Age: Any Age
Sex: Any
Travel: May be covered
Time Reimbursement: Varies
Trial Phase: Phase 3
Verified Trial
Recruiting
Sponsor: Areteia Therapeutics
Pivotal Trial (Near Approval)
Prior Safety Data
Trial Summary
What is the purpose of this trial?This trial is testing a medication called dexpramipexole to see if it can help people with severe eosinophilic asthma that isn't well-controlled by current treatments. The medication works by lowering the levels of certain cells in the blood that cause inflammation. The goal is to find out if this can improve asthma symptoms and be safe for patients.
Do I need to stop my current medications to join the trial?The trial does not specify that you need to stop your current medications. However, you must be on a stable dose of your asthma medications for at least 3 months before joining. Some specific medications, like certain monoclonal antibodies and pramipexole, must be stopped before the trial. Please consult with the trial team for more details.
Is the drug Dexpramipexole Dihydrochloride a promising treatment for asthma?The provided research articles do not contain information about Dexpramipexole Dihydrochloride or its use in treating asthma, so we cannot determine if it is a promising treatment for asthma based on this data.7891114
What data supports the idea that Dexpramipexole for Asthma is an effective drug?The available research does not provide any data on the effectiveness of Dexpramipexole for Asthma. Instead, it discusses other treatments like Fevipiprant, Tiotropium, and YM934, which have shown some effectiveness in treating asthma. For example, Fevipiprant showed improvement in lung function, and Tiotropium was effective as an add-on therapy for asthma. YM934 demonstrated potent anti-asthma activity in experimental models. However, there is no specific information on Dexpramipexole's effectiveness for asthma in the provided research.610121315
What safety data is available for Dexpramipexole in asthma treatment?The provided research does not contain specific safety data for Dexpramipexole or its other names in the context of asthma treatment. The studies focus on other potassium channel openers like cromakalim, lemakalim, and bimakalim, assessing their effects on airway smooth muscle and asthma symptoms. The study on bimakalim mentions that it was well tolerated with no significant adverse effects, but this does not directly apply to Dexpramipexole.12345
Eligibility Criteria
This trial is for adolescents and adults over 12 years old with severe eosinophilic asthma that isn't well-controlled. They should have had at least two asthma attacks in the last year needing steroids, an eosinophil count above a certain level, and not be current smokers or have a heavy smoking history. Women who can get pregnant must use birth control.Exclusion Criteria
I have had a severe asthma attack within 4 weeks before my first screening visit up to now.
I have not had a bronchial thermoplasty in the last year nor plan to have one this coming year.
I have not had a respiratory infection in the last 4 weeks.
Treatment Details
The study tests dexpramipexole's safety and effectiveness against a placebo in managing severe eosinophilic asthma. Participants will randomly receive either the actual drug or a placebo to compare outcomes between the two groups.
3Treatment groups
Experimental Treatment
Placebo Group
Group I: 75 mg BIDExperimental Treatment1 Intervention
Dexpramipexole 75 mg oral tablet taken twice a day
Group II: 150 mg BIDExperimental Treatment1 Intervention
Dexpramipexole 150 mg oral tablet taken twice a day
Group III: PlaceboPlacebo Group1 Intervention
Placebo oral tablet taken twice a day
Find a clinic near you
Research locations nearbySelect from list below to view details:
ClinCloud, VieraViera, FL
Tandem Clinical Research, MarreroMarrero, LA
ClinCloud, MaitlandMaitland, FL
LINQ Research LLCPearland, TX
More Trial Locations
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Who is running the clinical trial?
