Walking with age becomes both slower and less 'automated', requiring more attention and brain resources. As a result, older adults have a greater risk of negative outcomes and falls. There is an urgent need to identify factors that can help compensate for these harmful factors and reduce walking impairments, as there are currently no effective treatments available. Investigators have recently discovered that
20% of older adults maintain fast walking speed even in the presence of small blood vessel brain changes and leg problems, thus appearing to be protected against these harmful factors. The investigators work suggests that the brain dopamine (DA) system may be a source of this protective capacity. Investigators have also shown that lower levels of dopamine are associated with slow walking. Investigators will be investigating the role of dopamine on slow walking and other parkinsonian signs in this open-label study using detailed clinical assessment, assessment of dopamine activity, and clinical interventions.

Start Date01 Oct 2024

Sponsor / Collaborator

University of Michigan

[+1]

NCT06626152 / RecruitingPhase 2IIT

Measuring Psychomotor Response to L-DOPA Challenge As a Biomarker for Outcomes in Late-Life Depression: a Pilot Feasibility Trial

Background
Adults over the age of 60 with symptoms of major depressive disorder are said to have late-life depression (LLD), a condition that usually decreases a person's quality of life and is associated with other risks like physical frailty and dementia. A common feature of more severe LLD is psychomotor slowing, where a person's ability to think and move are impaired. For example, they might not be able to walk or process information as quickly, and they might have problems with their working memory.
Psychomotor slowing in LLD might be the result of a problem with the way a person's body produces or responds to the neurotransmitter dopamine. The drug Levodopa (L-DOPA), which can replace missing dopamine in the brain, has been used to treat to treat Parkinson's disease for many decades, and it might also affect psychomotor slowing in LLD.
Methods
In this study, participants are adults aged 60 years or older with moderate to severe major depression. Participants undergo the "L-DOPA challenge"-a 2-week period where they receive a dose of L-DOPA once a day for the first week and a dose of L-DOPA twice a day for the second week. Before and after a participant completes the L-DOPA challenge, the study team assesses their depressive symptoms and psychomotor function. After the L-DOPA challenge, if a participant still shows signs of moderate or severe depression, they receive an antidepressant for 12 weeks.
Aims
The first aim of this study is to test the feasibility of the L-DOPA challenge-that is, whether most of the 50 participants recruited for this study will complete the L-DOPA challenge. For example, participants might have to withdraw if they can't make the daily visits to the research site to receive their L-DOPA medication, if they can't tolerate the medication's side effects, or if their depressive symptoms get significantly worse. Our hypothesis is that 80% of the participants will complete the L-DOPA challenge.
The second aim of the study is to see if L-DOPA affects participants' depressive symptoms, processing speed, and working memory. Our hypothesis is that L-DOPA response, measured as an improvement in gait speed, is associated with a decrease in depressive symptoms and an increase in processing speed and working memory.

Start Date15 Aug 2024

Sponsor / Collaborator

University of British Columbia

[+1]

NCT06219915 / CompletedPhase 1/2IIT

Neurobiological Drivers of Mobility Resilience: The Dopaminergic System

Walking with age becomes both slower and less 'automated', requiring more attention and brain resources. As a result, older adults have a greater risk of negative outcomes and falls. There is an urgent need to identify factors that can help compensate for these harmful factors and reduce walking impairments, as there are currently no effective treatments available. Investigators have recently discovered that
20% of older adults maintain fast walking speed even in the presence of small blood vessel brain changes and leg problems, thus appearing to be protected against these harmful factors. The investigators work suggests that the brain dopamine (DA) system may be a source of this protective capacity. Investigators have also shown that lower levels of dopamine are associated with slow walking. Investigators will be investigating the role of dopamine on slow walking and other parkinsonian signs in this double-blinded, placebo-controlled study using detailed clinical assessment, assessment of dopamine activity, and clinical interventions.

Start Date15 Mar 2024

Sponsor / Collaborator

University of Michigan

[+1]

100 Clinical Results associated with Carbidopa

100 Translational Medicine associated with Carbidopa

100 Patents (Medical) associated with Carbidopa

2,767

Literatures (Medical) associated with Carbidopa

01 Nov 2024·Journal of Neural Transmission

Advanced therapies in Parkinson’s disease: an individualized approach to their indication

Review

Author: Rijntjes, Michel ; Sajonz, Bastian E A ; Schröter, Nils ; Groppa, Sergiu ; Jost, Wolfgang H ; Coenen, Volker A

