Clinical effect and safety profile of pegzilarginase in patients with arginase 1 deficiency.

Hyperargininemia in patients with arginase 1 deficiency (ARG1-D) is considered a key driver of disease manifestations, including spasticity, developmental delay, and seizures. Pegzilarginase (AEB1102) is an investigational enzyme therapy which is being developed as a novel arginine lowering approach. We report the safety and efficacy of intravenously (IV) administered pegzilarginase in pediatric and adult ARG1-D patients (n = 16) from a Phase 1/2 study (101A) and the first 12 weeks of an open-label extension study (102A). Substantial disease burden at baseline included lower-limb spasticity, developmental delay, and previous hyperammonemic episodes in 75%, 56%, and 44% of patients, respectively. Baseline plasma arginine (pArg) was elevated (median 389 µM, range 238-566) on standard disease management. Once weekly repeat dosing resulted in a median decrease of pArg of 277 µM after 20 cumulative doses (n = 14) with pArg in the normal range (40 to 115 µM) in 50% of patients at 168 hours post dose (mean pegzilarginase dose 0.10 mg/kg). Lowering pArg was accompanied by improvements in one or more key mobility assessments (6MWT, GMFM-D & E) in 79% of patients. In 101A, seven hypersensitivity reactions occurred in four patients (out of 162 infusions administered). Other common treatment-related adverse events (AEs) included vomiting, hyperammonemia, pruritus, and abdominal pain. Treatment-related serious AEs that occurred in five patients were all observed in 101A. Pegzilarginase was effective in lowering pArg levels with an accompanying clinical response in patients with ARG1-D. The improvements with pegzilarginase occurred in patients receiving standard treatment approaches, which suggests that pegzilarginase could offer benefit over existing disease management.

Testosterone 2% gel can normalize testosterone concentrations in men with low testosterone regardless of body mass index.

INTRODUCTION: Little is known about the effect of body mass index (BMI) on the efficacy and safety of testosterone therapy in hypogonadal men. A prior noncomparative trial demonstrated that testosterone 2% gel restored testosterone levels in hypogonadal men and was generally well tolerated. AIM: This post hoc analysis evaluated the influence of BMI on the pharmacokinetics of testosterone therapy in men with low testosterone. METHODS: Men (N = 149) aged 18-75 applied testosterone 2% gel to the front and inner thigh once daily for 90 days. Starting dose was 40 mg/day, which could be adjusted at days 14, 35, and 60. Patients were split into categories depending on baseline BMI: Tertile 1 (≤ 29.1 kg/m(2)), Tertile 2 (29.2-32.4 kg/m(2)), and Tertile 3 (>32.4 kg/m(2)). MAIN OUTCOME MEASURES: Efficacy end points were average serum total testosterone concentrations over 24 hours and maximum serum testosterone concentrations at day 90. Adverse events were recorded. RESULTS: The efficacy analysis included 129 men with low testosterone (mean age 52.9, 54.0, and 54.2 years for Tertiles 1, 2, and 3, respectively) defined as serum testosterone <250-300 ng/dL. Baseline testosterone levels were comparable across BMI tertiles. After 90 days of treatment with testosterone 2% gel (≥ 40 mg/day), 79.1%, 79.5%, and 73.8% of patients in Tertiles 1, 2, and 3, respectively, achieved serum testosterone concentrations in the physiologic range (i.e., ≥ 300 to ≤ 1,140 ng/dL). The mean average daily dose at day 90 was higher in participants in Tertiles 3 vs. 2 (P = 0.039) and Tertiles 3 vs. 1 (P = 0.010). The gel was generally well tolerated, with skin reactions the most commonly reported adverse event (16.1%; n = 24). CONCLUSIONS: In this study, daily application of testosterone 2% gel was effective at returning serum testosterone to physiologic levels in men with low testosterone and high BMI, although required dose was affected by BMI.

Reliability and validity of individual and composite recall pain measures in patients with cancer.

