Objective and self-reported evidence of dextromethorphan antitussive efficacy in children, aged 6-11 years, with acute cough due to the common cold.

OBJECTIVE: To determine objective and subjective endpoints most suitable for evaluating antitussive efficacy of dextromethorphan hydrobromide (DXM) in children. Spontaneous resolution of acute cough and large placebo effects are impediments to evaluating antitussive efficacy. Another impediment is paucity of age-appropriate, validated cough assessment tools. METHODS: This was a multiple-dose, double-blind, placebo-controlled, randomized, pilot clinical study in children, aged 6-11 years, with cough due to the common cold. Eligible subjects met entry criteria and qualified by completing a run-in period where coughs were recorded with a cough monitor after they were dosed with sweet syrup. They were subsequently randomized to receive DXM or placebo over 4 days. Coughs were recorded during the initial 24 h; subjective assessments of cough severity and frequency were self-reported daily during treatment. RESULTS: Data from 128 evaluable subjects (67 DXM; 61 placebo) were analyzed. Total coughs over 24-hours (primary endpoint) and cough frequency during daytime were reduced by 21.0% and 25.5%, respectively, with DXM relative to placebo. Also, greater reductions in cough severity and frequency were self-reported with DXM. These findings were statistically significant and medically relevant. No effects were detected between treatments for nighttime cough rates or impact of cough on sleep. Multiple doses of DXM and placebo were generally well-tolerated. CONCLUSION: Evidence of DXM antitussive efficacy was shown in children using objective and subjective assessment tools validated in pediatric populations. Diurnal variation of cough frequency over 24 h reduced the assay sensitivity needed to detect treatment differences at nighttime, as coughs/hour decreased during sleep for both groups.

Use of systemic therapies in adults with atopic dermatitis: 12-month results from the European prospective observational study in patients eligible for systemic therapy for atopic dermatitis (EUROSTAD).

BACKGROUND: The European Prospective Observational Study in Patients Eligible for Systemic Therapy for Atopic Dermatitis (EUROSTAD) is an ongoing observational study aiming to describe characteristics of patients with atopic dermatitis (AD) treated with systemic therapy over time and the management of their disease in a real-world setting. METHODS: Data from patients enrolled in EUROSTAD between March 2017 and April 2019 were analyzed for systemic therapy use and treatment change over 12 months. RESULTS: 288 patients reported taking systemic medications; 42.7% received cyclosporine, 35.3% dupilumab, 28.1% methotrexate, 25.4% oral corticosteroids, 6.8% azathioprine, 6.1% injectable corticosteroids, and 3.4% mycophenolate. The median duration of treatment was 1.1 months for oral systemic corticosteroids, 3.2 months for injectable corticosteroids, 4.8 months for cyclosporine, 7.3 months for methotrexate, and 14.9 months for dupilumab. The most frequent reasons for stopping treatment included lack of efficacy, patient decision, adverse events, and disease well controlled. CONCLUSION: The 12-month interim EUROSTAD study analysis highlights the current trends and outcomes of systemic treatments for moderate-to-severe AD. Among all systemic treatments for AD, dupilumab was the least likely to be discontinued, whereas cyclosporine and corticosteroids, whilst effective, were primarily limited to episodic flare management consistent with treatment guidelines.

Disease burden and treatment history among adults with atopic dermatitis receiving systemic therapy: baseline characteristics of participants on the EUROSTAD prospective observational study.

BACKGROUND: Insights into the real-world treatment paradigm and long-term burden of atopic dermatitis (AD) are needed to inform clinical and health policy decisions. METHODS: The prospective, observational EUROSTAD study enrolled adults with moderate-to-severe AD starting or switching systemic therapy (51 sites in 10 European countries). We report the baseline characteristics, treatment patterns, and outcomes of these patients using descriptive statistics. RESULTS: A 12-month enrollment period of EUROSTAD was completed and 308 patients were enrolled: average age 37 years, AD duration 25 years, 43% were female. Most patients reported use of systemic therapy (93%) and ≥1 atopic comorbidity (82%). Mean [standard deviation] disease severity/burden measures were high: Investigator's Global Assessment (3.1 [0.8]), Eczema Area and Severity Index (16.2 [10.9]), Peak Pruritus Numerical Rating Scale (5.5 [2.5]), sleep impairment Visual Analog Scale (49.8 [31.6]) scores, and time lost from work (4.1 [13.7] days/year) or usual activities (16.8 [38.7] days/year). Most patients showed borderline or clinical levels of anxiety (59%) and/or depression (63%) using the Hospital Anxiety and Depression Scale. CONCLUSIONS: Adults with moderate-to-severe AD starting/switching systemic treatment enrolled in EUROSTAD have a high burden of longstanding disease despite continuous use of topical drugs, emollients, and systemic therapies.

