# COMP005 Phase 3 Trial

**Sponsor:** Compass Pathways  
**Intervention:** COMP360 psilocybin 25mg single dose  
**Indication:** Treatment-resistant depression  
**Status:** Completed, positive primary endpoint  
**Reported:** June 23, 2025  

## Trial Design

- **Phase:** 3
- **Design:** Randomized, double-blind, placebo-controlled
- **Sample Size:** n=258
- **Sites:** 32 sites in the United States
- **Population:** Treatment-resistant depression (≥2 failed antidepressant courses)
- **Intervention:** Single dose COMP360 25mg vs. placebo
- **Protocol:** Embedded psychological support (preparation, monitored session, integration)

## Primary Endpoint

**MADRS change from baseline at Week 6:**
- Treatment difference: **-3.6 points** (95% CI [-5.7, -1.5])
- **p<0.001** (highly statistically significant)

## Secondary Outcomes

- **Response Rate:** 25% achieved clinically meaningful MADRS reduction (≥25%) at week 6
- **Durability:** Improvement maintained through 26-week follow-up after single dose
- **Rapid Onset:** Statistically significant benefit from next day after dosing

## Safety Profile

- All treatment-emergent adverse events: mild or moderate severity
- Most adverse events resolved within 24 hours
- Frequently reported: headache, nausea, anxiety, visual hallucination
- No clinically meaningful imbalance in suicidal ideation between arms
- No unexpected safety findings

## Historical Significance

- **First investigational psychedelic to report positive Phase 3 efficacy data**
- First classic psychedelic to reach Phase 3 evidence level
- Establishes proof-of-concept for FDA approval pathway for psychedelic therapeutics

## Clinical Context

- Effect size (-3.6 MADRS points) comparable to existing TRD augmentation strategies (2-4 points)
- Single-dose 26-week durability represents paradigm shift from daily-dosing chronic treatment model
- Psychological support protocol is mandatory component, not optional adjunct
- Treatment-resistant depression population: ~7M Americans who have failed 2+ antidepressant courses

## Timeline

- **2025-06-23** — Primary endpoint results announced: MADRS -3.6 (p<0.001), first positive Phase 3 data for any psychedelic