OBJECTIVES: To evaluate and compare the validity and reliability of individual and composite recall pain intensity measures. DESIGN: Secondary analyses using data from a published 14-day open-label crossover clinical trial comparing two active treatments. SETTING: Multiple settings. PARTICIPANTS: Fifty-two adults with a history of chronic cancer pain. MEASURES: Recall ratings of least, worst, and average pain during the past 2 days; composite score representing recalled characteristic pain in the past 2 days; and daily diary ratings of pain intensity from which "actual" least, worst, and average pain scores were derived. RESULTS: Recall ratings of least and average pain, and a composite score representing recalled characteristic pain were accurate (differed no more than three points from "actual" scores on a 0-100 scale). Although the recall rating of worst pain significantly (P < 0.05) overestimated actual worst pain, the differences were minor (i.e., seven to eight points on a 0-100 scale). All of the recall measures demonstrated validity via their strong associations with the measures of actual pain intensity. The recall measures also demonstrated excellent test-retest stability, although the diary-derived measures tended to be more stable than the recall measures did. The composite measure of recalled characteristic pain demonstrated a high level of internal consistency (Cronbach's α = 0.90). CONCLUSIONS: Individual recall ratings and a composite score representing recalled characteristic pain intensity are reliable and valid measures of actual pain in patients with cancer. The findings support their use as outcome measures in clinical trials.

Reflections on the experiences of attending peer support groups for fathers of children with cancer.

Fathers appear to be less researched than mothers, in particular with regard to their emotional well-being during their child's cancer diagnosis and treatment. This study investigates a small-scale service evaluation of a father's support group for fathers of children with cancer in a paediatric oncology and haematology service. The group was set up in October 2017 to enable a safe and supportive reflective space for fathers of children with cancer. The group was open to fathers with a child on the ward on treatment, as well as fathers with children out of treatment, and in remission in the community. Data were analysed using Interpretive Phenomenological Analysis. A number of themes are identified and discussed, including the emotional impact, ways of coping, gender roles, loss and feeling part of an oncology family. The fathers valued hearing each other's stories about their child's cancer diagnosis and experiences as this appeared to empower them in helping each other to feel a sense of normalisation for their feelings. They appreciated the group structure and discussed further ways for group improvement. Suggestions are made for developing services to meet emotional support needs of fathers of children with cancer.

Clinical evaluation of the safety and efficacy of preservative-free triamcinolone (triesence [triamcinolone acetonide injectable suspension] 40 mg/ml) for visualization during pars plana vitrectomy.

PURPOSE: To evaluate the safety and efficacy of preservative-free triamcinolone (TRIESENCE(R) suspension) for visualization during pars plana vitrectomy. METHODS: This phase III, observer-masked study was conducted in 6 centers by 10 surgeons and enrolled 60 patients undergoing pars plana vitrectomy. Preservative-free triamcinolone (up to 4 mg) was administered to all patients to enhance visualization of vitreous and membranes. During each surgery, video recordings captured visualization pre- and postinstillation of preservative-free triamcinolone. An independent, masked reader evaluated the videos for the degree of visualization using a five-point scale ranging from 0 (not visible) to 4 (clearly delineated). Surgeons used a five-point scale ranging from "strongly disagree" to "strongly agree" to assess whether preservative-free triamcinolone improved visualization. RESULTS: In 59 of 60 cases, the masked reader's scores for visualization of posterior segment structures were higher (i.e., structures were more clearly visible) after instillation of preservative-free triamcinolone. The preinstillation mean visualization score was 0.5 compared to 3.7 postinstillation (P < 0.0001). Greater than 90% of surgeon evaluations agreed or strongly agreed that preservative-free triamcinolone enhanced visualization of posterior segment structures. No safety issues were identified. CONCLUSIONS: Preservative-free triamcinolone (TRIESENCE(R) suspension) was well tolerated and effectively enhanced visualization of posterior segment structures during pars plana vitrectomy.

A single topical agent is clinically equivalent to the combination of topical and oral antibiotic treatment for otitis externa.

