Generalized Anxiety Disorder
Conditions
Brief summary
The purpose of this study is to characterize the safety and efficacy in patients with generalized anxiety disorder after short- (3 months) and long-term (6 months) use of Pregabalin (Lyrica).
Interventions
DRUGPregabalin
Pregabalin 150-300 mg given twice a day
DRUGLorazepam
Lorazepam 3-4 mg given twice a day
DRUGPlacebo
Placebo
Sponsors
Pfizer's Upjohn has merged with Mylan to form Viatris Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
* Diagnosis Generalized Anxiety Disorder * HAM-A score \>=18 and HAM-D (item 1) score \>=2 at screening and baseline * Needs pharmacological treatment
Exclusion criteria
* Current or past diagnosis of any other DSM IV Axis I disorders * A history of failed treatment with a benzodiazepine * Any clinically significant, serious, or unstable hematologic, autoimmune, endocrine, cardiovascular, renal, hepatic, gastrointestinal, or neurological disorder
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Last Visit on Treatment in Physician's Withdrawal Checklist (PWC) Score for Cohort 3 (6-Month Last Visit) at Discontinuation Week 1 | Last visit on treatment, Week 1 post-treatment discontinuation (discontinuation occurred after Week 15 to Week 24) | PWC: 20 item physician rated interview measuring anxiolytic drug withdrawal-related signs and symptoms (gastrointestinal, mood, sleep, motor, somatic, perception and cognition); range 0 (not present) to 3 (severe); total score range: 0 to 60; higher score = more affected. |
| Change From Last Visit on Treatment in Physician's Withdrawal Checklist (PWC) Score for Cohort 3 (6-Month Last Visit) at Discontinuation Week 2 | Last visit on treatment, Week 2 post-treatment discontinuation (discontinuation occurred after Week 15 to Week 24) | PWC: 20 item physician rated interview measuring anxiolytic drug withdrawal-related signs and symptoms (gastrointestinal, mood, sleep, motor, somatic, perception and cognition); range 0 (not present) to 3 (severe); total score range: 0 to 60; higher score = more affected. |
| Change From Baseline in Hamilton Anxiety Scale (HAM-A) for Cohort 1 (Less Than 3-Month Last Visit) at Discontinuation Week 1 | Baseline, Week 1 post-treatment discontinuation (discontinuation occurred prior to Week 9) | HAM-A measures treatment-related changes in generalized anxiety symptoms; 14 item questionnaire scored 0 (not present) to 4 (very severe); total possible range 0 to 56. Lower score indicates less affected. |
| Change From Baseline in Hamilton Anxiety Scale (HAM-A) for Cohort 1 (Less Than 3-Month Last Visit) at Discontinuation Week 2 | Baseline, Week 2 post-treatment discontinuation (discontinuation occurred prior to Week 9) | HAM-A measures treatment-related changes in generalized anxiety symptoms; 14 item questionnaire scored 0 (not present) to 4 (very severe); total possible range 0 to 56. Lower score indicates less affected. |
| Change From Baseline in Hamilton Anxiety Scale (HAM-A) for Cohort 2 (3-Month Last Visit) at Discontinuation Week 1 | Baseline, Week 1 post-treatment discontinuation (discontinuation occurred from Week 9 to Week 15) | HAM-A measures treatment-related changes in generalized anxiety symptoms; 14 item questionnaire scored 0 (not present) to 4 (very severe); total possible range 0 to 56. Lower score indicates less affected. |
| Change From Baseline in Hamilton Anxiety Scale (HAM-A) for Cohort 2 (3-Month Last Visit) at Discontinuation Week 2 | Baseline, Week 2 post-treatment discontinuation (discontinuation occurred from Week 9 to Week 15) | HAM-A measures treatment-related changes in generalized anxiety symptoms; 14 item questionnaire scored 0 (not present) to 4 (very severe); total possible range 0 to 56. Lower score indicates less affected. |
| Change From Baseline in Hamilton Anxiety Scale (HAM-A) for Cohort 3 (6-Month Last Visit) at Discontinuation Week 1 | Baseline, Week 1 post-treatment discontinuation (discontinuation occurred after Week 15 to Week 24) | HAM-A measures treatment-related changes in generalized anxiety symptoms; 14 item questionnaire scored 0 (not present) to 4 (very severe); total possible range 0 to 56. Lower score indicates less affected. |
