Effect of montelukast for treatment of asthma in cigarette smokers.

OBJECTIVE: Many asthmatic patients are unable to quit cigarettes; therefore information is needed on treatment options for smokers. This study evaluates 10 mg/d montelukast and 250 µg of fluticasone propionate twice daily, each compared with placebo, in patients with self-reported active smoking (unable to quit) and asthma. METHODS: Patients (ages 18-55 years, with asthma [≥1 year], FEV1 of 60% to 90% of predicted value, airway reversibility [≥12%], and self-reported active smoking [≥0.5 to ≤2 packs per day]) were randomized (after a 3-week, single-blind, placebo, run-in period) to 1 of 3 parallel, 6-month, double-blind treatment arms. The primary efficacy end point was the percentage of days with asthma control during treatment. Adverse experiences (AEs) were also evaluated. RESULTS: There were 347, 336, and 336 patients randomized to montelukast, fluticasone, and placebo, respectively. The mean percentage of days with asthma control over 6 months of treatment was 45% (montelukast, P < .05 vs placebo), 49% (fluticasone, P < .001 vs placebo), and 39% (placebo); the difference between montelukast and fluticasone was not significant (P = .14). Patients with a smoking history of ≤11 pack years (the median value) tended to show more benefit with fluticasone, whereas those with a smoking history of >11 pack years tended to show more benefit with montelukast. AEs occurred in similar proportions among treatment groups. CONCLUSIONS: In a population of asthmatic patients actively smoking cigarettes, both 10 mg/d montelukast and 250 µg of fluticasone propionate twice daily significantly increased the mean percentage of days with asthma control compared with placebo.

Indirect comparison of pembrolizumab monotherapy versus nivolumab + ipilimumab in first-line metastatic lung cancer.

Aim: This study indirectly compared the effectiveness of pembrolizumab monotherapy versus nivolumab + ipilimumab in metastatic non-small-cell lung cancer. Materials and methods: A matching-adjusted indirect comparison was conducted using pooled individual patient data from KEYNOTE-024 and KEYNOTE-042 and published aggregate data from CheckMate 227 Part 1A, with platinum doublet chemotherapy as the anchor. Results: After matching, estimated hazard ratios (95% CI) of pembrolizumab monotherapy versus nivolumab + ipilimumab for overall survival and progression-free survival were 1.07 (0.82, 1.39) and 1.16 (0.93, 1.45), respectively. For objective response rate, the estimated risk ratio (95% CI) was 0.93 (0.71, 1.22) and the risk difference (95% CI) was -2.86%(-11.38, 5.67). Conclusion: Matching-adjusted indirect comparison results demonstrated comparable effectiveness between pembrolizumab monotherapy and nivolumab + ipilimumab as first-line therapies for metastatic non-small-cell lung cancer with PD-L1 tumor-proportion score ≥1%.

The efficacy and tolerability of inhaled montelukast plus inhaled mometasone compared with mometasone alone in patients with chronic asthma.