OBJECTIVE: To demonstrate clinical equivalence (statistical noninferiority) of topical ciprofloxacin and hydrocortisone (CHC, Cipro HC) and topical neomycin/polymyxin b/hydrocortisone (NPH, Cortisporin) with systemic amoxicillin (AMX, Amoxil), for treatment of acute otitis externa (AOE). DESIGN: Randomized, active-control, observer-blind, multicenter trial. PATIENTS: Altogether, 206 patients were enrolled (CHC, 106; NPH + AMX, 100). Patients were > or =1 year of age, had AOE >2 days with at least mild symptoms, and gave informed consent. All were evaluable for safety, and 151 were evaluable for efficacy. INTERVENTIONS: Ciprofloxacin and hydrocortisone 3 drops twice daily for 7 days (adults and children) or NPH 4 drops (adults) or 2 drops (children) with AMX 250 mg (adults and children) 3 times daily for 10 days, as directed in approved product labeling. MAIN OUTCOME MEASURES: The primary efficacy variable was response to therapy 7 days after treatment ended (test of cure). Secondary variables included time to end of pain, symptom scores (otalgia and tenderness) and microbiological eradication. Noninferiority was declared if the lower confidence limit around the measurement difference was above -10 (nearer zero). RESULTS: Response to therapy was higher for CHC (95.71% vs 89.83%) but was statistically noninferior (lower confidence limit, -4.98) to NPH + AMX. Median time to end of pain was 6 days for both groups. Noninferiority was declared for symptom scores at all measurement periods and for microbiological eradication. No serious adverse events related to treatment were reported. CONCLUSIONS: Ciprofloxacin and hydrocortisone is clinically equivalent to NPH + AMX for the treatment of AOE in adults and children. However, low systemic exposure, absence of ototoxicity, and less frequent dosing clearly favor Cipro HC.

An assessment of the onset and duration of action of olopatadine nasal spray.

OBJECTIVE: Seasonal allergic rhinitis (SAR) is a highly prevalent disease. This study was conducted to evaluate the onset and duration of action of three concentrations of olopatadine nasal spray. METHODS: This was a randomized, double-blind, single-dose, placebo-controlled study, conducted in an environmental exposure chamber in patients with SAR. A total of 320 patients were exposed to ragweed allergen in the chamber and randomized to olopatadine nasal spray 0.2%, 0.4%, 0.6%, or placebo nasal spray. Symptoms (sneezing, runny, itchy, and stuffy nose) were self-assessed during a 12-hour study period. RESULTS: All concentrations of olopatadine nasal spray provided clinically meaningful reductions in total nasal symptom scores at 30 minutes compared to the placebo. Olopatadine nasal spray 0.6% was significantly more effective (P < 0.05) than placebo nasal spray at all time-points starting at 90 minutes post-dose and continuing over 12 hours. CONCLUSIONS: Olopatadine nasal spray 0.6% demonstrated a fast onset of action and maintained an effect for at least 12 hours after dosing.

Vehicle-Controlled, Phase 2 Clinical Trial of a Sustained-Release Dexamethasone Intracanalicular Insert in a Chronic Allergen Challenge Model.

PURPOSE: To evaluate the efficacy and safety of a sustained-release dexamethasone intracanalicular insert (Dextenza™) in a model of allergic conjunctivitis. METHODS: This was a randomized, double-masked, vehicle-controlled, Phase 2 study. Subjects had to have a positive conjunctival allergen challenge (CAC) reaction to allergen (bilateral +2 itching and redness on 5-point, 0-4 scales) at Visit 1, and for 2 of 3 time points on subsequent visits. Subjects who met entry criteria were randomized to receive Dextenza or PV (vehicle insert). Challenges occurred over 42 days, with efficacy assessed at 14 (primary endpoint visit), 28, and 40 days postinsertion. Outcome measures included the evaluation of ocular itching, redness, tearing, chemosis, eyelid swelling, rhinorrhea, and congestion. RESULTS: Twenty-eight subjects completed the study in the Dextenza group and 31 in the vehicle group. At 14 days postinsertion, Dextenza was statistically superior to PV, with least square mean differences for ocular itching of -0.76, -0.97, and -0.87 at 3, 5, and 7 min post-CAC, and for conjunctival redness of -0.46, -0.66, and -0.68 at 7, 15, and 20 min post-CAC. Clinical significance, defined as a 1-U decrease from PV, was not met for primary efficacy. Secondary endpoints, including number of subjects reporting itching and conjunctival redness, indicated superior performance of Dextenza compared with vehicle. Eleven Dextenza-treated (35.5%) and 10 vehicle-treated (30.3%) subjects each experienced a single adverse event. CONCLUSION: This Phase 2 study demonstrated preliminary efficacy and safety data of Dextenza for treatment of allergic conjunctivitis.