| Change From Baseline in Hamilton Anxiety Scale (HAM-A) for Cohort 3 (6-Month Last Visit) at Discontinuation Week 2 | Baseline, Week 2 post-treatment discontinuation (discontinuation occurred after Week 15 to Week 24) | HAM-A measures treatment-related changes in generalized anxiety symptoms; 14 item questionnaire scored 0 (not present) to 4 (very severe); possible range 0 to 56. Lower score indicates less affected. |
| Change From Last Visit on Treatment in Physician's Withdrawal Checklist (PWC) Score for Cohort 1 (Less Than 3-Month Last Visit) at Discontinuation Week 1 | Last visit on treatment, Week 1 post-treatment discontinuation (discontinuation occurred prior to Week 9) | PWC: 20 item physician rated interview measuring anxiolytic drug withdrawal-related signs and symptoms (gastrointestinal, mood, sleep, motor, somatic, perception and cognition); range 0 (not present) to 3 (severe); total score range: 0 to 60; higher score = more affected. |
| Change From Last Visit on Treatment in Physician's Withdrawal Checklist (PWC) Score for Cohort 1 (Less Than 3-Month Last Visit) at Discontinuation Week 2 | Last visit on treatment, Week 2 post-treatment discontinuation (discontinuation occurred prior to Week 9) | PWC: 20 item physician rated interview measuring anxiolytic drug withdrawal-related signs and symptoms (gastrointestinal, mood, sleep, motor, somatic, perception and cognition); range 0 (not present) to 3 (severe); total score range: 0 to 60; higher score = more affected. |
| Change From Last Visit on Treatment in Physician's Withdrawal Checklist (PWC) Score for Cohort 2 (3-Month Last Visit) at Discontinuation Week 1 | Last visit on treatment, Week 1 post-treatment discontinuation (discontinuation occurred from Week 9 to Week 15) | PWC: 20 item physician rated interview measuring anxiolytic drug withdrawal-related signs and symptoms (gastrointestinal, mood, sleep, motor, somatic, perception and cognition); range 0 (not present) to 3 (severe); total score range: 0 to 60; higher score = more affected. |
| Change From Last Visit on Treatment in Physician's Withdrawal Checklist (PWC) Score for Cohort 2 (3-Month Last Visit) at Discontinuation Week 2 | Last visit on treatment, Week 2 post-treatment discontinuation (discontinuation occurred from Week 9 to Week 15) | PWC: 20 item physician rated interview measuring anxiolytic drug withdrawal-related signs and symptoms (gastrointestinal, mood, sleep, motor, somatic, perception and cognition); range 0 (not present) to 3 (severe); total score range: 0 to 60; higher score = more affected. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Physician's Withdrawal Checklist (PWC) Score for Cohort 3 (6-Month Last Visit) | Week 1, 2 post-treatment discontinuation (discontinuation occurred after Week 15 to Week 24) | PWC: 20 item physician rated interview measuring anxiolytic drug withdrawal-related signs and symptoms (gastrointestinal, mood, sleep, motor, somatic, perception and cognition); range 0 (not present) to 3 (severe); total score range: 0 to 60; higher score = more affected. |
| Change From Last Visit of Treatment in Hamilton Anxiety Scale (HAM-A) for Cohort 1 (Less Than 3-Month Last Visit) at Discontinuation Week 1 and 2 | Last visit on treatment, Week 1, 2 post-treatment discontinuation (discontinuation occurred prior to Week 9) | HAM-A measures treatment-related changes in generalized anxiety symptoms; 14 item questionnaire scored 0 (not present) to 4 (very severe); total possible range 0 to 56. Lower score indicates less affected. |
| Change From Last Visit of Treatment in Hamilton Anxiety Scale (HAM-A) for Cohort 2 (3-Month Last Visit) at Discontinuation Week 1 and 2 | Last visit on treatment, Week 1, 2 post-treatment discontinuation (discontinuation occurred from Week 9 to Week 15) | HAM-A measures treatment-related changes in generalized anxiety symptoms; 14 item questionnaire scored 0 (not present) to 4 (very severe); possible range 0 to 56. Lower score indicates less affected. |
