Prospective Clinical Trial of Crisugabalin Capsules in the Treatment of Generalized Anxiety Disorder (CEASE-GAD)

Evaluation of the Efficacy and Safety of Crisugabalin Capsules Versus Placebo and Venlafaxine Extended-Release (XR) Capsules in Chinese Patients With Generalized Anxiety Disorder: A Prospective, Multicenter, Randomized, Double-Blind, Double-Dummy, Active- and Placebo-Controlled Clinical Trial.

A placebo-controlled superiority design was used to evaluate the efficacy of 40 mg/ day of Crisugabalin capsules in the treatment of GAD.

Study Overview

• Status: Recruiting
• Conditions: Generalized Anxiety Disorder
• Intervention / Treatment: Drug: Crisugabalin 20mg bid; Drug: Venlafaxine-XR 75mg bid; Drug: Crisugabalin capsules mimic 0mg/capsule bid

Detailed Description

This was a prospective, multicenter, randomized, double-blind, double-dummy, active- and placebo-controlled clinical trial.

Qualified subjects, according to the ratio of 1:1:1, were randomized into Crisugabalin group, Venlafaxine-control group and placebo-control group, and received a double-blind treatment course of 8 weeks. After completing the 8-week double-blind treatment period, subjects will officially conclude the study or voluntarily enter a 4-week open-label extension treatment phase. During the open-label extension phase, all subjects will receive Crisugabalin 80 mg/day (40 mg bid). Participants were followed from baseline outpatient visit until end of the follow-up period (14 weeks and 9 visits in total).

• Study Type: Interventional
• Enrollment (Estimated): 216
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Kai Wang; Phone Number: +8613805512494; Email: wangkai1964@126.com

Study Locations

• China
  • Anhui
    • Hefei, Anhui, China, 230000
      • Recruiting
      • The First Affiliated Hospital of Anhui Medical University
      • Contact: Kai Wang; Phone Number: +8613805512494; Email: wangkai1964@126.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Able to understand and voluntarily participate in the trial, and provide written informed consent form (ICF);
• Male or female aged ≥18 years (inclusive of the threshold value);
• 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.);
• Require pharmacological treatment for psychiatric symptoms;
• 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;

Exclusion Criteria:

