POC Study in Partially Responsive Generalized Anxiety Disorder

An 8-week, Randomized, Phase 2, Double-blind, Sequential Parallel-group Comparison Study Of Two Dose Levels Of Pf 06372865 Compared To Placebo As An Adjunctive Treatment In Outpatients With Inadequate Response To Standard Of Care For Generalized Anxiety Disorder

This study aims to evaluate whether PF-06372865 is safe and effective in the treatment of sub-optimally controlled symptoms of generalized anxiety disorder during two 4-week treatment periods using a Sequential Parallel Comparison Design (SPCD). The study will use the Hamilton Anxiety Rating Scale (HAM-A) to measure change in symptoms from baseline for two doses of PF-06372865 compared to placebo.

Study Overview

• Status: Terminated
• Conditions: Generalized Anxiety Disorder
• Intervention / Treatment: Drug: PF-06372865.

• Study Type: Interventional
• Enrollment (Actual): 90
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • California
    • Cerritos, California, United States, 90703
      • Comprehensive Clinical Development, Inc.
    • Encino, California, United States, 91316
      • Pharmacology Research Institute
    • Imperial, California, United States, 92251
      • Sun Valley Research Center
    • Oceanside, California, United States, 92056
      • Excell Research, Inc.
    • Orange, California, United States, 92868
      • NRC Research Institute
    • San Diego, California, United States, 92103
      • Artemis Institute for Clinical Research
    • San Diego, California, United States, 92102
      • California Neuorpsychopharmacology Clinical Research Institute, LLC (CNRI-San Diego, LLC)
    • Upland, California, United States, 91786
      • Pacific Clinical Research Medical Group
  • Connecticut
    • Hartford, Connecticut, United States, 06102
      • Hartford Hospital
    • Hartford, Connecticut, United States, 06106
      • Institute of Living
  • Florida
    • DeLand, Florida, United States, 32720
      • Avail Clinical Research, LLC
    • Fort Meyers, Florida, United States, 33912
      • Gulfcoast Clinical Center
    • Gainesville, Florida, United States, 32607
      • Sarkis Clinical Trials
    • Hialeah, Florida, United States, 33016
      • Berma Research Group
    • Jacksonville, Florida, United States, 32256
      • Clinical Neuroscience Solutions, Inc.
    • Lake City, Florida, United States, 32025
      • Sarkis Clinical Trials
    • Orange City, Florida, United States, 32763
      • Medical Research Group of Central Florida
    • Orlando, Florida, United States, 32801
      • Clinical Neuroscience Solutions, Inc.
    • Tampa, Florida, United States, 33613
      • Stedman Clinical Trials
  • Georgia
    • Alpharetta, Georgia, United States, 30005
      • Institute for Advanced Medical Research
    • Atlanta, Georgia, United States, 30331
      • Atlanta Center for Medical Research
    • Roswell, Georgia, United States, 30076
      • Northwest Behavioral Research Center
  • Illinois
    • Chicago, Illinois, United States, 60640
      • Great Lakes Clinical Trials
  • Kansas
    • Prairie Village, Kansas, United States, 66206
      • Phoenix Medica Research, Inc
  • Maryland
    • Baltimore, Maryland, United States, 21208
      • Pharmasite Research Inc
  • Massachusetts
    • Brockton, Massachusetts, United States, 02301
      • Beacon Clinical Research, LLC
    • Methuen, Massachusetts, United States, 01844
      • ActivMed Practices & Research, Inc
    • Natick, Massachusetts, United States, 07160
      • BCCR Trials
  • Nebraska
    • Lincoln, Nebraska, United States, 68526
      • Premier Psychiatric Research Institute. LLC.
  • New Jersey
    • Cherry Hill, New Jersey, United States, 08002
      • Center for Emotional Fitness
    • Toms River, New Jersey, United States, 08755
      • Bio Behavioral Health
  • New York
    • Brooklyn, New York, United States, 11235
      • SPRI Clinical Trials LLC
    • Cedarhurst, New York, United States, 11516
      • Neurobehavioral Research, Inc.
    • Jamaica, New York, United States, 11432
      • Comprehensive Clinical Development, Inc.
    • Mount Kisco, New York, United States, 10549
      • Bioscience Research LLC
    • New York, New York, United States, 10168
      • Fieve Clinical Research, Inc
  • Ohio
    • Cincinnati, Ohio, United States, 45227
      • CTI Clinical Research Center
    • Cincinnati, Ohio, United States, 45215
      • Patient Priority Clinical Sites, LLC
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73116
      • Cutting Edge Research Group
  • Oregon
    • Portland, Oregon, United States, 97210
      • Summit Research Network (Oregon) Inc.
  • Pennsylvania
    • Media, Pennsylvania, United States, 19063
      • Suburban Research Associates
  • Tennessee
    • Memphis, Tennessee, United States, 38119
      • Clinical Neuroscience Solutions, Inc.
  • Texas
    • Dallas, Texas, United States, 75231
      • FutureSearch Trials of Dallas
    • DeSoto, Texas, United States, 75115
      • InSite Clinical Research, LLC
    • The Woodlands, Texas, United States, 77381
      • Family Psychiatry of The Woodlands
  • Washington
    • Bellevue, Washington, United States, 98007
      • Northwest Clinical Research Center
    • Seattle, Washington, United States, 98104
      • Summit Research Network (Seattle) Llc

