12-week Maintenance Research Articles

Design and implementation of a community-based exercise program for breast cancer patients.

Research has indicated that exercise is critical in the recovery process for breast cancer patients, and yet this evidence has infrequently been translated into sustainable community programming. The present article describes the processes and operations of beauty (the Breast Cancer Patients Engaging in Activity and Undergoing Treatment program). This evidence-based 12-week exercise program, with an optional 12-week maintenance component, is supported by the Wings of Hope Foundation, allowing the program to be delivered at no cost to participants. The program was designed to restore and improve the physical well-being of women living with breast cancer as they undergo chemotherapy or radiation treatments. Evaluations measure safety and adherence to the program and the effects of the program on physiologic and psychological outcomes and quality of life. The beauty program addresses the gap between the level of evidence for the benefits of exercise after a cancer diagnosis and translation of that evidence into community programming by providing an accessible, individualized, and safe physical activity program for women during treatment for breast cancer.

Tapentadol Prolonged Release for Managing Moderate to Severe, Chronic Malignant TumorRelated Pain

Background: Tapentadol prolonged release (PR) is effective and well tolerated for chronic osteoarthritis, low back, and diabetic peripheral neuropathic pain. Objectives: To evaluate the efficacy and tolerability of tapentadol PR compared with placebo and morphine controlled release (CR) for managing moderate to severe chronic malignant tumor-related pain. Study Design: Randomized-withdrawal, parallel group, active- and placebo-controlled, double-blind phase 3 study (NCT00472303). Setting: Primary, secondary, and tertiary care settings in 16 countries. Methods: Eligible patients (pain intensity ≥ 5 [11-point numerical rating scale] on prior analgesics) were randomized (2:1) and titrated to their optimal dose of tapentadol PR (100 – 250 mg bid) or morphine sulfate CR (40 – 100 mg bid) over 2 weeks. Morphine sulfate immediate release 10 mg was permitted as needed for rescue medication (no maximum dose). Patients who completed titration and, during the last 3 days of titration, had mean pain intensity < 5 (based on twice-daily ratings) and mean rescue medication use ≤ 20 mg/day continued into a 4-week maintenance period; patients who received morphine CR during titration continued taking morphine CR, and those who received tapentadol PR were re-randomized (1:1) to tapentadol PR or placebo bid. Response during maintenance (primary efficacy endpoint) was defined as having: 1) completed the maintenance period, 2) a mean pain intensity < 5 during maintenance, and 3) used an average of ≤ 20 mg/day of rescue medication during maintenance. Response at the end of titration was defined similarly, with pain intensity and rescue medication averages based on the last 3 days of titration. Results: Of 622 patients screened, 496 were randomized, treated during titration, and evaluable for safety; 327 were re-randomized, treated during maintenance, and evaluable for safety; and 325 were evaluable for efficacy. The adjusted responder rate estimate during maintenance (logistic regression adjusting for treatment group, pooled center, and pain intensity at start of maintenance) was significantly higher with tapentadol PR (64.3%) than with placebo (47.1%; odds ratio (OR), 2.02 [95% confidence interval (CI), 1.12 – 3.65]; P = 0.02). Based on responder rates at the end of titration, tapentadol PR (76.0% [174/229]) was non-inferior to morphine CR (83.0% [83/100]). The lower limit of the 95% CI for the between-groups difference (−15.5%) was within the pre-specified 20% non-inferiority margin. During titration, incidences of treatment-emergent adverse events (TEAEs) were 50.0% (169/338) with tapentadol PR and 63.9% (101/158) with morphine CR; incidences of nausea, vomiting, and dry mouth were lower with tapentadol PR than with morphine CR. During maintenance, incidences of TEAEs were 56.3% (63/112), 62.3% (66/106), and 62.4% (68/109) with placebo, tapentadol PR, and morphine CR, respectively. Limitations: Statistical comparisons between tapentadol PR and morphine CR were limited to descriptive statistics during the maintenance period because of the pre-selection of responders to tapentadol PR or morphine CR during titration. Conclusions: Results obtained during maintenance indicate that tapentadol PR (100 – 250 mg bid) is effective compared with placebo for managing moderate to severe chronic malignant tumor-related pain. Based on results obtained during titration, tapentadol PR provides comparable efficacy to that of morphine sulfate CR (40 – 100 mg bid), but is associated with better gastrointestinal tolerability. Key words: Tapentadol PR, cancer pain, tumor-related pain, malignant pain, chronic pain, morphine CR, non-inferiority, efficacy, tolerability

