Predictors of Treatment Response to Tesamorelin, a Growth Hormone-Releasing Factor Analog, in HIV-Infected Patients with Excess Abdominal Fat

Tesamorelin, a synthetic analog of human growth hormone-releasing factor, decreases visceral adipose tissue (VAT) in human immunodeficiency virus (HIV)-infected patients with lipodystrophy

Baseline Characteristics of each Study and the Pooled Analysis Population.

<p>Abbreviations: ART, antiretroviral therapy; BMI, body mass index; BP, blood pressure; FRS, Framingham Risk Score; HIV, human immunodeficiency virus; MetS-IDF, International Diabetes Foundation definition of metabolic syndrome; MetS-NCEP, National Cholesterol Education Program defined metabolic syndrome; PI–HAART, protease inhibitor-based highly active antiretroviral therapy; SD, standard deviation; VAT; visceral adipose tissue; WC, waist circumference.</p><p>^a Statistically significant difference between Study 1 and Study 2 (p<0.05 from Student’s t-test for continuous or Fisher’s exact test for categorical data). No differences between the treatment and placebo groups were seen within the pooled analysis population after combining the studies.</p><p>Baseline Characteristics of each Study and the Pooled Analysis Population.</p

Mean change from baseline to 6 months in VAT by treatment and baseline disease-risk category.

<p>Baseline risk score (by FRS, MetS-NCEP or MetS-IDF) and the interaction between baseline risk score and treatment showed that the treatment effect of tesamorelin versus placebo was greater in patients with MetS-NCEP compared with those without MetS-NCEP (interaction p = 0.054). Abbreviation: FRS, Framingham Risk Score; MetS-IDF, International Diabetes Foundation definition of metabolic syndrome; MetS-NCEP, National Cholesterol Education Program-defined metabolic syndrome; VAT: visceral adipose tissue.</p

Proportion of Patients Reaching a Threshold of VAT <140 cm² by Treatment and BMI Category.

<p>Abbreviations: BMI, body mass index; VAT; visceral adipose tissue.</p><p>^a Statistically significant difference in the pattern of change in VAT for patients on tesamorelin treatment vs. placebo (p<0.0001 from exact likelihood ratio test of association).</p><p>Proportion of Patients Reaching a Threshold of VAT <140 cm² by Treatment and BMI Category.</p

Mean change from baseline to 6 months by race and baseline triglyceride levels.

<p>The difference in mean absolute change in VAT from baseline to 6 months for tesamorelin versus placebo was greater for patients with triglycerides > 1.7 mmol/L than for those with triglycerides ≤ 1.7 mmol/L (interaction p = 0.063), and greater for white patients compared with non-white patients (interaction p = 0.025).</p

Maladaptive behaviors in individuals with Angelman syndrome

Maladaptive behaviors are challenging and a source of stress for caregivers of individuals with Angelman Syndrome (AS). There is limited information on how these maladaptive behaviors vary over time among individuals with AS due to different genetic etiologies. In this study, caregivers of 301 individuals with AS were asked questions about their child's behavior and completed the Aberrant Behavior Checklist-Community version (ABC-C). Developmental functioning was evaluated with either the Bayley Scales of Infant Development, Third Edition (Bayley-III) or the Mullen Scales of Early Learning (MSEL). Family functioning was assessed using the parent-completed Parenting Stress Index (PSI) and the Family Quality of Life questionnaire (FQoL). Approximately 70% of participants had AS due to a deletion on the maternally-inherited copy of chromosome 15q11q13. Results revealed that at baseline, individuals with AS had low scores in the domains of lethargy (mean: 2.6-4.2 depending on genotype) and stereotypy (mean: 2.3-4.2 depending on genotype). Higher cognitive functioning was associated with increased irritability (r = 0.32, p &lt; .01). Hyperactivity (p &lt; .05) and irritability (p &lt; .05) increased with age across all genotypes and should be ongoing targets for both behavioral and pharmacological treatment. Concerns for short attention span were endorsed by more than 70% of caregivers at baseline. Maladaptive behaviors, particularly hyperactivity, irritability and aggression, adversely affected parental stress, and family quality of life

