clenbuterol (CST-103) / CuraSen Therap - LARVOL DELTA

CLIN-011: A Study of Clenbuterol (CST-103) Co-administered With Nadolol (CST-107) in Subjects With Neurodegenerative Disorders (clinicaltrials.gov) - P2 | N=41 | Completed | Sponsor: CuraSen Therapeutics, Inc. | Active, not recruiting ➔ Completed

Trial completion • Alzheimer's Disease • CNS Disorders • Cognitive Disorders • Dementia • Lewy Body Disease • Mental Retardation • Movement Disorders • Parkinson's Disease • Psychiatry • REM Sleep Behavior Disorder

Cognitive Effects of Three β-Adrenoceptor Acting Drugs in Healthy Volunteers and Patients with Parkinson's Disease. (PubMed, J Parkinsons Dis) - "In Part A, HVs received single doses of 32 mg salbutamol, 160μg clenbuterol, 60 mg pindolol and placebo administered in a randomized, 4-way cross-over study. This study demonstrates the pro-cognitive effects of clenbuterol in HVs with similar trends in PD-patients. The mechanism of action is likely activation of β2-ARs in the CNS."

Journal • Cardiovascular • CNS Disorders • Movement Disorders • Parkinson's Disease

A Study of CST-103 Co-administered With CST-107 in Subjects With Parkinson's Disease Having Freezing of Gait (CLIN-012) (clinicaltrials.gov) - P2 | N=0 | Withdrawn | Sponsor: CuraSen Therapeutics, Inc. | N=25 ➔ 0 | Not yet recruiting ➔ Withdrawn

Enrollment change • Trial withdrawal • CNS Disorders • Movement Disorders • Parkinson's Disease

Effects on cerebral blood flow after single doses of the β2 agonist, clenbuterol, in healthy volunteers and patients with mild cognitive impairment or Parkinson's disease. (PubMed, Br J Clin Pharmacol) - "The effects of clenbuterol on rCBF were evident both in the absence and presence of low-dose nadolol, suggesting central nervous system (CNS) involvement. Concomitant inhibition of the peripheral effects of clenbuterol by nadolol confirms that meaningful β2-AR antagonism in the periphery was achieved without interrupting the central effects of clenbuterol on rCBF."

Journal • Alzheimer's Disease • CNS Disorders • Cognitive Disorders • Movement Disorders • Parkinson's Disease

Effects of clenbuterol, an oral, CNS–penetrant β2 adrenoceptor agonist, on cognition and emotional processing in patients with parkinson's disease (ECNP 2023) - "PD patients in this study had impaired cognition at baseline and a reduced ability to recognize faces with varying degrees of happiness which were associated with a concomitant reduction in LC integrity. Both impairments were improved following 14-day treatment with a β2-AR agonist when administered with a peripherally restricted antagonist, a treatment regimen that was well-tolerated. These data support further development of clenbuterol+nadolol for the treatment of PD patients with cognitive impairment and low mood."

Clinical • Alzheimer's Disease • CNS Disorders • Cognitive Disorders • Parkinson's Disease

A Study of CST-103 Co-administered With CST-107 in Subjects With Parkinson's Disease Having Freezing of Gait (CLIN-012) (clinicaltrials.gov) - P2 | N=25 | Not yet recruiting | Sponsor: CuraSen Therapeutics, Inc. | Trial completion date: Mar 2024 ➔ Mar 2025 | Trial primary completion date: Dec 2023 ➔ Dec 2024

Trial completion date • Trial primary completion date • CNS Disorders • Movement Disorders • Parkinson's Disease

CLIN-011: A Study of CST-103 Co-administered With CST-107 in Subjects With Neurodegenerative Disorders (clinicaltrials.gov) - P2 | N=41 | Active, not recruiting | Sponsor: CuraSen Therapeutics, Inc. | Trial completion date: Mar 2023 ➔ Jul 2023

Trial completion date • Alzheimer's Disease • Behavior Disorders • CNS Disorders • Cognitive Disorders • Dementia • Lewy Body Disease • Mental Retardation • Movement Disorders • Parkinson's Disease • Psychiatry • REM Sleep Behavior Disorder

CuraSen Therapeutics to Present Phase 2 Data Showing Rapid-Onset Cognition and Mood Benefit with CST-103/CST-107 (Clenbuterol/Nadolol) in Parkinson’s Disease at the Alzheimer’s Disease and Parkinson’s Disease (AD/PD’23) Conference (Businesswire) - P2 | N=41 | NCT04739423| Sponsor: CuraSen Therapeutics, Inc. | "CuraSen Therapeutics...announced that it will present Phase 2 clinical data showing improvements in cognition and mood in Parkinson’s disease patients treated with CST-103/CST-107....Phase 2 Proof-of-Concept Study with Clenbuterol/Nadolol in Parkinson’s Disease....Statistically significant improvements in several quantitative test measures of episodic memory, attentiveness and depressive emotional bias in patients treated with clenbuterol/nadolol, with several effect sizes (Cohen’s d) in the range 0.3-0.6 which are predictive of clinically meaningful results in a larger, longer trial....CuraSen’s next Phase 2 study with clenbuterol/nadolol is anticipated later this year and will enroll Parkinson’s patients with significant non-motor symptoms with a similar combination dosing plan in a 12-week parallel design."