• subjects with serious suicide risk at present, or HAMD-17 item 3-suicide score ≥3;
• subjects with HAMD-17 > 17;
• subjects whose HAMA scores decreased by ≥20% in the baseline period compared with the screening period:
• Those who met the DSM-5 diagnostic criteria for other mental disorders except GAD;
• subjects 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;
• Alcohol or drug abuse or dependence within 180 days before screening;
• 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;
• History of inadequate response to at least two prior antidepressant drugs and/or benzodiazepines after adequate dose and duration of treatment (i.e., at least 4 weeks at a clinically appropriate dose), or failure to achieve sufficient clinical efficacy with pregabalin ≥300 mg/day (i.e., subject-reported insufficient response or lack of meaningful clinical improvement).
• History of severe hypersensitivity reactions (e.g., anaphylaxis) or allergies to at least two classes of drugs (including photosensitivity), or known hypersensitivity to pregabalin, the investigational drug, structurally related compounds, or any of their excipients.
• subjects 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);
• subjects with a history of epilepsy or any other disease that may induce seizures, except convulsions caused by febrile convulsions in children;
• Severe hematologic, hepatic or renal dysfunction during the screening period, the subject will be excluded if: a. Neutrophils < 1.5 × 10^9/L, or platelet < 90 × 10^9/L, or hemoglobin < 100 g/L; b. AST/ALT > 2.5 × upper limit of normal (ULN), or TBIL > 1.5 × ULN; c. Estimation of glomerular filtration rate (eGFR) < 60 mL/min / 1.73 m^2; d. Creatine kinase > 2.0 × ULN.
• 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;
• Subjects who had undergone psychiatric surgery, electroconvulsive therapy or transcranial magnetic stimulation within 90 days before screening;
• Use of β-blockers within 90 days prior to screening with an ongoing need for continued treatment;
• Receiving systemic psychotherapy or other non-pharmacological treatments (e.g., acupuncture, hypnosis, or phototherapy) within 6 weeks before the baseline visit;
• Subjects with dysphagia or inability to tolerate oral medications.
• Subjects with active gastrointestinal disorders (including any history of gastrointestinal surgery) that, in the investigator's judgment, may interfere with the absorption of the investigational drug.
• 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;
• Patients who discontinued traditional Chinese medicine, melatonin, and St. John's wort for less than 3 days before the baseline visit;
• Pregnant or preparing for pregnancy or breastfeeding during the study period, or subjects were not willing to use reliable contraceptives methods from the date of ICF signature until 28 days after the last trial drug administration, or planning to use progesterone contraceptives during this period;
• Individuals engaged in potentially hazardous mechanical operations such as working at heights or operating motor vehicles.
• Participants enrolled in other clinical trials within 30 days before screening;
• Subjects with other conditions deemed by the investigator to be ineligible for enrollment.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Crisugabalin 80mg/day group; Crisugabalin 20mg, orally twice a day; treatment period: 8 weeks fixed dose. Open-label extension phase: Crisugabalin 40mg, orally twice a day; treatment period: 4 weeks fixed dose.	Drug: Crisugabalin 20mg bid; Crisugabalin 20mg bid Crisugabalin 20mg, orally twice a day; treatment period: 8 weeks fixed dose. Open-label extension phase: Crisugabalin 40mg, orally twice a day; treatment period: 4 weeks fixed dose.; Other Names: HSK16149
Experimental: Venlafaxine Extended-Release (XR) Capsules 150mg/day group; Drug: Venlafaxine-XR 75mg bid Venlafaxine-XR 75mg, orally once a day and the second dose of placebo was administered; treatment period: 8 weeks fixed dose.	Drug: Venlafaxine-XR 75mg bid; Venlafaxine-XR 75mg bid Venlafaxine-XR 75mg, orally once a day and the second dose of placebo was administered; treatment period: 8 weeks fixed dose.; Other Names: Venlafaxine-XR
Placebo Comparator: Placebo-Control group; Drug: Crisugabalin capsules mimic 0mg/capsule bid Crisugabalin capsules mimic 0mg/capsule, orally twice a day; treatment period: 8 weeks fixed dose. Drug: Venlafaxine-XR capsules mimic, 0mg/capsule, bid Venlafaxine-XR capsules mimic, 0mg/capsule, orally twice a day; treatment period: 8 weeks fixed dose.	Drug: Crisugabalin capsules mimic 0mg/capsule bid; Crisugabalin capsules mimic 0mg/capsule, orally twice a day; treatment period: 8 weeks fixed dose. Drug: Venlafaxine-XR capsules mimic, 0mg/capsule, bid Drug: Venlafaxine-XR capsules mimic, 0mg/capsule, bid Venlafaxine-XR capsules mimic, 0mg/capsule, orally twice a day; treatment period: 8 weeks fixed dose.; Other Names: Crisugabalin capsules mimic; Venlafaxine-XR capsules mimic

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Hamilton Anxiety (HAMA) scale score after 8 week treatment	The Hamilton Anxiety (HAMA) scale score reflects the severity of the subjects anxiety symptoms. The primary efficacy end point was the change from baseline to week 8 in HAMA total score to determine the superiority of crisugabalin capsules over placebo. The larger the difference between crisugabalin capsules over placebo, the better the curative effect.The HAMA consists of 14 items that encompass both psychological and somatic symptoms of anxiety. Each item is scored on a scale of 0 (not present) to 4 (severe), with a total score range of 0-56, where <17 indicates mild severity, 18-24 mild to moderate severity and 25-30 moderate to severe.	from baseline to week 8

