatinine [mg/dL]) x 0.85 = CLcr (mL/min)
Mild: CLcr 60-89 mL/min
Moderate: CLcr 30-59 mL/min
Severe: CLcr 15-29 mL/min
Healthy Matched Controlled Subjects (Normal Renal Function):
1) Must, in the opinion of the investigator, be in good health based upon medical history and physical examination, including vital signs.
2) Have a creatinine clearance (CLcr) >=90 mL/min (using the Cockcroft-Gault method
based on serum creatinine and actual body weight as measured at screening, ie,
Male: (140 – Age [years]) x (Weight [kg]) / 72 x (Serum Creatinine [mg/dL]) = CLcr (mL/min)
Female: (140 – Age [years]) x (Weight [kg]) / 72 x (Serum Creatinine [mg/dL]) x 0.85 = CLcr (mL/min)
3) Match in age (+/- 10 years), gender, and body mass index (+/- 20
All Subjects:
1) Be a lactating female
2) Have received any investigational compound within 30 days prior to study dosing
3) Have current alcohol or substance abuse judged by the investigator to potentially interfere with subject compliance or subject safety as judged by the investigator
4) Have a positive test result for human immunodeficiency virus type 1 (HIV-1) antibody,
hepatitis B surface antigen (HBsAg), hepatitis B core antibody (HBcAb), or hepatitis C virus
(HCV) antibody
5) Have poor venous access that limits phlebotomy
6) Have been treated with systemic steroids, immunosuppressant therapies, or chemotherapeutic agents within 3 months prior to screening or is expected to receive these agents during the study (eg, corticosteroids, immunoglobulins, and other immune- or cytokine-based therapies)
7) Have a history of any of the following:
a) Significant serious skin disease, such as but not limited to rash, food allergy, eczema,
psoriasis, or urticaria
b) Significant drug sensitivity or drug allergy (such as anaphylaxis or hepatoxicity)
c) Known hypersensitivity to the study drugs, their metabolites or to formulation excipients
d) Significant cardiac disease (including history of myocardial infarction based on ECG
and/or clinical history, any history of ventricular tachycardia, congestive heart failure, or
dilated cardiomyopathy with left ventricular ejection fraction <40%), a family history of
long QT syndrome, or unexplained death in an otherwise healthy individual between the
ages of 1 and 30 years
e) Syncope, palpitations, or unexplained dizziness
f) Implanted defibrillator or pacemaker
g) Liver disease, including Gilbert disease
h) Severe peptic ulcer disease, gastroesophageal reflux disease, or other gastric acid
hypersecretory conditions requiring prolonged (>6 months) medical treatment.
i) Medical or surgical treatment that permanently altered gastric absorption (eg, gastric or intestinal surgery). A history of cholecystectomy is not exclusionary.
j) History of any major bleeding event defined as Grade 3 severity and above (as defined by the modified CTCAE 4.03) within the last year or personal or family history of bleeding disorder
k) Current use of chronic anticoagulant or anti-platelet agent, not including daily aspirin for cardiac prophylaxis.
8) Have any serious or active medical or psychiatric illness (including depression) that, in the opinion of the investigator, would interfere with subject treatment, assessment, or compliance with the protocol. This would include cardiac, hematological, hepatic, pulmonary (including chronic asthma), endocrine (including diabetes), central nervous, gastrointestinal (including an ulcer), vascular, metabolic (thyroid disorders, adrenal disease), immunodeficiency disorders, active infection, or malignancy that are clinically significant or requiring treatment.
9) Recent significant changes in the use of nicotine or nicotine containing products
(ie, initiation, substantial increase or decrease or cessation of use) in the 90 days prior to
study drug dosing, or anticipated significant changes in the use of nicotine or nicotine
containing products during the course of the study through the follow-up visit.
Subjects with Renal Impairment:
1) Require or are anticipated to require dialysis within 90 days of study dosing
2) Require during the study or have received moderate or strong inhibitors or inducers of
CYP3A within 2 weeks prior to study drug admi
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method To evaluate the pharmacokinetics (PK) of GS-9876 in subjects with impaired renal function relative to matched, healthy controls<br>The primary endpoints are PK parameters AUClast, AUCinf, and Cmax for GS-9876.[Intensive PK sampling will occur relative to dosing of GS-9876 at the following time points for each cohort.<br>Plasma PK:<br>Day 1: 0 (predose), 0.5, 1, 2, 3, 4, 5, 6, 8, 12, 16, 24, 36, 48, 60, 72, 96 and 120 hours postdose.<br>Urine PK:<br>Predose void, 0-6, 6-12, 12-24, 24-48, 48-72, 72-96, and 96-120 hours postdose.]
- Secondary Outcome Measures
Name Time Method To evaluate the safety and tolerability of GS-9876 in subjects with normal and impaired renal function. The secondary endpoints include incidences of AEs, laboratory abnormalities, abnormal findings in vital signs and safety ECG monitoring.[Safety will be evaluated throughout the study. Incidences of adverse events will be monitored continuously from screening to end of study. <br>Vital signs: Screening, Day-1, 1, 2, 3, 4, 5, 6, 15, and early termination <br>ECG: Screening, Day-1, 1, 6, 15, and early termination <br>Lab assessments: Screening, Day-1, 1, 2, 3, 6, 15, and early termination]