A Study to Assess the Efficacy and Safety of CD-008-0045 in Patients With Generalized Anxiety Disorder

A Multicenter, Randomized, Double-blind, Placebo- and Active- Controlled Study to Assess the Efficacy and Safety of CD-008-0045 in Patients With Generalized Anxiety Disorder

This is a multicenter, randomized, double-blind, placebo- and active-controlled study to assess the efficacy and safety of CD-008-0045 in patients with generalized anxiety disorder (GAD). Each patient will participate in the study for the period of approximately 37 weeks: Screening and Run-in period: 1 week; Study Treatment period: 32 weeks; Follow-up period: 4 weeks.

The study drug CD-008-0045 has a multi-targeted activity, i.e., able to inhibit adrenergic, dopamine, serotonin, and histamine receptors, thus allowing to assume its wide therapeutic potential. At Screening, the patients who meet the inclusion/exclusion criteria will be included into one-week single-blind Placebo Run-in period. At Week 0 the patients will be start double-blind Placebo and active comparator treatment period. The patients will be randomized to receive CD-008-0045 40 mg daily or Placebo or Afobazol (fabomotizole) for 8 weeks. After that, there will be an open-label treatment period for 26 weeks. The potential withdrawal syndrome will be assessed during four-week Follow-up Period.

Inclusion Criteria:

1. Signed Informed Consent Form;

2. Age ≥18 years old;

3. Generalized anxiety disorder diagnosed according to the Diagnostic and Statistical Manual of Mental Disorders (DSM-V) criteria and International Classification of Diseases (ICD-10);

4. Scores of the Hamilton Anxiety Rating Scale (SIGH-A) structured interview at Screening and Randomization Visits (Week 0):

   • Total score ≥20;
   • Item 1 (Anxious mood) and item 2 (Tension) scores ≥2 points;

5. Condition according to the CGI-S ≥4 (moderate severity and higher) at Screening and Randomization Visits (Week 0);

6. Consent of patients to use adequate contraception methods throughout the study. Adequate contraception methods include:

   • Condoms with spermicide for males;

   • For females (at their discretion):

     • oral contraceptives,
     • condoms with spermicide (for the partner),
     • diaphragm with spermicide,
     • cervical cap with spermicide,
     • intrauterine device (IUD);

7. Ability to comply with all Study Protocol requirements;

8. 80% to 120% compliance during Run-in period, as assessed at Randomization Visit (Week 0).

Exclusion Criteria:

1. Pregnant or lactating women, or women planning to get pregnant during the clinical study; women of childbearing potential (including those without history of surgical sterilization and women with <2 years of post-menopause) not using adequate contraception methods;
2. Total score >13 of the Montgomery-Åsberg Depression Rating Scale (MADRS) structured interview.
3. Confirmed diagnosis of depressive episode, recurrent depressive disorder, bipolar affective disorder in history or at Screening;
4. Confirmed diagnosis of schizophrenia in history or at Screening;
5. Confirmed diagnosis of panic disorder in history or at Screening;
6. Phobic anxiety disorders (agoraphobia, social phobia, unspecified phobic anxiety disorder) in history or at Screening;
7. Disorders of personality or behavior in history or at Screening;
8. Post-traumatic stress disorder diagnosed within 12 months prior to Screening;
9. Eating disorders diagnosed within 12 months prior to Screening;
10. Obsessive-compulsive disorder in history or at Screening;
11. Epilepsy, seizures, head trauma with loss of consciousness, tumors, inflammatory, or demyelinating diseases of the central nervous system, stroke in history;
12. Pheochromocytoma;
13. Malignancies diagnosed within the last 5 years (except for the cured basal cell carcinoma);
14. Significant cardiovascular diseases at present or within 12 months prior to Screening, including: Chronic class III or IV heart failure (according to the New York Heart Association classification), severe arrhythmia requiring treatment with class Ia, Ib, Ic or III antiarrhythmic drugs, unstable angina, myocardial infarction, heart and coronary artery surgery, significant valvular heart disease, uncontrolled hypertension with systolic blood pressure >180 mm Hg and diastolic blood pressure >110 mm Hg, pulmonary embolism or deep vein thrombosis;
15. Nephrotic syndrome, moderate to severe chronic renal failure or significant renal impairment with Creatinine level >1.5 mg/dL in men and >1.4 mg/dL in women or glomerular filtration rate (GFR) <60 ml/min;
16. HIV, hepatitis B or C, history of cirrhosis; elevation of AST, ALT or serum Alkaline Phosphatase ≥ 2.5 times above the upper limit of normal or elevation of total bilirubin level ≥ 2 times above the upper limit of normal at Screening;
17. Significant dysfunctions of the thyroid gland in decompensation stage;
18. Anemia (hemoglobin level ≤105 g/L in females or ≤115 g/L in males); significant blood loss, or collection of at least one volumetric unit of donated blood (≥ 500 ml), or blood transfusion within 12 weeks prior to Screening;
19. Any uncontrolled concomitant somatic disease, including that with a stable treatment regimen;
20. Administration of drugs for generalized anxiety disorder,within 7 days prior to Screening and during throughout the study, including antidepressants, Pregabalin, benzodiazepines, antipsychotics;
21. Administration of Fluoxetine within 21 days prior to Screening and during throughout the study;
22. Previous administration of the study drug;
23. Known allergy, hypersensitivity or contraindications for use of CD-008-0045 and/or Afobazol;
24. Electroconvulsive therapy 3 months prior to screening;
25. Psychotherapy 3 months prior to screening and/or at the time of inclusion in the study;
26. Use of excluded drug therapy from the moment of Screening and throughout the study;
27. Administration of any study drug or participation in another clinical study within 3 months prior to Screening (except for cases when the patient was not administered the study drug during the study);
28. Addiction to tranquilizers or psychoactive substance abuse, including alcohol (history of episodic use is acceptable);
29. Inability to read or write; unwillingness to understand and comply with the Protocol procedures; non-compliance with drug dosage regimen or procedures which, in the Investigator's opinion, may affect the study results or the patient's safety and prevent the patient's participation in the study; any other concomitant diseases or severe mental disorders, which make the patient ineligible for participation in the study, limit the legal basis for Informed Consent procedure, or may affect the patient's ability to participate in the study.