scholarly journals Randomized trial of preladenant, given as monotherapy, in patients with early Parkinson disease

Neurology ◽  
2017 ◽  
Vol 88 (23) ◽  
pp. 2198-2206 ◽  
Author(s):  
Fabrizio Stocchi ◽  
Olivier Rascol ◽  
Robert A. Hauser ◽  
Susan Huyck ◽  
Anjela Tzontcheva ◽  
...  
Keyword(s):  
Parkinson Disease ◽  
Active Control ◽  
Rating Scale ◽  
Double Blind ◽  
Clinical Trial Registration ◽  
Link Type ◽  
Parallel Group ◽  
Number Of Patients ◽  
Disease Rating ◽  
Post Hoc

Objective:To evaluate the adenosine 2a receptor antagonist preladenant as a nondopaminergic drug for the treatment of Parkinson disease (PD) when given as monotherapy.Methods:This was a randomized, 26-week, placebo- and active-controlled, parallel-group, multicenter, double-blind trial conducted in adults diagnosed with PD for <5 years who were not yet receiving l-dopa or dopamine agonists. Patients with a Unified Parkinson’s Disease Rating Scale (UPDRS) part 3 (motor function) score ≥10 and Hoehn & Yahr score ≤3 were randomized 1:1:1:1:1 to preladenant 2, 5, or 10 mg twice daily, rasagiline 1 mg (active-control) once daily, or placebo. The primary endpoint was the change from baseline at week 26 in the sum of UPDRS parts 2 (activities of daily living) and 3 scores (UPDRS2+3).Results:The number of patients treated was 1,007. Neither preladenant nor rasagiline was superior to placebo after 26 weeks. The differences vs placebo (95% confidence interval) in UPDRS2+3 scores (with a negative difference indicating improvement vs placebo) were preladenant 2 mg = 2.60 (0.86, 4.30), preladenant 5 mg = 1.30 (−0.41, 2.94), preladenant 10 mg = 0.40 (−1.29, 2.11), and rasagiline 1 mg = 0.30 (−1.35, 2.03). Post hoc analyses did not identify a single causal factor that could explain the finding of a failed trial. Preladenant was generally well-tolerated with few patients discontinuing due to adverse events (preladenant 7%, rasagiline 3%, placebo 4%).Conclusions:No evidence supporting the efficacy of preladenant as monotherapy was observed in this phase 3 trial. The lack of efficacy of the active control rasagiline makes it difficult to interpret the results.Clinical trial registration:Clinicaltrials.gov: NCT01155479.Classification of evidence:This study provides Class I evidence that for patients with early PD, preladenant is not effective as monotherapy at the doses studied (2, 5, 10 mg).

scholarly journals Efficacy and safety of rasagiline as an adjunct to levodopa treatment in Chinese patients with Parkinson's disease: a randomized, double-blind, parallel-controlled, multi-centre trial

2013 ◽  
Vol 16 (7) ◽  
pp. 1529-1537 ◽  
Author(s):  
Lina Zhang ◽  
Zhiqin Zhang ◽  
Yangmei Chen ◽  
Xinyue Qin ◽  
Huadong Zhou ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Rating Scale ◽  
Chinese Patients ◽  
Efficacy And Safety ◽  
Double Blind ◽  
Levodopa Treatment ◽  
Parallel Group ◽  
Disease Rating ◽  
Rasagiline Mesylate

Abstract Rasagiline mesylate is a highly potent, selective and irreversible monoamine oxidase type B (MAOB) inhibitor and is effective as monotherapy or adjunct to levodopa for patients with Parkinson's disease (PD). However, few studies have evaluated the efficacy and safety of rasagiline in the Chinese population. This study was designed to investigate the safety and efficacy of rasagiline as adjunctive therapy to levodopa treatment in Chinese PD patients. This was a randomized, double-blind, placebo-controlled, parallel-group, multi-centre trial conducted over a 12-wk period that enrolled 244 PD patients with motor fluctuations. Participants were randomly assigned to oral rasagiline mesylate (1 mg) or placebo, once daily. Altogether, 219 patients completed the trial. Rasagiline showed significantly greater efficacy compared with placebo. During the treatment period, the primary efficacy variable – mean adjusted total daily off time – decreased from baseline by 1.7 h in patients treated with 1.0 mg/d rasagiline compared to placebo (p < 0.05). Scores using the Unified Parkinson's Disease Rating Scale also improved during rasagiline treatment. Rasagiline was well tolerated. This study demonstrated that rasagiline mesylate is effective and well tolerated as an adjunct to levodopa treatment in Chinese PD patients with fluctuations.