Protocol for a prospective, observational, longitudinal study in paediatric patients with moderate-to-severe atopic dermatitis (PEDISTAD): study objectives, design and methodology.

INTRODUCTION: Atopic dermatitis (AD) is a chronic inflammatory skin disease often associated with atopic comorbidities and has significant impact on children and their families. There is a lack of robust and longitudinal long-term data on disease characteristics and typical clinical practice with currently available treatments in children with moderate-to-severe AD. Hence, an observational study is needed to evaluate AD characteristics and progression in paediatric patients with moderate-to-severe AD. METHODS AND ANALYSIS: Pediatric Study in Atopic Dermatitis (PEDISTAD) is a prospective, observational, longitudinal study in paediatric patients with moderate-to-severe AD who are currently receiving systemic or topical treatment and whose disease is not adequately controlled by topical prescription therapies or for whom those therapies are not medically advisable. 1300 children at 100-150 sites in approximately 20 countries worldwide will be enrolled and followed for 5 years. AD therapy is at the discretion of the investigator. Data collected will include: AD disease characteristics and comorbidities; current therapy for AD and initiation of new treatments/changes in current treatment; patient-reported/caregiver-reported outcomes; days missed from school/work for the patient/caregiver; healthcare professional visits; safety and biomarkers. ETHICS AND DISSEMINATION: This study is conducted in accordance with the principles established by the 18th World Medical Assembly and all subsequent amendments and the guidelines for Good Epidemiology Practice. Each individual country assures that ethics approval has been received and local regulatory requirements are met. Ethics approval has been obtained in all countries currently participating in PEDISTAD. Study data will be disseminated in manuscripts submitted to peer-reviewed medical journals as well as in abstracts submitted to congresses and in the resulting posters and presentations. TRIAL REGISTRATION NUMBER: NCT03687359; pre-results.

Efficacy and safety of dupilumab in perennial allergic rhinitis and comorbid asthma.

BACKGROUND: Dupilumab, an anti-IL-4 receptor α mAb, inhibits IL-4/IL-13 signaling, key drivers of type 2/TH2 immune diseases (eg, atopic/allergic disease). In a pivotal, phase 2b study (NCT01854047), dupilumab reduced severe exacerbations, improved lung function and quality of life, and was generally well tolerated in patients with uncontrolled persistent asthma despite using medium-to-high-dose inhaled corticosteroids plus long-acting ß2-agonists. OBJECTIVE: To examine dupilumab's effect on the 22-item Sino-Nasal Outcome Test (SNOT-22) total score and its allergic rhinitis (AR)-associated items in asthma patients with comorbid perennial allergic rhinitis (PAR). METHODS: A post hoc analysis reporting data from the phase 2b study for the 200 and 300 mg every 2 week (q2w) doses under investigation in phase 3 (NCT02414854) was carried out. PAR was defined at study entry as a specific response to typical perennial antigens (IgE ≥0.35 Ku/L). RESULTS: Overall, 241 (61%) patients had PAR. In asthma patients with PAR, dupilumab 300 mg q2w versus placebo significantly improved SNOT-22 total score (least squares mean difference, -5.98; 95% CI, -10.45 to -1.51; P = .009) and all 4 AR-associated symptoms evaluated (nasal blockage, -0.60; 95% CI, -0.96 to -0.25; runny nose, -0.67; 95% CI, -1.04 to -0.31; sneezing, -0.55; 95% CI, -0.89 to -0.21; postnasal discharge, -0.49; 95% CI, -0.83 to -0.16; all P < .01). Dupilumab 200 mg q2w demonstrated numerical, but not statistically significant, decreases in SNOT-22 total score (-1.82; 95% CI, -6.46 to 2.83; P = .443 vs placebo) and in each AR-associated symptom. In patients without PAR, no differences were observed for these measures versus placebo. CONCLUSIONS: Dupilumab 300 mg q2w significantly improved AR-associated nasal symptoms in patients with uncontrolled persistent asthma and comorbid PAR.