AbstractDevice aided therapies (DAT) comprising the intrajejunal administration of levodopa/carbidopa intestinal gel (LCIG) and levodopa/carbidopa/entacapone intestinal gel (LECIG), the continuous subcutaneous application of foslevodopa/foscarbidopa or apomorphine infusion (CSAI) and deep brain stimulation (DBS) are used to treat Parkinson’s disease with insufficient symptom alleviation under intensified pharmacotherapy. These DAT significantly differ in their efficacy profiles, indication, invasiveness, contraindications, and potential side effects. Usually, the evaluation of all these procedures is conducted simultaneously at the same point in time. However, as disease progression and symptom burden is extremely heterogeneous, clinical experience shows that patients reach the individual milestones for a certain therapy at different points in their disease course. Therefore, advocating for an individualized therapy evaluation for each DAT, requiring an ongoing evaluation. This necessitates that, during each consultation, the current symptomatology should be analyzed, and the potential suitability for a DAT be assessed. This work represents a critical interdisciplinary appraisal of these therapies in terms of their individual profiles and compares these DAT regarding contraindications, periprocedural considerations as well as their efficacy regarding motor- and non-motor deficits, supporting a personalized approach.

15 Oct 2024·Internal Medicine

Japanese <i>Mucuna pruriens</i> (Hasshou Beans) Showed Fast-acting and Long-lasting Effects in Parkinson's Disease

Article

Author: Nagashima, Yasuhiro ; Sakata, Mayumi ; Ito, Hidefumi ; Miyamoto, Katsuichi ; Kondo, Tomoyoshi ; Koh, Jinsoo

Objective Mucuna pruriens (MP) is a legume whose seeds contain levodopa (LD), which has potential therapeutic effects against Parkinson's disease (PD). However, further research is needed to thoroughly evaluate its efficacy and safety for treating this condition. In this study, we analyzed the pharmacokinetics of MP grown in Japan and investigated its mechanism of action in PD. Methods MP seeds ground after roasting (containing 4.02% LD per MP powder) were used as the reagent and compared with an equivalent LD/carbidopa (CD) preparation. This clinical trial was conducted using a crossover design among PD patients attending our institution. Each patient received a single dose of 100/10 mg LD/CD tablets and 11 g of MP reagent. Results Among the seven patients with PD, MP prolonged the ON time 2-fold compared to LD/CD. The LD concentrations after MP intake were higher than those after LD/CD intake, whereas dyskinesia did not increase. An analysis of the LD metabolites showed that the 3-O-methyl-dopa/LD metabolic ratio was significantly lower after MP ingestion than after LD/CD ingestion, indicating that MP has a catechol-O-methyl transferase inhibitory effect. Conclusions This is the first report of a pharmacokinetic analysis conducted on actual patients with PD showing that MP significantly prolongs the ON time. The advantages of MP as a treatment for PD have been confirmed: it is inexpensive, as effective as LD, works faster and longer than LD, and does not increase dyskinesia.

07 Oct 2024·Translational Vision Science & Technology

Retinal Function in Young Adults Following Topical Application of Levodopa to the Eye

Article

Author: Sabeti, Faran ; Leung, Myra ; Maddess, Ted ; Ashby, Regan ; Karouta, Cindy ; Jong, Tina ; Anstice, Nicola ; Thomson, Kate

PurposeLevodopa has been investigated as a therapeutic solution for ocular disorders involving dysregulation of the dopaminergic system, especially in the context of myopia. However, given the critical role dopamine plays in normal vision, this phase I trial examined whether levodopa/carbidopa eye drops induce any regional changes in retinal structure and function.MethodsTwenty-nine healthy male subjects 18 to 30 years of age were randomly assigned to receive either a low (1.4/0.34 µmoles/day, n = 14) or high (2.7/0.68 µmoles/day, n = 15) dose of levodopa/carbidopa eye drops in 1 eye for 28 consecutive days. A placebo solution was applied to all fellow eyes. Measures included visual acuity, regional frequency doubling perimetry, regional multifocal electroretinogram (mfERG) and optical coherence tomography (retinal thickness). Outcome measures were undertaken at baseline, end-of-treatment (4 weeks), and at a follow-up (4 months post-treatment).ResultsFor low dose treated eyes, regional analysis showed a small, statistically significant change in mfERG recordings (increase in ring 5 amplitude in low dose treated eyes, P < 0.05) and the retinal thickness map (localized retinal thinning in low dose treated eyes, P < 0.05). These changes were not clinically significant. No significant changes were observed in high dose treated eyes. Pharmacokinetic analysis (rabbits) demonstrated that levodopa was not detectable within blood and peaked within the eye at 15 to 30 minutes (and eliminated within 4 hours).ConclusionsNo clinically significant effects of levodopa/carbidopa eye drops were found with regard to normal retinal structure and function following short-term use.Translational RelevanceThis study further demonstrates the safety of topical levodopa, which may support its use in the treatment of ocular disorders in which the dopamine system is dysregulated.