scholarly journals Effect of the Nonsteroidal Mineralocorticoid Receptor Blocker, Esaxerenone, on Nocturnal Hypertension: A Post Hoc Analysis of the ESAX-HTN Study

2020 ◽  
Author(s):  
Kazuomi Kario ◽  
Sadayoshi Ito ◽  
Hiroshi Itoh ◽  
Hiromi Rakugi ◽  
Yasuyuki Okuda ◽  
...  
Keyword(s):  
Older Patients ◽  
Target Organ Damage ◽  
Organ Damage ◽  
Effective Treatment Option ◽  
Double Blind ◽  
Nocturnal Hypertension ◽  
Post Hoc Analysis ◽  
Nocturnal Dipping ◽  
Parallel Group ◽  
Post Hoc

Abstract BACKGROUND Nocturnal hypertension is an important phenotype of abnormal diurnal blood pressure (BP) variability and a known risk marker for target organ damage and cardiovascular events. This study aimed to assess the differential BP-lowering effects of esaxerenone vs. eplerenone on nocturnal BP in hypertensive patients with different nocturnal dipping patterns. METHODS This was a post hoc analysis of the “Esaxerenone (CS-3150) Compared to Eplerenone in Patients with Essential Hypertension” study (NCT02890173), which was a phase 3, multicenter, randomized, controlled, double-blind, parallel-group clinical study conducted in Japan. Ambulatory BP monitoring data were collected. RESULTS Patients (n = 1,001) were randomized to esaxerenone 2.5 mg/day (n = 331) or 5 mg/day (n = 338), or eplerenone 50 mg/day (n = 332). Reductions in nighttime systolic BP (95% confidence interval) were significantly greater with 2.5 and 5 mg/day esaxerenone vs. eplerenone (−2.6 [−5.0, −0.2] and −6.4 mm Hg [−8.8, −4.0], respectively). Esaxerenone significantly reduced nighttime BP from baseline compared with eplerenone in non-dippers with previously uncontrolled BP. In addition, esaxerenone did not markedly alter nighttime BP in extreme dipper patients. In the esaxerenone 5 mg/day group, esaxerenone-induced decreases in nighttime BP were greater than eplerenone-induced decreases in older patients. CONCLUSIONS Esaxerenone may be an effective treatment option for nocturnal hypertension, especially in older patients and those with a non-dipper pattern of nocturnal BP.

scholarly journals Early and sustained symptom improvement with umeclidinium/vilanterol versus monotherapy in COPD: a post hoc analysis of the EMAX randomised controlled trial

2020 ◽  
Vol 14 ◽  
pp. 175346662092694
Author(s):  
Edward M Kerwin ◽  
Isabelle H Boucot ◽  
Claus F Vogelmeier ◽  
Francois Maltais ◽  
Ian P Naya ◽  
...  
Keyword(s):  
Rescue Medication ◽  
Controlled Trial ◽  
Medication Use ◽  
Symptom Improvement ◽  
Chronic Obstructive ◽  
Electronic Diary ◽  
Double Blind ◽  
Clinical Trial Registration ◽  
Bronchodilator Therapy ◽  
Post Hoc

