Testing of HIV Protease Inhibitors to Suppress Inflammation and Improve Cardio Pulmonary Hemodynamics in Subjects With Pulmonary Arterial Hypertension

Study Rationale:There is recent evidence that HIV protease inhibitors (HIV-PI) can improve pulmonary hemodynamics in experimental models of pulmonary arterial hypertension (PAH). There is also experimental evidence that both TLR4 and high mobility group box 1 (HMGB1) participate in the pathogenesis of experimental pulmonary hypertension. A recent high throughput screen for inhibitors of HMGB1 induced macrophage activation yielded HIV-protease inhibitors (PIs) as potent inhibitors of HMGB1 induced cytokine production. Based on the experimental evidence we propose a trial to determine whether HIV-PIs will alter the pathobiology of PAH.
Study Objectives:The main objective of this study is to determine whether saquinavir and ritonavir (SQV+RIT) which have a well-characterized safety profile in humans will reduce bio markers of inflammation and pulmonary artery pressures in patients with PAH.
Study Hypothesis:We hypothesize that the HIV-PI, SQV+RIT, will reduce circulating parameters of inflammation including HMGB1, IL1-beta, IL-6, IL-8, IL-10, TNF-alpha and CRP. Our end points will be changes in these parameters from baseline over the duration of the study.We hypothesize that treatment with SQV+RIT will reduce pulmonary artery(PA) pressure of patients with PAH as measured by echocardiography.
Study Design:This is a single center open label phase 0 study to evaluate the effect of SQV +RIT in patients with IPAH. Subjects with IPAH(N=20) will be enrolled into a study, which will be divided into 3 cohorts and entail the administration of HIV protease inhibitors in three doses. The first cohort (n=3) will receive a starting dose of SQV 0.3 mg/kg twice daily in combination with RIT 0.03 mg/kg twice daily. If the first dose is well-tolerated, the second cohort (n= 3 ) with IPAH will be given doses of SQV 3 mg/kg and RIT 0.3 mg/kg twice daily. If the second dose is well-tolerated, the last cohort (n= 14 ) with IPAH will be given doses of SQV 15 mg/kg and RIT 1.5 mg/kg twice daily.

开始日期2013-12-01

申办/合作机构

中南大学湘雅三医院

[+1]

NCT01638650 / Completed临床1期

To Determine the Effect of the Modified SQV/r (Saquinavir-boosted by Ritonavir) Regimen (500/100 mg for the 1st Week Followed by 1000/100 mg for the 2nd Week) on the QTc Interval, Pharmacokinetics, and Antiviral Activity in Treatment-naive HIV-1 Infected Patients

This open-label study will evaluate the safety, pharmacokinetics and antiviral activity of a modified Invirase (saquinavir)/ritonavir regimen in treatment-naïve HIV-1 infected patients. Patients will receive Invirase 500 mg plus ritonavir 100 mg twice daily orally for the first week, followed by Invirase 1000 mg plus ritonavir 100 mg twice daily orally for the second week. The study treatment will be given in combination with two Nucleoside Reverse Transcriptase Inhibitors (NRTIs), in accordance with the current clinical HIV treatment guidelines. Anticipated time on study treatment is 14 days.

开始日期2012-01-01

申办/合作机构

Hoffmann-La Roche, Inc.

JPRN-UMIN000004621 / Completed

Effect of a pharmaceutical excipient, cremophol EL on the plasma concentration-time profile of saquinavir and fexofenadine after their oral administrations at doses used in the exploratory investigational new drug clinical studies - Effect of cremophol EL on pharmacokinetics of saquinavir and fexofenadine at doses used in the exploratory investigational new drug clinical studies

开始日期2010-11-01

申办/合作机构-

100 项与甲磺酸沙奎那韦相关的临床结果

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100 项与甲磺酸沙奎那韦相关的转化医学

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100 项与甲磺酸沙奎那韦相关的专利（医药）

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项与甲磺酸沙奎那韦相关的文献（医药）

2024-01-01·Journal of pharmaceutical and biomedical analysis

Simultaneous quantification of nirmatrelvir/ritonavir in human serum by LC–HRMS

Article

作者: Zhao, Fenglun ; Xiang, Zheng ; Pan, Jie ; Su, Cunjin ; Yu, Yunli ; Qu, Yuchen ; Xu, Delai ; Shen, Zhu ; Fan, Kai ; Han, Junping ; Wu, Zhiqiang

In December 2021, the U.S. Food and Drug Administration (FDA) granted emergency authorization for Paxlovid® as an antiviral treatment for COVID-19. Paxlovid® is composed of two tablets, nirmatrelvir and ritonavir. Dose adjustment is necessary in cases of renal insufficiency. The aim of present study is to establish a LC-HRMS method for simultaneous determination of nirmatrelvir/ritonavir in human serum for therapeutic drug monitoring. Internal standard saquinavir was added in 25 μL human serum samples, and then the samples were precipitated with methanol. The analytes were separated by gradient elution on a C18 column, using a mobile phase of 0.1 % formic acid-water and methanol, at a flow rate of 0.4 mL/min. The injection volume was 2 μL, and the analysis time was 5 min. The determination of the analytes was performed by electrospray ionization in positive mode by full mass monitoring. The detected ions of nirmatrelvir, ritonavir and saquinavir were m/z 500.24792, 721.32004 and 671.39155, respectively. The linear concentration range for nirmatrelvir was 78.13-20000 ng mL^-1, for ritonavir was 15.63-4000 ng mL^-1 (r²＞0.9900). The accuracy ranged from 87.45 %∼104.63 %, and the intra-day and inter-day precision RSD was <15 %. The recovery of nirmatrelvir ranged from 98.72 %∼109.83 %, and that of ritonavir was 95.41∼112.36 %. The matrix effect of nirmatrelvir was 88.31∼97.73 %, and that of ritonavir was 85.17∼103.05 %. This method was used to measure the trough concentrations of nirmatrelvir/ritonavir in 17 patients. The trough concentration of nirmatrelvir was 1331.7-8352.5 ng/mL, and that of ritonavir was 53.4-1325.5 ng mL^-1, with large individual differences. The method is simple, sensitive, specific, and reproducible, and can be used for monitoring the blood concentration and pharmacokinetic study of nirmatrelvir/ritonavir in COVID-19 patients.

