Evaluation of the efficacy of intradermal onabotulinumtoxinA for the treatment of accordion wrinkles: A 2-centre randomized double-blinded split face clinical trial

Start Date24 Feb 2014

Sponsor / Collaborator-

NCT01589263

/ CompletedPhase 2IIT

Effectiveness of OnabotulinumtoxinA (onaBoNT-A) vs Oral Tamsulosin in Men With Benign Prostatic Hyperplasia & Lower Urinary Track Symptoms (#02-10-10-05)

Benign prostatic hyperplasia (BPH) and its related symptoms are a common condition that affects nearly half of men over age 50 and 90% of men over 80. Lower urinary tract symptoms (LUTS) caused by BPH can be very troublesome, affect an individual's quality of life significantly, and are costly.
his Phase 2 clinical research trial is a double-blind, randomized, placebo-controlled, parallel-group study to compare the treatment effects of onaBoNT-A 200 U versus 0.4 mg per day of oral tamsulosin in male Veterans diagnosed with moderate to severe LUTS [American Urologic Association Symptom Score (AUASS) equal to or greater than 8] associated with BPH. A total of 74 volunteers will be recruited to participate in this clinical trial. Volunteers will include only males who are greater than 50 years of age and diagnosed with LUTS associated with BPH. They are Veterans who visit the Michael E. DeBakey Veterans Affairs Medical Center - Houston (MEDVAMC). There are no eligibility restrictions as to race or ethnicity.

Start Date01 Jun 2012

Sponsor / Collaborator

VA Office of Research and Development

100 Clinical Results associated with OnabotulinumtoxinA (VA Office of Research and Development)

100 Translational Medicine associated with OnabotulinumtoxinA (VA Office of Research and Development)

100 Patents (Medical) associated with OnabotulinumtoxinA (VA Office of Research and Development)

1,394

Literatures (Medical) associated with OnabotulinumtoxinA (VA Office of Research and Development)

01 Nov 2025·TOXICON

In silico multiscale computational modelling of botulinum toxin a diffusion for glabellar wrinkle treatment: Optimizing injection volumes across formulations

Article

Author: Carruthers, Jean D A ; Webb, William Richard ; Rao, Parinitha ; Goodman, Greg J ; Rahman, Eqram ; Ahmed, Munim

While botulinum neurotoxin A (BoNT/A) is a cornerstone in glabellar wrinkle treatment, inconsistencies in clinical outcomes often stem from formulation-dependent diffusion behaviour. Currently volumes recommendation per site lacks mechanistic justification, especially in anatomically confined regions like the glabella, where millimetric diffusion differences can produce significant adverse effects. A high-fidelity, multiscale in silico platform was developed, integrating quantum mechanical (TD-DFT) modelling of SV2-binding (ΔG_bind range: -9.2 to -11.7 kcal/mol), molecular dynamics-derived hydrodynamic radius (R_H: 9.4-11.2 nm), anisotropic finite element modelling of poroelastic muscle tissue, and agent-based receptor and immune kinetics. Simulations encompassed five formulations- AbobotulinumtoxinA (ABO), DaxibotulinumtoxinA (DAXI), IncobotulinumtoxinA (INCO), OnabotulinumtoxinA (ONA), and PrabotulinumtoxinA (PRABO)-across injection volumes from 0.025 to 0.1 mL, at fixed toxin unit dosing, within anatomically realistic glabellar meshes (n = 10,000 synthetic patient variants). Diffusion profiles varied significantly by formulation. ABO showed the largest Reff (1.64 ± 0.14 cm) and E_off, while PRABO and ONA remained spatially constrained (Reff = 0.96 ± 0.07 cm and 1.13 ± 0.08 cm, respectively). Increasing injection volume from 0.025 to 0.1 mL caused a 2.2-fold rise in E_off and a 36-49 % increase in off-target V_IC50 across formulations. Optimal containment was formulation-specific: PRABO and ONA achieved ≥95 % V_IC90 coverage with <10 % V_IC50 spillover at 0.025-0.035 mL; INCO and DAXI required 0.035-0.05 mL; ABO balanced broader coverage with acceptable diffusion at 0.04-0.045 mL. Agent-based models revealed 78 % receptor saturation at 0.025 mL versus 56 % at 0.1 mL, with immune clearance rates up to 42 % higher at high volumes due to increased perivascular redistribution. Volume emerged as the dominant spread driver (Sobol S₁ = 0.48), followed by hydrodynamic radius (S₁ = 0.35) and macrophage density (S₁ = 0.28); interaction terms were negligible (S_T - S₁ < 0.05). This study provides the first in-silico quantitative, multiscale evidence that reducing BoNT/A reconstitution volume to ≤0.045 mL/site significantly enhances target localization while minimizing off-target effects. Contrary to prevailing clinical heuristics, dilution amplifies mechanical spread and immune clearance risk.