P2 data • Trial status • CNS Disorders • Parkinson's Disease

EFFECTS OF A BETA-2 ADRENOCEPTOR (AR) AGONIST ON COGNITION IN PARKINSON'S DISEASE PATIENTS WITH REM SLEEP BEHAVIOR DISORDER (RBD) (ADPD 2023) - "Short-term treatment with the β 2 -AR agonist, CST-103, when administered with the peripherally restricted β-AR antagonist, CST-107, improved performance in tests of cognition and was well-tolerated. These data support further development of CST-103."

Clinical • Behavior Disorders • CNS Disorders • Mental Retardation • Movement Disorders • Parkinson's Disease • Psychiatry • REM Sleep Behavior Disorder • Sleep Disorder

CuraSen Therapeutics Announces Successful Completion of Phase 2 Safety, Tolerability and Proof of Concept Study in Patients with Parkinson’s Disease or Mild Cognitive Impairment (MCI) with CST-103/CST-107 Treatment (Businesswire) - P2 | N=41 | NCT04739423 | Sponsor: CuraSen Therapeutics, Inc. | "CuraSen Therapeutics, Inc...announced today positive top-line safety, tolerability and proof of concept data, with early efficacy benefit, in a Phase 2 clinical trial with CST-103 in patients with Parkinson’s disease (PD) or mild cognitive impairment (MCI)....Results showed that the combination of CST-103/CST-107 was both safe and well-tolerated, and importantly, that co-administration of CST-107 eliminated adverse events (AEs) common to the β2-AR agonist class of drugs when administered alone....Additionally, the study revealed improvements in several quantitative test measures of cognition in patients treated with CST-103/CST-107, as early as one day after treatment and lasting in some cases for longer than the two weeks of treatment. CuraSen will present complete results from this trial in an oral session at the AD/PD Conference in Gothenburg, Sweden, March 28-April 1, 2023."

P2 data • Trial completion • CNS Disorders • Cognitive Disorders • Parkinson's Disease

USE OF THE DIGIT SYMBOL SUBSTITUTION TEST (DSST) AS AN ENTRY CRITERION FOR A COGNITIVE STUDY OF A Β2-AR AGONIST. (CTAD 2022) - "CuraSen’s ongoing and completed early phase studies demonstrate that the β2-AR agonist CST-103 increases cerebral perfusion in healthy individuals and those living with Parkinson’s disease (PD) and mild cognitive impairment (MCI)... Selecting a patient population which has objectively identified cognitive deficits is essential in order to demonstrate positive drug effects on cognition. In the present study we have utilized an enrichment strategy based on use of the DSST, a well validated cognitive test which measures multiple cognitive domains. Use of the DSST as an entry requirement led to a number of screen failures but at a rate that is an acceptable trade-off to ensure that the population recruited into the study has cognitive deficits which can be remediated by treatment."

Alzheimer's Disease • CNS Disorders • Cognitive Disorders • Dementia • Lewy Body Disease • Movement Disorders • Parkinson's Disease

CLIN-011: A Study of CST-103 Co-administered With CST-107 in Subjects With Neurodegenerative Disorders (clinicaltrials.gov) - P2 | N=41 | Active, not recruiting | Sponsor: CuraSen Therapeutics, Inc. | Trial completion date: Aug 2022 ➔ Dec 2022

Trial completion date • Alzheimer's Disease • Behavior Disorders • CNS Disorders • Cognitive Disorders • Dementia • Lewy Body Disease • Mental Retardation • Movement Disorders • Parkinson's Disease • Psychiatry • REM Sleep Behavior Disorder

CLIN-011: A Study of CST-103 Co-administered With CST-107 in Subjects With Neurodegenerative Disorders (clinicaltrials.gov) - P2 | N=41 | Active, not recruiting | Sponsor: CuraSen Therapeutics, Inc. | Recruiting ➔ Active, not recruiting

Enrollment closed • Alzheimer's Disease • Behavior Disorders • CNS Disorders • Cognitive Disorders • Dementia • Lewy Body Disease • Mental Retardation • Movement Disorders • Parkinson's Disease • Psychiatry • REM Sleep Behavior Disorder

A Study of CST-103 Co-administered With CST-107 in Subjects With Parkinson's Disease Having Freezing of Gait (CLIN-012) (clinicaltrials.gov) - P2 | N=25 | Not yet recruiting | Sponsor: CuraSen Therapeutics, Inc. | Trial completion date: Mar 2023 ➔ Mar 2024 | Initiation date: Jun 2022 ➔ Jun 2023 | Trial primary completion date: Dec 2022 ➔ Dec 2023

