A phase 1, randomized, double-blind, placebo-controlled trial investigating the pharmacokinetics, pharmacodynamics, safety and tolerability of oral semaglutide in healthy Chinese subjects.

ABSTRACT

AIM: The trial (NCT04016974) investigated the pharmacokinetics, pharmacodynamics, safety and tolerability of oral semaglutide, the first orally administered glucagon-like peptide-1 analogue for type 2 diabetes, in healthy Chinese subjects. MATERIALS AND METHODS: This single-centre, multiple-dose, placebo-controlled trial randomized 32 healthy Chinese adults to once-daily oral semaglutide (3 mg escalating to 14 mg) or placebo for 12 weeks. Blood samples were collected regularly during treatment and follow-up. The primary endpoint was the area under the semaglutide concentration-time curve over a dosing interval (0-24 h) at steady state (AUC0-24h,sema,SS). Secondary pharmacokinetic endpoints included the maximum observed semaglutide plasma concentration at steady state (Cmax,sema,SS). Supportive secondary pharmacodynamics endpoints included changes in body weight and fasting plasma glucose. RESULTS: Treatment with all oral semaglutide doses showed dose-dependent increases in semaglutide exposure in healthy Chinese subjects at steady state, determined by AUC0-24h,sema,SS (233, 552 and 1288 h·nmol/L for 3, 7 and 14 mg of oral semaglutide, respectively) and Cmax,sema,SS. Oral semaglutide treatment was associated with significant reductions in body weight (p = .0001) and fasting plasma glucose (p = .0011) versus placebo at the end of treatment. The safety and tolerability of oral semaglutide were consistent with the known profile of glucagon-like peptide-1 receptor agonists, with no severe or blood-glucose-confirmed symptomatic hypoglycaemic events, serious adverse events or deaths. The most frequent adverse events were gastrointestinal disorders. CONCLUSIONS: At steady state, oral semaglutide exposure was dose dependent and close to dose proportionality in healthy Chinese subjects. This is consistent with previous clinical pharmacology results for oral semaglutide.