NCT05414422

A Randomized, Placebo-Controlled, Double-Blind Study to Assess Safety and Efficacy of PCN-101 in TRD

Completed Phase 2 Results posted Last updated 4 June 2024

What this trial tests

Phase 2 trial testing PCN-101 in Treatment Resistant Depression in 102 participants. Completed in 10 November 2022.

Timeline

1 February 2022

Primary endpoint
10 November 2022

10 November 2022

Quick facts

Lead sponsor	Perception Neuroscience
Phase	Phase 2
Status	Completed
Study type	INTERVENTIONAL
Allocation	randomized
Design	parallel
Masking	triple
Primary purpose	treatment
Enrollment	102
Start date	1 February 2022
Primary completion	10 November 2022
Estimated completion	10 November 2022
Sites	21 locations across United States, Germany, Poland

Drugs / interventions tested

• PCN-101 — full drug profile →
• Placebo

Conditions studied

• Treatment Resistant Depression — all drugs for Treatment Resistant Depression →

Sponsor

Perception Neuroscience — full company profile →

Who can join

Adults 18 to 65, any sex, with Treatment Resistant Depression. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Montgomery Asberg Depression Rating Scale (MADRS) 24 Hours Primary · 24 hours

Change from baseline to 24 hours after the start of infusion in the Montgomery Asberg Depression Rating Scale (MADRS). The overall score ranges from 0 to 60. Higher scores indicates more severe depression.

Group	Value	95% CI
PCN-101 30 mg	-13.7	± 1.75
PCN-101 60 mg	-15.3	± 1.69
Placebo	-13.7	± 1.76

Montgomery Asberg Depression Rating Scale (MADRS) >= 50% Improvement Secondary · 2 hours, 4 hours, 24 hours, 7 days and 14 days

Proportion of subjects with \>= 50% improvement in MADRS total score from predose. The overall score ranges from 0 to 60. Higher scores indicates more severe depression.

2 hours

Group	Value	95% CI
PCN-101 30 mg	9
PCN-101 60 mg	11
Placebo	6

4 hours

Group	Value	95% CI
PCN-101 30 mg	9
PCN-101 60 mg	13
Placebo	9

24 hours

Group	Value	95% CI
PCN-101 30 mg	19
PCN-101 60 mg	16
Placebo	16

7 days

Group	Value	95% CI
PCN-101 30 mg	9
PCN-101 60 mg	12
Placebo	9

14 days

Group	Value	95% CI
PCN-101 30 mg	5
PCN-101 60 mg	12
Placebo	7

Montgomery Asberg Depression Rating Scale (MADRS) <= 10 Secondary · 24 hours, 7 days and 14 days

Proportion of subjects with remission (MADRS total score \<= 10). The overall score ranges from 0 to 60. Higher scores indicates more severe depression.

24 hours

Group	Value	95% CI
PCN-101 30 mg	10
PCN-101 60 mg	15
Placebo	9

7 days

Group	Value	95% CI
PCN-101 30 mg	7
PCN-101 60 mg	9
Placebo	4

14 days

Group	Value	95% CI
PCN-101 30 mg	4
PCN-101 60 mg	10
Placebo	4

Hamilton Depression Rating Scale (HAM-D) Change From Baseline Secondary · 7 days and 14 days

Change from Baseline in HAM-D. The total score across the 17 items could range from 0 to 52. Higher scores indicate more severe depression

7 days

Group	Value	95% CI
PCN-101 30 mg	-8.6	± 7.61
PCN-101 60 mg	-9.3	± 8.09
Placebo	-9.4	± 7.07

14 days

Group	Value	95% CI
PCN-101 30 mg	-6.1	± 7.14
PCN-101 60 mg	-8.7	± 8.70
Placebo	-8.1	± 7.21

Generalized Anxiety Disorder (GAD-7) Change From Baseline Secondary · 24 hours, 7 days and 14 days

Change from Baseline in GAD-7. The total score of the 7 items range from 0 to 21. Higher scores indicate more anxiety.