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Hamilton anxiety scale score after treatment	One of the secondary efficacy end point was the change from baseline to week 8 in Hamilton anxiety scale to determine the superiority of crisugabalin capsules over placebo. The larger the difference between crisugabalin capsules over placebo, the better the curative effect.The HAMA consists of 14 items that encompass both psychological and somatic symptoms of anxiety. Each item is scored on a scale of 0 (not present) to 4 (severe), with a total score range of 0-56, where <17 indicates mild severity, 18-24 mild to moderate severity and 25-30 moderate to severe.	from baseline to week 8
Change in each factor score and item score of Hamilton anxiety scale	One of the secondary efficacy end point was the change from baseline to week 8 in each factor score and item score of Hamilton anxiety scale to determine the superiority of crisugabalin capsules over placebo. The larger the difference between crisugabalin capsules over placebo, the better the curative effect. The HAMA consists of 14 items that encompass both psychological and somatic symptoms of anxiety. Each item is scored on a scale of 0 (not present) to 4 (severe), with a total score range of 0-56, where <17 indicates mild severity, 18-24 mild to moderate severity and 25-30 moderate to severe.	from baseline to week 8
Clinical global impression of improvement score	Subjective improvement of crisugabalin capsules will be assessed using Clinical Global Impression of Improvement (CGI-I) score at week 4 and 8. The larger the difference between crisugabalin capsules over placebo, the better the curative effect. The CGI-I scale is used to measure the clinician's assessment of how much the participant's illness has improved or worsened relative to baseline. The CGI-I comprises one item with 7 possible ratings (1-7 points), where a lower score indicates improvement, and a higher score indicates worsening.	the end of week 4 and 8
Clinical global impression of severity score	Subjective severity of crisugabalin capsules will be assessed by the change from baseline to week 4 and 8 with Clinical global impression of severity (CGI-S) score, to determine the superiority of crisugabalin capsules over placebo. The larger the difference between crisugabalin capsules over placebo, the better the curative effect. The CGI-S scale assesses the clinician's impression of the participant's current severity of illness relative to the clinician's experience with patients who have the same diagnosis. The CGI-S comprises one item with 7 possible ratings (1-7 points), where a higher score indicates more severe illness.	the end of week 4 and 8
Complete remission rate	Complete remission rate was the proportion of subjects with HAMA total scale score ≤7 at the end of week 8. The larger the difference between crisugabalin capsules over placebo, the better the curative effect. The HAMA consists of 14 items that encompass both psychological and somatic symptoms of anxiety. Each item is scored on a scale of 0 (not present) to 4 (severe), with a total score range of 0-56, where <17 indicates mild severity, 18-24 mild to moderate severity and 25-30 moderate to severe.	the end of week 8
Response rate	Response rate was the proportion of subjects with HAMA total score decreased by ≥50% from baseline to week 8. The larger the difference between crisugabalin capsules over placebo, the better the curative effect. The HAMA consists of 14 items that encompass both psychological and somatic symptoms of anxiety. Each item is scored on a scale of 0 (not present) to 4 (severe), with a total score range of 0-56, where <17 indicates mild severity, 18-24 mild to moderate severity and 25-30 moderate to severe.	the end of week 8
Rapid-onset rate	Rapid-onset rate was the proportion of subjects with HAMA total score decreased by ≥20% from baseline to week 1 and 2. The larger the difference between crisugabalin capsules over placebo, the better the curative effect. The HAMA consists of 14 items that encompass both psychological and somatic symptoms of anxiety. Each item is scored on a scale of 0 (not present) to 4 (severe), with a total score range of 0-56, where <17 indicates mild severity, 18-24 mild to moderate severity and 25-30 moderate to severe.	the end of week 1 and 2

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Exploratory Analysis	A descriptive statistical analysis will be performed to evaluate the change from baseline in HAMA total score for Venlafaxine-XR. The HAMA consists of 14 items that encompass both psychological and somatic symptoms of anxiety. Each item is scored on a scale of 0 (not present) to 4 (severe), with a total score range of 0-56, where <17 indicates mild severity, 18-24 mild to moderate severity and 25-30 moderate to severe.	Form baseline to week 8
Adverse events (AEs）	number and severity of AEs	Form baseline to week 8

Collaborators and Investigators

• Sponsor: Anhui Medical University

Study record dates

Study Major Dates

• Study Start (Actual): October 10, 2025
• Primary Completion (Estimated): January 31, 2027
• Study Completion (Estimated): February 28, 2027

Study Registration Dates

• First Submitted: November 24, 2025
• First Submitted That Met QC Criteria: December 29, 2025
• First Posted (Actual): January 9, 2026

Study Record Updates

• Last Update Posted (Actual): January 9, 2026
• Last Update Submitted That Met QC Criteria: December 29, 2025
• Last Verified: October 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Mental Disorders; Anxiety Disorders; Generalized Anxiety Disorder; BID protein, human; tebufenozide
• Other Study ID Numbers: HSK16149-502

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No