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Aims The aims of the study were to assess the pharmacokinetics, pharmacodynamics, safety and tolerability of a novel, pegylated recombinant human consensus interferon-α variant ( PEG-IFN- SA) in healthy volunteers. A pharmacokinetic and pharmacodynamic comparison of PEG-IFN- SA and peginterferon-α-2a in healthy subjects was evaluated. Methods A randomized, dose-escalating, single administration dose phase I clinical study was conducted. Thirty healthy subjects received PEG-IFN- SA as a single dose of 0.5-2.0 μg kg−1 by subcutaneous (s.c.) injection in four parallel groups. Eight subjects received peginterferon-α-2a as a single dose of 180 μg s.c. Results The incidence rates of adverse events for PEG-IFN- SA and peginterferon-α-2a were 29 of 30 and 7 of 8, respectively. The adverse events for PEG-IFN- SA were mild to moderate and similar to those of peginterferon-α-2a. Within 168 h after injection, the mean values of maximal concentration and area under the plasma concentration-time curve from time of dosing to 168 h [ AUC(0-168h)] for 2′,5′-oligoadenylate, neopterin and β2-microglobulin for PEG-IFN- SA at 1.5 μg kg−1 s.c. were similar to or higher than those for peginterferon-α-2a at a dose of 180 μg s.c. After s.c. injection of PEG-IFN- SA at 1.5 μg kg−1, the mean geometric mean values of plasma half-life, time to maximal concentration, maximal concentration and AUC(0-168h) were 55.3 h, 26.9 h, 0.53 μg l−1 and 44.0 μg l−1 h, respectively. Conclusions The tolerance, pharmacokinetic and pharmacodynamic characteristics of PEG-IFN- SA support its administration by s.c. injection as a single dose of 1.5 μg kg−1 or at 2.0 μg kg−1 per week. [ABSTRACT FROM AUTHOR]

Yogliptin is a novel xanthine dipeptidyl peptidase-4 (DPP-4) inhibitor targeting type 2 diabetes. After promising preclinical pharmacological studies, the first human trial of yogliptin was designed. A randomized, double-blind, parallel, placebo-controlled phase I single-dose escalation study was designed to evaluate the pharmacokinetics, pharmacodynamics, and tolerability after single oral doses of yogliptin in healthy Chinese subjects. Healthy subjects were assigned to nine cohorts, which received a single dose of yogliptin at 2.5, 5, 10, 25, 50, 100, 200, 400, or 600 mg. Two subjects in each cohort received placebo. Blood samples were collected before dosing and up to 192 h afterwards. Urine samples were collected until 120 h after dosing. Plasma and urine drug concentrations were determined using liquid chromatography coupled with tandem mass spectrometry, and DPP-4 activity was measured using a semi-quantitative, fluorescence-based kinetic assay. A total of 104 subjects were enrolled, 103 of whom completed the study (mean age, 25.3 years; mean weight, 58.8 kg; mean BMI, 21.8 kg/m2). A total of 27 adverse events (AEs) occurred in 25 of 86 yogliptin subjects (29.1%), and 3 AEs occurred in 3 of 18 placebo subjects (16.7%). Yogliptin was absorbed with a median time of maximum observed concentration (T max) of 3.0 h and was eliminated slowly with a t 1/2 of 25.45–43.84 h. The maximum observed concentration (C max) and area under the curve (AUC) varied slightly more than dose-proportionally over the dose range from 2.5 to 400 mg. The fraction of drug excreted in urine ranged from 8.39% to 24.77%. Mean DPP-4 inhibition at 24 h after dosing ranged from 97.7% to 99.5%, and DPP-4 inhibition was >80% for 72 h at doses from 25 to 400 mg. DPP-4 inhibition was >80% for 1 week in the group receiving 400 mg. Yogliptin was well tolerated in healthy subjects, with no dose-limiting toxicity observed in the range from 2.5 to 600 mg. Yogliptin inhibited plasma DPP-4 activity for 72 h at single doses of 25–200 mg and for 1 week at 400 mg, suggesting that once-weekly dosing of yogliptin is possible in type 2 diabetes patients. Trial Registration: ChiCTR-IIR-17010311 (Chictr.org). Unlabelled Image [ABSTRACT FROM AUTHOR]