151

News (Medical) associated with Carbidopa

30 Oct 2024

·www.prnewswire.com

AbbVie Reports Third-Quarter 2024 Financial Results

Reports Third-Quarter Diluted EPS of $0.88 on a GAAP Basis, a Decrease of 12.0 Percent; Adjusted Diluted EPS of $3.00, an Increase of 1.7 Percent; These Results Include an Unfavorable Impact of $0.04 Per Share Related to Acquired IPR&D and Milestones Expense Delivers Third-Quarter Net Revenues of $14.460 Billion, an Increase of 3.8 Percent on a Reported Basis or 4.9 Percent on an Operational Basis Third-Quarter Global Net Revenues from the Immunology Portfolio Were $7.046 Billion, an Increase of 3.9 Percent on a Reported Basis, or 4.8 Percent on an Operational Basis; Global Humira Net Revenues Were $2.227 Billion; Global Skyrizi Net Revenues Were $3.205 Billion; Global Rinvoq Net Revenues Were $1.614 Billion Third-Quarter Global Net Revenues from the Oncology Portfolio Were $1.687 Billion, an Increase of 11.6 Percent on a Reported Basis, or 13.0 Percent on an Operational Basis; Global Imbruvica Net Revenues Were $828 Million; Global Venclexta Net Revenues Were $677 Million Third-Quarter Global Net Revenues from the Neuroscience Portfolio Were $2.363 Billion, an Increase of 15.6 Percent on a Reported Basis, or 16.0 Percent on an Operational Basis; Global Botox Therapeutic Net Revenues Were $848 Million; Global Vraylar Net Revenues Were $875 Million; Combined Global Ubrelvy and Qulipta Net Revenues Were $445 Million Third-Quarter Global Net Revenues from the Aesthetics Portfolio Were $1.239 Billion, a Decrease of 0.1 Percent on a Reported Basis, or an Increase of 1.8 Percent on an Operational Basis; Global Botox Cosmetic Net Revenues Were $671 Million; Global Juvederm Net Revenues Were $258 Million Successfully Completed Acquisition of Cerevel, Adding Pipeline of Highly Complementary Assets to AbbVie's Existing Neuroscience Portfolio Raises 2024 Adjusted Diluted EPS Guidance Range from $10.67 - $10.87 to $10.90 - $10.94, which Includes an Unfavorable Impact of $0.64 Per Share Related to Acquired IPR&D and Milestones Expense Incurred Year-To-Date Through the Third Quarter 2024 Announces 2025 Dividend Increase of 5.8 Percent, Beginning with Dividend Payable in February 2025 NORTH CHICAGO, Ill., Oct. 30, 2024 /PRNewswire/ -- AbbVie (NYSE:ABBV) announced financial results for the third quarter ended September 30, 2024. "We delivered another quarter of strong commercial execution and significant pipeline progress," said Robert A. Michael, chief executive officer, AbbVie. "Based upon the momentum of AbbVie's business and our confidence in the long-term growth outlook, we are once again raising our full-year guidance and are increasing our quarterly dividend." Third -Quarter Results Worldwide net revenues were $14.460 billion, an increase of 3.8 percent on a reported basis, or 4.9 percent on an operational basis. Global net revenues from the immunology portfolio were $7.046 billion, an increase of 3.9 percent on a reported basis, or 4.8 percent on an operational basis. Global Humira net revenues of $2.227 billion decreased 37.2 percent on a reported basis, or 36.5 percent on an operational basis. U.S. Humira net revenues were $1.765 billion, a decrease of 41.6 percent. Internationally, Humira net revenues were $462 million, a decrease of 12.4 percent on a reported basis, or 7.8 percent on an operational basis. Global Skyrizi net revenues were $3.205 billion, an increase of 50.8 percent on a reported basis, or 51.5 percent on an operational basis. Global Rinvoq net revenues were $1.614 billion, an increase of 45.3 percent on a reported basis, or 47.4 percent on an operational basis. Global net revenues from the oncology portfolio were $1.687 billion, an increase of 11.6 percent on a reported basis, or 13.0 percent on an operational basis. Global Imbruvica net revenues were $828 million, a decrease of 8.8 percent, with U.S. net revenues of $618 million and international profit sharing of $210 million. Global Venclexta net revenues were $677 million, an increase of 14.8 percent on a reported basis, or 18.2 percent on an operational basis. Global Elahere net revenues were $139 million. Global net revenues from the neuroscience portfolio were $2.363 billion, an increase of 15.6 percent on a reported basis, or 16.0 percent on an operational basis. Global Botox Therapeutic net revenues were $848 million, an increase of 13.4 percent on a reported basis, or 14.4 percent on an operational basis. Global Vraylar net revenues were $875 million, an increase of 16.6 percent. Global Ubrelvy net revenues were $269 million, an increase of 15.3 percent. Global Qulipta net revenues were $176 million, an increase of 33.6 percent. Global net revenues from the aesthetics portfolio were $1.239 billion, a decrease