Phase Ⅲ Clinical Trial of Buagafuran Capsules in the Treatment of GAD

Safety and Efficacy of Buagafuran Capsules in the Treatment of Generalized Anxiety Disorder: a Multi-center, Randomized, Double-blind, Double-dummy, Placebo-controlled, Positive-controlled, Flexible-dose Phase Ⅲ Clinical Trial

A placebo-controlled superiority design was used to evaluate the efficacy of 60-120 mg/ day of Buagafuran capsules in the treatment of GAD.

This was a multi-center, randomized, double-blind, double-dummy, placebo-controlled, positive-controlled, flexible-dose phase III clinical trial of Buagafuran capsules. The stratification factor was the presence or absence of new generalized anxiety disorder (GAD) (new GAD vs. Non-new GAD).

Qualified subjects, according to the ratio of 2:2:1, were randomized into experimental group, placebo-control group and positive-control group, and received a treatment course of 8 weeks. Participants were followed from baseline outpatient visit until end of the follow-up period( 10 weeks and 7 visits in total).

The dose of Buagafuran capsules/ Buagafuran capsules mimic can be adjusted from 60mg/ day to 120mg/ day according to treatment needs and tolerance in the follow-up period( at week 1, week 2, and week 4), and the dose of Buspirone tablets/ Buspirone tablets mimic can be adjusted from 10mg/ day to 20mg/ day at the same time.

Inclusion Criteria:

1. Outpatients aged 18-65 years old, of both sexes;
2. Met the diagnostic and Statistical Manual of Mental Disorders, 5th Edition (DSM-5) criteria for generalized anxiety disorder (GAD) and confirmed by the Brief International Neuropsychiatric Interview (M.I.N.I.);
3. The patient requires psychiatric medication;
4. Hamilton Anxiety Scale (HAMA) score ≥20, Hamilton Depression Scale (HAMD-17) score ≤2, Clinical Global Impression Scale (CGI-S) score ≥4 at screening and baseline Points;
5. Able to understand and voluntarily participate in this trial, signed informed consent.

Exclusion Criteria:

1. Patients with serious suicide risk at present, or HAMD-17 item 3-suicide score ≥3;
2. Patients with HAMD-17 > 17;
3. Patients whose HAMA scores decreased by ≥20% in the baseline period compared with the screening period:
4. Those who met the DSM-5 diagnostic criteria for other mental disorders except GAD;
5. Patients with previous history of depression, obsessive-compulsive disorder, bipolar disorder, psychotic disorder, factitious disorder and somatoform disorder; There were severe personality disorders, especially antisocial, borderline, or histrionic personality disorder, which were judged by the investigator to affect the patient's adherence to the study protocol;
6. Alcohol or drug abuse or dependence within 180 days before screening;
7. With severe or unstable has clinical significance of somatic disease, including any cardiovascular, cancer, kidney, respiratory, endocrine (including abnormal thyroid function), digestion, blood (such as with bleeding tendency) or nervous system diseases;
8. Patients whose physical examination or vital signs were abnormal and clinically significant (e.g. inadequately controlled hypertension, systolic blood pressure ≥160 mmHg and/or diastolic blood pressure ≥100 mmHg);
9. Patients with a history of epilepsy or any other disease that may induce seizures, except convulsions caused by febrile convulsions in children;
10. Important abnormalities in laboratory tests during the screening period, such as abnormal liver function tests (alanine aminotransferase or aspartate transaminase > 2 times the normal value); Renal insufficiency (blood urea nitrogen or creatinine > 1.2 times the upper limit of normal);
11. Clinically significant abnormalities on electrocardiography (QT interval corrected by Fridericia method: ≥450 ms for men or ≥470 ms for women) or conditions deemed ineligible by the investigators;
12. Patients who had undergone psychiatric surgery, electroconvulsive therapy or transcranial magnetic stimulation within 90 days before screening;
13. Patients treated with β-blockers within 90 days before screening；
14. Patients with severe hypersensitivity, or allergic to at least 2 kinds of drugs (including photosensitivity);
15. Patients who had previously used two or more antidepressants and/or benzodiazepines at a clinically appropriate dose for at least 4 weeks but were still ineffective;
16. Receiving systemic psychotherapy or other non-pharmacological treatments (e.g., acupuncture, hypnosis, or phototherapy) within 6 weeks before the baseline visit;
17. Those who had used benzodiazepines within -7 to -1 days before screening, such as lorazepam, oxazepam, and alprazolam for less than 5 half-lives; The use of benzodiazepines with longer half-lives, such as diazepam, clonazepam, nitrazepam, estazolam, and flurazepam, not more than 5 half-lives or less than 30 days from the screening period, or the use of barbiturates not more than 5 half-lives or less than 30 days from the screening period;
18. Patients treated with monoamine oxidase inhibitors within -7 to 1 day before screening; Patients treated with fluoxetine within 30 days before screening;
19. Patients using antipsychotics, antidepressants and mood stabilizers with less than 5 half-lives before the baseline washout period;
20. Patients who discontinued traditional Chinese medicine, melatonin, and St. John's wort for less than 3 days before the baseline visit;
21. In the experimental drug delivery within 7 days before and during the test, cannot fast grapefruit or grapefruit juice;
22. Women during pregnancy or lactation experiments have fertility requirement (including men), and not to the male, the female patients is safe and effective contraceptive measures;
23. Unable to take medicine as prescribed;
24. Participants enrolled in other clinical trials within 90 days before screening;
25. Patients with other conditions deemed by the investigator to be ineligible for enrollment.