scholarly journals MON-163 A Phase 3, Double-Blind, Randomized, Placebo-Controlled Study to Assess the Efficacy and Safety of a Selective Glucocorticoid Receptor Modulator, Relacorilant, in Patients with Autonomous Cortisol Secretion Due to Cortisol-Secreting Adrenal Adenoma(s)/Hyperplasia

2020 ◽  
Vol 4 (Supplement_1) ◽  
Author(s):  
Richard Joseph Auchus ◽  
Andreas Grauer ◽  
Andreas Moraitis
Keyword(s):  
Blood Pressure ◽  
Glucocorticoid Receptor ◽  
Adrenal Adenoma ◽  
Clinical Signs ◽  
Controlled Study ◽  
Cortisol Secretion ◽  
Efficacy And Safety ◽  
Phase 3 ◽  
Double Blind ◽  
Autonomous Cortisol Secretion

Abstract Relacorilant is a highly selective glucocorticoid receptor antagonist that modulates the effects of excess cortisol without interacting with the mineralocorticoid or progesterone receptor. A Phase 2 relacorilant study in patients with endogenous Cushing syndrome (CS) demonstrated improvements in glycemic control and hypertension with no instances of drug-related hypokalemia or antiprogesterone effects. An international, multicenter, Phase 3 clinical trial of relacorilant is currently underway to evaluate the efficacy and safety of relacorilant in CS of various etiologies with evidence of hypercortisolism documented through two independent biochemical tests and at least two clinical signs and symptoms of CS. It uses a randomized-withdrawal design after 22-weeks (22wk) of open-label treatment with relacorilant (GRACE Study: NCT03697109). Here we introduce a double-blind, randomized, placebo-controlled study in patients with less severe CS secondary to adrenal adenoma(s) or hyperplasia. Approximately 130 eligible patients 18-80 years old with a radiologically confirmed adrenal lesion, a biochemical diagnosis of autonomous cortisol secretion and either impaired glucose tolerance/diabetes mellitus (IGT/DM) or hypertension will receive relacorilant (100 mg/day, titrated to 400 mg/day, as tolerated) or placebo over 22WK. Biochemical criteria for entry into the study include a serum cortisol >1.8 µg/dL after dexamethasone suppression testing (DST) and low (<10 pg/dL) or suppressed morning ACTH levels. Patients must be stable on their antidiabetic and/or antihypertensive agents for at least 4 weeks prior to the first dose of relacorilant. The primary efficacy endpoints are the between-treatment difference in change from Baseline to 22wk in AUCglucose for the IGT/DM group and mean systolic blood pressure (based on ambulatory blood pressure monitoring) for the hypertension group. Secondary endpoints include changes in weight, waist circumference, quality of life and coagulation markers. The safety analysis will be performed for all patients who received at least one dose of study drug. This will be the first randomized, double-blind, placebo-controlled study to test if patients with adrenal autonomous hypercortisolism benefit from medical treatment.

scholarly journals 111 Phase 3, Randomized, Double-Blind, Placebo-Controlled Study (P301) Assessing Efficacy and Safety of Extended-Release Viloxazine in Children with ADHD

CNS Spectrums ◽  
2020 ◽  
Vol 25 (2) ◽  
pp. 272-272 ◽  
Author(s):  
Azmi Nasser ◽  
Joseph T. Hull ◽  
Fatima A. Chowdhry ◽  
Toyin Adewole ◽  
Tesfaye Liranso ◽  
...  
Keyword(s):  
Clinical Global Impression ◽  
Extended Release ◽  
Rating Scale ◽  
Controlled Study ◽  
Average Score ◽  
Efficacy And Safety ◽  
Phase 3 ◽  
Double Blind ◽  
T Score ◽  
Total Average