Trial completion date • Trial initiation date • Trial primary completion date • CNS Disorders • Movement Disorders • Parkinson's Disease

CLIN-011: A Study of CST-103 Co-administered With CST-107 in Subjects With Neurodegenerative Disorders (clinicaltrials.gov) - P2 | N=40 | Recruiting | Sponsor: CuraSen Therapeutics, Inc. | Trial primary completion date: Mar 2022 ➔ Jun 2022

Trial primary completion date • Alzheimer's Disease • Behavior Disorders • CNS Disorders • Cognitive Disorders • Dementia • Lewy Body Disease • Mental Retardation • Movement Disorders • Parkinson's Disease • Psychiatry • REM Sleep Behavior Disorder

A Study of CST-103 Co-administered With CST-107 in Subjects With Parkinson's Disease Having Freezing of Gait (CLIN-012) (clinicaltrials.gov) - P2 | N=25 | Not yet recruiting | Sponsor: CuraSen Therapeutics, Inc. | Trial completion date: Dec 2022 ➔ Mar 2023 | Initiation date: Feb 2022 ➔ Jun 2022 | Trial primary completion date: Sep 2022 ➔ Dec 2022

Trial completion date • Trial initiation date • Trial primary completion date • CNS Disorders • Movement Disorders • Parkinson's Disease

CLIN-011: A Study of CST-103 Co-administered With CST-107 in Subjects With Neurodegenerative Disorders (clinicaltrials.gov) - P2; N=40; Recruiting; Sponsor: CuraSen Therapeutics, Inc.; Trial completion date: Mar 2022 ➔ Jun 2022; Trial primary completion date: Dec 2021 ➔ Mar 2022

Clinical • Trial completion date • Trial primary completion date • Alzheimer's Disease • Behavior Disorders • CNS Disorders • Cognitive Disorders • Dementia • Lewy Body Disease • Mental Retardation • Movement Disorders • Parkinson's Disease • Psychiatry • REM Sleep Behavior Disorder

Detection of Clenbuterol-Induced Changes in Heart Rate Using At-Home Recorded Smartwatch Data: Randomized Controlled Trial. (PubMed, JMIR Form Res) - "We demonstrated the feasibility of using smartwatch-based HR estimates to detect clenbuterol-induced changes during clinical trials. The asleep HR estimates were most repeatable and sensitive to treatment effects. We conclude that smartwatch-based HR estimates obtained during daily living in a clinical trial can be used to detect and track treatment effects."

Clinical • Journal • Cardiovascular • CNS Disorders • Movement Disorders • Parkinson's Disease

Safety, Tolerability and Cerebral Blood Flow After Single Doses of the β2-agonist, Clenbuterol, in Patients with Mild Cognitive Impairment or Parkinson’s Disease (CTAD 2021) - "In patients with MCI or PD, clenbuterol administration resulted in significant increases in CBF in the hippocampus, thalamus and amygdala. Increases in CBF are expected under conditions of increased neuronal activity. This phenomenon of neurovascular coupling arises from integrated responses from multiple cell types, many of which are known to express β2 receptors, including neurons, cerebral blood vessels, microglia, oligodendrocytes and astrocytes."

Clinical • Alzheimer's Disease • Cardiovascular • CNS Disorders • Cognitive Disorders • Diabetes • Movement Disorders • Parkinson's Disease • Solid Tumor • MRI

CuraSen Therapeutics Presents Phase 1b Clinical Data with CST-103 Demonstrating Significant Increases in Cerebral Blood Flow in Patients with Mild Cognitive Impairment or Parkinson’s Disease (Yahoo Finance) - P1, N=N/A; "CuraSen Therapeutics, Inc…announced data from a Phase 1b trial...Results showed that: Patients who received the initial dose of CST-103 showed significant increases in cerebral blood flow in multiple areas of the brain, including the hippocampus. (20.3%, p=0.001), thalamus (13.1%, p=0.004) and amygdala (14.3%, p=0.005)….CuraSen is currently conducting a Phase 2 randomized, placebo-controlled, crossover study with CST-103, co-administered with CST-107, in 40 patients with mild cognitive impairment, Parkinson’s disease with rapid eye movement sleep disorder (RBD) or Lewy body dementia….Data are expected in the second quarter of 2022….Additionally, the company is planning to initiate a Phase 2a trial with CST-2032, a novel beta-2 adrenoceptor agonist, in patients with mild cognitive impairment or mild dementia due to either Parkinson's disease or Alzheimer’s disease in early 2022.”

New P2 trial • P1 data • CNS Disorders • Cognitive Disorders • Dementia • Parkinson's Disease

A Study of CST-103 Co-administered With CST-107 in Subjects With Parkinson's Disease Having Freezing of Gait (CLIN-012) (clinicaltrials.gov) - P2; N=25; Not yet recruiting; Sponsor: CuraSen Therapeutics, Inc.; Initiation date: Sep 2021 ➔ Feb 2022

Clinical • Trial initiation date • CNS Disorders • Movement Disorders • Parkinson's Disease