A Trial of AXS-05 in Patients With Major Depressive Disorder (GEMINI)

• ClinicalTrials.gov Identifier: NCT04019704
• Recruitment Status: Completed
• First Posted: July 15, 2019
• Results First Posted: October 12, 2022
• Last Update Posted: October 12, 2022
• Sponsor: Axsome Therapeutics, Inc.
• Information provided by (Responsible Party): Axsome Therapeutics, Inc.

Tracking Information

• First Submitted Date: July 11, 2019
• First Posted Date: July 15, 2019
• Results First Submitted Date: September 16, 2022
• Results First Posted Date: October 12, 2022
• Last Update Posted Date: October 12, 2022
• Actual Study Start Date: June 20, 2019
• Actual Primary Completion Date: November 26, 2019 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: September 16, 2022)

Change in MADRS Total Score From Baseline to Week 6 [ Time Frame: 6 weeks ]

The primary objective of the study was to evaluate the efficacy of AXS-05 as measured by the Montgomery-Åsberg Depression Rating Scale (MADRS) for change in severity of depressive symptoms from baseline to Week 6. The MADRS is a 10-item scale and items are scored between 0-6 points. For each item, a score of 0 indicates the absence of symptoms, and a score of 6 indicates symptoms of maximum severity. A maximum total score is 60 points.

Original Primary Outcome Measures (submitted: July 11, 2019)

• Safety outcomes: types and rates of adverse events [ Time Frame: 6 weeks ]
• Efficacy outcomes: Montgomery-Åsberg Depression Rating Scale (MADRS) [ Time Frame: 6 weeks ]
  For assessment of depressive symptomatology.

• Current Secondary Outcome Measures: Not Provided
• Original Secondary Outcome Measures: Not Provided
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: A Trial of AXS-05 in Patients With Major Depressive Disorder
• Official Title: AXS-05-MDD-301: A Randomized, Double-Blind, Placebo-Controlled Trial of AXS-05 in Subjects With Major Depressive Disorder
• Brief Summary: A Phase 3, randomized, double-blind, placebo-controlled, multicenter trial of AXS-05 in patients with major depressive disorder (MDD).
• Detailed Description: This study will evaluate AXS-05 in a randomized, double-blind, placebo-controlled study in patients with MDD. Eligible patients will be randomized in a 1:1 ratio to treatment with AXS-05 or placebo for 6 weeks.
• Study Type: Interventional
• Study Phase: Phase 3
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor); Primary Purpose: Treatment

Condition

• Depression
• Major Depressive Disorder

Intervention

• Drug: AXS-05
  Oral AXS-05 tablets, taken daily for 6 weeks.
• Drug: Placebo
  Placebo to match oral AXS-05 tablets, taken daily for 6 weeks.

Study Arms

• Experimental: AXS-05
  AXS-05 (bupropion and dextromethorphan) oral tablets
  Intervention: Drug: AXS-05
• Placebo Comparator: Placebo
  Placebo oral tablets to match AXS-05
  Intervention: Drug: Placebo

Publications *

• Iosifescu DV, Jones A, O'Gorman C, Streicher C, Feliz S, Fava M, Tabuteau H. Efficacy and Safety of AXS-05 (Dextromethorphan-Bupropion) in Patients With Major Depressive Disorder: A Phase 3 Randomized Clinical Trial (GEMINI). J Clin Psychiatry. 2022 May 30;83(4):21m14345. doi: 10.4088/JCP.21m14345.
• Dean RL, Hurducas C, Hawton K, Spyridi S, Cowen PJ, Hollingsworth S, Marquardt T, Barnes A, Smith R, McShane R, Turner EH, Cipriani A. Ketamine and other glutamate receptor modulators for depression in adults with unipolar major depressive disorder. Cochrane Database Syst Rev. 2021 Sep 12;9(9):CD011612. doi: 10.1002/14651858.CD011612.pub3.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: January 11, 2020): 327
• Original Estimated Enrollment (submitted: July 11, 2019): 300
• Actual Study Completion Date: December 5, 2019
• Actual Primary Completion Date: November 26, 2019 (Final data collection date for primary outcome measure)

Eligibility Criteria

Key Inclusion Criteria:

• Age 18 - 65
• Currently meets DSM-5 criteria for MDD
• Body Mass Index between 18 and 40 kg/m^2, inclusive

Key Exclusion Criteria:

• Suicide risk
• History of treatment resistance in current depressive episode
• History of electroconvulsive therapy, vagus nerve stimulation, transcranial magnetic stimulation or any experimental central nervous system treatment during the current episode or in the past 6 months
• Pregnant, breastfeeding, or planning to become pregnant or breastfeed during the study

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years to 65 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT04019704
• Other Study ID Numbers: AXS-05-MDD-301
• Has Data Monitoring Committee: No

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: No

• Current Responsible Party: Axsome Therapeutics, Inc.
• Original Responsible Party: Same as current
• Current Study Sponsor: Axsome Therapeutics, Inc.
• Original Study Sponsor: Same as current
• Collaborators: Not Provided
• Investigators: Not Provided
• PRS Account: Axsome Therapeutics, Inc.
• Verification Date: September 2022