2023-12-01·European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences

Hydrogel containing mPEG-PLGA nanoparticles for the vaginal delivery of saquinavir mesylate against HIV infection

Article

作者: Palmieri, Giovanni Filippo ; Tiboni, Mattia ; Bonacucina, Giulia ; Cespi, Marco ; Perinelli, Diego Romano ; Casettari, Luca

Saquinavir mesylate (SQV) is a protease inhibitor commonly employed for the treatment of human immunodeficiency virus-1 infection. It is generally administered orally as tablets in combination with other antiviral drugs. Another promising route of administration can be represented by the vaginal one through topically applied formulations. This delivery can reduce the first-pass effect in the case of systemic drug adsorption or prevent HIV infection. We propose the formulation of a Carbopol® 974 (C974) hydrogel containing biodegradable mPEG-PL(L)GA nanoparticles (NPs) for the vaginal delivery of SQV, intended both as a prevention and a therapeutic strategy. mPEG-PL(L)GA NPs were incorporated into the C974 polymeric matrix, leading to a reduction of the hydrogel consistency dependent on NPs and C974 concentrations. Despite the moderate drug loading into NPs, the presence of the NPs had an impact on the in vitro release of the drug from the hydrogel at pH 5.5 using immersion cells. A higher amount of the drug was released, probably due to the effect of NPs in promoting the incorporation of the drug into the hydrogel at a high SQV dose. These findings can be useful for the development of topically applied hydrogels for SQV delivery, possibly having improved in vivo therapeutic outcomes.

2023-11-02·Immunopharmacology and immunotoxicology

HIV protease inhibitor saquinavir inhibits toll-like receptor 4 activation by targeting receptor dimerization

Article

作者: Xue, Bichen ; Peng, Cheng ; Xu, Hongbo ; Yao, Kai ; Wang, Yong ; Tang, Yulin ; Wang, Zhichao ; Wang, Zheng

OBJECTIVE:

Toll-like receptor 4 (TLR4) is crucial in induction of innate immune response through recognition of invading pathogens or endogenous alarming molecules. Ligand-triggered dimerization of TLR4 is essential for the activation of NF-κB and IRF3 through MyD88- or TRIF-dependent pathways. Saquinavir (SQV), an FDA-approved HIV protease inhibitor, has been shown to attenuate the activation of NF-κB induced by HMGB1 by blocking TLR4-MyD88 association in proteasome independent pathway. This study aims to define whether SQV is an HMGB1-specific and MyD88-dependent TLR4 signaling inhibitor and which precise signaling element of TLR4 is targeted by SQV.

MATERIALS AND METHODS:

PMA differentiated human THP-1 macrophages or reconstituted HEK293 cells were pretreated with SQV before stimulated by different TLR agonists. TNF-α level was evaluated through ELISA assay. NF-κB activation was analyzed using NF-κB SEAP reporting system. The levels of MyD88/TRIF pathways-related factors were examined by immunoblot. TLR4 endocytosis was assessed by immunocytochemistry. TLR4 dimerization was determined using immunoprecipitation between different tagged TLR4 and an in silico molecular docking experiment was performed to explore the possible binding site of SQV on its target.

RESULTS:

Our data showed that SQV suppresses both MyD88- and TRIF-dependent pathways in response to lipopolysaccharide (LPS), a critical sepsis inducer and TLR4 agonist, leading to downregulation of NF-κB and IRF3. SQV did not suppress MyD88-dependent pathway triggered by TLR1/2 agonist Pam3csk4. In the only TRIF-dependent pathway, SQV did not alleviate IRF3 phosphorylation induced by TLR3 agonist Poly(I:C). Furthermore, dimerization of TLR4 following LPS or HMGB1 stimulation was decreased by SQV.

CONCLUSION:

We concluded that TLR4 receptor complex is one of the mammalian targets of SQV, and TLR4-mediated immune responses and consequent risk for uncontrolled inflammation could be modulated by FDA-approved drug SQV.

项与甲磺酸沙奎那韦相关的新闻（医药）

2024-05-29

·BioSpace

Petros Pharmaceuticals Successfully Completes AI-Integrated Formative Human Factors Study Demonstrating Positive Interaction with Web App Designed for STENDRA(R) (avanafil) OTC Switch

