This was an open-label, randomized, single-dose, 2-period, crossover clinical trial with an adaptive design to evaluate the bioequivalence and comparative pharmacokinetics of generic glecaprevir/pibrentasvir versus the brand name product in healthy White male and female volunteers under fed conditions. Safety profiles were also assessed. A total of 56 healthy adult volunteers were enrolled and randomly assigned in a 1:1 ratio to receive a single dose of either the generic or reference formulation. After a 7-day washout period, subjects received the alternate product. Blood samples were collected at pre-specified time points up to 48 hours post-dosing. Plasma concentrations of glecaprevir and pibrentasvir were determined using a validated high-performance liquid chromatography-tandem mass spectrometry method. The geometric mean ratios of the test to the reference formulation for maximum plasma concentration (Cmax) and area under the concentration-time curve from drug administration to the last measurable concentration (AUC0-t) fell within the predefined bioequivalence range of 80%-125%. Both formulations demonstrated comparable pharmacokinetic profiles for glecaprevir and pibrentasvir, and can be considered bioequivalent. No adverse events were reported, and both formulations were well tolerated by all participants.

UNASSIGNED: This study aims to determine whether the live birth rates were similar between GnRH antagonist original reference product Cetrotide® and generic Ferpront®, in gonadotropin-releasing hormone (GnRH) antagonist protocol for controlled ovarian stimulation (COS).
UNASSIGNED: This retrospective cohort study investigates COS cycles utilizing GnRH antagonist protocols. The research was conducted at a specialized reproductive medicine center within a tertiary care hospital, spanning the period from October 2019 to October 2021. Within this timeframe, a total of 924 cycles were administered utilizing the GnRH antagonist originator, Cetrotide® (Group A), whereas 1984 cycles were undertaken using the generic, Ferpront® (Group B).
UNASSIGNED: Ovarian reserve markers, including anti-Mullerian hormone, antral follicle number, and basal follicular stimulating hormone, were lower in Group A compared to Group B. Propensity score matching (PSM) was performed to balance these markers between the groups. After PSM, baseline clinical features were similar, except for a slightly longer infertile duration in Group A versus Group B (4.43 ± 2.92 years vs. 4.14 ± 2.84 years, P = 0.029). The duration of GnRH antagonist usage was slightly longer in Group B than in Group A (6.02 ± 1.41 vs. 5.71 ± 1.48 days, P < 0.001). Group B had a slightly lower number of retrieved oocytes compared to Group A (14.17 ± 7.30 vs. 14.96 ± 7.75, P = 0.024). However, comparable numbers of usable embryos on day 3 and good-quality embryos were found between the groups. Reproductive outcomes, including biochemical pregnancy loss, clinical pregnancy, miscarriage, and live birth rate, did not differ significantly between the groups. Multivariate logistic regression analyses suggested that the type of GnRH antagonist did not independently impact the number of oocytes retrieved, usable embryos, good-quality embryos, moderate to severe OHSS rate, clinical pregnancy, miscarriage, or live birth rate.
UNASSIGNED: The retrospective analysis revealed no clinically significant differences in reproductive outcomes between Cetrotide® and Ferpront® when used in women undergoing their first and second COS cycles utilizing the GnRH antagonist protocol.

This study was conducted as a single-site, open-label, randomized, replicated crossover trial with 4 treatment periods. The aim was to evaluate the bioequivalence of a generic test drug containing velpatasvir and sofosbuvir compared to an established brand-name medication in healthy White subjects under fasting conditions. Blood samples were collected at specified intervals up to 72 hours after dosing to measure the concentrations of velpatasvir and sofosbuvir using a certified high-performance liquid chromatography with tandem mass spectrometry method. The bioequivalence of the 2 formulations was confirmed when statistical analysis showed that confidence intervals for the log-transformed peak concentration and area under the concentration-time curve from time 0 to the last quantifiable sample were within an acceptable range from 80% to 125%. Criteria for bioequivalence were met for both area under the concentration-time curve from time 0 until the last quantifiable sample and peak concentration parameters. No adverse effects were reported during this trial in both groups.