Brompheniramine and Chlorpheniramine Pharmacokinetics Following Single-Dose Oral Administration in Children Aged 2 to 17 Years.

Two pediatric studies characterized brompheniramine and chlorpheniramine pharmacokinetics in a total of 72 subjects, aged 2 to 17 years. A single age-/weight-based oral dose, ranging from 1 to 4 mg, was administered with 2 to 6 oz of water at least 2 hours after a light breakfast. Plasma samples were obtained before and for 72 hours after dosing and analyzed using high-pressure liquid chromatography-tandem mass spectrometry. Pharmacokinetic parameters were estimated using noncompartmental methods; relationships with age were assessed using linear regression. Results indicated that for brompheniramine and chlorpheniramine, Cmax was similar across age groups, although it tended to occur earlier in the youngest group. AUC was ∼15% to 30% higher in the oldest age group. As expected, CLo and Vz /F increased with age; however, following allometric scaling, no age-related differences existed. Because the increase with age for both parameters was similar, no age-related differences in t1/2,z existed (∼15 hours). Overall, the single doses were well tolerated. Sedation was the most common reported AE and appeared to be more prevalent in the 2- to 5-year-old group. Overall, these results indicate that an age/weight dosing nomogram using a 4-fold range of doses achieves similar Cmax and AUC.

Single- and Multiple-Dose Pharmacokinetics of Immediate-Release/Extended-Release Ibuprofen Tablets.

A single-dose, randomized, open-label, crossover study (study 1; n = 35) and a multiple-dose, randomized, open-label, crossover study (study 2; n = 28) compared the pharmacokinetics of a new immediate-release/extended-release (IR/ER) bilayer tablet formulation of ibuprofen 600 mg every 12 hours with standard ibuprofen 200 mg IR every 4 hours. In both studies, the 2 formulations were bioequivalent to each other for the area under the plasma concentration-versus-time curve from time 0 to the last measurable concentration (AUCL), to infinity (AUC∞ ), and to 12 hours (AUC0-12 ) and maximum concentration (Cmax ). In study 1, food slowed the absorption of ibuprofen from ibuprofen 600 mg IR/ER (lower Cmax ) compared with the fasted state but did not affect the overall extent (AUC) of ibuprofen absorption. In study 2, there was no evidence of drug accumulation with multiple doses of ibuprofen IR/ER. In conclusion, ibuprofen 600 mg IR/ER provides a twice-daily over-the-counter analgesic option that is bioequivalent to standard ibuprofen 200 mg IR (every 4 hours) with regard to both the rate (Cmax ) and the extent (AUC) of absorption.

Analgesic Efficacy of a New Immediate-Release/Extended-Release Formulation of Ibuprofen: Results From Single- and Multiple-Dose Postsurgical Dental Pain Studies.

Analgesic effects of ibuprofen immediate-release/extended-release (IR/ER) 600-mg tablets were evaluated in 2 randomized, double-blind, placebo-controlled dental pain studies. Patients 16-40 years old with moderate-severe pain following third-molar extraction received single-dose ibuprofen 600 mg IR/ER (formulation A or B), naproxen sodium 220 mg, or placebo (2:2:2:1; study 1) or 4 doses of ibuprofen 600 mg IR/ER (formulation A) or placebo (1:1; study 2). In study 1 (n = 196), mean (standard deviation [SD]) time-weighted sum of pain intensity difference scores for placebo, ibuprofen IR/ER A, ibuprofen IR/ER B, and naproxen, respectively, were 0.05 (9.2), 16.87 (9.4), 17.34 (10.5), and 12.66 (10.0) over 0-12 hours and -0.03 (4.1), 6.57 (4.4), 7.14 (5.2), and 5.14 (5.0) over 8-12 hours (all P < .001 vs placebo). In study 2 (n = 106), mean (SD) time-weighted sum of pain relief and pain intensity difference scores were 18.2 (20.0) versus 41.5 (21.0) at 0-12 hours and 10.3 (12.0) versus 18.4 (12.1) at 8-12 hours for placebo versus ibuprofen IR/ER, respectively (P < .001 for both); efficacy was sustained over each of the four 12-hour dosing intervals with ibuprofen. Gastrointestinal adverse events predominated with placebo both after study medication administration and after rescue medication use, if applicable. Ibuprofen 600 mg IR/ER provided safe and effective analgesia after single and multiple doses.