01 Nov 2025·TOXICON

Targeting the glabellar frown lines with OnabotulinumtoxinA: In-silico evidence supporting concentrated, low-volume injection protocols

Article

Author: Flanagan, Aofie ; Carruthers, Jean DA ; Peng, Hsien-Li Peter ; Goodman, Greg J ; Rahman, Eqram ; Ahmed, Munim ; Wu, Woffles Tl ; Webb, William Richard

Botulinum Neurotoxin Type A (BoNT-A) remains the cornerstone of glabellar frown line treatment, yet conventional low-dose, high-volume protocols often result in limited durability and imprecise diffusion. This study presents multiscale, in silico framework specifically designed to evaluate high-dose (60-80 Units), low-volume (≤0.045 mL/site) BoNT-A glabellar injection strategies across anatomically realistic conditions. Using a synthetic cohort of 20,000 virtual patients, we integrated finite element modelling of anisotropic tissue diffusion, receptor-specific pharmacokinetics/pharmacodynamics (PK/PD), and machine learning-based off-target risk prediction. Our findings demonstrate that reduced-volume, concentrated dosing significantly enhances SV2 receptor occupancy (up to 93.7 %), confines toxin diffusion within target musculature, and prolongs clinical duration to 124.7 days-surpassing conventional benchmarks. To our knowledge, this is the first study to mechanistically simulate dose-volume interactions of BoNT-A in 3D facial anatomy using integrated PK/PD and Artificial Intelligence models. Our model revealed a 30-70 % variance in BoNT-A exposure and efficacy when comparing fixed-dose protocols (as per FDA labels) to weight-adjusted regimens across simulated populations. These results establish a data-driven rationale for transitioning toward precision-targeted toxin administration and lay the foundation for prospective clinical trials and personalized dosing algorithms. While robust, the study relies on synthetic data and model-driven assumptions; clinical validation is required to confirm translatability.

01 Nov 2025·TOXICON

Botulinum toxin treatment of lingual dystonia, oromandibular dystonia and bruxism-A review and update

Review

Author: Comtesse, Samira Marie ; Tavassoli, Fattaneh ; Jabbari, Bahman

Using Medline and Scopus search engines (up to January 1st, 2025), we identified 12 clinical reports on botulinum neurotoxinA therapy for lingual dystonia, 17 reports for oromandibular dystonia and 6 clinical trials on bruxism. In a majority of these studies, the investigated toxin was onabotulinumtoxinA. In most of these studies, local botulinum neurotoxin injections into the affected muscle(s) reduced involuntary movements and improved pain - the latter was specifically the case in oromandibular dystonia and bruxism. Dysphagia was the main concerning side effect after botulinum neurotoxin therapy; it was reported in 5 trials in lingual dystonia and 5 trials in oromandibular dystonia. Several studies had incomplete information i.e., lacked important information such as the type of toxin used, presence or absence of side effects and the effect of injected toxin on the quality of life. Controlled and blinded studies are needed to discern the true efficacy of botulinum toxin therapy in lingual dystonia, oromandibular dystonia and bruxism as well as discerning frequency and severity of post-injection short and long-term side effects.

News (Medical) associated with OnabotulinumtoxinA (VA Office of Research and Development)