| Change From Last Visit of Treatment in Hamilton Anxiety Scale (HAM-A) for Cohort 3 (6-Month Last Visit) at Discontinuation Week 1 and 2 | Last visit on treatment, Week 1, 2 post-treatment discontinuation (discontinuation [DC] occurred after Week 15 to Week 24) | HAM-A measures treatment-related changes in generalized anxiety symptoms; 14 item questionnaire scored 0 (not present) to 4 (very severe); total possible range 0 to 56. Lower score indicates less affected. |
| Hamilton Anxiety Scale (HAM-A) for Cohort 1 (Less Than 3-Month Last Visit) | Week 1, 2 post-treatment discontinuation (discontinuation occurred prior to Week 9) | HAM-A measures treatment-related changes in generalized anxiety symptoms; 14 item questionnaire scored 0 (not present) to 4 (very severe); total possible range 0 to 56. Lower score indicates less affected. |
| Hamilton Anxiety Scale (HAM-A) for Cohort 2 (3-Month Last Visit) | Week 1, 2 post-treatment discontinuation (discontinuation occurred from Week 9 to Week 15) | HAM-A measures treatment-related changes in generalized anxiety symptoms; 14 item questionnaire scored 0 (not present) to 4 (very severe); possible range 0 to 56. Lower score indicates less affected. |
| Hamilton Anxiety Scale (HAM-A) Score for Cohort 3 (6-Month Last Visit) | Week 1, 2 post-treatment discontinuation (discontinuation [DC] occurred after Week 15 to Week 24) | HAM-A measures treatment-related changes in generalized anxiety symptoms; 14 item questionnaire scored 0 (not present) to 4 (very severe); total possible range 0 to 56. Lower score indicates less affected. |
| Hamilton Anxiety Scale (HAM-A) Score for Period 1 | Baseline, Week 12 | HAM-A measures treatment-related changes in generalized anxiety symptoms; 14 item questionnaire scored 0 (not present) to 4 (very severe); total possible range 0 to 56. Lower score indicates less affected. |
| Hamilton Anxiety Scale (HAM-A) Score for Period 2 | Baseline, Week 24 | HAM-A measures treatment-related changes in generalized anxiety symptoms; 14 item questionnaire scored 0 (not present) to 4 (very severe); total possible range 0 to 56. Lower score indicates less affected. |
| Change From Baseline in Hamilton Anxiety Scale (HAM-A) Score at Week 12 | Baseline, Week 12 | HAM-A measures treatment-related changes in generalized anxiety symptoms; 14 item questionnaire scored 0 (not present) to 4 (very severe); total possible range 0 to 56. Lower score indicates less affected. |
| Change From Baseline in Hamilton Anxiety Scale (HAM-A) Score at Week 24 | Baseline, Week 24 | HAM-A measures treatment-related changes in generalized anxiety symptoms; 14 item questionnaire scored 0 (not present) to 4 (very severe); total possible range 0 to 56. Lower score indicates less affected. |
| Clinical Global Impression - Severity (CGI-S) Score for Period 1 | Baseline, Week 12 | CGI-S: 7-point clinician rated scale to assess severity of participant's current illness state; range: 1 (normal - not ill at all) to 7 (among the most extremely ill patients). Higher score = more affected. |
| Clinical Global Impression - Severity (CGI-S) Score for Period 2 | Baseline, Week 24 | CGI-S: 7-point clinician rated scale to assess severity of participant's current illness state; range: 1 (normal - not ill at all) to 7 (among the most extremely ill patients). Higher score = more affected |
| Change From Baseline in Clinical Global Impression - Severity (CGI-S) Score at Week 24 | Baseline, Week 24 | CGI-S: 7-point clinician rated scale to assess severity of participant's current illness state; range: 1 (normal - not ill at all) to 7 (among the most extremely ill patients). Higher score = more affected |
| Clinical Global Impression - Improvement (CGI-I) Score at the End of Period 1 | Week 12 | CGI-I: 7-point clinician rated scale ranging from 1 (very much improved) to 7 (very much worse). Improvement is defined as a score of 1 (very much improved), 2 (much improved), or 3 (minimally improved) on the scale. |
