Dataset Information

Efficacy and safety of once-monthly efpeglenatide in patients with type 2 diabetes: Results of a phase 2 placebo-controlled, 16-week randomized dose-finding study.

ABSTRACT:

Aims

To determine the optimal dose(s) of once-monthly administration of efpeglenatide, a long-acting glucagon-like peptide-1 receptor agonist (GLP-1RA), in patients with type 2 diabetes (T2D) inadequately controlled on metformin.

Materials and methods

In this phase 2, randomized, placebo-controlled, double-blind trial (NCT02081118), patients were randomized 1:1:1:1 to subcutaneous efpeglenatide (8, 12 or 16 mg once monthly; n = 158) or placebo (n = 51). The 16-week treatment period included a 4-week titration phase with once-weekly efpeglenatide 4 mg, followed by one dose of efpeglenatide 8 mg once monthly and two doses of the assigned once-monthly dose. The primary endpoint was change in glycated haemoglobin (HbA1c) from baseline to week 17.

Results

All efpeglenatide doses significantly reduced HbA1c versus placebo (P < 0.0001 for all). Overall, the least squares mean difference in HbA1c reductions between efpeglenatide and placebo was -7.7 mmol/mol (-0.71%; baseline to week 17). At week 17, a significantly greater proportion of efpeglenatide patients had an HbA1c level <53 mmol/mol (<7%) versus placebo (48.7% vs. 30.6%; P = 0.0320). Significant body weight loss occurred across all efpeglenatide doses (placebo-corrected reduction -2.0 kg [efpeglenatide overall]; P = 0.0003). The safety profile was consistent with GLP-1RAs, with gastrointestinal (GI) disorders being the most common treatment-emergent adverse events. Fluctuations in effects on glucose levels and rates of GI events occurred between peak and trough efpeglenatide concentrations.

Conclusions

Efpeglenatide once monthly (following once-weekly titration) has significant benefits with regard to HbA1c and weight reduction versus placebo in patients with T2D. Further studies are needed to evaluate the long-term efficacy and safety of efpeglenatide once monthly.

SUBMITTER: Del Prato S

PROVIDER: S-EPMC7383886 | biostudies-literature | 2020 Jul

REPOSITORIES: biostudies-literature

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Publications

Efficacy and safety of once-monthly efpeglenatide in patients with type 2 diabetes: Results of a phase 2 placebo-controlled, 16-week randomized dose-finding study.

Del Prato Stefano S Kang Jahoon J Trautmann Michael E ME Stewart John J Sorli Christopher H CH Derwahl Michael M Soto Alfonso A Yoon Kun-Ho KH

Diabetes, obesity & metabolism 20200406 7

<h4>Aims</h4>To determine the optimal dose(s) of once-monthly administration of efpeglenatide, a long-acting glucagon-like peptide-1 receptor agonist (GLP-1RA), in patients with type 2 diabetes (T2D) inadequately controlled on metformin.<h4>Materials and methods</h4>In this phase 2, randomized, placebo-controlled, double-blind trial (NCT02081118), patients were randomized 1:1:1:1 to subcutaneous efpeglenatide (8, 12 or 16 mg once monthly; n = 158) or placebo (n = 51). The 16-week treatment perio ...[more]