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 63 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion criteria:

1. Outpatient males and females 18 65 years of age (inclusive).
2. Diagnostic and Statistical Manual of Mental Disorders Fourth edition Text Revised (DSM IV TR) diagnosis of GAD (DSM IV TR, 300.02), confirmed as primary diagnosis by the Mini international neuropsychiatric interview (MINI) structured interview.
3. All subjects must have a total HAM A (via SIGH A) score 22 at screening. In addition, scores at the baseline visit must also be within 20% of scores at screening.
4. Subjects must also have a Covi Anxiety Scale score of 9 and a Raskin Depression Scale score 7 at the Screening (Visit 1) visit to ensure predominance of anxiety symptoms over depression symptoms.
5. Taking an FDA approved GAD treatment (escitalopram 10 to 20 mg total daily dose, paroxetine 20 to 50 mg total daily dose, duloxetine 60 to 120 mg total daily dose, or venlafaxine 75 to 225 mg total daily dose) at a stable FDA approved dosage for at least the two consecutive months in the current episode immediately prior to the screening visit. Sertraline or citalopram are also permitted as background treatment for GAD at doses of 50 to 200 mg total daily dose and 20 to 40 mg total daily dose, respectively.

Exclusion criteria:

1. Subjects with a history of daily benzodiazepine use within one month of the screening visit.
2. Recent (defined as meeting disorder diagnostic criteria during the last 6 months) of a DSM IV TR Axis I diagnosis other than generalized anxiety disorder, with the following exceptions: a. Subjects with recent (in the last 2 months) major depressive disorder may be enrolled if the anxiety symptoms are predominant over the depressive symptoms, as judged by the Covi/Raskin criteria listed above and confirmed GAD as the primary diagnosis by the MINI structured interview. b. Comorbid social phobia and/or specific phobias are permitted as long as the anxiety symptoms due to these disorders are clinically less significant than the anxiety symptoms due to GAD and GAD is confirmed as the primary diagnosis by the MINI structured interview.
3. Recent (defined as meeting disorder diagnostic criteria during the last 6 months) of a DSM IV TR Axis I of panic disorder with or without agoraphobia, Post Traumatic Stress Disorder (PTSD), dissociative disorder, obsessive compulsive disorder, attention deficit disorder. If a subject has a past misdiagnosis of any of these disorders, or if the subject has another psychiatric disorder that in the opinion of the investigator affects the suitability of a subject for this study based on safety or other considerations, the investigator will need to contact the sponsor prior to screening.
4. Past and/or current DSM IV TR diagnosis of schizophrenia, schizoaffective disorder, other psychotic disorders, bipolar disorders (I or II), factitious disorder or cognitive disorder (including delirium, dementia, and amnestic disorder).
5. Presence of comorbid personality disorders (Axis II) based on DSM IV TR.
6. Subjects who meet DSM IV TR defined diagnostic criteria for psychoactive substance dependence (excluding nicotine dependence) within 12 months of screening or DSM IV TR defined substance abuse within 3 months prior to screening.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

