Clinical therapeutics最新文献

{"title":"Expanding Nonhormonal Options for Menopausal Vasomotor Symptoms: Clinical Impact of Elinzanetant","authors":"Renee R. Eger MD, FACOG, MSCP","doi":"10.1016/j.clinthera.2026.01.003","DOIUrl":"10.1016/j.clinthera.2026.01.003","url":null,"abstract":"","PeriodicalId":10699,"journal":{"name":"Clinical therapeutics","volume":"48 2","pages":"Pages 210-212"},"PeriodicalIF":3.6,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146092274","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Study of Insulin Treatment Modalities in Adults With Cystic Fibrosis-Related Diabetes After Elexacaftor-Tezacaftor-Ivacaftor Therapy","authors":"Luc Rakotoarisoa MD ,&nbsp;François Lefebvre MD ,&nbsp;Baptiste Arnouat MD ,&nbsp;Olivia Ronsin MD ,&nbsp;Raphael Chiron MD ,&nbsp;Sophie Ramel MD ,&nbsp;Bruno Ravoninjatovo MD ,&nbsp;Pauline Mulette MD ,&nbsp;Julie Mankikian MD ,&nbsp;Pascaline Priou MD ,&nbsp;Anne Sophie Balavoine MD ,&nbsp;Rébecca Hamidfar MD ,&nbsp;Sylvie Leroy MD ,&nbsp;Stéphanie Jellimann MD ,&nbsp;Laurence Kessler MD, PhD","doi":"10.1016/j.clinthera.2025.12.016","DOIUrl":"10.1016/j.clinthera.2025.12.016","url":null,"abstract":"<div><h3>Background</h3><div>Several studies have shown improvements in glucose control after initiating elexacaftor/tezacaftor/ivacaftor (ETI) in cystic fibrosis-related diabetes (CFRD) patients. However, ETI’s impact on insulin treatment remains unclear. This observational multicenter study aimed to analyze insulin treatment characteristics in adults with preexisting CFRD after ETI treatment initiation.</div></div><div><h3>Methods</h3><div>Data on diabetes treatment and continuous glucose monitoring (CGM) were retrospectively collected for 1 year before and up to 2 years after ETI treatment initiation in adults with CFRD from 13 French CF centers. We analyzed the type of insulin treatment, insulin doses, daily distribution, and CGM parameters after 1 year of ETI therapy.</div></div><div><h3>Results</h3><div>From April to December 2024<em>,</em> 107 individuals were included. The mean age was 33.2 ± 9.3 years, 49% were female, and diabetes treatment was diet for 14%, multiple daily injections for 65%, and pump for 21% of patients. After 1 year of ETI, total and bolus insulin doses decreased significantly from 0.37 IU/kg/day (0.19–0.60) to 0.30 IU/kg/day (0.17–0.49) (<em>P</em> = 0.02) and from 0.27 IU/kg/day (0.14–0.50) to 0.17 IU/kg/day (0.10–0.30), <em>P</em> = 0.0003) respectively. Among patients on a diet, 33.3% started insulin treatment, while 6.5% of patients on insulin treatment discontinued insulin. CGM parameters showed significant decreases in time below the range &lt;70 mg/dL (from 3% [1–8.5] to 2% [0–4], <em>P</em> = 0.001) and coefficient of variation (from 35% [28.7–41.7] to 33.1% [26.8–39.2], <em>P</em> = 0.001).</div></div><div><h3>Conclusions</h3><div>These findings indicate a reduction in insulin doses, particularly prandial insulin, as well as decreased glucose variability and hypoglycemia following ETI therapy in CFRD patients. Further long-term studies are needed to confirm these results.</div></div>","PeriodicalId":10699,"journal":{"name":"Clinical therapeutics","volume":"48 2","pages":"Pages 202-205"},"PeriodicalIF":3.6,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146040621","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Analyzing Prescription Drug to Over-the-Counter Drug Switch Rejections: Understanding Regulatory Concerns, A Global Overview","authors":"Tais Uliana MBA ,&nbsp;Zeineb Lassoued MSc ,&nbsp;Sergio Moreno Restrepo MBA ,&nbsp;Shahper Rahman MSc ,&nbsp;Sambasiva Kolati MPharm ,&nbsp;Aritz Ateka MSc ,&nbsp;Kristie Sourial MRPharmS","doi":"10.1016/j.clinthera.2025.12.012","DOIUrl":"10.1016/j.clinthera.2025.12.012","url":null,"abstract":"<div><h3>Purpose</h3><div>Prescription-to-over-the-counter (Rx-to-OTC) switch applications face significant barriers, with many experiencing rejections despite potential public health benefits. The purpose of this article was to investigate the regulatory landscape and challenges associated with Rx-to-OTC switches, focusing on the reasons behind rejections and withdrawals across various countries. By examining unsuccessful switches and identifying potential solutions, this article aimed to provide insights into improving regulatory frameworks and enhancing access to safe and effective self-care options.