Efficacy and safety of topical ciprofloxacin/dexamethasone versus neomycin/polymyxin B/hydrocortisone for otitis externa.

OBJECTIVES: To compare the efficacy and safety of ciprofloxacin 0.3%/dexamethasone 0.1% (CIP/DEX) otic suspension with that of neomycin 0.35%/polymyxin B 10,000 IU/mL/hydrocortisone 1.0% (N/P/H) otic suspension in patients with acute otitis externa (AOE). STUDY DESIGN: Randomized, observer-masked, parallel-group, multicenter study. Patients were randomized to 7 days treatment with either CIP/DEX 3-4 drops twice daily or N/P/H 3-4 drops three times daily. POPULATION: Patients of either sex and older than 1 year, with a clinical diagnosis of mild, moderate, or severe AOE and intact tympanic membranes were recruited to participate. OUTCOMES MEASURED: Signs and symptoms of AOE, including ear inflammation, tenderness, edema and discharge (assessed on Days 3, 8 [End-of-Therapy] and 18 [Test-of-Cure]); microbiologic eradication (presumed or documented); and frequency of adverse events. RESULTS: Patients enrolled numbered 468. In culture-positive patients who met the inclusion criteria (N = 396), clinical cure rates at Day 18 were significantly higher with CIP/DEX than with N/P/H (90.9% vs. 83.9%; p = 0.0375), as were microbiologic eradication rates (94.7% vs. 86.0%; p = 0.0057). In addition, the clinical response was significantly better with CIP/DEX than with N/P/H at Days 3 and 18 (p = 0.0279 and p = 0.0321, respectively), as was the reduction in ear inflammation at Day 18 (p = 0.0268). Both preparations were well tolerated in pediatric and adult patients. CONCLUSIONS: 7 days treatment with CIP/DEX otic suspension administered twice daily is clinically and microbiologically superior to N/P/H otic suspension administered 3 times daily in the treatment of mild to severe AOE, and is equally well tolerated.

Topical ciprofloxacin/dexamethasone is superior to ciprofloxacin alone in pediatric patients with acute otitis media and otorrhea through tympanostomy tubes.

OBJECTIVE: To determine whether topical administration of a corticosteroid improves resolution of acute tympanostomy tube otorrhea when combined with topical antibiotic drops. STUDY DESIGN: Randomized, patient-masked, parallel-group, multicenter trial of topical otic ciprofloxacin/dexamethasone versus topical ciprofloxacin alone in 201 children aged 6 months to 12 years with acute otitis media with tympanostomy tubes (AOMT) of less than or equal to 3 weeks' duration and visible otorrhea. METHODS: Eligible patients were randomized to receive three drops of either ciprofloxacin 0.3%/dexamethasone 0.1% or ciprofloxacin 0.3% into the affected ear or ears twice daily for 7 days. Clinical signs and symptoms of AOMT were evaluated on days 1 (baseline), 3, 8 (end-of-therapy), and 14 (test-of-cure), and twice-daily assessments of otorrhea were recorded in patient diaries. RESULTS: The mean time to cessation of otorrhea in the microbiologically culture-positive patient population (n = 167) was significantly shorter with topical ciprofloxacin/dexamethasone than with ciprofloxacin alone (4.22 vs. 5.31 days; P =.004). This resulted in significantly better clinical responses on days 3 and 8 (P <.0001 and P =.0499, respectively). However, there were no significant differences between the two treatment groups in either the clinical response or the microbial eradication rate by day 14. CONCLUSIONS: Topical otic treatment with ciprofloxacin/dexamethasone is superior to treatment with ciprofloxacin alone and results in a faster clinical resolution in children with AOMT. The contribution of the corticosteroid in achieving a 20% reduction (1.1 day) in time to cessation of otorrhea is clinically meaningful and represents an important advance over single-agent antibiotic therapy.

