Oct 18, 2015 wilding jp, charpentier g, hollander p, et al. Food and drug administration fda has accepted the companys investigational new drug application ind for. Sep, 2017 new oral diabetes drug shows promise in phase 3 trial for patients with type 1 diabetes. The fda approved three new medicines containing the sglt2 inhibitor ertugliflozin with the indication of improving glycemic. Dapagliflozin for the treatment of type 2 diabetes. The coprimary endpoints were a threepoint mace endpoint and the combination of cv death or hospitalization for hf. Effects of dapagliflozin on symptoms, function and quality of life in patients with heart failure and reduced ejection fraction. Canagliflozincurrent status in the treatment of type 2. History of drug induced, immunemediated thrombocytopenia from exenatide products. A study to evaluate the effect of dapagliflozin on renal outcomes and cardiovascular mortality in patients with chronic kidney disease dapackd. Dapagliflozin propanediol pharmacokinetics absorption bioavailability. Jun 11, 2016 merck, pfizer amp up ertugliflozin outcomes study as sglt2 med scores in phiii. Based on new data from two large clinical trials, the fda has concluded that the type 2. Our pivotal intandem1 phase 3 clinical trial enrolled 793 patients with type 1 diabetes in the united states and canada in a randomized, doubleblind, placebocontrolled study of 200mg and 400mg once daily doses of sotagliflozin over a 24week treatment period, followed by a 28week extension.
Dapagliflozin in preserved ejection fraction heart failure. Dapagliflozin in patients with heart failure and reduced. A link to download a pdf version of the drug profile will be included in your email receipt. Vildagliptin versus dapagliflozin on glucagon full text. Sotagliflozin reduces aic in phase iii trial in type 1. Dapagliflozin is a new oral agent for type 2 diabetes with shortterm efficacy similar to dipeptidyl peptidase 4 inhibitors. Dapahf results in non diabetic patients clinical trial. The study started as a 4,000patient trial focused on. Dapagliflozin reduced the risk of worsening heart failure events and cardiovascular death and improved symptoms.
It is an inhibitor of the sodium glucose cotransporter, resident in the proximal nephron, which is responsible for the recovery of filtered glucose back into circulation. The food and drug administration fda or agency plays a critical role in protecting the united states from threats. Topline results from the global version of the trial intandem3 revealed a concerning increase in risk of dka 3% of those taking sotagliflozin experienced dka, compared to 0. Fda revises label of diabetes drug canagliflozin invokana, invokamet to include updates on bone fracture risk and new information on. Internal medicine, family practice, pharmacy, patient issue. Dec 21, 2017 endocrinology type 2 diabetes new oral ertugliflozin for t2d approved by fda okd in single and fixeddose combo therapies.
The eu clinical trials register currently displays 36867 clinical trials with a eudract protocol, of which. Demonstrating substantial evidence of effectiveness for. Some patients had more than 1 amputation, some involving both limbs. First results from phase 3 canvas trial show canagliflozin as. There is a combination product dapagliflozin metformin extendedrelease, called xigduo xr. One adequate and wellcontrolled large multicenter trial that can provide. Sep 09, 2016 the third type 1 diabetes phase 3 clinical trial, intandem3, is underway globally and is studying approximately 1,400 patients treated with sotagliflozin 400mg once daily or placebo on a background of any insulin therapy, but without insulin optimization prior to randomization. Canagliflozin, dapagliflozin warnings strengthened by fda. Multicenter trial to evaluate the effect of dapagliflozin on the incidence of cardiovascular events declaretimi58 this trial examines the cardiovascular safety and efficacy of dapagliflozin in patients with type 2 diabetes with either established cardiovascular disease.
