| 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 assess the efficacy of PD 0332334 in the treatment of GAD as measured by the change from Baseline in the HAM-A total score at Week 8.
• To assess the safety and tolerability of PD 0332334 in subjects with GAD. |
|
| E.2.2 | Secondary objectives of the trial |
• To assess the effects of PD 0332334 on disability associated with GAD.
• To assess the time course of action of PD 0332334 on the symptoms of GAD over the 8-week double-blind treatment period.
• To assess the effect of PD 0332334 on the somatic and psychic symptoms of GAD.
• To assess the effect of PD 0332334 on the patient reported symptom of GAD.
• To assess the Week 1 sustained response with PD 0332334 in the treatment of GAD.
• To assess the effects of PD 0332334 on sleep problems and depressive symptoms in subjects with GAD.
• To assess the efficacy of PD 0332334 in the treatment of GAD as assessed by
clinical and patient global impressions.
• To assess the effect of PD 0332334 on sexual functioning, quality of life enjoyment and satisfaction in subjects with GAD.
• To assess the effects associated with discontinuation of PD 0332334 following
short-term use in subjects with GAD.
• To compare the efficacy of PD 0332334 to paroxetine and paroxetine to placebo. |
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
1. Diagnosis of GAD (Diagnostic and Statistical Manual-IV [DSM-IV], 300.02) as established by the clinician (psychiatrist or licensed clinical psychologist) who has interviewed the subject using all sources of data including the Mini International Neuropsychiatric Interview (MINI) for DSM-IV Axis I disorders and other clinical information. Subjects with specific phobia(s) (as defined in DSM-IV) or dysthymic disorder will be allowed in the study.
2. Subjects must have a HAM-A total score not less than 20 at the screening (V1) and randomization (V2) visits. Subjects must also have a Covi Anxiety Scale score of not less than 9 and a Raskin Depression Scale score not less than 7 at the Screening (V1) visit to ensure predominance of anxiety symptoms over depression symptoms.
3. Otherwise healthy men or non-pregnant, non-lactating women (women must be using a hormonal or barrier method of contraception or be postmenopausal or surgically sterilized). Healthy is defined as no other clinically relevant abnormalities identified by a detailed medical history, full physical examination including sitting blood pressure (BP) and heart rate measurement, 12-lead ECG, and clinical laboratory tests.
4. Age 18 to 65 years, inclusive.
5. All women must have negative pregnancy tests at the Screening (V1) and Randomization (V2) visits.
6. Evidence of a personally signed and dated informed consent document indicating that the subject 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. Subjects with evidence or history of clinically significant medical disorders or drug allergies.
2. Any of the following current (within the past 6 mos - present) DSM-IV Axis I diagnoses: MDD; OCD; Panic disorder; Agoraphobia; PTSD; Anorexia; Bulimia; Caffeine-induced anxiety disorder; Alcohol or substance abuse or dependence unless in full remission for at least 6 months; Social anxiety disorder.
3. Any of the following past or current DSM-IV Axis I diagnoses: Schizophrenia; Psychotic disorder; Delirium; dementia; amnestic/other clinically significant cognitive disorders; Bipolar or schizoaffective disorder; Cyclothymic disorder; Dissociative disorders.
4. Antisocial or borderline personality disorder.
5. Serious suicidal risk per investigator’s judgment.
6. Current use of psychotropic medications that cannot be discontinued 2 weeks prior to randomization. Fluoxetine is prohibited within 5 weeks of randomization. If psychotropics are inadvertently administered during the 2 weeks prior to randomization, the investigator and medical monitor will assess subject’s continued eligibility.
7. Use of drugs, supplements, prescription or nonprescription, or food with psychoactive properties. If the products are inadvertently used during the 2 weeks prior to randomization, the investigator and medical monitor will assess subject’s continued eligibility. If subjects experience significant intolerable anxiety during the final week of the study, the medical monitor may authorize (after discussion with investigator) minimal anxiolytic (e.g. benzodiazepine) medication use.
8. Subjects who have been treated with MAO inhibitors in the 14 days prior to the baseline visit.
9. Regular use of benzodiazepines during the 3 months prior to Screening (for at least 5 out of 7 days per week).
10. Subjects initiating formal psychotherapy (e.g. psychodynamic, cognitive and interpersonal therapy) within 3 month prior to screening who intend to continue formal psychotherapy during the study.
11. Positive drug tests at Screening (V1) or Randomization (V2) visits for: amphetamines, barbiturates, opiates, benzodiazepines, sedatives and hypnotics, cocaine, phencyclidine (PCP), cannabinoids, or other illegal or illicit drugs. An exception to the exclusion for a positive benzodiazepine, opiate, or sedative and hypnotic drug test at the Screening (V1) visit may be granted by the Pfizer medical monitor if written evidence of a valid, current prescription is presented.
12. Any condition possibly affecting drug absorption (eg, gastrectomy).
13. Subjects with a current seizure disorder.
14. Subjects with a history of life-threatening neoplasms within 5 years prior to study entry, other than carcinoma in situ of the cervix or basal cell carcinoma of the skin.
15. Subjects with hypo- or hyperthyroidism, except euthyroid subjects who have been on stable doses of thyroid replacement for 6 months or more.
16. Subjects with any clinically unstable hematological, autoimmune, endocrine, neurological, renal, hepatic, retinal, gastrointestinal, or cardiovascular disorder.
17. Subjects with uncontrolled narrow angle glaucoma.
18. Subjects with a known hypersensitivity to paroxetine
19. History of allergy or intolerance to paroxetine.
20. Subjects with a prior history of insufficient response to an adequate trial of paroxetine in treating GAD.
21. Pregnant or nursing females; females of childbearing potential who are unwilling or unable to use an acceptable method of contraception for the duration of the study.
22. Treatment with an investigational drug within 60 days preceding the first dose of trial medication.
23. Estimated creatinine clearance (CLcr) <55 mL/min (using Cockcroft-Gault equation).
24. Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) levels >3 times the upper limit of normal at Screening (V1).
25. Male and Female subjects with a screening 12-lead ECG demonstrating QTcF (Fredericia’s correction) >450 msec, if confirmed with an unscheduled repeat 12-lead ECG’s at the screen visit. If QTcF values are discrepant (ie, >450 msec and <450 msec) after repeat unscheduled 12-lead ECG at screen, eligibility will be discussed and decided on a case by case basis by the investigator and medical monitor.
26. History of allergy, intolerance to or lack of efficacy for GAD treatment with other α2δ drugs (e.g. pregabalin, gabapentin).
27. Blood donation of approximately 1 pint (500 mL) or more within 56 days prior to dosing.
28. Other severe acute or chronic medical or psychiatric condition or laboratory abnormality that may increase the risk associated with trial participation or investigational product administration or may interfere with the interpretation of trial results and, in the judgment of the investigator, would make the subject inappropriate.
|
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
| Change from Baseline in HAM-A total score at Week 8. |
|
| 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 | No |
| 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 | No |
| E.7.1.2 | Bioequivalence study | No |
| E.7.1.3 | Other | No |
| E.7.1.3.1 | Other trial type description | |
| E.7.2 | Therapeutic exploratory (Phase II) | No |
| E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
| E.7.4 | Therapeutic use (Phase IV) | No |
| 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 | 2 |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 16 |
| 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 | 1 |
| E.8.9.1 | In the Member State concerned months | 3 |
| E.8.9.1 | In the Member State concerned days | 0 |
| 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 | 3 |
| E.8.9.2 | In all countries concerned by the trial days | 0 |
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