A Pharmacokinetic Study of Narlaprevir as a Single Dose or With Ritonavir Combination in Patients With Hepatic Impairment and Healthy Matched Volunteers

1. General criteria for exclusion of patients/volunteers:

* A minor, mentally or legally incompetent patient/volunteer with a significant emotional disturbance at the screening visit, or those patients/volunteers who were assumed to have the development of such disorders during the study, or those who had a history of clinically significant mental disorders.

* A patient/volunteer received any other study drug within 90 days prior to receiving the study drug dose.

* A patient/volunteer received narlaprevir in a previous clinical study, or as a means for treating the disease.

* A patient/volunteer had hypersensitivity to any component of narlaprevir or related substances.

* A patient/volunteer had a positive urine test for prohibited drugs at the screening visit and on Day -1.

* History of drug dependence of a patient/volunteer (defined as the use of any drug for entertainment) or alcoholism, or excessive drinking during the last year. Excessive drinking defined as consumption per week on average over 14 (for females) and 21 (for males) of alcoholic units (1 unit of alcohol = 8-10 g of alcohol and equivalent to about 200 ml of wine or 250 ml of beer, or standard measures for strong alcoholic beverages).

* A patient/volunteer consumed excessive amounts of coffee, cola, tea or other caffeine-containing drinks per day. Excessive drinking was considered more than 6 servings (1 serving or about 120 mg of caffeine) per day.

* A patient/volunteer received drugs, food supplements or food products prohibited in the study, with the exception of non-prescription drugs pre-approved for use by the Sponsor. When deciding on inclusion in the study, particular attention was paid to the use of such drugs as azole antifungals (ketoconazole, itraconazole), antibiotics, macrolides (erythromycin, clarithromycin), cimetidine, HIV protease inhibitors, nefazodone, rifampin, phenytoin, dexamethasone, troglitazone, barbiturates or any inducers or inhibitors of enzymes P-450 CYP3A or CYP2C9 and substrates or inhibitors of transport protein P-gp. In addition, drugs known under strong evidence for their ability to prolong the QT interval and cause polymorphic ventricular tachycardia should also have been considered as drugs of concern at inclusion.

* Pregnant and lactating females as well as females who planned to become pregnant or to deliver eggs for fertilization before, during, or within 1 month after taking part in the study. The males who planned to deliver sperm for fertilization during the study or within 12 weeks after it.

* A patient/volunteer had cancer in history other than basal cell carcinoma being in remission for at least 5 years before Day 1.

* At screening, a patient/volunteer had positive results of tests for surface antigen of hepatitis B virus (HBsAG), for antibodies to hepatitis C virus (HCV), for antigen/antibody to human immunodeficiency virus (HIV). Patients/volunteers with hepatitis B or C in history were not included in the study. The study could include patients/volunteers with a history of hepatitis A from which they recovered without any treatment, if there was no documentary evidence on complete resolution of the disease for at least 6 months prior to Day 1.

* A patient/volunteer underwent surgery, donated or lost 450 or more ml of blood (including plasmapheresis, or underwent transfusion of blood products within 90 days prior to Day 1.

* A patient/volunteer had a history of gastroesophageal reflux disease (GERD), eosinophilic esophagitis, duodenal ulcer, gastric ulcer, dyspepsia, Barrett's esophagus or Zollinger-Ellison syndrome, or had a history of or had at the time of the study (during 6 months before screening) gastrointestinal diseases that could conceivably affect the absorption of drugs.

* A history of strokes, seizures or severe chronic neurological disorders.

* A patient/volunteer had a history of or had at the time of the study clinically significant endocrine, gastrointestinal, cardiovascular, hematologic, immune, renal, respiratory or urinary disorders or diseases which the Investigator believed to affect the correct evaluation of the study or pose additional risks to a patient/volunteer's participation in the study.

* A patient/volunteer had creatinine clearance \<60 ml/min under Cockcroft-Gault calculation at screening.

* A patient/volunteer had multiple and/or severe allergy history or had a history of anaphylactic reactions or intolerance of certain prescription or nonprescription drugs or food.

* At the time of selection, a patient/volunteer regularly consumed any illicit drugs (including those for entertainment) or had a history of drug or alcohol addiction for about 2 years.

* The Investigator had any concerns about safety of a patient/volunteer participation in the study, or any other reason why the Investigator believed that the patient was not suitable for participation in the study.

* A patient/volunteer was not able to refrain from the use or intended use of any prescription or non-prescription drugs or herbal preparations (for example, St. John's wort \[hypericum perforatum\], green tea, ginkgo, coenzyme Q, ginseng, Echinacea, etc.) or dietary supplements (e.g., garlic supplements) starting about 2 weeks (or 5 half-lives) before the study drug dosing throughout the study and before and before the visit after the study. Patients with hepatic impairment administered with medication for treatment of this disease could participate in the study, if these drugs were administered at stable state for at least 4 weeks.

A Pharmacokinetic Study of Narlaprevir as a Single Dose or With Ritonavir Combination in Patients With Hepatic Impairment and Healthy Matched Volunteers

What this study is about

A Pharmacokinetic Study of Narlaprevir as a Single Dose or With Ritonavir Combination in Patients With Hepatic Impairment and Healthy Matched Volunteers

What this study is about