13 Aug 2024

·www.pharmaceutical-technology.com

China NMPA accepts Junshi Biosciences’ sNDA for melanoma

The sNDA is based on the results of the MELATORCH study in patients with unresectable or metastatic melanoma. Credit: Gorodenkoff/Shutterstock. The China National Medical Products Administration (NMPA) has accepted for review Junshi Biosciences’ supplemental new drug application (sNDA) for toripalimab (TUOYI) to treat unresectable or metastatic melanoma. This sNDA is underpinned by the results of the MELATORCH study, a Phase III clinical trial demonstrating positive outcomes for toripalimab in comparison to dacarbazine. The multicentre, randomised, open-label, positive-controlled study assessed the efficacy and safety of toripalimab plus dacarbazine as a first-line treatment for unresectable or metastatic melanoma in systemic treatment-naïve patients. It was carried out at 11 clinical centres across China. In September 2023, the trial met its primary endpoint of progression-free survival (PFS). See Also: Bavarian Nordic wins positive CHMP opinion to amend Imvanex approval EAN 2024: anti-CGRPs more effective than onabotulinumtoxinA in chronic migraine prevention in real world Patients treated with toripalimab experienced a significant prolongation of PFS compared to those receiving dacarbazine. The safety profile of toripalimab was consistent with previous studies, with no new safety concerns identified. Toripalimab is an anti-PD-1 monoclonal antibody designed to hinder the interactions of PD-1 with its ligands PD-L1 and PD-L2, enhancing the immune system’s capability to eliminate tumour cells. Junshi Biosciences general manager and CEO Dr Jianjun ZOU stated: “In 2018, toripalimab made history as the first domestically developed anti-PD-1 monoclonal antibody approved for second-line and beyond treatment of advanced melanoma, leaving its brilliant mark in China’s pharmaceutical and biotech development. “Today, our efforts continue with the NMPA’s acceptance of the 12th sNDA for toripalimab, and toripalimab is poised to become China’s first immunotherapy for melanoma. We will work closely with regulatory authorities to provide better clinical treatments to patients as soon as possible.” In June 2024, the NMPA approved Junshi Biosciences’ toripalimab injection, combined with paclitaxel injection (albumin-bound), for the first-line treatment of recurrent or metastatic triple-negative breast cancer.

