| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| Social Anxiety Disorder (SocAD) |
|
| MedDRA Classification |
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 8.1 |
| E.1.2 | Level | LLT |
| E.1.2 | Classification code | 10041242 |
| E.1.2 | Term | Social 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 anxiolytic efficacy of two dose ranges of GW876008 compared to
placebo in outpatients with SocAD. |
|
| E.2.2 | Secondary objectives of the trial |
To evaluate the efficacy of two dose ranges of GW876008 compared to placebo in
outpatients with SocAD on the following:
• Anxiety symptoms
• Disability
• Sleep |
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
A subject will be eligible for inclusion in this study only if all of the following criteria
apply:
1. Male or female subject must be 18-64 years of age inclusive.
2. Subject must have the ability to comprehend the key components of the consent
form, and provide written informed consent.
3. The subject must have a primary diagnosis of Generalized Social Anxiety
Disorder/Social Phobia as defined in the Diagnostic and Statistical Manual of Mental
Disorders, 4th Edition, (DSM-IV, 300.23) diagnosed using psychiatric confirmation
of diagnosis in conjunction with the Mini International Neuropsychiatric Interview
(MINI), Clinician Rated Version 5.0.0., 2006.
NOTE: A diagnosis of Generalized Social Anxiety Disorder will be considered to
have been established if the subject reports/admits to four or more phobic situations
including at least two which are interactional situations.
4. Subject is required to have a LSAS score ≥ 60 at Screening and Randomization Visits
5. If female, the subject is eligible to enter and participate in this study if she is not
lactating and is of:
a. non-childbearing potential (i.e., physiologically incapable of becoming
pregnant, including any female who is pre-menarchal or post-menopausal
[defined as one year without menses]); is surgically sterile [via hysterectomy
and/or removal of the ovaries] or,
b. child-bearing potential, has a negative pregnancy test at both Screen and
Randomization Visits (prior to Investigational Product administration), and
agrees to one of the following methods of contraception:
• complete abstinence from intercourse two weeks prior to administration of
study drug, throughout the clinical trial, until the completion of follow-up
procedures) or for two weeks following discontinuation of the
Investigational Product in cases where subject discontinues the study
prematurely. (Subjects utilizing this method must agree to use an alternate
method of contraception if they should become sexually active and will be
queried on whether they have been abstinent in the preceding 2 weeks when
they present to the clinic for the Follow-Up Visit.) or,
• has a male sexual partner who is surgically sterilized (vasectomy with
documentation of azoospermia) prior to the Screening Visit or,
• sexual partner(s) is/are exclusively female or,
• Oral contraceptives (either combined or progestogen only), injectable
progestogen, implants of levonorgestrel, estrogenic vaginal ring and
percutaneous contraceptive patches must be used with double-barrier
method of contraception (see below). Women of child-bearing potential
using an oral contraceptive in combination with a double-barrier method of
contraception are required to continue to use this form of contraception for
1 week following discontinuation of Investigational Product.
• Double barrier method: condom or occlusive cap (diaphragm or
cervical/vault caps) plus spermicidal agent
(foam/gel/film/cream/suppository). The subject must be using this method
for at least 1 week following the discontinuation of Investigational Product
or,
• Any intrauterine device (IUD) with published data showing that the highest
expected failure rate is less than 1% per year. Acceptable IUDs, for the
purposes of this study, include TCu-380A (Paragard), TCU-380 Slimline
(Gyne T Slimline), MULTILOAD-250 (MLCu-250) and 375,
Levonorgesterol LNG-20 Intrauterine System (Mirena/Levonova), and
Flexigard 330/CuFix PP330 (Gynefix).The subject must have had the
device inserted at least 2 weeks prior to the first Screen Visit, throughout
the study, and 2 weeks following the discontinuation of Investigational
Product.
6. Subject who has a history of peptic ulcer disease (PUD) with known aetiology must
provide documentation by a gastroenterologist of the aetiology of the PUD and that
effective treatment was provided with full eradication of ulcers and symptoms. For
such subjects appropriate steps must also have been taken to minimize reoccurrence
of risk (i.e. if PUD was nonsteroidal anti-inflammatory drug [NSAID] induced, the
subject should no longer be taking NSAID medications; if cause was H. pylori, the
subject should have been appropriately treated). Subjects with a history of PUD >10
years ago, without recurrence, may be included after discussion with the medical
monitor even if documentation from treating physician is not available or aetiology
unclear.
Sites are required to document their H. pylori status of all subjects at Screening,
regardless of whether there is a positive history of PUD. Entry into the study is
permitted for subjects who have positive urea breath test for H. pylori without a
history or concurrent symptoms of PUD; referral for treatment is recommended after
study participation at the discretion of the Principal Investigator. |
|
| E.4 | Principal exclusion criteria |
A subject will not be eligible for inclusion in this study if any of the following criteria apply:
1. Subject who scores 1 or 2 on the CGI-I score item at the Randomization Visit.
2. Subject who meets DSM-IV criteria for Major Depressive Disorder or who scores
≥15 on the HAMD-17 at Screening Visit.