Antipyretic Efficacy and Safety of Ibuprofen Versus Acetaminophen Suspension in Febrile Children: Results of 2 Randomized, Double-Blind, Single-Dose Studies.

Two blinded single-dose studies randomized children 6 months to 11 years old with fever to receive ibuprofen (IBU) pediatric suspension 7.5 mg/kg or acetaminophen (APAP) suspension 10 to 15 mg/kg. The primary efficacy parameter was time-weighted sum of temperature differences (TWSTD) from baseline through 8 hours for each study. Secondary end points included TWSTD from baseline through 6 hours, time to onset and duration of temperature control, and proportion with temperature control. Studies were pooled for post hoc analyses of efficacy and adverse event end points. The primary efficacy parameter significantly favored IBU over APAP in study 1 and the pooled analysis (both P < .001), but was not significant in study 2. Onset of temperature control significantly favored IBU in study 2 ( P = .007). Individual and pooled secondary efficacy outcomes supported significant advantages ( P < .05) of IBU over APAP. IBU pediatric suspension provided greater temperature reduction versus acetaminophen in febrile children, with a comparable safety profile.

Consumer self-selection, safety, and compliance with a novel over-the-counter ibuprofen 600-mg immediate-release and extended-release tablet.

OBJECTIVE: The extent to which people comply with labeled instructions for use of long-acting over-the-counter analgesics is largely unknown; this study evaluated whether consumers can correctly select and use a new long-acting ibuprofen 600-mg immediate-release and extended-release (IR/ER) product. DESIGN: A single open-label study with participants randomly assigned to 2 substudies. Self-selection substudy: participants estimated duration of their last pain episode, then selected ibuprofen IR/ER or standard ibuprofen IR for a similar episode. Compliance substudy: participants purchased and recorded real-world use of ibuprofen IR/ER in daily diaries over 30 days. SETTING: Eighteen U.S. pharmacies. PARTICIPANTS: Consumers age 12 years or older who used an average of ≥5 doses per month of an over-the-counter analgesic in the past 3 months. INTERVENTION: Self-selection: questionnaire only. Compliance: ibuprofen IR/ER as needed. MAIN OUTCOME MEASURES: Self-selection: percentage who correctly selected or avoided selecting ibuprofen IR/ER based on anticipated pain duration. Compliance: proportion who were excessive users (use for >10 of 30 days and averaging >1600 mg/d, or >20 tablets over ≤10 days and averaging >1600 mg/d). RESULTS: Self-selection substudy (N = 249): on the primary endpoint, 69.1% (95% confidence interval [CI], 63.3%-74.8%) overall made a correct selection-63.5% (95% CI, 57.5%-69.4%) correctly selected ibuprofen IR/ER for pain ≥6 hours and 5.6% (95% CI, 2.8%-8.5%) correctly avoided selecting ibuprofen IR/ER for shorter-lasting pain. Overall, 82.7% (95% CI, 77.6%-87.8%) chose correctly when subjects who picked ibuprofen IR for pain ≥6 hours (a "missed opportunity," not an incorrect selection) were excluded. Compliance substudy (N = 405): only 5 participants (1.2%; 95% CI, 0.2%-2.3%) were excessive users; all took ibuprofen IR/ER for >10 days, averaging 1821 mg/day (range, 1661.5-2072.7 mg/d). No excessive user experienced an adverse event. CONCLUSION: Although the study did not meet the a priori primary efficacy outcome target, the majority of participants selected and used ibuprofen 600-mg IR/ER tablets correctly per the labeled instructions.

Next-day residual effects of gabapentin, diphenhydramine, and triazolam on simulated driving performance in healthy volunteers: a phase 3, randomized, double-blind, placebo-controlled, crossover trial.