Tu1052 A Phase 3, Randomized, Double-Blind, Multicenter Study to Evaluate the Efficacy and Safety of TAK-438 (10 mg or 20 mg Once-Daily) Compared to Lansoprazole (15 mg Once-Daily) in a 24-Week Maintenance Treatment for Healed Erosive Esophagitis

Tu1052 A Phase 3, Randomized, Double-Blind, Multicenter Study to Evaluate the Efficacy and Safety of TAK-438 (10 mg or 20 mg Once-Daily) Compared to Lansoprazole (15 mg Once-Daily) in a 24-Week Maintenance Treatment for Healed Erosive Esophagitis

Maintenance of Efficacy and Safety of Rabeprazole in Children With Endoscopically Proven GERD

The aim of the present study was to evaluate 24-week maintenance of efficacy and safety of rabeprazole in children with endoscopically proven gastroesophageal reflux disease (GERD). Children ages 1 to 11 years who achieved endoscopic/histologic healing (defined as grade 0 of the Hetzel-Dent Classification scale and/or grade 0 of the Histological Features of Reflux Esophagitis scale) in a 12-week treatment phase were continued on the same dose for an additional 24 weeks during the maintenance phase. The dose was determined by weight: children weighing 6 to 14.9 kg (low-weight cohort) received 5 or 10 mg and children weighing ≥ 15 kg (high-weight cohort) received 10 or 20 mg. Healing was maintained in 90% of children (100% [low-weight cohort]; 89% [10 mg, high-weight cohort]; 85% [20 mg, high-weight cohort]). The Total GERD Symptom and Severity score continued to improve slightly in all of the children across all dose groups (P = 0.026) during the maintenance phase, except the 10-mg dose group (low-weight cohort), which experienced a slight worsening of 3.6 points. Overall, 71% children felt better on the GERD Symptom Relief score (P < 0.001); 95% of investigators and 92% of parent/caregivers rated "Good to Excellent" on the Global Treatment Satisfaction scale and Clinical Global Impressions Improvement scale, respectively. Overall incidence of treatment-emergent adverse events was 63%; upper respiratory tract infections (13%) and vomiting (11%) were the most commonly reported (>10%). Rabeprazole was effective in maintaining endoscopic/histologic healing during a 24-week maintenance period in children with endoscopically proven GERD. The clinical effect and safety profile were largely similar across dose groups.

Perampanel for adjunctive treatment of partial‐onset seizures: A pooled dose–response analysis of phase III studies

To better understand the relationship between efficacy and perampanel dose, integrated actual (last) dose data from three phase III trials and an extension study (blinded Conversion Period; open-label Maintenance Period) were analyzed. Seizure frequency data were analyzed in patients who were randomized to and completed the 13-week Maintenance Period of the phase III studies on perampanel 8mg, and who received an actual (last) dose of 12mg during (1) the extension 16-week blinded Conversion Period or (2) weeks 1-13 of the extension Maintenance Period. Due to a treatment-by-region interaction (p=0.042), analyses excluded patients from the Latin America region (n=162/1,480; 10.9% of the treated cohort). Of 372 patients randomized to 8mg in the phase III studies, 273 completed the Maintenance Period at 8mg and 267 entered the extension study. In patients who then had an actual (last) dose of 12mg during the extension blinded Conversion Period (n=217), median percent change in seizure frequency per 28days improved from -32.4% (8mg, phase III Maintenance Period) to -44.2% (12mg, extension blinded Conversion Period); 50% responder rates increased slightly from 37.3% to 42.9%. In patients who completed the phase III studies on 8mg and had an actual (last) dose of 12mg during weeks 1-13 of the extension Maintenance Period (n=181), median percent change in seizure frequency per 28days improved from -34.1% (phase III Maintenance Period) to -46.0% (weeks 1-13 extension Maintenance Period); 50% responder rates were 39.2% and 46.4%. Seizure control remained substantially unchanged in patients who completed the phase III studies at 12mg and continued on that dose during the extension. Increasing perampanel dose from 8 to 12mg can produce additional benefits in seizure control in at least some patients who tolerate the higher dose.

