scholarly journals Treatment of Menopausal Vasomotor Symptoms With Fezolinetant, a Neurokinin 3 Receptor Antagonist: A Phase 2a Trial

2019 ◽  
Vol 104 (12) ◽  
pp. 5893-5905 ◽  
Author(s):  
Herman Depypere ◽  
Dirk Timmerman ◽  
Gilbert Donders ◽  
Peter Sieprath ◽  
Steven Ramael ◽  
...  
Keyword(s):  
Quality Of Life ◽  
Primary Outcome ◽  
Gastrointestinal Disorder ◽  
Controlled Study ◽  
Vasomotor Symptoms ◽  
Electronic Diary ◽  
Double Blind ◽  
Menopausal Women ◽  
Neurokinin 3 Receptor

Abstract Context The thermoregulatory center in the hypothalamus is stimulated by neurokinin 3 receptor (NK3R) activation and inhibited by estrogen-negative feedback. This balance is disrupted in menopause, producing vasomotor symptoms (VMSs). Objective To evaluate safety and efficacy of the NK3R antagonist fezolinetant in menopausal VMSs. Design Twelve-week, double-blind, randomized, placebo-controlled study. Setting Eight Belgian centers from September 2015 to October 2016. Participants Generally healthy menopausal women aged 40 to 65 years with moderate/severe VMSs. Interventions Subjects were randomized (1:1) to 90 mg of fezolinetant twice daily or placebo for 12 weeks. Main Outcome Measures Subjects captured VMS severity and frequency using an electronic diary. The primary outcome was change from baseline to week 12 in total VMS score with fezolinetant vs placebo. Secondary outcomes included timing of changes in frequency and severity of moderate/severe VMSs and quality-of-life assessments at weeks 4, 8, and 12. Pharmacodynamic and pharmacokinetic effects were assessed, as were safety and tolerability. Results Of 122 subjects screened, 87 were randomized and 80 (92%) completed the study. At week 12, fezolinetant significantly reduced total VMS score vs placebo (−26.5 vs −12.2, P < 0.001) and decreased mean frequency of moderate/severe VMSs by five episodes per day vs placebo. Severity and frequency of moderate/severe VMSs were reduced from the first day of treatment. Improvements were achieved in all quality-of-life measures. Fezolinetant was well tolerated. The most common fezolinetant-related adverse event was gastrointestinal disorder (n = 6). Conclusions Fezolinetant rapidly and significantly reduced moderate/severe VMSs, supporting its potential as an effective nonhormonal treatment option for menopausal women.

scholarly journals OR11-03 NT-814, a Non-Hormonal Dual Neurokinin 1,3 Receptor Antagonist Markedly Improves Vasomotor Symptoms in Post-Menopausal Women; Results of a Randomised, Double-Blind, Placebo-Controlled, Dose-Finding Study (SWITCH-1)

2020 ◽  
Vol 4 (Supplement_1) ◽  
Author(s):  
James Simon ◽  
Richard A Anderson ◽  
Elizabeth Ballantyne ◽  
Hadine Joffe ◽  
Mary Kerr ◽  
...  
Keyword(s):  
Quality Of Life ◽  
Dose Finding ◽  
Vasomotor Symptoms ◽  
Phase 3 ◽  
Double Blind ◽  
Once Daily ◽  
Double Blind Placebo ◽  
Menopausal Women ◽  
Post Menopausal

Abstract Introduction: Vasomotor symptoms (VMS), caused by declining estrogen in menopausal women, are common and debilitating. Hormone therapy is effective in many women but carries risks and may be contraindicated. Biological and clinical evidence shows a modulatory role for neurokinin (NK) receptor antagonists acting primarily via hypothalamic KNDy (kisspeptin, NK, dynorphin) neurons on VMS. NT-814 is an oral non-hormonal dual NK1,3 receptor antagonist which has previously been shown to cause rapid and marked improvements in VMS in post-menopausal women. This Phase-2b trial (SWITCH-1) was undertaken to further evaluate efficacy and safety and to establish the optimum dose(s) for Phase 3 studies. Methods: SWITCH-1 was a double-blind, placebo-controlled, adaptive-randomization, dose-finding trial in 199 post-menopausal women. After a 2-week single-blind placebo run-in to establish symptom stability, women (40 to 65 years) with ≥7 moderate and/or severe VMS per day at baseline were randomized to 12 weeks of once daily treatment with placebo or one of 4 doses of NT-814: 40 mg, 80 mg, 120 mg, 160 mg. Subjects recorded the frequency and severity of VMS in electronic diaries twice daily throughout the study. Patient-reported measures of quality-of-life, sleep and mood were collected periodically. Adverse events (AEs) were recorded at each clinic visit. Results: VMS frequency was reduced in all treatment groups, including placebo. VMS reductions were significantly greater with the 2 higher NT-814 doses at most time-points, as early as the first week of treatment. Least squares mean reductions from baseline in moderate/severe VMS per day at week 4 were: placebo, 2.7; 40 mg, 4.3 (p=0.161 vs placebo); 80 mg, 4.1 (p=0.326); 120 mg, 6.7 (p&lt;0.0001); 160 mg, 5.5 (p=0.007). In week 12 the reductions were: placebo, 4.7; 40 mg, 6.5 (p=0.185); 80 mg, 5.6 (p=0.599); 120 mg, 7.8 (p=0.009); 160 mg, 6.6 (p=0.109). At the 160 mg dose the median reduction in week 12 was significantly greater than placebo (6.9 vs 4.4, p=0.0023), indicating an effect of high outliers on the mean. Average HF severity was also improved in a dose-related manner, with greater reductions compared to placebo with the 2 higher NT-814 doses. Improvements in HF were accompanied by statistically significant benefits on sleep (assessed using the Insomnia Severity Index and Pittsburgh Sleep Quality Index), mood (measured using the Beck Depression Inventory), and all four domains of the MenQoL menopause-specific quality-of-life instrument. NT-814 was well-tolerated; most AEs were mild or moderate and there were no serious AEs related to treatment. Conclusions: NT-814, a once daily non-hormonal NK antagonist, at doses of 120 & 160 mg reduced the frequency and severity of VMS and significantly improved quality of life, mood and sleep, in postmenopausal women. NT-814 was well tolerated, with a safety profile that supports further evaluation in Phase 3 trials.

