scholarly journals Efficacy, safety, and tolerability of adjunctive perampanel in patients from China with focal seizures or generalized tonic‐clonic seizures: Post hoc analysis of phase III double‐blind and open‐label extension studies

2020 ◽  
Author(s):  
Liao Weiping ◽  
Zhou Dong ◽  
Hong Zhen ◽  
Anna Patten ◽  
Amitabh Dash ◽  
...  
Keyword(s):  
Phase Iii ◽  
Open Label ◽  
Double Blind ◽  
Post Hoc Analysis ◽  
Focal Seizures ◽  
Open Label Extension ◽  
Clonic Seizures ◽  
Post Hoc

scholarly journals 935. Effect of Tesamorelin in People with HIV with and without Dorsocervical Fat: Post Hoc Analysis of Phase III Double Blind Placebo Control Trial

2020 ◽  
Vol 7 (Supplement_1) ◽  
pp. S500-S501
Author(s):  
Farah Rahman ◽  
Marilyn de Chantal ◽  
Pedro Mesquita ◽  
Judith A Aberg
Keyword(s):  
Growth Hormone ◽  
Abdominal Fat ◽  
Fat Deposition ◽  
Phase Iii ◽  
Placebo Control ◽  
People Living With Hiv ◽  
Anthropometric Parameters ◽  
Double Blind ◽  
Post Hoc Analysis ◽  
Post Hoc

Abstract Background Lipohypertrophy is defined as excess fat deposition in abdominal defined as visceral adipose tissue (VAT) as well as in the dorsocervical region, breasts, trunk, and along with possible fat deposition in liver, muscle, myocardium and epicardium. Multiple factors have been described as contributing to lipohypertrophy in people living with HIV (PLWH), including patient characteristics, antiretroviral therapy (ART) and also impaired growth hormone (GH) secretion. Tesamorelin, a synthetic form of growth-hormone-releasing hormone (GHRH), is indicated for reduction of excess abdominal fat in PLWH with lipodystrophy Methods Post-hoc analysis was done on phase 3 randomized, double-blind, multicenter trials. Patients were eligible if between 18 and 65 years of age, had confirmed HIV infection, had evidence of excess abdominal fat accumulation and on stable ART regimen for 8 weeks or more. Participants were randomized to receive tesamorelin 2 mg daily or placebo daily for 26 weeks. Only tesamorelin responders, defined as patients with at least 8% decrease in VAT and who were adherent to the medication, were used for this analysis. Results are reported for patients with and without dorsocervical (DC) fat deposition. Results Demographic characteristics of responders at week 26 are shown according to presence or absence of DC fat (Table 1). At week 26, on average, the patients with DC fat deposition had higher BMI and waist circumference (WC) than the group without DC fat. Most patients in both groups had lipoatrophy. Metabolic and anthropometric parameters were measured at week 26 in patients with and without DC fat (Table 2). There was a decrease in VAT and also an improvement in their WC at week 26 in both groups. Table 1: Baseline Characteristics of Tesamorelin Responder Subjects at Week 26, by Dorsocervical Status Table 2: Change in Abdominal Adiposity, Insulin-Like Growth Factor-1 Levels, and Metabolic Parameters Between Baseline and Week 26 Among Tesamorelin Responders Conclusion This data demonstrates that tesamorelin is effective at reducing VAT in both patients with and without DC fat. The medication was well tolerated without significant changes to metabolic based measurements. Treatment of excessive VAT with tesamorelin has seemingly positive results in fat reduction in patients with or without DC fat deposition and our study contributes to the growing literature. Disclosures Marilyn de Chantal, PhD, Theratechnologies Inc (Employee) Pedro Mesquita, PhD, Theratechnologies, Inc. (Employee) Judith A. Aberg, MD, Theratechnology (Consultant)

scholarly journals Experience of patisiran with transthyretin stabilizers in patients with hereditary transthyretin-mediated amyloidosis

