Definium’s DT120 ODT significantly reduced anxiety symptoms in Phase 3 Voyage, meeting primary and key secondary endpoints in generalized anxiety disorder.
Written By: Meghana Jinka, PharmD
Reviewed By: Pharmacally Editorial Team
Definium Therapeutics’ investigational DT120 orally disintegrating tablet (ODT), a 100µg formulation of lysergide, significantly reduced anxiety symptoms versus placebo in adults with generalized anxiety disorder (GAD) in the Phase 3 Voyage trial (NCT06741228). The drug, which holds FDA Breakthrough Therapy Designation for GAD, produced a 5.4-point placebo-adjusted reduction in Hamilton Anxiety Rating Scale (HAM-A) score at Week 12, with an effect size of 0.81.
DT120 is a proprietary ODT formulation of lysergide using Catalent’s Zydis fast-dissolve technology. Lysergide is a classic serotonergic psychedelic that acts as a partial agonist at the serotonin 5-HT2A receptor, although the mechanism underlying its potential therapeutic effects in psychiatric disorders remains incompletely understood.
Voyage Demonstrates Sustained Anxiety Reduction
Voyage was a randomized, double-blind, placebo-controlled Phase 3 study involving 214 adults with DSM-5-confirmed GAD across approximately 35 U.S. sites. Participants presented with moderate-to-severe GAD at study entry, with a mean baseline HAM-A score of approximately 28 points. Participants received a single 100 µg dose of DT120 ODT or placebo during the 12-week double-blind Part A, which is followed by a 40-week open-label extension (Part B) to evaluate long-term safety and potential re-dosing needs.
The primary endpoint was the change in HAM-A total score from baseline to Week 12. Participants receiving DT120 had an LS mean reduction of 11.6 points, compared with 6.2 points with placebo, producing a placebo-adjusted difference of 5.4 points (p<0.0001; Cohen’s d=0.81).
Treatment effects emerged rapidly. HAM-A improvement was evident by Day 2 and remained significant across all post-baseline assessments in Part A.
All three multiplicity-controlled key secondary endpoints also reached statistical significance. At Week 12, the Clinical Global Impression-Severity (CGI-S) score improved by 1.0 point with DT120 versus 0.4 points with placebo, a difference of 0.6 points (p<0.0001). At Week 1, HAM-A scores improved by 11.9 versus 4.2 points, respectively, while CGI-S improved by 1.0 versus 0.2 points at Day 2. Both comparisons had p<0.0001.
Response and Remission Outcomes
Additional analyses supported the primary findings. At Week 12, 43% of DT120-treated participants achieved at least a 50% reduction in HAM-A score compared with 16% receiving placebo (p<0.0001).
HAM-A remission, defined as a score of 7 or lower, occurred in 14% of participants receiving DT120 versus 4% with placebo (p=0.0222). A HAM-A score below 16, indicating mild or better symptoms, was reached by 51% and 23% of participants, respectively (p<0.0001).
Safety Profile and Dosing Experience
DT120 ODT was generally well tolerated. Treatment-emergent adverse events were predominantly mild to moderate, transient, and occurred on the day of dosing. The study identified no new safety signals, including no signal for suicidality or suicidal behavior.
Participants underwent hourly assessments beginning five hours after dosing using a structured end-of-session checklist. The average time to meet the criteria was 6.4 hours, with a median of 6.1 hours. By eight hours, 92% of participants had met the criteria.
Next Phase 3 GAD Readout Expected in September
Voyage is the first of two pivotal Phase 3 studies evaluating DT120 in GAD. The second study, Panorama (NCT06809595), includes 100 µg, 50 µg, and placebo arms and is expected to report topline results in September. Its primary endpoint is the change in HAM-A score from baseline to Week 12 for the 100 µg DT120 versus placebo comparison.
DT120 is also being evaluated in major depressive disorder and posttraumatic stress disorder. The latest results follow Definium’s positive Phase 3 Emerge readout in MDD reported in June.
If Panorama confirms the Voyage findings, the combined Phase 3 dataset could provide an important basis for the continued regulatory development of DT120 as a potential single-dose treatment for GAD, a disorder in which patients often require long-term pharmacologic therapy.
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About the Writer
Meghana Jinka (LinkedIn) is a Pharm.D graduate with a strong interest in clinical pharmacy, clinical research, pharmacovigilance, and medical writing. She has developed expertise in evaluating scientific literature, interpreting clinical data, and communicating complex medical information in a clear and accessible manner. Through clinical training, patient counseling, and healthcare awareness activities, she has gained practical experience in evidence-based medicine and patient-centered care. Passionate about healthcare communication, Meghana is committed to developing accurate, engaging, and evidence-based healthcare documents that support healthcare professionals and the wider community.