OBJECTIVE: Next-day residual effects of a nighttime dose of gabapentin 250 mg were evaluated on simulated driving performance in healthy participants in a randomized, placebo-controlled, double-blind, multicenter, four-period crossover study that included diphenhydramine citrate 76 mg and triazolam 0.5 mg. METHODS: At treatment visits, participants (n = 59) were dosed at ~23:30, went to bed immediately, and awakened 6.5 h postdose for evaluation. The primary endpoint was the standard deviation of lateral position for the 100-km driving scenario. Additional measures of driving, sleepiness, and cognition were included. RESULTS: Study sensitivity was established with triazolam, which demonstrated significant next-day impairment on all driving endpoints, relative to placebo (p < 0.001). Gabapentin demonstrated noninferiority to placebo on standard deviation of lateral position and speed deviation but not for lane excursions. Diphenhydramine citrate demonstrated significant impairment relative to gabapentin and placebo on speed deviation (p < 0.05). Other comparisons were either nonsignificant or statistically ineligible per planned, sequential comparisons. Secondary endpoints for sleepiness and cognitive performance were supportive of these conclusions. CONCLUSIONS: Together, these data suggest that low-dose gabapentin had no appreciable next-day effects on simulated driving performance or cognitive functioning. Copyright © 2016 John Wiley & Sons, Ltd.

Pharmacokinetic effects of simultaneous administration of single-dose gabapentin 500 mg and zolpidem tartrate 10 mg in healthy volunteers: a randomized, open-label, crossover trial.

OBJECTIVE: Gabapentin is being investigated as a potential treatment for occasional disturbed sleep. This study assessed the pharmacokinetics and tolerability of gabapentin 500 mg and the commonly prescribed sedative/hypnotic zolpidem tartrate 10 mg, administered separately and in combination. METHODS: Forty healthy participants (19 male, 21 female) were randomized into this three-period crossover study [mean (range) age 34.1 (18-45) years, weight 68.3 (51.4-92.7) kg; 60 % white]. Participants were dosed with gabapentin alone (n = 39), zolpidem tartrate alone (n = 38), and the combination (gabapentin + zolpidem) (n = 38) over three treatment periods, which were separated by ≥7 days. Blood samples were collected pre-dose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 18, 24 and 36 h post-dose. Plasma concentrations of each drug were assayed using validated methods. Pharmacokinetic parameters were estimated from plasma concentration-time data using standard non-compartmental methods. RESULTS: For gabapentin + zolpidem combination versus gabapentin alone, mean pharmacokinetic parameters were peak plasma concentration (C max) 4.61 versus 4.72 µg/mL, time to Cmax (t max) 4.63 versus 3.64 h and the area under plasma concentration-time curve extrapolated to infinity (AUC0-∞) 53.4 versus 51.0 µg h/mL. For the combination versus zolpidem alone, mean pharmacokinetic parameters were C max 154 versus 138 ng/mL, t max 1.45 versus 1.84 h and AUC0-∞ 912 versus 854 ng h/mL. The 90 % confidence intervals for C max (rate of absorption) and AUC0-∞ (extent of absorption) comparing the combination versus single drug administration fell within the 80-125 % range accepted for bioequivalence. All treatments were well tolerated. CONCLUSION: The pharmacokinetics of gabapentin 500 mg and zolpidem tartrate 10 mg are unaffected when both drugs are taken simultaneously, compared with each drug taken alone.

Safety of a novel formulation of ibuprofen sodium compared with standard ibuprofen and placebo.