2020 ◽  
Vol 10 (5) ◽  
pp. 289-300 ◽  
Author(s):  
Hollis Lin ◽  
Madeline Merkel ◽  
Cecilia Hale ◽  
Jing L Marantz
Keyword(s):  
Quality Of Life ◽  
Diabetic Neuropathy ◽  
Phase Ii ◽  
Phase Iii ◽  
Open Label ◽  
Safety And Efficacy ◽  
Impairment Score ◽  
Open Label Extension ◽  
Post Hoc

Aim: Examine safety and pharmacodynamics of patisiran alone or with concomitant transthyretin stabilizers from the Phase II open-label extension study and safety and efficacy of patisiran in patients with prior transthyretin stabilizer use from the Phase III APOLLO study. Patients & methods: Post hoc analyses in patients with hereditary transthyretin-mediated amyloidosis with polyneuropathy. Results: Patisiran safety was consistent regardless of concomitant or prior transthyretin stabilizers. In the Phase II open-label extension (n = 27), transthyretin reduction was similar over 24 months, regardless of concomitant transthyretin stabilizers. In APOLLO (n = 225), patisiran-treated groups showed stabilization or improvements in neurological function (modified Neuropathy Impairment Score +7) and quality of life (Norfolk Quality of Life-Diabetic Neuropathy questionnaire) at 18 months, regardless of prior transthyretin stabilizers. Conclusion: Patients benefit from patisiran regardless of transthyretin stabilizer use.

scholarly journals 14 Long-term Efficacy of Brexpiprazole in Patients with Schizophrenia with Clinically Relevant Levels of Negative Symptoms

CNS Spectrums ◽  
2019 ◽  
Vol 24 (1) ◽  
pp. 180-180
Author(s):  
Catherine Weiss ◽  
Peter Zhang ◽  
Ross A Baker ◽  
Mary Hobart ◽  
Nanco Hefting ◽  
...  
Keyword(s):  
Negative Symptoms ◽  
Extension Study ◽  
Short Term ◽  
Open Label ◽  
Term Study ◽  
Post Hoc Analysis ◽  
Long Term Study ◽  
Open Label Extension ◽  
Post Hoc

AbstractBackgroundEffective treatments for patients with high levels of negative symptoms of schizophrenia are lacking. Brexpiprazole is a serotonin–dopamine activity modulator that is a partial agonist at 5-HT1A and dopamine D2 receptors, and an antagonist at 5-HT2A and noradrenaline alpha1B/2C receptors, all with subnanomolar potency. Long-term treatment with brexpiprazole demonstrated broad efficacy across all five Marder factor groupings, including positive, negative, disorganized thoughts, uncontrolled hostility/excitement, and anxiety/depression. This post-hoc analysis of long-term effects of brexpiprazole in patients with clinically relevant levels of negative symptoms of schizophrenia is based on data from two similarly designed short-term, placebo-controlled studies (Vector; NCT01396421 or Beacon; NCT01393613) for the brexpiprazole-treated patients who continued into an open-label extension study (Zenith; NCT01397786).MethodsIn the short-term studies, patients with acute schizophrenia were randomly assigned to fixed once-daily doses of brexpiprazole 0.25mg (Vector), 1mg (Beacon), 2mg , 4mg or placebo for 6weeks. The long-term study was an open-label, 52-week (amended to 26weeks), safety extension study with flexible-dose (1–4mg/day) brexpiprazole. The post-hoc analyses were performed on brexpiprazole-treated patients from the short-term studies who continued into the long-term study, and who had clinically relevant negative symptoms, defined as PANSS Factor Score for Negative Symptoms (PANSS-FSNS; N1, N2, N3, N4, G7, G16) of ≥24, and score of ≥4 on at least two of three core negative symptom PANSS items at randomization in the parent study. The outcome of the analysis included change from baseline to up to 58weeks in PANSS-FSNS, PANSS Total, and PSP. Safety was also assessed.ResultsA total of 187 patients with clinically relevant levels of negative symptoms in the parent study rolled-over into the open-label extension study and were available for analysis. Eighty-three of these patients remained in the studies for 58weeks. Due to the study amendment, not all patients had the opportunity of complete 52weeks of open-label treatment. Baseline PANSS Total score was 104.4, while baseline PANSS-FSNS was 27.6 and baseline PSP Total score was 41.3. Mean change (SD) from baseline in PANSS-FSNS was –10.9 (5.0), and –44.2 (17.5) for PANSS Total score at Week 58. Change from baseline (SD) to Week 58 for PSP Total score was 24.8 (12.9) with improvement in all domains (socially useful activities, personal and social relationship, self-care, and disturbing and aggressive behaviors). The TEAEs reported ≥5% were schizophrenia (18.9%), insomnia (8.6%), weight increased (5.9%) and akathisia (5.9%).ConclusionThis post-hoc analysis suggests that brexpiprazole has long-term effectiveness on negative symptoms and functioning in patients with schizophrenia and clinically relevant levels of negative symptoms.Funding Acknowledgements: The study was funded by Otsuka Pharmaceutical Development & Commercialization Inc. and H. Lundbeck A/S