Merck and pfizer plan to submit ertugliflozin for fda. In february 2017, the fda approved a oncedaily combination of dapagliflozin and saxagliptin, as qtern. Dapagliflozin dapagliflozin added at 10 mg once daily for two weeks followed by four weeks washout and then vildagliptin 50 mg twice daily for two weeks. This material is provided for educational purposes only and is not intended for medical advice, diagnosis or treatment. The purpose of this study is to evaluate the effect of dapagliflozin on renal outcomes and cardiovascular mortality in patients with chronic kidney disease. Oral sotagliflozin succeeds in phase 3 diabetes trial. Safety and efficacy of ertugliflozin in the treatment of. This page provides links to commonly used clinical trial forms relevant to clinical trials. Dec 21, 2017 fda approves ertugliflozin for type 2 diabetes. Assessing bladder cancer risk in type 2 diabetes clinical trials.
Dapagliflozin and cardiovascular outcomes in type 2. Currently it is in phaseii trial for the treatment of obesity in the united states and europe. Before sharing sensitive information, make sure youre on a federal government site. There have been no clinical studies establishing conclusive evidence of macrovascular risk reduction with farxiga or any other antidiabetic drug. Listing a study does not mean it has been evaluated by the u. Canagliflozin kan a gli floe zin is a specific sglt2 inhibitor that in clinical trials was shown to result in a reduction in serum hba1c levels and improved glycemic control in type 2 diabetes, both as monotherapy in patients who failed to achieve adequate control on diet and exercise or in combination with insulin, metformin andor sulfonylureas. Dapagliflozin in preserved ejection fraction heart failure preservedhf. Bexagliflozin efficacy and safety trial best full text.
Sglt2 inhibitors are a class of prescription medicines that are fda approved for use with diet and exercise to lower blood sugar in adults with. On september 10, 2015, the fda issued a drug safety communication for canagliflozin to address risks for bone fracture and decreased bone density. Will a dmc help assure the scientific validity ofthe trial. Astrazeneca today announced positive results from the landmark phase iii dapahf trial which showed that farxiga dapagliflozin met the primary composite endpoint with a statisticallysignificant and clinicallymeaningful reduction of cardiovascular death or the worsening of heart failure defined as hospitalisation or an urgent heart failure visit, compared to placebo. Canagliflozin is also used to reduce the risk of endstage kidney disease, worsening of kidney function, needing to be hospitalized for heart failure, and cardiovascular death in people who have type 2 diabetes along with severe kidney disease. Dapagliflozin is the international nonproprietary name inn, and the united states adopted name usan. Sotagliflozin reduces aic in phase iii trial in type 1 diabetes september 19, 2016 lexicon pharmaceuticals announced that a phase iii clinical trial of sotagliflozin met its primary endpoint, demonstrating a significant reduction in a1c at 24 weeks in patients with type 1 diabetes on a background of optimized insulin. The declaretimi 58 trial was a randomized, doubleblind, multinational, placebocontrolled, phase 3 trial of dapagliflozin in patients with type 2 diabetes and. The dapahf trial showed that dapagliflozin was superior to placebo at preventing cardiovascular deaths and heart failure events.
For adults with type 2 diabetes, farxiga is a prescription medicine used to reduce the risk of hospitalization for heart failure in patients with known cardiovascular cv disease or multiple cv risk factors, and to improve blood sugar control along with diet and exercise. New oral diabetes drug shows promise in phase 3 trial for. Canagliflozin therapy is associated with an increased risk of requiring lower limb amputation. The fda new drug application for sotagliflozin is based on data from the intandem clinical trial program which includes three phase 3 clinical trials assessing the safety and efficacy of zynquista in approximately 3,000 adults with inadequately controlled type 1 diabetes. The goal of the trial was to evaluate dapagliflozin a sodiumglucose cotransporter 2 sglt2 inhibitor compared with placebo among patients with heart failure with reduced ejection fraction hfref. Canagliflozin invokana is a drug prescribed for the treatment of type 2 diabetes in combination with diet and exercise. A study to evaluate the effect of dapagliflozin on renal. New oral ertugliflozin for t2d approved by fda medpage today. Canagliflozin is in a class of medications called sodiumglucose cotransporter 2 sglt2 inhibitors. Dapagliflozin in heart failure in this randomized, placebocontrolled trial, investigators evaluated the effects of the sodiumglucose cotransporter 2 inhibitor dapagliflozin in patients with.