| Clinical Global Impression - Improvement (CGI-I) Score at the End of Period 2 | Week 24 | CGI-I: 7-point clinician rated scale ranging from 1 (very much improved) to 7 (very much worse). Improvement is defined as a score of 1 (very much improved), 2 (much improved), or 3 (minimally improved) on the scale. |
| Change From Baseline in Clinical Global Impression - Severity (CGI-S) Score at Week 12 | Baseline, Week 12 | CGI-S: 7-point clinician rated scale to assess severity of participant's current illness state; range: 1 (normal - not ill at all) to 7 (among the most extremely ill patients). Higher score = more affected. |
| Number of Participants With Rebound Anxiety for Cohort 1 (Less Than 3-Month Last Visit) | 2 weeks post-treatment discontinuation (discontinuation occurred prior to Week 9) | Rebound anxiety was defined as a rapid return of the participant's original symptoms following drug discontinuation, that were worse compared to baseline. This was characterized by a HAM-A score at the Discontinuation Week 1 or Week 2 greater than or equal to the baseline value. |
| Number of Participants With Rebound Anxiety for Cohort 2 (3-Month Last Visit) | 2 weeks post-treatment discontinuation (discontinuation occurred from Week 9 to Week 15) | Rebound anxiety was defined as a rapid return of the participant's original symptoms following drug discontinuation, that were worse compared to baseline. This was characterized by a HAM-A score at the Discontinuation Week 1 or Week 2 greater than or equal to the baseline value. |
| Number of Participants With Rebound Anxiety for Cohort 3 (6-Month Last Visit) | 2 weeks post-treatment discontinuation (discontinuation occurred after Week 15 to Week 24) | Rebound anxiety was defined as a rapid return of the participant's original symptoms following drug discontinuation, that were worse compared to baseline. This was characterized by a HAM-A score at the Discontinuation Week 1 or Week 2 greater than or equal to the baseline value. |
| Number of Participants With Discontinuation-Emergent Signs and Symptoms (DESS) for Cohort 1 (Less Than 3-Month Last Visit) | 2 weeks post-treatment discontinuation (discontinuation occurred prior to Week 9) | DESS adverse events, a subset of Treatment Emergent Signs and Symptoms (TESS), were defined as those spontaneously reported adverse events that developed or existed prior to but worsened during Discontinuation Week 1 and 2. |
| Number of Participants With Discontinuation-Emergent Signs and Symptoms (DESS) for Cohort 2 (3-Month Last Visit) | 2 weeks post-treatment discontinuation (discontinuation occurred from Week 9 to Week 15) | DESS adverse events, a subset of Treatment Emergent Signs and Symptoms (TESS), were defined as those spontaneously reported adverse events that developed or existed prior to but worsened during Discontinuation Week 1 and 2. |
| Number of Participants With Discontinuation-Emergent Signs and Symptoms (DESS) for Cohort 3 (6-Month Last Visit) | 2 weeks post-treatment discontinuation (discontinuation occurred after Week 15 to Week 24) | DESS adverse events, a subset of Treatment Emergent Signs and Symptoms (TESS), were defined as those spontaneously reported adverse events that developed or existed prior to but worsened during Discontinuation Week 1 and 2. |
| Change From Baseline in Physician's Withdrawal Checklist (PWC) Score for Cohort 1 (Less Than 3-Month Last Visit) at Discontinuation Week 1 and 2 | Baseline, Week 1, 2 post-treatment discontinuation (discontinuation occurred prior to Week 9) | PWC: 20 item physician rated interview measuring anxiolytic drug withdrawal-related signs and symptoms (gastrointestinal, mood, sleep, motor, somatic, perception and cognition); range 0 (not present) to 3 (severe); total score range: 0 to 60; higher score = more affected. |
