Generalized Anxiety DisorderPhase 3GADNCT00368745
Efficacy and Safety of Pregabalin vs Placebo for Generalized Anxiety Disorder (GAD) Symptoms in Subjects Discontinuing Benzodiazepine Treatment and Remaining 6 Weeks on Study Medication, Free From Benzodiazepine Use.
A Phase 3 study testing Pregabalin in people with Generalized Anxiety Disorder, run by Pfizer's Upjohn has merged with Mylan to form Viatris Inc. at 21 sites in 7 countries.
Trial summary
GAD subjects maintained on a stable dose of alprazolam for at least four weeks who meet eligibility criteria will be randomized to receive pregabalin vs matching placebo while simultaneously tapering off of alprazolam over 6 weeks. Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Generalized Anxiety Disorder
- What is being tested?
- Pregabalin
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 108 participants
- Where
- 21 sitesin 7 countries
- Study dates
- Sep 2006to Aug 2008
- Phase
- Phase 3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Provide written informed consent
- 18-65 years old
- male and female
- A primary lifetime diagnosis of DSM-IV-TR (2000) GAD (Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition)
Who cannot join
- Pregnant or lactating women
- History of non-response to alprazolam, other benzodiazepines, gabapentin or pregabalin given for the treatment of anxiety as indicated by a (screening or baseline) Hamilton Anxiety Scale (HAM-A) score > 18
Trial locations and contacts
21 sites in 7 countries.
21 sites in 7 countries
Czechia5 sites
Pfizer Investigational Site
Pilsen, 301 00
Pfizer Investigational Site
Prague, 100 00
Pfizer Investigational Site
Prague, 163 00
Pfizer Investigational Site
Prague, 170 00
Pfizer Investigational Site
Praha-Bubenec, 170 00
France5 sites
Pfizer Investigational Site
Arcachon, 33120
Pfizer Investigational Site
Caen, 14000
Pfizer Investigational Site
Élancourt, 78990
Pfizer Investigational Site
Nantes-Orvault, 44700
Pfizer Investigational Site
Paris, Cedex 12, 75571
Spain4 sites
Pfizer Investigational Site
Barcelona, 08025
Pfizer Investigational Site
Barcelona, 08036
Pfizer Investigational Site
Langreo, Principality of Asturias, 33900
Pfizer Investigational Site
Zamora, 49021
Mexico3 sites
Pfizer Investigational Site
Mexico City, 03740
Pfizer Investigational Site
San Luis Potosí City, 78216
Pfizer Investigational Site
Tepic, Nayarit, 63000
Italy2 sites
Pfizer Investigational Site
L’Aquila, 67100
Pfizer Investigational Site
Milan, 20157
Costa Rica1 site
Pfizer Investigational Site
San Pedro, Provincia de San José, 00
About this study
Official title: A Multicenter, Randomized, Double-Blind, Placebo-Controlled Study of Pregabalin in Subjects With Generalized Anxiety Disorder (GAD) Switching From Benzodiazepine Therapy.
GAD subjects maintained on a stable dose of alprazolam for at least four weeks who meet eligibility criteria will be randomized to receive pregabalin vs matching placebo while simultaneously tapering off of alprazolam over 6 weeks. Subjects return weekly for assessment of safety/tolerability of pregabalin vs placebo as well as for assessment of anxiety and benzodiazepine withdrawal symptoms. Subjects successfully able to discontinue alprazolam, will continue 6 weeks of treatment with pregabalin vs placebo (free of benzodiazepine use). The efficacy and safety of pregabalin vs placebo for anxiety symptoms and ability to discontinue/remain free of alprazolam will be compared among pregabalin and placebo treated groups. Hypothesis is that a greater proportion of subjects will be successful in discontinuing and remaining free from benzodiazepines who were treated with pregabalin as compared to subjects treated with placebo.
- Conditions
- Generalized Anxiety Disorder
- Being tested
- Pregabalin, Placebo
- Medical subject headings
- Generalized Anxiety Disorder
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PregabalinDrug
Also called Lyrica
GAD subjects on stable dose of alprazolam will be randomized to double-blind pregabalin at starting dose of 75mg twice daily. Weekly assessments of tolerability, need for rescue medication, anxiety/withdrawal symptoms will guide flexible dose titration of pregabalin at dose range between 75 and 300mg twice daily. Subjects successful in discontinuation of alprazolam while treated with pregabalin will continue to be maintained on pregabalin for 6 weeks and assessed weekly for ability to remain in the study.
