Explore the vast range of titles available.

Patients and clinicians share concerns that generic drug substitution might lead to loss of efficacy or emergence of adverse events. In this trial, we assessed US Food and Drug Administration (FDA) bioequivalence standards by studying the effects of switching between two disparate generic immediate-release lamotrigine products in patients with epilepsy. The Equivalence among Generic Antiepileptic Drugs (EQUIGEN) chronic-dose study was a randomised, double-blind, crossover study that enrolled adults (aged ≥18 years) with epilepsy from six epilepsy centres at academic institutions across the USA who were receiving immediate-release lamotrigine dosed at 100 mg, 200 mg, 300 mg, or 400 mg twice daily. Eligible patients were randomly allocated (1:1) to one of two treatment sequences (sequence 1 or sequence 2), comprising four study periods of 14 days each. During each 14-day treatment period, patients received balanced doses of an oral generic lamotrigine product every 12 h (200–800 mg total, identical to lamotrigine dose prior to study enrolment); after each 14-day period, patients were crossed over to receive the other generic product. Computer-based randomisation was done using random permuted blocks of size two or four for each site to prevent sequence predictability. Both patients and study personnel were masked to the generic products selected, their predicted exposure (ie, “high” vs “low”), and their group allocation. The primary outcome of this trial was bioequivalence between the generic products, which was assessed at the end of the study through a comparison of maximum plasma concentration (Cmax) and area under the concentration–time curve (AUC) for each product in the analysis population (all patients who completed all four treatment periods). Bioequivalence was established if the 90% CIs of the ratios of these two parameters for the two products were within equivalence limits (80–125%) in the analysis population. This study is registered with ClinicalTrials.gov\\, number NCT01713777. Between April 25, 2013, and Aug 12, 2014, 35 eligible patients were enrolled and randomly assigned to treatment sequence 1 (n=15) or treatment sequence 2 (n=20). 33 patients completed all four treatment periods and were included in the primary outcome analysis. The 90% CIs of the ratios of both Cmax and AUC were within equivalence limits (AUC 90% CI 98–103, Cmax 90% CI 99–105), showing that lamotrigine exposures were equivalent between the generic products. No significant changes in seizure frequency or adverse events were recorded. No deaths, study-related serious adverse events, or changes in clinical laboratory values or vital signs occurred during this study. Disparate generic lamotrigine products in patients with epilepsy showed bioequivalence with no detectable difference in clinical effects, confirming that US Food and Drug Administration bioequivalence standards are appropriate. American Epilepsy Society, Epilepsy Foundation, and US Food and Drug Administration.

Latuda ®  is a novel antipsychotic drug for schizophrenia and bipolar depression. A bioequivalence trial was performed to investigate the bioequivalence of Latuda ® and its generic drug lurasidone. Two independent trials were carried out, each involving 28 subjects. In the fasting trial, subjects were randomly assigned to two groups (1:1 ratio), receiving either 40 mg of generic lurasidone or Latuda ® . After a 7-day washout period, subjects entered the second period with a crossover administration of 40 mg of generic lurasidone or Latuda ® . The postprandial study design was similar to that of the fasting study. In the fasting study, the pharmacokinetic (PK) parameter values of generic lurasidone and Latuda ® were as follows: the C max was 28.84 ± 19.34 ng/ml and 28.22 ± 21.19 ng/ml, respectively; the AUC 0-t was 121.39 ± 58.47 h*ng/ml and 118.35 ± 52.24 h*ng/ml, respectively; and the AUC 0-∞ was 129.63 ± 63.26 h*ng/ml and 126.59 ± 57.99 h*ng/ml, respectively. The primary pharmacokinetic parameter, C max , was assessed for equivalence using reference-scaled average bioequivalence (RSABE), while other parameters (AUC 0-t , AUC 0-∞ ) were evaluated using average bioequivalence (ABE). The results indicate that both C max and AUC meet the equivalence criteria. In the postprandial study, the PK values of generic lurasidone and Latuda ® were as follows: the C max was 74.89 ± 32.06 ng/ml and 83.51 ± 33.52 ng/ml, respectively; the AUC 0-t was 274.77 ± 103.05 h*ng/ml and 289.26 ± 95.25 h*ng/ml, respectively; and the AUC 0-∞ was 302.44 ± 121.60 h*ng/ml and 316.32 ± 109.04 h*ng/ml, respectively. The primary pharmacokinetic parameters ( C max , AUC 0-t , AUC 0-∞ ) were assessed for equivalence using ABE, and both met the equivalence criteria. In the study, lurasidone and Latuda ® both exhibited acceptable safety and tolerability. The results displayed that lurasidone and Latuda ® were bioequivalent and safe in healthy Chinese participants. Clinical Trial Registry: This trial is registered at chinadrugtrials.org.cn (no.: CTR20191717, date: 2019.08.29).