Efficacy variables in patients with cancer versus patients without cancer treated with methylnaltrexone or placebo: An analysis of two placebo-controlled studies.

2018 ◽  
Vol 36 (34_suppl) ◽  
pp. 1-1
Author(s):  
Bruce Chamberlain ◽  
Michelle Rhiner ◽  
Neal E Slatkin ◽  
Nancy Stambler ◽  
Robert Joseph Israel
Keyword(s):  
Opioid Use ◽  
Advanced Illness ◽  
Open Label ◽  
Double Blind ◽  
Patients With Cancer ◽  
Pooled Data ◽  
Bowel Movements ◽  
Open Label Extension ◽  
Post Hoc ◽  
Clinical Trial Information

1 Background: A post-hoc analysis of pooled data from two randomized, double-blind studies and their open-label extensions evaluated whether baseline characteristics and efficacy endpoints differ between cancer and noncancer adults with advanced illness and opioid-induced constipation treated with methylnaltrexone (MNTX) or placebo. Methods: Patients received SC MNTX 0.15 mg/kg or placebo (study 302) and SC MNTX 8 mg (38≤62 kg), 12 mg (≥62 kg), or placebo (study 4,000) every other day for two weeks and received the same doses of MNTX as needed during the first 2 weeks of the open-label extensions. Double-blind populations were stratified by those with/without cancer. Efficacy endpoints included rescue-free bowel movements (RFBMs) within 4 hours after each dose for ≥2 of the first 4 doses; time to rescue-free laxation; rescue laxatives use; and ≥3 RFBMs/week and ≥1 RFBM/week in ≥3 of 4 weeks. Results: Median baseline opioid use (mg/day) was greater in cancer (187.9 placebo [n=114]; 180.0 MNTX [n=116]) versus noncancer patients (80.0 placebo [n=71]; 120.0 MNTX [n=62]). MNTX significantly ( P<0.0001) improved the proportion of cancer (56.9%) and noncancer (58.1%) patients with an RFBM within 4 hours after each dose for ≥ two of the first four doses versus placebo (5.3% cancer; 11.3% noncancer). Median time to laxation was significantly ( P≤0.0002) shorter in cancer (0.96 hours) and noncancer (1.25 hours) patients 24 hours after the first dose of MNTX versus placebo (22.53 and >24 hours, respectively). Rescue laxatives were used by 39.7% of cancer and 30.6% of noncancer MNTX patients versus 51.8% of cancer and 39.4% of noncancer placebo patients. Of 108 open-label extension double-blind MNTX patients, 79 (73.1%) achieved ≥3 RFBMs/week with ≥1 RFBM/week increase in ≥ three of four weeks versus 48 (46.6%) of 103 double-blind placebo patients (data from double-blind and first two weeks of open-label). Conclusions: MNTX treatment improved the laxation response, with a faster onset of laxation in patients with and without cancer, and reduced the need for rescue laxatives vs placebo. Improvements over placebo continued into the first two weeks of the open-label extensions for MNTX-treated patients. Clinical trial information: NCT00672477, NCT00402038.

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