| Change From Baseline in Physician's Withdrawal Checklist (PWC) Score for Cohort 2 (3-Month Last Visit) at Discontinuation Week 1 and 2 | Baseline, Week 1, 2 post-treatment discontinuation (discontinuation occurred from Week 9 to Week 15) | PWC: 20 item physician rated interview measuring anxiolytic drug withdrawal-related signs and symptoms (gastrointestinal, mood, sleep, motor, somatic, perception and cognition); range 0 (not present) to 3 (severe); total score range: 0 to 60; higher score = more affected. |
| Change From Baseline in Physician's Withdrawal Checklist (PWC) Score for Cohort 3 (6-Month Last Visit) at Discontinuation Week 1 and 2 | Baseline, Week 1, 2 post-treatment discontinuation (discontinuation [DC] occurred after Week 15 to Week 24) | PWC: 20 item physician rated interview measuring anxiolytic drug withdrawal-related signs and symptoms (gastrointestinal, mood, sleep, motor, somatic, perception and cognition); range 0 (not present) to 3 (severe); total score range: 0 to 60; higher score = more affected. |
| Physician's Withdrawal Checklist (PWC) Score for Cohort 1 (Less Than 3-Month Last Visit) | Week 1, 2 post-treatment discontinuation (discontinuation occurred prior to Week 9) | PWC: 20 item physician rated interview measuring anxiolytic drug withdrawal-related signs and symptoms (gastrointestinal, mood, sleep, motor, somatic, perception and cognition); range 0 (not present) to 3 (severe); total score range: 0 to 60; higher score = more affected. |
| Physician's Withdrawal Checklist (PWC) Score for Cohort 2 (3-Month Last Visit) | Week 1, 2 post-treatment discontinuation (discontinuation occurred from Week 9 to Week 15) | PWC: 20 item physician rated interview measuring anxiolytic drug withdrawal-related signs and symptoms (gastrointestinal, mood, sleep, motor, somatic, perception and cognition); range 0 (not present) to 3 (severe); total score range: 0 to 60; higher score = more affected. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Sheehan-Suicidality Tracking Scale (S-STS) Score | Baseline up to Week 24 | Sheehan-Suicidality Tracking Scale (S-STS): an 8-item prospective rating scale that tracked treatment-emergent suicidal ideation and behaviors. Items 1a, 2-6, 7a, and 8 were scored on a 5-point Likert scale (ranging from 0= not at all to 4=extremely). Items 1, 1b, and 7 required yes or no responses. Total score ranged from 0 to 35, higher score indicated higher suicidal tendency. |
| Number of Participants With Treatment-Emergent Adverse Events (AEs) | Baseline up to Week 12 (period 1), Week 13 up to Week 24 (period 2) | An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. Treatment-emergent are events between first dose of study drug and Week 12, for period 1, and between Week 13 and Week 24, for period 2, that were absent before treatment or that worsened relative to pretreatment state. |
Countries
Argentina, Austria, Costa Rica, Croatia, Czechia, Finland, Greece, India, Indonesia, Lithuania, Mexico, Russia, Serbia, Slovenia, Spain, Turkey (Türkiye)
Participant flow
Pre-assignment details
This study employed 3 treatments in Period 1 and 6 treatments in Period 2. Randomization occurred once, at the onset of Period 1.
Participants by arm
| Arm | Count |
|---|---|
| Pregabalin High Dose, Pregabalin High Dose Period 1 (treatment optimization): Pregabalin capsule 150 milligram per day (mg/day) orally twice daily in 2 equally divided doses in Week 1, pregabalin capsule 300 mg/day orally twice daily in 2 equally divided doses in Week 2 and pregabalin capsule 450 mg/day orally twice daily in 2 equally divided doses in Week 3 during 3-week upward titration. Flexible dosing of pregabalin capsule 450 mg/day or 600 mg/day orally twice daily in 2 equally divided doses depending on efficacy and tolerability up to Week 6. If participant had an adequate response at Week 6, fixed dosing of pregabalin capsule 450 mg/day or 600 mg/day orally twice daily in 2 equally divided doses up to Week 12. Period 2 (fixed dosing): Continued pregabalin capsule 450 mg/day or 600 mg/day orally twice daily in 2 equally divided doses up to Week 24. Period 3 (treatment discontinuation): A 1-week blinded dose tapering period (Week 25). Participants were followed-up after 1 week (Week 26). | 154 |