\"While the shockingly high prices of prescription drugs continue to dominate the news, the strategies used by pharmaceutical companies to prevent generic competition are poorly understood, even by the lawmakers responsible for regulating them. In this groundbreaking work, Robin Feldman and Evan Frondorf illuminate the inner workings of the pharmaceutical market and show how drug companies twist health policy to achieve goals contrary to the public interest. In highly engaging prose, they offer specific examples of how generic competition has been stifled for years, with costs climbing into the billions and everyday consumers paying the price. Drug Wars is a guide to the current landscape, a roadmap for reform, and a warning of what is to come. It should be read by policymakers, academics, patients, and anyone else concerned with the soaring costs of prescription drugs\"-- Provided by publisher.

Hypertensive crises require rapid blood pressure control to prevent stroke and myocardial injury. Despite Cleviprex's efficacy, its high cost limits accessibility in China. This Phase III, multicenter, randomized, double‐blind study evaluated the efficacy and safety of a generic clevidipine (China's first injectable generic clevidipine emulsion) versus the branded drug Cleviprex in managing hypertensive emergencies and urgencies among Chinese patients. A total of 377 patients of 33 medical centers from December 2021 to December 2022 were randomized, with 189 in the generic clevidipine group and 188 in the control. As a result, 95.6% of patients in the generic clevidipine group and 93.6% in the control achieved the target systolic blood pressure (SBP) reduction within 30 min (rate difference 0.020, 90% CI: −0.019 to 0.060). The mean area under the curve (AUC) of SBP outside the target range within the first hour was comparable between groups (329.8 ± 238.16 in generic clevidipine vs. 347.9 ± 302.79 in control). The median time to first achieve the target range within 30 min was 12.0 min in both groups. The proportion of patients successfully transitioning to oral therapy within 6 h was 93.4% in the generic clevidipine group and 93.6% in the control group. The incidence of drug‐related adverse events (AEs) was reported in 50 patients (27.3%) in the generic clevidipine group and in 48 (27.9%) in the control, with no unexpected safety signals. The generic clevidipine demonstrated comparable efficacy and safety to the branded drug, supporting its potential as an effective and accessible therapeutic alternative for acute hypertension management. Trial Registration: chinadrugtrials.org.cn identifier: ChiCTR20212877.

Hydroxychloroquine (HCQ) has a high variability and a long half-life in the human body. The purpose of this study was to evaluate the bioequivalence of a generic HCQ tablet (test preparation) versus a brand HCQ tablet (reference preparation) under fasting and fed conditions in a crossover design. This was an open-label, two-period randomized, single-dose, crossover study in 47 healthy Chinese subjects who were sequentially and randomly allocated either to the fed group (high-fat meal; n = 23) or the fasting group (n = 24). Participants in each group were randomized to the two arms to receive either a single 200-mg dose of the test preparation or a 200-mg dose of the reference preparation. The application of the two preparations in each patient was separated by a 28-day washout period, regarded as sufficiently long to avoid significant interference from residual drug in the body. Whole blood samples were collected over 72 hours after drug administration. A total of 23 subjects completed both the fed and the fasting parts of the trial. There were no significant differences in C , AUC , and T between the test and reference preparation (p < 0.05). Food had no significant effect on C and T (p < 0.05), but AUC values were significantly reduced under fed condition compared to fasting condition (p < 0.05). The 90% confidence intervals (CIs) for the geometric mean ratios (GMRs) of C and AUC were 0.84 - 1.05 and 0.89 - 0.98 in the fed study, and 0.97 - 1.07 and 0.97 - 1.05 in the fasting study, respectively. The carryover effect due to non-zero blood concentrations resulted in higher AUC values in the second period for both test and reference formulations and had no effect on the statistical results. No serious adverse events were reported. The investigation demonstrated that the test and reference preparations are bioequivalent and well tolerated under both fasting and fed conditions in healthy Chinese subjects.

