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The Safety and Efficacy of Psilocybin in Participants With Treatment Resistant Depression (P-TRD)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03775200
Recruitment Status : Completed
First Posted : December 13, 2018
Results First Posted : April 24, 2023
Last Update Posted : April 24, 2023
Sponsor:
Information provided by (Responsible Party):
COMPASS Pathways

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Condition Treatment Resistant Depression
Intervention Drug: Psilocybin
Enrollment 233
Recruitment Details First patient first visit: 1 March 2019 Last patients last visit: 27 September 2021
Pre-assignment Details  
Arm/Group Title 25 mg COMP360 Psilocybin 10 mg COMP360 Psilocybin 1 mg COMP360 Psilocybin
Hide Arm/Group Description 25 mg COMP360 Psilocybin 10 mg COMP360 Psilocybin 1 mg COMP360 Psilocybin
Period Title: Overall Study
Started 79 75 79
Completed 74 66 69
Not Completed 5 9 10
Arm/Group Title 25 mg COMP360 Psilocybin 10 mg COMP360 Psilocybin 1 mg COMP360 Psilocybin Total
Hide Arm/Group Description 25 mg COMP360 Psilocybin 10 mg COMP360 Psilocybin 1 mg COMP360 Psilocybin Total of all reporting groups
Overall Number of Baseline Participants 79 75 79 233
Hide Baseline Analysis Population Description
The Safety Analysis Set included all randomised participants who received study drug.
Age, Categorical  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 79 participants 75 participants 79 participants 233 participants
<=18 years
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Between 18 and 65 years
76
  96.2%
73
  97.3%
77
  97.5%
226
  97.0%
>=65 years
3
   3.8%
2
   2.7%
2
   2.5%
7
   3.0%
Age, Continuous   [1] 
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 79 participants 75 participants 79 participants 233 participants
40.2  (12.19) 40.6  (12.76) 38.7  (11.71) 39.8  (12.19)
[1]
Measure Description: Age at Screening
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 79 participants 75 participants 79 participants 233 participants
Female
35
  44.3%
34
  45.3%
43
  54.4%
112
  48.1%
Male
44
  55.7%
41
  54.7%
36
  45.6%
121
  51.9%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 79 participants 75 participants 79 participants 233 participants
American Indian or Alaska Native
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Asian
4
   5.1%
3
   4.0%
5
   6.3%
12
   5.2%
Native Hawaiian or Other Pacific Islander
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Black or African American
4
   5.1%
0
   0.0%
1
   1.3%
5
   2.1%
White
70
  88.6%
72
  96.0%
73
  92.4%
215
  92.3%
More than one race
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Unknown or Not Reported
1
   1.3%
0
   0.0%
0
   0.0%
1
   0.4%
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
 Number Analyzed 79 participants 75 participants 79 participants 233 participants
Canada 2 2 2 6
Netherlands 17 16 17 50
United States 32 32 32 96
Czechia 3 2 2 7
Ireland 3 3 5 11
Denmark 3 2 3 8
United Kingdom 11 10 12 33
Portugal 1 0 1 2
Germany 2 2 0 4
Spain 5 6 5 16
1.Primary Outcome
Title Montgomery Asberg Depression Rating Scale (MADRS) Change From Baseline to Week 3
Hide Description MADRS is a clinician-rated scale measuring depression symptom severity, consisting of 10 items, each scored from 0 (normal) to 6 (severe), for a total possible score of between 0 to 60; higher scores denote greater severity. Response >= 50% decrease and remission <= 10 total score.
Time Frame Change from Baseline to Week 3
Hide Outcome Measure Data
Hide Analysis Population Description
The full analysis set includes all participants randomised who receive study drug and have at least 1 post-dose efficacy assessment.
Arm/Group Title 25 mg COMP360 Psilocybin 10 mg COMP360 Psilocybin 1 mg COMP360 Psilocybin
Hide Arm/Group Description:
25 mg COMP360 Psilocybin
10 mg COMP360 Psilocybin
1 mg COMP360 Psilocybin
Overall Number of Participants Analyzed 79 75 79
Mean (Standard Deviation)
Unit of Measure: units on a scale
-12  (12.98) -8.9  (10.94) -6.8  (11.10)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection 25 mg COMP360 Psilocybin, 1 mg COMP360 Psilocybin
Comments The primary analysis was the comparison between COMP360 (25 mg or 10 mg) versus COMP360 1 mg. The null hypothesis was that there was no difference in mean change from Baseline in MADRS total score at Week 3 for COMP360 25 mg or COMP360 10 mg versus COMP360 1 mg. The alternative hypothesis was that were was a difference in mean change from Baseline in MADRS total score at Week 3 for COMP360 25 mg or COMP360 10 mg versus COMP360 1 mg.
