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

NCT ID: NCT01381835

Last Updated: 2013-10-14

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 16 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2011-07-31
• Study Completion Date: 2012-01-31

Brief 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.

Detailed Description

TMC435 is a protease inhibitor (PI) and is being investigated for treatment of chronic hepatitis C virus (HCV) infection, in combination with Peg-IFN (pegylated interferon) and RBV (ribavirin). The result of this study may provide dosing recommendations for TMC435 in patients with severe renal impairement. This is a Phase I, open-label (both participant and investigator know the name of the medication given at certain moment), to investigate the effect of severe renal impairment on the pharmacokinetics and safety of TMC435. Severe renal impairment will be defined by an estimated glomerular filtration rate (eGFR) = 29 mL/min/1.73m2. Participants with severe renal impairment are only allowed in this study if they are not on dialysis. Normal renal function will be considered as an eGFR = 80 mL/min/1.73m2. eGFR is a measured filtering capacity of the kidneys. The trial population will consist of a total of 16 male or female participants. Eight (8) healthy participants with a normal renal function and 8 participants with severe renal impairment will be included. A healthy participant will be matched to a participant with severe renal impairment with regards to sex, race, age (± 10 years), and body mass index (BMI) (± 20%). Dosing of the matched healthy participants can only start once the corresponding participants with severe renal impairment has completed Day 10 assessments (including physical examination). All participants will receive TMC435150 mg once a day (q.d.) for 7 days under fed conditions. Blood and urine samples, electrocardiogram (ECG) and vital signs (blood pressure and heart rate) will be taken at screening, on Day 1, Day 7, at the follow-up visit at 1 week after last dose of study medication and at the follow-up visit at 4-5 weeks after last dose of study medication. A physical examination will be performed at screening, on Day -1 (= day before first medication intake), on Day 10 and during the follow-up visits. A full pharmacokinetic profiles of bound TMC435 will be determined on Day 7 up to 72 hours postdose. In addition, unbound TMC435 plasma concentrations will be determined at specified timepoints. Safety and tolerability will be monitored throughout the trial. Participants will be admitted to the unit on Day-1 and discharged on Day10. Each participant will receive orally 150 mg TMC435, q.d. for 7 consecutive days.

Conditions

Hepatitis C Virus

Keywords

TMC435-TiDP16-C126; TMC435-C126; TMC435; HCV; Hepatitis C; Hep C; severe renal impairement

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

001

TMC435 150 mg capsule once daily for 7 days

Group Type: EXPERIMENTAL

TMC435

Intervention Type: DRUG

150 mg capsule once daily for 7 days

Interventions

TMC435

150 mg capsule once daily for 7 days

Intervention Type: DRUG

Eligibility 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.
• 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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 70 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Tibotec Pharmaceuticals, Ireland

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Tibotec Pharmaceuticals Clinical Trial

Role: STUDY_DIRECTOR

Tibotec Pharmaceutical Limited

Locations

Prague, , Czechia

Countries

Czechia

Related Links

http://filehosting.pharmacm.com/DownloadService.ashx?client=CTR_JNJ_6051&studyid=1120&filename=CR017953_CSR.pdf

A Phase I, open-label trial to investigate the effect of severe renal impairment on the pharmacokinetics and safety of TMC435

Other Identifiers

TMC435-TiDP16-C126

Identifier Type: OTHER

Identifier Source: secondary_id

CR017953

Identifier Type: -

Identifier Source: org_study_id