24 hours

Group	Value	95% CI
PCN-101 30 mg	-6.5	± 0.84
PCN-101 60 mg	-7.5	± 0.83
Placebo	-7.4	± 0.85

7 days

Group	Value	95% CI
PCN-101 30 mg	-5.8	± 0.89
PCN-101 60 mg	-5.8	± 0.85
Placebo	-5.8	± 0.89

14 days

Group	Value	95% CI
PCN-101 30 mg	-3.7	± 0.87
PCN-101 60 mg	-4.3	± 0.84
Placebo	-5.3	± 0.88

Clinical Global Impression - Severity (CGI-S) Change From Baseline Secondary · 24 hours, 7 days and 14 days

Change from Baseline in CGI-S. The score ranged from 0 to 7. Higher scores indicate a more severe or worsening of condition.

24 hours

Group	Value	95% CI
PCN-101 30 mg	3.0	± 0.23
PCN-101 60 mg	3.0	± 0.23
Placebo	3.4	± 0.23

7 days

Group	Value	95% CI
PCN-101 30 mg	3.4	± 0.26
PCN-101 60 mg	3.3	± 0.25
Placebo	3.5	± 0.27

14 days

Group	Value	95% CI
PCN-101 30 mg	3.9	± 0.29
PCN-101 60 mg	3.3	± 0.28
Placebo	3.7	± 0.31

Clinical Global Impression - Improvement (CGI-I) Secondary · 24 hours, 7 days and 14 days

This score ranges from 0 to 7. Higher scores indicate a more severe or worsening of the condition

24 hours

Group	Value	95% CI
PCN-101 30 mg	2.3	± 0.20
PCN-101 60 mg	2.2	± 0.20
Placebo	2.5	± 0.20

7 days

Group	Value	95% CI
PCN-101 30 mg	2.8	± 0.24
PCN-101 60 mg	2.3	± 0.23
Placebo	2.6	± 0.25

14 days

Group	Value	95% CI
PCN-101 30 mg	3.2	± 0.25
PCN-101 60 mg	2.5	± 0.24
Placebo	3.0	± 0.27

Quick Inventory of Depressive Symptomatology (QIDS-SR-16) Change From Baseline Secondary · 24 hours, 7 days and 14 days

Change from Baseline in QIDS-SR-16. Total score ranges from 0 to 42. Higher scores indicate more severe depression.

24 hours

Group	Value	95% CI
PCN-101 30 mg	-9.6	± 1.23
PCN-101 60 mg	-10.7	± 1.21
Placebo	-10.5	± 1.25

7 days

Group	Value	95% CI
PCN-101 30 mg	-8.4	± 1.30
PCN-101 60 mg	-10.1	± 1.26
Placebo	-9.4	± 1.32

14 days

Group	Value	95% CI
PCN-101 30 mg	-6.0	± 1.42
PCN-101 60 mg	-9.6	± 1.38
Placebo	-8.3	± 1.46

European Quality - 5 Dimensions - 3 Levels (EQ-5D-3L) Change From Baseline Secondary · 24 hours, 7 days and 14 days

Change from Baseline in EQ-5D-3L. The visual analogue scale ranges from 0 to 100. Higher scores indicate a better health state.

24 hours

Group	Value	95% CI
PCN-101 30 mg	13.9	± 3.30
PCN-101 60 mg	17.9	± 3.20
Placebo	14.9	± 3.24

7 days

Group	Value	95% CI
PCN-101 30 mg	12.9	± 3.46
PCN-101 60 mg	14.1	± 3.29
Placebo	14.4	± 3.40

14 days

Group	Value	95% CI
PCN-101 30 mg	8.2	± 3.75
PCN-101 60 mg	9.8	± 3.58
Placebo	11.0	± 3.70

Treatment-emergent Adverse Events Summarized by Treatment Group, System Organ Class and Preferred Term Secondary · 14 days