of 0.1 percent on a reported basis, or an increase of 1.8 percent on an operational basis. Global Botox Cosmetic net revenues were $671 million, an increase of 8.2 percent on a reported basis, or 9.9 percent on an operational basis. Global Juvederm net revenues were $258 million, a decrease of 19.7 percent on a reported basis, or 16.9 percent on an operational basis. On a GAAP basis, the gross margin ratio in the third quarter was 70.9 percent. The adjusted gross margin ratio was 84.4 percent. On a GAAP basis, selling, general and administrative (SG&A) expense was 29.1 percent of net revenues. The adjusted SG&A expense was 23.0 percent of net revenues. On a GAAP basis, research and development (R&D) expense was 14.7 percent of net revenues. The adjusted R&D expense was 14.2 percent of net revenues. Acquired IPR&D and milestones expense was 0.6 percent of net revenues. On a GAAP basis, the operating margin in the third quarter was 26.5 percent. The adjusted operating margin was 46.7 percent. Net interest expense was $591 million. On a GAAP basis, the tax rate in the quarter was 25.0 percent. The adjusted tax rate was 16.2 percent. Diluted EPS in the third quarter was $0.88 on a GAAP basis. Adjusted diluted EPS, excluding specified items, was $3.00. These results include an unfavorable impact of $0.04 per share related to acquired IPR&D and milestones expense. Note: "Operational" comparisons are presented at constant currency rates that reflect comparative local currency net revenues at the prior year's foreign exchange rates. Recent Events AbbVie announced that it completed its acquisition of Cerevel, adding a pipeline of highly complementary assets to AbbVie's existing neuroscience portfolio. Cerevel's pipeline includes emraclidine, a potential best-in-class, next-generation antipsychotic, that is being studied for the treatment of schizophrenia; tavapadon, a first-in-class dopamine D1/D5 selective partial agonist for the management of Parkinson's disease (PD); as well as CVL-354, a potential best-in-class kappa opioid receptor (KOR) antagonist being studied for the treatment of major depressive disorder (MDD). Cerevel is a strong strategic fit for AbbVie and has potential to meaningfully impact revenue into the next decade. AbbVie announced positive topline results from its pivotal Phase 3 TEMPO-1 trial evaluating tavapadon as a fixed-dose monotherapy treatment in early PD. In the study, tavapadon met the primary endpoint, demonstrating a statistically significant improvement from baseline in the Movement Disorder Society - Unified Parkinson's Disease Rating Scale (MDS-UPDRS) Parts II and III combined score at week 26. Tavapadon also met the key secondary endpoint, demonstrating statistically significant improvement from baseline in the MDS-UPDRS Part II score. Full results from the TEMPO-1 study will be submitted for presentation at future medical meetings and used to support regulatory submissions of tavapadon as a treatment for PD. Topline results from TEMPO-2, the Phase 3 flexible-dose monotherapy trial for tavapadon, are expected by the end of 2024. AbbVie announced the U.S. Food and Drug Administration (FDA) approved Vyalev (foscarbidopa and foslevodopa) as the first subcutaneous 24-hour infusion of levodopa-based therapy for the treatment of motor fluctuations in adults with advanced PD. The approval was supported by results from a pivotal Phase 3 head-to-head, randomized and controlled clinical trial that demonstrated a statistically significant improvement in "on" time without troublesome dyskinesia and decreased "off" time, compared to oral immediate-release carbidopa/levodopa (CD/LD). AbbVie and Aliada Therapeutics announced a definitive agreement under which AbbVie will acquire Aliada, a biotechnology company advancing therapies using a novel blood-brain barrier (BBB)-crossing technology to address challenging central nervous system (CNS) diseases. Aliada's lead investigational asset utilizing this delivery technology, ALIA-1758, is an anti-pyroglutamate amyloid beta (3pE-Aβ) antibody in development for the treatment of Alzheimer's disease (AD). The acquisition also allows AbbVie to utilize Aliada's novel BBB-crossing technology to enhance discovery and development efforts across neuroscience. AbbVie and Gedeon Richter announced a new discovery, co-development and license agreement to advance novel targets for the potential treatment of neuropsychiatric conditions. This collaboration expands upon the success of nearly two decades of partnership on CNS projects. AbbVie announced the European Commission (EC) approved Skyrizi (risankizumab) for the treatment of adult patients with moderately to severely active ulcerative colitis (UC) who have had an inadequate response, lost response, or were