A Phase 1, Randomized, Placebo-Controlled, Sequential Parallel Group, Multiple Dose Escalation Trial To Evaluate The Safety, Tolerability, Pharmacokinetics, And Pharmacodynamics Of 4, Once-Weekly Subcutaneous Doses Of PF-04603629 To Subjects With Type 2 Diabetes Mellitus
PF-04603629 is being investigated for the treatment of Type 2 diabetes mellitus (T2DM). Specifically, PF-04603629 is a protein that is a combination of exendin-4 (a glucagon-like peptide-1 (GLP-1) mimetic currently marketed as Byetta®) fused to human transferrin (a naturally occuring protein) in order to increase the concentration of exendin-4 in the blood. The purpose of this study is to characterize the safety, tolerability, pharmacokinetics, and pharmacodynamics of PF-04603629 following multiple escalating subcutaneous doses in adult subjects with T2DM.
A Phase 1, Placebo-Controlled, Randomized Study To Assess The Safety, Tolerability, Pharmacokinetics, And Pharmacodynamics Following Single, Escalating Subcutaneous Doses Of PF-04603629 In Type 2 Diabetic Adult Subjects
PF 04603629 is a long acting exendin proposed for the treatment of Type 2 diabetes mellitus. The purpose of this study is to characterize the safety, tolerability, pharmacokinetics and glucose lowering capabilities following a single subcutaneous dose.
2011-11-01·Diabetes, Obesity and Metabolism2区 · 医学
Effects of a long-acting GLP-1 mimetic (PF-04603629) on pulse rate and diastolic blood pressure in patients with type 2 diabetes mellitus
2区 · 医学
作者: Caile, Roberto A.
PF-04603629, an exendin-transferrin fusion protein, is a long-acting glucagon-like peptide-1 (GLP-1) mimetic. This randomized, double-blind study characterized the safety and pharmacodynamics of a single dose of PF-04603629 (n = 57; 1-70 mg) or placebo (n = 14) in subjects with type 2 diabetes mellitus (T2DM). There were dose-dependent decreases from baseline in day 6 glucose area under the curve following a mixed meal test (-27 ± 12% with 70 mg). Most treatment-related adverse events were gastrointestinal, with nausea and vomiting most frequent at 70 mg. Pulse rate (PR) and diastolic blood pressure (DBP) increased dose dependently within the normal range. At 24 h postdose mean PR increased 23 ± 9 bpm and mean DBP increased 10 ± 5 mmHg with 70 mg. In conclusion, PF-04603629 exhibited efficacy and tolerability consistent with its mechanism of action; however, PR and DBP increased. Similar effects have been reported occasionally with other GLP-1 mimetics. These data underscore the importance of careful assessments of haemodynamic effects in GLP-1 analogues.