Time to Endorse A Sensitive Method for Scoring Endoscopic Activity of Ulcerative Colitis in Clinical Research.

The endoscopic scoring of ulcerative colitis is routinely used for both individual patient management and as an endpoint in clinical trials. The most commonly used scoring system is the Mayo endoscopic subscore, which scores endoscopic disease activity on a scale between 0 and 3. With only four possible scores and consideration of only the most involved area of the colon, the Mayo endoscopic subscore lacks sensitivity to change in measuring the totality of the endoscopic inflammatory involvement in patients with ulcerative colitis.

PTG-100, an Oral α4β7 Antagonist Peptide: Preclinical Development and Phase 1 and 2a Studies in Ulcerative Colitis.

Background & Aims: Oral therapies targeting the integrin α4β7 may offer unique advantages for the treatment of inflammatory bowel disease. We characterized the oral α4β7 antagonist peptide PTG-100 in preclinical models and established safety, pharmacokinetic/pharmacodynamic relationships, and efficacy in a phase 2a trial in patients with ulcerative colitis (UC).

Methods: In vitro studies measured binding properties of PTG-100.

Adherence to pan-genotypic glecaprevir/pibrentasvir and efficacy in HCV-infected patients: A pooled analysis of clinical trials.

Background & Aims: Adequate adherence to hepatitis C virus (HCV) treatment is believed to be a key component of treatment success because non-adherence can potentially result in treatment failure and the emergence of resistant viral variants. This analysis assessed factors associated with non-adherence to glecaprevir/pibrentasvir (G/P) therapy and the impact of non-adherence on sustained virological response at post-treatment week 12 (SVR12) rates in HCV genotype (GT) 1-6-infected patients.

Methods: Adherence was calculated by pill counts at study visits during treatment, and defined as having a lowest treatment adherence of ≥80% and ≤120% at each study visit.

Drug-Drug Interactions of Tacrolimus or Cyclosporine With Glecaprevir and Pibrentasvir in Healthy Subjects.

A fixed-dose combination of glecaprevir and pibrentasvir is approved for treatment of chronic infection with hepatitis C virus (HCV) genotypes 1-6. Three phase 1 open-label studies were conducted in healthy volunteers to evaluate the potential for clinically relevant drug-drug interactions of the glecaprevir 300-mg and pibrentasvir 120-mg combination with the immunosuppressants tacrolimus (1 mg) or cyclosporine (100 and 400 mg). Glecaprevir and pibrentasvir exposure was unaffected by tacrolimus, whereas the tacrolimus area under the curve (AUC) value was 45% higher with glecaprevir and pibrentasvir.

Pharmacokinetics and safety of glecaprevir and pibrentasvir in HCV-negative subjects with hepatic impairment.

Purpose: This study characterized the effects of hepatic impairment on the pharmacokinetics and safety of glecaprevir and pibrentasvir, two direct-acting antivirals used for treatment of chronic HCV infection.

Methods: HCV-negative subjects with normal hepatic function, or with mild (Child-Pugh [CP]-A), moderate (CP-B), or severe (CP-C) hepatic impairment received single doses of pibrentasvir 120 mg alone or with glecaprevir 200 mg or 300 mg (n = 6/functional group/dose). Plasma pharmacokinetics and protein binding were evaluated.