2-deoxy-D-glucose as an adjunct to standard of care in the medical management of COVID-19: a proof-of-concept and dose-ranging randomised phase II clinical trial.

Background: At present, no single efficacious therapeutic exists for acute COVID-19 management and a multimodal approach may be necessary. 2-deoxy-D-glucose (2-DG) is a metabolic inhibitor that has been shown to limit multiplication of SARS-CoV-2 in-vitro. We evaluated the efficacy and safety of 2-DG as adjunct to standard care in the treatment of moderate to severe COVID-19 patients.

Tepilamide Fumarate (PPC-06) Extended Release Tablets in Patients with Moderate-to-Severe Plaque Psoriasis: Safety and Efficacy Results from the Randomized, Double-blind, Placebo-controlled AFFIRM Study.

Objective: Safe, effective, long-term oral therapies are needed for plaque psoriasis. This study aimed to assess the safety and effectiveness of tepilamide fumarate (a fumaric acid ester) extended-release tablets.

Methods: This Phase IIb, randomized, double-blind, placebo-controlled, 24-week, multicenter study treated adults with moderate-to-severe plaque psoriasis with tepilamide fumarate 400 mg once (QD) or twice daily (BID), 600 mg BID, or placebo.

A Multicenter, Randomized, Double-Blind, Placebo-Controlled Study of the Efficacy, Tolerability, and Safety of Celecoxib Oral Solution (ELYXYB) in Acute Treatment of Episodic Migraine with or without Aura.

Background: Safe, effective, oral therapies are needed for acute treatment of migraine. This clinical trial assessed the efficacy, tolerability, and safety of celecoxib oral solution (ELYXYB) in a single migraine attack associated with moderate-to-severe pain.

Methods: This was a phase III, randomized (1:1), double-blind, placebo-controlled trial, conducted at 41 US centers from December 2016 to October 2017.

Efficacy and safety of single-dose DFN-15 for treatment of acute postsurgical dental pain: a randomized, double-blind, placebo-controlled study.

The analgesic efficacy and safety of DFN-15, a new oral liquid formulation of celecoxib with more rapid absorption than the capsule, were evaluated in the treatment of acute pain in adult patients after dental surgery. In this randomized, double-blind, placebo-controlled, dose-ranging study, 120 otherwise healthy adults who underwent the extraction of bilateral impacted mandibular third molar teeth and experienced moderate to severe pain postsurgery were randomly assigned, in a 1:1:1:1 ratio, to receive one dose of either placebo or DFN-15 at 3 doses: 62.5, 125, and 250 mg.

Acute Treatment of Migraine with Celecoxib Oral Solution: Results of a Randomized, Placebo-Controlled Clinical Trial.

Background: Nonsteroidal anti-inflammatory drugs are widely used for migraine, but gastrointestinal tolerability limits use. We previously reported results from the first treatment period of this 2-period, randomized, controlled study comparing DFN-15-an oral, ready-made liquid solution of a selective cyclo-oxygenase-2 inhibitor celecoxib-with placebo for the acute treatment of a moderate-severe migraine attack. Herein, we report the effects of treatment for the second treatment period.

Burden of increasing opioid use in the treatment of migraine: Results from the Migraine in America Symptoms and Treatment Study.

Objective: We sought to assess factors associated with the frequency of self-reported prescription opioid use in persons with migraine, including demographic variables, comorbidities, headache characteristics, and patterns of consultation.

Background: Despite the dose-dependent effect of opioids on migraine progression and the association with negative outcomes, migraine treatment often includes opioids. The Migraine in America Symptoms and Treatment Study focuses on individuals with migraine who receive prescription acute medications, including those receiving and those not receiving opioids.

Comorbid and co-occurring conditions in migraine and associated risk of increasing headache pain intensity and headache frequency: results of the migraine in America symptoms and treatment (MAST) study.