A Randomized, Double-Blind, Placebo-Controlled, 16-Week Study of the H&lt;sub&gt;3&lt;/sub&gt; Receptor Antagonist, GSK239512 as a Monotherapy in Subjects with Mild-to-Moderate Alzheimer’s Disease

Histaminergic H3 receptors may play a role in modulating cholinergic and monoaminergic neurotransmission. This Phase II study evaluated the efficacy and safety of GSK239512, a highly potent, brain penetrant H3 receptor antagonist as monotherapy treatment for subjects with mild-to-moderate probable Alzheimer's disease (AD). In this 16-week, double-blind, randomized, parallel group study, 196 currently untreated subjects with mild-tomoderate AD (Mini Mental State Examination [MMSE] 16-24) received GSK239512 (n=97); or placebo (n=99) administered orally each morning. After a two-week placebo run-in period GSK239512 was up-titrated over 4 weeks in a flexible manner (10-20-40-80 microgram [µg]) followed by a 12-week Maintenance Phase. Co-primary efficacy endpoints were change from baseline in Episodic Memory and Executive Function/Working Memory composite scores from the CogState neuropsychological test battery (NTB) at Week 16. Compared to placebo, GSK239512 improved Episodic Memory at Week 16 (Effect Size [ES] =0.35; p=0.0495). No statistically significant differences were observed on other cognitive domains or on clinical measures including the Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADASCog). GSK239512 treatment was associated with mild to moderate adverse events with headache, dizziness and events related to sleep disturbances being the most common and more pronounced in the early titration period when subjects were first being exposed to GSK239512 at the lower 10µg and 20µg doses. There were no clinically relevant changes in other safety parameters. GSK239512, at doses up to 80µg/day, improved Episodic Memory in patients with mildto- moderate AD. However, no improvements were observed on Executive Function/Working Memory or other domains of cognition. No changes were observed on any of the clinical measures included as secondary endpoints (including ADAS-Cog) indicating that GSK239512 failed to show benefit in this population. GSK239512 had an acceptable safety and tolerability profile. These findings suggest that H3 antagonists may, at most, have modest and selective effects on cognitive function in patients with mild-to-moderate AD.

Safety and Efficacy Of a 12-Week Maintenance Interval In Patients Treated With Imported Fire Ant Immunotherapy

Safety and Efficacy Of a 12-Week Maintenance Interval In Patients Treated With Imported Fire Ant Immunotherapy

Efficacy of perampanel: A review of pooled data

Perampanel (PER) has been tested in three randomized placebo-controlled prospective phase III trials as an adjunctive antiepileptic drug (AED) in adult and adolescent patients age 12years and older who had ongoing focal epileptic seizures despite receiving one to three AEDs. Patients were randomized to once-daily placebo or maintenance dosages of 2, 4, or 8mg of PER daily in one trial or to dosages of 8 and 12mg of PER in the other two studies. Baseline and double-blind titration periods comprised 6weeks each before a 12-week maintenance phase. Primary endpoints were median change in partial seizure frequency (baseline vs. double-blind phase), and the percentage of patients achieving >50% reduction in seizure frequency (so-called responders, baseline vs. maintenance). All patients had the opportunity to enter an open follow-up study that allowed a titration of PER of up to 12mg. Pooled data of all three studies included 1,478 patients. There was a statistically significant median change in seizure frequency and responder rates with PER dosages of 4, 8, and 12mg (p<0.01, each dose vs. placebo). Both the results of each trial and the pooled data are reported in this review. For the open follow-up study, 1,218 patients were recruited. Ninety-one percent finally reached maintenance dosages of 10 or 12mg. After 1year, both median seizure reduction and responder rates reached almost 50%.

EPA-0666 – Long-term maintenance of efficacy of extended-release guanfacine hydrochloride (GXR) in children and adolescents with attention-deficit/hyperactivity disorder (ADHD): double-blind, placebo-controlled, multicentre, phase 3 randomized withdrawal study

