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An 8-Week, Randomized, Phase 2, Double-Blind, Sequential Parallel-Group Comparison Study of Two Dose Levels of the GABAA Positive Allosteric Modulator PF-06372865 Compared With Placebo as an Adjunctive Treatment in Outpatients With Inadequate Response to Standard of Care for Generalized Anxiety Disorder

Simen, Arthur, MD, PhD*; Whitlock, Mark, PhD; Qiu, Ruolun, PhD; Miceli, Jeff, PhD; Zumpano, Laura, BS; Du Metz, Michaele, BS; Dua, Pinky, PhD; Binneman, Brendon, MBChB, MRCPsych‡[LATIN CROSS]

Journal of Clinical Psychopharmacology: January/February 2019 - Volume 39 - Issue 1 - p 20–27
doi: 10.1097/JCP.0000000000000997
Original Contributions

Background Generalized anxiety disorder (GAD) is a common psychiatric disorder, but many patients experience only partial relief of symptoms with existing therapies. Benzodiazepines are effective in many cases but are limited by a number of significant adverse effects. PF-06372865 is a subtype-selective gamma-aminobutyric acid A (GABAA)–positive allosteric modulator lacking in functional activity at alpha 1–containing receptors that are believed to mediate many of these adverse effects.

Methods PF-06372865 was evaluated as an adjunct to current GAD treatment in a double-blind, placebo-controlled, sequential parallel comparison study in patients with GAD who showed an incomplete response to current standard-of-care pharmacotherapy. A total of 90 subjects (of the planned 384) were randomized into the study before the decision to terminate the study. Two doses of PF-06372865 (2.5 mg twice daily and 7.5 mg twice daily) were compared with placebo.

Results Neither dose of PF-06372865 differentiated from placebo on week 4 Hamilton Anxiety Inventory total (primary end point) or on the Sheehan Disability Scale total score (secondary end point). Adverse events including dizziness, headache, and somnolence were observed, and the 7.5 mg dose demonstrated some impairment on the Digit Symbol Substitution test and the Epworth Sleepiness Scale relative to placebo and the 2.5 mg dose.

Conclusions Factors contributing to the negative results include the limited sample size and failure to explore a broader range of doses.

From *Takeda Pharmaceuticals, Cambridge, MA;

Pfizer Inc, Cambridge, UK; and

Pfizer Incorporated, Cambridge, MA.

Received October 1, 2017; accepted after revision November 7, 2018.

Reprints: Arthur Simen, MD, PhD, Takeda International, 350 Massachusetts Avenue, Cambridge, MA 02139 (e-mail: Arthur.simen@takeda.com).

This study was funded by Pfizer Incorporated.

[LATIN CROSS]Coauthor Dr Brendon Binneman is deceased.

Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.