Evaluating the Efficacy of Dextromethorphan/Quinidine in Treating Irritability in Huntington's Disease

Inclusion Criteria:

• Verified HD mutation carriers;
• Irritable as diagnosed by the Irritability Scale with a score > 14;
• Stable concomitant medication (no change of medication during last 30 days prior toinclusion);
• Written informed consent by prospective study participant before conduct of anytrial-related procedure. Participant must be able to make an informed decision ofwhether or not to participate in the study.

Exclusion Criteria:

• Hypersensitivity to dextromethorphan (e.g., rash, hives), quinine, mefloquine,quinidine, or dextromethorphan/quinidine with a history of thrombocytopenia,hepatitis, bone marrow depression or lupus-like syndrome induced by these drugs;
• Pregnant or nursing women;
• Active suicidality based on the answer "yes" in questions 4 and 5 of theColumbia-Suicide Severity Rating Scale (baseline version);
• Woman of childbearing potential, not using highly effective methods of contraceptionsuch as oral, topical or injected contraception, IUD, contraceptive vaginal ring, ordouble barrier method such as diaphragm and condom with spermicide) or not surgicallysterile (via hysterectomy, ovarectomy or bilateral tubal ligation) or not at least oneyear post-menopausal;
• Male not using an acceptable barrier method for contraception;
• Presence of any medically not controllable disease (e.g. uncontrolled arterialhypertension or diabetes mellitus);
• Clinically significant renal (calculated creatinine clearance < 30 ml/min) or hepaticdysfunction;
• Patients with pre-existing hepatic disease;
• Individuals with a history or complete heart block, QTc prolongation or tornadoes depointes, or at high risk of complete AV block;
• Family history of congenital QT prolongation;
• History of unexplained syncope within the past year;
• Use of drugs containing quinidine, quinine, or mefloquine;
• Individuals currently taking strong CYP3A4 inhibitors or tetrabenazine;
• Use of certain antidepressants--amitriptyline, clomipramine, desipramine, fluoxetine,paroxetine, sertraline, venlafaxine;
• Use of certain heart rhythm medications--amiodarone, flecainide, procainamide,propafenone;
• Use of certain medicines to treat psychiatric disorders--chlorpromazine, haloperidol,perphenazine, pimozide, quetiapine, risperidone, thioridazine.
• Use of tamoxifen;
• Presence or history of seizures or diagnosed epilepsy;
• Severe cognitive disorders defined as a score < 18 on the MOCA;
• Clinically relevant abnormal findings in the ECG, the vitals, in the physicalexamination or laboratory values at screening that could interfere with the objectivesof the study or the safety of the subject as judged by the investigator;
• Participation in another investigative drug trial within 2 months;
• Subjects who are unlikely to be compliant and attend scheduled clinic visits asrequired as determined by the Investigator.