| Pregabalin High Dose, Placebo Period 1 (treatment optimization): Pregabalin capsule 150 mg/day orally twice daily in 2 equally divided doses in Week 1, pregabalin capsule 300 mg/day orally twice daily in 2 equally divided doses in Week 2 and pregabalin capsule 450 mg/day orally twice daily in 2 equally divided doses in Week 3 during 3-week upward titration. Flexible dosing of pregabalin capsule 450 mg/day or 600 mg/day orally twice daily in 2 equally divided doses depending on efficacy and tolerability up to Week 6. If participant had an adequate response at Week 6, fixed dosing of pregabalin capsule 450 mg/day or 600 mg/day orally twice daily in 2 equally divided doses up to Week 12. Period 2 (fixed dosing): Pregabalin was discontinued with a blinded dose tapering over 1-week followed by matching placebo capsule orally twice daily up to Week 24. Period 3 (treatment discontinuation): Continued matching placebo capsule orally twice daily for 1 week (Week 25). Participants were followed-up after 1 week (Week 26). | 52 |
| Pregabalin Low Dose, Pregabalin Low Dose Period 1 (treatment optimization): Pregabalin capsule 150 mg/day orally twice daily in 2 equally divided doses during 3-week upward titration. Flexible dosing of pregabalin capsule 150 mg/day or 300 mg/day orally twice daily in 2 equally divided doses depending on efficacy and tolerability up to Week 6. If participant had an adequate response at Week 6, fixed dosing of pregabalin capsule 150 mg/day or 300 mg/day orally twice daily in 2 equally divided doses up to Week 12. Period 2 (fixed dosing): Continued pregabalin capsule 150 mg/day or 300 mg/day orally twice daily in 2 equally divided doses up to Week 24. Period 3 (treatment discontinuation): A 1-week blinded dose tapering period (Week 25). Participants were followed-up after 1 week (Week 26). | 154 |
| Pregabalin Low Dose, Placebo Period 1 (treatment optimization): Pregabalin capsule 150 mg/day orally twice daily in 2 equally divided doses during 3-week upward titration. Flexible dosing of pregabalin capsule 150 mg/day or 300 mg/day orally twice daily in 2 equally divided doses depending on efficacy and tolerability up to Week 6. If participant had an adequate response at Week 6, fixed dosing of pregabalin capsule 150 mg/day or 300 mg/day orally twice daily in 2 equally divided doses up to Week 12. Period 2 (fixed dosing): Pregabalin was discontinued with a blinded dose tapering over 1-week followed by matching placebo capsule orally twice daily up to Week 24. Period 3 (treatment discontinuation): Continued matching placebo capsule orally twice daily for 1 week (Week 25). Participants were followed-up after 1 week (Week 26). | 52 |
| Lorazepam, Lorazepam Period 1 (treatment optimization): Lorazepam capsule 2 mg/day orally twice daily in 2 equally divided doses in Week 1, lorazepam capsule 3 mg/day orally in 2 divided doses (1 mg in morning, 2 mg at night) in Week 2 and 3, during 3-week upward titration. Flexible dosing of lorazepam capsule 3 or 4 mg/day orally twice daily in 2 divided doses (1 or 2 mg in morning, 2 mg at night) depending on efficacy and tolerability up to Week 6. If participant had an adequate response at Week 6, fixed dosing of lorazepam capsule 3 or 4 mg/day orally twice daily in 2 divided doses (1 or 2 mg in morning, 2 mg at night) up to Week 12. Period 2 (fixed dosing): Continued lorazepam capsule 3 or 4 mg/day orally twice daily in 2 divided doses (1 or 2 mg in morning, 2 mg at night) up to Week 24. Period 3 (treatment discontinuation): A 1-week blinded dose tapering period (Week 25). Participants were followed-up after 1 week (Week 26). | 153 |