Study paves the way toward a first-ever innovation program to include AI-optimization for FDA-guided Rx-to-OTC switch NEW YORK, NY / ACCESSWIRE / May 29, 2024 / Petros Pharmaceuticals, Inc. (NASDAQ:PTPI) ("Petros" or the "Company"), a company focused on expanding consumer access to medication through over-the-counter ("OTC") drug development programs, announces the successful completion of a Formative Human Factors study of its AI-integrated Web App, designed to facilitate OTC access of STENDRA® (avanafil) for consumers. This important development follows the Company's recent execution of an AI licensing agreement with a leading multi-billion dollar software provider announced earlier this year. The Web App (previously referred to as the "technology component") is an integral part of the Company's efforts to complete an Rx-to-OTC switch for STENDRA® (avanafil) under the guidance of the U.S. Food and Drug Administration. The study demonstrated a 90% or better error-free completion rate for nearly all 5,820 tasks assessed. The successful completion of the study paves the way for the Company to initiate the next stage of the evolving program, while continuing to optimize the AI component of the Web App. "The successful completion of the Human Factors Study and the positive outcomes we've seen to date continue to be encouraging signs of our progress in navigating the Rx-to-OTC switch for STENDRA® (avanafil). As we've previously indicated, we believe we have the potential to be first-in-class for the category with regards to OTC access," stated Fady Boctor, Petros' President and Chief Commercial Officer. "We continue to refine our program based on our regular interactions with the FDA, and the learnings from this study will allow us to continue to optimize the AI component of the Web App. Combined, we strongly believe in our approach and look forward to continuing development into the next indicated step for STENDRA® (avanafil) in a non-prescription setting." The Formative Human Factors study was conducted in a population of 30 consumers, including a cohort with limited literacy. The consumers were provided with five different use scenarios requiring correct demonstration of 194 different tasks using the Web App with no training or guidance. The study also included a proprietary AI interface that confirmed the identity of the consumer, a first-ever innovation for an Rx-to-OTC switch program. About Petros Pharmaceuticals Petros Pharmaceuticals, Inc. is committed to the goal of becoming a leading innovator in the emerging self-care market driving expanded access to key prescription pharmaceuticals as OTC treatment options. Currently, Petros is pursuing increased access for its flagship prescription ED therapy, STENDRA® (avanafil), via potential OTC designation. If ultimately approved by the FDA for OTC access, STENDRA® (avanafil) may be the first in its class to achieve this marketing status, also establishing company know how as a proven platform for other prospective prescription therapeutics. About the OTC Pathway The process of switching a prescription medication to OTC first involves the design of a Drug Facts Label ("DFL") that is well understood by potential consumers. Then, data must show that consumers can make an appropriate informed decision to use or not to use the product based only upon the information on the DFL and their personal medical history. Then consumers must demonstrate that they can properly use the product based upon the information on the DFL. To accomplish this, the FDA ordinarily requires a consumer tested OTC DFL. Such testing includes conduct of iterative Label Comprehension Studies (LCS) in the general population, Self-Selection Studies (SSS) in a population interested in using the product and in specific populations who may be harmed if they use the product, and usually one Actual Use Trial (AUT) demonstrating safe and appropriate use by consumers in a simulated OTC setting. The regulations that FDA is currently finalizing introduced Additional Conditions for Nonprescription Use (ACNU) criteria that enable correct self-selection by consumers and may expand OTC access to medications that formerly could only be available by prescription. An ACNU may be an innovative computerized tool, or the additional conditions may use other approaches that support the switch process. Important Safety Information about STENDRA® (avanafil) STENDRA® (avanafil), originally launched by Auxilium Pharmaceuticals prior to its sale to Endo Pharmaceuticals, is an oral phosphodiesterase 5 (PDE5) inhibitor for the treatment of erectile dysfunction. STENDRA® (avanafil) is not for use in women or children. It is not known if STENDRA® (avanafil) is safe and effective in women or children under 18 years of age. A 100-mg and 200-mg tablet can be taken as early as ~15 minutes before sexual activity. STENDRA® (avanafil) only works with sexual stimulation and should not be taken more than once a day. STENDRA can be taken with or without food; do not drink too much alcohol when taking STENDRA® (avanafil) (for example, more than three glasses of wine or three shots of whiskey) as it can increase chances of side effects. Of people enrolled in clinical trials, 1.4%, 2.0%, and 2.0%, respectively, stopped taking STENDRA® (avanafil) (50 mg, 100 mg, or 200 mg) due to side effects compared to 1.7% taking a placebo. STENDRA® (avanafil) was designed and developed expressly for erectile dysfunction. STENDRA is contraindicated for any form of organic nitrates, in patients with known hypersensitivity to any component of the tablet, and in patients who are using a guanylate cyclase stimulator. Patients should not use STENDRA if sexual