PlaceboDrug
GAD subjects on stable dose of alprazolam will be randomized to double-blind placebo matching assessments and study medication titration as detailed under the pregabalin arm description. Subjects successful in discontinuation of alprazolam while treated with placebo will continue to be maintained on placebo for 6 weeks and assessed weekly for ability to remain in the study.
| Study group | Role | What they receive |
|---|---|---|
| Pregabalin | Active comparator | Pregabalin treatment for GAD during 6 week taper/discontinuation from alprazolam treatment; followed by 6 weeks pregabalin treatment 'alprazolam free'. Receives: Drug: Pregabalin |
| Placebo | Placebo comparator | Placebo treatment of GAD during 6 week taper/discontinuation of alprazolam treatment followed by 6 weeks continuation of placebo treatment 'alprazolam free'. Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Subjects at Endpoint (Post Alprazolam Free Week 6 or Last Observation Carried Forward [LOCF] Post Alprazolam Free Week 1) Who Are Benzodiazepine Free
Number of subjects benzodiazepine free: < 2 doses rescue medication; negative urine benzodiazepine psychoactive toxicology assay (each visit Alprazolam Free phase); negative serum benzodiazepine alcohol assay (endpoint or LOCF).
Measured: Endpoint (Post Alprazolam Free Week 6 or LOCF Post Alprazolam Free Week 1)
Secondary outcomes (11)
Mean Change From Baseline in Hamilton Anxiety Scale (HAM-A) Scores
HAM-A measures treatment-related changes in generalized anxiety symptoms; 14 item questionnaire scored 0 (not present) to 4 (very severe); lower score indicates less affected. Change from baseline: mean at observation minus mean at baseline.
Measured: Baseline, Alprazolam Taper Weeks 1 through 6, Alprazolam Free Weeks 1 through 6, and Endpoint (Alprazolam Free [AF] Week 6)
Number of Subjects With > = 6 Point Increase in Physician's Withdrawal Checklist (PWC) Scores
PWC: 20 item physician rated interview (0 = not present; 3 = severe; score range: 0 to 60) measuring: signs of anxiolytic drug withdrawal and gastrointestinal (GI), mood, sleep, motor, somatic, perception and cognition symptoms. Data not analyzed: PWC not measured at baseline.
Measured: Baseline, Alprazolam Free Weeks 1 through 6, Endpoint (AF Week 6)
Number of Subjects With > = 5 New PWC Symptoms
PWC: 20 item physician rated interview (0 = not present; 3 = severe; score range: 0 to 60) measuring: signs of anxiolytic drug withdrawal and gastrointestinal (GI), mood, sleep, motor, somatic, perception and cognition symptoms. Data not analyzed: PWC not measured at baseline.
Measured: Baseline, Alprazolam Free Weeks 1 through 6, Endpoint (AF Week 6)
Mean Change From Baseline in Physician's Withdrawal Checklist (PWC) Scores
PWC: 20 item physician rated interview (0 = not present; 3 = severe; score range: 0 to 60) measuring: signs of anxiolytic drug withdrawal and gastrointestinal (GI), mood, sleep, motor, somatic, perception and cognition symptoms. Change from baseline not analyzed as PWC was not measured at baseline. Mean PWS scores presented in Post-hoc outcome measure Mean PWS scores.
Measured: Baseline, Alprazolam Taper Weeks 1 through 6, Alprazolam Free Weeks 1 through 6, Endpoint (AF Week 6)
Mean Change From Baseline in Clinical Global Impression Severity (CGI-S) Scale Scores.
CGI-S: 7-point scale to assess global change in subject condition compared to baseline; range 1 (no evidence of illness) to 7 (among the most severely ill); higher score = more affected. Change from baseline: mean at observation minus mean at baseline.
Measured: Baseline, Alprazolam Taper Weeks 1 through 6, Alprazolam Free Weeks 1 through 6, and Endpoint (AF Week 6 )
Mean Scores for Clinical Global Impression-Improvement (CGI-I) Scale
CGI-I: 7-point scale to assess global change in subject condition compared to baseline; range 1 (very much improved) to 7 (very much worse); higher score = more affected.
Measured: Alprazolam Taper Weeks 1 through 6, Alprazolam Free Weeks 1 through 6, and Endpoint (AF Week 6 )
Mean Scores for Patient Global Impression-Improvement (PGI-I)
PGI-I: subject rated 7-point scale measures change in overall status; range 1 (very much improved) to 7 (very much worse).
