Demonstration of non-inferiority between MYL-1501D and reference insulin glargine for reduction of HbA1c during 24 weeks of treatment was achieved. The two treatment groups were similar in terms of secondary endpoints, including hypoglycaemia and nocturnal hypoglycaemia, local and systemic reactions, other safety variables, and immunogenicity.
Aims
To assess the efficacy, insulin dose, safety and immunogenicity when people with type 1 diabetes mellitus switched between MYL‐1501D and reference insulin glargine (Lantus®; Sanofi‐Aventis US LLC, Bridgewater, New Jersey).
Materials and methods
Eligible participants from INSTRIDE 1 who completed 52 weeks of reference insulin glargine treatment were randomized 1:1 to the reference sequence (n = 63; reference insulin glargine for 36 weeks) or to the treatment‐switching sequence (n = 64; MYL‐1501D [weeks 0–12], reference insulin glargine [weeks 12–24] and MYL‐1501D [weeks 24–36]). Change in glycated haemoglobin (HbA1c) from baseline to week 36 was the primary efficacy endpoint used to demonstrate equivalence between the two treatment sequences. Secondary endpoints included: change in fasting plasma glucose (FPG), self‐monitored blood glucose (SMBG) and insulin dose; immunogenicity; and adverse events, including hypoglycaemia.
Results
Mean changes in HbA1c (least squares [LS] mean [SE]) from baseline to week 36 were −0.05 (0.032) and −0.06 (0.034) for the treatment‐switching and reference sequences, respectively (LS mean difference 0.01 [95% CI −0.085 to 0.101]). Treatment sequences were comparable in terms of secondary endpoints, including FPG, SMBG and insulin dose, and the safety and immunogenicity profiles of the two sequences were similar.
Conclusions
Switching participants between MYL‐1501D and reference insulin glargine demonstrated equivalent efficacy and similar safety and immunogenicity, showing that people taking reference insulin glargine can safely switch to MYL‐1501D.
Smoking has been known to cause endothelial dysfunction and is an important risk factor for ischemic stroke. In our study we investigated whether chronic cigarette smoking affects the cerebral blood flow velocity response to a physiological, visual stimulus. By using a visual cortex stimulation paradigm, the flow velocity response in the posterior cerebral arteries (PCA) was measured bilaterally, in 32 young healthy adults (16 smokers, 16 non-smokers). Infectious disease and hyperlipidaemia were also ruled out by measurement of sensitive Creactive protein and serum lipids. This is the first functional TCD study demonstrating impaired visually evoked flow velocity response caused by chronic cigarette smoking in otherwise healthy, young subjects. The impaired cerebral vasodilatory mechanism together with atherosclerosis may influence stroke occurrence and outcome in chronic smokers.3
Background
MYL-1501D is a proposed biosimilar to insulin glargine. The noninferiority of MYL-1501D was demonstrated in patients with type 1 diabetes and type 2 diabetes in 2 phase 3 trials. Immunogenicity of MYL-1501D and reference insulin glargine was examined in both studies.
Methods
INSTRIDE 1 and INSTRIDE 2 were multicenter, open-label, randomized, parallel-group studies. In INSTRIDE 1, patients with type 1 diabetes received MYL-1501D or insulin glargine over a 52-week period. In INSTRIDE 2, patients with type 2 diabetes treated with oral antidiabetic drugs, insulin naive or not, received MYL-1501D or reference insulin glargine over a 24-week period. Incidence rates and change from baseline in relative levels of antidrug antibodies (ADA) and anti–host cell protein (anti-HCP) antibodies in both treatment groups were determined by a radioimmunoprecipitation assay and a bridging immunoassay, respectively. Results were analyzed using a mixed-effects model (INSTRIDE 1) or a nonparametric Wilcoxon rank sum test (INSTRIDE 2).
Results
Total enrollment was 558 patients in INSTRIDE 1 and 560 patients in INSTRIDE 2. The incidence of total and cross-reactive ADA was comparable between treatment groups in INSTRIDE 1 and INSTRIDE 2 (P > 0.05 for both). A similar proportion of patients had anti-HCP antibodies in both treatment groups in INSTRIDE 1 at week 52 (MYL-1501D, 93.9 %; reference insulin glargine, 89.6 %; P = 0.213) and in INSTRIDE 2 at week 24 (MYL-1501D, 87.3 %; reference insulin glargine, 86.9 %; P > 0.999).
Conclusions
In INSTRIDE 1 and INSTRIDE 2, similar immunogenicity profiles were observed for MYL-1501D and reference insulin glargine in patients with type 1 diabetes and type 2 diabetes, respectively.
Trial registration
ClinicalTrials.gov, INSTRIDE 1 (NCT02227862; date of registration, August 28, 2014); INSTRIDE 2 (NCT02227875; date of registration, August 28, 2014).
Aim: To evaluate the pharmacokinetic (PK) and pharmacodynamic (PD) bioequivalence (BE) of MYL-1601D biosimilar with originator, NovoLog (Ref-InsAsp-US), and NovoRapid (Ref-InsAsp-EU).Materials and Methods: This was a double-blind, randomized, crossover study that enrolled 71 healthy subjects to receive a single subcutaneous dose (0.2 U/kg) of each formulation under automated euglycaemic clamp conditions (ClampArt, level 81 mg/dL, duration 12 hours postdose). Primary PK endpoints were area under the plasma insulin aspart concentration-time curve from 0 to 12 hours (AUC 0-12h ) and maximum plasma insulin aspart concentration (C max ). Primary PD endpoints were area under the glucose infusion rate (GIR) time curve from 0 to 12 hours (AUC GIR0-12h ) and maximum GIR (GIR max ). Insulin aspart in plasma was quantified using immunoaffinity purification followed by ultraperformance liquid chromatography and tandem mass spectrometric detection. The pairwise comparisons of geometric least square mean (LS-mean) ratio for a 90% confidence interval (CI) of primary PK, and 90% CIs (MYL-1601D vs. Ref-InsAsp-US) and 95% CIs (MYL-1601D vs. Ref-InsAsp-EU) of primary PD variables, were to be within 80% to 125% to show BE.Results: MYL-1601D showed PK BE to both Ref-InsAsp-US (AUC 0-12h geometric LS-mean ratio 102.17, 90% CI [100.26; 104.11]; C max 106.13 [100.71; 111.85]) and Ref-InsAsp-EU
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