Onset-of-Efficacy of Azelastine HCl 0.15% Nasal Spray for allergic rhinitis in an environmental exposure chamber.

BACKGROUND: Azelastine nasal spray is effective in relieving symptoms of seasonal and perennial allergic rhinitis. OBJECTIVE: The objective of this single center, double-blinded, placebo-controlled, crossover study was to evaluate the time to onset of efficacy of azelastine HCl 0.15% vs placebo in participants with seasonal allergic rhinitis. METHODS: 110 participants aged 18 to 65 years were randomized to receive azelastine HCl 0.15% two sprays per nostril vs placebo nasal spray after being continuously exposed to ragweed pollen in an environmental exposure chamber (EEC). Symptoms were evaluated subjectively by the total nasal symptom score (TNSS) scale. The primary efficacy parameter was the time to onset of efficacy of azelastine as measured by the change from baseline in TNSS 15, 30, 45, 60, 90, 120, 180, and 240-minute post-dose. RESULTS: The azelastine nasal spray group had statistically significant improvement in TNSS compared with placebo 30 minutes post-dose (p=0.0002), and the effect was sustainable throughout the EEC session for all subsequent time points (p<0.0001). Adverse events were mild, including bitter taste, nasal discomfort, epistaxis, sinusitis, and nausea. No major adverse events were reported during the study. CONCLUSION: Azelastine HCl 0.15% nasal spray relieves nasal symptoms associated with allergic rhinitis and has a fast onset of action within 30 minutes. The overall safety profile of azelastine has also been proven to be safe. These results, along with prior findings on efficacy and improved quality of life for people suffering from allergic rhinitis, establish the important clinical role of azelastine HCl 0.15%.

Analgesic efficacy of naproxen sodium versus hydrocodone/acetaminophen in acute postsurgical dental pain: a randomized, double-blind, placebo-controlled trial.

OBJECTIVES: Opioid/acetaminophen combinations may be overly prescribed in many post-surgical situations where a non-steroidal anti-inflammatory drug with equal or greater efficacy, fewer central nervous system side effects, and no risk for opioid abuse could be substituted. We compared a single, non-prescription dose of naproxen sodium 440 mg (NapS) against hydrocodone plus acetaminophen 10/650 mg (HYD+APAP) in post-impaction surgery pain. METHODS: Single-center, randomized, double-blind, placebo-controlled study in moderate-severe pain after surgical removal of impacted third molars (ClinicalTrials.gov: NCT04307940). Patients (n = 212) received NapS, HYD+APAP, or placebo and were assessed over 12 hours. Primary endpoint: summed pain intensity difference from 0 to 12 hours (SPID0-12). Secondary endpoints: pain intensity, pain relief, time to rescue medication, duration of pain at least half gone. Others: onset of pain relief, global assessment of treatment, adverse events. RESULTS: All 221 randomized patients formed the safety population and were included in the intention-to-treat sensitivity analysis. Nine patients discontinued treatment or had protocol violations, and 212 patients were included in the per-protocol, primary efficacy population. Both active treatments were significantly more effective than placebo. NapS was significantly more effective than HYD+APAP regarding SPID0-12 (p = 0.01; primary endpoint), total pain relief (0-6 and 0-12 hours; p < 0.05), time to rescue medication (p < 0.001), and duration of pain at least half gone (p < 0.001). HYD+APAP was not statistically superior to NapS for any endpoint. More adverse events were reported with HYD+APAP (n = 63) than NapS (n = 2) and placebo (n = 20), including nausea, vomiting, and dizziness. CONCLUSION: In moderate-to-severe postsurgical dental pain, a single dose of NapS was at least as effective as HYD+APAP in the early hours, significantly more effective at reducing pain intensity and providing greater pain relief over 12 hours, and was better tolerated. When not contraindicated, NapS should be considered a preferred alternative to opioid combinations for acute pain. (ClinicalTrials.gov, Identifier: NCT04307940; https://clinicaltrials.gov/ct2/show/NCT04307940).

Longer analgesic effect with naproxen sodium than ibuprofen in post-surgical dental pain: a randomized, double-blind, placebo-controlled, single-dose trial.

