This will be an open-label, parallel-group study to investigate the effect of renal impairment on the pharmacokinetics of a new drug following a single oral 125 mg dose. A total of approximately 28 subjects (7 subjects per group) with the different degrees of renal function (http://www.availclinical.com/
To be eligible, applicants must demonstrate stable renal function during the screening period, as shown by two CLcr values obtained within a two week period being within 20% of each other. The average value will be used for study enrollment. The CLcr value on Day 1 will be the value used to categorize the subjects’ renal function for the subsequent PK analysis. The eGFR value on Day 1 will be recorded but not used to categorize the subjects.
Physical examinations, 12-lead electrocardiogram (ECG), vital sign measurements, and clinical laboratory tests (http://www.availclinical.com/
BACKGROUND & RATIONALE
This new form of renal impairment medication is a highly selective, reversible inhibitor of cyclin-dependent kinases (CDK) 4 and 6. Inhibition of CDK 4/6 blocks deoxyribonucleic acid (DNA) synthesis by prohibiting progression of the cell cycle from G1 to S phase. Data from nonclinical studies indicate that the experimental therapy may produce cytoreductive as well as cytostatic effects.
To evaluate the impact of renal impairment (http://www.availclinical.com/
Subject eligibility (http://www.availclinical.com/
Male and/or female subjects of non-childbearing potential between the ages of 18 and 75 years, inclusive. Female subjects of non-childbearing potential must meet at least one of the following criteria:
Achieved postmenopausal status, defined as: cessation of regular menses for at least 12 consecutive months with no alternative pathological or physiological cause; and have a serum follicle stimulating hormone (FSH) level within the laboratory’s reference range for postmenopausal females;
Have undergone a documented hysterectomy and/or bilateral oophorectomy;
Have medically confirmed ovarian failure.
All other female subjects (including females with tubal ligations and females that do NOT have a documented hysterectomy, bilateral oophorectomy and/or ovarian failure) will be considered to be of childbearing potential.
Body Mass Index (BMI) of 18 to 40 kg/m2; and a total body weight >50 kg (110 lbs).
Evidence of a personally signed and dated informed consent document indicating that the subject (or a legal representative)
Subjects who are willing and able to comply with all scheduled visits, treatment plan, laboratory tests, and other study procedures.
GROUP 1 INCLUSION CRITERIA
Healthy male and/or female subjects of non-childbearing potential between the ages of 18 and 75 years, inclusive. (Healthy is defined as no clinically relevant abnormalities identified by a detailed medical history, full physical examination, including blood pressure and pulse rate measurement, 12-lead ECG and clinical laboratory tests).
Normal renal function (CLcr 90 mL/min) during the screening period, based on the average of the two CLcr values (calculated by the Cockcroft-Gault equation) obtained within a 2-week period. The two CLcr values need to be within 20% of each other.
Matched for age (5 years), weight (10 kg), gender and race to subjects in the impaired renal function groups.
GROUPS 2-4 INCLUSION CRITERIA
Good general health commensurate with the population with chronic kidney disease (renal impairment). ‘Health’ is defined as no clinically relevant abnormalities (with the exception of hypertension)
Stable drug regimen defined as not starting a new drug or changing dosage within seven days or five half-lives (whichever is longer) before dosing the study drug.
Any form of renal impairment except acute nephritic syndrome (subjects with history of previous nephritic syndrome but in remission can be included).
Meet one of the following CLcr criteria during the screening period based on the average of two CLcr values (calculated by the Cockcroft-Gault equation) obtained within a 2-week period, but not requiring hemodialysis. The two CLcr values need to be within 20% of each other.
Mild: CLcr 60 mL/min and <90 mL/min, or
Moderate: CLcr 30 mL/min and <60 mL/min, or
Severe: CLcr <30 mL/min but not requiring hemodialysis.
*Avail Clinical Research conducts a variety of Clinical Research Studies in Florida (http://www.availclinical.com/