Background: Migraine has many presumed comorbidities which have rarely been compared between samples with and without migraine. Examining the association between headache pain intensity and monthly headache day (MHD) frequency with migraine comorbidities is novel and adds to our understanding of migraine comorbidity.

Methods: The MAST Study is a prospective, web-based survey that identified US population samples of persons with migraine (using modified International Classification of Headache Disorders-3 beta criteria) and without migraine.

Most Bothersome Symptom in Persons With Migraine: Results From the Migraine in America Symptoms and Treatment (MAST) Study.

Objectives: The objectives of this study were to determine the rates of nausea, phonophobia, and photophobia reported overall and as the most bothersome symptom (MBS) in individuals with migraine and to identify individual characteristics associated with each of the 3 candidate MBSs.

Background: The MBS has emerged as an important coprimary efficacy endpoint in clinical trials of acute treatments for migraine, as recommended by the Food and Drug Administration. The current understanding of how persons with migraine designate an associated symptom as the most bothersome has been assessed primarily in the context of randomized trials.

Efficacy, Tolerability, and Safety of DFN-15 (Celecoxib Oral Solution, 25 mg/mL) in the Acute Treatment of Episodic Migraine: A Randomized, Double-Blind, Placebo-Controlled Study.

Objective: The objective of this study was to evaluate the efficacy, tolerability, and safety of 120 mg DFN-15 vs placebo for the acute treatment of migraine.

Background: Certain nonsteroidal anti-inflammatory drugs (NSAIDs) are guideline-recommended therapies for the acute treatment of migraine, but patients who use them may have issues with gastrointestinal tolerability. Celecoxib, a selective inhibitor of cyclooxygenase-2, produces analgesia similar to nonselective NSAIDs.

Unmet Acute Treatment Needs From the 2017 Migraine in America Symptoms and Treatment Study.

Objectives: To characterize unmet treatment needs in a sample of Migraine in America Symptoms and Treatment (MAST) Study participants using oral, acute prescription migraine medications.

Background: The MAST Study is a 2017 study of US adults with migraine that profiles current treatment patterns and identifies and quantifies unmet treatment needs.

Methods: Cross-sectional data from an online survey of US adults meeting ICHD-3 beta criteria for migraine.

DFN-02, Sumatriptan 10 mg Nasal Spray with Permeation Enhancer, for the Acute Treatment of Migraine: A Randomized, Double-Blind, Placebo-Controlled Study Assessing Functional Disability and Subject Satisfaction with Treatment.

Background: The commercial formulation of sumatriptan nasal spray is an effective option for migraine patients requiring or preferring a non-oral route of drug administration, but its utility is limited by poor absorption and tolerability issues. DFN-02, a new formulation of sumatriptan 10 mg nasal spray, is co-formulated with a permeation enhancer that gives it pharmacokinetics comparable to subcutaneous sumatriptan. As reported previously, DFN-02 was significantly better than placebo on multiple efficacy endpoints at 2 h postdose, including pain freedom, absence of the most bothersome symptom, and pain relief, and its safety and tolerability profiles were excellent.

Predictors of allodynia in persons with migraine: Results from the Migraine in America Symptoms and Treatment (MAST) study.

Background: Cutaneous allodynia is a common clinical feature of migraine that has been associated with reduced efficacy of acute migraine treatments and an increased risk of disease progression.

Objective: Identify factors associated with allodynia in a sample of adults with migraine.

Methods: An online survey panel was used to identify adults with migraine who averaged at least 1 monthly headache day over the previous 3 months.

Migraine in America Symptoms and Treatment (MAST) Study: Baseline Study Methods, Treatment Patterns, and Gender Differences.

Objectives: To summarize the baseline methods for the Migraine in America Symptoms and Treatment (MAST) Study and evaluate gender differences in sociodemographics and headache features; consultation and diagnosis patterns; and patterns of acute and preventive treatment use for migraine among study participants.

Background: The MAST Study is a longitudinal, internet-based panel study of symptoms, approaches to management, and unmet treatment needs among US adults with migraine. This analysis focuses on the initial cross-sectional survey, conducted beginning in 2016, and is intended to update results from earlier national epidemiologic surveys of people with migraine in the United States.