BACKGROUND: The efficacy of oral montelukast in chronic asthma is well established. Montelukast is also an effective adjunctive therapy to inhaled corticosteroids (ICS) in asthma uncontrolled on ICS alone. Inhaled montelukast was recently shown to provide significant bronchodilation compared with placebo in patients with chronic asthma. The purpose of this study was to evaluate the efficacy of inhaled montelukast added to inhaled mometasone. METHODS: This was an 8-week, multicenter, randomized, double-blind, placebo-controlled study comparing once-daily inhaled montelukast 1 mg plus inhaled mometasone 220 µg (delivered by separate dry powder inhalers) with placebo plus inhaled mometasone 220 µg. Men and women aged 15-85 years with chronic asthma, forced expiratory volume in 1 second (FEV(1)) 50-80% of the predicted value, and ß-agonist reversibility ≥12% were eligible. Patients were required to meet a minimum symptom threshold while receiving open-label inhaled mometasone during a 3-week prestudy/run-in period. Patients received blinded (montelukast vs. placebo) treatment for 2 weeks, entered a 1-week washout period, then crossed over to the other treatment for 2 weeks. The primary endpoint was the average change from baseline in FEV(1) over the 2-week treatment period. Secondary endpoints included daytime and nighttime symptom scores. Other endpoints included short-acting ß-agonist (SABA) use, asthma exacerbations, asthma control, peak expiratory flow (PEF), and blood eosinophil count. RESULTS: A total of 134 patients were randomized. For the primary endpoint, change from baseline in FEV(1), inhaled montelukast plus inhaled mometasone was significantly more effective than placebo plus inhaled mometasone (least squares mean 0.22 L vs. 0.17 L; p = .033 [two-sided at α = 0.05]). Inhaled montelukast plus inhaled mometasone was also significantly more effective than placebo plus inhaled mometasone in improving daytime asthma symptom scores (p = .005) and nighttime asthma symptom scores (p = .015), increasing the percentage of days with asthma control (p = .004), decreasing the percentage of days with asthma exacerbations (p ≤ .001), and decreasing the blood eosinophil count (p = .013). Differences were not significant on AM or PM PEF or SABA use, although the latter approached significance (p = .073). Both treatments were well tolerated. CONCLUSION: Inhaled montelukast plus inhaled mometasone was significantly more effective than placebo plus inhaled mometasone in improving FEV(1), symptoms, asthma control, and blood eosinophil count.

Pembrolizumab+chemotherapy versus atezolizumab+chemotherapy+/-bevacizumab for the first-line treatment of non-squamous NSCLC: A matching-adjusted indirect comparison.

OBJECTIVES: Multiple immunotherapy and chemotherapy combinations are approved for the management of advanced NSCLC which have not been directly compared in randomized clinical trials. This study indirectly compared the effectiveness of pembrolizumab + chemotherapy versus atezolizumab + chemotherapy+/-bevacizumab for previously untreated non-squamous NSCLC patients without EGFR/ALK aberrations. MATERIALS AND METHODS: A matching-adjusted indirect comparison (MAIC) was conducted using individual patient data (IPD) from KEYNOTE-021 Cohort G (KN021 G) (pembrolizumab + carboplatin + pemetrexed; N = 59) and KEYNOTE-189 (KN189) (pembrolizumab + pemetrexed + platinum chemotherapy; N = 410) and published aggregate data from IMpower 130 (atezolizumab + carboplatin + nab-paclitaxel; N = 451) and IMpower 150 (atezolizumab + carboplatin + paclitaxel + bevacizumab; N = 356). To adjust for cross-trial differences in baseline characteristics, data from patients randomized to pembrolizumab + chemotherapy in KN021 G/KN189 were reweighted to match the baseline characteristics of patients randomized to atezolizumab + chemotherapy from IMpower 130 or atezolizumab + chemotherapy + bevacizumab from IMpower 150. Outcomes included overall survival (OS), blinded independent review-assessed progression-free survival (PFS) and objective response rate (ORR). OS and PFS follow-up were truncated to the trial with shorter follow-up. Sensitivity analyses were conducted without truncation of follow-up of OS and PFS. RESULTS: After matching for cross-trial differences, the effective sample size of pembrolizumab + chemotherapy was 428 and 389 for the IMpower 130 and IMpower 150 comparisons, respectively. The estimated HRs (95 % CIs) of pembrolizumab + chemotherapy versus atezolizumab + chemotherapy were 0.80 (0.67,0.95) and 0.79 (0.67,0.93) with regard to OS and PFS, respectively. For pembrolizumab + chemotherapy versus atezolizumab + chemotherapy + bevacizumab, the estimated HR (95 % CIs) was 0.86 (0.72,1.03) for OS and 0.81 (0.68,0.96) for PFS. For ORR, the estimated risk ratio (95 % CI) and the risk difference (95 % CI) was 0.9 (0.8,1.1) and -3.5 % (-10.0,3.1) for pembrolizumab + chemotherapy versus atezolizumab + chemotherapy, respectively, and 0.8 (0.7,0.9) and -12.2 % (-19.6,-4.8) for pembrolizumab + chemotherapy versus atezolizumab + chemotherapy + bevacizumab, respectively. Findings were consistent across sensitivity analyses for both outcomes. CONCLUSION: MAIC results showed a significantly better OS and PFS for pembrolizumab + chemotherapy compared with atezolizumab + chemotherapy and a significantly better PFS for pembrolizumab + chemotherapy compared with atezolizumab + chemotherapy + bevacizumab.