</div></div><div><h3>Methods</h3><div>A qualitative analysis of 19 International Nonproprietary Names spanning 10 therapeutic areas was conducted across eight countries to identify and categorize the reasons for rejection of the switch of these medicines from prescription to nonprescription status.</div></div><div><h3>Findings</h3><div>The study identified concerns leading to the rejection of Rx-to-OTC switch applications, including safety issues, challenges in diagnoses and self-management, and behavioral risks. Inconsistencies in regulatory decisions were observed across different countries.</div></div><div><h3>Implications</h3><div>The analysis identified opportunities to improve regulatory frameworks through risk-balanced approaches, innovative technologies, pharmacist-led models, and harmonized standards across regions. These opportunities could enhance access to self-care options while easing healthcare system burdens and ensuring safety.</div></div>","PeriodicalId":10699,"journal":{"name":"Clinical therapeutics","volume":"48 2","pages":"Pages 148-158"},"PeriodicalIF":3.6,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146028619","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Disease Severity and Healthcare Costs Associated With Chronic Kidney Disease in Patients With Systemic Lupus Erythematosus","authors":"Amy G. Edgecomb ,&nbsp;Shirley P. Huang ,&nbsp;Carlyne Averell ,&nbsp;Christopher F. Bell ,&nbsp;Bernard Rubin","doi":"10.1016/j.clinthera.2025.12.015","DOIUrl":"10.1016/j.clinthera.2025.12.015","url":null,"abstract":"<div><h3>Purpose</h3><div>Systemic lupus erythematosus (SLE) is a chronic autoimmune disease characterized by immune-mediated tissue injury. It frequently affects the kidneys, and lupus nephritis (LN) is the most severe manifestation affecting approximately 40% of patients with SLE. Persistent or inadequately managed LN can progress to chronic kidney disease (CKD) and kidney failure (end-stage kidney disease [ESKD]). Data on healthcare costs for patients with SLE and CKD are limited. The aim of this retrospective observational cohort study described the impact of CKD on clinical characteristics, healthcare costs and healthcare resource utilization (HCRU) among patients with SLE in the United States using claims data.</div></div><div><h3>Methods</h3><div>This retrospective, descriptive, observational cohort study (GSK Study 217378) identified patients with SLE between January 1, 2018, and December 31, 2018. Patient demographics and clinical characteristics were assessed in the 12-month baseline period preceding index (date of first SLE diagnosis [without CKD] or date of first occurrence of highest CKD stage [SLE with CKD]). HCRU and associated costs were reported for 12 months’ follow-up.</div></div><div><h3>Findings</h3><div>Of 12,114 patients with SLE included in the study (2666 with CKD; 9448 without CKD), most were female, with moderate SLE. The proportion of patients with severe disease increased with advancing CKD stage (Stage 1: 23.0%–Stage 5: 77.7%). The incidence of SLE flares, renal-related events, SLE clinical manifestations and organ involvement were numerically higher in patients with versus without CKD, and increased as CKD advanced. The mean (standard deviation [SD]) number of healthcare interactions and total healthcare costs were numerically greater among patients with CKD versus without CKD (112.5 [83.3] versus 76.9 [62.1]; $59,956 [100,785] versus $31,652 [57,781], respectively). Healthcare interactions and costs appeared to increase numerically with advancing CKD (Stage 1: 84.3 [68.7]–Stage 5: 173.7 [106.9]; Stage 1: $36,417 [56,028]–Stage 5: $152,169 [177,656], respectively). Among patients with CKD, healthcare costs were largely driven by outpatient and inpatient costs.