NCT02417064: TRANSFORM-1

A Study to Evaluate the Efficacy, Safety, and Tolerability of Fixed Doses of Intranasal Esketamine Plus an Oral Antidepressant in Adult Participants With Treatment-resistant Depression

Completed Phase 3 Results posted Last updated 29 April 2025

What this trial tests

Phase 3 trial testing Esketamine in Treatment-resistant Depression in 346 participants. Completed in 20 February 2018.

Timeline

10 August 2015

Primary endpoint
20 February 2018

20 February 2018

Quick facts

Lead sponsor	Janssen Research & Development, LLC
Phase	Phase 3
Status	Completed
Study type	INTERVENTIONAL
Allocation	randomized
Design	parallel
Masking	double
Primary purpose	treatment
Enrollment	346
Start date	10 August 2015
Primary completion	20 February 2018
Estimated completion	20 February 2018
Sites	90 locations across United States, France, Slovakia, Hungary, Estonia, Canada, Brazil, Belgium

Drugs / interventions tested

• Esketamine (ESKETAMINE) — full drug profile →
• Placebo
• Duloxetine (Oral Antidepressant) — full drug profile →
• Escitalopram (Oral antidepressant) — full drug profile →
• Sertraline (Oral Antidepressant) — full drug profile →
• Venlafaxine Extended Release (XR) (Oral Antidepressant) — full drug profile →

Conditions studied

• Treatment-resistant Depression — all drugs for Treatment-resistant Depression →

Sponsor

Janssen Research & Development, LLC — full company profile →

Who can join

Adults 18 to 64, any sex, with Treatment-resistant Depression. Patients with the condition only — healthy volunteers not accepted.

Sponsor's own description

The purpose of this study is to compare the efficacy and safety of switching treatment-resistant depression (TRD) participants from a prior antidepressant treatment (to which they have not responded) to either intranasal esketamine plus a new oral antidepressant or switching to a new oral antidepressant plus intranasal placebo.

Publications & conference data

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

1. Efficacy and Safety of Fixed-Dose Esketamine Nasal Spray Combined With a New Oral Antidepressant in Treatment-Resistant Depression: Results of a Randomized, Double-Blind, Active-Controlled Study (TRANSFORM-1).
   Fedgchin M, Trivedi M, Daly EJ, Melkote R, et al · · 2019 · cited 308× · PMID 31290965 · DOI 10.1093/ijnp/pyz039
2. Convergent Mechanisms Underlying Rapid Antidepressant Action.
   Zanos P, Thompson SM, Duman RS, Zarate CA, et al · · 2018 · cited 133× · PMID 29516301 · DOI 10.1007/s40263-018-0492-x
3. A new generation of antidepressants: an update on the pharmaceutical pipeline for novel and rapid-acting therapeutics in mood disorders based on glutamate/GABA neurotransmitter systems.
   Wilkinson ST, Sanacora G. · · 2019 · cited 111× · PMID 30447328 · DOI 10.1016/j.drudis.2018.11.007
4. Glutamatergic Neurotransmission: Pathway to Developing Novel Rapid-Acting Antidepressant Treatments.
   Kadriu B, Musazzi L, Henter ID, Graves M, et al · · 2019 · cited 110× · PMID 30445512 · DOI 10.1093/ijnp/pyy094
5. Ketamine for treatment-resistant depression: recent developments and clinical applications.
   Schwartz J, Murrough JW, Iosifescu DV. · · 2016 · cited 85× · PMID 27053196 · DOI 10.1136/eb-2016-102355
6. Long-term safety and maintenance of response with esketamine nasal spray in participants with treatment-resistant depression: interim results of the SUSTAIN-3 study.
   Zaki N, Chen LN, Lane R, Doherty T, et al · · 2023 · cited 83× · PMID 37173512 · DOI 10.1038/s41386-023-01577-5
7. Clinically meaningful changes on depressive symptom measures and patient-reported outcomes in patients with treatment-resistant depression.
   Turkoz I, Alphs L, Singh J, Jamieson C, et al · · 2021 · cited 60× · PMID 33249552 · DOI 10.1111/acps.13260
8. Ketamine and other glutamate receptor modulators for depression in adults with unipolar major depressive disorder.
   Dean RL, Hurducas C, Hawton K, Spyridi S, et al · · 2021 · cited 52× · PMID 34510411 · DOI 10.1002/14651858.cd011612.pub3