Background: Non-steroidal anti-inflammatory drugs (NSAIDs) are recommended as first-line medications in mild-to-moderate acute pain. However, comparative data regarding the duration of analgesia for commonly-used NSAIDs at non-prescription doses is lacking. This study evaluated the time to rescue medication following a single dose of naproxen sodium (NAPSO) vs ibuprofen (IBU) and placebo in subjects with moderate-to-severe post-surgical dental pain.Methods: This single-center, randomized, double-blind, parallel group, placebo-controlled study included healthy subjects with moderate-to-severe baseline pain (Categorical Pain Intensity Scale) who also rated their pain ≥ 5 on a 0-10 pain intensity Numerical Rating Scale following extraction of two impacted mandibular third molars. A single oral dose of NAPSO (440 mg), IBU (400 mg), or placebo was administered. The primary efficacy endpoint was the time to first rescue medication, while secondary endpoints included the sum of pain intensity difference (SPID) and total pain relief (TOTPAR) over 24 h. ClinicalTrials.gov trial registration number: NCT03404206 (EudraCT 2017-005049-67).Results: In the per protocol population (n = 385; mean age = 19 years), the time to rescue medication was significantly (p < .001) longer with NAPSO than IBU and placebo. After treatment, the greatest separation of NAPSO from IBU occurred at 9-14 h and from placebo at 1-6 h. Fewer NAPSO subjects required rescue medication (58/166, 34.9%) compared with IBU (137/165, 83.0%) and placebo (44/54, 81.5%). SPID 0-24 h and TOTPAR 0-24 h were both greater with NAPSO than IBU or placebo.Conclusions: The duration of pain relief after a single dose of NAPSO was significantly longer than after IBU, and significantly fewer NAPSO-treated subjects required rescue medication over a 24-h period.

Thromboxane inhibition during concurrent therapy with low-dose aspirin and over-the-counter naproxen sodium.

Aspirin is the dominant antiplatelet therapy for cardiovascular disease. Naproxen is frequently used in aspirin-treated patients and may influence the antiplatelet effect of aspirin. We evaluated the pharmacodynamic interaction (lower bound of the one-sided 95% CI for serum TxB2 inhibition < 95%) between 220 mg immediate-release naproxen sodium (once or twice daily) and 81 mg daily immediate release aspirin at various dosing intervals. There was no interaction during the first day of concurrent treatment. After 10 days, irrespective of the timing and dose of naproxen in relation to aspirin dosing, a pharmacodynamic interaction occurred which persisted after discontinuing naproxen. In the control group (aspirin alone), the lower bound for serum TxB2 inhibition was > 98% at all time points. The clinical relevance of these observations remains unknown and merits further investigation since over-the-counter naproxen is widely used to relieve pain by individuals taking low dose aspirin for cardioprotection. CLINICAL TRIAL REGISTRATION: NCT02229461.

Survey of the performance of commercial dose calibrators for measurement of ¹²³I activity.

UNLABELLED: The accuracy with which (123)I activity is measured by a dose calibrator depends on the composition and geometry of the source. The present study assessed the variability of current commercial dose calibrators in assaying liquid (123)I samples. METHODS: A calibration procedure for (123)I measurement was performed on 177 dose calibrators (11 manufacturers) at 138 sites in North America and Europe. Using the standard (123)I push-button or dial setting, activity in a 5-mL (123)I calibration source in a 10-mL U.S. Pharmacopeia type 1 glass vial (actual activity previously determined using a National Institute of Standards and Technology-traceable standard metrology chamber) was measured. A portion of the source was then transferred to a plastic syringe (10-, 5-, and 3-mL sizes at different sites), and the activity in the syringe was measured. Calibration factors (CFs) for converting the dose calibrator readings to the reference activities were then determined for the vial and the syringes. Data were analyzed for all calibrators combined and based on device manufacturers. Measurements using a copper attenuator (sleeve) were made for a subset of 10 dose calibrators at sites that used these devices in clinical practice. RESULTS: Mean CFs for the different measurements were as follows: 10-mL vial, 1.278; 10-mL syringe, 0.811; 5-mL syringe, 0.815; 3-mL syringe, 0.792. Almost half of the dose calibrators had vial CFs between 1.2 and 1.3 and 10-mL syringe CFs between 0.7 and 0.8, whereas less than 16% of the instruments had uncorrected readings within ±10% of the reference activities. Although there was a wide range of CFs for different calibrators using the copper sleeve, for each unit the CFs for the glass vial and the 10-mL plastic syringe were virtually identical. CONCLUSION: On most commercial dose calibrators, the standard (123)I settings result in significant errors in activity measurements for sources in glass vials and plastic syringes. The difference in ionization chamber detection caused by the container composition (glass vs. plastic) is a much larger source of measurement variation than source volume or geometry.