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

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ClinicalTrials.gov Identifier: NCT04019704

Recruitment Status : Completed

First Posted : July 15, 2019

Results First Posted : October 12, 2022

Last Update Posted : October 12, 2022

View this study on Beta.ClinicalTrials.gov

Sponsor:

Information provided by (Responsible Party):

Axsome Therapeutics, Inc.

Study Type	Interventional
Study Design	Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor); Primary Purpose: Treatment
Conditions	Depression Major Depressive Disorder
Interventions	Drug: AXS-05 Drug: Placebo
Enrollment	327

Participant Flow

Recruitment Details
Pre-assignment Details


Arm/Group Title	AXS-05	Placebo
Arm/Group Description	AXS-05 (bupropion and dextromethorp...	Placebo oral tablets to match AXS-0...
Arm/Group Description	AXS-05 (bupropion and dextromethorphan) oral tablets AXS-05: Oral AXS-05 tablets, taken daily for 6 weeks.	Placebo oral tablets to match AXS-05 Placebo: Placebo to match oral AXS-05 tablets, taken daily for 6 weeks.
Period Title: Overall Study
Started	163	164
Completed	123	147
Not Completed	40	17

Baseline Characteristics

Arm/Group Title		AXS-05	Placebo	Total
Arm/Group Description		AXS-05 (bupropion and dextromethorp...	Placebo oral tablets to match AXS-0...	Total of all reporting groups
Arm/Group Description		AXS-05 (bupropion and dextromethorphan) oral tablets AXS-05: Oral AXS-05 tablets, taken daily for 6 weeks.	Placebo oral tablets to match AXS-05 Placebo: Placebo to match oral AXS-05 tablets, taken daily for 6 weeks.	Total of all reporting groups
Overall Number of Baseline Participants		163	164	327
Baseline Analysis Population Description		...
Baseline Analysis Population Description		Participants randomized
Age, Continuous Mean (Standard Deviation) Unit of measure: Years
	Number Analyzed	163 participants	164 participants	327 participants
		42.1 (12.71)	41.1 (13.78)	41.6 (13.25)
Sex: Female, Male Measure Type: Count of Participants Unit of measure: Participants
	Number Analyzed	163 participants	164 participants	327 participants
	Female	98 60.1%	117 71.3%	215 65.7%
	Male	65 39.9%	47 28.7%	112 34.3%
Race (NIH/OMB) Measure Type: Count of Participants Unit of measure: Participants
	Number Analyzed	163 participants	164 participants	327 participants
	American Indian or Alaska Native	1 0.6%	1 0.6%	2 0.6%
	Asian	9 5.5%	8 4.9%	17 5.2%
	Native Hawaiian or Other Pacific Islander	1 0.6%	2 1.2%	3 0.9%
	Black or African American	61 37.4%	55 33.5%	116 35.5%
	White	88 54.0%	92 56.1%	180 55.0%
	More than one race	3 1.8%	3 1.8%	6 1.8%
	Unknown or Not Reported	0 0.0%	3 1.8%	3 0.9%

Outcome Measures

1.Primary Outcome


Title	Change in MADRS Total Score From Baseline to Week 6
Description	The primary objective of the study was to evaluate the efficacy of AXS...
Description	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.
Time Frame	6 weeks

Outcome Measure Data

Analysis Population Description

modified Intent-to-Treat (mITT) Population


Arm/Group Title	AXS-05	Placebo
Arm/Group Description:	AXS-05 (bupropion and dextromethorp...	Placebo oral tablets to match AXS-0...
Arm/Group Description:	AXS-05 (bupropion and dextromethorphan) oral tablets AXS-05: Oral AXS-05 tablets, taken daily for 6 weeks.	Placebo oral tablets to match AXS-05 Placebo: Placebo to match oral AXS-05 tablets, taken daily for 6 weeks.
Overall Number of Participants Analyzed	156	162
Least Squares Mean (Standard Error) Unit of Measure: score on a scale
	15.91 (0.921)	12.04 (0.862)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	AXS-05, Placebo
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]

Statistical Test of Hypothesis	P-Value	0.002
	Comments	[Not Specified]
	Method	Mixed Models Analysis
	Comments	[Not Specified]

Adverse Events

Time Frame	Treatment-emergent adverse events (TEAEs) were AEs with an onset date on or after the date of first dose. TEAEs were collected through 30 days after the last dose.
Adverse Event Reporting Description	Safety Population

Arm/Group Title	AXS-05		Placebo
Arm/Group Description	AXS-05 (bupropion and dextromethorp...		Placebo oral tablets to match AXS-0...
Arm/Group Description	AXS-05 (bupropion and dextromethorphan) oral tablets AXS-05: Oral AXS-05 tablets, taken daily for 6 weeks.		Placebo oral tablets to match AXS-05 Placebo: Placebo to match oral AXS-05 tablets, taken daily for 6 weeks.
All-Cause Mortality
	AXS-05		Placebo
	Affected / at Risk (%)		Affected / at Risk (%)
Total	0/162 (0.00%)		0/164 (0.00%)
Serious Adverse Events Serious Adverse Events
	AXS-05		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/162 (0.62%)		0/164 (0.00%)
Gastrointestinal disorders
Pancreatitis ^* 1 [1]	1/162 (0.62%)	1	0/164 (0.00%)	0
1 Term from vocabulary, MedDRA Dictionary * Indicates events were collected by non-systematic assessment [1] Not related to study drug.
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	5%
	AXS-05		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	100/162 (61.73%)		74/164 (45.12%)
Gastrointestinal disorders
Nausea ^* 1	21/162 (12.96%)	24	14/164 (8.54%)	14
Diarrhea ^* 1	11/162 (6.79%)	11	5/164 (3.05%)	5
Dry mouth ^* 1	9/162 (5.56%)	9	4/164 (2.44%)	4
General disorders
All Others, occurring in <5% of Subjects ^* 1 [1]	47/162 (29.01%)		43/164 (26.22%)
Nervous system disorders
Dizziness ^* 1	26/162 (16.05%)	29	10/164 (6.10%)	12
Headache ^* 1	13/162 (8.02%)	16	6/164 (3.66%)	6
Somnolence ^* 1	11/162 (6.79%)	11	5/164 (3.05%)	5
1 Term from vocabulary, MedDRA Dictionary * Indicates events were collected by non-systematic assessment [1] All other events

Limitations and Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

Results Point of Contact

Layout table for Results Point of Contact information

Name/Title:	Caroline Streicher, Senior Director, Clinical Operations
Organization:	Axsome Therapeutics, Inc.
Phone:	212-332-5061
EMail:	cstreicher@axsome.com

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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.

Layout table for additonal information

Responsible Party:	Axsome Therapeutics, Inc.
ClinicalTrials.gov Identifier:	NCT04019704
Other Study ID Numbers:	AXS-05-MDD-301
First Submitted:	July 11, 2019
First Posted:	July 15, 2019
Results First Submitted:	September 16, 2022
Results First Posted:	October 12, 2022
Last Update Posted:	October 12, 2022

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