GXR, a selective α2A-adrenergic agonist, is a non-stimulant ADHD treatment approved in the USA for children and adolescents, and in Canada for children. To evaluate long-term maintenance of efficacy of GXR in children and adolescents with ADHD who respond to an initial open-label, short-term trial. To determine if there is a higher rate of treatment failure for placebo vs GXR during the double-blind randomised-withdrawal phase (RWP) (NCT01081145). Patients (6–17 years) meeting DSM-IV-TR criteria for ADHD, baseline ADHD Rating Scale-IV (ADHD-RS-IV) ≥32 and Clinical Global Impressions-Severity (CGI-S) ratings ≥4 were enrolled. Following 7-week dose optimization and 6-week maintenance periods on open-label GXR (1–7 mg/day), eligible patients entered a 26-week, double-blind, RWP with GXR or placebo. The primary endpoint was rate of treatment failure (≥50% increase in ADHD-RS-IV total score and ≥2-point increase in CGI-S at two consecutive visits, compared to the RWP baseline). The key secondary endpoint was time-to-treatment failure. Safety assessments included treatment-emergent adverse events (TEAEs), electrocardiograms and vital signs. Of 528 patients enrolled, 316 (60.0%) entered the RWP. At study end, 49.3% (GXR) and 64.9% (placebo) (95%CI; −26.6, −4.5, p<0.01) of patients had relapsed (Figure). Time-to-treatment failure was 56 days (placebo) versus 218 days (GXR), p=0.003. During the RWP, the most common GXR TEAEs (≥5% patients) were headache, somnolence and nasopharyngitis. GXR demonstrated long-term maintenance of efficacy versus placebo in children and adolescents with ADHD.

Restorative yoga and metabolic risk factors: The Practicing Restorative Yoga vs. Stretching for the Metabolic Syndrome (PRYSMS) randomized trial

AimsIntensive lifestyle change prevents type 2 diabetes but is difficult to sustain. Preliminary evidence suggests that yoga may improve metabolic factors. We tested a restorative yoga intervention vs. active stretching for metabolic outcomes. MethodsIn 2009–2012, we conducted a 48-week randomized trial comparing restorative yoga vs. stretching among underactive adults with the metabolic syndrome at the Universities of California, San Francisco and San Diego. We provided lifestyle counseling and a tapering series of 90-min group classes in the 24-week intervention period and 24-week maintenance period. Fasting and 2-h glucose, HbA1c, triglycerides, HDL-cholesterol, insulin, systolic blood pressure, visceral fat, and quality of life were assessed at baseline, 6- and 12-months. Results180 participants were randomized and 135 (75%) completed the trial. At 12months, fasting glucose decreased more in the yoga group than in the stretching group (−0.35mmol/L vs. −0.03mmol/L; p=0.002); there were no other significant differences between groups. At 6months favorable changes within the yoga group included reductions in fasting glucose, insulin, and HbA1c and an increase in HDL-cholesterol that were not sustained at 1year except changes in fasting glucose. The stretching group had a significant reduction in triglycerides at 6months which was not sustained at 1year but had improved quality of life at both time-points. ConclusionsRestorative yoga was marginally better than stretching for improving fasting glucose but not other metabolic factors.

A Randomized, Double-blind Evaluation of Buprenorphine Taper Duration in Primary Prescription Opioid Abusers

Although abuse of prescription opioids (POs) is a significant public health problem, few experimental studies have investigated the treatment needs of this growing population. To evaluate, following brief stabilization with a combination of buprenorphine hydrochloride and naloxone hydrochloride dihydrate, the relative efficacy of 1-, 2-, and 4-week buprenorphine tapering regimens and subsequent naltrexone hydrochloride therapy in PO-dependent outpatients. A double-blind, 12-week randomized clinical trial was conducted in an outpatient research clinic. Following a brief period of buprenorphine stabilization, 70 PO-dependent adults were randomized to receive 1-, 2-, or 4-week tapers followed by naltrexone therapy. During phase 1 (weeks 1-5 after randomization), participants visited the clinic daily; during phase 2 (weeks 6-12), visits were reduced to thrice weekly. Participants received behavioral therapy and urine toxicology testing throughout the trial. The percentage of participants negative for illicit opioid use, retention, naltrexone ingestion, and favorable treatment response (ie, retained in treatment, opioid abstinent, and receiving naltrexone at the end of the study). Opioid abstinence at the end of phase 1 was greater in the 4-week compared with the 2- and 1-week taper conditions (P = .02), with 63% (n = 14), 29% (n = 7), and 29% (n = 7) of participants abstinent in the 4-, 2-, and 1-week conditions, respectively. Abstinence at the end of phase 2 was also greater in the 4-week compared with the 2- and 1-week conditions (P = .03), with 50% (n = 11), 16% (n = 4), and 20% (n = 5) of participants abstinent in the 4-, 2-, and 1-week conditions, respectively. There were more treatment responders in the 4-week condition (P = .03), with 50% (n = 11), 17% (n = 4), and 21% (n = 5) of participants in the 4-, 2-, and 1-week groups considered responders at the end of treatment, respectively. Retention and naltrexone ingestion also were superior in the 4-week vs briefer tapers (both P = .04). Experimental condition (ie, taper duration) was the strongest predictor of treatment response, followed by buprenorphine stabilization dose. This study represents a rigorous experimental evaluation of outpatient buprenorphine stabilization, brief taper, and naltrexone maintenance for treatment of PO dependence. Results suggest that a meaningful subset of PO-dependent outpatients may respond positively to a 4-week taper plus naltrexone maintenance intervention.