5

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: PF 06372865 2.5 mg BID then placebo.; PF 06372865 2.5 mg tablet 2 times daily for 4 weeks (Stage 1), followed by placebo 2 times daily for 4 weeks (Stage 2).	Drug: PF-06372865.; Blinded PF 06372865 and matching placebo will be provided as tablets for oral administration.
Experimental: PF 06372865 7.5 mg BID then placebo.; PF 06372865 2.5 mg tablet 2 times daily for one week, then PF 06372865 7.5 mg tablet 2 times daily for 3 weeks (Stage 1), followed by placebo (2 times daily) for 4 weeks (Stage 2).	Drug: PF-06372865.; Blinded PF 06372865 and matching placebo will be provided as tablets for oral administration.
Experimental: Placebo then PF 06372865 2.5 mg BID.; Placebo 2 times daily for 4 weeks (Stage 1), followed by PF 06372865 2.5 mg tablet 2 times daily for 4 weeks	Drug: PF-06372865.; Blinded PF 06372865 and matching placebo will be provided as tablets for oral administration.
Experimental: Placebo then PF 06372865 7.5 mg BID.; Placebo 2 times daily for 4 weeks (Stage 1), followed by PF 06372865 2.5 mg tablet 2 times daily for one week, then PF 06372865 7.5 mg tablet 2 times daily for 3 weeks (Stage 2).	Drug: PF-06372865.; Blinded PF 06372865 and matching placebo will be provided as tablets for oral administration.
Placebo Comparator: Placebo followed by placebo.; Placebo 2 times daily for 4 weeks (Stage 1) followed by Placebo 2 times daily for 4 weeks (Stage 2).	Drug: PF-06372865.; Blinded PF 06372865 and matching placebo will be provided as tablets for oral administration.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Hamilton Anxiety Rating Scale (HAM-A) Total Scores at Baseline: Stage 1 and 2	The HAM-A scale was a clinician rated interview scale designed to measure the signs and symptoms of anxiety. It had 14-items to rate the intensity of psychic and somatic anxiety on a 5-point severity scale. Each item ranging from 0 (not present) to 4 (very severe) were summed up to give a total possible score of 0 (not present) to 56 (very severe), where lower scores indicates less anxiety.	Stage 1: Baseline (Day 1 ), Stage 2: Baseline (Day 28)
Change From Baseline in Hamilton Anxiety Rating Scale (HAM-A) Total Scores at Week 4: Stage 1	The HAM-A scale was a clinician rated interview scale designed to measure the signs and symptoms of anxiety. It had 14-items to rate the intensity of psychic and somatic anxiety on a 5-point severity scale. Each item ranging from 0 (not present) to 4 (very severe) were summed up to give a total possible score of 0 (not present) to 56 (very severe), where lower scores indicates less anxiety.	Week 4
Hamilton Anxiety Rating Scale (HAM-A) Total Scores at Week 4 During Stage 1 and at Week 8 During Stage 2	The HAM-A scale was a clinician rated interview scale designed to measure the signs and symptoms of anxiety. It had 14-items to rate the intensity of psychic and somatic anxiety on a 5-point severity scale. Each item ranging from 0 (not present) to 4 (very severe) were summed up to give a total possible score of 0 (not present) to 56 (very severe), where lower scores indicates less anxiety.	Stage 1: Week 4, Stage 2: Week 8

