Fosmanogepix (FMGX, APX001), a first-in-class, intravenous (i.v.) and oral (p.o.) antifungal prodrug candidate is currently in clinical development for the treatment of invasive fungal infections. Manogepix (MGX, APX001A), active moiety FMGX, interferes with cell wall synthesis by targeting glycosylphosphatidylinositol-anchored transfer protein 1, thereby causing loss viability. Data from two phase placebo-controlled, single-ascending dose (SAD) multiple-ascending (MAD) studies evaluating...

Abstract Objective To evaluate the impact of two calcitonin gene–related peptide (CGRP)‐targeted monoclonal antibodies (mAbs), erenumab and galcanezumab, on pharmacokinetic (PK) profile, safety, tolerability ubrogepant. Background People taking CGRP‐targeted mAbs for migraine prevention sometimes take ubrogepant, an oral small‐molecule CGRP receptor antagonist, acute treatment breakthrough attacks. Design In this two‐arm, multicenter, open‐label, phase 1b trial, adults with were randomized...

Abstract Atogepant is a selective oral calcitonin gene‐related peptide receptor antagonist in development for migraine prevention. Here, we report the pharmacokinetics (PK) and safety of single‐dose 60 mg atogepant participants with severe, moderate, or mild hepatic impairment matched normal function from an open‐label, parallel‐group, phase 1 trial. Thirty‐two aged 45 to 72 years were enrolled, which included 8 each mild, no impairment. All completed study. was rapidly absorbed (median time...

Objectives: Rimegepant orally disintegrating tablet (ODT) is indicated for acute treatment of migraine (with and without aura) at 75 mg up to once per day preventive episodic every other (EOD) in adults [1]. The objective this study was refine rimegepant population pharmacokinetic (PPK) model using adult pediatric PK data, predict exposures, provide dosing selection, populations across different age body-weight ranges efficacy safety studies. Methods: An established PPK further developed...

Background Ubrogepant is a novel, oral calcitonin gene–related peptide (CGRP) receptor antagonist in development for the acute treatment of migraine. This trial evaluated safety and tolerability ubrogepant, focusing on hepatic safety, when administered intermittently with high-frequency dosing to healthy participants. Methods In this phase 1, multicenter, double-blind, parallel-group trial, adults (age 18–50 years) were randomized 1:1 placebo or ubrogepant. was dosed at 100 mg (2 × 50...

ABSTRACT Immunocompromised patients are susceptible to fungal infections, and drug-drug interactions with antifungals may occur due concomitant medications. Fosmanogepix [FMGX; active moiety manogepix (MGX)] targets glycosylphosphatidylinositol-anchored mannoprotein synthesis maturation, essential for virulence. This phase 1, fixed-sequence study in healthy participants evaluated the effect of strong CYP3A4 inhibitor itraconazole [Cohort 1 ( n = 18); FMGX 500 mg intravenous (IV) twice a day...

Abstract Ceftaroline fosamil is a parenteral cephalosporin indicated for the treatment of acute bacterial skin and structure infections community‐acquired pneumonia. Ceftaroline, active component ceftaroline fosamil, exhibits broad‐spectrum bactericidal activity against gram‐positive organisms, including methicillin‐resistant Staphylococcus aureus Streptococcus pneumoniae , as well common gram‐negative pathogens. The objective studies presented herein was to establish pharmacokinetic profile...

Background The full utility of an acute treatment requires examination the entire time course effect during a migraine attack. Here ubrogepant is evaluated. Methods ACHIEVE-I and -II were double-blind, single-attack, Phase 3 trials. Adults with randomised 1:1:1 to placebo or (50mg 100mg, ACHIEVE-I; 25 mg 50 mg, ACHIEVE-II). Pain freedom, absence most bothersome symptom, pain relief assessed at various timepoints. Samples collected for pharmacokinetic analysis. Data pooled this post-hoc...

Aim: To evaluate pharmacokinetic interactions of atogepant with sumatriptan, an open-label, randomized, crossover study was conducted. Patients & methods: Thirty healthy adults received 60 mg, sumatriptan 100 or coadministered drugs. Primary end point geometric mean ratios (GMRs) and 90% CIs interventions for area under the plasma concentration–time curve from time 0 to t (AUC0-t) infinity (AUC0-∞) peak concentration (Cmax). Results: Atogepant GMRs AUC0-t AUC0-∞ versus were within CI...

ABSTRACT Fosmanogepix [FMGX, APX001; active form: manogepix (MGX), APX001A] is a first-in-class, intravenous (IV)/oral antifungal currently being evaluated for invasive fungal disease treatment. Data from two phase 1, placebo-controlled studies [IV–oral switch (study 1) and multiple IV doses 2)] evaluating FMGX tolerability, pharmacokinetics (PK) are presented. Healthy adults 1: 18–65 years; study 2: 18–55 years) were eligible (randomized 3:1 to FMGX: placebo). Eleven participants completed...