Abstract:Study Objective:SPN-812 (extended-release viloxazine) is a structurally distinct, bicyclic, Serotonin Norepinephrine Modulating Agent (SNMA) in development as a treatment for attention-deficit/hyperactivity disorder (ADHD) in children and adolescents. This Phase 3, randomized, double-blind study (P301) evaluated the efficacy and safety of once-daily SPN-812 at doses of 100 and 200 mg compared to placebo in children ages 6-11yrs with ADHD.Method:Inclusion criteria required subjects have a confirmed Diagnostic and Statistical Manual of Mental Disorders, 5th edition (DSM-5) ADHD diagnosis, ADHD-Rating Scale-5 (ADHD-RS-5) score ≥28, a Clinical Global Impression-Severity score ≥4, and be free of ADHD medication ≥1 week before randomization. This investigation was conducted at 34 study sites in the United States. Subjects (N=477) were randomized 1:1:1 to placebo:100 mg SPN-812:200 mg SPN-812. The 6-week treatment period included up to 1 week of titration and 5 weeks of maintenance (intent-to-treat population: N=460; placebo=155, 100 mg=147, 200 mg=158). The primary efficacy endpoint was the change from baseline (CFB) at end of study (EOS) in ADHD-RS-5 total score. Key secondary endpoints included Clinical Global Impression-Improvement (CGI-I) scores at EOS, and CFB at EOS in Conners 3-Parent Short Form (Conners 3-PS) Composite T-score and in Weiss Functional Impairment Rating Scale-Parent Version (WFIRS-P) total average score. Safety assessments included adverse events (AEs), laboratory tests, vital signs, physical exams, electrocardiograms, and the Columbia-Suicide Severity Rating Scale.Results:Compared to placebo, a significantly greater improvement in ADHD-RS-5 total score was observed in the 100 mg and 200 mg SPN-812 treatment groups beginning at week 1 (p=0.0004, p=0.0244; respectively) through EOS (p=0.0004, p<0.0001; respectively). Significant improvement at EOS for both 100 mg and 200 mg SPN-812 compared to placebo was also observed in CGI-I score (p=0.0020, p<0.0001; respectively), Connors 3-PS Composite T-score (p=0.0003, p=0.0002; respectively), and in WFIRS-P total average score (p=0.0019, p=0.0002, respectively). The most common (≥5%) treatment-related AEs reported were somnolence, decreased appetite, and headache.Conclusions:In this study, SPN-812 at 100 mg and 200 mg doses met the primary and secondary objectives with statistical significance. AE-related dropouts were ≤5%, indicating SPN-812 treatment was well tolerated.This study is an encore of a poster presentation at the 2019 Annual Meeting of the American Academy of Child and Adolescent Psychiatry (AACAP).Funding Acknowledgements:This research was funded by Supernus Pharmaceuticals, Inc., Rockville, MD.

scholarly journals 112 A Phase 3, Randomized, Double-Blind, Placebo-Controlled Study (P302): Efficacy and Safety of Extended-Release Viloxazine in Adolescents with ADHD

CNS Spectrums ◽  
2020 ◽  
Vol 25 (2) ◽  
pp. 272-273 ◽  
Author(s):  
Azmi Nasser ◽  
Joseph T. Hull ◽  
Fatima A. Chowdhry ◽  
Toyin Adewole ◽  
Tesfaye Liranso ◽  
...  
Keyword(s):  
Clinical Global Impression ◽  
Extended Release ◽  
Rating Scale ◽  
Controlled Study ◽  
Average Score ◽  
Efficacy And Safety ◽  
Phase 3 ◽  
Double Blind ◽  
T Score ◽  
Total Average

Abstract:Study Objective:SPN-812 (extended-release viloxazine) is a structurally distinct, bicyclic, Serotonin Norepinephrine Modulating Agent (SNMA) in development as a treatment for attention-deficit/hyperactivity disorder (ADHD) in children and adolescents. This Phase 3, randomized, double-blind study (P302) evaluated the efficacy and safety of once-daily SPN-812 at doses of 200 and 400 mg compared to placebo in adolescents ages 12-17yrs with ADHD.Method:Inclusion criteria required subjects have a confirmed Diagnostic and Statistical Manual of Mental Disorders, 5th edition (DSM-5) ADHD diagnosis, ADHD-Rating Scale-5 (ADHD-RS-5) score ≥28, Clinical Global Impression-Severity score ≥4, and be free of ADHD medication ≥1 week before randomization. This investigation was conducted at 34 study sites in the United States. Subjects (N=310) were randomized 1:1:1 to placebo:200 mg SPN-812:400 mg SPN-812. The treatment period included up to 1 week of titration and 5 weeks of maintenance (intent-to-treat population: N=301; placebo=104, 200 mg=94, 400 mg=103). The primary efficacy endpoint was change from baseline (CFB) at end of study (EOS) in ADHD-RS-5 total score. Key secondary endpoints included Clinical Global Impression-Improvement (CGI-I) score at EOS, and CFB at EOS in Conners 3-Parent Short Form (Conners 3-PS) Composite T-score and Weiss Functional Impairment Rating Scale-Parent Form (WFIRS-P) total average score. Safety assessments included adverse events (AEs), laboratory tests, vital signs, physical exams, electrocardiograms, and the Columbia-Suicide Severity Rating Scale.Results:Compared to placebo, a significantly greater improvement in ADHD-RS-5 total score was observed in the 200 mg and 400 mg SPN-812 treatment group at EOS (p=0.0232, p=0.0091; respectively). Significant improvement in CGI-I score at EOS for both 200 mg and 400 mg SPN-812 compared to placebo was also observed (p=0.0042, p=0.0003; respectively). No significant change was observed at either dose compared to placebo in the Conners 3-PS Composite T-score (p=0.6854, p=0.0518; respectively), or the WFIRS-P total average score (p=0.2062, p=0.0519; respectively). The most common (≥5%) treatment-related AEs were somnolence, decreased appetite, fatigue, headache, and nausea.Conclusions:In this study, SPN-812 met the primary objective for both the 200 and 400 mg doses, and a key secondary objective (CGI-I) for both the 200 and 400 mg doses. AE-related dropouts were ≤5%, indicating SPN-812 treatment was well tolerated.This study is an encore of a poster presentation at the 2019 Annual Meeting of the American Academy of Child and Adolescent Psychiatry (AACAP).Funding Acknowledgements:This research was funded by Supernus Pharmaceuticals, Inc., Rockville, MD.

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