Cost-effectiveness of pembrolizumab + chemotherapy versus chemotherapy and pembrolizumab monotherapy in first line treatment of NSCLC in the US - updated analyses with additional trial follow-up.

OBJECTIVE: Pembrolizumab + chemotherapy substantially extends life expectancy for metastatic non-small cell lung cancer (NSCLC) patients. Its cost-effectiveness (CE) was previously evaluated based on interim trial analyses (follow-up ∼1 year). The present analysis describes CE incorporating additional follow-up based on protocol-specified final trial analyses (1-1.5 years additional follow-up), from a US healthcare payer perspective. METHODS: A partitioned survival model is used to compare pembrolizumab + chemotherapy vs chemotherapy using data from the KN189 (non-squamous patients) and KN407 (squamous patients) clinical trials. An indirect treatment comparison vs pembrolizumab monotherapy is made for patient subgroups with PD-L1 TPS ≥50% and 1-49% based on data from the KN024 and KN042 trials. Efficacy, treatment utilization, health utility, and safety data are derived from trials and projected over 20 years. Costs for drugs, non-drug disease management, and adverse events are also incorporated. RESULTS: Overall, versus chemotherapy alone, pembrolizumab + chemotherapy is projected to increase life expectancy by 1.12 years (3.35 vs 2.23) and 0.67 years (3.17 vs 2.50) in non-squamous and squamous patients, respectively. Resultant ICERs ($158,030/QALY and $178,387/QALY) are below a US 3-times GDP per capita threshold ($195,000/QALY). ICERs vs chemotherapy also generally fall below the threshold within PD-L1 sub-groups (except in squamous PD-L1 < 1%, which may have differed due to small sample size) while ICERs vs pembrolizumab monotherapy in PD-L1 ≥ 50% and 1-49% sub-groups generally exceed it (except in squamous PD-L1 1-49%); largely a result of the higher drug acquisition cost of pembrolizumab + chemotherapy relative to differences in life expectancy. CONCLUSIONS: Taken together, with longer-term trial follow-up and in the context of prior literature, in the US, one of the two options for pembrolizumab use (either pembrolizumab + chemotherapy or pembrolizumab monotherapy), represents a cost-effective treatment in virtually all non-squamous and squamous metastatic NSCLC patient populations and PD-L1 sub-groups evaluated.

A phase I randomized, placebo-controlled, dose-exploration study of single-dose inhaled montelukast in patients with chronic asthma.