Efficacy and safety of DFN-11 (sumatriptan injection, 3 mg) in adults with episodic migraine: a multicenter, randomized, double-blind, placebo-controlled study.

Background: In a previous randomized, double-blind, proof-of-concept study in rapidly escalating migraine, a 3 mg dose of subcutaneous sumatriptan (DFN-11) was associated with fewer and shorter triptan sensations than a 6 mg dose. The primary objective of the study was to assess the efficacy and safety of acute treatment with DFN-11 compared with placebo in episodic migraine.

Methods: This was a multicenter, randomized, double-blind, placebo-controlled efficacy and safety study of DFN-11 in the acute treatment of adults with episodic migraine (study RESTOR).

Efficacy and safety of DFN-11 (sumatriptan injection, 3 mg) in adults with episodic migraine: an 8-week open-label extension study.

Background: DFN-11, a 3 mg sumatriptan subcutaneous (SC) autoinjector for acute treatment of migraine, has not been assessed previously in multiple attacks. The objective of this study was to evaluate the efficacy, tolerability, and safety of DFN-11 in the acute treatment of multiple migraine attacks.

Methods: This was an 8-week open-label extension of multicenter, randomized, double-blind, placebo-controlled US study.

DFN-02 (Sumatriptan 10 mg With a Permeation Enhancer) Nasal Spray vs Placebo in the Acute Treatment of Migraine: A Double-Blind, Placebo-Controlled Study.

Objective: The objective of this study was to evaluate the efficacy, safety, and tolerability of DFN-02 - a nasal spray comprising sumatriptan 10 mg and a permeation-enhancing excipient (0.2% 1-O-n-Dodecyl-β-D-Maltopyranoside [DDM]) - for the acute treatment of migraine with or without aura in adults.

Background: Prior work has shown that DFN-02, which contains only half the recommended adult dose of sumatriptan found in the original formulation (10 mg vs 20 mg), is more rapidly absorbed than commercial nasal spray of sumatriptan, with favorable pharmacokinetic and safety profiles.

Factors associated with acute medication overuse in people with migraine: results from the 2017 migraine in America symptoms and treatment (MAST) study.

Background: The MAST Study is a longitudinal, cross-sectional survey study of US adults with migraine. These analyses were conducted to estimate rates of acute medication overuse (AMO) and determine associations of AMO with individual and headache characteristics.

Methods: Eligible respondents had ICHD-3-beta migraine, reported ≥3 monthly headache days (MHDs) in the past 3 months, ≥1 MHD in the past 30 days, and currently took acute headache medication.

Efficacy and safety of DFN-15, an oral liquid formulation of celecoxib, in adults with migraine: a multicenter, randomized, placebo-controlled, double-blind, crossover study.

Background: The objective of this proof-of-concept study was to assess the safety, efficacy, and potential for dose response of a new oral liquid formulation of celecoxib, DFN-15, in adults with migraine. Variability in patient-identified most bothersome symptom (MBS) across 3 migraine attacks was also evaluated.

Methods: This was a randomized, placebo-controlled, double-blind, 3-treatment, 6-sequence, 3-period, crossover study of 3 treatments (DFN-15 120 mg, DFN-15 240 mg, and placebo) administered at the onset of moderate to severe headache.

Pharmacokinetics of DFN-15, a Novel Oral Solution of Celecoxib, Versus Celecoxib 400-mg Capsules: A Randomized Crossover Study in Fasting Healthy Volunteers.

Background: COX-2 inhibitors can be effective for acute migraine, but none is supplied in a rapidly absorbed, ready-to-use oral liquid formulation. DFN-15, a novel oral liquid formulation of celecoxib, is being developed for the acute treatment of migraine with or without aura. Clinical studies with this formulation are ongoing.