Background: In chronic obstructive pulmonary disease (COPD), both the time needed for patients to gain symptom improvement with long-acting bronchodilator therapy and whether an early response is predictive of a sustained response is unknown. This study aimed to investigate how quickly meaningful symptom responses are seen in patients with COPD with bronchodilator therapy and whether these responses are sustained. Methods: Early MAXimisation of bronchodilation for improving COPD stability (EMAX) was a 24-week, double-blind, double-dummy, parallel-group trial that randomised patients to umeclidinium/vilanterol (UMEC/VI), umeclidinium or salmeterol. Daily Evaluating Respiratory Symptoms in COPD (E-RS:COPD) score and rescue salbutamol use were captured via an electronic diary and analysed initially in 4-weekly periods. Post hoc analyses assessed change from baseline in daily E-RS:COPD score and rescue medication use weekly (Weeks 1–8), and association between E-RS:COPD responder status at Weeks 1–4 and later time points. Results: In the intent-to-treat population ( n = 2425), reductions from baseline in E-RS:COPD scores and rescue medication use were apparent from Day 2 with all treatments. Treatment differences for UMEC/VI versus either monotherapy plateaued by Week 4–8 and were sustained at Weeks 21–24; improvements were consistently greater with UMEC/VI. For all treatments, most patients (60–85%) retained their Weeks 1–4 E-RS:COPD responder/non-responder status at Weeks 21−24. Among patients receiving UMEC/VI who were E-RS:COPD responders at Weeks 1–4, 70% were responders at Weeks 21–24. Conclusion: Patients with symptomatic COPD had greater potential for early symptom improvements with UMEC/VI versus either monotherapy. This benefit was generally maintained for 24 weeks. Early monitoring of treatment response can provide clinicians with an early indication of a patient’s likely longer-term response to prescribed bronchodilator treatment and will facilitate appropriate early adjustments in care. Clinical Trial Registration: NCT03034915, 2016-002513-22 (EudraCT Number). The reviews of this paper are available via the supplemental material section.

scholarly journals Acoustic Voice Modifications in Individuals with Parkinson Disease Submitted to Deep Brain Stimulation

2019 ◽  
Vol 23 (02) ◽  
pp. 203-208 ◽  
Author(s):  
Aline Juliane Romann ◽  
Bárbara Costa Beber ◽  
Carla Aparecida Cielo ◽  
Carlos Roberto de Mello Rieder
Keyword(s):  
Deep Brain Stimulation ◽  
Parkinson Disease ◽  
Brain Stimulation ◽  
Statistical Difference ◽  
Rating Scale ◽  
Acoustic Measures ◽  
Disease Rating ◽  
The Voice ◽  
Stn Dbs ◽  
Deep Brain

Introduction Subthalamic nucleus deep brain stimulation (STN-DBS) improves motor function in individuals with Parkinson disease (PD). The evidence about the effects of STN-DBS on the voice is still inconclusive. Objective To verify the effect of STN-DBS on the voice of Brazilian individuals with PD. Methods Sixteen participants were evaluated on the Unified Parkinson Disease Rating Scale—Part III, and by the measurement of the acoustic modifications in on and off conditions of stimulation. Results The motor symptoms showed significant improvement with STN-DBS on. Regarding the acoustic measures of the voice, only the maximum fundamental frequency (fhi) showed a statistical difference between on- and off-conditions, with reduction in off-condition. Conclusion Changes in computerized acoustic measures are more valuable when interpreted in conjunction with changes in other measures. The single finding in fhi suggests that DBS-STN increases vocal instability. The interpretation of this result should be done carefully, since it may not be of great value if other measures that also indicate instability are not significantly different.

scholarly journals Bilateral Subthalamic Nucleus Deep Brain Stimulation in Elderly Patients With Parkinson Disease: A Case-Control Study

2020 ◽  
Vol 19 (3) ◽  
pp. 234-240
Author(s):  
Kyle T Mitchell ◽  
John R Younce ◽  
Scott A Norris ◽  
Samer D Tabbal ◽  
Joshua L Dowling ◽  
...  
Keyword(s):  
Deep Brain Stimulation ◽  
Parkinson Disease ◽  
Subthalamic Nucleus ◽  
Brain Stimulation ◽  
Rating Scale ◽  
Intracerebral Hemorrhages ◽  
Disease Rating ◽  
Equivalent Reduction ◽  
Stn Dbs ◽  
Deep Brain

Abstract BACKGROUND Subthalamic nucleus deep brain stimulation (STN DBS) is an effective adjunctive therapy for Parkinson disease. Studies have shown improvement of motor function but often exclude patients older than 75 yr. OBJECTIVE To determine the safety and effectiveness of STN DBS in patients 75 yr and older. METHODS A total of 104 patients (52 patients &gt;75 yr old, 52 patients &lt;75 yr old) with STN DBS were paired and retrospectively analyzed. The primary outcome was change in Unified Parkinson Disease Rating Scale (UPDRS) subscale III at 1 yr postoperatively, OFF medication. Secondary outcomes were changes in UPDRS I, II, and IV subscales and levodopa equivalents. Complications and all-cause mortality were assessed at 30 d and 1 yr. RESULTS Both cohorts had significant improvements in UPDRS III at 6 mo and 1 yr with no difference between cohorts. Change in UPDRS III was noninferior to the younger cohort. The cohorts had similar worsening in UPDRS I at 1 yr, no change in UPDRS II, similar improvement in UPDRS IV, and similar levodopa equivalent reduction. There were similar numbers of postoperative intracerebral hemorrhages (2/52 in each cohort, more severe in the older cohort) and surgical complications (4/52 in each cohort), and mortality in the older cohort was similar to an additional matched cohort not receiving DBS. CONCLUSION STN DBS provides substantial motor benefit and reduction in levodopa equivalents with a low rate of complications in older patients, which is also noninferior to the benefit in younger patients. STN DBS remains an effective therapy for those over 75 yr.