intolerant to conventional or biologic therapy. The approval was supported by data from two pivotal Phase 3 trials in which Skyrizi achieved the primary endpoint of clinical remission as well as key secondary endpoints. This marketing authorization for Skyrizi marks its fourth approved indication in the European Union (EU). Skyrizi is part of a collaboration between Boehringer Ingelheim and AbbVie, with AbbVie leading development and commercialization globally. At the European Academy of Dermatology and Venerology (EADV) Congress 2024, AbbVie shared more than 30 presentations that showcased the depth and strength of AbbVie's dermatology portfolio. Presentations highlighted data for Rinvoq (upadacitinib), Skyrizi and lutikizumab across a multitude of dermatological conditions. AbbVie announced that the EC granted conditional marketing authorization for Tepkinly (epcoritamab) as a monotherapy for the treatment of adult patients with relapsed or refractory (r/r) follicular lymphoma (FL) after two or more lines of prior therapy. Tepkinly is the first subcutaneous bispecific antibody conditionally approved as a monotherapy in the EU to treat both r/r FL and r/r diffuse large B-cell lymphoma (DLBCL), after two or more lines of prior therapy. The EC approval is supported by data from the Phase 1/2 EPCORE NHL-1 clinical trial, which evaluated the safety and efficacy of Tepkinly in adult patients with r/r FL. Tepkinly is being co-developed by AbbVie and Genmab. AbbVie announced the European Medicines Agency's (EMA) Committee for Medicinal Products for Human Use (CHMP) adopted a positive opinion recommending the marketing authorization of Elahere (mirvetuximab soravtansine) for the treatment of adult patients with folate receptor alpha (FRα)-positive, platinum-resistant and high-grade serous epithelial ovarian, fallopian tube or primary peritoneal cancer who have received one to three prior treatment regimens. The CHMP's opinion is supported by results of the Phase 3 MIRASOL clinical trial and the EC decision on this indication for Elahere is anticipated later this year. AbbVie announced submission of a Biologics License Application (BLA) to the FDA for accelerated approval (AA) of Teliso-V (telisotuzumab vedotin) in adult patients with previously treated, locally advanced or metastatic epidermal growth factor receptor (EGFR) wild type, nonsquamous non-small cell lung cancer (NSCLC) with c-Met protein overexpression. The BLA is supported by data from the Phase 2 LUMINOSITY clinical trial and review of the BLA will be conducted under FDA's Oncology Center of Excellence (OCE) Real-Time Oncology Review (RTOR) program. There are currently no approved anti-cancer therapies specifically for c-Met overexpressing NSCLC and if approved, Teliso-V would be the first-in-class therapy for this patient population. At the European Society for Medical Oncology (ESMO) Congress 2024, AbbVie showcased new data from its innovative antibody-drug conjugate (ADC) platform in tumor types with high unmet needs. Highlights included full data from the primary analysis of the positive, single-arm Phase 2 PICCOLO trial, evaluating Elahere for high FRα expressing platinum-sensitive ovarian cancer (PSOC); patient reported outcomes from the Phase 2 LUMINOSITY trial, evaluating Teliso-V in advanced NSCLC; as well as new safety and efficacy data in pre-treated patients with advanced NSCLC and gastroesophageal (GEA) cancer, from a Phase 1 study of ABBV-400 (telisotuzumab adizutecan). Allergan Aesthetics announced the FDA approved Botox Cosmetic (onabotulinumtoxinA) for temporary improvement in the appearance of moderate to severe vertical bands connecting the jaw and neck (platysma bands) in adults. Botox Cosmetic is the first product with four aesthetic indication areas: forehead lines, frown lines, crow's feet lines, and now platysma bands, making it the first product of its kind to go beyond the face. Allergan Aesthetics announced the launch of Botox Cosmetic for the treatment of masseter muscle prominence (MMP) in China. The approval is supported by Botox Cosmetic's well-established safety profile as well as clinical trial data that demonstrated Botox Cosmetic is effective in reducing the prominence of the masseter muscle. Botox Cosmetic is the first neurotoxin approved in China for MMP, the largest global MMP market. Allergan Aesthetics intends to develop Botox Cosmetic treatment for MMP in additional global markets and expand the use of Botox Cosmetic in the lower face. At the American Society for Dermal Surgery (ASDS), Allergan Aesthetics presented a total of 12 abstracts that showcased its commitment to patient outcomes and detailed insights and understanding of key concerns across differentiated patient segments. Highlights included four Best of