E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
ACR16 belongs to a new class of CNS active agents called dopaminergic stabilizers. Dopaminergic stabilizers are compounds that can both enhance and counteract dopamine dependent functions in the CNS, depending on the initial level of dopaminergic activity. The stabilizing feature of such compounds is illustrated by their interaction with dopaminergic agonists. |
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MedDRA Classification |
E.1.3 | Condition being studied is a rare disease | Yes |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
The primary objective is to assess the effects of cognitive function of ACR16 treatment in Huntington disease patients. Symptomatic treatment alternatives for Huntington disease are meagre, particularly for the cognitive symptoms. Although the motor disorder of Huntington disease is severe and ultimately fatal, the most important aspects that cause suffering to patients and families are the neuropsychiatric ones, striatal abnormalities correlate with the degree of cognitive impairment, particularly with the frontal lobe deficits characteristic for the disease. The preclinical and profile of ACR16 suggests that the compound can be used to normalize states of functional dopaminergic hyperactivity without producing unwanted effects associated with antidopaminergic activity such as akinesia, rigidity and dystonia. This conception has been confirmed in a limited number of Huntington disease patients where ACR16 was shown to improve cognitive functions after 14 days of ACR16 treatment. |
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E.2.2 | Secondary objectives of the trial |
Secondary objectives are to assess effects on motor function, CGI, HADS and LSEQ scores. Secondary objectives will also be to assess the safety and tolerability of ACR16 in the predefined dose level. Secondary objectives relating to safety and tolerability will be frequency and severity of adverse events, drop out frequency as well as ECG morphology measured by 12-lead ECG. |
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E.2.3 | Trial contains a sub-study | Information not present in EudraCT |
E.3 | Principal inclusion criteria |
Huntington disease diagnosed with the aid of clinical features and the presence of > 35 CAG repeats in the Huntington gene.
Ambulatory and willing and able to comply with the study specific procedures.
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E.4 | Principal exclusion criteria |
Second or third degree AV block or sick sinus syndrome; resting heart rate below 50 beats per minute; congestive heart failure classified as functional Class III or IV by the New York Heart Association; myocardial infarction within six months of baseline; a prolonged QTc interval at screen or pre-treatment (defined as a QTc interval of > 450 msec for males or > 470 msec for females); other clinically significant heart conditions which would negatively impact on the patient completing the study.
Serum creatinine concentrations above 200 mmol/l.
Any other clinically significant condition or laboratory assay abnormality that would interfere with the patient’s ability to participate in the study.
Female of childbearing potential.
Antichoreic medication, with exception of Risperidon, within 30 days before inclusion. If Risperidon has been taken the dose should have been kept stable for 30 days before inclusion and should remain stable throughout the study. |
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary endpoint will be the change in the weighted total cognitive score during the study period. |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | Information not present in EudraCT |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
E.8.7 | Trial has a data monitoring committee | Information not present in EudraCT |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | |
E.8.9.1 | In the Member State concerned months | 4 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial months | 4 |