| 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 (as measured by the change from baseline at Week 8 in the Sheehan Disability total score) associated with GAD.
• To assess the time course of action of PD 0332334 on the symptoms of GAD (as measured by the change from baseline HAM-A) over the 8-week double-blind treatment period.
• To assess the effect of PD 0332334 on the somatic symptoms of GAD.
• To assess the effect of PD 0332334 on the 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 (based on the HAM-A total score) with PD 0332334 in the treatment of GAD.
• To assess the effects of PD 0332334 on sleep problems in subjects with GAD.
• To assess the effect of PD 0332334 on 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. |
|
| 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 ≥20 at the screening (V1) and randomization (V2) visits. Subjects must also have a Covi Anxiety Scale score of ≥9 and a Raskin Depression Scale score ≤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 hematological, renal, endocrine, pulmonary, gastrointestinal, cardiovascular, hepatic, pancreatic, neurologic, active infections, immunological, or allergic disease ( including drug allergies but not seasonal allergies)
2. Any of the following current DSM-IV Axis I diagnoses:
Major depressive disorder; Obsessive compulsive disorder; Panic disorder; Agoraphobia; Posttraumatic stress disorder; 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, and other clinically significant cognitive disorders; Bipolar or schizoaffective disorder; Cyclothymic disorder; Dissociative disorders
4. Antisocial or borderline personality disorder
5. Serious suicidal risk per the clinical investigator’s judgment ( MINI)
6. Current use of psychotropic medications that cannot be discontinued 2 weeks prior to randomization. Fluoxetine is prohibited within 5 weeks of randomization. In the event of inadvertent administration of psychotropic medications during the 2 weeks prior to randomization, continued eligibility will be assessed on a case by case basis by the investigator and the medical monitor
7. Use of drugs, supplements, prescription or nonprescription, or food that have psychoactive properties. In the event of inadvertent use of such products during the 2 weeks prior to randomization, continued eligibility will be assessed on a case by case basis by the investigator and the medical monitor
8. Subjects who have been treated with monoamine oxidase inhibitors in the 14 days prior to the baseline visit
9. Regular use of benzodiazepines during the 3 months prior to Screening
10. Subjects initiating formal psychotherapy within 3 month prior to screening who intend to continue formal psychotherapy during the study. This includes psychodynamic, cognitive, and interpersonal therapies
11. Positive drug tests at Screening or Randomization visits for any of the following substances or classes of compounds: amphetamines, barbiturates, opiates, benzodiazepines, sedatives and hypnotics, cocaine, phencyclidine, 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 or Randomisation visits 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
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 hypothyroidism or hyperthyroidism, except subjects who are euthyroid and 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 paroxetine in the treatment of generalized anxiety disorder
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 <55 mL/min (using Cockcroft-Gault equation).
24. Alanine aminotransferase or aspartate aminotransferase levels >3 times the upper limit of normal at Screening
25.Male and Female subjects with a screening 12 lead ECG demonstrating QTcF >450 msec, if confirmed with an unscheduled repeat 12 lead ECG’s at the screen visit. In the event of discrepant QTcF values after repeat unscheduled 12 lead ECG at screen, a decision with regards protocol eligibility will be made on a case by case basis between the investigator and medical monitor.
26.History of lack of efficacy for treatment of GAD with, or allergy or intolerance to, other α2δ drugs
27.Blood donation of approximately 1 pint 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 for entry into this trial.
|
|
| 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 | Information not present in EudraCT |
| E.6.2 | Prophylaxis | Information not present in EudraCT |
| E.6.3 | Therapy | Yes |
| E.6.4 | Safety | Yes |
| 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 | Yes |
| E.6.12 | Pharmacoeconomic | Information not present in EudraCT |
| E.6.13 | Others | Yes |
| E.6.13.1 | Other scope of the trial description |
|
| 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 | 5 |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 42 |
| 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 | 16 |
| E.8.9.1 | In the Member State concerned days | |
| E.8.9.2 | In all countries concerned by the trial months | 20 |
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