TMC435-TiDP16-C126 - Trial to Investigate the Effect of Severe Renal Impairment on the Pharmacokinetics and Safety of TMC435

• Status: Completed
• Trial end date: 2012-01-01
• Target enrollment: 0
• Participant gender: All

Summary

The purpose of this study is to assess the steady-state pharmacokinetics of TMC435 in participants with severe renal impairment and to compare these with the TMC435 pharmacokinetics in matched participants with normal renal function. We will also study the short-term safety and tolerability of TMC435, when administered in participants with severe renal impairment and in participants with normal renal function. Steady-state is a term that means that the drug has been given long enough so that the plasma concentrations will remain the same with each subsequent dose. TMC435 is being investigated for the treatment of chronic hepatitis C virus (HCV) infection. Pharmacokinetics (PK) means how the drug is absorbed into the bloodstream, distributed in the body, and eliminated from the body.

• Phase: Phase 1
• Accepts Healthy Volunteers?: Accepts Healthy Volunteers

Details

• Lead Sponsor: Tibotec Pharmaceuticals, Ireland
• Treatments: Simeprevir

Criteria

Inclusion Criteria:

• Nonsmoking or smoking no more than 10 cigarettes, or 2 cigars, or 2 pipes per day for at least 3 months before study screening. Body Mass Index of 18.0 to 35.0 kg/m2

• Healthy based on a medical evaluation including medical history, physical examination, blood tests, vital signs, and electrocardiogram.

• Volunteers with severe renal impairment must also meet the following inclusion criteria: 1. Consistent with the disease process causing the chronic renal failure and associated symptoms, otherwise judged to be in good health in the opinion of the investigator on the basis of a medical evaluation (including a physical examination, medical history, electrocardiogram (ECG), vital signs, and the results of blood biochemistry, blood coagulation and hematology tests and a urinalysis carried out at screening). 2. Volunteers with severe renal impairment with an estimated glomerular filtration rate (eGFR) = 29 mL/min/1.73m2, who are not on dialysis and are not expected to start dialysis in the next 3 months. 3. Severity of renal disease has to be stable: no significant change in renal function as evidenced by the serum creatinine value within ±25% from the last determination, obtained within at least 6 months before study entry. 4. Volunteers with diabetes mellitus can be included provided that the disease is controlled (i.e., HbA1c <7%). 5. Stable treatment regimen for renal impairment from 2 months prior to treatment start. Diuretics are allowed when needed. 6. Concomitant medications to treat underlying disease states or medical conditions related to renal insufficiency may be used, except when specifically excluded by name or pharmacological class, and provided that dosages are stable for at least 2 months prior to treatment start.

• Matched healthy participants must also meet the following inclusion criteria: 1. Judged to be in good health in the opinion of the investigator on the basis of a medical evaluation that reveals the absence of any clinically relevant abnormality and includes a physical examination, medical history, ECG, vital signs, and the results of blood biochemistry, blood coagulation and hematology tests and a urinalysis carried out at screening. 2. Normal renal function, i.e., eGFR = 80 mL/min/1.73m2. 3. Matched to a participant with severe renal impairment with regards to sex, race, age (± 10 years) and BMI (± 20%). Exclusion Criteria:

• Infection with hepatitis A, B or C virus

• Infection with the human immunodeficiency virus (HIV)

• History of or any current medical condition which could impact the safety of the participant in the study

• Having previously been dosed with TMC435 in a multiple-dose trial with TMC435

• Having previously been dosed with TMC435 in more than 3 single-dose trials with TMC435.

• Participants with severe renal impairment must also not have any of the following characteristics: 1. History of renal transplant or renal carcinoma. Participants with a history of renal carcinoma who have been cancer free for at least 5 years may be included. 2. Uncontrolled hypertension. 3. Hepatorenal syndrome. 4. Imminent renal replacement therapy (i.e., during the trial period).

• Matched healthy subjects must also not have the following characteristics: History of congenital or hereditary kidney disease (including polycystic kidney disease), nephrectomy, renal transplant or nephrolitiasis.