Assessing bladder cancer risk in type 2 diabetes clinical. Efficacy and safety of dapagliflozin in hfref according to age. Dapagliflozin was the first drug in a class of therapies that took a new approach to glycemic control in adults with type 2 diabetes t2d. Epub ahead of print dapagliflozin effects on biomarkers, symptoms, and functional status in patients with heart failure with reduced ejection fraction. Two of the five new trials trials 18 and 19 contributed the largest sample size and the longest exposure duration in.
The 2019 dapahf trial was conducted to study whether the addition of the sglt2 inhibitor dapagliflozin could benefit patients with hfref, either with or without t2dm. The most common adverse reactions observed with dapagliflozin in clinical trials were female genital mycotic infections, urinary tract infections, and nasopharyngitis. Farxiga met primary endpoint in landmark phase iii dapahf. Oct 02, 2012 first results from phase 3 canvas trial show canagliflozin as addon therapy to insulin lowered blood sugar levels in patients with type 2 diabetes at an elevated risk for cardiovascular disease. The risk of lower limb amputations has been observed at both the 100 mg and 300 mg doses. Nonmetastatic, castrationresistant prostate cancer fda.
Participation in any interventional clinical trial with an investigational drug or device that is not an observational registry within 15 days of the screening visit. Janssen files with fda for cv indication for canagliflozin. This guidance document is for comment purposes only. Multicenter trial to evaluate the effect of dapagliflozin. Element of informed consent for applicable clinical trials. Dapagliflozin is a small molecule drug for reducing blood glucose and treating type2 diabetes mellitus. Data sources include ibm watson micromedex updated 28 feb 2020, cerner multum updated 2 mar 2020, wolters kluwer updated. The efficacy and safety of invokana for glycemic control were evaluated in a trial that included patients with moderate renal impairment egfr 30 to dapagliflozin is the international nonproprietary name inn, and the united states adopted name usan. Dapagliflozin effect on cardiovascular events a multicenter, randomized, doubleblind, placebocontrolled trial to evaluate the effect of dapagliflozin 10 mg once daily on the incidence of cardiovascular death, myocardial infarction or ischemic stroke in patients with type 2 diabetes. Sep 09, 2016 oral sotagliflozin succeeds in phase 3 diabetes trial september 9, 2016 a pivotal phase 3 study of oral sotagliflozin lexicon pharmaceuticals has met its primary endpoint, showing a statistically significant reduction in hemoglobin a 1c hba 1c at 24 weeks in patients with type1 diabetes on a background of optimized insulin. The european trial results were similar, with 32% of trial participants benefitting from sotagliflozin, compared to only 15% of the placebo group. Canagliflozin treatment in patients with type 2 diabetes mellitus. Farxiga dapagliflozin is indicated as an adjunct to diet and exercise to improve glycemic.
The function of the controlled clinical trial is not the discovery of a new drug or. Fda revises label of diabetes drug canagliflozin invokana, invokamet to include updates on bone fracture risk and new information on decreased bone mineral density. For questions on clinical trial conduct during the covid19 pandemic. Dapagliflozin is a cglycosyl comprising betadglucose in which the anomeric hydroxy group is replaced by a 4chloro34ethoxybenzylphenyl group.
There is a vast, ambitious, and promising ongoing clinical investigation program with dapagliflozin and other sglt2 inhibitors, which may result in changes to the therapeutic approach to hf in a relatively short time. Farxiga should not be used in patients with active bladder cancer and should be used with caution in patients with a prior history of bladder cancer. The recently published dapagliflozin effects on biomarkers, symptoms, and functional status in patients with heart failure with reduced ejection fraction definehf trial is. Evaluation of dapagliflozin taken twicedaily full text. Canagliflozin showed mutagenicity in laboratory mouse lymphoma assay, but only in the activated state. Dapahf randomly assigned nearly 5,000 patients receiving standard medical care to dapagliflzin or placebo. Jun 15, 2014 it was initially rejected by fda due to serious concerns about bladder and breast cancer. If you have problems opening a pdf form in your browser, try downloading it instead. Sep 23, 2015 bexagliflozin efficacy and safety trial best best the safety and scientific validity of this study is the responsibility of the study sponsor and investigators.
