scholarly journals Liquid Formulation of AbobotulinumtoxinA: A 6-Month, Phase 3, Double-Blind, Randomized, Placebo-Controlled Study of a Single Treatment, Ready-to-Use Toxin for Moderate-to-Severe Glabellar Lines

2019 ◽  
Vol 40 (1) ◽  
pp. 93-104 ◽  
Author(s):  
Benjamin Ascher ◽  
Berthold Rzany ◽  
Philippe Kestemont ◽  
Said Hilton ◽  
Marc Heckmann ◽  
...  
Keyword(s):  
Patient Satisfaction ◽  
Botulinum Toxin A ◽  
Controlled Trial ◽  
Placebo Patient ◽  
Controlled Study ◽  
Phase 3 ◽  
Double Blind ◽  
Duration Of Action ◽  
Appearance Time ◽  
Time Points

Abstract Background Safety and efficacy of botulinum toxin A for glabellar line (GL) treatment are well established. Currently approved formulations require reconstitution before injection. Objectives The authors sought to assess 6-month efficacy, safety, and patient satisfaction of new ready-to-use abobotulinumtoxinA solution for injection (ASI) in patients with moderate-to-severe GL at maximum frown. Methods The authors conducted a phase 3, double-blind, randomized, placebo-controlled trial (NCT02353871). Patients (N = 185) were randomized (2:1) to receive ASI 50 U or placebo. GL severity was evaluated at days 8, 15, 29, 57, 85, 113, 148, and 183 employing a 4-point scale for investigator’s live assessment (ILA) and subject's self-assessment (SSA). Primary endpoint was ILA of GL at maximum frown at day 29, and secondary endpoints were ILA and SSA of GL at maximum frown (all time points), patient satisfaction with GL appearance, time to onset, and duration of action. Results Responder rates were significantly higher for ASI vs placebo (88.3% vs 1.4%; P < 0.0001) at day 29 by ILA and all time points by ILA (P < 0.0001-0.0441) and SSA (P < 0.0001-0.0036). Sixty percent of patients reported onset of treatment response on or before day 3 (P < 0.0001 vs placebo), and in 5% of patients, efficacy by ILA lasted 6 months (day 183; P = 0.0441 vs placebo). Patient satisfaction rates were significantly higher for ASI vs placebo at all visits (P < 0.0001). Safety was comparable with the known abobotulinumtoxinA profile. Conclusions ASI was significantly efficacious for improving moderate or severe GL vs placebo by investigator and patient assessment. ASI was associated with high patient satisfaction, a long duration of action, and comparable safety profile to abobotulinumtoxinA. Level of Evidence: 1

A phase 3, multicenter, double-blind, placebo-controlled trial of lenvatinib (E7080) in patients with 131I-refractory differentiated thyroid cancer (SELECT).

2014 ◽  
Vol 32 (18_suppl) ◽  
pp. LBA6008-LBA6008 ◽  
Author(s):  
Martin Schlumberger ◽  
Makoto Tahara ◽  
Lori J. Wirth ◽  
Bruce Robinson ◽  
Marcia S. Brose ◽  
...  
Keyword(s):  
Weight Loss ◽  
Thyroid Cancer ◽  
Adverse Events ◽  
Differentiated Thyroid Cancer ◽  
Kinase Inhibitor ◽  
Controlled Trial ◽  
Controlled Study ◽  
Phase 3 ◽  
Double Blind ◽  
Double Blind Placebo