BACKGROUND: The efficacy of oral montelukast has been well established in asthma and allergic rhinitis in adults and children. The purpose of this study was to evaluate dose-related bronchodilation and tolerability of inhaled montelukast. METHODS: Randomized, double-blind, crossover, adaptive-design study comparing single-dose administration of inhaled montelukast versus placebo in patients age 15-65 years with chronic asthma (n = 68). Montelukast was delivered as a witnessed dose through dry powder inhaler at doses of 25, 250, or 1000 µg, and doses of 50, 100, and 500 µg could be used if needed based on a prespecified dose-response algorithm. Each administration was followed by a 4- to 7-day washout period before crossing over to the next treatment. The primary endpoint was the change from baseline in a forced expiratory volume in 1 second (FEV1) over the first 4 hours after administration, calculated as a time-weighted average (ΔFEV1 [0-4 hours]). Other endpoints included the onset and duration of bronchodilation and the effect of albuterol when added to inhaled montelukast. RESULTS: Over 4 hours postdose, and compared with placebo (least-squares [LS] mean 0.03 L), inhaled montelukast 100 µg (0.13 L; p ≤ .001), 250 µg (0.10 L; p < .01), and 1000 µg (0.12 L; p ≤ .001) had significantly greater ΔFEV1 (0-4 hours). At 24 hours postdose, inhaled montelukast 100 µg (0.10 L) and 1000 µg (0.09 L) had significantly greater bronchodilation compared with placebo (0.02 L; p < .05 vs. montelukast). Montelukast 1000 µg provided significant bronchodilation versus placebo within 20 minutes of administration (0.03 L vs. -0.05 L), whereas montelukast 100 µg provided significant bronchodilation relative to placebo within 2 hours of dosing (0.09 L vs. 0.01 L). Montelukast (pooled doses) plus albuterol was significantly more effective than montelukast plus placebo for ΔFEV1 (0-90 minutes) (0.34 L vs. 0.15 L; p = .015). The tolerability of inhaled montelukast was similar to that of placebo. No serious adverse experiences were reported. CONCLUSIONS: Inhaled montelukast provided significant bronchodilation compared with placebo as early as 20 minutes after the administration that persisted for 24 hours and provided additive bronchodilation to albuterol.

A Matching-Adjusted Indirect Comparison of Pembrolizumab + Chemotherapy vs. Nivolumab + Ipilimumab as First-Line Therapies in Patients with PD-L1 TPS ≥1% Metastatic NSCLC.

BACKGROUND: In the absence of head-to-head trials, this study indirectly compared the effectiveness of pembrolizumab + chemotherapy vs nivolumab + ipilimumab for the first-line treatment of metastatic stage IV NSCLC patients with PD-L1 tumor proportion score (TPS) ≥1%. METHODS: An anchored matching-adjusted indirect comparison (MAIC) was conducted using pooled individual patient data (IPD) from the ITT population in KEYNOTE-021G, KEYNOTE-189 and KEYNOTE-407 (n = 816) and published aggregate data of nivolumab + ipilimumab from CheckMate 227 Part 1A (n = 793). To adjust for cross-trial differences in baseline characteristics, data from KEYNOTE-021G/KEYNOTE-189/KEYNOTE-407 were re-weighted to match the baseline characteristics of CheckMate 227 Part 1A. Outcomes included OS, PFS and ORR. Base case analyses were restricted to patients with PD-L1 TPS ≥1%, with sub-group analyses in PD-L1 TPS ≥50% and 1-49%. RESULTS: The estimated HR (95% CI) of pembrolizumab + chemotherapy vs nivolumab + ipilimumab was 0.80 (0.59,1.09) and 0.53 (0.41,0.68) for OS and PFS, respectively. For ORR, the estimated risk ratio was 1.8 (1.3,2.4) for pembrolizumab + chemotherapy vs nivolumab + ipilimumab and the risk difference was 25.5% (15.0,36.0). PD-L1 TPS ≥50% and 1-49% sub-groups showed an OS HR of 0.89 (0.58,1.36) and 0.68 (0.46,1.01), respectively. CONCLUSION: These MAIC results suggest that pembrolizumab + chemotherapy leads to a greater clinical benefit vs nivolumab + ipilimumab in patients with PD-L1 TPS ≥1% across multiple endpoints.

Cost-effectiveness of pembrolizumab in combination with chemotherapy versus chemotherapy and pembrolizumab monotherapy in the first-line treatment of squamous non-small-cell lung cancer in the US.

