Bioequivalence Study of Two Tablet Formulations of Clonazepam 2 mg: A Randomized, Open-Label, Crossover Study in Healthy Mexican Volunteers Under Fasting Conditions.

INTRODUCTION: The prevalence of neurological disorders is high among the Mexican population. Clonazepam is primarily indicated to treat panic disorders, certain kinds of epilepsy such as status epilepticus, childhood motor seizures (petit mal absence, Lennox-Gastaut syndrome, and infantile spasms), anxiety, and muscle spasm. This study was performed to compare bioequivalence between two oral tablet formulations of clonazepam 2 mg in healthy Mexican volunteers under fasting conditions. METHODS: This phase I, randomized, open-label, two-treatment, crossover study included 30 healthy volunteers. Subjects were randomly assigned to either test or reference formulation of clonazepam 2 mg. Each study period was separated by 21-day washout period. Blood samples were collected at pre-dose and up to 72 h after drug administration. Clonazepam concentrations were determined using a validated ultra-flow liquid chromatography-tandem mass spectrometric method. Pharmacokinetic parameters were determined using a non-compartmental method. Two formulations were considered bioequivalent if geometric mean ratios (test/reference) were between 80% and 125%. Safety was evaluated by recording adverse events. RESULTS: Pharmacokinetic parameters were comparable between test and reference formulations. The mean maximum plasma concentration (Cmax) was ≈ 13 ng/mL, area under the plasma concentration-time curve from time 0 to last measurable concentration (AUC0-t) was ≈ 360 ng h/mL, time to reach maximum plasma concentration (Tmax) was ≈ 3 h, and elimination half-life (t1/2) was ≈ 43 h. Geometric mean ratios (90% confidence interval) of Cmax (99.2-115.3%), AUC0-t (100.6-110.6%), and AUC0-∞ (98.5-111.6%) were within the bioequivalence range. Seven non-serious adverse events (mostly asymptomatic hypotension) were recorded. CONCLUSION: The test and reference formulations of clonazepam 2 mg were bioequivalent and well tolerated in healthy Mexican volunteers under fasting conditions. PROTOCOL AUTHORIZATION NUMBER: 213301410B0051 (Approved on April 13, 2021).

Advancing therapy in people with suboptimally controlled basal insulin-treated type 2 diabetes: Subanalysis of the SoliMix trial in participants in Latin American countries.

AIMS: This subanalysis of the SoliMix trial assessed the efficacy and safety of advancing basal insulin (BI) therapy with iGlarLixi versus BIAsp 30 in people with type 2 diabetes (T2D) living in Latin American (LATAM) countries, i.e. Argentina and Mexico (N = 160). MATERIALS AND METHODS: SoliMix (EudraCT: 2017-003370-13) was a 26-week, open-label, multicentre study, where adults with T2D suboptimally controlled with BI plus one or two oral glucose-lowering drugs and glycated haemoglobin (HbA1c) ≥7.5% to ≤10% were randomized to once-daily iGlarLixi or twice-daily BIAsp 30. Primary efficacy endpoints were non-inferiority in HbA1c reduction (margin 0.3%) or superiority in body weight change for iGlarLixi versus BIAsp 30. RESULTS: Both primary efficacy endpoints were met in the LATAM region. After 26 weeks, HbA1c was reduced by 1.8% with iGlarLixi and 1.4% with BIAsp 30, meeting non-inferiority [least squares mean difference -0.47% (95% confidence interval: -0.82, -0.11); p < .001]. iGlarLixi was superior to BIAsp 30 for body weight change [least squares mean difference -1.27% (95% confidence interval: -2.41, -0.14); p = .028]. iGlarLixi was also superior to BIAsp 30 for HbA1c reduction (p = .010). A greater proportion of participants achieved HbA1c <7% without weight gain and HbA1c <7% without weight gain and without hypoglycaemia with iGlarLixi versus BIAsp 30. Incidence and rates of American Diabetes Association Level 1 and 2 hypoglycaemia were lower with iGlarLixi versus BIAsp 30. CONCLUSIONS: Once-daily iGlarLixi provided better glycaemic control with weight benefit and less hypoglycaemia than twice-daily premix BIAsp 30. iGlarLixi may be a favourable alternative to premix BIAsp 30 in people with suboptimally controlled T2D to advance BI therapy in the LATAM region.