Randomized, placebo-controlled evaluation of Cerumenex and Murine earwax removal products.

OBJECTIVE: To evaluate the efficacy of 2 ceruminolytic products, Cerumenex Eardrops (Purdue Frederick Company, Norwalk, Conn) and Murine Ear Drops (Abbott Laboratories, Abbott Park, Ill), in subjects with partial or complete occlusion of the ear canal due to cerumen. DESIGN: Randomized, subject- and observer-blind, placebo-controlled, clinical trial. SETTING: Corporate research clinic. PARTICIPANTS: From among 230 volunteers screened, 74 subjects (age, 22-66 [mean, 45] years) were enrolled in the study. Participants had baseline occlusion levels of mild (n = 10), moderate (n = 26), or complete (n = 38) impairment of tympanic membrane visualization. INTERVENTIONS: Subjects were randomly assigned to 1 of 3 treatments: Cerumenex (10% triethanolamine polypeptide oleate-condensate), Murine (6.5% carbamide peroxide), and a placebo, BSS Sterile Irrigating Solution (Alcon Laboratories Inc, Ft Worth, Tex). The test medication was instilled into 1 occluded ear for up to two 15-minute applications. Following the treatment, the subject's ear was irrigated with 50 mL of lukewarm water delivered at low pressure via a WaterPik irrigator equipped with a Grossan irrigator tip. Main Outcome Measure The degree of occlusion, measured against a previously established 4-point scale, was assessed and recorded at baseline and after each instillation and irrigation procedure. RESULTS: Neither Cerumenex nor Murine was superior to saline placebo. By the end of treatment, 29.2%, 15.4%, and 41.7% of subjects treated with Cerumenex, Murine, and placebo, respectively, experienced resolution of cerumen occlusion. These values were not statistically significantly different from one another. CONCLUSION: The currently marketed ceruminolytic products, Cerumenex and Murine, are no more effective than a saline placebo in removing earwax.

Topical ciprofloxacin/dexamethasone otic suspension is superior to ofloxacin otic solution in the treatment of granulation tissue in children with acute otitis media with otorrhea through tympanostomy tubes.

OBJECTIVE: Comparison of topical ciprofloxacin/dexamethasone otic suspension (CIP/DEX) to ofloxacin otic solution (OFL) for treatment of granulation tissue in children with AOMT. STUDY DESIGN: 599 children aged >/=6 months to 12 years with AOMT of up to 3 weeks' duration were enrolled. Patients received either CIP/DEX 4 drops twice daily for 7 days or OFL 5 drops twice daily for 10 days. Granulation tissue severity was graded at clinic visits on days 1, 3, 11, and 18. RESULTS: Granulation tissue was present in 90 of 599 AOMT patients (15.0%) at baseline. CIP/DEX treatment was superior to OFL for reduction of granulation tissue at the day 11 visit (81.3% compared with 56.1%, P = 0.0067) and the day 18 visit (91.7% compared with 73.2%, P = 0.0223). Both topical otic preparations are safe and well tolerated in pediatric patients. CONCLUSION: CIP/DEX was superior to OFL in the treatment of granulation tissue in children with AOMT.

Single vs composite measures of pain intensity: relative sensitivity for detecting treatment effects.

Assay sensitivity remains a significant issue in pain clinical trials. One possible method for increasing assay sensitivity for detecting changes in pain intensity is to increase the reliability of pain intensity assessment by increasing the number of intensity ratings obtained, and combining these ratings into composite scores. The current study performed secondary analyses from a published clinical trial to test this possibility. The reliability and assay sensitivity pain intensity scores made up of 1 to 9 24-hour pain intensity recall ratings were compared. Although the reliability of the outcome measures improved as the number of items increased, this increase in reliability was not associated with an increase in assay sensitivity. A single 24-hour recall rating was about as valid (sensitive) for detecting treatment effects as composite scores made up of 2 to 9 different ratings. If this finding replicates in other pain populations, it has significant implications for the design and conduct of pain clinical trials. Specifically, it suggests the possibility that assessment burden (and associated costs and problems related to missing data) might be greatly reduced by specifying a single recall rating as the primary outcome variable. Research is needed to explore this possibility further.