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in Hamilton Anxiety Rating Scale (HAM-A) Total Scores at Week 5, Week 6, Week 7 and Week 8: Stage 2	The HAM-A scale was a clinician rated interview scale designed to measure the signs and symptoms of anxiety. It had 14-items to rate the intensity of psychic and somatic anxiety on a 5-point severity scale. Each item ranging from 0 (not present) to 4 (very severe) were summed up to give a total possible score of 0 (not present) to 56 (very severe), where lower scores indicates less anxiety.	Week 5, 6, 7, 8
Sheehan Disability Scale (SDS) Total Score and Social, Work, Family Subscale Scores at Baseline: Stage 1 and Stage 2	SDS was a copyrighted, three question instrument designed to assess functional impairment associated with mental disorders in three domains: work impairment, social impairment, and impairment of family life or home responsibilities. Disability scores were reported for each of the questions (subscale scores range from 0 to 10) and a total disability score was calculated as the sum of scores for each question (total scores range from 0 to 30). Higher scores reflect greater impairment.	Stage 1: Baseline (Day 1 ), Stage 2: Baseline (Day 28)
Change From Baseline in Sheehan Disability Scale (SDS) Total Score and Social, Work, Family Subscale Scores: Stage 1 and Stage 2	SDS was a copyrighted, three question instrument designed to assess functional impairment associated with mental disorders in three domains: work impairment, social impairment, and impairment of family life or home responsibilities. Disability scores were reported for each of the questions (subscale scores range from 0 to 10) and a total disability score was calculated as the sum of scores for each question (total scores range from 0 to 30). Higher scores reflect greater impairment.	Stage 1: Week 4, Stage 2: Week 8
Change From Baseline in Hamilton Anxiety Rating Scale (HAM-A) Total Scores at Week 1, Week 2 and Week 3: Stage 1	The HAM-A scale was a clinician rated interview scale designed to measure the signs and symptoms of anxiety. It had 14-items to rate the intensity of psychic and somatic anxiety on a 5-point severity scale. Each item ranging from 0 (not present) to 4 (very severe) were summed up to give a total possible score of 0 (not present) to 56 (very severe), where lower scores indicates less anxiety.	Week 1, 2, 3
Percentage of Responders of Total Hamilton Anxiety Rating Scale (HAM-A): Stage 1 and Stage 2	A responder was defined as a participant with >= to 50 percent decrease in their total HAM-A score from baseline to the last week in the stage (Week 4 in Stage 1, Week 8 in Stage 2). The HAM-A scale was a clinician rated interview scale designed to measure the signs and symptoms of anxiety. It had 14-items to rate the intensity of psychic and somatic anxiety on a 5-point severity scale. Each item ranging from 0 (not present) to 4 (very severe) were summed up to give a total possible score of 0 (not present) to 56 (very severe), where lower scores indicates less anxiety. Percentage of responders of total HMA scale were reported.	Stage 1: Week 4, Stage 2: Week 8
Change From Baseline in Clinical Global Impression - Improvement (CGI-I) Scale Score at Week 1, 2, 3, 4 in Stage 1 and Week 5, 6, 7, 8 in Stage 2	CGI-I was a 7-point clinician rated scale ranging from 1 (very much improved) to 7 (very much worse). Improvement was defined as a score of 1 (very much improved), 2 (much improved), or 3 (minimally improved), 4 (no change), 5 (minimally worse), 6 (much worse) or 7 (very much worse) on the scale. Higher score indicated more affected. Change is equal to score at observation minus score at baseline.	Stage 1 (S1): Baseline (Day 1), Week 1 (W1), 2 (W2), 3 (W3), 4 (W4) and Stage 2 (S2): Baseline (Day 28), Week 5 (W5), 6 (W6), 7 (W7), 8 (W8)
Change From Baseline in Clinical Global Impression -Severity (CGI-S) Scale Score at Week 1, 2, 3, 4 in Stage 1 and Week 5, 6, 7, 8 in Stage 2	The CGI-S consisted of a single 7-point rating score of illness severity, was completed by a clinician. Raters selected one response based on the following question, "Considering your total clinical experience with that particular population, how mentally ill was your participant at that time?" Scores were: 1 (normal, not ill at all), 2 (borderline mentally ill), 3 (mildly ill), 4 (moderately ill), 5 (markedly ill) 6 (severely ill) or 7 (among the most severely ill participants). Higher scores indicate more severity.	Stage 1 (S1): Baseline (Day 1), Week 1 (W1), 2 (W2), 3 (W3), 4 (W4) and Stage 2 (S2): Baseline (Day 28), Week 5 (W5), 6 (W6), 7 (W7), 8 (W8)
Plasma Concentration Versus Time Summary of PF-06372865: Stage 1	Concentration versus time summary was calculated by setting concentration values below the lower limit of quantification (LLOQ =0.0100 nanogram per milliliter (ng/mL) to zero. Summary statistics were not to be presented if number of observations above lower limit of quantification (NALQ) = 0.	Pre-dose (0 hour), 2, 4, 10 hours post dose on Day 1 of Week 2, 3, 4
Plasma Concentration Versus Time Summary of PF-06372865: Stage 2	Concentration versus time summary was calculated by setting concentration values below the lower limit of quantification (LLOQ =0.0100 ng/mL) to zero. Summary statistics were not to be presented if number of observations above lower limit of quantification (NALQ) =0.	Pre-dose (0 hour), 2, 4, 10 hours post dose on Day 1 of Week 6, 7, 8
Change From Baseline in the Hamilton Anxiety Rating Scale (HAM-A): Psychic Subscale Score at Week 1, 2, 3, 4, 5, 6, 7, 8	The HAM-A scale was a clinician interview-administered scale designed to measure the signs and symptoms of anxiety. It had 14-items to rate the intensity of psychic and somatic anxiety on a 5-point severity scale. Psychic subscale of the HAM-A was the sum of 7 items. Each item ranging from 0 (not present) to 4 (very severe) were summed up to give a total possible score of 0 (not present) to 28 (very severe), where lower scores indicates less anxiety.	Stage 1 (S1): Baseline (Day 1), Week 1 (W1), 2 (W2), 3 (W3), 4 (W4) and Stage 2 (S2): Baseline (Day 28), Week 5 (W5), 6 (W6), 7 (W7), 8 (W8)
Change From Baseline in the Hamilton Anxiety Rating Scale (HAM-A): Somatic Subscale Score at Week 1, 2, 3, 4, 5, 6, 7, 8	The HAM-A scale was a clinician interview-administered scale designed to measure the signs and symptoms of anxiety. It had 14-items to rate the intensity of psychic and somatic anxiety on a 5-point severity scale. Somatic subscale of the HAM-A was the sum of 7 items. Each item ranging from 0 (not present) to 4 (very severe) were summed up to give a total possible score of 0 (not present) to 28 (very severe), where lower scores indicates less anxiety.	Stage 1 (S1): Baseline (Day 1), Week 1 (W1), 2 (W2), 3 (W3), 4 (W4) and Stage 2 (S2): Baseline (Day 28), Week 5 (W5), 6 (W6), 7 (W7), 8 (W8)
Percentage of Participants With Remission of Total Hamilton Anxiety Rating Scale (HAM-A) Scores	Percentage of participants with HAM-A total score less than or equal to 7 in the last week of the Stage (Week 4 in Stage 1, Week 8 in Stage 2). The HAM-A scale was a clinician rated interview scale designed to measure the signs and symptoms of anxiety. It had 14-items to rate the intensity of psychic and somatic anxiety on a 5-point severity scale. Each item ranging from 0 (not present) to 4 (very severe) were summed up to give a total possible score of 0 (not present) to 56 (very severe), where lower scores indicates less anxiety.	Stage 1: Week 1 up to Week 4 and Stage 2: Week 5 up to Week 8

