A Phase 1/2 Unblinded Trial of Carboxyamidotriazole Orotate (CTO) Alone or in Combination With Lomustine for Bevacizumab-Naïve Adult Patients With Recurrent Malignant Glioma

This is a Phase 1/2 study of the combination of CTO with lomustine in patients with recurrent malignant glioma to be treated at the Preston Robert Tisch Brain Tumor Center (PRTBTC) at Duke. The Primary Objectives are:
Phase 1: To determine the maximum tolerated dose (MTD) of CTO when combined with lomustine among patients with recurrent malignant glioma (World Health Organization (WHO) grade III or IV) who have not been previously treated with bevacizumab.
Phase 2: To assess the efficacy of CTO (either in monotherapy or in combination with lomustine) compared to lomustine alone in patients with recurrent WHO grade IV malignant gliomas that have not been previously treated with bevacizumab based upon 6-month progression free survival (PFS6).
Note: This study was terminated early due to funding issues. At the time of termination, the study was still in Phase 1 and no MTD for the combination of CTO and lomustine had been determined for this population. Phase 2 will not proceed.

Start Date01 May 2014

Sponsor / Collaborator

Duke University

[+1]

NCT01954030 / TerminatedPhase 1IIT

A Phase 1/2 Trial of Carboxyamidotriazole Orotate (CTO) Alone or in Combination With Bevacizumab for Adult Patients With Recurrent Malignant Glioma Post-Bevacizumab Failure

The primary objectives of the study are to determine the maximum tolerated dose (MTD) of Carboxyamidotriazole Orotate (CTO) when combined with standard dosing of bevacizumab among patients with recurrent malignant glioma (WHO grade III or IV) that have previously failed bevacizumab (Phase 1); to determine the activity of CTO alone in bevacizumab-failure WHO grade IV malignant glioma patients (Phase 2, Arm 1); to determine the activity of CTO plus bevacizumab in bevacizumab-failure WHO grade IV malignant glioma patients (Phase 2, Arm 2).
This study was terminated early due to funding issues. At the time of termination, the study was still in Phase 1 and no MTD for the combination of CTO and bevacizumab had been determined for this population. Phase 2 will not proceed.

Start Date01 Oct 2013

Sponsor / Collaborator

Duke University

[+1]

NCT01107522 / Active, not recruitingPhase 1

A Phase I Study of Oral Carboxyamidotriazole Orotate (CTO) Titrated as a Single Agent in Patients With Advanced or Metastatic Solid Tumors and Titrated in Combination Therapy With Temodar® for Patients With Glioblastoma and Other Recurrent Malignant Gliomas or in Combination With Temodar® and Radiation Therapy for Patients With Newly Diagnosed Glioblastoma and Malignant Gliomas

The purpose of this study is to determine the safety, tolerability, and the maximum tolerated dose/recommended phase II dose of carboxyamidotriazole orotate (CTO) as a single agent in patients with advanced or metastatic solid tumors; in combination with oral Temodar® in patients with glioblastoma or other recurrent malignant gliomas; or in combination with oral Temodar® and radiation therapy in patients with newly diagnosed glioblastoma or other malignant gliomas.

Start Date01 May 2010

Sponsor / Collaborator

Tactical Therapeutics, Inc.

100 Clinical Results associated with Carboxyamidotriazole orotate

100 Translational Medicine associated with Carboxyamidotriazole orotate

100 Patents (Medical) associated with Carboxyamidotriazole orotate

218

Literatures (Medical) associated with Carboxyamidotriazole orotate

01 Oct 2024·JOURNAL OF AOAC INTERNATIONAL

Green and Versatile High-Throughput Microwell Oxidation-Based Spectrophotometric Methods for Determination of Galidesivir in Capsules

Article

Author: Alzoman, Nourah Z ; Darwish, Ibrahim A

Abstract:

Background:

Galidesivir (GDV) is a promising new antiviral drug for the potent and safe treatment of a broad spectrum of viral diseases, including COVID-19. In the literature, no analytical method exists for the determination of GDV in bulk and dosage form.

Objective:

The aim of this study was the development of versatile green and simple microwell spectrophotometric methods (MW-SPMs) for the determination of GDV in its bulk form and capsules.

Methods:

Three MW-SPMs were developed involving the oxidation of GDV by ammonium metavanadate (AMV), chromium trioxide (CTO), and potassium iodate (PIO) in an acid medium. The reactions were carried out in 96-well plates at room temperature and the absorbances of chromogenic reaction products were measured by an absorbance microplate reader at 780, 595, and 475 nm for AMV, CTO, and PIO, respectively. Variables influencing the reactions were carefully investigated and optimized.

