ABSTRACT
INTRODUCTION: Chronic cough is a highly problematic symptom for patients with idiopathic pulmonary fibrosis (IPF); limited therapeutic options are available. We evaluated gefapixant, a P2X3 receptor antagonist, for the treatment of chronic cough in IPF. METHODS: This randomized, double-blind, placebo-controlled, crossover study included subjects with IPF. Sequence A included gefapixant 50 mg BID (period 1; 14 days) followed by placebo (period 2; 14 days); sequence B had the opposite sequence of treatments. This regimen was specified in a protocol amendment that modified the original active treatment regimen of gefapixant 50 mg BID for 10 days and 150 mg BID for 4 days. Patients randomized to the original treatment regimen were excluded from efficacy analyses but included in safety assessments. The primary efficacy endpoint was change from baseline in awake cough frequency (coughs/hour) from periods 1 and 2 combined. Adverse events (AEs) were monitored throughout the study. RESULTS: A total of 51 subjects were randomized, 44 of whom were randomized to treatment sequences evaluated in the primary efficacy analysis (i.e., 22 subjects in sequence A and 22 subjects in sequence B); seven subjects received the treatment assigned before the protocol amendment and were excluded from efficacy analyses. The change from baseline in awake cough frequency from periods 1 and 2 combined (mixed model for repeated measures analysis) did not demonstrate a significant reduction versus placebo in cough at day 14 (p = 0.90); in a post hoc analysis of log-transformed data p value for reduction versus placebo at day 14 was 0.07. The most common AEs were related to taste (dysgeusia and ageusia). CONCLUSIONS: Gefapixant was generally well tolerated but was not associated with a significant improvement in chronic cough in subjects with IPF as defined by the primary endpoint in this study. TRIAL REGISTRATION: NCT02502097.
ABSTRACT
Direct-acting antiviral agents (DAAs) represent the standard of care for patients with hepatitis C virus (HCV) infection. Combining DAAs with different mechanisms may allow for shorter treatment durations that are effective across multiple genotypes. The aim of the C-SWIFT study was to identify the minimum effective treatment duration across multiple genotypes. C-SWIFT was an open-label, single-center trial in treatment-naïve patients with chronic HCV genotype (GT)1 or 3 infection. All patients received elbasvir (EBR) 50 mg/grazoprevir (GZR) 100 mg with sofosbuvir (SOF) 400 mg for 4-12 weeks. Patients with GT1 infection who failed therapy were eligible for retreatment with EBR/GZR+SOF and ribavirin for 12 weeks. The primary efficacy endpoint was sustained virological response [SVR]12 (SVR of HCV RNA <15 IU/mL 12 weeks after the end of therapy). Rates of SVR12 were 32% (10 of 31) and 87% (26 of 30) in patients without cirrhosis with GT1 infection treated for 4 and 6 weeks and 80% (16 of 20) and 81% (17 of 21) in GT1-infected patients with cirrhosis treated for 6 and 8 weeks. Among GT3-infected patients without cirrhosis, SVR12 was 93% (14 of 15) and 100% (14 of 14) after 8 and 12 weeks. SVR12 in GT3-infected patients with cirrhosis was 83% (10 of 12) after 12 weeks of treatment. Twenty-three GT1-infected patients who relapsed following initial treatment completed retreatment; all achieved SVR12. In the initial treatment phase, there was one serious adverse event of pneumonia, which led to treatment discontinuation, and during retreatment, 1 patient discontinued ribavirin because of pruritus. CONCLUSION: Data from this study support the use of 8-week treatment regimens that maintain high efficacy, even for patients with HCV GT3 infection. Retreatment of patients who failed short-duration therapy was achieved through extended treatment duration and addition of ribavirin. (Hepatology 2017;65:439-450).