The effect of rotigotine on nocturnal blood pressure changes and periodic limb movements of sleep in patients with idiopathic RLS: The encore study

Introduction Rotigotine transdermal system reduces periodic leg movements (PLM) during sleep in patients with restless legs syndrome (RLS). Episodic nocturnal blood pressure (BP) excursions coincide with PLM, possibly increasing the risk of hypertension and cardiovascular disease. We examined the effect of rotigotine on PLM-associated and total nocturnal systolic BP (NSBP) elevations in patients with moderate-to-severe RLS (IRLS ⩾ 15). Materials and methods This double-blind, placebo-controlled study (SP0977 ENCORE [NCT01455012]) randomized patients (1:1) to optimal dose rotigotine (1–3 mg/24 h) or placebo. Continuous beat-by-beat BP and heart rate assessments were performed at baseline and end of 4-week maintenance (EoM). Primary outcome was change from baseline to EoM in PLM-associated NSBP elevations (defined: a slope of linear regression ⩾2.5 over 5 consecutive heartbeats [equivalent to ⩾10 mmHg]). Change in total NSBP elevations and PLM index (PLMI) were also assessed. Efficacy data are reported for the full analysis set (FAS). Results 81 patients (mean ± SD age: 57.2 ± 10.5 years; 63% female) were randomized (rotigotine: 40; placebo: 41); 66 (rotigotine: 37; placebo: 29) comprised the FAS. Mean (±SD) baseline PLMI was similar between rotigotine (72.9 ± 55.6) and placebo (69.9 ± 47.9). Reductions from baseline (∼300 elevations) in PLM-associated NSBP elevations were greater with rotigotine vs. placebo (LS mean [95% CI]: −239.95 [−275.34, −204.56] vs −79.61 [119.25, −39.97]; treatment difference: −160.34 [−213.23, −107.45]; p p = 0.0028). Greater decreases from baseline to EoM in PLMI were observed for rotigotine (−49.4 [−57.4, −41.4]) vs. placebo (−16.6 [−25.6, −7.7]) (−32.8 [−44.7, −20.8]; p Conclusion Rotigotine reduced PLM-associated and total NSBP elevations in patients with RLS. Further investigation is required to determine whether decreases in PLMI-related and total nocturnal BP translate into reductions in cardiovascular risk in patients with RLS. Acknowledgement This study was supported by UCB Pharma, Monheim am Rhein, Germany.

COMPARISON OF ZONISAMIDE AND CARBAMAZEPINE MONOTHERAPY IN ADULTS WITH NEWLY DIAGNOSED PARTIAL EPILEPSY: PRELIMINARY RESULTS OF A PHASE III, RANDOMISED, DOUBLE-BLIND, NON-INFERIORITY TRIAL

PurposeTo compare efficacy and safety of once-daily zonisamide (ZNS) and twice-daily controlled-release carbamazepine (CBZ) monotherapy in adults with newly diagnosed partial epilepsy.MethodsPhase III, international, randomised, double-blind, non-inferiority trial, in which...

Maintenance of response after open-label treatment with atomoxetine hydrochloride in international European and non-European adult outpatients with attention-deficit/hyperactivity disorder: a placebo-controlled, randomised withdrawal study