</div></div><div><h3>Implications</h3><div>CKD contributes to a substantial economic burden in patients with SLE compared with those without CKD, highlighting the importance of effective screening and comprehensive SLE disease management to limit kidney complications and prevent progression to LN, CKD and ESKD.</div></div>","PeriodicalId":10699,"journal":{"name":"Clinical therapeutics","volume":"48 2","pages":"Pages 138-147"},"PeriodicalIF":3.6,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146028664","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A Phase III Randomized Controlled Trial Evaluating the Efficacy and Safety of Azilsartan Medoxomil and Amlodipine Combination Therapy in Patients With Mild-to-Moderate Essential Hypertension Inadequately Controlled on Monotherapy","authors":"Dae-Hee Kim MD, PhD ,&nbsp;Sang Hyun Lee MD, PhD ,&nbsp;Kyung Ah Han MD, PhD ,&nbsp;Moo Hyun Kim MD, PhD ,&nbsp;Dong-Ju Choi MD, PhD ,&nbsp;Marcin Grabowski MD, PhD ,&nbsp;Pawel Miekus MD ,&nbsp;Tzung-Dau Wang MD, PhD ,&nbsp;Ching-Pei Chen MD ,&nbsp;Sungha Park MD, PhD","doi":"10.1016/j.clinthera.2025.08.003","DOIUrl":"10.1016/j.clinthera.2025.08.003","url":null,"abstract":"<div><h3>Purpose</h3><div>To assess the antihypertensive efficacy and safety of azilsartan medoxomil (AZM) and amlodipine (AML) combination therapy in patients with mild-to-moderate hypertension inadequately controlled by AZM or AML monotherapy.</div></div><div><h3>Methods</h3><div>In this multicenter, randomized, double-blind Phase III study (NCT05385770), patients with mild-to-moderate hypertension inadequately controlled with AZM 40/80 mg or AML 5/10 mg were randomized (1:1:1) to receive low-dose or high-dose AZM/AML combination therapy or continued monotherapy as control. Eligible patients completed a 4-week active run-in period before randomization. The primary endpoint was change from baseline in mean sitting systolic blood pressure (SBP) after 8 weeks of treatment.</div></div><div><h3>Findings</h3><div>A total of 890 patients were randomized. AZM/AML combination therapy resulted in significantly greater reductions in mean sitting SBP compared with AZM or AML monotherapy across all dose groups. Least-squares mean reductions in mean sitting SBP at week 8 ranged from 5.2 to 9.0 mm Hg across all monotherapy nonresponder groups, with all comparisons showing statistical significance (<em>P</em> &lt; 0.05). Reductions in mean sitting diastolic blood pressure also favored combination therapy. Safety profiles were comparable across all treatment arms, with most adverse events mild or moderate in severity. No additional safety concerns were identified compared with monotherapy.</div></div><div><h3>Implications</h3><div>AZM/AML combination therapy was more effective than monotherapy in patients with mild-to-moderate hypertension inadequately controlled with either agent alone, even at maximum doses. Both low-dose and high-dose combinations were well tolerated. AZM/AML combination therapy may offer enhanced BP-lowering efficacy compared with other angiotensin II receptor blocker-based regimens.</div></div>","PeriodicalId":10699,"journal":{"name":"Clinical therapeutics","volume":"48 2","pages":"Pages 159-169"},"PeriodicalIF":3.6,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145058556","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Effect of Itraconazole on the Pharmacokinetics of Vepdegestrant, a PROteolysis TArgeting Chimera Estrogen Receptor Degrader, in Healthy Adult Participants","authors":"Lana Tran PharmD ,&nbsp;Jennifer A. Winton MS ,&nbsp;Kyle T. Matschke MAS ,&nbsp;Alexandre Stouffs MD ,&nbsp;Kimberly C. Lee MBA ,&nbsp;Yuanyuan Zhang PhD ,&nbsp;Weiwei Tan PhD","doi":"10.1016/j.clinthera.2025.12.007","DOIUrl":"10.1016/j.clinthera.2025.12.007","url":null,"abstract":"<div><h3>Purpose</h3><div>Vepdegestrant (ARV-471) is an orally administered PROteolysis TArgeting Chimera estrogen receptor (ER) degrader that directly binds an E3 ligase and ER to trigger ubiquitination and subsequent proteasomal degradation of ER. Based on findings from a first-in-human phase 1/2 trial, vepdegestrant 200 mg once daily was selected as the recommended phase 3 dose and was evaluated in the phase 3 clinical study VERITAC-2 (NCT05654623) for the treatment of patients with ER-positive human epidermal growth factor receptor 2–negative breast cancer. Vepdegestrant is a substrate of cytochrome P450 (CYP)3A4 in vitro; therefore, its plasma exposure may increase when coadministered with CYP3A4 inhibitors, such as the strong index CYP3A4 inhibitor itraconazole. This study evaluated the effect of itraconazole on the pharmacokinetics (PK) and safety of vepdegestrant in healthy adults.