| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| GENERALIZED ANXIETY DISORDER (GAD) |
|
| 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 characterize the safety and efficacy of pregabalin in subjects with GAD at low and high doses relative to placebo and lorazepam following 3 and 6 months of treatment. |
|
| E.2.2 | Secondary objectives of the trial |
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
1. Men and women age 18 to 65 years. Women of childbearing potential must use a reliable method of birth control during the study period.
2. Primary DSM IV diagnosis of GAD (DSM IV, 300.02)8 as established by a psychiatrist or licensed clinical psychologist and confirmed by the Mini-International Neuropsychiatric Interview (MINI) structured interview.
3. HAM A total score ≥18 and item #1 on the HAM D with a depressed mood score ≤2 at both the Screening (Visit 1) and Baseline (Visit 2) visits to ensure predominance of anxiety symptoms over depression.
4. Subjects who require pharmacologic treatment for GAD.
5. Able to understand and cooperate with study procedures and to give informed consent.
6. Evidence of a personally signed and dated informed consent document indicating that the subject (or a legally acceptable representative) has been informed of all pertinent aspects of the study.
7. Subjects who are willing and able to comply with scheduled visits, treatment plan, laboratory tests, and other study procedures. |
|
| E.4 | Principal exclusion criteria |
1. Current or past diagnosis of any other DSM IV Axis I disorders (including current premenstrual dysphoric disorder) with the following exceptions:
• Current or past depression not otherwise specified, specific phobia, or somatization disorder; and
• Past history of major depressive disorder, social phobia, panic disorder, or of an eating disorder.
2. Current or past DSM IV substance (except for nicotine and caffeine) abuse or dependence.
3. Presence of comorbid borderline and antisocial personality disorders, based on DSM IV criteria per the investigator’s clinical judgment.
4. Suicide risk per criteria described in the Section 7.5.5 of the protocol and by history
within past 2 years, self-report, or clinically judged to be at serious suicidal or
homicidal risk.
5. Stopping or initiating psychotherapy for GAD during the study. Subjects with psychotherapy of stable intensity for at least 6 weeks or more are allowed to enter the study.
6. Daily use of benzodiazepines for treating GAD (≥ 5 days/week) during the 4 weeks prior to screening. Occasional use of benzodiazepine for insomnia (e.g. 2 or 3 times per month) is allowed but not within 2 weeks of baseline.
7. Current use of psychotropic medications that can not be discontinued 2 weeks prior to baseline (5 weeks for fluoxetine).
8. A history of failed treatment with benzodiazepine as determined by the clinical judgment of the investigator and taking into account adequacy of dose and the duration of treatment.
9. Known sensitivity to lorazepam or other benzodiazepines.
10. Prior exposure to pregabalin.
11. A positive urine drug screen at screening for any of the following substances or classes of compounds: amphetamines, barbiturates, benzodiazepines, narcotics, sedatives and hypnotics, cocaine, phencyclidine, cannabinoids, or other illegal or illicit drugs. An exception to the exclusion for a positive benzodiazepine drug test at the Screening (V1) may be granted by the Pfizer medical monitor if written evidence of a valid, current prescription is presented.
12. A positive breathalyzer test at screening.
13. Any clinically significant, serious, or unstable hematologic, autoimmune, endocrine, cardiovascular, renal, hepatic, gastrointestinal, or neurological disorder, including, but not limited to:
• Any current seizure disorder.
• Uncorrected hypothyroidism or hyperthyroidism. Subjects must be on stable thyroid replacement therapy for hypothyroidism for at least 6 weeks prior to screening and thyroid hormones (FT4 and TSH) must be within normal range at Screening.
• History of life-threatening neoplasm treated within the last 5 years, other than carcinoma in situ of the cervix or basal cell carcinoma of the skin.
• History of migraine headaches occurring more than once a month for the past year other than those associated with menstruation.
• Narrow angle glaucoma.
14. Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) levels >3 times the upper limit of normal.
15. Platelet count <100,000/mm3.
16. Serum sodium >150 or <130 mEq/L.
17. Creatinine clearance (CLcr) <60 mL/min (estimated by Cockroft-Gault method).
18. Clinically significant electrocardiogram (ECG) abnormalities.
19. Pregnancy or lactation.
20. Participation in an experimental drug study within the last 30 days.
21. Other severe acute or chronic medical or psychiatric condition or laboratory abnormality that may increase the risk associated with study participation or investigational product administration or may interfere with the interpretation of study results and, in the judgment of the investigator or sponsor, would make the subject inappropriate for entry into this study.
|
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
Efficacy Endpoints
• Hamilton Anxiety Rating Scale (HAM A total): A 14 question rating scale that assesses anxiety symptoms which will be measured at baseline (prior to treatment) and at 3 and 6 months post treatment.
• Clinical Global Impressions Severity and Improvement (CGI S and CGI I) will be collected at the same time points as the HAM A.
Safety Endpoints
• Adverse events from spontaneous reports will be monitored throughout the trial. Adverse events will be summarized by treatment group following 3 and 6 months of GAD treatment.
• Drug Discontinuation and Rebound Anxiety:
• Physicians Withdrawal Checklist (PWC): A questionnaire to collect information to determine whether subjects experience discontinuation symptoms after cessation of study medication.
• Rebound Anxiety: The HAM A will be used to characterize rebound anxiety, defined as a rapid return of the subject’s original symptoms following drug discontinuation, that are worse compared to baseline.
• Discontinuation Emergent Signs and Symptoms (DESS) associated with drug discontinuation will be characterized at 3 and 6 months: DESS will be determined from spontaneously reported treatment emergent adverse events that either newly developed during the taper, or existed prior to but worsened during the tapering period.
|
|
| E.6 and E.7 Scope of the trial |
| E.6 | Scope of the trial |
| E.6.1 | Diagnosis | No |
| E.6.2 | Prophylaxis | No |
| E.6.3 | Therapy | Yes |
| E.6.4 | Safety | Yes |
| E.6.5 | Efficacy | Yes |
| E.6.6 | Pharmacokinetic | No |
| E.6.7 | Pharmacodynamic | No |
| E.6.8 | Bioequivalence | No |
| E.6.9 | Dose response | No |
| E.6.10 | Pharmacogenetic | No |
| E.6.11 | Pharmacogenomic | No |
| E.6.12 | Pharmacoeconomic | No |
| E.6.13 | Others | No |
| E.7 | Trial type and phase |
| E.7.1 | Human pharmacology (Phase I) | No |
| 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) | No |
| E.7.3 | Therapeutic confirmatory (Phase III) | No |
| E.7.4 | Therapeutic use (Phase IV) | Yes |
| 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 | Yes |
| 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) | Yes |
| E.8.2.2 | Placebo | Yes |
| E.8.2.3 | Other | No |
| 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 | 4 |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 80 |
| 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 | 3 |
| E.8.9.1 | In the Member State concerned months | 9 |
| E.8.9.1 | In the Member State concerned days | 0 |
| E.8.9.2 | In all countries concerned by the trial years | 3 |
| E.8.9.2 | In all countries concerned by the trial months | 9 |
| E.8.9.2 | In all countries concerned by the trial days | 0 |
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