Objective To evaluate the potential for pharmacokinetic interaction and safety tolerability when ubrogepant sumatriptan are coadministered in a Phase 1 study healthy participants, to inform of alone combination with triptans 3 trials participants migraine. Background Calcitonin gene–related peptide is potent vasodilatory neurotransmitter believed play key role pathophysiology Ubrogepant (UBRELVY™) selective antagonist human calcitonin receptor approved acute treatment Sumatriptan serotonin...

Ubrogepant is a novel, oral calcitonin gene‐related peptide (CGRP) receptor antagonist intended for the acute treatment of migraine attacks. has chemical structure distinct from previous small‐molecule CGRP antagonists that were associated with elevated serum alanine aminotransferase (ALT) in clinical trials. Here, we report overall and hepatic safety data two placebo‐controlled phase I trials ubrogepant, spray‐dried compressed tablet (SD‐OCT) healthy male volunteers. Trial A was...

Ubrogepant is a novel, oral calcitonin gene-related peptide receptor antagonist currently under US Food and Drug Administration (FDA) review for the acute treatment of migraine attacks. This double-blind, four-period crossover study compared cardiac repolarization effect therapeutic (100 mg) supratherapeutic (400 ubrogepant doses vs. placebo in healthy adults. Moxifloxacin 400 mg was used as an open-label active control, primary end point change from baseline Fridericia-corrected QT...

Purpose: This study aimed to characterize the pharmacokinetic (PK) properties, safety, and tolerability of asenapine, develop a population PK model in pediatric patients with schizophrenia, bipolar disorder, or other psychiatric disorders. Methods: Two Phase I multiple ascending-dose studies were conducted evaluate PK, sublingual asenapine (age 10–17 years) schizophrenia disorder. Patients received 1–10 mg twice daily for up 12 days. parameters (maximum concentration [C max ], area under...

Background: Ubrogepant is a novel, oral calcitonin gene–related peptide receptor antagonist approved by the US Food and Drug Administration for acute treatment of migraine with or without aura in adults. Objectives: To assess potential pharmacokinetic (PK) drug–drug interactions healthy participants inform safety tolerability ubrogepant alone combination acetaminophen nonsteroidal anti-inflammatory drugs (NSAIDs) migraine. Methods: Two phase 1, three-way crossover studies randomized adults...

Abstract Micronized droplets of olive oil loaded with docetaxel and coated functional fibrinogen were administered intraperitoneally to mice bearing the fibrin(ogen)-rich ascites form TA3/St mammary tumor. When compared as its commercial formulation (i.e., Taxotere), docetaxel-loaded murine prolonged median survival time tumor-bearing from 14.5 29.5 days. Drug-free provided no therapeutic benefit. Significantly more was associated tumor cells 24 48 hours after administration drug in...

Background: Ubrogepant is a novel, oral calcitonin gene–related peptide receptor antagonist for acute treatment of migraine. This study evaluated potential drug–drug interactions between ubrogepant and an contraceptive containing ethinyl estradiol (EE) norgestimate (NGM). Methods: open-label, single-center, two-period, fixed-sequence enrolled healthy, postmenopausal or oophorectomized, adult women. In period 1, participants received single dose EE 0.035 mg/NGM 0.25 mg (EE-NGM) followed by...

Dexloxiglumide is a new CCK(1) receptor antagonist under investigation for treatment of functional gastrointestinal disorders and metabolized by CYP3A4 CYP2C9. The objectives these two separate randomized, two-period, two-treatment crossover studies were to investigate the effects steady-state ketoconazole, model inhibitor (Study 1), fluconazole, CYP2C9 2), on pharmacokinetics dexloxiglumide in healthy subjects.Plasma samples analysed its primary metabolites: O-demethyl (ODM; Study 1 2)...

This study was undertaken to evaluate the effect of dexloxiglumide, a selective cholecystokinin receptor antagonist, on pharmacokinetics combination oral contraceptive (OC). A single-blind, placebo-controlled, 2-period crossover conducted in 24 healthy young female subjects who received Ortho Tri-Cyclen containing ethinyl estradiol (EE, 0.035 mg) and norgestimate (NE, 0.180 mg/0.215 mg/0.250 mg per 7-day phase, respectively) for 5 days (days 17-21) concurrently with either 200 dexloxiglumide...

Fosmanogepix [FMGX; active form manogepix (MGX)], a novel antifungal, is currently being studied for the treatment of invasive fungal diseases caused by