HIV MedDRA version: 14.1 Level: PT Classification code 10062237 Term: Renal impairment System Organ Class: 10038359 - Renal and urinary disorders
Conditions
Interventions
Trade Name: Celsentri
Pharmaceutical Form: Tablet
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 150-
Trade Name: Norvir
Pharmaceutical Form: Capsule
Concentratio
Sponsors
Pfizer Inc.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Male or female subjects (female subjects must be of non childbearing potential, between the ages of 18 and 85 years, inclusive. 2. Body Mass Index (BMI) of approximately 18 to 40 kg/m2 inclusive; and a total body weight >50 kg (110 lbs) determined at screening. 3. Subjects must meet one of the following renal function categories: • Normal renal function (CLCR >80 mL/min). • Mild renal impairment (CLCR >50 and =80 mL/min). • Moderate renal impairment (CLCR =30 and =50 mL/min). • Severe renal impairment (CLCR =65 years) yes F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: 1. Women who are pregnant or nursing or women of childbearing potential. 2. Subjects with known contraindications to maraviroc (and/or boosted saquinavir for subjects with normal, mild or moderate renal impairment) according to local labeling. 3. Subjects with recent (within the last 3 months) history of myocardial infarction, unstable angina, coronary revascularization, stroke or TIA. 4. Subjects with severe heart failure (New York Heart Association Functional Class IV) at screening. 5. Subjects with acute renal disease. 6. Subjects with a history of renal transplant. However, subjects with a history of renal transplant who have rejected the organ and are no longer receiving immunosuppressive drugs are eligible for the study provided that the graft has been non-functional for at least one year. 7. For subjects receiving hemodialysis, subjects who have been hemodynamically unstable during or at the conclusion of dialysis, during the 2 weeks prior to dosing, as marked by symptomatic hypotension. 8. Subjects with liver disease as assessed by clinical evaluation or subjects with an ALT or AST at Screening that is >2.5 x-upper limit of the reference range (ULRR) or a total bilirubin that is >1.5 x-ULRR at Screening. 9. Subjects with any prior history of malignancy except for: • Basal cell carcinoma of the skin. • Squamous cell carcinoma of the skin that has been cancer free for >5 years. • Other malignancies (regardless of site) that have been cancer free for >10 years. 10. Healthy subjects: Use of prescription drugs, vitamins and dietary supplements within seven days or 5 half-lives (whichever is longer) prior to the first dose of study medication. 11. Herbal supplements and hormone replacement therapy must be discontinued 28 days prior to the first dose of study medication. As an exception, acetaminophen may be used at doses of =1 g/day. Other exceptions may be granted by a qualified member of the Pfizer study management. 12. Renal Impaired subjects: Received any of the following medications/supplements within 7 days or 5 half-lives (whichever was longer) prior to the first dose of study medication or during the study. These medications and supplements are prohibited for the duration of the study. • Any drug known to be a potent inhibitor of CYP3A, including erythromycin, clarithromycin, telithromycin, systemic azole antifungal therapy (including ketoconazole, itraconazole, voriconazole and fluconazole), nefazodone, fluvoxamine. • Any immunosuppressive drugs, including cyclosporine, tacrolimus, sirolimus. • Any protease inhibitors (with the exemption of boosted saquinavir as scheduled as part of the Study Design). • Any potent enzyme-inducing drug, including rifampin, phenytoin, St John’s Wort and carbamazepine. • Cimetidine, trimethoprim and cibenzoline. • Grapefruit juice. 13. Positive urine (or saliva; for subjects with ESRD) drug screen for drugs of abuse or recreational drugs. Subjects with renal impairment will be eligible to participate if their urine drug screen is positive for a prescribed medication (eg, benzodiazepine, opioid, etc). 14. History of regular alcohol consumption exceeding 7 drinks/week for women or 14 drinks/week for men (1 drink = 5 ounces (150 mL) of wine, 12 ounces (360 mL) of beer, or 1.5 ounces (45 mL) of hard liquor) within 6 months of study medication. 15. Treatment with an investigational drug within 28 days prior to the dose of study medication. 16. Screening 12-lead ECG demo
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Primary objectives: • Characterize the pharmacokinetics of MVC (150 mg) in the presence of Saquinavir/Ritonavir (SQV/r, a potent CYP3A4 inhibitor) in both healthy subjects and subjects with mild and moderate renal impairment. • Characterize the pharmacokinetics of MVC (300 mg) in healthy subjects, subjects with severe renal impairment and those receiving chronic hemodialysis. • Calculate the hemodialysis clearance of MVC in subjects with end stage renal disease (ESRD) undergoing hemodialysis.;Secondary Objective: Assess the safety and tolerability of MVC in the absence and presence of a potent CYP3A4 inhibitor in subjects with various degrees of renal impairment or undergoing hemodialysis.;Primary end point(s): AUCtlast/tau and Cmax for all subjects, secondary pharmacokinetic endpoints for MVC will be plasma protein binding, AUCinf, Tmax, and half-life (t1/2), as data permits. In addition, renal clearance (CLr) will be determined for subjects with normal, mild, moderate, and severe renal function and hemodialysis clearance will be determined for subjects with ESRD on hemodialysis | — |
Countries
Germany
Outcome results
None listed