Drug ApprovalClinical ResultPhase 3ImmunotherapyBiosimilar

19 Apr 2023

·pipelinereview.com

U.S. FDA Approves QULIPTA® (atogepant) for Adults With Chronic Migraine

QULIPTA® now the first and only oral CGRP receptor antagonist approved to prevent migraine across frequencies, including episodic and chronic Expanded indication provides an additional treatment option for those with chronic migraine whose frequent disabling attacks negatively impact performance of daily activities Approval based on a clinical trial that demonstrated statistically significant reduction from baseline in mean monthly migraine days and improvements in function and reduction in activity impairment AbbVie is the only company with three prescription treatments designed to meet patient needs across the full spectrum of migraine AbbVie (NYSE: ABBV) today announced that the U.S. Food and Drug Administration (FDA) has approved expanding the indication of QULIPTA® (atogepant) for the preventive treatment of migraine in adults. The approval makes QULIPTA the first and only oral calcitonin gene-related peptide (CGRP) receptor antagonist approved to prevent episodic and chronic migraine. People living with chronic migraine experience headaches for 15 or more days per month, with at least eight of those days associated with migraine.1 Experience the full interactive Multichannel News Release here: https://www.multivu.com/players/English/9120951-abbvie-qulipta-migraine/ "Since September 2021, QULIPTA has helped people living with episodic migraine prevent migraine attacks, reducing the daily burden of migraine. Now, those with the most challenging to treat chronic migraine can also rely on QULIPTA to significantly reduce their migraine days," said Roopal Thakkar, senior vice president, chief medical officer, AbbVie. "This approval makes AbbVie the only company with three treatments across the spectrum of migraine, including QULIPTA as a preventive treatment for both episodic and chronic migraine; BOTOX® (onabotulinumtoxinA), our foundational, first FDA-approved preventive treatment for chronic migraine; and UBRELVY® (ubrogepant), an acute treatment for migraine attacks." QULIPTA's expanded chronic migraine indication is based on the pivotal Phase 3 PROGRESS trial evaluating QULIPTA 60 mg once daily in adult patients with chronic migraine, which met its primary endpoint of statistically significant reduction from baseline in mean monthly migraine days compared to placebo across the 12-week treatment period.2 The average monthly migraine days (MMDs) for patients at baseline during the clinical trial was 19.3 The trial also demonstrated that treatment with QULIPTA resulted in statistically significant improvements in all six secondary endpoints.3 This includes key secondary endpoints that measured the proportion of patients that achieved at least a 50 percent reduction in mean monthly migraine days across the 12-week treatment period and improvements in function and reduction in activity impairment due to migraine.4 These efficacy results are consistent with those in the ADVANCE episodic migraine trial.5 "The FDA approval is an important milestone, providing those most impacted by migraine with a new, safe and effective treatment option in a convenient, once-daily pill," said Peter McAllister, M.D., Director of the New England Center for Neurology and Headache. "QULIPTA's data demonstrate that it helps reduce the burden of migraine by delivering improvements in function, with high response rates and sustained efficacy over 12 weeks. These are critical factors neurologists and headache specialists consider when prescribing a treatment option, particularly for those with chronic migraine." QULIPTA blocks CGRP through a once-daily dose and is available in three strengths for the preventive treatment of episodic migraine – 10 mg, 30 mg and 60 mg. Only the 60 mg dose of QULIPTA is indicated for the preventive treatment of chronic migraine. The overall safety profile of QULIPTA is consistent with the episodic migraine patient population, with the most common adverse events including constipation, nausea and fatigue/sleepiness.6 "For years, I felt hopeless and struggled to find a treatment that not only reduced the number of migraine attacks but could also help reduce how often migraine impacted my daily activities like taking my kids to school or practices," said Latoya Lawrence, a patient who has lived with migraine for more than 20 years. "After I started taking QULIPTA for my episodic migraine, I wasn't as worried about when my next migraine attack might strike. I'm glad people living with chronic migraine now have a treatment option that has the potential to make a substantial impact on their lives." About the Phase 3 PROGRESS Clinical Trial The Phase 3 PROGRESS clinical trial evaluated the safety, tolerability and efficacy of oral QULIPTA 60mg once daily (QD) for the preventive treatment of chronic migraine.7 The patient population for the study included patients with a diagnosis of chronic migraine for at least one year, and greater than or equal to 15 headache days with greater than or equal to eight migraine days in the 28 days prior to randomization.7 The primary endpoint measured the reduction from baseline in mean monthly migraine days compared to placebo across a 12-week treatment period.7 Key secondary endpoints across the 12-week treatment period included: change from baseline in mean monthly headache days; change from baseline in mean monthly acute medication use days; proportion of participants with at least a 50% reduction in mean monthly migraine days; and change from baseline in Migraine Specific Quality of Life Questionnaire version 2.1 (MSQ v2.1) Role Function-Restrictive domain score at Week 12. The MSQ v2.1 is a questionnaire designed to measure health-related quality of life impairments attributed to migraine in the past four weeks. Key secondary endpoints also included change from baseline in Activity Impairment in Migraine-Diary (AIM-D) Performance of Daily Activities and Physical Impairment domain scores. The AIM-D is a novel questionnaire designed to evaluate difficulty with performance of daily activities and physical impairment due to migraine. About QULIPTA® (atogepant) QULIPTA® is approved by the U.S. Food and Drug Administration (FDA) and is available in the United States for the preventive treatment of migraine in adults. QULIPTA is the only oral calcitonin gene-related peptide (CGRP) receptor antagonist approved to prevent migraine across frequencies, including episodic and chronic. CGRP and its receptors are expressed in regions of the nervous system associated with migraine pathophysiology, and studies have shown that CGRP levels are elevated during migraine attacks. QULIPTA blocks CGRP through a once-daily dose and is available in three strengths for the preventive treatment of episodic migraine – 10 mg, 30 mg and 60 mg. Only the 60 mg dose of QULIPTA is approved for the preventive treatment of chronic migraine. About UBRELVY® (ubrogepant) UBRELVY® is an orally administered calcitonin gene-related peptide (CGRP) receptor antagonist (gepant) for the acute treatment of migraine with or without aura in adults that is an option for a wide range of patients who experience migraine attacks. UBRELVY® is the first pill of its kind to directly block CGRP, a protein released during a migraine attack, from binding to its receptors. About Migraine and Chronic Migraine Migraine is a complex neurological disease with recurrent attacks that are often incapacitating and characterized by severe, throbbing headache pain as well as compounding associated symptoms like extreme sensitivity to light, sound or nausea.8 It is highly prevalent, affecting more than 1 billion people worldwide, including nearly 40 million people in the United States alone, and is the highest cause of disability worldwide for people under 50 years of age.9-12 People living with chronic migraine experience headaches or migraine for 15 or more days per month, with at least eight of those days associated with migraine.13 It is differentiated from episodic migraine, which is characterized by 0-14 headache days per month,14 by its more debilitating disease profile including greater prevalence of comorbid conditions as well as higher frequency of headache and migraine days.14-16 Individuals with chronic migraine experience frequent disabling migraine attacks, preventing them from performing daily activities and significantly affecting their quality of life. This results in substantial societal and familial burden.17-21 Significant direct and indirect costs are also associated with chronic migraine, leading to economic burden for patients and healthcare systems.22-24 About AbbVie AbbVie's mission is to discover and deliver innovative medicines that solve serious health issues today and address the medical challenges of tomorrow. We strive to have a remarkable impact on people's lives across several key therapeutic areas: immunology, oncology, neuroscience, eye care, virology and gastroenterology, in addition to products and services across our Allergan Aesthetics portfolio. For more information about AbbVie, please visit us at www.abbvie.com. Follow @abbvie on Twitter, Facebook, Instagram, YouTube and LinkedIn. SOURCE: AbbVie