LBA6008 Background: Lenvatinib (LEN) is an oral tyrosine kinase inhibitor of the VEGFR1-3, FGFR1-4, PDGFRβ, RET, and KIT signaling networks. Based on efficacy results of the phase 2 study of patients (pts) with 131I-refractory differentiated thyroid cancer (RR-DTC), this phase 3 Study of (E7080) Lenvatinib in Differentiated Cancer of the Thyroid (SELECT) was developed. Methods: This randomized, double-blind, placebo (PBO)-controlled study enrolled pts with RR-DTC with documented disease progression within 13 months (mo). Pts were stratified by age (≤65, >65 years), region and ≤1 prior VEGFR-targeted therapies and randomized 2:1 to LEN or PBO (24mg/d, 28-d cycle). Upon progression, pts receiving PBO could crossover to open-label LEN. The primary endpoint was PFS assessed by Independent Radiologic Review; secondary endpoints included overall response rate (ORR; complete response [CR] + PR), overall survival (OS) and safety. Results: 392 pts (63.0 years median age; 51.0% male) were randomized. Pts on LEN had a significantly prolonged PFS vs PBO (hazard ratio 0.21, 95% confidence interval [CI] 0.14–0.31; P <.0001); median PFS was LEN: 18.3 mo (95% CI 15.1–not evaluable), PBO: 3.6 mo (95% CI 2.2–3.7). A LEN PFS benefit was observed in all predefined subgroups; median LEN PFS for pts with prior vs no prior VEGF-therapy was 15.1 mo (n=66) and 18.7 mo (n=195), respectively. Rates (n) of CRs were LEN: 1.5% (4), PBO: 0; PRs were LEN: 63.2% (165), PBO: 1.5% (2).Median exposure duration was LEN: 13.8 mo, PBO: 3.9 mo; median time to LEN response was 2.0 mo. Median OS has not been reached; deaths per arm were LEN: 71 (27.2%), PBO: 47 (35.9%). The 5 most common LEN treatment-related adverse events (TRAEs; any grade) were hypertension (68%), diarrhea (59%), appetite decreased (50%), weight loss (46%), nausea (41%). LEN grade ≥3 TRAEs (≥5%) were hypertension (42%), proteinuria (10%), weight loss (10%), diarrhea (8%), appetite decreased (5%). The dose was reduced in 78.5% of pts and discontinued due to adverse events (AEs) in 14.2% of pts. Conclusions: LEN significantly improved PFS compared with PBO in pts with progressive RR-DTC. There were no unexpected toxicities and AEs were manageable. Clinical trial information: NCT01321554.

A phase 3 (COSMIC-311), randomized, double-blind, placebo-controlled study of cabozantinib in patients with radioiodine (RAI)-refractory differentiated thyroid cancer (DTC) who have progressed after prior VEGFR-targeted therapy.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. TPS6097-TPS6097 ◽  
Author(s):  
Marcia S. Brose ◽  
Bruce Robinson ◽  
Candy Bermingham ◽  
Soham Puvvada ◽  
Anne E. Borgman ◽  
...  
Keyword(s):  
Thyroid Cancer ◽  
Targeted Therapy ◽  
Differentiated Thyroid Cancer ◽  
Controlled Trial ◽  
Objective Response ◽  
Controlled Study ◽  
Clinical Activity ◽  
Phase 3 ◽  
Double Blind ◽  
Double Blind Placebo

TPS6097 Background: Treatment options are limited for patients with RAI-refractory DTC that is resistant to VEGFR-targeted therapy. Cabozantinib inhibits receptor tyrosine kinases including VEGFR2, MET, AXL, and RET, which are implicated in the development of DTC, and has shown clinical activity in early-phase studies of patients with RAI-refractory DTC. This study evaluates the efficacy and safety of cabozantinib in patients with RAI-refractory DTC who have progressed during or after prior VEGFR-targeted therapy. Methods: This is a phase 3, multicenter, randomized, double-blind, placebo-controlled trial (NCT03690388). The co-primary endpoints are progression-free survival and objective response rate evaluated by blinded independent radiology committee (BIRC) per RECIST v 1.1. Additional endpoints include safety, overall survival, quality of life, and changes in relevant biomarker levels (eg, thyroglobulin). Approximately 300 patients will be randomized in a 2:1 ratio to receive either cabozantinib (60 mg QD orally) or placebo. Randomization is stratified by prior treatment with lenvatinib and age (≤ 65 yrs vs > 65 yrs). Eligible patients must have a pathologic diagnosis of DTC and must have been previously treated with or deemed ineligible for treatment with iodine-131 for DTC. Patients must have received lenvatinib or sorafenib for DTC and progressed during or following treatment with a VEGFR inhibitor. Up to 2 prior VEGFR-targeting TKI agents are allowed. Patients randomized to placebo may be eligible for real time on-study crossover to cabozantinib based on BIRC confirmation of disease progression. Unblinded patients randomized to cabozantinib may continue on study treatment if there is clinical benefit per investigator. Key words: Radioiodine-refractory differentiated thyroid cancer, cabozantinib, VEGFR-targeted therapy, trial-in-progress. Clinical trial information: NCT03690388.