Measured: Alprazolam Taper Weeks 1 through 6, Alprazolam Free Weeks 1 through 6, and Endpoint (AF Week 6 )
Mean Change From Baseline in Digit Symbol Substitution Test (DSST) Scores
DSST: subject-rated; evaluates aspects of cognition (includes attending to directions, processing speed, sustained attention, visual-motor integration, learning and psychomotor speed). Subject matches symbol (1 to 9) with corresponding number key (1 to 9); number of correct symbol-number pairs completed by subject over a 90-second test period determines DSST score. Change: mean at observation minus mean at baseline. Data summarized as change from baseline to endpoint.
Measured: Baseline, Endpoint (AF Week 6 )
Time to Discontinuation
The 25th percentile estimate of time until discontinuation is based on Kaplan-Meier estimates. Event day is the study day when the subject discontinued from study.
Measured: Baseline, Week 13 (Final Visit/Early Termination)
Time to First Use of Rescue Medication
The 25th percentile estimate of time until first use of rescue medication is based on Kaplan-Meier estimates. Event day is the study day when the subject first used rescue medication. Rescue medication: packet with 2 doses alprazolam to take only in the event subject experiences severe symptoms of benzodiazepine withdrawal or rebound anxiety.
Measured: Baseline, Week 13 (Final Visit/Early Termination)
Number of Subjects in Relapse Free State at 6-week Benzodiazepine-free Endpoint (Alprazolam Free Week 6)
Number of subjects benzodiazepine free: < 2 doses rescue medication; negative urine toxicology assay (each visit Alprazolam Free phase), negative urine alcohol assay (Alprazolam Free Week 6 = endpoint or LOCF). Relapse: > = 2 intakes rescue medication, positive urine and /or alcohol assays, unable to tolerate alprazolam taper, or discontinuation.
Measured: Alprazolam Free Week 6
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 Aug 2006 (estimated)
- Study startSep 2006
- Primary completionAug 2008
- Study completionAug 2008
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Generalized Anxiety DisorderStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 108 participants (actual)
Sponsor and investigators
- Lead sponsor
- Pfizer's Upjohn has merged with Mylan to form Viatris Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Pfizer CT.gov Call Center, Study director, Pfizer
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00368745
- Sponsor's protocol ID
- A0081092
- Acronym
- GAD
- Status last verified
- Nov 2009
- First submitted
- 23 Aug 2006
- Last updated
- 9 Feb 2021
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 9 Feb 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Multicenter, Randomized, Double-Blind, Placebo-Controlled Study of Pregabalin in Subjects With Generalized Anxiety Disorder (GAD) Switching From Benzodiazepine Therapy.
- ClinicalTrials.gov ID
- NCT00368745
- Acronym / sponsor ID
- GAD / A0081092
- Conditions
- Generalized Anxiety Disorder
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 108 participants (actual)
- Lead sponsor
- Pfizer's Upjohn has merged with Mylan to form Viatris Inc.Industry (pharma, biotech, devices)
- Study start
- Sep 2006
- Primary completion
- Aug 2008 (actual)
- Study completion
- Aug 2008 (actual)
- First posted
- 25 Aug 2006 (estimated)
- Results
- Posted 9 Nov 2009
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
GAD subjects maintained on a stable dose of alprazolam for at least four weeks who meet eligibility criteria will be randomized to receive pregabalin vs matching placebo while simultaneously tapering off of alprazolam over 6 weeks. Subjects return weekly for assessment of safety/tolerability of pregabalin vs placebo as well as for assessment of anxiety and benzodiazepine withdrawal symptoms. Subjects successfully able to discontinue alprazolam, will continue 6 weeks of treatment with pregabalin vs placebo (free of benzodiazepine use). The efficacy and safety of pregabalin vs placebo for anxiety symptoms and ability to discontinue/remain free of alprazolam will be compared among pregabalin and placebo treated groups. Hypothesis is that a greater proportion of subjects will be successful in discontinuing and remaining free from benzodiazepines who were treated with pregabalin as compared to subjects treated with placebo.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Pregabalin | Active comparator | Drug: PregabalinPregabalin treatment for GAD during 6 week taper/discontinuation from alprazolam treatment; followed by 6 weeks pregabalin treatment 'alprazolam free'. |
| Placebo | Placebo comparator | Drug: PlaceboPlacebo treatment of GAD during 6 week taper/discontinuation of alprazolam treatment followed by 6 weeks continuation of placebo treatment 'alprazolam free'. |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- Provide written informed consent