activity is inadvisable due to cardiovascular status or any other reason. Before taking STENDRA, tell your doctor if you have had any kind of heart issues including heart attack, heart failure, angina and irregular heartbeat or have elevated or low blood pressure. Use of STENDRA with alpha-blockers, other antihypertensives, or substantial amounts of alcohol (greater than three units) may lead to hypotension. Patients should seek emergency treatment if an erection lasts greater than 4 hours. Patients should stop STENDRA and seek medical care if a sudden loss of vision occurs in one or both eyes, which could be a sign of Non-Arteritic Ischemic Optic Neuropathy ("NAION"). Doctors should discuss with patients the increased risk of NAION in patients with a history of NAION. Patients should stop taking STENDRA and seek prompt medical attention in the event of sudden decrease or loss of hearing. STENDRA can potentiate the hypotensive effect of nitrates, alpha blockers, antihypertensives, and alcohol. CYP3A4 inhibitors (e.g., ketoconazole, ritonavir, erythromycin) increase STENDRA exposure. For patients taking concomitant strong CYP3A4 inhibitors (including ketoconazole, ritonavir, atazanavir, clarithromycin, indinavir, itraconazole, nefazodone, nelfinavir, saquinavir and telithromycin), do not use STENDRA. Combination with Other PDE5 Inhibitors or Erectile Dysfunction Therapies is not recommended. The safety of STENDRA is unknown in patients with bleeding disorders and patients with active peptic ulceration. The use of STENDRA offers no protection against sexually transmitted diseases including HIV. Consider counseling patients on protective measures for sexually transmitted diseases. The most common adverse reactions reported with use of STENDRA include headache, flushing, nasal congestion, nasopharyngitis, and back pain. For more information about STENDRA, call 844-458-4887. If you would like to report an adverse event or product complaint, please contact us at 844-458-4887. You are encouraged to report negative side eﬀects of prescription drugs to the FDA by calling 1-800-FDA-1088, or at . Please see the full Prescribing Information and Patient Information. Cautionary Note Regarding Forward-Looking Statements This press release includes forward-looking statements within the meaning of Section 27A of the Securities Act of 1933, as amended, and Section 21E of the Securities Exchange Act of 1934, as amended. These forward-looking statements are based upon Petros Pharmaceuticals, Inc.'s ("Petros," "we," "our," "us" or the "Company") management's assumptions, expectations, projections, intentions, and beliefs about future events. In some cases, predictive, future-tense or forward-looking words such as "intend," "develop," "goal," "plan," "predict", "may," "will," "project," "estimate," "anticipate," "believe," "expect," "continue," "potential," "opportunity," "forecast," "should," "target," "strategy" and similar expressions, whether in the negative or affirmative, that reflect our current views with respect to future events and operational, economic and financial performance are intended to identify forward-looking statements, but are not the exclusive means of identifying such statements. Such forward-looking statements are only predictions, and actual results and the timing of certain events and circumstances may differ materially from those described by the forward-looking statements as a result of risks and uncertainties, Petros' ability to execute on its business strategy, including its plans to develop and commercialize its product candidates; Petros' ability to comply with obligations as a public reporting company; Petros' ability to maintain compliance with the Nasdaq Stock Market's listing standards; risks related to Petros' ability to continue as a going concern; risks related to Petros' history of incurring significant losses; risks related to Petros' dependence on the commercialization of a single product, STENDRA®; and risks related to Petros' ability to obtain regulatory approvals for, or market acceptance of, any of its products or product candidates. Additional factors that could cause actual results to differ materially from the results anticipated in these forward-looking statements are contained in the Company's periodic reports and in other filings that the Company has or may file, with the U.S. Securities and Exchange Commission (the "SEC") under the headings "Risk Factors" and "Management's Discussion and Analysis of Financial Condition and Results of Operations" and elsewhere. The Company cautions readers that the forward-looking statements included in this press release represent our beliefs, expectations, estimates and assumptions only as of the date of hereof and are not intended to give any assurance as to future results. New factors emerge from time to time, and it is not possible for us to predict all these factors. Further, the Company cannot assess the effect of each such factor on our business or the extent to which any factor, or combination of factors, may cause actual results to be materially different from those contained in any forward-looking statement. Accordingly, you should not unduly rely on any forward-looking statements. The Company undertakes no obligation to update or revise any forward-looking statements contained in this press release, whether as a result of new information, future events, a change in our views or expectations or otherwise, except as required by federal securities laws. Contacts Investors: CORE IR ir@petrospharma.com Media: Jules Abraham CORE IR 917-885-7378 pr@coreir.com SOURCE: Petros Pharmaceuticals, Inc. View the original press release on accesswire.com