Results:

Linear relations with excellent correlation coefficients (0.9991–0.9997) were found between the absorbances and GDV concentrations in the range of 25–500 µg/mL. The LODs were ≥8.3 µg/mL. The accuracy and precision of the three MW-SPMs were confirmed by recovery and replicate analysis, respectively. The recovery values were 98.6–101.2% and the RSDs were ≤1.02%. The proposed MW-SPMs were successfully applied to the analysis of GDV in bulk drug and capsules with high accuracy and precision. The greenness of the MW-SPMs was confirmed by three comprehensive metric tools.

Conclusion:

The proposed MW-SPMs combined the inherent advantages of microwell-based analysis and the use of common laboratory reagents for the reactions involved. These advantages include high-throughput, ready automation, reduced sample/reagent volume, precise measurements, and versatility. The advantages of the use of common laboratory reagents include availability, consistency, compatibility, safety, and cost-effectiveness.

Highlights:

Overall, the proposed MW-SPMs are versatile valuable tools for the quantitation of GDV during its pharmaceutical manufacturing.

01 Sep 2024·JOURNAL OF AFFECTIVE DISORDERS

Human brain 7Li-MRI following low-dose lithium dietary supplementation in healthy participants

Article

Author: Strawbridge, Rebecca ; Cousins, David A ; Thelwall, Peter E ; Wing, Victoria C ; Neal, Mary A

BACKGROUND:

Lithium is an effective mood stabiliser, but its mechanism of action is incompletely defined. Even at very low doses, lithium may have neuroprotective effects, but it is not clear if these relate to brain lithium concentration in vivo. We have developed magnetic resonance imaging (⁷Li-MRI) methods to detect lithium in the brain following supplementation at a very low dose.

METHODS:

Lithium orotate supplements were taken by nine healthy adult male subjects (5 mg daily) for up to 28 days, providing 2-7 % of the lithium content of a typical therapeutic lithium carbonate dose. One-dimensional ⁷Li-images were acquired on a 3.0 T MRI scanner. All subjects were scanned on day 14 or 28; seven were scanned on both, one at baseline and one after 7-days washout.

RESULTS:

⁷Li-MR signal amplitude was broadly stable between days 14 and 28. Two subjects had notably higher ⁷Li-signal intensities (approximately 2-4×) compared to other study participants.

LIMITATIONS:

Lithium adherence was self-reported by all participants without formal validation. The coarse spatial resolution necessary for detection of low concentrations of ⁷Li exhibits imperfect spatial separation of signal from adjacent pixels.

CONCLUSIONS:

⁷Li-MRI performed using a clinical 3T scanner demonstrated detection of lithium in the brain at very low concentration, in the range of approximately 10-60 mM. The methods are suited to studies assessing low dose lithium administration in psychiatric and neurodegenerative disorders, and permit the comparison of different lithium salt preparations at a time of emerging interest in the field.

01 Sep 2024·JOURNAL OF VASCULAR SURGERY

Impact of early intervention on health status outcomes in peripheral artery disease patients with chronic total occlusion lesions using the PORTRAIT registry

Article

Author: Hussain, Yasin ; Callegari, Santiago ; Cerrud-Rodriguez, Roberto C ; Mena-Hurtado, Carlos ; Romain, Gaëlle ; Smolderen, Kim G ; Cleman, Jacob ; Scierka, Lindsey

OBJECTIVE:

To analyze the impact of noninvasive and early invasive treatments on health status in patients with lower extremity peripheral arterial disease (PAD) without and with chronic total occlusions (CTOs) after 12 months of follow-up.

METHODS:

Using the international (the United States, the Netherlands, and Australia) observational longitudinal Patient-Centered Outcomes Related to Treatment Practices in Peripheral Arterial Disease: Investigating Trajectories registry, we included patients with recent PAD symptoms between June 2011 and December 2015. We assessed the PAD-specific health status at initial visit and the 3-, 6-, and 12-month follow-up using the Peripheral Arterial Questionnaire. On a propensity matched-weighted cohort, we compared patients' characteristics by CTO status and treatment groups as early invasive (revascularization in the 3 months) vs noninvasive (exercise, medical therapies, or smoking cessation). We then assessed the health status trajectory over 12 months, as a three-way interaction between CTO status, treatment groups, and months, using a multilevel generalized linear regression model for repeated measures adjusted for baseline health status with random effects at the site and patient levels.