Objective: To describe the cost-effectiveness of pembrolizumab plus chemotherapy (carboplatin and paclitaxel or nab-paclitaxel; P + C) in metastatic, squamous, non-small-cell lung cancer (NSCLC) patients in the US. Methods: A model comparing P + C versus C alone is developed utilizing partitioned survival analysis. Primary clinical efficacy, treatment utilization, health utility and safety data are derived from the KEYNOTE-407 trial and projected over 20 years. Costs for drugs and non-drug disease management are also incorporated. Additionally, the cost-effectiveness of P + C vs. pembrolizumab monotherapy (P) is evaluated via an indirect treatment comparison, for patient subgroups with PD-L1 Tumor Proportion Score (TPS) ≥ 50% and 1-49%. Results: Overall, P + C is projected to increase life expectancy by 1.95 years vs. C (3.86 versus 1.91). The resultant ICER is $86,293/QALY. In patients with PD-L1 ≥ 50%, 1-49% and <1 the corresponding incremental cost-effectiveness ratios (ICERs) are $99,777/QALY, $85,986/QALY and $87,507/QALY, respectively. Versus P, in the PD-L1 ≥ 50% subgroup, P + C appears cost saving; however, this result should be interpreted with caution as there is considerable uncertainty in the relative efficacy of these comparators. Conclusions: Across all eligible patients, the addition of pembrolizumab to chemotherapy is projected to approximately double life expectancy, yielding an extension to a point not previously seen in metastatic squamous NSCLC. Overall, and within all relevant PD-L1 subgroups, use of P + C yields an ICER below $100,000/QALY, and can be a cost-effective first-line treatment for eligible metastatic squamous NSCLC patients for whom chemotherapy is currently administered. In the PD-L1 ≥ 50% subgroup, additional follow-up within trials of pembrolizumab plus chemotherapy and pembrolizumab monotherapy are needed to better define cost-effectiveness between these comparators.

Updated Analysis of KEYNOTE-024: Pembrolizumab Versus Platinum-Based Chemotherapy for Advanced Non-Small-Cell Lung Cancer With PD-L1 Tumor Proportion Score of 50% or Greater.

PURPOSE: In the randomized, open-label, phase III KEYNOTE-024 study, pembrolizumab significantly improved progression-free survival and overall survival (OS) compared with platinum-based chemotherapy in patients with previously untreated advanced non-small-cell lung cancer (NSCLC) with a programmed death ligand 1 tumor proportion score of 50% or greater and without EGFR/ALK aberrations. We report an updated OS and tolerability analysis, including analyses adjusting for potential bias introduced by crossover from chemotherapy to pembrolizumab. PATIENTS AND METHODS: Patients were randomly assigned to pembrolizumab 200 mg every 3 weeks (for up to 2 years) or investigator's choice of platinum-based chemotherapy (four to six cycles). Patients assigned to chemotherapy could cross over to pembrolizumab upon meeting eligibility criteria. The primary end point was progression-free survival; OS was an important key secondary end point. Crossover adjustment analysis was done using the following three methods: simplified two-stage method, rank-preserving structural failure time, and inverse probability of censoring weighting. RESULTS: Three hundred five patients were randomly assigned (pembrolizumab, n = 154; chemotherapy, n = 151). At data cutoff (July 10, 2017; median follow-up, 25.2 months), 73 patients in the pembrolizumab arm and 96 in the chemotherapy arm had died. Median OS was 30.0 months (95% CI, 18.3 months to not reached) with pembrolizumab and 14.2 months (95% CI, 9.8 to 19.0 months) with chemotherapy (hazard ratio, 0.63; 95% CI, 0.47 to 0.86). Eighty-two patients assigned to chemotherapy crossed over on study to receive pembrolizumab. When adjusted for crossover using the two-stage method, the hazard ratio for OS for pembrolizumab versus chemotherapy was 0.49 (95% CI, 0.34 to 0.69); results using rank-preserving structural failure time and inverse probability of censoring weighting were similar. Treatment-related grade 3 to 5 adverse events were less frequent with pembrolizumab compared with chemotherapy (31.2% v 53.3%, respectively). CONCLUSION: With prolonged follow-up, first-line pembrolizumab monotherapy continues to demonstrate an OS benefit over chemotherapy in patients with previously untreated, advanced NSCLC without EGFR/ALK aberrations, despite crossover from the control arm to pembrolizumab as subsequent therapy.