Background and Objectives:We evaluated maintenance of response to atomoxetine during a 25-week, double-blind, placebo-controlled, randomised withdrawal period in adults with attention-deficit/hyperactivity disorder (ADHD) who previously responded to atomoxetine during a 12 week open-label treatment period and maintained that response during a 12-week double-blind maintenance period. Methods: Patients (N = 2017), 18 to 50 years of age, diagnosed with ADHD from 152 outpatient sites in 18 countries received 12 weeks of open-label atomoxetine (40-100 mg/day) followed by 12 weeks of double-blind maintenance (80 or 100 mg/day). Responders were randomized to atomoxetine (N = 266) or placebo (N = 258) for 25-weeks of double-blind treatment. The percentage of patients with a reduction .30% in their baseline Conners�f ADHD Rating Scale Investigator-Rated: Screening Version (CAARS-Inv:SV) total score and a score of .3 on the Clinical Global Impression ADHD-Severity (CGIADHD- S) after 25 weeks was compared between treatment groups with a Fisher�fs exact test. Mean changes from baseline in the CAARS-Inv:SV and Adult Attention-Deficit/Hyperactivity Disorder Quality of Life (AAQoL) were analysed. Results: Most patients enrolled (60%) were from Europe. More atomoxetine- than placebo- treated patients maintained a satisfactory response postrandomisation (64.3% vs. 50.0%; p <.001). Time-to-relapse was significantly longer for atomoxetine than placebo (p = .004). Atomoxetine maintained greater improvements in ADHD symptoms compared with placebo (LS mean worsening in the CAARS-Inv:SV total score was 0.9 vs. 4.8 [p <.001] and in the CGI-ADHD-S rating was 0.0 vs. 0.5 [p <.001]). These results were supported by self- or observer- rated measures. Lastly, atomoxetine maintained greater improvements in quality of life compared with placebo (AAQoL total score was 0.4 vs. -4.0; p = .002). Conclusions: This study demonstrated that atomoxetine was superior to placebo in maintaining significantly greater treatment responses for up to 1 year in adults with ADHD.

Efficacy and Tolerability Exposure–Response Relationship of Retigabine (Ezogabine) Immediate-Release Tablets in Patients With Partial-Onset Seizures

BackgroundRetigabine (international nonproprietary name)/ezogabine (United States adopted name) is an antiepileptic drug (AED) that enhances KCNQ (Kv7) potassium channel activity. ObjectivesThe aim of this study was to explore the relationship between retigabine/ezogabine systemic exposure and efficacy and adverse events (AEs) of retigabine/ezogabine from Phase III clinical trials. MethodsData were combined from Studies 301 and 302, which were both randomized, double-blind, placebo-controlled, multicenter, parallel-group studies with similar inclusion and exclusion criteria. All patients had partial-onset seizures and were receiving 1 to 3 concomitant AEDs. Systemic exposure was predicted for each patient as the average steady-state AUC0–τ during the 12-week maintenance phase, based on a population pharmacokinetic model developed for retigabine/ezogabine. Efficacy end points included reduction in total partial-seizure frequency from baseline and probability of ≥50% reduction from baseline in seizure frequency. The probabilities of occurrence of 6 AEs were also evaluated. ResultsAUC0–τ values increased linearly over the 600- to 1200-mg/d dose range. Over the entire AUC0–τ range, the probability of efficacy was greater than that for any AE. The slopes of the exposure–response relationship for probability of dizziness and abnormal coordination were similar to that for efficacy, whereas the slopes for dysarthria, somnolence, tremor, and blurred vision were shallower, indicating that the probability of these events occurring was less affected than the probability of efficacy by increases in retigabine/ezogabine AUC0–τ. ConclusionsBased on the summary statistics of pharmacokinetic parameters, systemic exposure to retigabine/ezogabine increased linearly with dose (600–1200 mg/d). Population pharmacokinetics and pharmacodynamics showed that the probability of efficacy and AEs increased with increasing systemic retigabine/ezogabine exposure, and the probability of efficacy was higher than the probability of any of the AEs. The 35%–50% between-patient variability and overlap between retigabine/ezogabine dose levels in AUC0-τ values indicate that, as with other AEDs, doses should be individually titrated based on a balance between efficacy and tolerability.

A randomized phase III trial of adjunctive zonisamide in pediatric patients with partial epilepsy