- 18-65 years old
- male and female
- A primary lifetime diagnosis of DSM-IV-TR (2000) GAD (Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition)
Key exclusion criteria (2 listed)
- Pregnant or lactating women
- History of non-response to alprazolam, other benzodiazepines, gabapentin or pregabalin given for the treatment of anxiety as indicated by a (screening or baseline) Hamilton Anxiety Scale (HAM-A) score > 18
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| PregabalinAlso: LyricaGAD subjects on stable dose of alprazolam will be randomized to double-blind pregabalin at starting dose of 75mg twice daily. Weekly assessments of tolerability, need for rescue medication, anxiety/withdrawal symptoms will guide flexible dose titration of pregabalin at dose range between 75 and 300mg twice daily. Subjects successful in discontinuation of alprazolam while treated with pregabalin will continue to be maintained on pregabalin for 6 weeks and assessed weekly for ability to remain in the study. | Drug | Pregabalin |
| PlaceboGAD subjects on stable dose of alprazolam will be randomized to double-blind placebo matching assessments and study medication titration as detailed under the pregabalin arm description. Subjects successful in discontinuation of alprazolam while treated with placebo will continue to be maintained on placebo for 6 weeks and assessed weekly for ability to remain in the study. | Drug | Placebo |
Primary outcome
Number of Subjects at Endpoint (Post Alprazolam Free Week 6 or Last Observation Carried Forward [LOCF] Post Alprazolam Free Week 1) Who Are Benzodiazepine Free
Time frame: Endpoint (Post Alprazolam Free Week 6 or LOCF Post Alprazolam Free Week 1)
Number of subjects benzodiazepine free: < 2 doses rescue medication; negative urine benzodiazepine psychoactive toxicology assay (each visit Alprazolam Free phase); negative serum benzodiazepine alcohol assay (endpoint or LOCF).
11 secondary outcomes
Mean Change From Baseline in Hamilton Anxiety Scale (HAM-A) Scores
Time frame: Baseline, Alprazolam Taper Weeks 1 through 6, Alprazolam Free Weeks 1 through 6, and Endpoint (Alprazolam Free [AF] Week 6)
Number of Subjects With > = 6 Point Increase in Physician's Withdrawal Checklist (PWC) Scores
Time frame: Baseline, Alprazolam Free Weeks 1 through 6, Endpoint (AF Week 6)
Number of Subjects With > = 5 New PWC Symptoms
Time frame: Baseline, Alprazolam Free Weeks 1 through 6, Endpoint (AF Week 6)
Mean Change From Baseline in Physician's Withdrawal Checklist (PWC) Scores
Time frame: Baseline, Alprazolam Taper Weeks 1 through 6, Alprazolam Free Weeks 1 through 6, Endpoint (AF Week 6)
Mean Change From Baseline in Clinical Global Impression Severity (CGI-S) Scale Scores.
Time frame: Baseline, Alprazolam Taper Weeks 1 through 6, Alprazolam Free Weeks 1 through 6, and Endpoint (AF Week 6 )
Mean Scores for Clinical Global Impression-Improvement (CGI-I) Scale
Time frame: Alprazolam Taper Weeks 1 through 6, Alprazolam Free Weeks 1 through 6, and Endpoint (AF Week 6 )
Mean Scores for Patient Global Impression-Improvement (PGI-I)
Time frame: Alprazolam Taper Weeks 1 through 6, Alprazolam Free Weeks 1 through 6, and Endpoint (AF Week 6 )
Mean Change From Baseline in Digit Symbol Substitution Test (DSST) Scores
Time frame: Baseline, Endpoint (AF Week 6 )
Time to Discontinuation
Time frame: Baseline, Week 13 (Final Visit/Early Termination)
Time to First Use of Rescue Medication
Time frame: Baseline, Week 13 (Final Visit/Early Termination)
Number of Subjects in Relapse Free State at 6-week Benzodiazepine-free Endpoint (Alprazolam Free Week 6)
Time frame: Alprazolam Free Week 6
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 9 Feb 2021.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- To obtain contact information for a study center near you, click here.Link provided by the sponsor.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Pfizer CT.gov Call Center study director
Pfizer
21 sites in 7 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Pregabalin in people with Generalized Anxiety Disorder, run by Pfizer's Upjohn has merged with Mylan to form Viatris Inc. at 21 sites in 7 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 2 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 9 Feb 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 21 sites in Czechia, France, Spain, Mexico, Italy and 2 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 9 Nov 2009). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of Subjects at Endpoint (Post Alprazolam Free Week 6 or Last Observation Carried Forward [LOCF] Post Alprazolam Free Week 1) Who Are Benzodiazepine Free (time frame: Endpoint (Post Alprazolam Free Week 6 or LOCF Post Alprazolam Free Week 1)). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 9 Feb 2021.