UNASSIGNED: This article presents a strategy that a Drug Delivery Device Developer (DDDD) has adopted to support Abbreviated New Drug Application (ANDA) submissions of drug-device combination products. As per the related FDA guidance, a threshold analysis should be compiled. If \'other differences\' between the Reference Listed Drug (RLD) and the generic drug devices are identified, a Comparative Use Human Factors (CUHF) study may be requested.
UNASSIGNED: The DDDD performed task analysis and physical comparison to assess the pen injector design differences. Then, a formative CUHF study with 25 participants simulating injections using both RLD and the generic pen injectors was conducted.
UNASSIGNED: After each participant completed four simulated injections, similar type and rates of use error between the RLD (0.70) and generic (0.68) pen injectors were observed.
UNASSIGNED: DDDDs can support pharmaceutical companies in the ANDA submission strategy of their drug-device combination product by initiating comparative task analysis and physical comparison of the device as inputs for the threshold analysis. If \'other differences\' are identified, a formative CUHF study can be performed. As shown in our case study, this approach can be leveraged to support the sample size calculation and non-inferiority margin determination for a CUHF study with the final combination product.

OBJECTIVE: Clozapine is considered the most reliable drug for treatment-resistant schizophrenia. In 2014, a generic formulation of clozapine (Clzapine) was introduced in Korea. This study was performed to provide clinical information regarding the use of clozapine and to compare efficacy and tolerability when converting from the brand-name formulation (Clozaril) to the generic formulation during longterm maintenance treatment among Korean patients with schizophrenia.
METHODS: This mirror-image study retrospectively investigated the electronic medical records of patients who had switched from Clozaril to Clzapine with a ≥1-year duration for each formulation. Clinical data were collected, including information regarding clozapine use, psychiatric hospitalization, co-medications, and blood test findings. Data before and after the switch were compared using paired t-tests.
RESULTS: Among 332 patients, the mean 1-year dosages were 233.32±149.35 mg/day for Clozaril and 217.36±136.66 mg/day for Clzapine. The mean clozapine concentration-to-dose ratios were similar before and after the switch (Clozaril, 1.33±0.68; Clzapine, 1.26±0.80). Switching from Clozaril to Clzapine resulted in no significant differences in the hospitalization rate, hospitalization duration, or laboratory findings (liver function parameters, serum cholesterol level, and serum glucose level). Equivalent doses of co-prescribed antidepressants were decreased, but concomitant medications otherwise showed no significant differences.
CONCLUSIONS: Clinical efficacy and tolerability appear comparable when switching to Clzapine during clozapine maintenance treatment. This study offers descriptive real-world clinical insights into clozapine maintenance treatment in Korea, thereby providing patients with more treatment options and contributing to the development of maintenance guidelines tailored to the Korean population.

UNASSIGNED: To evaluate an in vitro antiplatelet effect of generic ticagrelor 90 mg (ticaspan) alone and in combination with aspirin 75 mg as compared to the innovator formulation of ticagrelor alone and in combination with aspirin among healthy Indian volunteers.
UNASSIGNED: 18 volunteers were enrolled and platelet viability was tested using lactate dehydrogenase (LDH) assay in six of 18 volunteers. In 12 volunteers, maximum platelet aggregation (MPA) and percentage inhibition of platelet aggregation (PI) were assessed using a platelet aggregometer in six study groups.
UNASSIGNED: There was no significant increase in LDH levels when platelets were incubated with an innovator or generic drug alone and in combination with aspirin as compared to the dimethyl sulfoxide [DMSO] group. All five study groups showed a significant reduction in the MPA values compared to the DMSO group (P < 0.01). The extent of decrease in MPA observed with the generic drug was not significantly different from the innovator drug (P = 0.325). Similarly, the MPA observed with the two combination groups did not differ from each other (P = 1.000), but it was significantly different from the MPA observed with aspirin (P = 0.039, each). The PI of platelet aggregation was significantly more in four study groups [generic drug alone; innovator alone; generic drug + aspirin; and innovator drug + aspirin] (P < 0.01) as compared to the aspirin group.
UNASSIGNED: The generic ticagrelor and its combination with aspirin demonstrated an antiplatelet effect equivalent to the innovator drug and its combination with aspirin.