Efficacy of the selective extrasynaptic GABA A agonist, gaboxadol, in a model of transient insomnia: a randomized, controlled clinical trial.

OBJECTIVE: The hypnotic efficacy of gaboxadol, a selective extrasynaptic GABA A agonist (SEGA), was evaluated in a phase-advance model of transient insomnia. METHODS: Healthy subjects (18-64 years) completed a randomized, double-blind, parallel group study in which the sleep period was advanced 4h from habitual sleep time. Polysomnographic (PSG) and self-reported sleep measures were used to compare gaboxadol 10mg (N =271) and 15 mg (N =274) versus placebo (N =277). RESULTS: In the placebo group, the phase-advance procedure disrupted sleep maintenance as measured by PSG wakefulness after sleep onset (WASO) and self-reported WASO (sWASO), and also, to a lesser extent, disrupted sleep onset as measured by PSG latency to persistent sleep (LPS) and self-reported time to sleep onset (sTSO). Both doses of gaboxadol decreased WASO and sWASO versus placebo (p

Cost-effectiveness of pembrolizumab in combination with chemotherapy in the 1st line treatment of non-squamous NSCLC in the US.

AIMS: To describe cost-effectiveness of pembrolizumab plus platinum and pemetrexed chemotherapy in metastatic, non-squamous, NSCLC patients in the US. MATERIALS AND METHODS: A model is developed utilizing partitioned survival analysis to estimate the cost-effectiveness of KEYNOTE-189 trial comparators pembrolizumab + chemotherapy (carboplatin/cisplatin + pemetrexed) vs chemotherapy alone. Clinical efficacy, treatment utilization, health utility, and safety data are derived from the trial and projected over 20 years. For extrapolating survival beyond the trial, a novel SEER population-data approach is applied (primary analysis), with separate estimation via traditional parametric extrapolation methods. Costs for drugs and non-drug disease management are also incorporated. Based on an indirect treatment comparison, cost-effectiveness of pembrolizumab + chemotherapy vs pembrolizumab monotherapy is evaluated for patients with programmed death-ligand 1 (PD-L1) ≥ 50%. RESULTS: In the full non-squamous population, pembrolizumab + chemotherapy is projected to increase life expectancy by 2.04 years vs chemotherapy (3.96 vs 1.92), for an approximate doubling of life years. Resultant incremental cost-effectiveness ratios (ICERs) are $104,823/QALY and $87,242/life year. In patients with PD-L1 ≥ 50% and 1-49%, life expectancy is more than doubled (4.53 vs 1.88 years) and (4.87 vs 2.01 years), with a 32% (2.60 vs 1.97 years) increase in PD-L1 < 1% patients. Corresponding incremental costs/quality-adjusted life year (QALY) are $103,402, $66,837, and $183,529 for PD-L1 ≥ 50%, 1-49%, and <1% groups, respectively. Versus pembrolizumab monotherapy in PD-L1 ≥ 50% patients, representing current standard of care, pembrolizumab + chemotherapy increases life expectancy by 65% (4.53 vs 2.74 years) at an ICER of $147,365/QALY. LIMITATIONS AND CONCLUSIONS: The addition of pembrolizumab to chemotherapy is projected to extend life expectancy to a point not previously seen in previously untreated metastatic non-squamous NSCLC. Although ICERs vary by sub-group and comparator, results suggest pembrolizumab + chemotherapy yields ICERs near, or in most cases, well below a 3-times US per capita GDP threshold of $180,000/QALY, and may be a cost-effective first-line treatment for metastatic non-squamous NSCLC patients.

Alendronate prevents loss of bone density associated with discontinuation of hormone replacement therapy: a randomized controlled trial.

