Adjunctive Lanicemine (AZD6765) in Patients with Major Depressive Disorder and History of Inadequate Response to Antidepressants: A Randomized, Placebo-Controlled Study.
The objective of this study was to investigate the efficacy and safety of adjunctive lanicemine (NMDA channel blocker) in the treatment of major depressive disorder (MDD) over 12 weeks. This phase IIb, randomized, parallel-arm, double-blind, placebo-controlled study was conducted at 49 centers in four countries between December 2011 and August 2013 in 302 patients aged 18-70 years, meeting criteria for single episode or recurrent MDD and with a history of inadequate treatment response. Patients were required to be taking an allowed antidepressant for at least four weeks prior to screening. Patients were randomized equally to receive 15 double-blind intravenous infusions of adjunctive lanicemine 50 mg, lanicemine 100 mg, or saline over a 12-week course, in addition to ongoing antidepressant. The primary efficacy end point was change in Montgomery-Åsberg Depression Rating Scale (MADRS) total score from baseline to week 6. Secondary efficacy outcome variables included change in MADRS score from baseline to week 12, response and remission rates, and changes in Clinical Global Impression scale, Quick Inventory of Depressive Symptomology Self-Report score, and Sheehan Disability Scale score. Of 302 randomized patients, 240 (79.5%) completed treatment. Although lanicemine was generally well tolerated, neither dose was superior to placebo in reducing depressive symptoms on the primary end point or any secondary measures. There was no significant difference between lanicemine and placebo treatment on any outcome measures related to MDD. Post hoc analyses were performed to explore the possible effects of trial design and patient characteristics in accounting for the contrasting results with a previously reported trial.
Yale University School of Medicine, New Haven, CT, USA.
Gerard
G
Sanacora
Sarkis Clinical Trials, Gainesville, FL, USA.
Michael R
MR
Johnson
Northwest Clinical Research Center, Bellevue, WA, USA and Department of Psychiatry, Duke University School of Medicine, Durham, NC, USA.
Arif
A
Khan
Finger Lakes Clinical Research, Rochester, NY, USA.
Sarah D
SD
Atkinson
Atlanta Center for Medical Research, Atlanta, GA, USA.
Robert R
RR
Riesenberg
Welgemoed Medical Centre, Cape Town, South Africa.
Juan P
JP
Schronen
iResearch Atlanta, Decatur, GA, USA.
Michael A
MA
Burke
Rush University Medical Center, Chicago, IL, USA.
John M
JM
Zajecka
Universidad de Antofagasta, Antofagasta, Chile.
Luis
L
Barra
AstraZeneca Pharmaceuticals LP, Wilmington, DE, and Cambridge, MA, USA.
Hong-Lin
HL
Su
AstraZeneca Pharmaceuticals LP, Wilmington, DE, and Cambridge, MA, USA.
Joel A
JA
Posener
AstraZeneca Pharmaceuticals LP, Wilmington, DE, and Cambridge, MA, USA.
Khanh H
KH
Bui
AstraZeneca Pharmaceuticals LP, Wilmington, DE, and Cambridge, MA, USA.
Michael C
MC
Quirk
AstraZeneca Pharmaceuticals LP, Wilmington, DE, and Cambridge, MA, USA.
Timothy M
TM
Piser
Baylor College of Medicine, Houston and Michael E. Debakey VA Medical Center, Houston, TX, USA.
Sanjay J
SJ
Mathew
AstraZeneca Pharmaceuticals LP, Wilmington, DE, and Cambridge, MA, USA.
Sanjeev
S
Pathak
D000328:Adult; D000928:Antidepressive Agents / Q000008:administration & dosage / Q000494:pharmacology*; D003865:Major Depressive Disorder / Q000188:drug therapy*; D061218:Depressive Disorder, Treatment-Resistant / Q000188:drug therapy*; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D017063:Outcome Assessment, Health Care; D010627:Phenethylamines / Q000008:administration & dosage / Q000494:pharmacology*; D011725:Pyridines / Q000008:administration & dosage / Q000494:pharmacology*
C585977:AZD6765; D000928:Antidepressive Agents; D010627:Phenethylamines; D011725:Pyridines
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