title: The combination of elbasvir and grazoprevir for the treatment of chronic HCV infection in Japanese patients: a randomized phase II/III study.
abstract: BACKGROUND
  Elbasvir (EBR) in combination with grazoprevir (GZR) has demonstrated efficacy in patients with hepatitis C virus (HCV) infections in trials primarily conducted in the USA and Europe. We investigated the safety and efficacy of EBR in combination with GZR in Japanese patients with chronic HCV infection, with or without cirrhosis.
  
  
  METHODS
  The study was conducted in two parts. In part 1, noncirrhotic patients were randomized 1:1 to receive EBR (50 mg) in combination with GZR (50 or 100 mg) once daily for 12 weeks. In part 2, noncirrhotic patients were randomized 3:1 to receive immediate or deferred treatment with EBR (50 mg) and GZR (100 mg, determined in part 1) for 12 weeks; cirrhotic patients received open-label immediate treatment. The primary efficacy end point was the rate of sustained virologic response 12 weeks after completion of the study treatment.
  
  
  RESULTS
  In part 1, 63 patients were randomized to receive EBR in combination with GZR at a dose of 50 mg (n = 31) or 100 mg (n = 32). The SVR12 rates were 100% with GZR at a dose of 50 mg and 96.8% with GZR at a dose of 100 mg. Tolerability was similar in both arms. In part 2, 301 noncirrhotic patients were randomized to receive immediate treatment (n = 227) or deferred treatment (n = 74), and 35 cirrhotic patients were enrolled. The SVR12 rates were 96.5% and 97.1% after immediate treatment in noncirrhotic and cirrhotic patients respectively. Safety was generally similar between immediate and deferred treatment.
  
