Clinical Trial to Determine Tolerable Dosis of Vorinostat in Patients With Mild Alzheimer Disease (VostatAD01)
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|ClinicalTrials.gov Identifier: NCT03056495|
Recruitment Status : Recruiting
First Posted : February 17, 2017
Last Update Posted : August 1, 2019
|Condition or disease||Intervention/treatment||Phase|
|Alzheimer Disease||Drug: N-hydroxy-N'-phenyl-octanediamide (Vorinostat)||Phase 1|
The MTD of Vorinostat in the treatment of Alzheimer's patients is to be determined by using an open, non-randomized, multicentric dose-finding study with adaptive design. This Clinical Trial will take place in 2 parts.
The first part will be performed as a dose escalation part in cohorts of three subjects. Possible dosages will be: one, two, three or four capsules (100 mg per capsule) once per day. The first cohort receives a dose of 100 mg per day. After the treatment, a Vorinostat-free follow-up phase will take place. For the following cohorts, dose increases, a repetition of the previous dose or a dose reduction are possible.
After the dose escalation with a determination of the MTD, a dosage confirmation is carried out with additional subjects. The subjects are given a dose of Vorinostat of MTD over 4 weeks followed by a Vorinostat-free follow-up phase.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||44 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Primary Purpose:||Basic Science|
|Official Title:||Multicenter, Open-label Phase Ib Dose-escalation and Dose-confirmational Study for the Tolerability and Safety of N-hydroxy-N'-Phenyl-octanediamide (Vorinostat) in Patients With Mild Alzheimer's Disease|
|Actual Study Start Date :||September 28, 2017|
|Estimated Primary Completion Date :||January 2022|
|Estimated Study Completion Date :||March 2022|
Experimental: Investigational drug
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)
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
Other Name: Vorinostat
- Determination of the maximum-tolerated dose (MTD) in elderly subjects during dose escalation [ Time Frame: 12 months ]
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
- Incidence of treatment - Emergent Adverse Events (Safety) [ Time Frame: during dose escalation and during 4 weeks treatment with MTD every week ]
The analysis of safety assessments will include the following data collected for each subject:
- Adverse Events (AEs) in the context of Drug Exposure (days)
- Quantification of Vorinostat concentration in blood - pharmacokinetics [ Time Frame: d21 by 4 weeks treatment with MTD ]
Blood and plasma area under the concentration time curve of Vorinostat from time zero to 8 hours postdose.
The pharmacokinetic study will investigate the correlation between dose administered and concentration of Vorinostat in blood.
- association of alterations in the genome-wide transcriptome profile with the dose administered, toxicity and treatment response - pharmacodynamics [ Time Frame: d21 by 4 weeks treatment with MTD ]The genome-wide transcriptome profile will be determined as a pharmacodynamic surrogate parameter. Alterations between baseline and after dose administered will be compared. The pharmacodynamic study will investigate the correlation between dose administered, alterations in the genome-wide transcriptome profile as well as treatment responses (memory performance) and toxicities.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03056495
|Contact: Sandra Kuhs, Dr. rer. email@example.com|
|German Center for Neurodegenerative Diseases||Recruiting|
|Bonn, Germany, 53127|
|Contact: Anja Schneider, Prof. Dr. med. 0049-228-287-1137 firstname.lastname@example.org|
|University Medical Center Göttingen, Department of Psychiatry and Psychotherapy||Recruiting|
|Göttingen, Germany, 37075|
|Contact: Jens Wiltfang, Prof. Dr. med. 0049-551-3966601 email@example.com|