To assess the efficacy and safety/tolerability of adjunctive zonisamide treatment in pediatric patients with partial epilepsy. In this phase III, double-blind, randomized, placebo-controlled, multicenter trial, 207 patients (age 6-17 years) with partial epilepsy, receiving one or two antiepileptic drugs, were randomized to receive adjunctive zonisamide or placebo. Zonisamide was initiated at 1 mg/kg/day, titrated to a target dose of 8 mg/kg/day over 8 weeks (one down-titration permitted), and maintained for 12 weeks. The primary efficacy end point was the proportion of responders (≥ 50% seizure frequency reduction from baseline) during the 12-week maintenance period. Safety/tolerability assessments included the incidence of treatment-emergent adverse events (TEAEs). In total, 93 (86.9%) of 107 patients randomized to zonisamide and 90 (90.0%) of 100 patients randomized to placebo completed the trial. Responder rates were 50% for zonisamide versus 31% for placebo (p = 0.0044; intention-to-treat population, last observation carried forward). The overall incidence of TEAEs was similar for zonisamide (55.1%) versus placebo (50.0%), with low rates of serious TEAEs with zonisamide and placebo (3.7% vs. 2.0%) and TEAEs leading to withdrawal (0.9% vs. 3.0%). TEAEs reported more frequently with zonisamide versus placebo were decreased appetite (6.5% vs. 4.0%), decreased weight (4.7% vs. 3.0%), somnolence (4.7% vs. 2.0%), vomiting (3.7% vs. 2.0%), and diarrhea (3.7% vs. 1.0%). Adjunctive zonisamide treatment was shown to be effective and well tolerated in pediatric patients with partial epilepsy. No new or unexpected safety findings emerged.

Web-basierte Rehabilitationsnachsorge nach stationärer psychosomatischer Therapie (W-RENA)

High relapse rates following treatment for mental health disorders are a challenge for psychosomatic rehabilitation treatments. The goal of the present study is to evaluate the feasibility, acceptance and process-quality of a 12-week transdiagnostic Internet-based maintenance treatment (W-RENA) following psychosomatic rehabilitation treatment. Findings regarding effectiveness and moderators of treatment outcome that were already reported elsewhere are briefly summarized.In a preliminary study we first assessed whether rehab patients have the technical requirements and abilities to successfully participate in Internet-based treatments. Patients expressing interest for participation in W-RENA (N=400) were compared with non-participants (N=1789) with regard to sociodemographic and clinical characteristics. In a 2-arm randomized controlled trial (N=400) we subsequently compared participants of W-RENA with participants of a treatment as usual group (TAU). Self-report measures were assessed at the beginning of inpatient treatment (t1), at discharge from inpatient treatment/start of W-RENA (t2), and at 3- (t3) and 12-months follow-ups (t4). The majority of assessed rehab-patients had the technical prerequisites (78.79%) and necessary skills (79.9%) to successfully participate in an Internet-based intervention. A third of the patients (32%) which were invited to take part in the intervention (and the study) expressed interest to participate. Study participants and non-participants differed only slightly. Most participants (80.6%) reported to have gained benefit from participating. Treatment achievements as well as quality of therapist alliance were rated high from both patients and therapists. Moreover, participants of the W-RENA group could stabilize their inpatient treatment outcomes up to 3- and 12-months follow-up better than controls could do (differences in symptom change from discharge to 3-months follow-up: d=0.38; to 12-months follow-up: d=0.55). Clinical significant symptom deterioration from discharge to 1-year follow-up could be reduced by 2/3 (29.45% vs. 11.45%). We could not identify any subgroup not profiting from study participation. Patients with low education benefited particularly. Internet-based aftercare interventions are a feasible, accepted and effective approach to successfully sustain treatment outcomes achieved in inpatient psychosomatic rehabilitation.

Six-Month Follow-Up of a Randomized Controlled Trial Augmenting Serotonin Reuptake Inhibitor Treatment With Exposure and Ritual Prevention for Obsessive-Compulsive Disorder

This article describes the long-term effects of augmenting serotonin reuptake inhibitors (SRIs) with exposure and ritual prevention or stress management training in patients with DSM-IV obsessive-compulsive disorder (OCD). Between November 2000 and November 2006, 111 OCD patients from 2 academic outpatient centers with partial SRI response were randomized to the addition of exposure and ritual prevention or stress management training, delivered twice weekly for 8 weeks (acute phase); 108 began treatment. Responders (38 of 52 in the exposure and ritual prevention condition, 11 of 52 in the stress management training condition) entered a 24-week maintenance phase. The Yale-Brown Obsessive Compulsive Scale (YBOCS) was the primary outcome measure. After 24 weeks, patients randomized to and receiving exposure and ritual prevention versus stress management training had significantly better outcomes (mean YBOCS scores of 14.69 and 21.37, respectively; t = 2.88, P = .005), higher response rates (decrease in YBOCS scores ≥ 25%: 40.7% vs 9.3%, Fisher exact test P < .001), and higher rates of excellent response (YBOCS score ≤ 12: 24.1% vs 5.6%, Fisher exact test P = .01). During the maintenance phase, the slope of change in YBOCS scores was not significant in either condition (all P values ≥ .55), with no difference between exposure and ritual prevention and stress management training (P > .74). Better outcome was associated with baseline variables: lower YBOCS scores, higher quality of life, fewer comorbid Axis I diagnoses, and male sex. Augmenting SRIs with exposure and ritual prevention versus stress management training leads to better outcome after acute treatment and 24 weeks later. Maintenance outcome, however, was primarily a function of OCD severity at entrance. Greater improvement during the acute phase influences how well patients maintain their gains, regardless of treatment condition.