BACKGROUND: Ibuprofen (IBU) is an efficacious over-the-counter analgesic/antipyretic with adverse event (AE) rates comparable to placebo. IBU sodium (IBU(Na)) is a newer, more soluble form that is absorbed faster than standard IBU, leading to more rapid analgesia. Although its safety and tolerability are expected to be comparable to standard IBU, this has not yet been reported. METHODS: Pooled analysis comparing the safety of single-dose IBU(Na) (512 mg; equivalent to 400 mg IBU free acid; n = 362) with standard IBU tablets (400 mg; n = 342) and placebo (n = 187) across five Phase III, randomized, placebo-controlled, double-blind studies evaluating IBU(Na) for treatment of postoperative dental pain, tension-type headache, or fever. RESULTS: Treatment-emergent AEs (TEAEs) occurred in 5% of cases in the IBU(Na) group (25 events), 6.4% of cases in the standard IBU group (41 events), and 10.2% of cases in the placebo group (31 events). The most frequent TEAEs were in the following Medical Dictionary for Regulatory Activities (MedDRA) System Organ Classes: gastrointestinal disorders (2.8, 3.2, and 5.9% for IBU(Na), standard IBU, and placebo, respectively), nervous system disorders (1.4, 3.5, and 3.7% for IBU(Na), standard IBU, and placebo, respectively), and general disorders and administration-site conditions (1.1, 1.5, and 2.1% for IBU(Na), standard IBU, and placebo, respectively). Nausea was the most common TEAE (2.5, 2.6, and 5.9% for IBU(Na), standard IBU, and placebo, respectively). Only two AEs were considered related to treatment: pruritus (n = 1, IBU(Na)) and nausea (n = 1, placebo). Of those subjects reporting ≥ 1 TEAE, 44.4, 36.4, and 89.5% of subjects in the IBU(Na), standard IBU, and placebo groups, respectively, received rescue medication. CONCLUSION: IBU(Na) has a favorable safety profile comparable to those of standard IBU tablets and placebo in single-dose studies evaluating analgesic or antipyretic efficacy. ClinicalTrials.gov Registry Numbers: Dental pain studies: NCT01098747 and NCT01216163; headache studies: NCT01077973 and NCT01362491; pyresis study: NCT01035346.

A randomized, double-blind, single-dose, placebo-controlled, multicenter, polysomnographic study of gabapentin in transient insomnia induced by sleep phase advance.

STUDY OBJECTIVES: To evaluate the effects of single doses of gabapentin 250 and 500 mg on polysomnographic (PSG) and participant-reported sleep measures in a 5-h phase advance insomnia model. METHODS: Adults reporting occasional disturbed sleep received gabapentin 500 mg (n = 125), 250 mg (n = 125), or placebo (n = 127) 30 min prior to bedtime and were in bed from 17:00 to 01:00, ∼5 h before their habitual bedtime. Sleep was assessed by PSG, post-sleep questionnaire, and the Karolinska Sleep Diary (KSD). Next-day residual effects (Digit Symbol Substitution Test [DSST] and Stanford Sleepiness Scale [SSS]) and tolerability were assessed. RESULTS: Demographics were comparable among groups. Among PSG endpoints, wake after sleep onset (primary endpoint) (135.7 [placebo], 100.7 [250 mg], and 73.2 [500 mg] min) was significantly lower and total sleep time (TST) (311.4, 356.5, and 378.7 min) significantly greater in both gabapentin groups versus placebo. Latency to persistent sleep was not significantly different among groups. Percent slow wave sleep (12.6%, 15.4%, and 17.0%, respectively) was significantly greater and percent stage 1 (15.1%, 11.8%, and 10.8%, respectively) significantly lower relative to placebo. Gabapentin was associated with significantly higher values of KSD Sleep Quality Index and reported TST versus placebo; no other reported outcomes were significant. Neither gabapentin dose produced evidence of next-day residual effects as measured by DSST and SSS. Adverse events were infrequent (< 5%). CONCLUSION: Participants with occasional disturbed sleep treated with gabapentin showed significantly longer sleep duration and greater depth (versus placebo) in response to a phase advance manipulation known to disrupt sleep maintenance.

A randomized, double-blind, placebo-controlled, multicenter, 28-day, polysomnographic study of gabapentin in transient insomnia induced by sleep phase advance.

