A double-blind, placebo-controlled study of a CCK-B receptor antagonist, CI-988, in patients with generalized anxiety disorder.
This multicenter, double-blind, placebo-controlled, parallel-group, randomized study assessed the efficacy, safety, and tolerability of a novel CCK-B antagonist CI-988 in the treatment of generalized anxiety disorder (GAD). Patients received placebo or CI-988 (300 mg/day, thrice daily) for 4 weeks. Patients with a primary diagnosis of GAD according to DSM-III-R criteria were randomized. The study design included a 1- to 2-week single-blind placebo baseline phase, followed by a 4-week double-blind treatment phase. Efficacy was measured weekly by Hamilton Rating Scale for Anxiety (HAM-A), Clinical Global Impressions of Severity and Change, UCLA-Multi Dimensional Anxiety Scale, and Hamilton Rating Scale for Depression. Patients were also evaluated to determine whether they met criteria for irritable bowel syndrome (IBS) at screening and were evaluated with a gastrointestinal visual analog scale at each visit. Eighty-eight patients were randomized to CI-988 (N = 45) and placebo (N = 43) at three centers. CI-988 did not demonstrate an anxiolytic effect superior to placebo in this clinical trial. There was no significant difference in mean change in HAM-A total between placebo (-7.73) and CI-988 (-8.64). However, a significant treatment-by-center interaction and a highly variable placebo response rate among the three centers limit the interpretation of the results. CI-988 did not have an effect on symptoms of IBS other than diarrhea, which worsened in patients with IBS. Other than a higher incidence of some gastrointestinal symptoms (diarrhea, dyspepsia, flatulence, and nausea), CI-988 was well tolerated. Results suggest that testing higher oral doses of CI-988 may be warranted.
Adams
J B
JB
Parke-Davis Pharmaceutical Research, Division of Warner-Lambert, Ann Arbor, Michigan 48105, USA.
Pyke
R E
RE
Costa
J
J
Cutler
N R
NR
Schweizer
E
E
Wilcox
C S
CS
Wisselink
P G
PG
Greiner
M
M
Pierce
M W
MW
Pande
A C
AC
D000328:Adult; D014151:Anti-Anxiety Agents / Q000009:adverse effects / Q000627:therapeutic use*; D001008:Anxiety Disorders / Q000188:drug therapy* / Q000503:physiopathology / Q000523:psychology; D003109:Colonic Diseases, Functional / Q000188:drug therapy / Q000503:physiopathology / Q000523:psychology; D003866:Depressive Disorder / Q000188:drug therapy / Q000503:physiopathology / Q000523:psychology; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D007211:Indoles / Q000009:adverse effects / Q000627:therapeutic use*; D008297:Male; D008536:Meglumine / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D016584:Panic Disorder / Q000188:drug therapy / Q000503:physiopathology / Q000523:psychology; D010555:Personality Inventory; D010698:Phobic Disorders / Q000188:drug therapy / Q000503:physiopathology / Q000523:psychology; D043887:Receptor, Cholecystokinin B; D011949:Receptors, Cholecystokinin / Q000037:antagonists & inhibitors* / Q000502:physiology; D013001:Somatoform Disorders / Q000188:drug therapy / Q000503:physiopathology / Q000523:psychology; D016896:Treatment Outcome
D014151:Anti-Anxiety Agents; D007211:Indoles; D043887:Receptor, Cholecystokinin B; D011949:Receptors, Cholecystokinin; C065599:PD 134308; D008536:Meglumine