ISA247: Quality of Life Results from a Phase II, Randomized, Placebo-Controlled Study

2008 ◽  
Vol 12 (6) ◽  
pp. 268-275 ◽  
Author(s):  
Aditya K. Gupta ◽  
Richard G. Langley ◽  
Charles Lynde ◽  
Kirk Barber ◽  
Wayne Gulliver ◽  
...  
Keyword(s):  
Quality Of Life ◽  
Phase Ii ◽  
Life Quality ◽  
Skin Condition ◽  
Controlled Study ◽  
Double Blind ◽  
Plaque Type ◽  
Psoriasis Disability Index ◽  
Stable Plaque

Background: Psoriasis is a chronic skin condition that can negatively affect a patient's quality of life (QoL), often hindering social functioning. ISA247, a novel psoriatic agent, has shown clinical efficacy in moderate to severe psoriasis sufferers, but its effect on QoL is currently not reported. Objective: The objective of this study was to assess the effect of ISA247 on the QoL in patients with stable, plaque-type psoriasis. Methods: A phase II, randomized, double-blind, placebo-controlled, parallel-group, multicenter study assessed the effects of ISA247 doses of 0.5 mg/kg/d ( n = 77) or 1.5 mg/kg/d ( n = 83) compared with placebo ( n = 41) for 12 weeks. QoL was assessed using the Dermatology Life Quality Index (DLQI) and Psoriasis Disability Index (PDI) scales. Results: ISA247 treatment (pooled groups) significantly improved QoL scores as assessed by both the DLQI and the PDI compared with those receiving placebo ( p < .05). Treatment with the higher dose of 1.5 mg/kg/d demonstrated a significantly greater response to many of the QoL scales compared with the 0.5 mg/kg/d group ( p < .05). Conclusions: ISA247 appears to improve the QoL while also providing effective treatment for chronic, moderate to severe, plaque-type psoriasis.

scholarly journals Efficacy of Lactobacillus paracasei HA-196 and Bifidobacterium longum R0175 in Alleviating Symptoms of Irritable Bowel Syndrome (IBS): A Randomized, Placebo-Controlled Study

Nutrients ◽  
2020 ◽  
Vol 12 (4) ◽  
pp. 1159 ◽  
Author(s):  
Erin D. Lewis ◽  
Joseph M. Antony ◽  
David C. Crowley ◽  
Amanda Piano ◽  
Renu Bhardwaj ◽  
...  
Keyword(s):  
Quality Of Life ◽  
Irritable Bowel Syndrome ◽  
Bifidobacterium Longum ◽  
Well Being ◽  
Lactobacillus Paracasei ◽  
Controlled Study ◽  
Double Blind ◽  
Gi Symptoms ◽  
Irritable Bowel

Specific probiotic strains can alleviate the gastrointestinal (GI) symptoms and psychiatric comorbidities of irritable bowel syndrome (IBS). In this randomized, double-blind, placebo-controlled study, the efficacy of Lactobacillus paracasei HA-196 (L. paracasei) and Bifidobacterium longum R0175 (B. longum) in reducing the GI and psychological symptoms of IBS was evaluated in 251 adults with either constipation (IBS-C), diarrhea (IBS-D), or mixed-pattern (IBS-M). Following a 2-week run-in period, participants were randomized to one of three interventions: L. paracasei (n = 84), B. longum (n = 83) or placebo (n = 81). IBS symptoms, stool frequency and consistency and quality of life were assessed by questionnaires. The differences from baseline in the severity of IBS symptoms at 4 and 8 weeks were similar between groups. Participants in this study were classified, after randomization, into subtypes according to Rome III. Within the L. paracasei group, complete spontaneous and spontaneous bowel movement frequency increased in participants with IBS-C (n = 10) after 8 weeks of supplementation (both p < 0.05) and decreased in participants with IBS-D (n = 10, p = 0.013). Both L. paracasei and B. longum supplementation improved the quality of life in emotional well-being and social functioning compared with baseline (all p < 0.05). In conclusion, L. paracasei and B. longum may reduce GI symptom severity and improve the psychological well-being of individuals with certain IBS subtypes.