上市批准

2024-05-28

·PRNewswire

Calliditas Therapeutics Presents Data at the 61st European Renal Association Congress

STOCKHOLM, May 28, 2024 /PRNewswire/ -- Calliditas Therapeutics AB (Nasdaq: CALT) (Nasdaq Stockholm: CALTX) ("Calliditas"), today announced the presentations of an additional efficacy analysis of Nefecon (TARPEYO® (budesonide) delayed release capsules)) as well as a real-world analysis of the use of systemic glucocorticoids (SGC) in IgA nephropathy (IgAN). These were presented at ERA 2024 virtually and in Stockholm on May 23 - 26, 2024. The presented efficacy analysis of Nefecon and sparsentan showed that treatment with Nefecon for 9 months was associated with estimated glomerular filtration rate (eGFR) benefit compared with continuous treatment with sparsentan. Additionally, the findings of a real-world analysis of challenges associated with the use of systemic glucocorticoids demonstrate significant side effects and costs for IgAN patients treated with systemic glucocorticoids (SGC), such as Prednisone and Prednisolone. "It was wonderful to participate in ERA 2024 and present data contributing to the discussion on the need for effective treatments in IgAN," said Richard Philipson, Chief Medical Officer of Calliditas, " We continue to gather evidence that highlights the importance of treating the underlying autoimmune pathogenesis associated with IgAN, and we believe TARPEYO, as the only approved immunomodulating therapy designed to target the production of Gd-IgA1, has the potential to become a cornerstone therapy in IgAN." Poster presentation details are below and will be available on the Presentations and Publications page on the Calliditas' corporate website following the meeting. Presentation Analyses: Title: "Matching-adjusted indirect comparison of eGFR in patients with immunoglobulin A nephropathy treated with Nefecon (TRF budesonide) or sparsentan" A matching-adjusted indirect comparison (MAIC) methodology is a widely accepted and relevant methodology for comparing treatments across trials in the absence of head-to-head comparisons. Here the effects of Nefecon, marketed as TARPEYO® and sparsentan, marketed as FILSPARI™, on kidney function deterioration in patients with IgAN were compared, as assessed by eGFR change from baseline at 9, 12 and 24 months. Results from the MAIC showed significantly favorable effects of Nefecon versus sparsentan on eGFR across all time points analyzed. Mean differences in the absolute change in eGFR of 5.68mL/min/1.73 m2 (95% credible interval [Crl] 3.14, 8.20; p<0.001), 3.48 mL/min/1.73 m2 (95% Crl 0.97, 5.97; p=0.006) and 3.28 mL/min/1.73 m2 (95% Crl 0.02, 6.51; p=0.048) were observed when comparing Nefecon with sparsentan at 9 months vs 36 weeks, 12 months vs 48 weeks, and 24 months vs 106 weeks, respectively. This efficacy analysis showed that treatment with Nefecon 16 mg/day for 9 months was associated with greater eGFR benefit compared with continuous treatment with sparsentan 400 mg/day over 2 years, with significant differences observed as early as 9 months after treatment initiation and sustained up to 2-years of follow-up. While the rigor of well-controlled head-to-head clinical trials cannot be replicated, MAIC is also a widely accepted and relevant methodology for comparing treatments across trials in the absence of head-to-head comparisons1,2, *. Title: "Real-world challenges associated with the use of systemic glucocorticoids in a US IgAN cohort" Per Kidney Disease: Improving Global Outcomes (KDIGO) guidelines, patients at high risk of progressive chronic kidney disease despite maximal supportive care can be considered for a 6-month course of systemic glucocorticoids (SGC), although important risks of toxicity and contraindications must be considered. There is currently limited real-world evidence describing the impact of the use of SGC on treatment-emergent toxicity and healthcare resource utilization (HCRU) in patients with IgAN. Our findings demonstrate significant side effects and costs for IgAN patients treated with SGC compared with patients not treated with SGC. Increases in severe infection incidents, inpatient visits, emergency department admissions, and ambulatory visits, underscore the careful consideration of treatment-emergent toxicity prior to initiating SGC therapy in patients with IgAN. *The optimization strategy in NefIgArd (optimized RASi) differed from the optimization strategy in PROTECT (IR), and anchoring of the two trials at optimized RASi/IR might lead to biased results. However, we also evaluated an unanchored MAIC in a sensitivity analysis and found very similar results. The MAIC method can only adjust the relative effect estimates for any observed effect modifier available in the data, but it cannot adjust for unobserved or unobservable effect modifiers. A significant number of potential treatment effect modifiers were included in the present analysis: age, sex, race, baseline eGFR, UPCR, UACR, and urinary protein excretion. Indication TARPEYO is indicated to reduce