Abstract 474: Efficacy and Safety of LCZ696 Compared with Olmesartan in Japanese Patients with Systolic Hypertension

Hypertension ◽  
2014 ◽  
Vol 64 (suppl_1) ◽  
Author(s):  
Hiromi Rakugi ◽  
Kazuomi Kario ◽  
Masako Yamaguchi ◽  
Naoko Okino ◽  
Hiromi Gotou ◽  
...  
Keyword(s):  
Systolic Hypertension ◽  
Age Groups ◽  
Japanese Patients ◽  
Primary Objective ◽  
Efficacy And Safety ◽  
Once Daily ◽  
Treatment Groups ◽  
Neprilysin Inhibitor ◽  
Angiotensin Receptor Neprilysin Inhibitor ◽  
Secondary Endpoints

Objective: To evaluate the efficacy and safety of LCZ696, a first-in-class angiotensin receptor neprilysin inhibitor (ARNI) vs olmesartan in Japanese patients with systolic hypertension (SH). Methods: Patients aged ≥20 yrs with mean sitting (ms) SBP ≥150-<180 mmHg were randomized to once-daily LCZ696 200 mg or 400 mg (forced-titrated from 1-week LCZ696 200 mg), or olmesartan 20 mg for 8 weeks. The primary objective of this study was to test if LCZ696 200 mg is superior over olmesartan in msSBP reductions from baseline at week 8. Secondary endpoints were reductions in msSBP with LCZ696 400 mg, reductions in msDBP and ms pulse pressure (PP), BP control rate, and safety for all treatment groups at week 8. Efficacy and safety was also assessed by age (<65 and ≥65 years). Results: A total of 1161 patients (LCZ696 200 mg, n=387; LCZ696 400 mg, n=385; olmesartan, n=389) were randomized. Demographic and baseline characteristics were generally comparable across the treatment groups with mean age of 58.7 yrs (<65 yrs, 771 [67.1%]; ≥65 yrs, 382[32.9%]). The msSBP reductions at week 8 with LCZ696 200 mg were statistically significantly superior to olmesartan and significantly greater with LCZ696 400 mg than olmesartan (Table). Reductions in msDBP and msPP were significantly greater and BP control rates were significantly higher with LCZ696 vs olmesartan. Greater BP and PP lowering with LCZ696 vs olmesartan was independent of age. The incidence of AEs was similar across the treatment and age groups. Conclusion: Treatment with LCZ696 is effective and generally well-tolerated in Japanese patients with SH regardless of age and LCZ696 200 mg showed superior BP lowering effect than olmesartan 20 mg.

scholarly journals Efficacy and safety of galcanezumab for prevention of migraine headache in Japanese patients with episodic migraine: A phase 2 randomized controlled clinical trial

2020 ◽  
Vol 3 ◽  
pp. 251581632093257 ◽  
Author(s):  
Fumihiko Sakai ◽  
Akichika Ozeki ◽  
Vladimir Skljarevski
Keyword(s):  
Migraine Headache ◽  
Japanese Patients ◽  
Episodic Migraine ◽  
Secondary Outcome ◽  
Controlled Study ◽  
Controlled Clinical Trial ◽  
Life Questionnaire ◽  
Efficacy And Safety ◽  
Double Blind ◽  
Secondary Endpoints

Objective: This study was designed to assess the efficacy and safety of galcanezumab in comparison with placebo for the prevention of migraine in Japanese patients with episodic migraine. Methods: In this double-blind, placebo-controlled study, which was conducted over 6 months, randomized adult patients received subcutaneous injections of galcanezumab (120 mg n = 115, 240 mg n = 114) or placebo ( n = 230) once monthly. The primary endpoint was the overall mean change from baseline in the number of monthly migraine headache days. The key secondary outcome measures were response rates (≥50%, ≥75%, and 100%); the Migraine-Specific Quality-of-Life Questionnaire Role Function-Restrictive score; monthly migraine headache days requiring acute treatment; and Patient Global Impression of Severity (PGI-S). Results: The mean change from baseline in monthly migraine headache days over months 1–6 was significantly ( p < 0.001) greater for the 120-mg galcanezumab dose (−3.60 days) and the 240-mg galcanezumab dose (−3.36 days) compared with placebo (−0.59 days). Both the 120-mg and 240-mg doses of galcanezumab were superior compared with placebo for each of the key secondary endpoints except for PGI-S (only the 240-mg dose was superior). The most commonly reported treatment-emergent adverse events were local injection-site reactions; erythema, swelling, pruritus, and pain were more commonly reported by patients who were treated with galcanezumab than those treated with placebo. Conclusion: The number of monthly migraine headache days was reduced with both doses of galcanezumab, and both doses were safe and well tolerated in Japanese patients with episodic migraine.