We assessed the effectiveness and safety of switching to generic dolutegravir/lamivudine (DTG/3TC) among People living with Human Immunodeficiency Virus (PWH) in Western India. In this single-center, retrospective observational study, PWH, who switched to DTG/3TC, were followed for virologic, immunologic, and clinical effectiveness, and safety, including weight changes, hyperglycemia, and dyslipidemia. Multivariate linear mixed-effects models were used to predict average change in weight adjusted for age, sex, duration of previous antiretroviral (ARV) regimens, and baseline weight. From May 2017 to July 2022, out of 434 PWH switched to DTG/3TC, 304 with at least 1 follow-up visit were included. Median [interquartile range (IQR)] age was 54 (IQR 49-61) years and 70.1% were male. Prevalence of baseline comorbidities was 57.9% (hypertension-41.5%, chronic kidney disease-40.9%, and diabetes mellitus-18.8%). Reasons for switch were affordability (47.4%), desire for simplification (41.8%), ARV toxicities (19.1%), and concern about potential toxicities (10.2%). Median (IQR) duration of follow-up on DTG/3TC was 40 (IQR 31-49) weeks. No virologic failure was observed. Rates of virologic suppression [viral load (VL) ≤20 copies/mL or target not detected (TND)] at 12, 24, 48, 72, 96 and 120 weeks were 95.2%, 95.9%, 90%, 100%, 81.3%, and 88.4%, respectively. Only 9 (3%) PWH permanently discontinued DTG/3TC. Predicted adjusted mean weight gain of +3.3 kg was observed at 96 weeks. Switching from tenofovir disoproxil fumarate (TDF)/emtricitabine or lamivudine (XTC)/non-nucleoside reverse transcriptase inhibitor (NNRTI) and duration on DTG/3TC were significantly associated with weight gain. Apart from trend in worsening hyperglycemia (nine PWH with new onset diabetes), no clinically significant change in lipids and estimated glomerular filtration rate (eGFR) was documented. Switching to DTG/3TC is an effective and safe option among virologically suppressed PWH with high comorbidity burden in India. In view of the several advantages of DTG/3TC, it may be considered for potential scale-up in the right population, both in private and public health care settings in India.

Ferumoxytol is becoming more widely used as an off-label blood-pool contrast agent for MR angiography (MRA) and four-dimensional (4D) flow imaging in pediatric cardiovascular disease. Brand and generic versions of ferumoxytol are available with no information on relative efficacy as a contrast agent and safety profiles.
This study evaluates patient safety and image quality of comparable dosages of generic ferumoxytol (GF) versus brand ferumoxytol (BF) with the following hypotheses: (1) Reducing the contrast dosage from 3 to 2 mg/kg will not affect imaging quality and diagnostic accuracy of MRA and four-dimensional 4D flow. (2) GF and BF have similar image quality. (3) GF and BF have similar patient safety profiles.
In an IRB-approved retrospective study, changes in vitals/clinical status between baseline, during infusion, and 30 min post-infusion were analyzed in 3 groups: group 1 (3 mg/kg BF, 216 patients, age: 19.29 ± 11.71 years ranging from 2 months to 62 years), group 2 (2 mg/kg BF, 47 patients, age: 15.35 ± 8.56 years ranging from 10 days to 41 years), and group 3 (2 mg/kg GF, 127 patients, age: 17.16 ± 12.18 years ranging from 6 days to 58 years). Both pediatric and adult patients with congenital heart disease (CHD) indications were included within the study. Adverse reactions were classified as mild, moderate, or severe. Quantitative analysis of MR image quality was performed with signal-to-noise ratio (SNR) on MRA and velocity-to-noise ratio (VNR) on 4D flow. Qualitative grading of imaging features was performed by 2 experienced observers. Two-way analysis of variance (ANOVA) and chi-square tests were used for comparison with a P value of ≤ 0.05 used for significance.
No statistical difference was found in clinical status and vital signs (P>0.05). No severe reactions were reported. 7.9% of GF patients experienced an adverse reaction compared to 2.3% with 3 mg/kg BF and 8.4% with 2 mg/kg BF. There was no statistical difference in SNR between the 3 groups (P>0.05). For 4D flow, 2 mg/kg GF demonstrated an increase in VNR compared to 2 mg/kg BF (P = 0.005). The qualitative scores for MRA and 4D flow were high (≥ 3) across all 3 groups.
No significant difference was identified between 2 mg/kg GF and BF in terms of safety profile and image quality. Given the small sample size of this study, further studies are required to confirm these results.