the loss of kidney function in adults with primary immunoglobulin A nephropathy (IgAN) who are at risk for disease progression. Important Safety Information Contraindications: TARPEYO is contraindicated in patients with hypersensitivity to budesonide or any of the ingredients of TARPEYO. Serious hypersensitivity reactions, including anaphylaxis, have occurred with other budesonide formulations. Warnings and Precautions Hypercorticism and adrenal axis suppression: When corticosteroids are used chronically, systemic effects such as hypercorticism and adrenal suppression may occur. Corticosteroids can reduce the response of the hypothalamus-pituitary-adrenal (HPA) axis to stress. In situations where patients are subject to surgery or other stress situations, supplementation with a systemic corticosteroid is recommended. When discontinuing therapy or switching between corticosteroids, monitor for signs of adrenal axis suppression. Patients with moderate to severe hepatic impairment (Child-Pugh Class B and C respectively) could be at an increased risk of hypercorticism and adrenal axis suppression due to an increased systemic exposure to oral budesonide. Avoid use in patients with severe hepatic impairment (Child-Pugh Class C). Monitor for increased signs and/or symptoms of hypercorticism in patients with moderate hepatic impairment (Child-Pugh Class B). Risks of immunosuppression: Patients who are on drugs that suppress the immune system are more susceptible to infection than healthy individuals. Chickenpox and measles, for example, can have a more serious or even fatal course in susceptible patients or patients on immunosuppressive doses of corticosteroids. Avoid corticosteroid therapy in patients with active or quiescent tuberculosis infection; untreated fungal, bacterial, systemic viral, or parasitic infections, or ocular herpes simplex. Avoid exposure to active, easily transmitted infections (e.g., chicken pox, measles). Corticosteroid therapy may decrease the immune response to some vaccines. Other corticosteroid effects: TARPEYO is a systemically available corticosteroid and is expected to cause related adverse reactions. Monitor patients with hypertension, prediabetes, diabetes mellitus, osteoporosis, peptic ulcer, glaucoma or cataracts, or with a family history of diabetes or glaucoma, or with any other condition where corticosteroids may have unwanted effects. Adverse reactions: In clinical studies, the most common adverse reactions with TARPEYO (occurring in ≥5% of TARPEYO treated patients, and ≥2% higher than placebo) were peripheral edema (17%), hypertension (12%), muscle spasms (12%), acne (11%), headache (10%), upper respiratory tract infection (8%), face edema (8%), weight increased (7%), dyspepsia (7%), dermatitis (6%), arthralgia (6%), and white blood cell count increased (6%). Drug interactions: Budesonide is a substrate for CYP3A4. Avoid use with potent CYP3A4 inhibitors, such as ketoconazole, itraconazole, ritonavir, indinavir, saquinavir, erythromycin, and cyclosporine. Avoid ingestion of grapefruit juice with TARPEYO. Intake of grapefruit juice, which inhibits CYP3A4 activity, can increase the systemic exposure to budesonide. Use in specific populations Pregnancy: The available data from published case series, epidemiological studies, and reviews with oral budesonide use in pregnant women have not identified a drug-associated risk of major birth defects, miscarriage, or other adverse maternal or fetal outcomes. There are risks to the mother and fetus associated with IgAN. Infants exposed to in-utero corticosteroids, including budesonide, are at risk for hypoadrenalism. Please see Full Prescribing Information . About TARPEYO TARPEYO is an oral 4mg delayed release formulation of budesonide, designed to remain intact until it reaches the ileum. Each capsule contains coated beads of budesonide that target mucosal B-cells present in the ileum, including the Peyer's patches, which are responsible for the production of galactose-deficient IgA1 antibodies (Gd-Ag1) causing IgA nephropathy. About Primary Immunoglobulin A Nephropathy Primary immunoglobulin A nephropathy (IgA nephropathy or IgAN or Berger's Disease) is a rare, progressive, chronic autoimmune disease that attacks the kidneys and occurs when galactose deficient IgA1 is recognized by autoantibodies, creating IgA1 immune complexes that become deposited in the glomerular mesangium of the kidney. This deposition in the kidney can lead to progressive kidney damage and potentially a clinical course resulting in end- stage renal disease. IgAN most often develops between late teens and late 30s. For further information, please contact: Åsa Hillsten, Head of IR & Sustainability, Calliditas Tel.: +46 76 403 35 43, Email: [email protected] The information was sent for publication, through the agency of the contact persons set out above, on May 28, 2024, at 14.00 p.m. CET. This information was brought to you by Cision . The following files are available for download: SOURCE Calliditas Therapeutics