Areteia TherapeuticsLead Sponsor
References
RP 49356 and cromakalim relax airway smooth muscle in vitro by opening a sulphonylurea-sensitive K+ channel: a comparison with nifedipine. [2014]RP 49356 is a novel compound which relaxes airway smooth muscle in vitro. Like cromakalim, RP 49356 reduced contractility in guinea pig isolated trachealis under basal conditions or when challenged with low (less than 20 mM) but not high K+. These effects were antagonized by the sulphonylureas glibenclamide and glipizide. This spectrum of action is typical of the class of compounds known as potassium channel openers (KCOs). Unlike RP 49356 and cromakalim, nifedipine had no effect on basal tone, relaxed tissues contracted with low or high K+ and was not antagonized by the sulphonylureas. These data suggest that the KCOs are not acting directly at the voltage-gated Ca++ channel in this tissue. RP 49356 and cromakalim were similar to nifedipine by being more potent at relaxing tissues precontracted with carbachol or histamine (spasmolytic effects) than they were at preventing initiation of the response to these spasmogens (antispasmogenic effects). Because the maintained phase of contraction in airway smooth muscle may be associated with some Ca++ influx, the data presented here suggests that, like nifedipine, the KCOs are more active smooth muscle relaxants under conditions of Ca++ influx. In summary, RP 49356, like cromakalim, is a compound which relaxes airway smooth muscle in vitro by opening a sulphonylurea-sensitive K+ channel which may be similar to the ATP-sensitive K+ channel found in other tissues.
Attenuation of nocturnal asthma by cromakalim. [2019]In a randomised, double-blind, crossover study, single oral doses of cromakalim, a potassium-channel activator, or placebo were given to 23 patients with nocturnal asthma. There was a significant reduction (p less than 0.005) in the early morning fall in forced expiratory volume in 1 s (FEV1) after 0.5 mg cromakalim (fall 9.8% [SEM 3.2%]) compared with placebo (18.5 [2.8]%). In a repeat dosing study, administration of 0.25 mg and 0.5 mg cromakalim on 5 consecutive nights to a further group of 8 asthmatic subjects significantly reduced the early morning fall in FEV1 from 28.7 (6.5)% after placebo to 19 (4.2)% after 0.25 mg and 14.9 (6.5)% after 0.5 mg. Potassium-channel activators may be useful in the treatment of asthma, especially for nocturnal symptoms.
The action of a potassium channel activator, BRL 38227 (lemakalim), on human airway smooth muscle. [2014]Potassium (K+) channels are present on airway smooth muscle cells, and their activation results in hyperpolarization and relaxation. Because these effects may have therapeutic relevance to asthma, we examined the activity of the active L-enantiomer of cromakalim, BRL 38227 (lemakalim), a selective K+ channel activator, against a variety of spasmogens in human bronchi in vitro. BRL 38227 produced relaxation of bronchi with either resting tone or tone induced by histamine, carbachol, neurokinin A, or KCl (20 mM) with an efficacy (%Emax) of 60 to 80% of that of isoproterenol and an EC50 (the concentration producing 50% of the maximal response) of 0.2 to 0.6 microM. However, BRL 38227 had a significantly lower potency and efficacy against 80 mM KCl than against the other spasmogens (%Emax, 12% of isoproterenol and EC50, 7.2 microM; p less than 0.005 and p less than 0.001, respectively), supporting the view that BRL 38227 acts on K+ channels. The D-enantiomer BRL 38226 was less potent (EC50, 2.6 microM) than BRL 38227 and produced only 43% of the isoproterenol relaxation. BRL 38227-induced relaxation was significantly inhibited by the ATP-sensitive K+ channel antagonist glibenclamide (0.1 and 1 microM), with a three-fold and eight-fold shift to the right of the dose-response curve, respectively. In the presence of a maximal relaxation induced by the calcium voltage-dependent channel antagonist verapamil, BRL 38227 was able to produce an additional 37% relaxation response. Thus, BRL 38227 is an effective relaxant of human airway smooth muscle, and this activity results from an action at K+ channels.(ABSTRACT TRUNCATED AT 250 WORDS)
Bradykinin-induced bronchoconstriction: inhibition by nedocromil sodium and sodium cromoglycate. [2019]1. The effects of inhaled nedocromil sodium and sodium cromoglycate on bradykinin-induced bronchoconstriction have been studied in a double-blind, placebo controlled study, in eight mild asthmatic subjects. 2. The subjects attended on four occasions. Fifteen minutes after drug pre-treatment a bradykinin challenge was performed. Increasing concentrations were inhaled until a greater than 40% fall in expiratory flow at 30% of vital capacity from a partial flow volume manoeuvre (V p30) was demonstrated. 3. Inhaled bradykinin (0.06-8.0 mg ml-1) caused dose-related bronchoconstriction with the geometric mean cumulative dose causing a 40% fall in V p30 (PD40) of 0.035 (95% CI: 0.02-0.07) mumol, after placebo inhalation, which was similar to that measured before the trial (0.04: 0.02-0.09 mumol). 4. Both nedocromil sodium (4 mg) and sodium cromoglycate (10 mg) gave significant protection (P less than 0.05) against bradykinin-induced bronchoconstriction (PD40 0.37: 0.19-0.72 mumol after nedocromil sodium and 0.22: 0.11-0.49 after sodium cromoglycate). 5. Since bradykinin-induced bronchoconstriction is probably neurally mediated we conclude that both nedocromil sodium and sodium cromoglycate have an action on neural pathways which may be useful in the control of asthma symptoms.