STUDY OBJECTIVE: To evaluate multiple doses of gabapentin 250 mg on polysomnography (PSG) and participant-reported sleep assessments in a 5-h phase advance insomnia model. METHODS: Adults reporting occasional disturbed sleep received gabapentin 250 mg (n = 128) or placebo (n = 128). On Days 1 and 28, participants received medication 30 min before bedtime and were in bed from 17:00 to 01:00, ∼5 h before their habitual bedtime. Sleep was assessed by PSG, a post sleep questionnaire, and the Karolinska Sleep Diary. Next-day residual effects and tolerability were evaluated. On Days 2-27, participants took medication at home 30 min before their habitual bedtime. RESULTS: Treatment-group demographics were comparable. Gabapentin resulted in significantly less PSG wake after sleep onset (WASO) compared with placebo on Day 1 (primary endpoint, mean: 107.0 versus 149.1 min, p ≤ 0.001) and Day 28 (113.6 versus 152.3 min, p = 0.002), and significantly greater total sleep time (TST; Day 1: 347.6 versus 283.9 min; Day 28: 335.3 versus 289.1 min) (p ≤ 0.001). Participant-reported WASO and TST also showed significant treatment effects on both days. Gabapentin was associated with less %stage1 on Day 1, and greater %REM on Day 28, versus placebo. During home use, gabapentin resulted in significantly less participant-reported WASO and higher ratings of sleep quality. Gabapentin was well tolerated (most common adverse events: headache, somnolence) with no evidence of next-day impairment. CONCLUSION: Gabapentin 250 mg resulted in greater PSG and participant-reported sleep duration following a 5-h phase advance on Day 1 and Day 28 of use without evidence of next-day impairment, and greater sleep duration during at-home use.

Common cold symptoms in children: results of an Internet-based surveillance program.

BACKGROUND: Conducting and analyzing clinical studies of cough and cold medications is challenging due to the rapid onset and short duration of the symptoms. The use of Internet-based surveillance tools is a new approach in clinical studies that is gradually becoming popular and may become a useful method of recruitment. As part of an initiative to assess the safety and efficacy of cough and cold ingredients in children 6-11 years of age, a surveillance program was proposed as a means to identify and recruit pediatric subjects for clinical studies. OBJECTIVE: The objective of the study was to develop an Internet-based surveillance system and to assess the feasibility of using such a system to recruit children for common cold clinical studies, record the natural history of their cold symptoms, and determine the willingness of parents to have their children participate in clinical studies. METHODS: Healthy potential subjects were recruited via parental contact online. During the 6-week surveillance period, parents completed daily surveys to record details of any cold symptoms in their children. If a child developed a cold, symptoms were followed via survey for 10 days. Additional questions evaluated the willingness of parents to have their children participate in a clinical study shortly after onset of symptoms. RESULTS: The enrollment target of 248 children was reached in approximately 1 week. Children from 4 distinct geographic regions of the United States were recruited. Parents reported cold symptoms in 163 children, and 134 went on to develop colds. The most prevalent symptoms were runny nose, stuffed-up nose, and sneezing. The most severe symptoms were runny nose, stuffed-up nose, and sore/scratchy throat. The severity of most symptoms peaked 1-2 days after onset. Up to 54% of parents expressed willingness to bring a sick child to a clinical center shortly after the onset of symptoms. Parents found the Internet-based surveys easy to complete. CONCLUSIONS: Internet-based surveillance and recruitment can be useful tools to follow colds in children and enroll subjects in clinical studies. However, study designs should account for a potentially high dropout rate and low rate of adherence to study procedures.

Modeling the onset and offset of dental pain relief by ibuprofen.

Onset and offset of dental pain relief by ibuprofen following third molar extraction were modeled in a randomized, double-blind, placebo-controlled, parallel-group, 8-hour study of patients receiving either a novel effervescent ibuprofen tablet (400 mg; N = 30), standard ibuprofen tablets (Nurofen(®) 2 × 200 mg; N = 22), or placebo (N = 37). An Emax model was fit to pain relief scores. Linear hazard models were used to analyze the time to first perceptible relief (TFPR), the time to meaningful pain relief (TMPR), and time to remedication (REMD). Nomograms were created to correlate TFPR, TMPR, and REMD with different ibuprofen pharmacokinetic profiles. Effervescent ibuprofen was absorbed rapidly with 95% completion within 15 minutes. Maximum pain relief score by ibuprofen was 1.8 units greater than placebo, with an EC50 (effect-site) for ibuprofen concentration of 10.2 µg·mL(-1). The likelihood to achieve TFPR and TMPR was doubled for every 10 µg·mL(-1) increase in ibuprofen plasma concentration. REMD risk decreased 40-fold as the categorical pain relief score increased from 0 to 3. Rapid absorption of ibuprofen effervescent resulted in an earlier TFPR and TMPR, and a lower REMD rate than standard ibuprofen. The nomograms may be useful in predicting the onset and offset of new faster acting ibuprofen formulations, based on pharmacokinetic profiles.