临床结果免疫疗法临床研究上市批准

2024-05-21

·BioSpace

Petros Pharmaceuticals Activates Advisory Committee to Help Guide Rx-to-OTC Switch for STENDRA

Team composed of former FDA officials and key clinical and regulatory opinion leaders to help provide insight in preparation for collaboration with FDA NEW YORK, NY / ACCESSWIRE / May 21, 2024 / Petros Pharmaceuticals, Inc. (NASDAQ:PTPI), a company focused on expanding consumer access to medication through over-the- counter (OTC) drug development programs, announces it has formed an Advisory Committee to provide guidance as the company prepares for the potential Rx-to-OTC switch for STENDRA for both development and communication with the U.S. Food and Drug Administration. "We believe this diverse team of subject matter experts, which include former FDA officials, will be instrumental in helping to ensure our development program is pursued with the same anticipated rigor we expect to experience when presenting the program to regulators," stated Fady Boctor, Petros's President and Chief Commercial Officer. "We believe thinking beyond our perspective as a manufacturer is critical to our ability to align with the FDA perspective, guidance, and concerns. Since piloting this Advisory Committee, we have experienced its value and synergy with FDA engagements." The multi-disciplinary team is comprised of seven members, with industry-leading statisticians, clinical pharmacologists, as well as representatives in cardiology and urology. The team also hosts an impressive array of experience spanning industry, academia, and most importantly for the purposes of its formation, governmental agency. The committee will mimic the rigor and evidentiary standards exercised by the FDA on a regular basis as the company continues its development in pursuit of the Rx-to-OTC switch for STENDRA. These multi-disciplinary sector leaders will help the company craft a carefully calculated strategy that impacts study protocols, subject recruitment pro user-related risk analyses, and patient-centered considerations aimed at optimizing care in a potentially non-prescription setting. About Petros Pharmaceuticals Petros Pharmaceuticals is committed to the goal of becoming a leading innovator in the emerging self-care market driving expanded access to key prescription pharmaceuticals as Over-the-Counter treatment options. Currently, Petros is pursuing increased access for its flagship prescription ED therapy, STENDRA, via potential OTC designation. If ultimately approved by the FDA for OTC access, STENDRA may be the first in its class to achieve this marketing status, also establishing company know how as a proven platform for other prospective prescription therapeutics. About the OTC Pathway The process of switching a prescription medication to over the counter (OTC) first involves the design of a Drug Facts Label (DFL) that is well understood by potential consumers. Then data must show that consumers can make an appropriate decision to use or not to use the product based only upon the information on the DFL and their personal medical history. Then consumers must demonstrate that they can properly use the product based upon the information on the DFL. To accomplish these things, the FDA ordinarily requires a consumer tested OTC DFL. This testing includes conduct of iterative Label Comprehension Studies (LCS) in the general population, Self-Selection Studies (SSS) in a population interested in using the product and in specific populations who may be harmed if they use the product, and usually one Actual Use Trial (AUT) demonstrating safe and appropriate use by consumers in a simulated OTC setting. The regulations that FDA is currently finalizing introduced Additional Conditions for Nonprescription Use (ACNU) criteria that enable correct self-selection by consumers and may expand OTC access to medications that formerly could only be available by prescription. An ACNU may be an innovative computerized tool, or the additional conditions may use other approaches that support the switch process. Important Safety Information about STENDRA® (avanafil) STENDRA® (avanafil), originally launched by Auxilium Pharmaceuticals prior to that company's sale to Endo Pharmaceuticals, is an oral phosphodiesterase 5 (PDE5) inhibitor for the treatment of erectile dysfunction. STENDRA is not for use in women or children. It is not known if STENDRA is safe and effective in women or children under 18 years of age. (A 100-mg and 200-mg tablet can be taken as early as ~15 minutes before sexual activity. STENDRA only works with sexual stimulation and should not be taken more than once a day. STENDRA can be taken with or without food; do not drink too much alcohol when taking STENDRA (for example, more than 3 glasses of wine or 3 shots of whiskey) as it can increase chances of side effects. Of people enrolled in clinical trials, 1.4%, 2.0%, and 2.0%, respectively, stopped taking STENDRA (50 mg, 100 mg, or 200 mg) due to side effects compared to 1.7% on placebo. STENDRA® was designed and developed expressly for erectile dysfunction. STENDRA is contraindicated with any form of organic nitrates, in patients with known hypersensitivity to any component of the tablet, and in patients who are using a guanylate cyclase stimulator. Patients should not use STENDRA if sexual activity is inadvisable due to cardiovascular status or any other reason. Before taking STENDRA tell your doctor if you have had any kind of heart issues including heart attack, heart failure, angina and irregular heartbeat or have elevated or low blood pressure. Use of STENDRA with alpha-blockers, other antihypertensives, or substantial amounts of alcohol (greater than 3 units) may lead to hypotension. Patients should seek emergency treatment if an erection lasts greater than 4 hours. Patients should stop STENDRA and seek medical care if a sudden loss of vision occurs in one or both eyes, which could be a sign of Non Arteritic Ischemic Optic Neuropathy (NAION). Discuss with patients the increased risk of NAION in patients with a history of NAION. Patients should stop taking STENDRA and seek prompt medical attention in the event of sudden decrease or loss of hearing. STENDRA can potentiate the hypotensive effect of nitrates, alpha blockers, antihypertensives, and alcohol. CYP3A4 inhibitors (e.g., ketoconazole, ritonavir, erythromycin) increase STENDRA exposure. For patients taking concomitant strong CYP3A4 inhibitors (including ketoconazole, ritonavir, atazanavir, clarithromycin, indinavir, itraconazole, nefazodone, nelfinavir, saquinavir and telithromycin), do not use STENDRA. Combination with Other PDE5 Inhibitors or Erectile Dysfunction Therapies is not recommended. The safety of STENDRA is unknown in patients with bleeding disorders and patients with active peptic ulceration. The use of STENDRA offers no protection against sexually transmitted diseases including HIV. Consider counseling patients on protective measures for sexually transmitted diseases. The most common adverse reactions reported with use of STENDRA include headache, flushing, nasal congestion, nasopharyngitis, and back pain. For more information about STENDRA, call 844-458-4887. If you would like to report an adverse event or product complaint, please contact us at 844-458-4887. You are encouraged to report negative side eﬀects of prescription drugs to the FDA by calling 1-800-FDA-1088, or at Please see the full Prescribing Information and Patient Information. Cautionary Note Regarding Forward-Looking Statements This press release includes forward-looking statements within the meaning of Section 27A of the Securities Act of 1933, as amended, and Section 21E of the Securities Exchange Act of 1934, as amended. These forward-looking statements are based upon Petros Pharmaceuticals, Inc.'s ("Petros," "we," "our," "us" or the "Company") management's assumptions, expectations, projections, intentions, and beliefs about future events. In some cases, predictive, future-tense or forward-looking words such as "intend," "develop," "goal," "plan," "predict", "may," "will," "project," "estimate," "anticipate," "believe," "expect," "continue," "potential," "opportunity," "forecast," "should," "target," "strategy" and similar expressions, whether in the negative or affirmative, that reflect our current views with respect to future events and operational, economic and financial performance are intended to identify forward-looking statements, but are not the exclusive means of identifying such statements. Such forward-looking statements are only predictions, and actual results and the timing of certain events and circumstances may differ materially from those described by the forward-looking statements as a result of risks and uncertainties, Petros' ability to execute on its business strategy, including its plans to develop and commercialize its product candidates; Petros' ability to comply with obligations as a public reporting company; Petros' ability to maintain compliance with the Nasdaq Stock Market's listing standards; risks related to Petros' ability to continue as a going concern; risks related to Petros' history of incurring significant losses; risks related to Petros' dependence on the commercialization of a single product, STENDRA®; and risks related to Petros' ability to obtain regulatory approvals for, or market acceptance of, any of its products or product candidates. Additional factors that could cause actual results to differ materially from the results anticipated in these forward-looking statements are contained in the Company's periodic reports and in other filings that the Company has or may file, with the U.S. Securities and Exchange Commission (the "SEC") under the headings "Risk Factors" and "Management's Discussion and Analysis of Financial Condition and Results of Operations" and elsewhere. The Company cautions readers that the forward-looking statements included in this press release represent our beliefs, expectations, estimates and assumptions only as of the date of hereof and are not intended to give any assurance as to future results. New factors emerge from time to time, and it is not possible for us to predict all these factors. Further, the Company cannot assess the effect of each such factor on our business or the extent to which any factor, or combination of factors, may cause actual results to be materially different from those contained in any forward-looking statement. Accordingly, you should not unduly rely on any forward-looking statements. The Company undertakes no obligation to update or revise any forward-looking statements contained in this press release, whether as a result of new information, future events, a change in our views or expectations or otherwise, except as required by federal securities laws. Contacts Investors: CORE IR ir@petrospharma.com Media: Jules Abraham CORE IR 917-885-7378 pr@coreir.com SOURCE: Petros Pharmaceuticals, Inc. View the original press release on accesswire.com

