A MULTICENTER, RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED STUDY OF PREGABALIN IN SUBJECTS WITH GENERALIZED ANXIETY DISORDER (GAD) SWITCHING FROM BENZODIAZEPINE THERAPY - Not applicable

• Register: EUCTR
• Last refreshed on: 12 June 2012
• Main ID: EUCTR2006-001347-66-CZ
• Date of registration: 23/10/2007
• Prospective Registration: Yes
• Primary sponsor: Pfizer Inc., 235 East 42nd Street, New York, NY 10017
• Public title: A MULTICENTER, RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED STUDY OF PREGABALIN IN SUBJECTS WITH GENERALIZED ANXIETY DISORDER (GAD) SWITCHING FROM BENZODIAZEPINE THERAPY - Not applicable
• Scientific title: A MULTICENTER, RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED STUDY OF PREGABALIN IN SUBJECTS WITH GENERALIZED ANXIETY DISORDER (GAD) SWITCHING FROM BENZODIAZEPINE THERAPY - Not applicable
• Date of first enrolment: 19/12/2007
• Target sample size: 120
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2006-001347-66
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: no Single blind: no Double blind: yes Parallel group: no Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: no Placebo: yes Other: yes Other specify the comparator: Alprazolam is the previous and concomitant drug the subjects will take and switch from

Countries of recruitment

Czech Republic, Italy, Spain

Key inclusion & exclusion criteria

Inclusion criteria:
1. Written informed consent must be obtained from all subjects prior to study entry. At the screening visit the investigator will be responsible for obtaining witnessed (if applicable), written informed consent and documenting this in the source documents. A copy of the signed and dated informed consent form should be provided to the subject.
2. Age range: 18-65 years.
3. Both men and women are eligible for the study. Women of childbearing potential or <2 years post-menopausal must be practicing an approved method of contraception (e.g. IUD, oral contraceptive for a least one cycle, implant or double barrier method) and have a negative serum ß-HCG pregnancy test at screening. Women who are breastfeeding are excluded from study participation. Complete abstinence may be considered acceptable, but must first be discussed on a case-by-case basis with the Pfizer monitor prior to any screening tests or procedures for the study.
4. A primary lifetime diagnosis of DSM-IV-TRTM (2000) GAD. GAD will be diagnosed with the MINI International Neuropsychiatric Interview (M.I.N.I) Version 5.0.028. The more detailed Module P GAD from the M.I.N.I. Plus (Version 5.0.0) 11 will be used to assess the GAD diagnosis specifically. Subjects can sub-threshold for current GAD diagnosis.
5. Stable use of a benzodiazepine. The subject must be currently taking a benzodiazepine as prescribed by a licensed physician for at least 8 weeks prior to the screening visit, and not more than 52 weeks prior to the screening visit.
6. Screening laboratory values must be within normal limits and within sponsor’s guidelines, or if abnormal, considered and documented as not clinically significant by the investigator. Liver function tests>2 times the upper limit or normal are considered significant.
Are the trial subjects under 18?
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years)
F.1.3.1 Number of subjects for this age range

Exclusion criteria:
1. Pregnant or lactating women.
2. Hamilton Depression Rating Scale (HAM-D) – 17 Item total score =15
3. History of non-response to alprazolam, other benzodiazepines, gabapentine or pregabalin given for the treatment of anxiety as indicated by a [screening or baseline] HAM-A total score > 18
4. Subjects at screening requiring a total daily dose of alprazolam lower than 1 mg or higher than 4mg (or similar therapeutic equivalent dose of another benzodiazepine).
5. A current DSM-IV-TMTM (2000) diagnosis of major depressive disorder, dysthymia, social phobia, post-traumatic stress disorder, body dysmorphic disorder or eating disorder at screening or with the past 6 months.
6. A current or past DSM-IV diagnosis of schizophrenia, psychotic disorder, bipolar affective disorder or obsessive-compulsive disorder.
7. Meet DSM-IV criteria for any substance dependence in the past 5 years or abuse in past 12 months excluding nicotine dependence.
8. Receiving psychotherapy (e.g. cognitive therapy, cognitive-behavioral therapy, supportive therapy or others) in which the specific focus of the therapy is generalized anxiety disorder (GAD) and its symptoms or another anxiety disorder. Subjects who are contemplating beginning a course of psychotherapy and/or behavioral therapy during the course of the study.
9. A history of seizure disorder, except febrile seizures of childhood.
10. A history of neuropathic pain
11. A history of narrow angle glaucoma
12. Use of fluoxetine within 5 weeks prior to the screening visit.
13. Use of psychotropic (including antiepileptic) medication other than benzodiazepines within 2 weeks prior to the screening visit.
14. Positive urine drug screen at the screening visit for the following substances or classes of drugs: amphetamines, barbiturates, ethanol, narcotics, non-benzodiazepine sedatives and hypnotics, cocaine, phencyclidine (PCP), cannabinoids, or other illegal or illicit drugs.
15. Mental condition, including mental retardation, rendering the individual unable to understand the nature, scope, and possible consequences of the study and/or evidence of any uncooperative attitude.
16. Considered by the Investigator to be at risk for suicide or aggressive behavior.
17. Any serious or uncontrolled medical illness, in the opinion of the investigator, will render the subject unsuitable for the study.
18. Any significant, serious, unstable hematological, autoimmune, endocrine, cardiovascular, renal, hepatic, gastrointestinal, or neurological disorder that in the opinion of the Investigator will render the subject unsuitable for the study.
19. Creatinine clearance =60 ml/min estimated from serum creatinine, body weight, age and sex using the Cockroft-Gault equation. Subjects who have an estimated creatinine clearance of less than 60 ml/min by this screening method may, at the investigator’s discretion, have their creatinine clearance measured with a 24-hour urine collection, performed at the central laboratory. If this 24-hour urine creatinine clearance is greater than 60 ml/min, the subject may be eligible for the study.
20. Received or have received electroconvulsive therapy within six (6) months prior to study entry.
21. In the judgment of the investigator, the subject is unable to follow the protocol, or otherwise might not be suitable for the study.
22. Known sensitivity to pregabalin, other drugs structurally related to the neurotransmitter GABA, alprazolam or other benzodiazepines.
23. Participation i

Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Generalised Anxiety Disorder
MedDRA version: 9.1 Level: LLT Classification code 10018105 Term: Generalized anxiety disorder

Intervention(s)

Trade Name: Lyrica
Product Name: Pregabalin
Product Code: PD0144723 (CI-1008)
Pharmaceutical Form: Capsule*
INN or Proposed INN: Pregabalin
CAS Number: 148553-50-8
Current Sponsor code: Lyrica
Other descriptive name: (s)-3-(aminomethyl)-5-methylhexanoic acid
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 75-
Pharmaceutical form of the placebo: Capsule*
Route of administration of the placebo: Oral use

Trade Name: Lyrica
Product Name: Pregabalin
Product Code: PD0144723 (CI-1008)
Pharmaceutical Form: Capsule*
INN or Proposed INN: Pregabalin
CAS Number: 148553-50-8
Current Sponsor code: Lyrica
Other descriptive name: (s)-3-(aminomethyl)-5-methylhexanoic acid
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 150-
Pharmaceutical form of the placebo: Capsule*
Route of administration of the placebo: Oral use

Trade Name: Lyrica
Product Name: Pregabalin
Product Code: PD0144723 (CI-1008)
Pharmaceutical Form: Capsule*
INN or Proposed INN: Pregabalin
CAS Number: 148553-50-8
Current Sponsor code: Lyrica
Other descriptive name: (s)-3-(aminomethyl)-5-methylhexanoic acid
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 225-
Pharmaceutical form of the placebo: Capsule*
Route of administration of the placebo: Oral use

Trade Name: Lyrica
Product Name: Pregabalin
Product Code: PD0144723 (CI-1008)
Pharmaceutical Form: Capsule*
INN or Proposed INN: Pregabalin
CAS Number: 148553-50-8
Current Sponsor code: Lyrica
Other descriptive name: (s)-3-(aminomethyl)-5-methylhexanoic acid
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 300-
Pharmaceutical form of the placebo: Capsule*
Route of administration of the placebo: Oral use

Trade Name: Alprazolam
Product Name: Alprazolam
Pharmaceutical Form: Tablet
INN or Proposed INN: Alprazolam
CAS Number: 28981-97-7
Other descriptive name: 8-Chloro-1-methyl-6-phenyl-4H-1,2,4-triazole (4,3-a)(1-4)benzodiazepine
C

Primary Outcome(s)

Secondary Objective: To obtain additional data on the efficacy of pregabalin in reducing the severity of symptoms of GAD, rebound anxiety, benzodiazepine withdrawal, and titration regimen in comparison to placebo after switching from a stable therapeutics dose of alprazolam to treatment with pregabalin or placebo

Main Objective: To evaluate the efficacy of pregabalin in maintaining the benzodiazepine-free state in subjects with prior stable alprazolam use

Primary end point(s): The primary endpoint of this study is the proportion of subjects who are free of benzodiazepine and other psychoactive drugs during the six weeks of the Alprazolam-Free Phase of Double-Blind Treatment.
Being free of bezodiazepine and/or other psychoactive drugs is defined as:
Negative urine benzodiazepine/pzychoactive toxicology assay (done at each visit of the Alprazolam-Free Phase of Double-Blind Treatment) and negative serum benzodiazepine/alcohol assay (done at endpoint).

Secondary ID(s)

2006-001347-66-ES

not applicable

A0081092