Type of Statistical Test Other
Comments For this primary analysis, a sample size of 216 randomised participants (72:72:72) will provide 90% power at the alpha = 0.05 level to detect a 6-point difference in average MADRS total score between the optimal therapeutic dose of COMP360 and COMP360 1 mg, assuming the common standard deviation (SD) is 11.0.
Statistical Test of Hypothesis P-Value <0.05
Comments [Not Specified]
Method Mixed Models Analysis
Comments Hypothetical strategy estimand - missing not at random (MNAR) and missing at random (MAR) imputation for missing data.
Method of Estimation Estimation Parameter Least Mean Square Difference
Estimated Value -6.6
Confidence Interval (2-Sided) 95%
-10.2 to -2.9
Parameter Dispersion
Type: Standard Error of the Mean
Value: 1.86
Estimation Comments LSM difference of COMP360 25 mg compared to COMP360 1 mg.
2.Primary Outcome
Title MADRS Change From Baseline to Week 3, Sensitivity Analysis
Hide Description MADRS is a clinician-rated scale measuring depression symptom severity, consisting of 10 items, each scored from 0 (normal) to 6 (severe), for a total possible score of between 0 to 60; higher scores denote greater severity. Response >= 50% decrease and remission <= 10 total score.
Time Frame Change from Baseline to Week 3
Hide Outcome Measure Data
Hide Analysis Population Description
The per-protocol analysis set includes all participants in the Full Analysis Set who do not have a protocol deviation that is thought to significantly affect the integrity of the participant's efficacy data.
Arm/Group Title 25 mg COMP360 Psilocybin 10 mg COMP360 Psilocybin 1 mg COMP360 Psilocybin
Hide Arm/Group Description:
25 mg COMP360 Psilocybin
10 mg COMP360 Psilocybin
1 mg COMP360 Psilocybin
Overall Number of Participants Analyzed 77 65 68
Mean (Standard Deviation)
Unit of Measure: units on a scale
-12  (12.98) -8.9  (11.11) -6.7  (11.18)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection 25 mg COMP360 Psilocybin, 1 mg COMP360 Psilocybin
Comments Sensitivity analysis of the primary endpoint using the per-protocol analysis set.
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.05
Comments [Not Specified]
Method Mixed Models Analysis
Comments Hypothetical strategy estimand - MNAR and MAR imputation for missing data.
Method of Estimation Estimation Parameter Least Mean Square Difference
Estimated Value -5.6
Confidence Interval (2-Sided) 95%
-9.4 to -1.8
Parameter Dispersion
Type: Standard Error of the Mean
Value: 1.93
Estimation Comments [Not Specified]
Time Frame Up to 12 Weeks
Adverse Event Reporting Description The Safety Analysis Set included all randomised participants who received study drug.
 
Arm/Group Title 25 mg COMP360 Psilocybin 10 mg COMP360 Psilocybin 1 mg COMP360 Psilocybin
Hide Arm/Group Description 25 mg COMP360 Psilocybin 10 mg COMP360 Psilocybin 1 mg COMP360 Psilocybin
All-Cause Mortality
25 mg COMP360 Psilocybin 10 mg COMP360 Psilocybin 1 mg COMP360 Psilocybin
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   0/79 (0.00%)      0/75 (0.00%)      0/79 (0.00%)    
Hide Serious Adverse Events
25 mg COMP360 Psilocybin 10 mg COMP360 Psilocybin 1 mg COMP360 Psilocybin
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   5/79 (6.33%)      6/75 (8.00%)      1/79 (1.27%)    
General disorders       
Drug withdrawal syndrome † 1  1/79 (1.27%)  1 0/75 (0.00%)  0 0/79 (0.00%)  0
Psychiatric disorders       
Suicidal behaviour † 1  3/79 (3.80%)  3 0/75 (0.00%)  0 0/79 (0.00%)  0
Intentional self-injury † 1  2/79 (2.53%)  2 2/75 (2.67%)  2 1/79 (1.27%)  2
Adjustment disorder with anxiety † 1  1/79 (1.27%)  1 0/75 (0.00%)  0 0/79 (0.00%)  0