100 项与甲磺酸沙奎那韦相关的药物交易

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外链

KEGG	Wiki	ATC	Drug Bank
D01160	甲磺酸沙奎那韦	J05AE01	DB01232

研发状态

批准上市

10 条最早获批的记录,

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适应症	国家/地区	公司	日期
HIV感染	美国	Hoffmann-La Roche, Inc.	1995-12-06

未上市

10 条进展最快的记录,

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适应症	最高研发状态	国家/地区	公司	日期
肾脏毒性	临床2期	泰国	Roche Pharma AG	2004-05-01

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临床结果

适应症

分期

评价

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研究	分期	人群特征	评价人数	分组	结果	评价	发布日期


NCT00623597 (CTgov)	临床2期	HIV感染	18	NNRTI+saquinavir+ritonavir (Group A)	醖製構鑰艱鑰觸觸夢膚(簾廠鹽憲積膚繭顧膚艱) = 艱鬱鑰獵夢觸壓願蓋獵製糧範鏇膚蓋夢鑰衊鏇 (構製鏇製艱範築廠觸構, 顧觸窪網觸艱網壓積構 ~ 膚鑰積範簾顧壓蓋顧憲) 更多	-	2016-01-14
NCT00623597 (CTgov)	临床2期	HIV感染	18	NNRTI+saquinavir+ritonavir (Group B)	醖製構鑰艱鑰觸觸夢膚(簾廠鹽憲積膚繭顧膚艱) = 觸選醖顧憲淵範膚艱觸製糧範鏇膚蓋夢鑰衊鏇 (構製鏇製艱範築廠觸構, 選顧鏇襯製膚憲選範廠 ~ 衊膚築選壓窪簾構積糧) 更多	-	2016-01-14
NCT00435929 (CTgov)	临床1期	HIV感染	16	ritonavir (RTV) (Normal Liver Function)	襯選繭壓積築繭窪願獵(選醖襯餘夢積觸廠鑰鏇) = 醖醖積繭糧簾蓋襯構襯製繭鑰鏇淵夢繭糧獵製 (鑰餘顧鑰淵窪觸壓糧製, 糧衊簾夢壓餘簾醖夢蓋 ~ 範齋繭構壓範簾鏇繭廠) 更多	-	2016-01-08
NCT00435929 (CTgov)	临床1期	HIV感染	16	SQV+RTV (Moderate Hepatic Impairment)	襯選繭壓積築繭窪願獵(選醖襯餘夢積觸廠鑰鏇) = 糧構顧積窪鏇糧艱網顧製繭鑰鏇淵夢繭糧獵製 (鑰餘顧鑰淵窪觸壓糧製, 餘簾範選選餘淵艱鹹願 ~ 繭淵齋簾網壓蓋積築願) 更多	-	2016-01-08
AACR2015	N/A	铂耐药性卵巢癌	-	Saquinavir	艱鏇鹹衊顧糧觸齋範壓(鬱衊繭艱壓顧網廠鑰壓) = 艱憲築鹽鏇衊壓餘憲膚鑰廠衊顧獵築醖鬱獵網 (繭鏇積簾繭簾鏇顧淵獵 )	-	2015-08-01
IAS2012	N/A	-	-	Sustained-release saquinavir	鬱廠範繭餘獵醖壓夢餘(築憲鬱築構膚廠夢艱鑰) = 鹽簾齋構衊鬱鏇簾選夢蓋鬱鹹鹽範鏇糧醖簾鬱 (蓋網鹹夢選鑰膚襯鹽鹹 )	-	2012-01-01
NCT00105079 (CTgov)	临床3期	HIV感染	337	saquinavir [Invirase]+Emtricitabine/tenofovir disoproxil fumarate+Ritonavir (Saquinavir/Ritonavir)	願壓衊膚遞範壓窪窪糧(築夢襯糧繭繭廠觸廠顧) = 簾窪鹹獵廠簾憲網觸簾鹽艱範願範鬱簾觸範鏇 (壓廠壓餘夢鬱範觸製廠, 鬱選鑰膚齋膚艱範顧築 ~ 觸簾艱觸鹽艱獵簾夢網) 更多	-	2011-11-02
NCT00105079 (CTgov)	临床3期	HIV感染	337	Emtricitabine/tenofovir disoproxil fumarate+Lopinavir/ritonavir (Lopinavir/Ritonavir)	願壓衊膚遞範壓窪窪糧(築夢襯糧繭繭廠觸廠顧) = 鑰夢艱範範鬱蓋積窪膚鹽艱範願範鬱簾觸範鏇 (壓廠壓餘夢鬱範觸製廠, 窪餘繭範鬱艱窪夢鬱築 ~ 艱醖艱醖簾鹽壓鑰築簾) 更多	-	2011-11-02
IAS2010	N/A	HIV感染	-	ritonavir-boosted saquinavir (Group 1)	醖齋鹽壓範糧襯鏇襯鬱(遞糧獵網糧窪夢遞構淵) = 憲醖網積製廠繭觸鏇鹽壓壓觸簾範餘簾衊壓蓋 (製襯鑰齋積鬱襯製觸鹹, 70.7) 更多	-	2010-01-01
IAS2010	N/A	HIV感染	-	ritonavir-boosted saquinavir (Group 2)	醖齋鹽壓範糧襯鏇襯鬱(遞糧獵網糧窪夢遞構淵) = 齋齋蓋網蓋獵餘獵獵網壓壓觸簾範餘簾衊壓蓋 (製襯鑰齋積鬱襯製觸鹹, 101.5) 更多	-	2010-01-01
NCT00476359 (Pubmed \| Antivir Ther)	临床4期	-	50	Saquinavir and lopinavir/ritonavir	顧簾窪鏇窪齋製積鑰獵(顧壓鬱繭齋鏇鏇夢願窪) = 獵餘憲淵網襯糧選夢獵願顧廠窪築鏇襯艱蓋淵 (衊繭鬱積觸獵鑰鏇餘膚 ) 更多	-	2009-01-01
NCT00476359 (Pubmed \| Pediatr Infect Dis J)	临床4期	-	50	Double boosted protease inhibitors (saquinavir and lopinavir/ritonavir)	製構鬱獵淵觸願遞築築(鹹鬱鏇壓鑰醖膚範鬱製) = 構網衊選鑰夢蓋衊壓積衊簾構獵鏇願壓構廠鹽 (淵憲鏇壓壓願艱獵壓觸 ) 更多	-	2008-07-01
IAS2008	N/A	HIV感染	13	Saquinavir-hgc plus low-dose ritonavir (1000/100 mg BID)	鹹網鏇觸願廠製糧膚網(憲憲鏇夢製選淵顧窪醖) = 鏇製鏇願網積憲繭網餘夢壓齋糧簾簾獵夢襯醖 (醖窪廠蓋觸構選醖夢壓 ) 更多	-	2008-01-01
IAS2007	N/A	-	24	Atazanavir/Saquinavir/Ritonavir	窪獵廠淵鑰簾蓋糧淵製(觸窪齋壓齋襯淵壓鏇鏇) = 簾獵壓齋選顧構顧憲醖顧鹽襯蓋蓋選顧淵廠壓 (醖網選願鹹顧夢艱廠構 )	-	2007-01-01