BACKGROUND: Many women using hormone replacement therapy (HRT) will discontinue HRT and lose its bone-protective effect. Methods to preserve bone density in these women need to be explored. This multicenter, international, randomized, blinded, 12-month study was conducted to assess the effect of alendronate sodium on bone density in women who had recently discontinued HRT. METHODS: The 144 postmenopausal women included in the study were diagnosed as having low bone mineral density (BMD) and had recently discontinued HRT. They were randomized to receive either a daily dose of 10 mg of alendronate sodium or matching placebo. The main outcome measures were spine, hip, and total body BMD; biochemical markers of bone turnover; and tolerability. RESULTS: Alendronate treatment was associated with a 2.3% mean increase (95% confidence interval [CI], 1.7%-3.0%) in spine BMD compared with a mean loss of 3.2% (95% CI, - 4.6% to - 1.7%) in patients receiving placebo, for a difference of 5.5% (95% CI, 4.2%-6.8%) between alendronate and placebo. Greater hip and total body BMD preservation was also observed with alendronate use. Bone turnover decreased significantly with alendronate (bone-specific alkaline phosphatase levels decreased by 20% and urinary N-telopeptide/creatinine ratio by 47%), but increased in the placebo group (by 18% and 36%, respectively). Alendronate was well tolerated, with no increase in adverse events compared with placebo. CONCLUSIONS: A high rate of bone loss was observed in the first 12 to 15 months after discontinuation of HRT in postmenopausal women with low BMD. Treatment with alendronate increased or maintained both spine and hip BMD and prevented the increase in bone resorption seen with withdrawal of HRT in this population.

A comparison of visual analog scale and categorical ratings of headache pain in a randomized controlled clinical trial with migraine patients.

A visual analog scale (VAS) method of assessing headache pain was compared with a standard categorical four-grade scale (4GS) in a randomized, placebo-controlled, double-blind, clinical trial involving 792 treated migraine outpatients who received oral rizatriptan 5 mg, sumatriptan 50 mg, or placebo for a moderate or severe headache. The VAS and 4GS were equally useful in demonstrating that the active drugs were superior to placebo at reducing headache pain, and in showing that the active drugs were similarly effective. For both rizatriptan and sumatriptan, slightly larger effect sizes were observed with the 4GS compared with the VAS. In analyses using data combined across all treatment groups, VAS and 4GS scores were highly correlated. Use of the VAS imposed additional administrative burdens. These findings suggest that the 4GS may be the preferred scale for assessing headache pain in clinical trials involving adult migraineurs.

Weekly oral alendronic Acid in male osteoporosis.

OBJECTIVE: To evaluate the efficacy and tolerability of alendronic acid 70mg once weekly for the treatment of male osteoporosis. PATIENTS AND METHODS: This randomised, double-blind, placebo-controlled, 12-month trial compared the effect of alendronic acid 70mg once weekly or placebo (randomised 2 : 1) on bone mineral density (BMD) in 167 men with spine or hip BMD at least 2 standard deviations (SD) below the mean for young normal white males or nontraumatic fracture. All patients received calcium and vitamin D (colecalciferol). We measured lumbar spine, hip and total body BMD, and biochemical markers of bone turnover. Fractures were collected as adverse events. RESULTS: Alendronic acid 70mg once weekly produced significant BMD increases from baseline of 4.3% at the spine, 2.1% at the femoral neck, 2.4% at the trochanter, and 1.4% at the total body, which were all significantly greater than placebo (p < 0.05). The increase at the lumbar spine was significant relative to baseline and placebo after 6 months of treatment (p < 0.001). The treatment effect was consistent regardless of BMD, age, height, weight, body mass index (BMI) and hypogonadal status at baseline. Alendronic acid significantly decreased biochemical markers of bone turnover relative to baseline and placebo. Alendronic acid was generally well tolerated, with an incidence of gastrointestinal adverse events similar to placebo. CONCLUSION: Alendronic acid 70mg administered once weekly is an effective and convenient alternative to daily dosing for the treatment of male osteoporosis.

Etoricoxib in the treatment of Korean patients with osteoarthritis in a double-blind, randomized controlled trial.