scholarly journals Efficacy and safety of lanreotide autogel compared with lanreotide 40 mg prolonged release in Chinese patients with active acromegaly: Results from a phase 3, prospective, randomized, and open-label study (LANTERN)

2020 ◽  
Author(s):  
Zhenmei An ◽  
Ting Lei ◽  
Lian Duan ◽  
Pei Hu ◽  
Zhongping Gou ◽  
...  
Keyword(s):  
Chinese Patients ◽  
Prolonged Release ◽  
Efficacy And Safety ◽  
Open Label ◽  
Phase 3 ◽  
Treatment Groups ◽  
Intention To Treat ◽  
Secondary Endpoints ◽  
Active Acromegaly ◽  
Lanreotide Autogel

Abstract Background: Lanreotide autogel is a somatostatin analog (SSA) approved for the treatment of acromegaly in 73 countries worldwide; however, it is not yet approved in China. The aim of this study was to evaluate the efficacy and safety of lanreotide autogel compared with lanreotide 40 mg prolonged release (PR) in Chinese patients with active acromegaly. Methods: LANTERN was a Phase 3, randomized, open-label, non-inferiority study. Patients with active acromegaly who had undergone surgery ≥3 months prior, or were unlikely or unable to undergo surgery, were treated with lanreotide autogel 60/90/120 mg (monthly deep subcutaneous injection) or lanreotide 40 mg PR (intramuscular injection every 7, 10, or 14 days) for 32 weeks. Primary endpoint was mean change-from-baseline in age-adjusted insulin-like growth factor-1 (IGF-1) standard deviations scores (SDS) at the end-of-study. Secondary endpoints included: growth hormone (GH) levels ≤2.5 µg/L or ≤1.0 µg/L, ≥20% reduction in tumor volume (TV) and safety. Results: In total, 128 patients were randomized and received study treatment. Lanreotide autogel was non-inferior to lanreotide 40 mg PR: treatment difference (95% CI) for IGF-1 SDS between groups was −0.32 (−0.74, 0.11; per protocol population) and −0.27 (−0.63, 0.09; intention-to-treat [ITT] population), respectively. Reductions in IGF-1 (−6.453 vs −7.003) and GH levels (−9.548 µg/L vs −13.182 µg/L), and the proportion of patients with ≥1 acromegaly symptom (−20.3% vs −32.5%) were observed from baseline to end-of-study in lanreotide autogel and lanreotide 40 mg PR groups, respectively. In the lanreotide autogel group, 45.5% (25/55) patients achieved ≥20% reduction in TV compared with 50.9% (25/53) in lanreotide 40 mg PR group (ITT). Safety profiles were similar in both treatment groups. Conclusions: Lanreotide autogel was non-inferior to lanreotide 40 mg PR in Chinese patients with active acromegaly after 32 weeks of treatment.

scholarly journals 110. A Phase 3, Multicenter, Double-blind, Randomized Clinical Trial to Evaluate the Efficacy and Safety of Ceftolozane/Tazobactam Plus Metronidazole Versus Meropenem in Chinese Participants With Complicated Intra-abdominal Infections

2021 ◽  
Vol 8 (Supplement_1) ◽  
pp. S67-S68
Author(s):  
Yihong Sun ◽  
Jia Fan ◽  
Gang Chen ◽  
Xiaofei Chen ◽  
Xiaoling Du ◽  
...  
Keyword(s):  
Clinical Cure ◽  
Additional Treatment ◽  
Double Blind Study ◽  
Efficacy And Safety ◽  
Phase 3 ◽  
Double Blind ◽  
Study Drug Administration ◽  
Treatment Groups ◽  
Secondary Endpoints ◽  
Abdominal Infections