The meaning of global outcome measures in pain clinical trials: more than just change in pain intensity.

OBJECTIVES: To understand the factors that contribute to patient and physician global outcome ratings and the extent to which receiving different doses of opioids or placebo might influence the importance of these factors better. METHODS: A secondary analysis was performed using data from a prospective, multicenter, double-blind placebo-controlled, and active-controlled parallel group dose-ranging study comparing the efficacy of oxymorphone extended release (ER) 20 mg (ER20, N=121); oxymorphone ER 40 mg (ER40, N=121); oxycodone controlled release 20 mg (Oxy20, N=125); and placebo (N=124) in a sample of patients with osteoarthritis. We performed 2 regression analyses to identify the predictors of pretreatment to posttreatment improvement in patient and physician global ratings of arthritis status. RESULTS: Improvement in global ratings of arthritis status was strongly associated with a decrease in pain intensity. Pretreatment to posttreatment improvement in physical and psychological functioning made independent contributions to the prediction of both criterion variables. DISCUSSION: The findings underscore the importance of change in pain intensity as a key correlate of ratings of global improvement. However, pain intensity is not the only important factor. In the current sample, improvement in both physical and psychological functioning made independent contributions to improvements in ratings of osteoarthritis status, supporting global ratings as assessing multicomponent domains. Overall, the findings suggest that when a patient or physician reports that the patient is "doing better," the patient is likely reporting less pain intensity and engaging in more physical activity and feeling better emotionally.

Tolerability of concomitant use of selective serotonin reuptake inhibitors or serotonin-norepinephrine reuptake inhibitors and oxymorphone extended release.

BACKGROUND: Opioids and antidepressants are frequently prescribed for chronic low back pain (cLBP). This post hoc analysis was conducted to assess the tolerability of oxymorphone extended release (ER) for cLBP in patients taking selective serotonin reuptake inhibitors (SSRIs) or serotonin-norepinephrine reuptake inhibitors (SNRIs) compared with patients not taking SSRIs/SNRIs. METHODS: Patients in 2 clinical trials (NCT00225797, November 22, 2004 to July 18, 2005; NCT00226421, October 13, 2004 to August 19, 2005) aged ≥ 18 years with moderate to severe cLBP were titrated to a stabilized dose of oxymorphone ER during an open-label titration phase and then randomized to treatment with this dose or placebo every 12 hours for 12 weeks. In a post hoc analysis, adverse events (AEs) were compared between patients taking versus not taking SSRIs/SNRIs. Treatment efficacy was assessed as change from baseline in average daily pain intensity on a 100-mm visual analog scale. RESULTS: Of 575 patients enrolled, 45 of 89 (50.6%) taking SSRIs/SNRIs and 303 of 486 (62.3%) not taking SSRIs/SNRIs successfully titrated to oxymorphone ER. The frequency of any AE did not differ significantly between the 2 subpopulations. During the titration phase, serious AEs occurred more frequently in patients taking SSRIs/SNRIs (3/89; 3.4%) compared with those not taking SSRIs/SNRIs (4/486; 0.8%; P = 0.04); however, during the double-blind treatment phase, there was no significant difference in the frequency of serious AEs in patients treated with oxymorphone ER taking (1/29; 3.4%) versus those not taking (3/146; 2.0%) SSRIs/SNRIs. Visual analog scale scores were similar in patients taking versus those not taking SSRIs/SNRIs throughout the study. CONCLUSION: The concomitant use of oxymorphone ER with SSRIs or SNRIs was well tolerated in patients with cLBP.

Positive and negative subjective effects of extended-release oxymorphone versus controlled-release oxycodone in recreational opioid users.