OBJECTIVE: Lacosamide is a widely used third-generation antiseizure medication. However, there is a lack of evidence regarding the safety of substituting brand-name lacosamide with its generic version. This study aimed to determine the clinical outcomes associated with switching from the brand-name to the generic form of lacosamide (LCM) in patients with epilepsy.
METHODS: This prospective observational study involved patients undergoing treatment with LCM at the university epilepsy clinic. In 2018, the price of the brand-name LCM in Poland increased up to 110-fold compared to generic products. Anticipating that most patients would opt to switch to the generic formulations due to financial constraints, we chose to follow up them prospectively to assess the safety of transitioning from the brand-name to the generic form of LCM.
RESULTS: A total of 81 patients, aged 18-62 years, diagnosed with focal epilepsy and undergoing LCM treatment at our institution, decided to switch from the brand-name (Vimpat) to generic variations (Lacosamide TEVA, Lacosamide Glenmark, and Lacosamide Accord). Following the switch, no significant difference was observed in terms of seizure frequency before and after (p = 0.55, Wilcoxon signed-rank test). Subsequently, adverse events were recorded in four patients (4.9%) during the initial follow-up visit post-switch, including somnolence (2 patients) and dizziness (2 patients). Notably, all adverse events resolved by the second follow-up visit without necessitating treatment modification. Importantly, no patient switched back to brand-name medication CONCLUSION: The generic substitution of lacosamide was found to be generally safe in our study. Nonetheless, to confirm our findings, larger prospective studies are required.

In Japan, four different types of hypotonic infusion fluids, namely, types 1-4, are available and used depending on the patient\'s condition. Although branded and generic products for each type of hypotonic infusion fluid are available, their physicochemical properties are unknown. For types 1 and 3 fluids, differences in the physicochemical properties of branded and generic products lead to different adverse events when administered. In the present study, we measured titration acidity, pH, and osmolality of branded and generic type 2 hypotonic infusion fluids, which have recently been recognized as useful for maintenance infusion among pediatric patients. We herein assessed their physicochemical information required while selecting a product in clinical practice. Experiments were performed using one branded and two generic products of type 2 hypotonic infusion fluids. Titration acidity was measured via neutralization titration, osmolality was measured via freezing point depression, and pH was measured via potentiometry using a glass electrode. Significant differences in titration acidity, which is a risk factor for metabolic acidosis, and pH, which is a risk factor for pH-dependent changes upon mixing, were observed between the branded and generic products. Our study indicates that titration acidity and pH should be evaluated appropriately to avoid adverse events in clinical practice while selecting a product of type 2 hypotonic infusion fluids. Our findings highlight the importance of evaluating the differences between branded and generic products, specifically when selecting it for pediatric patients with incompletely developed renal function and patients with impaired renal function.