Date: 2015-12-08
Type of
information: Results
phase: 2
Announcement: results
Company: Amarantus BioScience (USA – CA)
Product: eltoprazine
Action
mechanism: Eltoprazine is a selective 5HT1a/1b partial agonist in development by Amarantus for the treatment Parkinson's disease levodopa-induced dyskinesia, and is now poised for further clinical development as a symptomatic treatment in adult ADHD and Alzheimer's aggression.
Disease: elderly patients with Alzheimer's dementia who are aggressive
Therapeutic
area: Neurodegenerative diseases
Country:
Trial
details:
- The study was designed as a multi-centre (6) parallel-group study in demented elderly with aggressive behavior. Following screening subjects were directly randomized per block of 3 to receive eltoprazine or placebo (2:1) in the double-blind treatment phase. Before entering the double-blind treatment phase all subjects were placed in a single-blind placebo run-in period over 3-weeks to establish a baseline of aggressive behavior. Other psychotropic medications were anticipated to have been washed-out before the on-drug portion of the study. 29 subjects entered the study. 20 were randomized to receive eltoprazine, with a mean age of 83.6 years (range 74-92); 14 were female, 6 were male. Nine subjects were randomised to receive placebo, with a mean age of 81.1 years (range 70-86); 6 were female, 3 were male.
- All subjects had to have been diagnosed with Senile Dementia of Alzheimer's Type (SDAT) or mixed SDAT/Multi-Infarct Dementia according to DSM-III-R criteria. Subjects had to score less than 60 points on the CAMCOG, a test assessing cognitive functioning. All subjects had to have been hospitalized for at least 2 months and have shown a minimum of 4 episodes of hostile or disruptive behavior per week over the 4 weeks preceding entry to the study. Eltoprazine was provided in capsules containing either 1mg Eltoprazine or 5mg Eltoprazine for oral use. The maximum daily dose was 10mg b.i.d.
- The double-blind treatment phase lasted 29 days including a 5 day taper-on period and a 6-8 day taper-off period depending on the final dose reached (5 or 10mg b.i.d.; at day 13 the dose could be optionally increased from 5 to 10mg b.i.d. in the course of 4 days).
- The safety and tolerability were monitored by means of haematological and biochemical laboratory tests, urinalysis, assessment of vital signs, ECG recording and clinical observation to detect potential side-effects.
- Potential influences on the demented state were evaluated by the Sandoz Clinical Assessment Geriatric Scale. The anti-aggressive properties of the study medication were evaluated by the Social Dysfunction and Aggression Scale and the Staff Observation Scale.
Latest
news:
- • On December 8, 2015, Amarantus Bioscience announced positive data for eltoprazine in a Phase 2 clinical trial of elderly patients with Alzheimer's dementia who are aggressive. The data demonstrate a significant improvement in eltoprazine-treated patients in the severely aggressive eltoprazine-treated population (25.1 to 16.9) versus placebo (22.5 to 21.5). There were four primary study objectives:
- ¤ 1. To collect data on safety on tolerability of multiple dose treatment of Eltoprazine in elderly subjects;
- ¤ 2. To evaluate the feasibility of the assessment methods;
- ¤ 3. To obtain information on the effects of eltoprazine on hostile or disruptive behaviour in hospitalized demented elderly;
- ¤ 4. To obtain preliminary information on possible relations between plasma concentrations and eventual side-effects.
- Of the 20 subjects randomised to receive eltoprazine, two dropped out during the placebo run-in phase, one because of fatal lung infection, the other subject refusing to eat or drink. One subject was prematurely withdrawn because of physical deterioration due to lung carcinoma. One subject had to be excluded from the efficacy analysis because of an erratic dosing regimen. Of the 9 subjects randomised to receive placebo, one dropped out during the placebo run-in phase due to a heart failure. There were no worrying safety problems related to eltoprazine treatment. In general, eltorpazine was reasonably well tolerated. Treatment emergent signs and symptoms were confusion (4 subjects), insomnia (2), somnolence (3) and anxiety (2). One male experienced delusions, which spontaneously disappeared within one week.
- There was no influence of eltoprazine on the demented state per se. The overall aggression level was modest and mainly of a verbal or mild physical nature. Clinically significant reductions in aggressive behavior in eltoprazine-treated subjects were especially apparent from the descriptions in the case summaries, which were partly substantiated by the scorings on the Social Dysfunction and Aggression Scale.
- Using a dosing regimen with phases of gradual dose increase followed by reduction eltorpazine appeared safe and reasonably well tolerated in a population of demented elderly subjects with aggressive behavior. There are clear hints of anti-aggressive efficacy in more severely aggressive subjects which merit further research. The study design proved feasible and useful. Further research needs to be done into the correlation between overt aggressive events and basal aggression. Measurements of anti-aggressive efficacy should preferably address both components of aggressive behavior.
Is
general: Yes
