The primary objective is to determine the efficacy, safety, and tolerability of venlafaxine extended release (ER) capsules in the treatment of outpatients with panic disorder (PD) in comparison to those of placebo.

Condition	Treatment or Intervention	Phase
Panic Disorder	Drug: Venlafaxine ER	Phase III

Ages Eligible for Study:  18 Years and above,  Genders Eligible for Study:  Both

Criteria

Inclusion Criteria:

• A male or female outpatient.
• Must be at least 18 years of age.
• Meet DSM-IV criteria for PD (with or without agoraphobia) for at least 3 months before study day 1.
• Have sufficient symptoms to require anxiolytic drug therapy.
• Have a score of greater than or equal to 4 on the Clinical Global Impressions Scale (CGI) severity of illness item at screening and baseline.
• Have a minimum of 8 full-symptom panic attacks during the 4 weeks before the screening visit.
• Have a minimum of 4 full-symptom panic attacks during the 14 +/- 3 day placebo lead-in period between the screening and baseline (study day -1) visits.
• Provide a signed and a dated written informed consent.
• Have a Covi Anxiety Scale total score greater than the Raskin Depression Scale total score at screening and baseline.
• Women of childbearing potential must have a negative serum pregnancy test at screening. The signed informed consent should reflect an awareness of the stipulations concerning the use of contraception. A woman of childbearing potential is defined as one who is biologically capable of becoming pregnant. This includes women who are using contraceptives or whose sexual partners are either sterile or using contraceptives. Sexually active women participating in the study must use a medically acceptable form of contraception. Medically acceptable forms of contraception include oral contraceptives, injectable or implantable methods, intrauterine devices, or properly used barrier contraception. Additionally, the use of condoms is suggested as an adjunct to the methods previously addressed to protect against sexually transmitted diseases and to provide additional protection against accidental pregnancy.

Exclusion Criteria:

• Treatment with venlafaxine (IR or ER) or paroxetine within 6 months of study day 1.
• Known hypersensitivity to venlafaxine (IR or ER), related compounds, or paroxetine.
• History or presence of any clinically important hepatic, renal, or other medical disease that might compromise the study or be detrimental to the patient (eg, clinically important cardiac arrhythmia, unstable diabetes, carcinoma [except basal cell epithelioma], uncontrolled hypertension).
• Clinically important abnormality on screening physical examination, vital signs, electrocardiogram (ECG), laboratory tests or urine drug screen.
• Pregnancy, lactation, plans to become pregnant during the study.
• Oral contraceptives that have been taken for less than 3 months before study day 1 if not using another medically accepted form of birth control.
• Use of any herbal products intended to treat anxiety, insomnia, or depression within 14 days of study day 1.
• Myocardial infarction within 6 months of study day 1.
• History or presence of a mental disorder due to a general medical condition.
• History or presence of seizure disorder or a known history of more than one childhood febrile seizure.
• History or presence of clinically important head trauma.
• History or presence of any psychotic illness, bipolar affective disorder, or organic brain disease.
• DSM-IV diagnosis of major depressive disorder, or generalized anxiety disorder (GAD) that is considered by the investigator as being primary, causing a higher degree of distress of impairment than PD. Patients with a diagnosis of secondary major depression or GAD may be eligible provided other exclusionary requirements are not met.
• Any other clinically significant Axis I or Axis II disorder current or predominant within 6 months of study day 1 other than PD (with or without agoraphobia).
• Screening or baseline Hamilton Depression Rating Scale (HAM-D) score greater than or equal to 18.
• Screening or baseline HAM-D item 1 (depressed mood) score > 2.
• History of drug or alcohol dependence or abuse as defined in DSM-IV within 1 year of study day 1.
• Regular use of alcohol (more than 750 mL of beer/day or the equivalent).
• Acutely suicidal to such a degree that precautions against suicide must be employed.
• Screening urine drug screen positive for a drug of abuse.
• A screening or baseline Raskin Depression Scale score greater than 3 on any single item or a Raskin total score >9.
• Investigational drugs, investigational procedures, antipsychotics, fluoxetine, warfarin, sumatriptan, naratriptan, zolmitriptan or drugs with a similar mechanism of action indicated for the treatment of migraine within 30 days of study day 1.
• Regular use (defined as 4 or more days a week) of benzodiazepines within 14 days of the screening visit.
• Antidepressants (other than fluoxetine), monoamine oxidase inhibitors, nonbenzodiazepine anxiolytics within 14 days of study day 1.
• Psychopharmacologic drugs (including anxiolytics, other antidepressants, lithium, stimulants, and sedative hypnotics other than zaleplon or zolpidem) within 14 days of study day 1.
• Theophylline, cimetidine, propafenone, flecainide, encainide within 7 days of study day 1.
• Nonpsychopharmacologic drugs with psychotropic effects taken within 7 days of study day 1, unless taken at a stable dose for at least 3 months before study day 1.
• Cognitive behavioral therapy within 30 days of study day 1.
• Introduction or change in intensity of formal psychotherapy (regularly scheduled sessions employing specific techniques) within 60 days of study day 1.
• Electroconvulsive therapy (ECT) within 6 months of study day 1.
• Known history or presence of raised intraocular pressure or narrow angle glaucoma.

Study ID Numbers:  0600B5-399-AC
Record last reviewed:  January 2005
Last Updated:  January 25, 2005
Record first received:  September 4, 2002
ClinicalTrials.gov Identifier:  NCT00044772
Health Authority: United States: Food and Drug Administration
ClinicalTrials.gov processed this record on 2005-04-08