PMID: 32128957

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Project description:AimTo assess the efficacy, safety and pharmacokinetic/pharmacodynamic properties of efpeglenatide, a long-acting glucagon-like peptide-1 receptor agonist, in patients with type 2 diabetes (T2D).Research design and methodsTwo randomized, double-blind, placebo-controlled phase 2 trials were conducted. The single-dose study (n = 48) was a first-in-patient, sequential dose-escalation study. Patients received a single subcutaneous injection of efpeglenatide (2-100 μg/kg) or placebo. The repeated-dose study (n = 71) was a multiple-ascending-dose trial. Patients received weekly (1, 2 or 4 mg once weekly; 8-week period) or monthly (8, 12 or 16 mg once monthly; 9-week period) subcutaneous injections of efpeglenatide or placebo (without titration).ResultsBoth studies demonstrated dose-proportional increases in efpeglenatide serum concentrations. The median time to attain maximum serum concentration (tmax ) for efpeglenatide ranged from 72 to 144 hours in the single-dose study and from 48 to 120 hours in the repeated-dose study (following final dose). Geometric mean t1/2 ranged from 135 to 180 hours across studies. Peak-to-trough ratios in the repeated-dose study ranged from 1.3 to 1.4 with once-weekly dosing and from 5.9 to 12.9 with once-monthly dosing. Following a single dose of efpeglenatide 14-100 μg/kg, fasting plasma glucose and postprandial plasma glucose levels were decreased at week 1 and remained below baseline levels for ≥3 weeks post-dosing. Repeated doses of efpeglenatide led to significant reductions in glycated haemoglobin vs placebo. In both studies, efpeglenatide was generally well tolerated. Gastrointestinal disorders were the most frequently reported treatment-emergent adverse events in efpeglenatide-treated patients.ConclusionsThe delayed tmax, long half-life, and low peak-to-trough ratios observed demonstrate potential for improved efficacy and dosing flexibility, with good tolerability of efpeglenatide in patients with T2D.

Project description:BACKGROUND:The long-acting injectable antipsychotic aripiprazole once-monthly 400 mg (AOM 400) was recently approved for maintenance treatment of bipolar I disorder (BP-I). The purpose of this study was to evaluate the safety, tolerability, and efficacy of AOM 400 as long-term maintenance treatment for BP-I. METHODS:This open-label multicenter study evaluated the effectiveness of AOM 400 as maintenance treatment for BP-I by assessing safety and tolerability (primary objective) and efficacy (secondary objective). The study enrolled AOM 400-naive ("de novo") patients as well as AOM 400-experienced ("rollover") patients with BP-I from a lead-in randomized, placebo-controlled clinical trial that demonstrated the efficacy of AOM 400 in the maintenance treatment of BP-I (Calabrese et al. in J Clin Psychiatry 78:324-331, 2017). Safety variables included frequency and severity of treatment-emergent adverse events (TEAEs) and TEAEs resulting in study discontinuation. Efficacy was assessed by the proportion of patients maintaining stability throughout the maintenance phase, as well as mean changes from baseline in Young Mania Rating Scale (YMRS), Montgomery-Asberg Depression Rating Scale, and Clinical Global Impressions for Bipolar Disorder-Severity of Illness Scale (CGI-BP-S) total scores. Patient acceptability and tolerability of treatment was assessed using the Patient Satisfaction with Medication Questionnaire-Modified. RESULTS:Of 464 patients entering the maintenance phase, 379 (82%) were de novo and 85 (18%) were rollover. TEAEs were more common in de novo than rollover patients. The overall discontinuation rate due to TEAEs was 10.3% (48/464). Improvements in YMRS and CGI-BP-S total scores were maintained during the study, and the vast majority of both de novo (87.0%) and rollover (97.6%) patients maintained stability through their last visit. Overall, the need for rescue medication during the maintenance phase was minimal (<?10% of patients). Patient satisfaction levels were high, with both de novo and rollover patients rating the side effect burden of AOM 400 as greatly improved relative to previous medications. CONCLUSION:AOM 400 was safe, effective, and well tolerated by both de novo and AOM 400-experienced patients with BP-I for long-term maintenance treatment. Trial registration ClinicalTrials.gov, NCT01710709.

Dataset Information

Efficacy and safety of once-monthly efpeglenatide in patients with type 2 diabetes: Results of a phase 2 placebo-controlled, 16-week randomized dose-finding study.

Aims

Materials and methods

Results

Conclusions

Publications

Efficacy and safety of once-monthly efpeglenatide in patients with type 2 diabetes: Results of a phase 2 placebo-controlled, 16-week randomized dose-finding study.

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