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
Overview
- Phase
- Phase 3
- Intervention
- CD-008-0045
- Conditions
- Anxiety Disorder Generalized
- Sponsor
- ChemRar Research and Development Institute, LLC
- Enrollment
- 200
- Primary Endpoint
- Change in total score of the Hamilton Anxiety Rating Scale structured interview (SIGH-A) at Week 8 from baseline.
- Last Updated
- 5 years ago
Overview
Brief Summary
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.
Detailed Description
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.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Signed Informed Consent Form;
- •Age ≥18 years old;
- •Generalized anxiety disorder diagnosed according to the Diagnostic and Statistical Manual of Mental Disorders (DSM-V) criteria and International Classification of Diseases (ICD-10);
- •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;
- •Condition according to the CGI-S ≥4 (moderate severity and higher) at Screening and Randomization Visits (Week 0);
- •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):
Exclusion Criteria
- •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;
- •Total score \>13 of the Montgomery-Åsberg Depression Rating Scale (MADRS) structured interview.
- •Confirmed diagnosis of depressive episode, recurrent depressive disorder, bipolar affective disorder in history or at Screening;
- •Confirmed diagnosis of schizophrenia in history or at Screening;
- •Confirmed diagnosis of panic disorder in history or at Screening;
- •Phobic anxiety disorders (agoraphobia, social phobia, unspecified phobic anxiety disorder) in history or at Screening;
- •Disorders of personality or behavior in history or at Screening;
- •Post-traumatic stress disorder diagnosed within 12 months prior to Screening;
- •Eating disorders diagnosed within 12 months prior to Screening;
- •Obsessive-compulsive disorder in history or at Screening;
Arms & Interventions
CD-008-0045 40 mg/day
Patients assigned to the CD-008-0045 40 mg/day group will receive 1 capsule of CD-008-0045 (20 mg) before breakfast and before dinner for 32 weeks.
Intervention: CD-008-0045
Placebo
Patients assigned to the Placebo group will receive 1 placebo capsule before breakfast, and dinner for 8 weeks.
Intervention: Placebo
Afobazol 30 mg/day
Patients assigned to the Afobazol 30 mg/day group will receive 1 tablet of Afobazol (10 mg) before breakfast, before lunch and before dinner for 8 weeks.
Intervention: Afobazol
Outcomes
Primary Outcomes
Change in total score of the Hamilton Anxiety Rating Scale structured interview (SIGH-A) at Week 8 from baseline.
Time Frame: Baseline to Week 8
Mean change of the Hamilton Anxiety Rating Scale structured interview (SIGH-A) score \[the values from 0 to 56; the higher scores mean a worse outcome\] \[score\]
Secondary Outcomes
- Change of score of items 1 (Anxious mood) and 2 (Tension) of the Hamilton Anxiety Rating Scale structured interview (SIGH-A) from baseline at Week 2, Week 4, Week 8, Week 16, Week 24 and Week 32(Baseline to Week 2, Week 4, Week 8, Week 16, Week 24 and Week 32)
- Proportion of patients who reached a medically induced remission (the sum of scores of the SIGH-A ≤ 7) at Week 8 and Week32(Baseline to Week 8 and Week 32)
- Changes in the sum of scores of the Montgomery-Asberg Depression Rating Scale (MADRS) at Week 2, Week 4, Week 8, Week 16, Week 24 and Week 32 from baseline(Baseline to Week 2, Week 4, Week 8, Week 16, Week 24 and Week 32)
- The frequency of decrease in total score of the Hamilton Anxiety Rating Scale structured interview (SIGH-A) by 50% or more at week 8 from baseline(Baseline to Week 8)
- Change in total score and sum of scores of the subscales for assessment of the mental and somatic anxiety of the Hamilton Anxiety Rating Scale (SIGH-A) structured interview for each parameter at Week 2, Week 4, Week 8, Week 16, Week 24 and Week 32(Baseline to Week 2, Week 4, Week 8, Week 16, Week 24 and Week 32)
- Change in the Clinical Global Impression-Severity (CGI-S) at Week 2, Week 4, Week 8, Week 16, Week 24 and Week 32 from baseline(Time Frame: Baseline to Week 2, Week 2 to Week 4, Week 4 to Week 8, Week 8 to Week 16, Week 16 to Week 24, Week 24 to Week 32)
- Change in the Clinical Global Impression-Improvement (CGI-I) at Week 2, Week 4, Week 8, Week 16, Week 24 and Week 32(Week 2, Week 4, Week 8, Week 16, Week 24 and Week 32)
- Change of daytime somnolence level based on Visual Analogue Scale (VAS)(Baseline to Week 2, Week 4, Week 8, Week 16, Week 24 and Week 32)
- Change in total score of the Visual Analog Sheehan Disability Scale (SDS) at Weeks 4 after the last dose of therapy and baseline(Baseline to Weeks 4 after the last dose of therapy. The last dose of therapy to 4 Weeks after that)
- Change in the Clinical Global Impression-Improvement (CGI-I) at Weeks 4 after the last dose of therapy(The last dose of therapy to 4 Weeks after that)
- Impact of CYP2D6 polymorphism on the pharmacokinetic values of the study drug([Time Frame: Week 4, Week 8])
- Change in total score of the Visual Analog Sheehan Disability Scale (SDS) at Week 8, Week 16, Week 24 and Week 32 from baseline(Baseline to Week 8, Week 16, Week 24 and Week 32)
- Change in results of the Trail Making Test (TMT) at Week 4, Week 8, Week 16, Week 24 and Week 32 from baseline(Baseline to Week 4, Week 8, Week 16, Week 24 and Week 32)
- Change in total score of the Quality of Life Scale (SF-20) at Week 8, Week 16, Week 24 and Week 32 from baseline(Baseline to Week 8, Week 16, Week 24 and Week 32)
- Change in total score of the Hamilton Anxiety Rating Scale structured interview (SIGH-A) at Week 4 after the last dose of therapy and baseline(Baseline to Weeks 4 after the last dose of therapy. The last dose of therapy to 4 Weeks after that)
- Change in total score of the Montgomery-Asberg Depression Rating Scale (MADRS) at Week 4 after the last dose of therapy and baseline(Baseline to Weeks 4 after the last dose of therapy. The last dose of therapy to 4 Weeks after that)
- Change in the Clinical Global Impression-Severity (CGI-S) score at Week 4 after the last dose of therapy and baseline(Baseline to Weeks 4 after the last dose of therapy. The last dose of therapy to 4 Weeks after that)
- Concentration of CD-008-0045 and its metabolite М1 1 hour after first dose of the study drug and before next doses at visits (Ctrough)([Time Frame: Week 4, Week 8])