| Lorazepam, Placebo Period 1 (treatment optimization): Lorazepam capsule 2 mg/day orally twice daily in 2 equally divided doses in Week 1, lorazepam capsule 3 mg/day orally in 2 divided doses (1 mg in morning, 2 mg at night) in Week 2 and 3, during 3-week upward titration. Flexible dosing of lorazepam capsule 3 or 4 mg/day orally twice daily in 2 divided doses (1 or 2 mg in morning, 2 mg at night) depending on efficacy and tolerability up to Week 6. If participant had an adequate response at Week 6, fixed dosing of lorazepam capsule 3 or 4 mg/day orally twice daily in 2 divided doses (1 or 2 mg in morning, 2 mg at night) up to Week 12. Period 2 (fixed dosing): Lorazepam was discontinued with a blinded dose tapering over 1-week followed by matching placebo capsule orally twice daily up to Week 24. Period 3 (treatment discontinuation): Continued matching placebo capsule orally twice daily for 1 week (Week 25). Participants were followed-up after 1 week (Week 26). | 50 |
| Total | 615 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 |
|---|---|---|---|---|---|---|---|
| Fixed Dosing (Week 13 to Week 24) | Adverse Event | 5 | 4 | 5 | 2 | 3 | 1 |
| Fixed Dosing (Week 13 to Week 24) | Lack of Efficacy | 2 | 1 | 2 | 5 | 5 | 2 |
| Fixed Dosing (Week 13 to Week 24) | Lost to Follow-up | 1 | 0 | 1 | 0 | 1 | 1 |
| Fixed Dosing (Week 13 to Week 24) | Other | 5 | 3 | 4 | 1 | 4 | 3 |
| Fixed Dosing (Week 13 to Week 24) | Withdrawal by Subject | 2 | 3 | 6 | 3 | 6 | 2 |
| Follow-up (Week 26) | Adverse Event | 0 | 0 | 0 | 0 | 1 | 0 |
| Follow-up (Week 26) | Death | 0 | 0 | 1 | 0 | 0 | 0 |
| Follow-up (Week 26) | Lost to Follow-up | 0 | 0 | 1 | 0 | 1 | 0 |
| Follow-up (Week 26) | Other | 1 | 1 | 0 | 0 | 0 | 0 |
| Follow-up (Week 26) | Withdrawal by Subject | 1 | 0 | 0 | 0 | 0 | 0 |
| Treatment Discontinuation (Week 25) | Adverse Event | 1 | 0 | 2 | 1 | 0 | 1 |
| Treatment Discontinuation (Week 25) | Lack of Efficacy | 1 | 0 | 0 | 0 | 0 | 0 |
| Treatment Discontinuation (Week 25) | Lost to Follow-up | 0 | 0 | 1 | 0 | 0 | 0 |
| Treatment Optimization (Up to Week 12) | Adverse Event | 7 | 5 | 15 | 3 | 9 | 5 |
| Treatment Optimization (Up to Week 12) | Lack of Efficacy | 5 | 2 | 10 | 5 | 9 | 1 |
| Treatment Optimization (Up to Week 12) | Lost to Follow-up | 1 | 0 | 2 | 0 | 2 | 1 |
| Treatment Optimization (Up to Week 12) | Other | 10 | 4 | 8 | 2 | 9 | 0 |
| Treatment Optimization (Up to Week 12) | Withdrawal by Subject | 10 | 2 | 7 | 4 | 10 | 4 |
Baseline characteristics
| Characteristic | Pregabalin High Dose, Pregabalin High Dose | Pregabalin High Dose, Placebo | Pregabalin Low Dose, Pregabalin Low Dose | Pregabalin Low Dose, Placebo | Lorazepam, Lorazepam | Lorazepam, Placebo | Total |
|---|---|---|---|---|---|---|---|
| Age, Customized 18 to 44 years | 75 participants | 30 participants | 100 participants | 28 participants | 86 participants | 27 participants | 346 participants |
| Age, Customized 45 to 64 years | 79 participants | 22 participants | 51 participants | 24 participants | 66 participants | 23 participants | 265 participants |
| Age, Customized Greater than or equal to 65 years | 0 participants | 0 participants | 3 participants | 0 participants | 1 participants | 0 participants | 4 participants |
| Sex: Female, Male Female | 89 Participants | 30 Participants | 101 Participants | 32 Participants | 95 Participants | 27 Participants | 374 Participants |
| Sex: Female, Male Male | 65 Participants | 22 Participants | 53 Participants | 20 Participants | 58 Participants | 23 Participants | 241 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk |
|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 110 / 154 | 40 / 52 | 108 / 154 | 38 / 52 | 100 / 153 | 35 / 50 |
| serious Total, serious adverse events | 2 / 154 | 0 / 52 | 5 / 154 | 2 / 52 | 4 / 153 | 0 / 50 |
Outcome results
Primary
Change From Baseline in Hamilton Anxiety Scale (HAM-A) for Cohort 1 (Less Than 3-Month Last Visit) at Discontinuation Week 1
HAM-A measures treatment-related changes in generalized anxiety symptoms; 14 item questionnaire scored 0 (not present) to 4 (very severe); total possible range 0 to 56. Lower score indicates less affected.