OBJECTIVE: To compare the subjective effects of oxymorphone extended release (OM-ER) versus oxycodone controlled release (OC-CR). DESIGN: Randomized, double-blind, crossover study. SETTING: Inpatient unit. SUBJECTS: Healthy, nondependent recreational opioid users. INTERVENTIONS: Single intact oral tablets that were placebo or contained OM-ER (15 and 30 mg) or OC-CR (30 and 60 mg). Doses were representative of mid-range doses for chronic pain and were calculated using an established opioid conversion table. MAIN OUTCOME MEASURES: Visual Analog Scales, Subjective Drug Value (SDV), and Addiction Research Center Inventory (ARCI) measured positive, negative, and balance effects and pupillometry. Equianalgesic comparisons were between OM-ER 15 mg versus OC-CR 30 mg (low doses) and OM-ER 30 mg versus OC-CR 60 mg (high doses). RESULTS: Thirty-five subjects received all five treatments. Positive subjective effects were lower for OM-ER 15 mg versus OC-CR 30 mg and for OM-ER 30 mg versus OC-CR 60 mg in ARCI Morphine Benzedrine Group (< or = 0.01 for both), Good Effects (p < 0.001 for both), Rush (p < 0.001 for both), and High VAS (p < 0.001 for both). Nausea was higher with OC-CR (p < or = 0.02), and Bad Effects were higher for OC-CR 60 mg versus OM-ER 30 mg (p < 0.001). Balance effects were lower for OM-ER versus OC-CR (Drug Liking, p < 0.001; Overall Drug Liking, p < or = 0.006; SDV, p < or = 0.008), except for Take Drug Again (p < 0.001 for OC-CR 30 mg versus OM-ER 15 mg; p = 0.18 for high-dose group). Euphoric mood, nausea, somnolence, vomiting, and dizziness were more common with OC-CR than OM-ER. LIMITATIONS: Single-dose design; use of healthy, recreational opioid users. CONCLUSIONS: At equianalgesic doses, single oral intact OM-ER produced lower positive, negative, and balance subjective effects than OC-CR, indicating that analgesic potency may not necessarily be reflected in subjective/objective effects.

Safety and efficacy of olopatadine hydrochloride nasal spray for the treatment of seasonal allergic rhinitis.

BACKGROUND: A nasal spray containing the antiallergy agent olopatadine hydrochloride is being developed for the treatment of seasonal allergic rhinitis (SAR). OBJECTIVE: To evaluate the safety and efficacy of 2 concentrations of olopatadine nasal spray vs placebo in patients with SAR. METHODS: This was a multicenter, randomized, double-blind, placebo-controlled study. After a 3- to 21-day placebo run-in, 565 patients aged 12 to 80 years were randomized to receive 0.4% or 0.6% olopatadine or placebo, 2 sprays per nostril twice daily for 2 weeks. Patients evaluated morning and evening reflective and instantaneous nasal symptoms (sneezing, stuffy nose, runny nose, and itchy nose, which compose the total nasal symptom score [TNSS]) and ocular symptoms and completed the Rhinoconjunctivitis Quality of Life Questionnaire (RQLQ). RESULTS: Olopatadine spray (0.4% and 0.6%) was significantly superior to placebo for percentage change from baseline in overall reflective (P = .004 and P < .001, respectively) and instantaneous (P = .02 and P = .003, respectively) TNSSs. Also, 0.6% olopatadine was significantly superior to placebo for reducing the reflective and instantaneous assessments of sneezing, runny and itchy nose, and itchy eyes; the instantaneous assessments of watery eyes; and the overall and all 7 domain scores of the RQLQ (P < .05). Olopatadine spray exhibited a safety profile comparable with that of placebo. CONCLUSIONS: Olopatadine nasal spray (0.4% and 0.6%) provided statistically significant improvements in allergic rhinitis symptoms compared with placebo regarding TNSSs (reflective and instantaneous) and in quality-of-life variables in patients with SAR. Olopatadine nasal spray administered twice daily was safe and well tolerated in adolescents and adults.

Topical ciprofloxacin/dexamethasone otic suspension is superior to ofloxacin otic solution in the treatment of children with acute otitis media with otorrhea through tympanostomy tubes.

OBJECTIVE: To determine the efficacy and safety of topical ciprofloxacin/dexamethasone otic suspension compared with ofloxacin otic solution in the treatment of acute otitis media with otorrhea through tympanostomy tubes (AOMT) in pediatric patients. METHODS: This multicenter, prospective, randomized, observer-masked, parallel-group study was conducted at 39 sites in 599 children aged >or=6 months to 12 years with an AOMT episode of