RESULTS:

We included 581 participants, with a mean age of 66.62 ± 9.33 years, 34.3% female, and 90.8% White, of whom 353 (60.8%) were without and 228 (39.2%) had a CTO lesion. Respectively, 96 (27.2%) and 70 (30.7%) patients underwent early invasive treatment (d = 0.07). Although patients with CTO were more likely to have lower resting ABI, multilevel disease, and to experience severe claudication vs their counterparts (|d| ≥ 0.20), patient health status at baseline with CTO was not different from those without CTO, with mean summary scores of 45.14 ± 20.26 vs 45.90 ± 21.24 (d = 0.04), respectively. The trajectory did not differ by CTO status (interaction CTO status × month; P = .517) and was higher in early invasive vs noninvasive treatment (treatment × month; P < .001), regardless of CTO status (CTO status × treatment; P = .981 and CTO status × treatment × month; P = .264). The score increased over time with the largest improvement occurring at 3 months in both noninvasive (non-CTO, +7.82 [95% confidence interval (CI), 4.03-11.60] and CTO, +9.27 95% CI, 4.45-14.09) and early invasive (non-CTO, +26.17 [95% CI, 20.06-32.28] and CTO, +24.52 [95% CI, 17.40-31.64] groups. The mean score in CTO vs non-CTO groups did not differ at each timepoint, with a 12-month mean score of 70.26 (95% CI, 67.87-74.65) vs 71.17 (95% CI, 65.91-76.44) (P = .99) in the noninvasive treatment and 84.93 (95% CI, 78.90-90.97) vs 79.20 (95% CI, 72.77-86.14) (P = .31) in the early invasive treatment.

CONCLUSIONS:

Patients with symptomatic PAD undergoing early revascularization exhibited better health status over time vs those undergoing noninvasive treatment strategy, irrespective of the presence of CTOs. The degree of the improvement was greater in the 3 months after the initial visit, especially in patients undergoing early revascularization.

News (Medical) associated with Carboxyamidotriazole orotate

08 Jun 2023

·www.pharmaceutical-technology.com

UK’s MHRA expands approval for Merz Therapeutics’ XEOMIN

Merz Therapeutics’ XEOMIN is injected intramuscularly to improve muscle tone. Credit: Mufid Majnun on Unsplash. The UK’s medicines and healthcare products regulatory agency (MHRA) has granted approval for a new indication for Merz Therapeutics’ XEOMIN (incobotulinumtoxinA) to treat focal spasticity of the lower limbs affecting the ankle joint. The therapy was previously approved in the UK to treat upper limb spasticity. Recommended Reports Reports LOA and PTSR Model - Carboxyamidotriazole Orotate in Glioblastoma Multiforme (GBM) GlobalData Reports LOA and PTSR Model - Valbenazine Tosylate in Chorea GlobalData View all The expanded approval allows the company to provide holistic support to those living with spasticity who need comprehensive treatment. The active ingredient in XEOMIN is incobotulinumtoxinA. It is injected intramuscularly to improve muscle tone. The therapy blocks nerve impulses to the muscles to weaken voluntary muscle contraction. It relieves abnormal muscle tone by inhibiting the release of acetylcholine from the peripheral nerve endings. Merz Therapeutics stated that XEOMIN can now be used to treat lower and upper limbs individually or simultaneously, by adjusting the dose as required. Merz Therapeutics CEO Stefan König stated: “The label extension in the UK is an important step for Merz Therapeutics and the patients that we serve. “With the UK becoming the second market, following Japan, to grant approval for the treatment of lower limb spasticity affecting the ankle joint, it establishes the UK as the pioneering European country in this area.” The company noted that 400 units per injection is the maximum dose of XEOMIN required to treat lower limbs. 500 units is the maximum dose for the combined treatment of upper and lower limb spasticity. XEOMIN has already received approval in more than 75 countries across the world for the treatment of blepharospasm, cervical dystonia, upper and lower limb spasticity and sialorrhea.

Drug Approval

13 Dec 2022

·www.prnewswire.com

Tactical Therapeutics, Inc., Developer of CTO Treatments for Glioblastoma, Selected to Present at MedInvest Oncology Investor Conference December 14-15 in New York