Abstract Background In China, the prevalence of infections due to multidrug-resistant gram-negative bacteria is high and additional treatment options for complicated intra-abdominal infections (cIAI) are needed. This study compared the efficacy and safety of ceftolozane/tazobactam (C/T) + metronidazole (MTZ) versus meropenem (MEM) + placebo (pbo) for the treatment of cIAI in adult Chinese participants. Methods This was a phase 3, double-blind study conducted at 21 centers in China (NCT03830333). Participants aged 18-75 years with cIAI requiring surgical intervention within 24 hours of study drug administration were stratified by site of infection and randomized 1:1 to receive 1.5 g C/T (1 g ceftolozane and 0.5 g tazobactam) + 0.5 g MTZ administered intravenously (IV) every 8 hours (q8h) or 1 g MEM + pbo administered IV q8h for 4-14 days. The primary endpoint was clinical cure at test of cure (TOC) in the clinically evaluable (CE) population. Secondary endpoints included rates of clinical cure, per-participant microbiologic response, per-pathogen microbiologic response, and adverse events (AE). Non-inferiority for clinical cure at TOC in the CE population was confirmed if the lower bound of the 2-sided 95% CI for the between-treatment difference in the clinical cure rate was larger than −12.5%. Results A total of 134 participants were randomized to each treatment group. Demographics and baseline characteristics were generally well balanced between treatment groups (Table 1). The median (range) age in the ITT population was 50 (18-75) years and 61% were men. The most frequent sites of infection were the appendix (C/T + MTZ, 50.0%; MEM + pbo, 49.3%) and gallbladder (C/T + MTZ, 27.6%; MEM + pbo, 29.1%). Overall, the most frequently isolated pathogens were Escherichia coli (61.4%) and Klebsiella pneumoniae (17.3%); few anaerobes were isolated (Table 1). C/T + MTZ was non-inferior to MEM + pbo for clinical cure in the CE population (C/T + MTZ, 95.2%; MEM + pbo, 93.1%; difference, 2.1% [95% CI, −4.7% to 8.8%]). Results for key secondary endpoints were comparable between treatment groups (Table 2). Rates of AEs were generally similar between treatment groups (Table 3). Conclusion C/T + MTZ was non-inferior to MEM + pbo in the treatment of adult Chinese participants with cIAI and demonstrated a favorable safety profile. Disclosures Xiaofei Chen, n/a, MSD, China (Employee) Xiaoling Du, n/a, MSD, China (Employee) Ye Wang, n/a, MSD, China (Employee) Hui Wang, n/a, MSD, China (Employee) Fang Sun, n/a, MSD, China (Employee) Matthew G. Johnson, MD, Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA (Employee) Mekki Bensaci, PhD, Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA (Employee) Jennifer A. Huntington, PharmD, Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA (Employee) Christopher Bruno, MD, Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA (Employee)

scholarly journals THU0439 EFFICACY AND SAFETY OF ANAKINRA IN THE TREATMENT OF RECURRENT GOUT FLARES: RESULTS FROM THE EXTENSION PHASE OF THE ANAGO STUDY

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 456.1-457
Author(s):  
K. Saag ◽  
P. Khanna ◽  
R. Keenan ◽  
S. Ohlman ◽  
E. Sparve ◽  
...  
Keyword(s):  
Pain Intensity ◽  
Pain Reduction ◽  
Extension Phase ◽  
Acute Gout ◽  
Efficacy And Safety ◽  
Research Support ◽  
Treatment Groups ◽  
Study Enrollment ◽  
Secondary Endpoints ◽  
Gout Flares