</div></div><div><h3>Methods</h3><div>During this phase 1, open-label, 2-period, fixed-sequence study (NCT05538312), participants received 2 doses of vepdegestrant and multiple doses of itraconazole. In period 1, participants received a single dose of vepdegestrant 200 mg under fed conditions followed by a washout period of at least 10 days. In period 2, participants received itraconazole 200 mg once daily under fasted conditions on days 1–11 and a single dose of vepdegestrant 200 mg under fed conditions on day 5 with concomitant itraconazole administration. Plasma samples were collected predose and serially following each vepdegestrant dose. PK parameters calculated for vepdegestrant and its epimer metabolite, ARV-473, included area under the plasma concentration-time curve from time 0 extrapolated to infinity (AUC_inf) and maximum plasma concentration (C_max). Safety was monitored throughout the study.</div></div><div><h3>Findings</h3><div>A total of 12 healthy adult participants received vepdegestrant with (test) and without (reference) itraconazole. The vepdegestrant test/reference ratios of the adjusted geometric means (90% confidence intervals) for AUC_inf and C_max were 168.9% (157.7–180.9) and 152.2% (136.9–169.2), respectively. Similar increases in exposure were observed for ARV-473. All adverse events were mild or moderate, and no participants discontinued from the study due to adverse events.</div></div><div><h3>Implications</h3><div>Coadministration of multiple doses of itraconazole, a strong CYP3A4 inhibitor, increased vepdegestrant exposure by 69%, suggesting the involvement of CYP3A4-mediated metabolism, albeit not predominantly, in vepdegestrant elimination.</div></div>","PeriodicalId":10699,"journal":{"name":"Clinical therapeutics","volume":"48 2","pages":"Pages 179-185"},"PeriodicalIF":3.6,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146008646","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Time Trends in Prescribing of Anxiolytic, Sedative, and Hypnotic Drugs in the United States","authors":"Zhengzhe Yang,&nbsp;Richard I. Shader MD,&nbsp;David J. Greenblatt MD","doi":"10.1016/j.clinthera.2025.12.014","DOIUrl":"10.1016/j.clinthera.2025.12.014","url":null,"abstract":"<div><h3>Purpose</h3><div>Sedative, anxiolytic, and hypnotic (sleep-promoting) medications are extensively prescribed in clinical practice. Most are benzodiazepine (BZ) receptor agonists, but other drug classes are prescribed as well. Reliable quantitative data on the extent of prescribing, and changes in prescribing patterns over time, are needed to support risk-benefit decisions for individual patients and physicians, as well as public policy and regulatory decisions on product labeling, dosing recommendations, and use restrictions as applicable.</div></div><div><h3>Methods</h3><div>Retail and mail-order pharmacy dispensing data from 2006 to 2023 was evaluated using the Medical Expenditure Panel Survey component of the Agency for Healthcare Research and Quality, as appearing in the public domain (ClinCalc.com). Also evaluated was 2019 and 2023 data from the Centers for Medicare &amp; Medicaid Services (CMS), providing federal health care coverage under Medicare Part D and Medicaid programs. Specific medications targeted were: BZ derivatives, zolpidem, and non-BZs taken for anxiety disorders and insomnia (buspirone, trazodone, and dual orexin receptor antagonists).</div></div><div><h3>Findings</h3><div>ClinCalc data indicated that prescribing of BZ-agonist agents (inclusive of zolpidem) was maximal in year 2014, then declined annually to about 50% of that maximum by year 2023. CMS Medicare Part D and Medicaid data reported a similar trend. The non-BZ sedating antidepressant trazodone was the most commonly prescribed hypnotic medication, with trazodone numbers more than double those for zolpidem by 2023. CMS Medicare Part D and Medicaid data reported similar trends. The dual orexin receptor antagonist hypnotics, available only as brand names at high cost, were not listed by ClinCalc, but CMS data indicated only modest use compared with trazodone.