Clinical Trial to Determine Tolerable Dosis of Vorinostat in Patients With Mild Alzheimer Disease

NCT03056495 | Terminated Phase 1 DMC FDA Drug

• 2 other identifiers: VostatAD012014-005311-17
• Study Type: interventional
• Target: 9
• Locations: 1 country
• Sites: 2

Brief Summary

This Clinical Trial is an open, non-randomized Phase Ib study to determine the maximal tolerable dose (MTD) of Vorinostat in Alzheimer disease (AD) patients between (including) 55 and 90 years with mild symptoms. The MTD in this study is defined as the dose that leads to maximum toxicity with Common Toxicity Criteria (CTC) grade 1 symptoms.The safety and tolerability of Vorinostat in this group of study participants should be tested.

Conditions

Alzheimer Disease

Outcome Measures

Primary Outcomes (1)

• Determination of the maximum-tolerated dose (MTD) in elderly subjects during dose escalation

  A MTD is defined as the highest dose with no \> grade 1 toxicity according to Common Toxicity Criteria (CTC). The dose-limiting toxicity (DLT) is defined as the dose, which leads with a 30% chance of toxicity to CTC Grade 2 or higher and / or leads to corrected QT interval (QTc)≥480ms and/or increase of QTc \>= 50ms compared to baseline

  12 months

Secondary Outcomes (3)

• Incidence of treatment - Emergent Adverse Events (Safety)

  during dose escalation and during 4 weeks treatment with MTD every week

• Quantification of Vorinostat concentration in blood - pharmacokinetics

  d21 by 4 weeks treatment with MTD

• association of alterations in the genome-wide transcriptome profile with the dose administered, toxicity and treatment response - pharmacodynamics

  d21 by 4 weeks treatment with MTD

Study Arms (1)

Investigational drug

EXPERIMENTAL

N-hydroxy-N'-phenyl-octanediamide (Vorinostat) capsules once a day, three weeks of treatment; dose escalation with different dosages per cohort; One cohort of three subjects

Drug: N-hydroxy-N'-phenyl-octanediamide (Vorinostat)

Interventions

N-hydroxy-N'-phenyl-octanediamide (Vorinostat) DRUG

N-hydroxy-N'-phenyl-octanediamide capsules once a day, three weeks of treatment; dose escalation with different dosages per cohort; One cohort of three subjects

Also known as: Vorinostat

Investigational drug

Eligibility Criteria

• Age: 55 Years - 90 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• written informed consent to participate in the study
• verified capacity to consent by a doctor not involved in the study
• mild Alzheimer's disease (NINCDS / ADRDA criteria and Mini-Mental State Examination (MMSE) 22-27)
• age (including) from 55 to 90 years
• subjects must be able to meet the requirements described in the study protocol
• outpatient living
• Informant lives with subject in the same household
• Rosen modified Hachinski ischemia score ≤4
• concerning only female patients: postmenopausal
• concerning only male patients: commitment to use a suitable contraceptive
• cerebral imaging study (CT or cMRI), which is consistent with a diagnosis of probable Alzheimer's disease (not older than 3 years)

You may not qualify if:

• other neurological and psychiatric diseases explaining cognitive deficits better than an AD diagnosis
• conspicuous MRI / CCT scan explaining the cognitive deficits better than an AD diagnosis
• severe physical, neurological or psychiatric disorders that interfere with the participation in the study
• history of malignant tumors except non- metastasizing basal cell carcinoma of the skin
• history of seizures
• dysphagia leading to the inability to swallow capsules
• untreated severe acute infections with clinical symptoms such as respiratory infections, pneumonia, bronchitis, acute diarrhea, influenza, untreated urinary tract infections
• in the family history, unexplained sudden cases of heart failure before the age of 50 years
• long QT syndrome in the family history
• evidence of QTc prolongation ≥480 ms at screening (Fridericia adjusted QT interval), of arrhythmias especially of severe uncontrolled ventricular arrhythmias or atrial fibrillation in ECG
• not sufficiently treated angina
• heart failure (NYHA III, IV)
• myocardial infarction
• known infection with HBV, HCV and / or HIV
• occurrence of venous thrombosis or embolism

Sponsors & Collaborators

• German Center for Neurodegenerative Diseases (DZNE): lead
• University Hospital, Bonn: collaborator
• University of Göttingen: collaborator

Study Sites (2)

German Center for Neurodegenerative Diseases

Bonn, 53127, Germany

Location

University Medical Center Göttingen, Department of Psychiatry and Psychotherapy

Göttingen, 37075, Germany

Location

Related Publications (1)

• Garcia AA, Koperniku A, Ferreira JCB, Mochly-Rosen D. Treatment strategies for glucose-6-phosphate dehydrogenase deficiency: past and future perspectives. Trends Pharmacol Sci. 2021 Oct;42(10):829-844. doi: 10.1016/j.tips.2021.07.002. Epub 2021 Aug 10.

  PMID: 34389161 DERIVED

MeSH Terms

Conditions

Alzheimer Disease

Interventions

Vorinostat

Condition Hierarchy (Ancestors)

Dementia; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Tauopathies; Neurodegenerative Diseases; Neurocognitive Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Anilides; Amides; Organic Chemicals; Aniline Compounds; Amines; Hydroxamic Acids; Hydroxylamines; Hydroxy Acids; Carboxylic Acids

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 27, 2016
• First Posted: February 17, 2017
• Study Start: September 28, 2017
• Primary Completion: March 4, 2024
• Study Completion: March 4, 2024
• Last Updated: April 10, 2024

Record last verified: 2019-07

Data Sharing

• IPD Sharing: Will not share

Locations

DE (2)