Real-world effectiveness and safety of insulin glargine 300 U/ml in insulin-naïve people with type 2 diabetes in the Latin America region: A subgroup analysis of the ATOS.

AIM: To evaluate the real-world effectiveness and safety of insulin glargine 300 U/ml (Gla-300) in achieving glycaemic goals in insulin-naïve people with type 2 diabetes (T2D) in Mexico, Colombia and Peru (Latin America region) in the A Toujeo Observational Study (ATOS). MATERIALS AND METHODS: ATOS was a multicentre, prospective, 12-month observational study, which included 4422 insulin-naïve adults (age ≥ 18 years) with T2D uncontrolled (HbA1c > 7% and ≤11%) on at least one oral antidiabetic drug (OAD) who initiated Gla-300 treatment as per routine practice. The primary endpoint was the percentage of participants achieving their predefined individualized HbA1c goal at month 6. Key secondary endpoints included change from baseline in HbA1c, fasting plasma glucose (FPG), fasting self-monitored blood glucose (SMBG), body weight and incidence of hypoglycaemia. RESULTS: In this subgroup analysis, a total of 314 participants with T2D received Gla-300. At baseline, mean ± SD age was 56.0 ± 11.6 years, duration of diabetes was 9.7 ± 6.6 years and 65.9% of participants were on at least two OADs. The individualized HbA1c target was achieved by 25.8% of participants (95% confidence interval [CI]: 20.3-31.9) at month 6 and by 35.3% (95% CI: 28.5-42.5) at month 12. Gla-300 treatment improved glycaemic control with meaningful reductions in mean HbA1c, FPG and fasting SMBG. The incidence of hypoglycaemia reported was low and body weight remained stable. CONCLUSIONS: In a real-world setting in the Latin America region, the initiation of Gla-300 in people with T2D uncontrolled on OADs resulted in improved glycaemic control with a low incidence of hypoglycaemia and no change in body weight.

A Single-blind, Randomized, Single-dose, Two-sequence, Two-period, Crossover Study to Assess the Bioequivalence between Two Oral Tablet Formulations of Rivaroxaban 20 mg in Healthy Mexican Volunteers.

The objective of this study was to demonstrate the bioequivalence of 2 oral tablet formulations of rivaroxaban 20 mg in healthy Mexican volunteers under fed conditions. This phase I, single-blind, single-dose, randomized, two-sequence, two-period crossover study included 32 volunteers. Subjects were randomly assigned to one of two sequences: test formulation (single 20 mg dose) in the first period followed by the reference formulation (single 20 mg dose) in the second, or vice versa. Blood samples were collected predose and at predefined timepoints across a 48-hour period after drug intake. Rivaroxaban plasma concentrations were measured using a validated high-performance liquid chromatography-tandem mass spectrometry method. Pharmacokinetic parameters included maximum plasma concentration (Cmax ), area under the plasma concentration-time curve from time zero to last measurable concentration and to infinity (AUC0-t , AUC0-∞ ), time to reach Cmax , and half-life. Safety was evaluated through adverse-event monitoring using subject interviews and recording of vital signs. The 90% confidence intervals for the test/reference geometric mean ratios of Cmax (100.4%-112.7%), AUC0-t (96.5%-111.6%), and AUC0-∞ (95.5%-109.5%) were within the bioequivalence acceptance range (80-125%). Two adverse events (headaches) were recorded. Both formulations of rivaroxaban 20 mg tablets were bioequivalent and well tolerated in a healthy population of Mexican volunteers under fed conditions.