Table 3.
Effect of V1B receptor antagonists in clinical trials (depression)
| Compound | Trial | Dose regimen | Patients | Primary endpoint | Results | ClinicalTrial.gov identifier | Reference |
|---|---|---|---|---|---|---|---|
| SSR149415 | Randomized, double-blinded, placebo-controlled study (DFI5878) | SSR149415 (100 mg, 250 mg) or placebo, BID for 8 wk (active control: escitalopram, 10 mg QD) | MDD patients SSR149415 100 mg (n = 80) SSR149415 250 mg (n = 79) placebo n = 75 escitalopram n = 84 | Changes from baseline HDRS total score at wk 8 | • SSR149415 (250 but not 100 mg) had significantly greater reductions in HDRS changes from baseline compared with placebo, while escitalopram had nonsignificant reduction in HDRS • Similar trends of greater improvements in SSR149415 observed in secondary endpoints (CGI-S, MADRS), while these effects did not reach statistical significance |
NCT00358631 | Griebel et al., 2012 |
| Randomized, double-blinded, placebo-controlled study (DFI5879) | SSR149415 (100 mg, 250 mg) or placebo, BID for 8 wk (active control: paroxetine, 20 mg QD) | MDD patients SSR149415 100 mg (n = 82) SSR149415 250 mg (n = 81) placebo n = 77 escitalopram n = 80 |
Changes from baseline HDRS total score at wk 8 | • Differences between placebo and each SSR149415 dose on HDRS score not statistically significant, while paroxetine significantly reduced HDRS score • No statistical difference between placebo and each SSR149414 dose on secondary endpoints (CGI-S, MADRS). |
NCT00361491 | ||
| Randomized, double-blinded, placebo-controlled study (PDY5467) | SSR149415 (100 mg, 250 mg) or placebo, BID for 4 wk | MDD patients SSR149415 100 mg (n = 25) SSR149415 250 mg (n = 24) placebo n = 24 | Plasma cortisol concentration response to CRF administration before and after 27 d dosing | • Differences between placebo and each SSR149415 dose on primary endpoint not statistically significant • SSR149415 group showed greater mean improvements from baseline HDRS score and CGI-S than placebo group, although differences not statistically significant |
NCT01606384 | ||
| ABT-436 | Randomized, double-blinded, placebo-controlled study | ABT-436 (800 mg) or placebo, QD for 7 d | MDD patients ABT-436 800 mg (n = 31) placebo n = 20 | Basal HPA parameters at d 7 | • Basal HPA parameters (urine total glucocorticoids, plasma ACTH, urine/serum/ saliva cortisol, etc.) lower in ABT-436 group than in placebo group • Dynamic HPA parameters (plasma ACTH and serum cortisol response to CRF) lower in ABT- 436 group than in placebo group • ABT-436 had favorable symptom responses on 2 of 5 MASQ subscale compared with placebo but no differences on HDRS score |
NCT01380704 | Katz et al., 2017 |
| TS-121 | Randomized, double-blinded, placebo-controlled study | TS-121 (10 mg, 50 mg) or placebo, QD for 6 wk (adjunctive treatment) | MDD patients with inadequate response to current antidepressant treatment TS-121 10 mg (n = 16) TS-121 50 mg (n = 17) placebo n = 18 | Changes from baseline MADRS score at wk 6 | • TS-121 had greater reductions in MADRS change from baseline compared with placebo but changes not statistically significant • Similar trends of non-significantly greater improvements in TS-121 observed in secondary endpoints (CGI-S, HAM-A, SDQ, etc.), but effects not statistically significant • Higher baseline urinary and hair cortisol associated with greater separation between TS-121 and placebo in MADRS score |
NCT03093025 | Kamiya et al., 2020 |
Abbreviations: ACTH, adrenocorticotropic hormone; CGI-S, Clinical Global Impressions-Severity of Illness Score; CRF, corticotropin-releasing factor; HAM-A, Hamilton Anxiety Rating Scale; HDRS, Hamilton Depression Rating Scale; HPA, hypothalamus-pituitary-adrenal; MADRS, Montgomery-Åsberg Depression Rating Scale; MASQ, Mood and Anxiety Symptom Questionnaire; MDD, major depressive disorder; SDQ, Symptoms of Depression Questionnaire.