Consider patient factors that may increase the risk of the need for. Administration with a highfat meal decreased peak plasma concentration by up to 50% and prolonged time to peak plasma concentration by approximately 1 hour. Used in the formo f its propanediol monohydrate to improve glycemic control, along with diet and exercise, in adults with type 2 diabetes. Research finds sotagliflozin may be first to improve glucose control without weight gain or increase in. Jan 15, 2014 a phase iii, multicenter, randomized, doubleblind, placebocontrolled, parallelgroup clinical trial to evaluate the safety and efficacy of ertugliflozin mk8835pf04971729 in the treatment of subjects with type 2 diabetes mellitus who have inadequate glycemic control on metformin and sitagliptin.
Dapagliflozin is an oral, oncedaily, sodium glucose cotransporter type 2. Lexicon reports positive topline results in pivotal phase 3. Food and drug administration fda has strengthened the existing warning about the risk of acute kidney injury for the type 2 diabetes medicines canagliflozin invokana. In the credence trial, the rate of lower limb amputations associated with the use of canagliflozin 100 mg relative to placebo was 12. John j v mcmurrays presentation slides pdf discussant slides pdf dapahf circulation. Avolynt, a privately held biotech company focused on the development of therapeutics for metabolic diseases, announced today that the u.
Fda revises label of diabetes drug canagliflozin invokana, invokamet. Dapagliflozin effects on biomarkers, symptoms, and. For patients requiring a dose of 5 mg dapagliflozin and 2000 mg metformin hcl extendedrelease, use two of the 2. Dapagliflozin propanediol monograph for professionals. The fda new drug application for sotagliflozin is based on data from the intandem clinical trial program which includes three phase 3 clinical trials assessing the safety and efficacy of zynquista. Please read for full product information, including boxed warning, and medication guide for invokana. A clinical trial that we required the manufacturer of.
Ipragliflozin, empagliflozin and many other sglt2 inhibitors are under. Food and drug administration fda is alerting the public about interim safety results from an ongoing clinical trial that found an increase in leg and foot amputations. Innovative trial designs for drugs and biological products. The declaretimi 58 trial is by a considerable margin the largest of the sglt2 inhibitor cv outcome trials, and like the canvas trial specifically included both a primary and secondary prevention population. Fda guidance on conduct of clinical trials of medical products. Canagliflozin was the first of its kind to get approval from fda on march 29, 20. Informed consent information sheet draft guidance fda. Clinical trials for dapagliflozin the european union clinical trials register allows you to search for protocol and results information on. Invokana canagliflozin dose, indications, adverse effects. The fda has strengthened its drug label warnings about the risk for acute kidney injury in patients taking canagliflozin or dapagliflozin for type 2 diabetes. Merck, pfizer amp up ertugliflozin outcomes study as sglt2.
The fda is continuing to investigate the issue, and cautions that patients should not stop taking canagliflozin without first talking to their doctor. For patients not already taking dapagliflozin, the recommended starting dose for dapagliflozin is 5 mg once daily. The carcinogenic risk of canagliflozin was assessed in 2year studies completed in both cd1 mice and spraguedawley rats. Evaluation of dapagliflozin taken twicedaily the safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Symptoms of a serious allergic reaction may include skin rash, raised red patches on your skin hives, swelling of the face, lips, tongue, and throat that may cause difficulty in breathing or swallowing. Invokana canagliflozin janssen prescription assistance. Efficacy and safety of canagliflozin in patients with type 2 diabetes mellitus inadequately controlled with metformin and sulphonylurea. Fda approves farxiga dapagliflozin to reduce the risk of. Effect of dapagliflozin on worsening heart failure and. Call your doctor for medical advice about side effects. Drug safety communication increased risk of leg and foot amputations posted 05162017 audience.
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