Cosmetic Abstracts as well as a panel discussion on the impact of social media on patient experience and expectations when considering aesthetic treatment. Full-Year 2024 Outlook AbbVie is raising its adjusted diluted EPS guidance for the full year 2024 from $10.67 - $10.87 to $10.90 - $10.94, which includes an unfavorable impact of $0.64 per share related to acquired IPR&D and milestones expense incurred year-to-date through the third quarter 2024. The company's 2024 adjusted diluted EPS guidance excludes any impact from acquired IPR&D and milestones that may be incurred beyond the third quarter of 2024, as both cannot be reliably forecasted. Any potential IPR&D and milestones expense related to the recently announced acquisition of Aliada Therapeutics is also excluded from AbbVie's 2024 adjusted diluted EPS guidance, as the transaction is expected to close in the fourth quarter of 2024. Company Declares Dividend Increase of 5.8 Percent AbbVie is announcing today that its board of directors declared an increase in the company's quarterly cash dividend from $1.55 per share to $1.64 per share beginning with the dividend payable on February 14, 2025 to shareholders of record as of January 15, 2025. This reflects an increase of approximately 5.8 percent, continuing AbbVie's strong commitment to returning cash to shareholders through a growing dividend. Since the company's inception in 2013, AbbVie has increased its quarterly dividend by 310 percent. AbbVie is a member of the S&P Dividend Aristocrats Index, which tracks companies that have annually increased their dividend for at least 25 consecutive years. 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 and eye care - and products and services across our Allergan Aesthetics portfolio. For more information about AbbVie, please visit us at . Follow @abbvie on X (formerly Twitter), Facebook, Instagram, YouTube or LinkedIn. Conference Call AbbVie will host an investor conference call today at 8:00 a.m. Central Time to discuss our third-quarter performance. The call will be webcast through AbbVie's Investor Relations website at investors.abbvie.com. An archived edition of the call will be available after 11:00 a.m. Central Time. Non-GAAP Financial Results Financial results for 2024 and 2023 are presented on both a reported and a non-GAAP basis. Reported results were prepared in accordance with GAAP and include all revenue and expenses recognized during the period. Non-GAAP results adjust for certain non-cash items and for factors that are unusual or unpredictable, and exclude those costs, expenses, and other specified items presented in the reconciliation tables later in this release. AbbVie's management believes non-GAAP financial measures provide useful information to investors regarding AbbVie's results of operations and assist management, analysts, and investors in evaluating the performance of the business. Non-GAAP financial measures should be considered in addition to, and not as a substitute for, measures of financial performance prepared in accordance with GAAP. Forward-Looking Statements Some statements in this news release are, or may be considered, forward-looking statements for purposes of the Private Securities Litigation Reform Act of 1995. The words "believe," "expect," "anticipate," "project" and similar expressions and uses of future or conditional verbs, generally identify forward-looking statements. AbbVie cautions that these forward-looking statements are subject to risks and uncertainties that may cause actual results to differ materially from those expressed or implied in the forward-looking statements. Such risks and uncertainties include, but are not limited to, challenges to intellectual property, competition from other products, difficulties inherent in the research and development process, adverse litigation or government action, and changes to laws and regulations applicable to our industry. Additional information about the economic, competitive, governmental, technological and other factors that may affect AbbVie's operations is set forth in Item 1A, "Risk Factors," of AbbVie's 2023 Annual Report on Form 10-K, which has been filed with the Securities and Exchange Commission, as updated by its Quarterly Reports on Form 10-Q and in other documents that AbbVie subsequently files with the Securities and Exchange Commission that update, supplement or supersede such information. AbbVie undertakes no obligation, and specifically declines, to release publicly any revisions to forward-looking statements as a result of subsequent events or developments, except as required by law. SOURCE AbbVie WANT YOUR COMPANY'S NEWS FEATURED ON PRNEWSWIRE.COM? 440k+ Newsrooms & Influencers 9k+ Digital Media Outlets 270k+ Journalists Opted In GET STARTED