</div></div><div><h3>Implications</h3><div>The overall shift away from BZ agonist prescribing in the last decade has potential public health drawbacks as well as benefits, the balance of which is not established. The net clinical implications need close analysis using validated and objective biomedical and epidemiologic methodologies.</div></div>","PeriodicalId":10699,"journal":{"name":"Clinical therapeutics","volume":"48 2","pages":"Pages 196-201"},"PeriodicalIF":3.6,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146028657","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Safeguarding Cannabis for Medical Use: Clinical Risks, Regulatory Gaps, and the Path Toward Equitable Standards.","authors":"Shawn P Collins","doi":"10.1016/j.clinthera.2025.12.011","DOIUrl":"https://doi.org/10.1016/j.clinthera.2025.12.011","url":null,"abstract":"<p><p>Cannabis has moved into mainstream clinical use, yet the systems that should guarantee patient safety still lag. Oversight in the United States remains fragmented across states, with inconsistent thresholds, variable testing panels, and enforcement that often follows rather than prevents harm. Microbial contamination persists in regulated markets. Pathogenic Aspergillus has been detected in products that passed culture-based screens. Case reports in immunocompromised patients underscore real clinical consequences. Chemical contaminants, pesticides, heavy metals, and solvents, add cumulative risk and plausibly affect drug metabolism. State reforms have tried to tighten controls. Massachusetts required single-laboratory testing and digital certificate uploads. Those changes limited obvious lab shopping but left a fundamental flaw in place: cultivators and manufacturers still choose the samples. When sampling is compromised, even excellent laboratory work cannot protect patients. The 2025 suspension of Assured Testing Laboratories, along with recalls and lab actions in other states, shows the system's weakest points. International models demonstrate better paths. Canada uses pathogen-specific assays and broad pesticide panels, with high compliance. The European Medicines Agency has drafted pharmacopoeial standards for cannabis flos. Germany and Israel regulate cannabis as a medical product and link quality to reimbursement and distribution. My position is that U.S. policy should move to pathogen-specific molecular testing, harmonized chemical limits, and independent, regulator-controlled sampling. Equity protections are essential so safe products are accessible, not exclusive. Patients deserve cannabis regulated with the seriousness we expect for any therapeutic agent.</p>","PeriodicalId":10699,"journal":{"name":"Clinical therapeutics","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2026-01-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146092399","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Bioequivalence and Safety Study of Ranolazine Extended-Release Tablets in Chinese Healthy Subjects Under Fasting and Fed Conditions: A Randomized, Open-Label, Single-Dose, Cross-Over, Comparative Pharmacokinetic Study","authors":"Xing Chen MM ,&nbsp;Yaming Li MM ,&nbsp;Genshan Ma PhD","doi":"10.1016/j.clinthera.2025.11.002","DOIUrl":"10.1016/j.clinthera.2025.11.002","url":null,"abstract":"<div><h3>Purpose</h3><div>The bioequivalence of the generic (Test formulation, T) and the originator (Reference formulation, R) ranolazine extended-release tablets was assessed in Chinese healthy subjects under fasting and fed conditions.