Abstract TMP42: Safety and Efficacy of High-dose OnabotulinumtoxinA for Post-stroke Upper Limb Spasticity: Results of a Double-blind, Placebo-controlled Trial

Stroke ◽  
2017 ◽  
Vol 48 (suppl_1) ◽  
Author(s):  
Atul T Patel ◽  
Carolyn Geis ◽  
Katharine Alter ◽  
Grace Pan ◽  
Adele Thorpe ◽  
...  
Keyword(s):  
Upper Limb ◽  
Controlled Trial ◽  
Controlled Study ◽  
Similar Proportion ◽  
High Dose ◽  
Double Blind ◽  
Safety And Efficacy ◽  
Time Points ◽  
Post Stroke ◽  
Limb Spasticity

Introduction: OnabotulinumtoxinA (onabotA) is approved for treatment of post-stroke upper limb spasticity (PSULS) at a maximum dose of 400U across elbow, wrist, and finger sites. Safety and efficacy of a higher dose for PSULS were evaluated in elbow and shoulder sites not previously assessed. Methods: A multicenter, double-blind, randomized, placebo-controlled study evaluated a single treatment of onabotA 300U (150U: elbow flexors; 150U: shoulder adductors) or 500U (250U; 250U) vs placebo in adults with PSULS (Modified Ashworth Scale [MAS] score ≥3). Safety and efficacy were assessed at weeks 2, 4, 6, 8, and 12. The study was terminated early for administrative reasons. Results: All 53 enrolled patients completed the study. Baseline characteristics were similar between groups, except the onabotA 500U group had more men. Most patients were Caucasian and had a cerebral ischemic stroke of moderate severity (mean=101.7 months before enrollment). Mean change from baseline in elbow MAS for onabotA 500U was significantly greater than placebo at all time points (300U at wks 2 and 4, Figure 1) . Significant tone reductions were also observed in the shoulder adductors with 500U (wks 2 and 4). The proportion of treatment responders (≥1-grade reduction in elbow MAS) was numerically greater for onabotA 500U and 300U than placebo at all time points (300U significant [ P <0.05] at wks 2, 4, and 8). CGI generally improved more with onabotA than placebo (not significant). AEs were typically mild/moderate, not related to treatment, and occurred in a similar proportion of both onabotA dose groups and a greater proportion of the placebo group (300U, 27.8%; 500U, 29.4%; placebo, 50%). Conclusions: Preliminary results from this randomized trial investigating the safety and efficacy of higher-dose onabotA for elbow and shoulder spasticity indicate a dose-related benefit. At the higher dose of 500U onabotA, no new safety signals were observed; AEs did not appear to be dose-related. Funding: Allergan

Integrate II: A randomised phase 3 double-blind placebo-controlled study of regorafenib in refractory advanced gastro-oesophageal cancer (AGOC)—An international study organized by the Australasian Gastrointestinal Trials Group (AGITG).

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. TPS4136-TPS4136 ◽  
Author(s):  
Katrin Marie Sjoquist ◽  
Nick Pavlakis ◽  
Andrew James Martin ◽  
Eric Tsobanis ◽  
Sonia Yip ◽  
...  
Keyword(s):  
Kinase Inhibitor ◽  
Controlled Trial ◽  
Locally Advanced ◽  
Predictive Biomarkers ◽  
Phase Iii ◽  
Controlled Study ◽  
Phase 3 ◽  
Double Blind ◽  
Double Blind Placebo ◽  
Geographical Regions