Maladaptive behaviors in individuals with Angelman syndrome

Maladaptive behaviors are challenging and a source of stress for caregivers of individuals with Angelman Syndrome (AS). There is limited information on how these maladaptive behaviors vary over time among individuals with AS due to different genetic etiologies. In this study, caregivers of 301 individuals with AS were asked questions about their child’s behavior and completed the Aberrant Behavior Checklist-Community version (ABC-C). Developmental functioning was evaluated with either the Bayley Scales of Infant Development, Third Edition (Bayley-III) or the Mullen Scales of Early Learning (MSEL). Family functioning was assessed using the parent-completed Parenting Stress Index (PSI) and the Family Quality of Life questionnaire (FQoL). Approximately 70% of participants had AS due to a deletion on the maternally-inherited copy of chromosome 15q11q13. Results revealed that at baseline, individuals with AS had low scores in the domains of lethargy (mean: 2.6–4.2 depending on genotype) and stereotypy (mean: 2.3–4.2 depending on genotype). Higher cognitive functioning was associated with increased irritability (r = 0.32, p < .01). Hyperactivity (p < .05) and irritability (p < .05) increased with age across all genotypes and should be ongoing targets for both behavioral and pharmacological treatment. Concerns for short attention span were endorsed by more than 70% of caregivers at baseline. Maladaptive behaviors, particularly hyperactivity, irritability and aggression, adversely affected parental stress, and family quality of life

DUET: A Phase 2 Study Evaluating the Efficacy and Safety of Sparsentan in Patients with FSGS.

BACKGROUND: We evaluated and compared the effects of sparsentan, a dual endothelin type A (ET METHODS: In this phase 2, randomized, double-blind, active-control Efficacy and Safety of Sparsentan (RE-021), a Dual Endothelin Receptor and Angiotensin Receptor Blocker, in Patients with Focal Segmental Glomerulosclerosis (FSGS): A Randomized, Double-blind, Active-Control, Dose-Escalation Study (DUET), patients aged 8-75 years with biopsy-proven FSGS, eGFR\u3e30 ml/min per 1.73 m RESULTS: Of 109 patients randomized, 96 received study drugs and had baseline and week 8 UP/C measurements. Sparsentan-treated patients had greater reductions in UP/C than irbesartan-treated patients did when all doses (45% versus 19%; CONCLUSIONS: Patients with FSGS achieved significantly greater reductions in proteinuria after 8 weeks of sparsentan versus irbesartan. Sparsentan was safe and well tolerated

DUET: A phase 2 study evaluating the efficacy and safety of sparsentan in patients with FSGS

Background: We evaluated and compared the effects of sparsentan, a dual endothelin type A (ETA) and angiotensin II type 1 receptor antagonist, with those of the angiotensin II type 1 receptor antagonist irbesartan in patients with primary FSGS. Methods: In this phase 2, randomized, double-blind, active-control Efficacy and Safety of Sparsentan (RE-021), a Dual Endothelin Receptor and Angiotensin Receptor Blocker, in Patients with Focal Segmental Glomerulosclerosis (FSGS): A Randomized, Double-blind, Active-Control, Dose-Escalation Study (DUET), patients aged 8-75 yearswith biopsy-proven FSGS, eGFR>30ml/min per 1.73m2, and urinary protein-to-creatinine ratio (UP/C)≥1.0 g/g received sparsentan (200, 400, or 800 mg/d) or irbesartan (300mg/d) for 8 weeks, followed by open-label sparsentan only. End points atweek 8 were reduction from baseline inUP/C(primary) and proportion of patients achieving FSGS partial remission end point (FPRE) (UP/C:≤1.5 g/g and>40%reduction [secondary]). Results: Of 109 patients randomized, 96 received study drugs and had baseline and week 8 UP/C measurements. Sparsentan-treated patients had greater reductions in UP/C than irbesartan-treated patients didwhen all doses (45%versus 19%; P=0.006) or the 400 and 800mg doses (47%versus 19%; P=0.01) were pooled for analysis. The FSGS partial remission end point was achieved in 28% of sparsentan-treated and 9% of irbesartan-treated patients (P=0.04). After 8 weeks of treatment, BP was reduced with sparsentan but not irbesartan, and eGFR was stable with both treatments. Overall, the incidence of adverse events was similar between groups. Hypotension and edema were more common among sparsentan-treated patients but did not result in study withdrawals. Conclusions: Patients with FSGS achieved significantly greater reductions in proteinuria after 8 weeks of sparsentan versus irbesartan. Sparsentan was safe and well tolerated