</div></div><div><h3>Methods</h3><div>The study was conducted in accordance with a randomized, open, single-dose, 2-period, self-crossover design, with 36 subjects enrolled in each of the fasting and fed trials. Each subject received a 500 mg T or R tablet under fasting or fed conditions. Blood samples collected up to 48 h post-dose were determined for plasma concentrations of ranolazine by LC-MS/MS. The primary pharmacokinetic parameters were analyzed using a non-compartmental model, and geometric mean ratio (GMRs) for T/R and their 90% confidence interval (CI) were calculated for bioequivalence assessment. Adverse events (AEs) were monitored throughout, with safety assessments performed.</div></div><div><h3>Results</h3><div>The 90% CIs for the GMRs of the primary pharmacokinetic parameters (C_max, AUC_0-t, and AUC_0-∞) between the T and R administered under fasting conditions were 95.17% (85.48%–105.96%), 97.55% (87.52%–108.73%), and 94.75% (85.26%–105.30%), respectively. Similarly, under fed conditions, the 90% CIs for the GMRs of C_max, AUC_0-t, and AUC_0-∞ were 92.88% (84.25%–102.40%), 98.41% (92.66%–104.52%) and 97.60% (92.13%–103.41%), respectively. All values fell within the 80.00% to 125.00% range, thus meeting bioequivalence criteria. No serious AEs were reported during the study, indicating favorable safety and tolerability.</div></div><div><h3>Implications</h3><div>The test formulation, ranolazine extended-release tablets, demonstrated a similar safety profile to the reference formulation, Ranexa, and was shown to be bioequivalent in healthy Chinese subjects in both fasting and fed conditions.</div></div><div><h3>Clinical trial registration</h3><div>ClinicalTrials.gov, identifier: NCT07054255.</div></div>","PeriodicalId":10699,"journal":{"name":"Clinical therapeutics","volume":"48 1","pages":"Pages 88-94"},"PeriodicalIF":3.6,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145630998","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Letters From the Field: Challenges and Opportunities in the Development of Botanical Drugs From Cannabis","authors":"Justyna Kulpa PhD,&nbsp;Schuyler A. Pruyn MS,&nbsp;George Hodgin MBA","doi":"10.1016/j.clinthera.2025.11.010","DOIUrl":"10.1016/j.clinthera.2025.11.010","url":null,"abstract":"<div><div>Cannabis and cannabis-derived products (CCDPs) have gained recognition for their therapeutic potential, driving legal and social shifts worldwide. In the United States, state-level medical cannabis programs exist alongside the federal drug development framework, which remains the gold standard for ensuring safety and efficacy. The Food and Drug Administration (FDA) botanical drug development guidance provides a structured approval pathway for plant-derived products, including CCDPs, accounting for their unique chemical complexity. Despite this guidance, significant gaps persist in preclinical and clinical data, particularly for minor cannabinoids. Development of botanical drugs from cannabis is further complicated by regulatory oversight from the Drug Enforcement Administration, which constrains the cultivation, handling, and distribution of cannabis and imposes logistical and security requirements during drug development. This article discusses the unique experience of drug developers navigating the scientific and regulatory challenges inherent in advancing CCDPs toward FDA drug approval. Collaborative efforts among federally compliant drug developers, regulatory bodies, healthcare providers, academic institutions, investors, and patients/patient advocacy groups are critical to generate rigorous, reproducible evidence to support the safe and effective use of CCDPs in medical conditions where they hold the greatest therapeutic potential. Such partnerships can advance studies that elucidate cannabinoid pharmacology, optimize dosing with rigorously characterized materials via clinically relevant routes, and identify clinical outcomes that are meaningful to patients. Advancing CCDPs through federally compliant drug development pathways will enable the translation of promising botanical therapies into safe, effective, and evidence-based treatments, ultimately informing clinical practice and benefiting patients.</div></div>","PeriodicalId":10699,"journal":{"name":"Clinical therapeutics","volume":"48 1","pages":"Pages 38-45"},"PeriodicalIF":3.6,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145800206","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}