The lack of bronchodilator effect and the short-term safety of cumulative single doses of an inhaled potassium channel opener (bimakalim) in adult patients with mild to moderate bronchial asthma. [2019]The aim of this study was to assess the bronchodilator effect and short-term safety of cumulative single doses of inhaled bimakalim (E Merck, Darmstadt), a potassium channel opener, compared to placebo in 12 adult patients with chronic, mild to moderate, non-allergic bronchial asthma. The study was a randomized, placebo-controlled, cross-over study and the only efficacy variable measured was the forced expiratory volume in one second (FEV1). The patients had an FEV-1 > 50% of predicted normal value and a reversibility of more than 15% at entrance to the study. Inhaled bimakalim and placebo were delivered by a Pariboy nebulizer. The doses tested in a cumulative manner were 10, 25, 40 and 100 micrograms (total cumulative dose 175 micrograms), each individual dose given at 60-min intervals. Plasma bimakalim concentrations were measured at time 0 and 60 min after each dose. No bronchodilator effect was shown, with inhaled bimakalim at the doses tested. Reasons for the lack of efficacy of inhaled bimakalim in this study may be due to low doses of administered drug or to a true lack of bronchodilatation effect in the study patients. Inhaled bimakalim was well tolerated. No headache or cardiovascular events were seen with the cumulative dose of 175 micrograms bimakalim.
Effect of YM934, a novel potassium-channel opener, in various experimental asthma models in guinea-pigs. [2019]YM934 is a novel synthetic potassium-channel opener. We have investigated its anti-asthma effect after intravenous (i.v.) and oral (p.o.) administration in various experimental asthma models in the guinea-pig, and compared the results with those for lemakalim, theophylline and salbutamol. In an ovalbumin-active sensitization anaphylaxis asthma model, YM934, lemakalim, theophylline and salbutamol dose-dependently prolonged the time before the occurrence of asthma attacks and reduced the mortality rate. The respective ED50 values (dose required to prolong by 50% the time before the occurrence of attacks) of the anti-asthma effects of YM934, lemakalim, theophylline and salbutamol were 6, 340, 30000, and 45 micrograms kg-1 (i.v.); the efficacy ratios were YM934 (1) > salbutamol (1/9) > lemakalim (1/57) > > theophylline (1/5000). YM934 also prolonged the period before the occurrence of attacks in the anti-BSA (bovine serum albumin) serum-passive sensitization anaphylaxis, histamine-induced and methacho-line-induced asthma models, with respective ED50 values for these models of 15, 22 and 20 micrograms kg-1 (i.v.). Among these models a reduction in mortality rate was seen in the histamine- and methacholine-induced asthma models. After oral administration, YM934 showed an anti-asthma effect in the ovalbumin-active sensitization anaphylaxis, histamine-induced and methacholine-induced asthma models, with respective ED50 values of 38, 44 and 193 micrograms kg-1. YM934 was 5-6 times more potent than salbutamol. These results indicate that YM934 has potent anti-asthma activity, and that this activity is mainly attributable to bronchodilation, most likely mediated through its potassium-channel opening activity.