3. Subject’s LSAS assessment increases or decreases by more than 25% between the Screening and Randomization Visits.
4. Subject:
• Has symptoms of the presenting illness which are better accounted for by another diagnosis; or
• Meets DSM-IV criteria for any other Axis I disorder such as stated in protocol, as a primary diagnosis currently or within 6 months prior to the Screening Visit.
• Has current DSM-IV-TR diagnosis of Antisocial or Borderline Personality
Disorder, Dementia, or another current DSM-IV-TR Axis II diagnosis that would suggest non-responsiveness to pharmacotherapy or non-compliance with the protocol; or
• Has a current diagnosis of anorexia nervosa or bulimia; or a history of Schizophrenia, Schizoaffective or Bipolar Disorder.
5. Subject who poses a current, serious suicidal or homicidal risk, or has attempted suicide within the past 6 months or has ever been homicidal.
6. Subject has had electroconvulsive therapy or transcranial magnetic
stimulation within the 6 months prior to the Screening Visit.
7. Subject who is currently receiving regularly scheduled psychotherapy or plans to initiate psychotherapy during the trial or has received regularly scheduled psychotherapy during the 12 week period prior to the Screening Visit.
8. Subject has a positive urine test at screening for illegal drug use and/or history of
substance abuse or dependence within the past 12 months. Subject has a blood alcohol level of ≥ 15mg/dL at the Screening Visit.
9. Subject has an unstable medical disorder; or a disorder that would likely interfere
with GW876008, or paroxetine
10. Subject has any laboratory abnormality that in the investigator’s judgment is
considered to be clinically significant and not resolved by the Randomization Visit.
11. Subject has a systolic blood pressure > 160 mmHg or a diastolic blood
pressure ≥ 100 mmHg at the Screening or Randomization Visit.
12. Subject has a documented history of hepato-biliary disease including a history of, or positive laboratory results for hepatitis at Screening.
13. Subject who is not euthyroid as evidenced by normal Thyroid stimulating hormone.
14. Female subject who has a positive serum HCG pregnancy test at the Screen Visit, a positive urine dipstick test at the Randomization Visit , or who is lactating or planning to become pregnant within the next 18 weeks following the Screen Visit.
15. Subject has any electrocardiographic parameter outside of the Sponsor specified ranges at either screen or randomization visit.
16. Subject has taken other psychoactive drugs within two weeks prior to the
Randomization Visit including
• All antidepressants as described in protocol. All psychotropic drugs described in the protocol, are not allowed for the duration of the study, including the 2-week period preceding the mandatory 14-day Follow-up Visit.
17. Subject has taken systemic corticosteroids within two weeks of the Randomization Visit.
18. Subject who is likely to require the use of the following medications:
• Chronic (for more than 2 weeks), regular NSAID use unless administered concomitantly with an anti-secretory agent, i.e. proton-pump inhibitor or histamine-2 receptor antagonist.
• Concomitant use of aspirin and NSAID.
19. Subject has a stool positive for occult blood at Screening.
20. Subject has taken other prescription, non prescription, dietary, or herbal products as described in protocol.
21. Subject has taken other types of medicinal products as stated in protocol.
22. Subject has failed to respond to previous treatment for this disorder with an SSRI.
23. Subject has previously participated in an investigational trial involving GW876008 and/or paroxetine.
24. Subject who is currently participating in another clinical trial.
25. Subjects who would be noncompliant with the visit schedule or study procedures as outlined in the protocol.
|
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
Key Decision Making Endpoints
• Change from randomization in the clinician-administered LSAS total score at the end
of the treatment phase (Week 12).
• Change from randomization on the LSAS Fear subscale score at Week 12.
• Change from randomization on the LSAS Avoidance subscale score at Week 12.
• Change from randomization on the Social Avoidance and Distress Scale (SADS)
total score at Week 12. |
|
| 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 | Yes |
| E.6.7 | Pharmacodynamic | Yes |
| E.6.8 | Bioequivalence | No |
| E.6.9 | Dose response | Yes |
| 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 | 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) | Yes |
| E.7.3 | Therapeutic confirmatory (Phase III) | No |
| E.7.4 | Therapeutic use (Phase IV) | No |
| E.8 Design of the trial |
| E.8.1 | Controlled | Yes |
| E.8.1.1 | Randomised | No |
| 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 | Yes |
| E.8.1.7.1 | Other trial design description |
|
| E.8.2 | Comparator of controlled trial |
| E.8.2.1 | Other medicinal product(s) | Information not present in EudraCT |
| E.8.2.2 | Placebo | Yes |
| E.8.2.3 | Other | Yes |
| E.8.2.3.1 | Comparator description |
|
| 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 | 14 |
| 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 | Yes |
| 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 | 0 |
| E.8.9.1 | In the Member State concerned months | 12 |
| E.8.9.1 | In the Member State concerned days | 0 |
| E.8.9.2 | In all countries concerned by the trial years | 0 |
| E.8.9.2 | In all countries concerned by the trial months | 12 |
| E.8.9.2 | In all countries concerned by the trial days | 0 |
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