The number of participants in each treatment group with treatment-emergent adverse events categorized using MedDRA v24.0 or higher

Group	Value	95% CI
PCN-101 30 mg	11
PCN-101 60 mg	19
Placebo	18

Adverse events — posted to ClinicalTrials.gov

Time frame: 14 days. Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

PCN-101 30 mg

Serious: 0/33 (0%)

Deaths: 0/33

PCN-101 60 mg

Serious: 0/35 (0%)

Deaths: 0/35

Placebo

Serious: 0/34 (0%)

Deaths: 0/34

Other adverse events (8 terms — click to expand)

Reaction	System	PCN-101 30 mg	PCN-101 60 mg	Placebo
Somnolence	Nervous system disorders	—	—	—
Dizziness	Nervous system disorders	—	—	—
Derealisation	Psychiatric disorders	—	—	—
Headache	Nervous system disorders	—	—	—
Nausea	Gastrointestinal disorders	—	—	—
Dysarthria	Nervous system disorders	—	—	—
Paraesthesia	Nervous system disorders	—	—	—
Feeling drunk	General disorders	—	—	—

Data from ClinicalTrials.gov NCT05414422 adverse events section.

Sponsor's own description

This is a double-blind, randomized, placebo-controlled, multicenter study comprised of 3 phases:screening (up to 2 weeks \[Day -15 to Day -2\]), In-Clinic Treatment (Day -1 to Day 2; including double-blind treatment \[Day 1\]), and post-treatment follow-up (7 and 14 days after infusion on Days 8 and 15, respectively). A total of 93 adult subjects with TRD will be randomly allocated in equal cohorts of 31 subjects/arm to the 3 arms of the study in a blinded manner.

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

1. Ketamine in neuropsychiatric disorders: an update.
   Johnston JN, Kadriu B, Kraus C, Henter ID, et al · · 2024 · cited 54× · PMID 37340091 · DOI 10.1038/s41386-023-01632-1
2. Ketamine and serotonergic psychedelics: An update on the mechanisms and biosignatures underlying rapid-acting antidepressant treatment.
   Johnston JN, Kadriu B, Allen J, Gilbert JR, et al · · 2023 · cited 42× · PMID 36646310 · DOI 10.1016/j.neuropharm.2023.109422
3. Pharmacotherapies Targeting GABA-Glutamate Neurotransmission for Treatment-Resistant Depression.
   Vecera CM, C Courtes A, Jones G, Soares JC, et al · · 2023 · cited 23× · PMID 38004437 · DOI 10.3390/ph16111572
4. Single arketamine in treatment resistant depression: Presentation of 3 cases with regard to sick-leave duration.
   Włodarczyk A, Słupski J, Szarmach J, Cubała WJ. · · 2024 · cited 9× · PMID 38554563 · DOI 10.1016/j.ajp.2024.104016
5. Ketamine and its two enantiomers in anesthesiology and psychiatry: A historical review and future directions.
   Hashimoto K, Zhao M, Zhu T, Wang X, et al · · 2024 · cited 8× · PMID 41929866 · DOI 10.1016/j.jatmed.2024.07.001
6. Emerging Medications for Treatment-Resistant Depression: A Review with Perspective on Mechanisms and Challenges.
   Lucido MJ, Dunlop BW. · · 2025 · cited 7× · PMID 40002494 · DOI 10.3390/brainsci15020161
7. Advancing past ketamine: emerging glutamatergic compounds for the treatment of depression.
   Freudenberg F, Reif-Leonhard C, Reif-Leonhard C, Reif A. · · 2025 · cited 7× · PMID 39207462 · DOI 10.1007/s00406-024-01875-z
8. Mechanism of antidepressant action of ketamine and differences between its two enantiomers.
   Zhan J, Zhang Y, Tian H, Zhu X, et al · · 2025 · PMID 41929374 · DOI 10.1016/j.jatmed.2025.06.001