Clinical ResultDrug ApprovalPhase 3License out/inAcquisition

25 Oct 2024

·www.biospace.com

Evecxia Therapeutics Announces Successful Completion of Pre-IND Meeting with the FDA Regarding Development of EVX-101 For Depression

No concerns raised regarding presented non-clinical or clinical safety data Meeting provides clear path forward for filing an IND for conducting a Phase 2 trial in depression patients responding inadequately to standard of care RESEARCH TRIANGLE PARK, N.C.--(BUSINESS WIRE)--Evecxia Therapeutics—the first company dedicated to realizing the therapeutic potential of Serotonin Synthesis Amplification to treat central nervous system disorders—today announced the completion of a pre-Investigational New Drug (pre-IND) meeting with the U.S. Food and Drug Administration (FDA) Division of Psychiatry, Office of Neuroscience, Center for Drug Evaluation and Research. FDA Feedback & Guidance The focus of the pre-IND meeting was to receive FDA feedback and guidance on the non-clinical data, clinical data, and Phase 2 trial design for EVX-101, a novel adjunctive antidepressant candidate for depression patients responding inadequately to first-line serotonin reuptake inhibitor monotherapy. The pre-IND meeting was completed through written responses. The FDA expressed no concerns regarding the three months GLP non-clinical safety data presented and provided useful guidance on further non-clinical development of EVX-101, including on elements that can be omitted, given the favorable historical safety record on 5‑hydroxytryptophan (5‑HTP), the key active pharmaceutical ingredient in EVX-101. The FDA expressed no concerns regarding the safety, tolerability, pharmacokinetic, and pharmacodynamic data from a Phase 1 trial of adjunctive EVX-101 in healthy volunteers, in terms of supporting a subsequent Phase 2 trial. The pre-IND meeting enabled alignment with the FDA regarding submission of an IND to conduct a Phase 2 trial of EVX-101 in depression. “We are delighted with the outcome of the pre-IND meeting written responses from the FDA,” said Jacob Jacobsen, CEO of Evecxia Therapeutics. “The positive and helpful feedback from the FDA is a significant milestone for our development program to develop EVX-101 as a potentially safer and more effective option for the millions of mood disorder patients not responding adequately to first-line serotonin reuptake inhibitors.” About EVX-101 EVX-101 is a first-in-class, proprietary gastro-retentive, sustained-release tablet formulation of 5‑hydroxytryptophan (5-HTP), the immediate precursor to serotonin, and low-dose carbidopa (multiplies 5-HTP’s bioavailability). EVX-101 is in development for next-line adjunctive therapy in depression and obsessive compulsive disorder. Adjunctive EVX-101 is intended to elevate brain serotonin activity beyond the effect of first-line serotonin reuptake inhibitor monotherapy. Multiple published clinical studies support this serotonin augmentation pharmacology is safe and effective in treating depression patients responding inadequately to serotonin reuptake inhibitors (1-4); but, it is not used in any marketed antidepressants. Hence, EVX-101 for depression is risk-mitigated, as based in clinical evidence, yet novel. All marketed antidepressants are based in clinical evidence. EVX-101 appears safe and devoid of abuse potential and could be scalable to broad outpatient mood disorder care. About 5-HTP 5-HTP is the immediate precursor of the neurotransmitter serotonin. Decades of clinical reports support a consensus that 5-HTP has demonstrated therapeutic potential in mood and others central nervous system disorders (5-7). 5-HTP has a benign human safety record (6, 8). 5-HTP’s putative therapeutic action is via Serotonin Synthesis Amplification, creating a stronger, more resilient brain serotonin system, a pharmacology distinct from available serotonin drugs, e.g., serotonin reuptake inhibitors and psychedelics. But the 5-HTP molecule is impractical for clinical practice, as 5-HTP is minimally absorbed by the body and very short-acting (9). No FDA-approved 5-HTP drug exists. Evecxia deploys pharmaceutical technologies to ensure sufficient absorption and prolonged action of 5-HTP in the body, thus enabling practical Serotonin Synthesis Amplification therapy. About Evecxia Therapeutics Evecxia is the first company dedicated to realizing the therapeutic potential of Serotonin Synthesis Amplification to treat central nervous system disorders. Evecxia has two Phase 2 clinical-stage drug candidates in development. EVX-101 is being developed as an adjunctive treatment for depression and obsessive-compulsive disorder when first-line serotonin reuptake inhibitor antidepressants alone are inadequate. EVX-301 is being developed as rescue therapy for patients hospitalized for acute suicidal crisis. For additional information about Evecxia, please visit . References 1. van Praag HM (1982): Adv Biochem Psychopharmacol. 34:259-286. 2 Nardini M, et al. (1983): Int J Clin Pharmacol Res. 3:239-250. 3. Walinder J, et al. (1976): Arch Gen Psychiatry. 33:1384-1389. 4. Papakostas GI, et al. (2012): Am J Psychiatry. 169:1267-1274. 5. Shaw K, et al. (2002): Cochrane Database Syst Rev.CD003198. 6. Turner EH, et al. (2006): Pharmacol Ther. 109:325-338. 7. Levy A, et al. (2016): Curr Treat Options Neurol. 18:21. 8. Das YT, et al. (2004): Toxicol Lett. 150:111-122. 9. Evecxia (2024): Data on file. Contacts Jacob Jacobsen, CEO Evecxia Therapeutics, Inc. Info@evecxia.com

Phase 2Phase 1

18 Oct 2024

·www.pharmaceutical-technology.com

FDA approves AbbVie’s VYALEV for advanced Parkinson’s treatment

Parkinson’s disease is a chronic neurological disorder marked by symptoms such as tremors and muscle rigidity. Credit: chainarong06/Shutterstock. The US Food and Drug Administration (FDA) has approved AbbVie ‘s VYALEV (foscarbidopa and foslevodopa) to treat motor fluctuations in adults with advanced Parkinson’s disease (PD). The chronic neurological disorder is marked by symptoms such as tremors and muscle rigidity, and affects more than ten million people globally. VYALEV, also known as PRODUODOPA, is the first and only subcutaneous 24-hour infusion of levodopa-based therapy approved for this indication. The treatment is approved in 35 countries and is available as a 120mg foscarbidopa dose and a 2,400mg foslevodopa per 10ml solution dose. AbbVie research and development executive vice-president and chief scientific officer Roopal Thakkar stated: “People living with advanced Parkinson’s disease experience daily challenges as a result of uncertainty in managing motor fluctuations, especially as their disease progresses. See Also: Health Canada approves Acadia’s DAYBUE for Rett syndrome COPD market expected to grow to $30.8bn in the 7MM by 2033 “We are proud to bring this innovation to patients who may benefit from motor symptom control through continuous 24-hour administration of VYALEV.” The FDA’s approval is based on the results from the pivotal Phase III M15-736 study. This 12-week trial assessed the efficacy of VYALEV’s continuous infusion in advanced PD patients against oral immediate-release carbidopa/levodopa (CD/LD IR). A 52-week open-label study was also conducted to evaluate the long-term efficacy and safety of the treatment. In PD, “on” time indicates when patients have optimal motor symptom control, while “off” time refers to the return of symptoms. The primary endpoint of the study was the quality of “on” time, averaged over three consecutive days and normalised to a waking period of 16 hours. Results from the pivotal study demonstrated that patients treated with VYALEV experienced significant improvements in motor fluctuations and had an increased “on” time and decreased “off” time without troublesome dyskinesia, compared to those receiving oral CD/LD IR. In June 2024, the FDA issued a complete response letter for the new drug application of ABBV-951.