Background:The anaGO (anakinra ingout) study was a multi-center, randomized, double-blind, double-dummy, phase 2 study investigating the efficacy and safety of anakinra for recurrent gout flares. Results from subsequent flares (extension phase) are presented in relation to the previously reported results from the 1stflare (flare at study enrollment).Objectives:The objective of the extension phase was to evaluate the efficacy, safety and immunogenicity of two anakinra regimens (100 or 200 mg daily s.c. injections for 5 days) compared to triamcinolone (single i.m. injection 40 mg) for subsequent flares after initial study enrollment flare. The primary endpoint of the study was change in patient-assessed flare pain intensity from baseline to 24-72 hours (average of 24, 48 and 72 hours) in the most affected joint measured on a visual analogue scale (0-100 VAS). Secondary endpoints included: patient’s and physician’s assessments of global response, anti-drug antibodies (ADA) and safety.Methods:The study included patients with acute gout (ACR/EULAR 2015 gout classification criteria) unsuitable for anti-inflammatory therapy with NSAIDs and colchicine due to contraindication, intolerance or inefficacy. Patients were eligible for treatment of subsequent flares for up to 2 years. Each patient received the same treatment for all flares, starying with the flare at enrollment.Results:161 patients were treated for 1 flare, 61 patients for 2 flares, 31 patients for 3, and 20 patients for 4 or more flares with 1 patient treated for 9 flares. In total, 300 flares were treated in the full study; anakinra 100 mg and 200 mg, 107 and 106 flares, respectively; and triamcinolone, 87 flares. Both anakinra doses and triamcinolone provided a clinical meaningful reduction in patient-assessed pain intensity in both the 1stand subsequent flares. Mean changes in pain intensity from baseline to 24–72 hours for total anakinra and triamcinolone were: 1stflare -41.2 and -39.4; 2ndflare -33.9 and -31.1; 3rdflare -31.8 and -51.2, respectively. Mean differences in pain reduction between anakinra and triamcinolone treatment groups were (negative value favors anakinra): 1stflare -1.8, 2ndflare -2.8 3rdflare 19.4. The majority of secondary endpoints favored anakinra, including patient’s and physician’s global assessement of response and physician’s assessement of the joint. No unexpected safety findings during subsequent flares were identified. 21 patients (19.6%) developed ADA to anakinra in low titers at some time point; 7 (6.5%) had pre-existing ADA at baseline and 12 (11.2%) developed treatment induced ADA. 2 patients had pre-existing ADA to triamcinolone at baseline. 4 patients on anakinra (3.7%) developed neutralizing antibodies (NAbs). Pre-dose 72 hour anakinra serum concentrations were in similar range for ADA+ and ADA- patients. Presence of ADA was not associated with adverse events or had an impact on pain reduction.Conclusion:The efficacy and safety of anakinra and triamcinolone in subsequent flares were similar to the findings from 1stflare in patients with acute gout. Patient-assessed pain in the 1stand 2ndflare was reduced to similar degrees in all treatment groups, but to a larger extent in the 3rdflare in the small triamcinolone group. Secondary endpoints were in favor of anakinra across flares 1 to 3. The overall incidence of ADA and NAb was low also after repeated anakinra dosing and did not appear to impact exposure, efficacy or safety. In conclusion, anakinra was shown to be an option in the treatment of recurrent gout flares in patients for whom conventional therapy is unsuitable.Disclosure of Interests: :Kenneth Saag Grant/research support from: Horizon, Sobi, Shanton, Grant/research support from: Horizon Pharma, Sobi, Shanton, Consultant of: Horizon and Sobi, Consultant of: Horizon Pharma, Amgen, Radius, LG-Pharma, Takeda, Sobi, Atom, Arthrosi, Puja Khanna Grant/research support from: Dyve, Selecta, Sobi, Consultant of: Sobi, Horizon, Robert Keenan Consultant of: Sobi, Selecta, Horizon, Sven Ohlman Shareholder of: Sobi, Employee of: Former employee of Sobi, Erik Sparve Shareholder of: Sobi, Employee of: Sobi, Daniel Lindqvist Employee of: Sobi, Ann-Charlotte Åkerblad Shareholder of: Sobi, Employee of: Sobi, Margareta Wikén Shareholder of: Sobi, Employee of: Former employee of Sobi, Alexander So Consultant of: Sobi, Grünenthal, Michael H. Pillinger Grant/research support from: Horizon, Hikma, Consultant of: Sobi, Horizon, Robert Terkeltaub Consultant of: Sobi, Selecta, Horizon, Astra-Zeneca

scholarly journals The Efficacy and Safety of Sacubitril/Valsartan in Heart Failure Patients: A Review

2022 ◽  
Vol 27 ◽  
pp. 107424842110586
Author(s):  
Rui Zhang ◽  
Xiaotong Sun ◽  
Ya Li ◽  
Wenzheng He ◽  
Hongguang Zhu ◽  
...  
Keyword(s):  
Heart Failure ◽  
Ejection Fraction ◽  
Renin Angiotensin System ◽  
Efficacy And Safety ◽  
Reduced Ejection Fraction ◽  
Neprilysin Inhibitor ◽  
Regulation Of Metabolism ◽  
Angiotensin Receptor Neprilysin Inhibitor ◽  
Peptide System ◽  
Near Future

Heart failure (HF) is one of the leading causes of morbidity and mortality worldwide. Sacubitril/valsartan, an angiotensin receptor-neprilysin inhibitor, has been approved for the treatment of HF. At present, there have been few systematic and detailed reviews discussing the efficacy and safety of sacubitril/valsartan in HF. In this review, we first introduced the pharmacological mechanisms of sacubitril/valsartan, including the reduction in the degradation of natriuretic peptides in the natriuretic peptide system and inhibition of the renin-angiotensin system. Then, we summarized the efficacy of sacubitril/valsartan in HF patients with reduced ejection fraction (HFrEF) or preserved ejection fraction (HFpEF) including the reduction in risks of mortality and hospitalization, reversal of cardiac remodeling, regulation of biomarkers of HF, improvement of the quality of life, antiarrhythmia, improving renal dysfunction and regulation of metabolism. Finally, we discussed the safety and tolerability of sacubitril/valsartan in the treatment of HFrEF or HFpEF. Compared with ACEIs/ARBs or placebo, sacubitril/valsartan showed good safety and tolerability, although the risk of hypotension might be high. In conclusion, the overwhelming majority of studies show that sacubitril/valsartan is effective and safe in the treatment of HFrEF patients but that it has little benefit in HFpEF patients. Sacubitril/valsartan will probably be a promising anti-HF drug in the near future.

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