Allodynia Is Associated With Initial and Sustained Response to Acute Migraine Treatment: Results from the American Migraine Prevalence and Prevention Study.

Objective: In a population sample of persons with migraine treating with a single category of acute migraine medication, to identify rates and factors associated with acute treatment outcomes, including 2-hour pain freedom (2hPF), 24-hour pain response (24hPR), and 24-hour sustained pain response (24hSPR). Key predictors include acute treatment type (triptans and other medication categories), the influence of allodynia on response to medication, and the interaction between medication category and presence of allodynia in response to treatment among people with migraine.

Background: Cutaneous allodynia was previously associated with inadequate 2hPF, 24hPR, and 24hSPR (sustained response at 24 hours among those with adequate 2hPF) among people with migraine in the American Migraine Prevalence and Prevention (AMPP) Study.

Pharmacokinetic Characterization and Dose Selection of a Novel Sumatriptan Nasal Spray Formulation, DFN-02.

This 3-way, single-dose, randomized crossover study evaluated the pharmacokinetics (PK) and dose proportionality of 5-, 10-, and 15-mg doses of intranasal sumatriptan (DFN-02) coformulated with a permeation enhancer (DDM) in 18 healthy adults. The objective was to determine which DFN-02 dose approximates the PK of a 6-mg dose of sumatriptan delivered via subcutaneous injection in the deltoid muscle of the arm. Sumatriptan plasma concentrations peaked with DFN-02 between 10 and 15 minutes postdose, declining thereafter, with a t of about 2.

A multicenter, open-label, long-term safety and tolerability study of DFN-02, an intranasal spray of sumatriptan 10 mg plus permeation enhancer DDM, for the acute treatment of episodic migraine.

Background: DFN-02 is a novel intranasal spray formulation composed of sumatriptan 10 mg and a permeation-enhancing excipient comprised of 0.2% 1-O-n-Dodecyl-β-D-Maltopyranoside (DDM). This composition of DFN-02 allows sumatriptan to be rapidly absorbed into the systemic circulation and exhibit pharmacokinetics comparable to subcutaneously administered sumatriptan.

Subcutaneous sumatriptan delivery devices: comparative ease of use and preference among migraineurs.

Background: Several sumatriptan subcutaneous autoinjector devices for acute treatment of migraine patients are available, each device differs with respect to design and features. Determining device preference and ease of use is important because patients experiencing a migraine attack are often functionally impaired.

Objective: The objective of this human factors study was to compare migraine patients' device use performance and preferences for three sumatriptan subcutaneous autoinjectors: a disposable two-step device (Zembrace SymTouch), a disposable three-step device (Sumavel DosePro), and a multistep reloadable device (Imitrex STATdose), using simulated injections.

Randomized, double-blind, crossover study comparing DFN-11 injection (3 mg subcutaneous sumatriptan) with 6 mg subcutaneous sumatriptan for the treatment of rapidly-escalating attacks of episodic migraine.

Background: A 6-mg dose of SC sumatriptan is the most efficacious and fast-acting acute treatment for migraine, but a 3-mg dose of SC sumatriptan may improve tolerability while maintaining efficacy.

Methods: This randomized, double-blind, crossover study compared the efficacy and tolerability of 3 mg subcutaneous (SC) sumatriptan (DFN-11) with 6 mg SC sumatriptan in 20 adults with rapidly-escalating migraine attacks. Eligible subjects were randomized (1:1) to treat 1 attack with DFN-11 and matching placebo autoinjector consecutively or 2 DFN-11 autoinjectors consecutively and a second attack similarly but with the alternative dose (3 mg or 6 mg).

Predicting Inadequate Response to Acute Migraine Medication: Results From the American Migraine Prevalence and Prevention (AMPP) Study.

Background: Pain freedom at 2 hours and sustained pain response at 24 hours are important outcomes of acute migraine therapy. Some studies have examined rates and predictors of successful treatment outcomes for single attacks in clinical trials. However, little is known about predictors of typical response to acute treatment over multiple attacks in the population.