Single-dose euglycaemic clamp studies demonstrating pharmacokinetic and pharmacodynamic similarity between MK-1293 insulin glargine and originator insulin glargine (Lantus) in subjects with type 1 diabetes and healthy subjects.

AIMS: MK-1293 is an insulin glargine that has an amino acid sequence identical to that of Lantus, the originator insulin glargine. Two euglycaemic clamp studies, 1 in subjects with type 1 diabetes (T1D) and 1 in healthy subjects, were conducted to demonstrate pharmacokinetic (PK) and pharmacodynamic (PD) similarity between MK-1293 and Lantus commercially procured in both the European Union (EU-Lantus) and the USA (US-Lantus). MATERIALS AND METHODS: Both studies were single-dose, randomized, double-blind, single-centre, crossover studies with ≥7 days between dosing periods. A 2-treatment, 4-period replicate crossover study in T1D subjects (N = 76) compared the PK and PD of MK-1293 to EU-Lantus for 30 hours after dosing. A 3-period crossover study in healthy subjects (N = 109) compared the PK and PD of MK-1293, EU-Lantus and US-Lantus for 24 hours after dosing. In both studies, all subjects received single 0.4 units/kg subcutaneous doses of MK-1293 or Lantus in all dosing periods. Pharmacokinetic assessment was based on LC-MS/MS-based measurement of the major insulin glargine metabolite (M1) and PD was characterized using the euglycaemic clamp platform. RESULTS: In both studies, pre-specified similarity criteria were met between MK-1293 and Lantus for comparison of PK (AUC0-24 and Cmax of M1) and PD (GIR-AUC0-24 , GIR-AUC0-12 , GIR-AUC12-24 , and GIRmax ) primary endpoints. All treatments were well tolerated. CONCLUSION: Based on comparative assessment in both T1D and healthy subjects, it can be concluded that the PK and PD properties of MK-1293 are highly similar to those of Lantus. (ClinicalTrials.gov: NCT02059174).

Effect of telcagepant on spontaneous ischemia in cardiovascular patients in a randomized study.

OBJECTIVE: The primary purpose of the study was to explore the safety and tolerability of telcagepant in patients with stable coronary artery disease. BACKGROUND: Triptans are effective acute anti-migraine drugs whose vasoconstrictive effects limit their use in patients at risk for adverse cardiovascular events. Telcagepant, a calcitonin gene-related peptide receptor antagonist, is being developed for the acute treatment of migraine. Antagonism of calcitonin gene-related peptide, which does not appear to cause vasoconstriction, may allow for treatment of migraine in patients with coronary artery disease. METHODS: In this randomized, double-blind, placebo-controlled, crossover study, patients with documented stable coronary artery disease were assigned to 1 of 2 treatment sequences: telcagepant then placebo, or placebo then telcagepant. In each treatment period, patients received 2 doses of telcagepant 300-mg or placebo 2 hours apart. They remained in the research center for 24 hours after receiving the first dose of each period, during which time continuous 12-lead ambulatory electrocardiographic (Holter) monitoring was performed. RESULTS: Twenty-eight patients were enrolled; all patients completed the study and were included in all analyses. Telcagepant was generally well tolerated. No laboratory or serious adverse experiences were reported, and no patient discontinued due to an adverse experience. There were no consistent treatment-related changes in laboratory, vital signs or electrocardiogram safety parameters. Three patients (2 after receiving placebo and 1 after receiving telcagepant) experienced ST segment depression during the study; none of these patients reported chest pain. CONCLUSIONS: Two doses of 300-mg telcagepant, administered 2 hours apart, did not appear to exacerbate spontaneous ischemia and were generally well tolerated in a small cohort of patients with stable coronary artery disease. Results of this study support further evaluation of telcagepant in patients with stable coronary artery disease.