TPS4136 Background: AGOC has a poor prognosis with no established standard treatment following failure of chemotherapy (CT). Regorafenib (BAY 73-4506)(REG) is an oral multi-kinase inhibitor targeting kinases involved in angiogenesis (VEGFR1-3, TIE-2), tumor microenvironment (PDGFR-β, FGFR), and oncogenesis (RAF, RET and KIT). INTEGRATE (phase 2) demonstrated REG was highly effective in prolonging PFS across a range of AGOC pts, with a positive OS trend. Regional differences were found in magnitude of effect, but REG was effective in all regions/subgroups. The phase 3 INTEGRATE II will explore whether REG is effective in prolonging survival in patients overall, and in the Asian sub-population. Methods: International (Australia/New Zealand (NHMRC CTC); Canada (CCTG), Korea, Japan, Taiwan, USA (ACCRU)) randomised phase III, double-blind, placebo-controlled trial with 2:1 (REG:placebo)(PBO) randomisation and stratification by: Location of tumour, Geographic region, prior VEGF inhibitors. Eligible patients (histologically confirmed AGOC), with evaluable metastatic or locally advanced disease refractory to, or relapsed following second line CT, will receive best supportive care plus 160mg REG or matched placebo orally on days 1-21 of each 28 day cycle until disease progression or prohibitive adverse events. Primary endpoint is OS. Secondary endpoints: PFS, response rate, quality of life, safety, identification of prognostic/predictive biomarkers for study endpoints, and REG PK across geographical regions. 350 patients (50% from Asia) randomized in a 2:1 ratio will provide 90% power to detect a hazard ratio (HR) for OS of 0.67 with a 2-sided α of 0.05 assuming PBO median survival is 4.5 mos. The sample size accommodates 2 interim analyses undertaken at 1/3 and 2/3 of required events. As of January 2017, 12 of 28 planned ANZ sites are open, with 4 patients enrolled. Regulatory approval has been received for 12 Canadian sites, and 12 Korean sites. Korean recruitment is expected to commence in February 2017. Regulatory submissions are pending in Taiwan, Japan, and the USA. Clinical trial information: NCT02773524.

IP 1184. ZX008 (Fenfluramine) in Dravet’s Syndrome: First Results of a Phase 3 Randomized, Double-Blind, Placebo-Controlled Trial

2018 ◽  
Author(s):  
Tilman Polster ◽  
Lieven Lagae ◽  
Joseph Sullivan ◽  
Ulrich Brandl ◽  
Arne Herting ◽  
...  
Keyword(s):  
Controlled Trial ◽  
Phase 3 ◽  
Double Blind ◽  
Double Blind Placebo ◽  
First Results

scholarly journals Safe and persistent growth-promoting effects of vosoritide in children with achondroplasia: 2-year results from an open-label, phase 3 extension study

2021 ◽  
Author(s):  
Ravi Savarirayan ◽  
Louise Tofts ◽  
Melita Irving ◽  
William R. Wilcox ◽  
Carlos A. Bacino ◽  
...  
Keyword(s):  
Growth Velocity ◽  
Bone Growth ◽  
Growth Factor Receptor ◽  
Extension Study ◽  
Controlled Study ◽  
Open Label ◽  
Phase 3 ◽  
Double Blind ◽  
Pathogenic Variants ◽  
Growth Promoting

Abstract Purpose Achondroplasia is caused by pathogenic variants in the fibroblast growth factor receptor 3 gene that lead to impaired endochondral ossification. Vosoritide, an analog of C-type natriuretic peptide, stimulates endochondral bone growth and is in development for the treatment of achondroplasia. This phase 3 extension study was conducted to document the efficacy and safety of continuous, daily vosoritide treatment in children with achondroplasia, and the two-year results are reported. Methods After completing at least six months of a baseline observational growth study, and 52 weeks in a double-blind, placebo-controlled study, participants were eligible to continue treatment in an open-label extension study, where all participants received vosoritide at a dose of 15.0 μg/kg/day. Results In children randomized to vosoritide, annualized growth velocity increased from 4.26 cm/year at baseline to 5.39 cm/year at 52 weeks and 5.52 cm/year at week 104. In children who crossed over from placebo to vosoritide in the extension study, annualized growth velocity increased from 3.81 cm/year at week 52 to 5.43 cm/year at week 104. No new adverse effects of vosoritide were detected. Conclusion Vosoritide treatment has safe and persistent growth-promoting effects in children with achondroplasia treated daily for two years.

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