Adjustment disorder with mixed anxiety and depressed mood † 1  1/79 (1.27%)  1 0/75 (0.00%)  0 0/79 (0.00%)  0
Depression † 1  0/79 (0.00%)  0 1/75 (1.33%)  1 0/79 (0.00%)  0
Suicidal ideation † 1  2/79 (2.53%)  2 2/75 (2.67%)  3 0/79 (0.00%)  0
Surgical and medical procedures       
Hospitalisation † 1  0/79 (0.00%)  0 1/75 (1.33%)  1 0/79 (0.00%)  0
1
Term from vocabulary, MedDRA 23.0
†
Indicates events were collected by systematic assessment
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
25 mg COMP360 Psilocybin 10 mg COMP360 Psilocybin 1 mg COMP360 Psilocybin
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   60/79 (75.95%)      51/75 (68.00%)      50/79 (63.29%)    
Gastrointestinal disorders       
Nausea † 1  18/79 (22.78%)  19 7/75 (9.33%)  7 4/79 (5.06%)  4
Abdominal pain upper † 1  4/79 (5.06%)  4 2/75 (2.67%)  2 1/79 (1.27%)  1
General disorders       
Fatigue † 1  12/79 (15.19%)  12 5/75 (6.67%)  5 7/79 (8.86%)  8
Musculoskeletal and connective tissue disorders       
Back pain † 1  6/79 (7.59%)  6 0/75 (0.00%)  0 3/79 (3.80%)  4
Myalgia † 1  5/79 (6.33%)  5 2/75 (2.67%)  2 1/79 (1.27%)  1
Nervous system disorders       
Headache † 1  27/79 (34.18%)  34 16/75 (21.33%)  22 20/79 (25.32%)  30
Dizziness † 1  6/79 (7.59%)  6 1/75 (1.33%)  1 1/79 (1.27%)  1
Paraesthesia † 1  3/79 (3.80%)  3 4/75 (5.33%)  4 1/79 (1.27%)  1
Psychiatric disorders       
Insomnia † 1  8/79 (10.13%)  8 11/75 (14.67%)  11 14/79 (17.72%)  16
Anxiety † 1  7/79 (8.86%)  7 13/75 (17.33%)  16 3/79 (3.80%)  3
Depression † 1  4/79 (5.06%)  4 5/75 (6.67%)  5 5/79 (6.33%)  5
Euphoric mood † 1  4/79 (5.06%)  4 5/75 (6.67%)  5 4/79 (5.06%)  5
Depressed mood † 1  3/79 (3.80%)  3 5/75 (6.67%)  5 4/79 (5.06%)  5
Suicidal ideation † 1  5/79 (6.33%)  5 3/75 (4.00%)  3 4/79 (5.06%)  5
Mood altered † 1  7/79 (8.86%)  8 3/75 (4.00%)  3 1/79 (1.27%)  1
Irritability † 1  4/79 (5.06%)  4 2/75 (2.67%)  2 1/79 (1.27%)  1
Panic reaction † 1  4/79 (5.06%)  4 1/75 (1.33%)  1 1/79 (1.27%)  1
Thinking abnormal † 1  0/79 (0.00%)  0 4/75 (5.33%)  4 0/79 (0.00%)  0
1
Term from vocabulary, MedDRA 23.0
†
Indicates events were collected by systematic assessment
[Not Specified]
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: Medical Director
Organization: Compass Pathways
Phone: 07443136539
EMail: info@compasspathways.com
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Goodwin GM, Aaronson ST, Alvarez O, Arden PC, Baker A, Bennett JC, Bird C, Blom RE, Brennan C, Brusch D, Burke L, Campbell-Coker K, Carhart-Harris R, Cattell J, Daniel A, DeBattista C, Dunlop BW, Eisen K, Feifel D, Forbes M, Haumann HM, Hellerstein DJ, Hoppe AI, Husain MI, Jelen LA, Kamphuis J, Kawasaki J, Kelly JR, Key RE, Kishon R, Knatz Peck S, Knight G, Koolen MHB, Lean M, Licht RW, Maples-Keller JL, Mars J, Marwood L, McElhiney MC, Miller TL, Mirow A, Mistry S, Mletzko-Crowe T, Modlin LN, Nielsen RE, Nielson EM, Offerhaus SR, O'Keane V, Palenicek T, Printz D, Rademaker MC, van Reemst A, Reinholdt F, Repantis D, Rucker J, Rudow S, Ruffell S, Rush AJ, Schoevers RA, Seynaeve M, Shao S, Soares JC, Somers M, Stansfield SC, Sterling D, Strockis A, Tsai J, Visser L, Wahba M, Williams S, Young AH, Ywema P, Zisook S, Malievskaia E. Single-Dose Psilocybin for a Treatment-Resistant Episode of Major Depression. N Engl J Med. 2022 Nov 3;387(18):1637-1648. doi: 10.1056/NEJMoa2206443.
Layout table for additonal information
Responsible Party: COMPASS Pathways
ClinicalTrials.gov Identifier: NCT03775200    
Other Study ID Numbers: COMP001
First Submitted: December 11, 2018
First Posted: December 13, 2018
Results First Submitted: February 7, 2023
Results First Posted: April 24, 2023
Last Update Posted: April 24, 2023