Clinical ResultDrug Approval

100 Deals associated with OnabotulinumtoxinA (VA Office of Research and Development)

R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Lower Urinary Tract Symptoms	Phase 2	United States	VA Office of Research and Development	01 Jun 2012
Prostatic Hyperplasia	Phase 2	United States	VA Office of Research and Development	01 Jun 2012

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


PREEMPT (AAN2024)	Phase 3	Migraine Disorders	-	OnabotulinumtoxinA (Female and female-assigned patients)	rtzrzvyjib(hgjnasgrgq) = vvsmteqode vuqxjuaetf (phstpsgfsi ) View more	Positive	09 Apr 2024
				OnabotulinumtoxinA (Male and male-assigned patients)	rtzrzvyjib(hgjnasgrgq) = xdrbtzspmb vuqxjuaetf (phstpsgfsi ) View more
AUA2023	Not Applicable	Urinary Bladder, Overactive Second line \| Third line	272	Discontinued BTX-A therapy	gxpdulixuu(qsyrfptlnk) = ylzwwcoumu baoawntkes (efhcmoabiw ) View more	-	01 Apr 2023
				Continued BTX-A therapy	gxpdulixuu(qsyrfptlnk) = kgezdydudk baoawntkes (efhcmoabiw ) View more
AUA2023	Not Applicable	Third line	209	Intravesical onabotulinumtoxinA	kmizraozrr(laqwkmjrgw) = uummbshseo dhbdnsrcwc (mujujqgdwk )	-	01 Apr 2023
NCT02678377 (CTgov)	Phase 4	Urinary Incontinence, Stress	100	Placebo (Placebo Group)	loxubstghj = senlsotunc tvbrsmxpqi (lzjxhznyxk, sqtjeznssj - obovzbnlic) View more	-	14 Mar 2023
				Onabotulinim Toxin A (Onabotulinim Toxin A Group)	loxubstghj = ersiloyhhf tvbrsmxpqi (lzjxhznyxk, wzwhomxbao - wudlljlkfq) View more
CD-PROBE (MDS2022)	Not Applicable	cervical dystonia	59	OnabotulinumtoxinA	iercddlxlb(atfcnxxmji) = Dysphagia was reported in 4 patients dlenpaxuwy (mbxfblqkun )	Positive	15 Sep 2022
NCT01589263 (CTgov)	Phase 2	Prostatic Hyperplasia \| Lower Urinary Tract Symptoms	63	Tamsulosin + placebo+onaBoNT-A + placebo (ARM 1: onaBoNT-A + Placebo)	fopverywxc(vxidogdqes) = fjyzjevqoz zhopqmaalo (ymnlpcdwev, 0.07) View more	-	05 Oct 2021
				Tamsulosin + placebo+onaBoNT-A + placebo (ARM 2: Saline + Tamsulosin)	fopverywxc(vxidogdqes) = jptcxvzlcq zhopqmaalo (ymnlpcdwev, 0.05) View more
CD PROBE (MDS2021)	Not Applicable	cervical dystonia	-	OnabotulinumtoxinA	qecweviivr(wpmehbqrxh) = The most common AEs (dysphagia, muscular weakness) were similar cmbmhuqgcz (jfgtyjgyua )	-	17 Sep 2021
				OnabotulinumtoxinA
AUA2018	Not Applicable	-	-	OnabotulinumtoxinA 100U	ucibzzkilp(hdzxvnsyor) = xipnzwdebv lhdslpaaak (tgccgixswf )	Positive	01 Apr 2018
				Placebo	ucibzzkilp(hdzxvnsyor) = eqokcqeelk lhdslpaaak (tgccgixswf )
AUA2018	Not Applicable	Third line	-	ONABOTULINUMTOXINA (Elderly cohort)	inmezqders(mngcbhzrog) = fjzqlrrexy fyrmhhvtus (bjuclukcxu ) View more	-	01 Apr 2018
				ONABOTULINUMTOXINA (Younger cohort)	inmezqders(mngcbhzrog) = xpvcwokjbv fyrmhhvtus (bjuclukcxu ) View more
AUA2017	Phase 3	Urinary Bladder, Overactive	-	OnabotulinumtoxinA 100U	kzrltejbaj(vqyoeozial) = vpylqptwak shjallvbsk (nulqdgddfz ) View more	Positive	01 Apr 2017
				Placebo	kzrltejbaj(vqyoeozial) = bsfshcfakt shjallvbsk (nulqdgddfz ) View more

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OnabotulinumtoxinA (VA Office of Research and Development)

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