Clinical Development of Antidepressive Drugs - the Viewpoint of the Industry

2009 ◽  
Vol 24 (S1) ◽  
pp. 1-1
Author(s):  
C. de Bodinat ◽  
B. Delalleau
Keyword(s):  
Depressive Disorders ◽  
Rating Scale ◽  
Development Program ◽  
Placebo Response ◽  
Clinical Development ◽  
Short Term ◽  
Double Blind ◽  
Clinical Development Program ◽  
Term Efficacy ◽  
Number Of Patients

The clinical development program strategy of a new treatment of depression to be registered in Europe must be built in agreement with recommendations of the CHMP guidance.Demonstration that an antidepressant is effective in treatment of major depressive disorders requires consideration of specific recommendations notably regarding the use of placebo and reference drugs, efficacy assessment, designs features and safety aspects.In the field of depression, comparisons between test medicinal product and reference drugs are difficult to interpretate since the level of placebo response is high and variable. An adequate evaluation of antidepressant efficacy is firstly based on randomised double blind comparison versus placebo. For short term efficacy, studies with 6 week-treatment period are required and three arm trials including placebo and active control are recommended. Regarding the long term efficacy, relapse prevention study is the design recommended for demonstrating that the short term effect can be maintained over time.Assessment of efficacy criteria includes both clinical relevance and statisitical significance, particularly:Improvement expressed as difference between baseline and post-treatment score in symptomatology and as proportion of responders.Remission, defined as a condition where no or only few signs remained, with a justified cut-off on a validated rating-scale.In randomised withdrawal trials, efficacy is expressed as number of patients relapsing and/or time to relapse.The acceptable scales for use as primary endpoint include the HAM-D17 scale, the MADRS scale. Cautions regarding designs features, safety assessment and the global methodological issues faced in conducting such program will be detailed in the presentation.

scholarly journals A Randomized Controlled Trial of Chinese Medicine on Nonmotor Symptoms in Parkinson’s Disease

2017 ◽  
Vol 2017 ◽  
pp. 1-8 ◽  
Author(s):  
Ka-Kit Chua ◽  
Adrian Wong ◽  
Kam-Wa Chan ◽  
Yin-Kei Lau ◽  
Zhao-Xiang Bian ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Chinese Medicine ◽  
Rating Scale ◽  
Controlled Trial ◽  
Nonmotor Symptoms ◽  
Double Blind ◽  
Term Administration ◽  
Post Hoc ◽  
Chinese Medicine Theory

Nonmotor symptoms (NMS) of Parkinson’s disease (PD) have devastating impacts on both patients and their caregivers. Jiawei-Liujunzi Tang (JLT) has been used to treat some NMS of PD based on the Chinese medicine theory since Qing dynasty. Here we report a double-blind, randomized, placebo-controlled, add-on clinical trial aiming at evaluating the efficacy and safety of the JLT in treating NMS in PD patients. We randomly assigned 111 patients with idiopathic PD to receive either JLT or placebo for 32 weeks. Outcome measures were baseline to week 32 changes in Movement Disorder Society-Sponsored Revision of Unified PD Rating Scale (MDS-UPDRS) Parts I–IV and in NMS assessment scale for PD (NMSS). We observed improvements in the NMSS total score (p=0.019), mood/cognition (p=0.005), and reduction in hallucinations (p=0.024). In addition, post hoc analysis showed a significant reduction in constipation (p<0.001). However, there was no evidence of improvement in MDS-UPDRS Part I total score (p=0.216) at week 32. Adverse events (AEs) were mild and comparable between the two groups. In conclusion, long-term administration of JLT is well tolerated and shows significant benefits in improving NMS including mood, cognition, and constipation.

Sign in / Sign up

Export Citation Format

Share Document