scholarly journals Evaluation of efficacy and safety of montelukast and levocetirizine FDC tablet compared to montelukast and levocetirizine tablet in patients with seasonal allergic rhinitis: a randomized, double blind, multicentre, phase III trial

2020 ◽  
Vol 7 (1) ◽  
pp. 83
Author(s):  
Sagar Panchal ◽  
Saiprasad Patil ◽  
Hanmant Barkate
Keyword(s):  
Quality Of Life ◽  
Allergic Rhinitis ◽  
Seasonal Allergic Rhinitis ◽  
Phase Iii ◽  
Fixed Dose ◽  
Controlled Study ◽  
Global Evaluation ◽  
Double Blind ◽  
Nasal Symptoms

<p class="abstract"><strong>Background:</strong> To evaluate efficacy, safety and tolerability of Montelukast 10 mg+levocetirizine 5 mg  FDC compared to either montelukast 10 mg or levocetirizine 5 mg given alone in seasonal allergic rhinitis (SAR) patients.</p><p class="abstract"><strong>Methods:</strong> Phase III, multicentre, randomized, double blind, parallel group, active controlled study was conducted in 279 SAR patients at 16 sites across India. Efficacy was assessed using daytime nasal symptoms score (Primary efficacy outcome), night-time symptoms score, daytime eye symptom score, patient's global evaluation, physician's global evaluation, rhino-conjunctivitis quality-of-life score.  </p><p class="abstract"><strong>Results:</strong> At end of treatment there was statistically significant evidence from the per protocol analysis that patients on FDC had a greater improvement in change from baseline in daytime nasal symptoms score than patients who received Montelukast (p=0.0266) or Levocetirizine (p=0.0409). These results were consistent with the Intent to treat analysis. Analysis of the secondary efficacy endpoints provided numerically greater improvement in the nighttime symptoms score, daytime eye symptoms score, and rhinoconjunctivitis quality-of-life scores in the FDC group as compared to the Montelukast group or Levocetirizine group. The FDC of Montelukast and Levocetirizine was found to be safe and generally well tolerated. The majority of adverse events were mild in severity, resolved without treatment and were unrelated to study medication.</p><p class="abstract"><strong>Conclusions:</strong> Fixed dose combination of Montelukast and Levocetirizine was safe, generally well tolerated and superior on efficacy compared to Montelukast or Levocetirizine in patients of seasonal allergic rhinitis.</p>

Daflon 500 mg: Symptoms and Edema

Angiology ◽  
2005 ◽  
Vol 56 (6_suppl) ◽  
pp. S25-S32 ◽  
Author(s):  
Albert-Adrien Ramelet
Keyword(s):  
Quality Of Life ◽  
Controlled Study ◽  
Venous Disease ◽  
Double Blind Study ◽  
Life Questionnaire ◽  
Double Blind ◽  
Randomized Controlled ◽  
Randomized Controlled Studies ◽  
Significant Difference

Patients suffering from any class of the Clinical, Etiological, Anatomical, Pathophysiological (CEAP) classification of chronic venous disease (CVD) may be symptomatic (C0s-C6s). Leg heaviness, discomfort, itching, cramps, pain, paresthesia, and edema (C3) are the most frequent manifestations of CVD and a major reason for medical consultation. Daflon 500 mg (micronized purified flavonoid fraction [MPFF]) is an effective treatment for symptoms and edema in CVD as demonstrated in several randomized controlled studies. A 2-month, double-blind study in 40 patients established the superiority of Daflon 500 mg over placebo with regard to symptoms and objective signs. This was confirmed in another double-blind, placebo-controlled trial (2 months’ treatment, 160 patients), and in the Reflux assEssment and quaLity of lIfe improvEment with micronized Flavonoids (RELIEF) study. The latter included 5,052 patients in 23 countries, using a visual analog scale for evaluating pain, leg heaviness, cramps, and a sensation of swelling. All symptoms showed significant and progressive improvement. The quality-of-life results (scores on the ChronIc Venous Insufficiency quality of life Questionnaire [CIVIQ]) paralleled those of symptoms. The decrease in the ankle and calf circumferences was significantly greater (p<0.001) in the group of patients treated with Daflon 500 mg in two studies, and correlated well with the improvement in the sensation of swelling (p<0.001). This was confirmed with more sophisticated measurement techniques as in the RELIEF study or in a trial assessing edema with an optoelectronic volumeter in 20 patients. A further double-blind, randomized, controlled study established a statistically significant difference in favor of Daflon 500 mg in comparison with diosmin, both on symptoms and edema. The therapeutic efficacy of Daflon 500 mg on CVD symptoms and edema has been demonstrated in double-blind, randomized, controlled studies. Further studies using a new approach may define the most precise and validated methodology for application in future research in phlebology.

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