Clinical ResultDrug ApprovalPhase 3

100 Deals associated with Carbidopa

External Link

KEGG	Wiki	ATC	Drug Bank
D00558	Carbidopa	N04BA03	DB00190

R&D Status

10 top approved records.

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Indication	Country/Location	Organization	Date
Parkinson Disease	CN	Nantong Senxuan Pharmaceutical Co. Ltd.	01 Jan 1990
Nausea	US	Aton Pharma, Inc.	25 Apr 1977
Parkinson Disease, Postencephalitic	US	Aton Pharma, Inc.	25 Apr 1977
Vomiting	US	Aton Pharma, Inc.	25 Apr 1977

Clinical Result

Indication

Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT00983814 (ADD201, CTgov)	Phase 2	Attention Deficit Disorder With Hyperactivity	20	Carbidopa+Droxidopa (Droxidopa+Carbidopa: Double-Blind)	eyapvjverh(yvwfewgvmo) = jilophromz pojperlgik (irioiznhce, bfkrjfaunz - afrkmrumoc) View more	-	18 Apr 2024
				placebo+carbidopa+droxidopa (Placebo: Double-Blind)	eyapvjverh(yvwfewgvmo) = odhlmskjgy pojperlgik (irioiznhce, asuxbepofd - ifzkubvrfe) View more
NCT02553265 (CarbiFD, CTgov)	Phase 2	Pure Autonomic Failure \| Dysautonomia, Familial	22	Placebo (Placebo)	qyhorihjum(jszmnukxuh) = kazrgodhyy lootkcqqkm (qrbjcwzaqz, kucmdcdpqu - uiwxpkwoyw) View more	-	09 Feb 2022
				Carbidopa Low-Dose (Low-Dose Carbidopa)	qyhorihjum(jszmnukxuh) = kkvygicwqv lootkcqqkm (qrbjcwzaqz, hlpzqtwxfh - cvrasjcgrd) View more
NCT00685919 (CTgov)	Phase 2/3	Postural Orthostatic Tachycardia Syndrome	32	Placebo (Healthy Participants Who Received Placebo as Treatment A or Treatment B)	fuuldnejfr(nukyldqtaq) = udbhpgrhjz hqtemktuju (keqyermnww, qiotbwmkqp - uttwwgqnbf) View more	-	20 Sep 2021
				Carbidopa (Healthy Participants Who Received Carbidopa as Treatment A or Treatment B)	fuuldnejfr(nukyldqtaq) = neajmtlgaf hqtemktuju (keqyermnww, wktvwxjzds - pdrmdgzqce) View more
MDS2020	Not Applicable	Parkinson Disease	255	Carbidopa (10 mg)	(rrsntoomnj) = zlvkskaazc uglpzpcfrn (oqszelgwfa )	Positive	12 Sep 2020
				Benserazide (25 mg)	(rrsntoomnj) = qqxddcjqmd uglpzpcfrn (oqszelgwfa )
NCT03115827 (CTgov)	Phase 4	Parkinson Disease	15	Carbidopa+Droxidopa	yfarwdpqec(mwhepdhevc) = rawrjukfmv mjlzccvlge (blluysdjos, jywplyglbq - nesoqxqlnn) View more	-	27 Jan 2020
MDS2016	Not Applicable	-	-	Levodopa + Carbidopa	foukpzushx(klnkjlptjh) = uairyyfkcy vtrwcjmaws (dbrihajprj ) View more	-	19 Jun 2016
				Saline	foukpzushx(klnkjlptjh) = qbrvxfzote vtrwcjmaws (dbrihajprj ) View more
NCT01568073 (CTgov)	Phase 3	Parkinson Disease	600	Placebo+Carbidopa+Benserazide+Levodopa (Placebo)	gidistrota(bfajcadbed) = gpmgxvegnb kglvoxllrt (twldwrgcru, dbmxwidqth - khnfvaemrz) View more	-	08 Jan 2015
				Carbidopa+Benserazide+Entacapone+Levodopa (Entacapone)	gidistrota(bfajcadbed) = wqyyefecav kglvoxllrt (twldwrgcru, ranqwadgoa - hrkrpmtdut) View more
AAN2014	Not Applicable	Hypertension	15	Carbidopa	rdqkgsqxbw(bfderchriw) = bbdyvqhzte zwmyianquc (mxdpayvyas ) View more	-	08 Apr 2014

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