Oral bioavailability of a novel paclitaxel formulation (Genetaxyl) administered with cyclosporin A in cancer patients. [2021]The formulation excipient Cremophor EL (CrEL) is known to limit the absorption of oral paclitaxel given together with cyclosporin A. We hypothesized that the use of oral Genetaxyl, a paclitaxel formulation containing only 20% CrEL would have an improved oral bioavailability. Cohorts of six patients were treated with oral Genetaxyl at a dose of 60, 120, or 180 mg/m2 and 10 mg/kg of oral cyclosporin A in cycle 1. In cycle 2, patients received intravenous (i.v.) Genetaxyl (175 mg/m2, 3-h infusion). Three additional patients received one dose of generic i.v. paclitaxel (Genaxol, containing 50% CrEL; 175mg/m2, 3-h infusion). The median area under the plasma concentration-time curve (AUC) and peak concentration of total paclitaxel following i.v. Genetaxyl were lower than those for i.v. Genaxol, as a result of significantly increased clearance (P = 0.017), and the AUC ratio for unbound to total paclitaxel for i.v. Genetaxyl was about two times higher than that for i.v. Genaxol (P = 0.0077). After oral administration of Genetaxyl at doses of 60, 120, and 180 mg/m2, the median total paclitaxel AUCs were 1.29, 1.60, and 1.85 microg x h/ml, respectively, suggesting a less than proportional increase in systemic exposure with increasing doses. The corresponding median values for the apparent bioavailability of oral Genetaxyl were similar when compared with i.v. Genetaxyl, when calculated either on the basis of data for total paclitaxel (30.1%) or unbound paclitaxel (30.6%).
Current state of the art of new tubulin inhibitors in the clinic. [2019]For years the microtubule stabilizing agents docetaxel and paclitaxel belong to the most successful clinical chemotherapeutic agents. Several attempts have been made over the years to equal and better these drugs. Both taxanes are associated with the notorious side effect neurotoxicity and are often accompanied with increased drug resistance and cross resistance with other chemotherapeutic agents. In addition their high lipophilicity demands use of co-solvents, which are associated with less favorable side effects such as hypersensitivity. To prevent these disadvantages and improve the clinical application of the taxanes several new agents have entered clinical testing. The agents that are discussed are the drug class of the discodermolides; XAA296A and the epothilones; BMS-247550, BMS-310705, epo906, kos-862 and the agents ABT-751 and D-24851. Here we present an overview of recently performed clinical studies to determine the current state of the art of the tubulin inhibitors which are intended to enlarge and improve the clinical use of the taxanes docetaxel and paclitaxel.
Preparation and evaluation of Cremophor-free paclitaxel solid dispersion by a supercritical antisolvent process. [2015]To avoid the major adverse effects induced by Cremophor EL formulated in the commercial paclitaxel products of Taxol.
Efficacy of anticholinergic drugs in asthma. [2012]Although bronchial hyperresponsiveness to cholinergic agents is a main feature of asthma, the role of anticholinergic drugs in chronic asthma management has been largely underestimated. Several single-dose studies comparing acute bronchodilation induced by ipratropium bromide with salbutamol have shown that salbutamol was more effective than ipratropium in asthma treatment. Recently, tiotropium has been studied in asthma, when added to low-dose inhaled corticosteroids in unselected moderate asthmatics or in patients with uncontrolled asthma, or patients with chronic obstructive pulmonary disease and history of asthma. Later, studies on patients with Arg/Arg β(2)-receptor polymorphism demonstrated a similar efficacy of tiotropium in comparison with salmeterol when both were added to low-dose inhaled corticosteroids. Further long-term studies are currently in progress, for the evaluation of the efficacy of tiotropium on clinical asthma control, and on the rate and severity of asthma exacerbations, as well as the potential modification of inflammatory mechanisms and varying efficacy in specific asthma phenotypes (such as smoking asthmatics).
Update on taxane development: new analogs and new formulations. [2022]The taxanes (paclitaxel and docetaxel) represent an important class of antineoplastic agents that interfere with microtubule function leading to altered mitosis and cellular death. Paclitaxel (Taxol(®)) was originally extracted from a yew tree (Taxus spp., Taxaceae) a small slow-growing evergreen, coniferous tree. Due to the initial scarcity of paclitaxel, docetaxel (Taxotere(®)) a semisynthetic analog of paclitaxel produced from the needles of European yew tree, Taxus baccata was developed. Docetaxel differs from paclitaxel in two positions in its chemical structure and this small alteration makes it more water soluble. Today, paclitaxel and docetaxel are widely prescribed antineoplastic agents for a broad range of malignancies including lung cancer, breast cancer, prostate cancer, Kaposi's sarcoma, squamous cell carcinoma of the head and neck, gastric cancer, esophageal cancer, bladder cancer, and other carcinomas. Although very active clinically, paclitaxel and docetaxel have several clinical problems including poor drug solubility, serious dose-limiting toxicities such as myelosuppression, peripheral sensory neuropathy, allergic reactions, and eventual development of drug resistance. A number of these side effects have been associated with the solvents used for dilution of these antineoplastic agents: Cremophor EL for paclitaxel and polysorbate 80 for docetaxel. In addition, reports have linked these solvents to the alterations in paclitaxel and docetaxel pharmacokinetic profiles. In this review, we provide preclinical and clinical data on several novel taxanes formulations and analogs which are currently US Food and Drug Administration (FDA)-approved or in clinical development in various solid tumor malignancies. Of the new taxanes nab-paclitaxel and cabazitaxel have enjoyed clinical success and are FDA-approved; while many of the other compounds described in this review are unlikely to be further developed for clinical use in daily practice. Furthermore, the successful clinical emergence of novel nontaxane microtubule-targeting chemotherapy agents such as epothilones and eribulin is liable to further restrict the development of novel taxanes.