The quality of the chemical starting points for small-molecule drug discovery is a key factor in improving the likelihood of clinical success. In this article, experts from several organizations involved in drug discovery for malaria, tuberculosis and neglected tropical diseases present disease-specific criteria for hits and leads, and discuss the underlying rationale. Reducing the burden of infectious diseases that affect people in the developing world requires sustained collaborative drug discovery efforts. The quality of the chemical starting points for such projects is a key factor in improving the likelihood of clinical success, and so it is important to set clear go/no-go criteria for the progression of hit and lead compounds. With this in mind, the Japanese Global Health Innovative Technology (GHIT) Fund convened with experts from the Medicines for Malaria Venture, the Drugs for Neglected Diseases initiative and the TB Alliance, together with representatives from the Bill & Melinda Gates Foundation, to set disease-specific criteria for hits and leads for malaria, tuberculosis, visceral leishmaniasis and Chagas disease. Here, we present the agreed criteria and discuss the underlying rationale.

Estradiol valerate (Progynova ) is used as hormone therapy to supplement estrogen deficiency. This study aimed to assess the bioequivalence of an estradiol valerate tablet and its generic form, under fasting and fed conditions. A randomized, open-label, single-dose, 2-period crossover study was conducted on healthy postmenopausal Chinese female volunteers under fasting and fed conditions. For each period, the subjects received either a 1 mg tablet of estradiol valerate or its generic. Blood samples were collected before dosing and up to 72 hours after administration. Plasma levels of total estrone, estradiol, and unconjugated estrone were quantified using a validated liquid chromatography-tandem mass spectrometry method. A total of 54 volunteers were enrolled in this study. The primary pharmacokinetic parameters, including C , AUC , and AUC , were similar for the two drugs under both fasting and fed conditions, with 90% confidence intervals for the geometric mean ratios of these parameters, all meeting the bioequivalence criterion of 80-125%. A total of 48 adverse events (AEs) were reported in the fed study compared with 24 AEs in the fasting study. Estradiol valerate and its generic form were bioequivalent and well tolerated under both fasting and fed conditions.

Purpose The therapeutic index (TI) is the range of doses at which a medication is effective without unacceptable adverse events. Drugs with a narrow TI (NTIDs) have a narrow window between their effective doses and those at which they produce adverse toxic effects. Generic drugs may be substituted for brand-name drugs provided that they meet the recommended bioequivalence (BE) limits. However, an appropriate range of BE for NTIDs is essential to define due to the potential for ineffectiveness or adverse events. Flecainide is an antiarrhythmic agent that has the potential to be considered an NTID. This review aims to evaluate the literature surrounding guidelines on generic substitution for NTIDs and to evaluate the evidence for flecainide to be considered an NTID. Methods A review of recommendations from various regulatory authorities regarding BE and NTIDs, and publications regarding the NTID characteristics of flecainide, was carried out. Results Regulatory authorities generally recommend reduced BE limits for NTIDs. Some, but not all, regulatory authorities specify flecainide as an NTID. The literature review demonstrated that flecainide displays NTID characteristics including a steep drug dose–response relationship for safety and efficacy, a need for therapeutic drug monitoring of pharmacokinetic (PK) or pharmacodynamics measures and intra-subject variability in its PK properties. Conclusions There is much evidence for flecainide to be considered an NTID based on both preclinical and clinical data. A clear understanding of the potential of proarrhythmic effects or lack of efficacy, careful patient selection and regular monitoring are essential for the safe and rational administration of flecainide.