| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| Generalised Anxiety Disorder |
|
| MedDRA Classification |
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 9.1 |
| E.1.2 | Level | LLT |
| E.1.2 | Classification code | 10018105 |
| E.1.2 | Term | Generalized anxiety disorder |
|
| E.1.3 | Condition being studied is a rare disease | No |
| E.2 Objective of the trial |
| E.2.1 | Main objective of the trial |
| To evaluate the efficacy of pregabalin in maintaining the benzodiazepine-free state in subjects with prior stable alprazolam use |
|
| E.2.2 | Secondary objectives of the trial |
| 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 |
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal 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 β-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. |
|
| E.4 | Principal 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 in any other studies involving investigational or marketed products, concomitantly or within 3 months prior to study entry. |
|
| E.5 End points |
| E.5.1 | 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). |
|
| E.6 and E.7 Scope of the trial |
| E.6 | Scope of the trial |
| E.6.1 | Diagnosis | Information not present in EudraCT |
| E.6.2 | Prophylaxis | Information not present in EudraCT |
| E.6.3 | Therapy | Information not present in EudraCT |
| E.6.4 | Safety | Information not present in EudraCT |
| E.6.5 | Efficacy | Yes |
| E.6.6 | Pharmacokinetic | Information not present in EudraCT |
| E.6.7 | Pharmacodynamic | Information not present in EudraCT |
| E.6.8 | Bioequivalence | Information not present in EudraCT |
| E.6.9 | Dose response | Information not present in EudraCT |
| E.6.10 | Pharmacogenetic | Information not present in EudraCT |
| E.6.11 | Pharmacogenomic | Information not present in EudraCT |
| E.6.12 | Pharmacoeconomic | Information not present in EudraCT |
| E.6.13 | Others | Information not present in EudraCT |
| E.7 | Trial type and phase |
| E.7.1 | Human pharmacology (Phase I) | Information not present in EudraCT |
| E.7.1.1 | First administration to humans | Information not present in EudraCT |
| E.7.1.2 | Bioequivalence study | Information not present in EudraCT |
| E.7.1.3 | Other | Information not present in EudraCT |
| E.7.1.3.1 | Other trial type description | |
| E.7.2 | Therapeutic exploratory (Phase II) | Information not present in EudraCT |
| E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
| E.7.4 | Therapeutic use (Phase IV) | Information not present in EudraCT |
| E.8 Design of the trial |
| E.8.1 | Controlled | Yes |
| E.8.1.1 | Randomised | Yes |
| E.8.1.2 | Open | No |
| E.8.1.3 | Single blind | No |
| E.8.1.4 | Double blind | Yes |
| E.8.1.5 | Parallel group | No |
| E.8.1.6 | Cross over | No |
| E.8.1.7 | Other | No |
| E.8.2 | Comparator of controlled trial |
| E.8.2.1 | Other medicinal product(s) | No |
| E.8.2.2 | Placebo | Yes |
| E.8.2.3 | Other | Yes |
| E.8.2.3.1 | Comparator description |
| Alprazolam is the previous and concomitant drug the subjects will take and switch from |
|
| E.8.3 |
The trial involves single site in the Member State concerned
| No |
| E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
| E.8.4.1 | Number of sites anticipated in Member State concerned | 5 |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 15 |
| E.8.6 Trial involving sites outside the EEA |
| E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
| E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
| E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
|
| E.8.7 | Trial has a data monitoring committee | No |
| E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
| |
| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | |
| E.8.9.1 | In the Member State concerned months | 4 |
| E.8.9.1 | In the Member State concerned days | |
| E.8.9.2 | In all countries concerned by the trial years | 1 |
| E.8.9.2 | In all countries concerned by the trial months | 5 |
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