Safety and tolerability of once-daily tiotropium Respimat(®) as add-on to at least inhaled corticosteroids in adult patients with symptomatic asthma: A pooled safety analysis. [2018]Tiotropium, a long-acting anticholinergic bronchodilator, has demonstrated efficacy and safety as add-on therapy to inhaled corticosteroids (ICS), with or without other maintenance therapies, in patients with symptomatic asthma.
Fevipiprant, an oral prostaglandin DP2 receptor (CRTh2) antagonist, in allergic asthma uncontrolled on low-dose inhaled corticosteroids. [2022]Dose-related efficacy and safety of fevipiprant (QAW039), an oral DP2 (CRTh2) receptor antagonist, was assessed in patients with allergic asthma uncontrolled by low-dose inhaled corticosteroids (ICS).Adult patients were randomised to 12 weeks' treatment with once-daily (1, 3, 10, 30, 50, 75, 150, 300 or 450 mg q.d) or twice-daily (2, 25, 75 or 150 mg b.i.d) fevipiprant (n=782), montelukast 10 mg q.d (n=139) or placebo (n=137). All patients received inhaled budesonide 200 μg b.i.dFevipiprant produced a statistically significant improvement in the primary end-point of change in pre-dose forced expiratory volume in 1 s at week 12 (p=0.0035) with a maximum model-averaged difference to placebo of 0.112 L. The most favourable pairwise comparisons to placebo were for the fevipiprant 150 mg q.d and 75 mg b.i.d groups, with no clinically meaningful differences between q.d and b.i.d Montelukast also demonstrated a significant improvement in this end-point. No impact on other efficacy end-points was observed. Adverse events were generally mild/moderate in severity, and were evenly distributed across doses and treatments.Fevipiprant appears to be efficacious and well-tolerated in this patient population, with an optimum total daily dose of 150 mg. Further investigations into the clinical role of fevipiprant in suitably designed phase III clinical trials are warranted.
Paclitaxel. [2019]Paclitaxel is the first microtubule-stabilizing agent identified and considered to be the most significant advance in chemotherapy of the past two decades. It is considered one of the most widely used antineoplastic agents with broad activity in several cancers including breast cancer, endometrial cancer, non-small-cell lung cancer, bladder cancer, and cervical carcinoma. It is also used for treating AIDS-related Kaposi sarcoma as a second line treatment. This comprehensive profile of paclitaxel gives overview of nomenclature, formulae, elemental analysis, appearance, application and uses. In addition, mechanism of action and resistance, different dosage forms and methods of drug preparation are elaborated. Moreover, the physicochemical properties involving X-ray powder diffraction pattern, drug solubility, melting point, differential scanning calorimetry, and stability were summarized. Furthermore, method of drug analysis including compendial, spectrophotometric, and chromatographic was discussed.
New perspectives on the role of muscarinic antagonists in asthma therapy. [2021]Label="INTRODUCTION">There is increasing evidence that tiotropium, a long-acting muscarinic agent (LAMA), is useful in the presence of severe-uncontrolled asthma despite the optimization of therapy with inhaled corticosteroids (ICSs) and long-acting β2 agonists (LABAs) as recommended by the current guidelines. Furthermore, in recent years there have been several  preclinical and clinical studies on the pharmacological and therapeutic impact of other LAMAs in asthma.