Clinical trial NCT00725725: Org 25935 Versus Placebo as Augmentation to Cognitive-behavioral Therapy to Treat Panic Disorder (P05705)
Official title: A Multi-center, Double-blind, Fixed Dose Trial Examining the Efficacy and Safety of Org 25935 Versus Placebo as Augmentation to Cognitive Behavioral Therapy in Subjects With Panic Disorder
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Panic Disorder
Lead sponsor: Merck Sharp & Dohme LLC
Sponsor class: INDUSTRY
First posted: 2008-07-30
Enrollment: 46
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to evaluate the effectiveness of Org 25935 vs. placebo given in combination with cognitive-behavioral therapy (CBT) to reduce the symptoms of panic disorder. It is hypothesized that treatment with Org 25935 at a dose of 4 mg or 12 mg will differ significantly from placebo with respect to the Panic Disorder Severity Scale (PDSS) total score over 3 weeks of therapy.


Eligibility criteria: Inclusion Criteria:

* is a male, or a female who is not of childbearing potential or who is non-pregnant, non-lactating and using a medically accepted method of contraception.
* is between the ages of 18 and 65, inclusive;
* signed written informed consent after the scope and nature of the investigation have been explained to them before Screening evaluations;
* is fluent in English;
* is diagnosed at Screening with current panic disorder, with or without agoraphobia;
* has a Clinical Global Impressions (CGI)-Severity score at Screening of \>= 4 and \<= 6;
* is currently taking no psychotropic medications or is able and willing to discontinue these medications prior to the first CBT session. Anti-depressant and anxiolytic medications are acceptable only if they are stabilized for at least 8 weeks prior to Screening;
* is able to complete all scheduled assessment and treatment visits and is willing to comply with the requirements of the study protocol.

Exclusion Criteria:

* is diagnosed with a primary Axis I disorder other than panic disorder;
* has a Screening Montgomery-Asberg Depression Rating Scale (MADRS) score of \>= 35 (severe depression);
* has any history of bipolar disorder, psychotic disorder, or obsessive compulsive disorder;
* has a diagnosis of post traumatic stress disorder, eating disorder, or substance abuse or dependence (excluding nicotine) within the past six months;
* is known or suspected to have significant personality dysfunction that could, in the investigator's opinion, interfere with trial participation. Participants with known borderline or avoidant personality disorder are excluded;
* are at imminent risk of self-harm or harm to others, in the investigator's opinion based on clinical interview and responses provided on the Columbia Suicide Severity Rating Scale (C-SSRS). Participants must be excluded if they report suicidal ideation of Type 4 or 5 in the past 3 months or suicidal behavior in the past 12 months as measured by the C-SSRS at Screening;
* is currently a psychiatric inpatient or has been hospitalized for a psychiatric condition within the past year;
* has ever been diagnosed with organic brain syndrome, mental retardation, or other cognitive dysfunction that could interfere with their capacity to participate in CBT or to complete safety and efficacy assessments;
* has any history of head trauma causing ongoing cognitive impairment;
* has any history of seizures (apart from childhood febrile seizures);
* has an uncontrolled, unstable clinically significant medical condition (e.g., renal, endocrine, hepatic, respiratory, cardiovascular, hematologic, immunologic or cerebrovascular disease, or malignancy) that may interfere with the interpretation of safety and efficacy evaluations in the opinion of the investigator;
* has a clinically relevant visual disturbance, such as cataract, color blindness, macular degeneration, glaucoma, or retinal disease;
* has clinically significant abnormal laboratory, vital sign, physical examination, or electrocardiogram (ECG) findings at Screening that may interfere with the interpretation of safety or efficacy assessments in the opinion of the investigator;
* has a Corrected QT interval (QTc) value \>450 milliseconds at Screening using Bazett's QTc formula;
* for females, has a positive result on serum pregnancy test (at Screening), or plan to become pregnant during the course of the trial;
* has a positive urine drug or alcohol breath test at Screening, unless the positive finding can be accounted for by documented prescription use;
* is unable or unwilling to comply with the investigator's instructions regarding drug and alcohol use during the trial period;
* has a history of sensitivity/idiosyncrasy to glutamatergic drugs or chemically related compounds or excipients which may be employed in the trial or to any other unknown drug used in the past;
* are receiving concurrent psychotherapy for the treatment of panic disorder \[general supportive psychotherapy is acceptable if therapy was initiated at least 3 months prior to Screening\] or have received a prior adequate trial of CBT for panic disorder;
* has been exposed to an investigational drug within 6 months prior to Screening.

Primary outcomes:
measure: Change in Panic Disorder Severity Scale (PDSS) Score From Baseline to End-of-Treatment (EOT)
timeFrame: Screening and Day 36
Secondary outcomes:
measure: Change in PDSS Score From Baseline to Visit 4
timeFrame: Screening and Visit 4 (Day 22)
measure: Change in PDSS Score From Baseline to Follow-Up
timeFrame: Screening and Follow-Up (Day 59)
measure: Structured Clinical Interview for DSM-IV-TR Axis 1 Disorders, Patient Edition With Psychotic Screen (SCID-I/P With Psy Screen) Score at Screening
timeFrame: Screening
measure: SCID-I/P With Psy Screen Score at EOT
timeFrame: Day 36
measure: Change in Clinical Global Impression-Severity (CGI-S) Score
timeFrame: Screening and Day 36
measure: Change in Structured Interview Guide for the Hamilton Anxiety Scale (SIGH-A) Score
timeFrame: Screening and Day 36
measure: Change in Anxiety Sensitivity Index (ASI) Score
timeFrame: Screening and Day 36
measure: Change in Montgomery-Asberg Rating Scale for Depression (MADRS) Score
timeFrame: Screening and Day 36
measure: Change in Quality of Life Enjoyment and Satisfaction Questionnaire (Q-LES-Q) Score
timeFrame: Screening and Day 36
measure: Number of Participants Experiencing an Adverse Event (AE)
timeFrame: Up to 59 days
measure: Number of Participants Discontinuing Study Therapy Due to AEs
timeFrame: Up to 2 weeks
Other outcomes:
Locations:
Study officials:
affiliation: Merck Sharp & Dohme LLC
name: Medical Director
role: STUDY_DIRECTOR
References:
citation: Nations KR, Smits JA, Tolin DF, Rothbaum BO, Hofmann SG, Tart CD, Lee A, Schipper J, Sjogren M, Xue D, Szegedi A, Otto MW. Evaluation of the glycine transporter inhibitor Org 25935 as augmentation to cognitive-behavioral therapy for panic disorder: a multicenter, randomized, double-blind, placebo-controlled trial. J Clin Psychiatry. 2012 May;73(5):647-53. doi: 10.4088/JCP.11m07081. Epub 2012 Feb 21.