  
  CONCLUSIONS
  Treatment with EBR in combination with GZR for 12 weeks is effective and well tolerated in Japanese patients with chronic HCV infection. CLINICALTRIALS.
  NCT02203149.
authors.affiliation: Department of Hepatology, Toranomon Hospital, 1-3-1 Kajigaya, Takatsu-ku, Kawasaki, Kanagawa, 213-8587, Japan. kumahiro@toranomon.gr.jp.
authors.forename: Hiromitsu
authors.initials: H
authors.lastname: Kumada
authors.affiliation: Department of Hepatology, Toranomon Hospital, 1-3-1 Kajigaya, Takatsu-ku, Kawasaki, Kanagawa, 213-8587, Japan.
authors.forename: Yoshiyuki
authors.initials: Y
authors.lastname: Suzuki
authors.affiliation: Department of Gastroenterology, Sapporo Kosei General Hospital, North-3 East-8, Chuou-ku, Sapporo, Hokkaido, 060-0033, Japan.
authors.forename: Yoshiyasu
authors.initials: Y
authors.lastname: Karino
authors.affiliation: Department of Gastroenterology and Metabolism, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima, 734-8551, Japan.
authors.forename: Kazuaki
authors.initials: K
authors.lastname: Chayama
authors.affiliation: Department of Hepatology, Osaka City University Medical School, 1-4-3 Asahimachi, Abeno-ku, Osaka, 545-8585, Japan.
authors.forename: Norifumi
authors.initials: N
authors.lastname: Kawada
authors.affiliation: Department of Gastroenterology and Hepatology, Saiseikai Suita Hospital, 1-2 Kawazono-cho, Suita-Shi, Osaka, 564-0013, Japan.
authors.forename: Takeshi
authors.initials: T
authors.lastname: Okanoue
authors.affiliation: Department of Molecular Gastroenterology and Hepatology, Kyoto Prefectural University of Medicine, 465 Kajii-cho, Kawaramachi Hirokoji, Kamigyo-ku, Kyoto, 602-8566, Japan.
authors.forename: Yoshito
authors.initials: Y
authors.lastname: Itoh
authors.affiliation: Department of Gastroenterology and Hepatology, Saitama Medical University, 38 Morohongo, Moroyama-machi, Iruma-gun, Saitama, 350-0495, Japan.
authors.forename: Satoshi
authors.initials: S
authors.lastname: Mochida
authors.affiliation: Department of Gastroenterology, Ogaki Municipal Hospital, 4-86 Minaminokawa, Ogaki, 503-8502, Japan.
authors.forename: Hidenori
authors.initials: H
authors.lastname: Toyoda
authors.affiliation: Third Department of Internal Medicine, Nara Medical University, 840 Shijo-cho, Kashihara, Nara, 634-8522, Japan.
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Yoshiji
authors.affiliation: Department of Gastroenterology/Liver Center, Hiroshima Red Cross Hospital and Atomic-Bomb Survivors Hospital, 1-9-6, Senda-machi, Naka-ku, Hiroshima, 730-8619, Japan.
authors.forename: Shintaro
authors.initials: S
authors.lastname: Takaki
authors.affiliation: MSD K.K., 1-13-12 Kudan-kita, Chiyoda-ku, Tokyo, 102-8667, Japan.
authors.forename: Naoyoshi
authors.initials: N
authors.lastname: Yatsuzuka
authors.affiliation: MSD K.K., 1-13-12 Kudan-kita, Chiyoda-ku, Tokyo, 102-8667, Japan.
authors.forename: Etsuo
authors.initials: E
authors.lastname: Yodoya
authors.affiliation: MSD K.K., 1-13-12 Kudan-kita, Chiyoda-ku, Tokyo, 102-8667, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Iwasa
authors.affiliation: MSD K.K., 1-13-12 Kudan-kita, Chiyoda-ku, Tokyo, 102-8667, Japan.
authors.forename: Go
authors.initials: G
authors.lastname: Fujimoto
authors.affiliation: Merck & Co.Inc., 2000 Galloping Hill Road, Kenilworth, NJ, 07033, USA.
authors.forename: Michael N
authors.initials: MN
authors.lastname: Robertson
authors.affiliation: Merck & Co.Inc., 2000 Galloping Hill Road, Kenilworth, NJ, 07033, USA.
authors.forename: Stuart
authors.initials: S
authors.lastname: Black
authors.affiliation: Merck & Co.Inc., 2000 Galloping Hill Road, Kenilworth, NJ, 07033, USA.
authors.forename: Luzelena
authors.initials: L
authors.lastname: Caro
authors.affiliation: Merck & Co.Inc., 2000 Galloping Hill Road, Kenilworth, NJ, 07033, USA.
authors.forename: Janice
authors.initials: J
authors.lastname: Wahl
mesh_terms: D000284:Administration, Oral; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000577:Amides; D000998:Antiviral Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000097:blood / Q000627:therapeutic use*; D001572:Benzofurans / Q000008:administration & dosage / Q000009:adverse effects / Q000097:blood / Q000627:therapeutic use*; D002219:Carbamates; D003521:Cyclopropanes; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D024882:Drug Resistance, Viral; D004359:Drug Therapy, Combination; D005260:Female; D016174:Hepacivirus / Q000187:drug effects / Q000235:genetics / Q000302:isolation & purification; D019698:Hepatitis C, Chronic / Q000097:blood / Q000150:complications / Q000188:drug therapy* / Q000821:virology; D006801:Humans; D007093:Imidazoles / Q000008:administration & dosage / Q000009:adverse effects / Q000097:blood / Q000627:therapeutic use*; D008103:Liver Cirrhosis / Q000188:drug therapy / Q000821:virology; D008297:Male; D008875:Middle Aged; D011810:Quinoxalines / Q000008:administration & dosage / Q000009:adverse effects / Q000097:blood / Q000627:therapeutic use*; D012367:RNA, Viral / Q000097:blood; D013449:Sulfonamides; D000072230:Sustained Virologic Response; D016896:Treatment Outcome; D055815:Young Adult; D047029:Lactams, Macrocyclic
chemical_list: D000577:Amides; D000998:Antiviral Agents; D001572:Benzofurans; D002219:Carbamates; D003521:Cyclopropanes; D007093:Imidazoles; D011810:Quinoxalines; D012367:RNA, Viral; D013449:Sulfonamides; C578009:grazoprevir; D047029:Lactams, Macrocyclic; C000589335:elbasvir
keywords: Clinical trial; Efficacy; Genotype; Sustained virologic response; Therapy