OBJECTIVE: We evaluated the COX-2 inhibitors, etoricoxib and celecoxib, in Korean patients with osteoarthritis (OA). METHODS: This study included patients (≥ 40 years of age) with a clinical and radiographic diagnosis of knee OA. Patients were randomized to etoricoxib 30 mg (qd) or celecoxib 200 mg (qd) in a 12 week randomized, controlled, double-blind study. Prior NSAID users were to demonstrate a worsening of symptoms upon withdrawal of medication. Efficacy endpoints included the time-weighted average change from baseline in the WOMAC VA 3.0 Pain Subscale (100 mm Visual Analog Scale [VAS]; primary endpoint), the WOMAC VA 3.0 Physical Function Subscale (100 mm VAS), and Patient Global Assessment of Disease Status (PGAD) (100 mm VAS). The primary hypothesis was that etoricoxib 30 mg is non-inferior to celecoxib 200 mg as assessed by the primary endpoint (the non-inferiority margin was set at 10 mm VAS). Adverse events (AEs), laboratory parameters, and vital signs were monitored. RESULTS: There were 239 patients (89.5% female; mean age: 63.3 years) randomized to etoricoxib 30 mg (n = 120) and celecoxib 200 mg (n = 119). The differences (etoricoxib vs celecoxib) in least square (LS) mean change (95% CI) for WOMAC Pain, WOMAC Physical Function, and PGAD were -1.63 mm (-5.37, 2.10), -1.32 mm (-4.88, 2.23), and -1.09 mm (-5.48, 3.30), respectively. Drug-related clinical AEs occurred in 6.7% (etoricoxib) and 2.5% (celecoxib) of patients. This study was limited because it was not designed or powered to adequately capture and evaluate rare AEs associated with NSAID treatment. CONCLUSIONS: Etoricoxib 30 mg administered once daily in Korean patients with knee OA demonstrated non-inferior clinical efficacy to celecoxib 200 mg over 12 weeks of treatment as assessed by all primary and secondary outcomes. Etoricoxib 30 mg qd and celecoxib 200 mg qd were generally safe and well tolerated. CLINICAL TRIAL REGISTRATION: NCT01554163.

Effect of gaboxadol on patient-reported measures of sleep and waking function in patients with Primary Insomnia: results from two randomized, controlled, 3-month studies.

OBJECTIVE: To evaluate the efficacy and safety of gaboxadol in the treatment of Primary Insomnia. METHODS: Two studies were performed in patients 18 to 65 years of age with Primary Insomnia. After a 7-day single-blind placebo run-in, patients were randomized to double-blind treatment with gaboxadol 15 mg (N = 310), 10 mg (N = 308), or placebo (N = 309) over 3 months in Study 1; and gaboxadol 15 mg (N = 304) or placebo (N = 301) over 12 months in Study 2. Treatment was administered at bedtime. The primary efficacy endpoints in each study were change from baseline in patient-reported total sleep time (sTST) and time to sleep onset (sTSO) at month 3. Safety was assessed primarily by adverse event reports. RESULTS: In Study 1, gaboxadol 15 mg significantly improved sTST (difference vs. placebo of 20.4 min, p < 0.01) and sTSO (difference vs. placebo of -9.8 min, p < 0.05) at 3 months, while gaboxadol 10 mg had no significant effects on these measures. In Study 2, gaboxadol 15 mg showed numerical superiority for improvements on sTST (difference vs. placebo of 14.5 min) and sTSO (difference vs. placebo of -4.9 min) at 3 months, but these differences were not significant. In both studies, there was evidence that the efficacy of gaboxadol was more pronounced in women than men. Gaboxadol was generally well tolerated over 3 months in Study 1, and over 12 months in Study 2. CONCLUSION: Gaboxadol 15 mg showed variable efficacy on measures of sleep duration and onset at 3 months in adult patients with Primary Insomnia in these studies and appeared to be more effective in women than men. Gaboxadol 10 mg was not effective in these studies. (Clinical trial registration numbers: NCT00103818, NCT00095069).