Founder and CEO Rashida Karmali Ph.D., J.D., is a respected pioneer in cancer research, specializing in drug discovery and development Carboxyamidotriazole Orotate (CTO) shows promising results in pre-clinical and Phase I trials A privately funded clinical stage company, TTI is raising money for Phase II clinical trials NEW YORK, Dec. 13, 2022 /PRNewswire/ -- Tactical Therapeutics, Inc. (TTI), a clinical stage biopharma, has been selected to present at the MedInvest Oncology Investor Conference taking place December 14-15, 2022, in New York, N.Y. "We are honored to be selected to present at this unique event," said Rashida Karmali, Ph.D., CEO of Tactical Therapeutics . "We welcome the chance to interact with many of the world's most accomplished leaders and investors who are all dedicated to improving the health and lives of patients with glioblastoma (GBM) and difficult to treat solid cancers." About Glioblastoma, recurrent (rGBM) and newly diagnosed (nGBM) Glioblastoma, the brain tumor that killed Senator Ted Kennedy, Beau Biden and Senator John McCain, is still mostly untreatable. Recent reports suggest veterans of Vietnam, Iraq and Afghanistan wars who were exposed to burn pits later developed GBM. GBM exhibits debilitating neurological symptoms and suicide rates for GBM patients are higher compared to those with other cancers. Since 2005, GBM, an orphan disease (approximately 18,000/yr), has a median overall survival (OS) of between 12 to 20 months in newly diagnosed GBM with surgery, radiotherapy (with temozolomide) and adjuvant temozolomide, plus tumor treating fields. rGBM recurs frequently within a year with a median OS of 10 months. TTI's oral, safe and brain-penetrating drug, Carboxyamidotriazole Orotate (CTO), showed efficacy with significantly improved OS from 10 months to 28 months+ in nGBM in Phase IB trial, with published results (J. Clin Oncology, (2018)36:1702-1709). Dr. Antonio Omuro, who oversaw the CTO Phase I clinical trial, had this to say about the promising treatment: "In 27 Recurrent GBM patients, 1 complete and 6 partial responses were observed in patients who had been in several previous trials, including patients previously exposed to bevacizumab, who are the most challenging patients to treat. Radiographic responses are rarely seen in glioblastoma trials, therefore these are really promising results. Excellent survival was observed in 15 newly diagnosed GBM (13/15), with median overall survival not reached after 28 months; 2-year survival 62%; 1-year survival 93%. Two patients remain recurrence free at 5 years. "The safety profile was excellent, and we were also able to demonstrate that CTO crosses the blood brain barrier and can achieve high concentrations in brain tumors. Overall, the Phase IB trials of CTO in GBM patients showed highly promising efficacy and safety in patients with very advanced disease." About Carboxyamidotriazole Orotate (CTO) & Intellectual Property (IP) CTO is a patented first-in-class inhibitor of genes of non-voltage dependent calcium signaling associated with multiple oncolytic pathways and calcium channels. At clinically relevant CTO levels, differential expression of some mRNA showed inhibition of transcriptional signatures of several oncogenes, and in contrast activation of tumor suppressors. The IP portfolio includes 8 U.S. and 75 International patents lasting to 2033. About Tactical Therapeutics, Inc Tactical Therapeutics, Inc., is a privately funded company that has developed a patented lead therapeutic, CTO, for glioblastoma and other solid cancers. Three Phase I trials have been completed. Two Phase II trials are planned for rGBM and nGBM. The company is pursuing partnering and licensing strategies. Contact for Tactical Therapeutics, Inc: Rashida Karmali, 212-651-9653; 917-763-7196; [email protected] SOURCE Tactical Therapeutics, Inc.

Phase 1Clinical ResultPhase 2ASCO

100 Deals associated with Carboxyamidotriazole orotate

R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Glioma	Phase 2	US	Tactical Therapeutics, Inc.	18 Jun 2018
Recurrent Glioma	Phase 1	US	Tactical Therapeutics, Inc.	01 Oct 2013
Recurrent Malignant Glioma	Phase 1	US	Tactical Therapeutics, Inc.	01 Oct 2013
Glioblastoma	Phase 1	US	Tactical Therapeutics, Inc.	01 May 2010

Clinical Result

Indication

Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT01107522 (Pubmed \| J Urol)	Phase 1	Glioma \| Recurrent Glioblastoma	-	Carboxyamidotriazole orotate	axcmflwlrx(bgjwltdhtt) = fcrsxjwphb wzyfrypqja (vurldnezgv ) View more	-	10 Jun 2018
NCT01107522 (ASCO2016)	Phase 1	Glioblastoma Multiforme	15	Carboxyamidotriazole orotate (CTO)	koriicvgqi(amobfxrmkh) = decreased platelets and neutrophils qvaxdxibuo (ptgrlgdsfy ) View more	Positive	20 May 2016
NCT01989052 (ASCO2015)	Phase 1	Recurrent Malignant Glioma	9	Carboxyamidotriazole orotate (CTO)	jypmvtvjxz(kxuhekiley) = ttspuyotcv okpiworihp (mwbgtgesqh )	-	20 May 2015
NCT01954030 (ASCO2015)	Phase 1	Recurrent Malignant Glioma	15	Carboxyamidotriazole orotate (CTO)	watvlyghsr(sbfppbvhce) = surgkkrdqr taqxuwmzdx (vmpsidqqeu ) View more	-	20 May 2015
NCT01107522 (ASCO2014)	Phase 1	Recurrent Malignant Glioma	15	Carboxyamidotriazole orotate (CTO)	meklknqzgx(jsdjdorclw) = qkqzorjrcg owevpazmud (znceobatvy )	-	20 May 2014
NCT01107522 (ASCO2014)	Phase 1	Recurrent Malignant Glioma	15	Temozolomide (TMZ)	meklknqzgx(jsdjdorclw) = wulgisdsbe owevpazmud (znceobatvy )	-	20 May 2014

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