Collaborators and Investigators

• Sponsor: Pfizer

Publications and helpful links

General Publications

• Targum SD, Murphy C, Khan J, Zumpano L, Whitlock M, Simen AA, Binneman B. Audio Recording for Independent Confirmation of Clinical Assessments in Generalized Anxiety Disorder. Innov Clin Neurosci. 2018 Apr 1;15(3-4):37-42.

Helpful Links

• To obtain contact information for a study center near you, click here.

Study record dates

Study Major Dates

• Study Start: November 1, 2014
• Primary Completion (Actual): October 1, 2015
• Study Completion (Actual): October 1, 2015

Study Registration Dates

• First Submitted: October 24, 2014
• First Submitted That Met QC Criteria: December 3, 2014
• First Posted (Estimate): December 8, 2014

Study Record Updates

• Last Update Posted (Estimate): January 9, 2017
• Last Update Submitted That Met QC Criteria: November 16, 2016
• Last Verified: September 1, 2016

More Information

Terms related to this study

• Keywords: safety; efficacy; outpatient; generalized anxiety disorder; PF 06372865; suboptimal response
• Additional Relevant MeSH Terms: Mental Disorders; Pathologic Processes; Disease; Anxiety Disorders; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; GABA Modulators; GABA Agents; PF-06372865
• Other Study ID Numbers: B7431007