A randomized open-label observational study to compare the efficacy and tolerability between topiramate and valproate in juvenile myoclonic epilepsy

Juvenile myoclonic epilepsy (JME) is managed with valproate in most patients; however, valproate is an antiepileptic drug that has relatively severe adverse effects, especially in women. We performed a prospective, open-label, randomized observational study for comparison of efficacy and tolerability between topiramate and valproate in patients with JME. The inclusion criteria were patients with newly diagnosed JME or previously diagnosed JME with a history of a poor response or adverse effects to other antiepileptic drugs. The primary endpoint of this study was percentage of patients who were free of myoclonic seizures for 24weeks in the two groups. The frequency and severity of adverse effects were also assessed. Sixteen patients were randomized to topiramate and 17 to valproate. In the topiramate arm, 11 of 16 patients (68.9%) completed 24-week maintenance therapy and seven of the 11 (64%) were seizure-free. In the valproate arm, 16 of 17 patients (94.1%) completed 24-week follow-up and nine of 16 (56%) were seizure-free. The difference (64% topiramate versus 56% valproate) did not reach statistical significance in this study group (p=0.08, Fisher’s exact test). However, the severity of adverse effects was significantly different. Only 1 of 10 adverse effects from topiramate was ranked moderate-to-severe (10%), in comparison with severe rankings for 10 of 17 adverse effects from valproate (59%) (p=0.018, Fisher’s exact test). In summary, the efficacy of topiramate and valproate was not different, but the severity of adverse effects was favourable for topiramate. Our findings suggest that valproate may be replaced with topiramate, especially for the patients with JME who do not tolerate valproate.

Efficacy and safety of adjunctive perampanel for the treatment of refractory partial seizures: A pooled analysis of three phase III studies

Three phase III studies (304 [ClinicalTrials.gov identifier: NCT00699972], 305 [NCT00699582], 306 [NCT00700310]) evaluated perampanel, an α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor antagonist, as adjunctive therapy for refractory partial seizures. We report post hoc analyses of pooled study data by randomized dose. Patients with partial seizures despite receiving 1-3 antiepileptic drugs were randomized to once-daily placebo, perampanel 8 or 12 mg (studies 304, 305), or placebo, perampanel 2, 4, or 8 mg (study 306). Studies included a 6-week baseline period and double-blind treatment phase (6-week titration; 13-week maintenance). Primary end points were median change in partial seizure frequency (baseline vs. double-blind phase) and percentage of patients achieving ≥ 50% reduction in seizure frequency (baseline vs. maintenance). Here, these end points, together with secondary, exploratory, and safety end points, were assessed using pooled study data. The pooled intent-to-treat analysis set (randomized, treated patients with any seizure data) included 1,478 patients. Median changes in partial seizure frequency were greater with perampanel than placebo (perampanel 4 mg, -23.3%; 8 mg, -28.8%; 12 mg, -27.2%; placebo, -12.8%; p < 0.01, each dose vs. placebo), as were 50% responder rates (perampanel 4 mg, 28.5%; 8 mg, 35.3%; 12 mg, 35.0%; placebo, 19.3%; p < 0.05, each dose vs. placebo). In addition, median changes in complex partial plus secondary generalized seizure frequency were also greater with perampanel than placebo (perampanel 4 mg, -31.2%; 8 mg, -35.6%; 12 mg, -28.6%; placebo, -13.9%). Perampanel was generally well tolerated. The most frequent treatment-emergent adverse events (TEAEs) were dizziness, somnolence, and headache. Most TEAEs were mild/moderate; relatively few patients experienced severe TEAEs (placebo, 5.4%; perampanel, 8.9%) or serious TEAEs (placebo, 5.0%; perampanel, 5.5%). There were no deaths and no clinically important mean changes in laboratory values, electrocardiography (ECG) findings, or vital signs. Perampanel reduced partial seizure frequency and improved responder rates compared with placebo, with an acceptable tolerability profile.