Time frame: Baseline, Week 1 post-treatment discontinuation (discontinuation occurred prior to Week 9)
Population: Per-protocol analysis set: all randomized participants who had baseline with at least 1 discontinuation or efficacy visit, and were not major protocol violators. Cohort 1: Participants who discontinued study prior to Week 9 and had at least 1 discontinuation assessment were included. n=participants evaluable at given time points for each group.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Pregabalin High Dose | Change From Baseline in Hamilton Anxiety Scale (HAM-A) for Cohort 1 (Less Than 3-Month Last Visit) at Discontinuation Week 1 | Baseline (n=15,19,21) | 25.8 units on a scale | Standard Deviation 4.23 |
| Pregabalin High Dose | Change From Baseline in Hamilton Anxiety Scale (HAM-A) for Cohort 1 (Less Than 3-Month Last Visit) at Discontinuation Week 1 | Change at Discontinuation Week 1 (n=15,19,18) | -7.7 units on a scale | Standard Deviation 6.75 |
| Pregabalin Low Dose | Change From Baseline in Hamilton Anxiety Scale (HAM-A) for Cohort 1 (Less Than 3-Month Last Visit) at Discontinuation Week 1 | Baseline (n=15,19,21) | 24.9 units on a scale | Standard Deviation 4.15 |
| Pregabalin Low Dose | Change From Baseline in Hamilton Anxiety Scale (HAM-A) for Cohort 1 (Less Than 3-Month Last Visit) at Discontinuation Week 1 | Change at Discontinuation Week 1 (n=15,19,18) | -5.9 units on a scale | Standard Deviation 7.2 |
| Lorazepam | Change From Baseline in Hamilton Anxiety Scale (HAM-A) for Cohort 1 (Less Than 3-Month Last Visit) at Discontinuation Week 1 | Baseline (n=15,19,21) | 24.4 units on a scale | Standard Deviation 4.88 |
| Lorazepam | Change From Baseline in Hamilton Anxiety Scale (HAM-A) for Cohort 1 (Less Than 3-Month Last Visit) at Discontinuation Week 1 | Change at Discontinuation Week 1 (n=15,19,18) | -9.9 units on a scale | Standard Deviation 10.81 |
Primary
Change From Baseline in Hamilton Anxiety Scale (HAM-A) for Cohort 1 (Less Than 3-Month Last Visit) at Discontinuation Week 2
HAM-A measures treatment-related changes in generalized anxiety symptoms; 14 item questionnaire scored 0 (not present) to 4 (very severe); total possible range 0 to 56. Lower score indicates less affected.
Time frame: Baseline, Week 2 post-treatment discontinuation (discontinuation occurred prior to Week 9)
Population: Per-protocol analysis set. Cohort 1: Participants who discontinued study prior to Week 9 and had at least 1 discontinuation assessment were included in less-than Month 3 last visit analysis. Here, 'N' (Number of Participants Analyzed) signifies those participants who were evaluable for this measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Pregabalin High Dose | Change From Baseline in Hamilton Anxiety Scale (HAM-A) for Cohort 1 (Less Than 3-Month Last Visit) at Discontinuation Week 2 | -12.0 units on a scale | Standard Deviation 7.24 |
| Pregabalin Low Dose | Change From Baseline in Hamilton Anxiety Scale (HAM-A) for Cohort 1 (Less Than 3-Month Last Visit) at Discontinuation Week 2 | -5.9 units on a scale | Standard Deviation 5.46 |
| Lorazepam | Change From Baseline in Hamilton Anxiety Scale (HAM-A) for Cohort 1 (Less Than 3-Month Last Visit) at Discontinuation Week 2 | -9.7 units on a scale | Standard Deviation 11.08 |
Primary
Change From Baseline in Hamilton Anxiety Scale (HAM-A) for Cohort 2 (3-Month Last Visit) at Discontinuation Week 1
HAM-A measures treatment-related changes in generalized anxiety symptoms; 14 item questionnaire scored 0 (not present) to 4 (very severe); total possible range 0 to 56. Lower score indicates less affected.
Time frame: Baseline, Week 1 post-treatment discontinuation (discontinuation occurred from Week 9 to Week 15)
Population: Per-protocol analysis set: all randomized participants who had baseline with at least 1 discontinuation or efficacy visit, and were not major protocol violators. Cohort 2: Participants who discontinued study from Week 9 to Week 15 and had at least 1 discontinuation assessment were included in Month 3 last visit analysis.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Pregabalin High Dose | Change From Baseline in Hamilton Anxiety Scale (HAM-A) for Cohort 2 (3-Month Last Visit) at Discontinuation Week 1 | Baseline | 25.0 units on a scale | Standard Deviation 5.37 |
| Pregabalin High Dose | Change From Baseline in Hamilton Anxiety Scale (HAM-A) for Cohort 2 (3-Month Last Visit) at Discontinuation Week 1 | Change at Discontinuation Week 1 | -15.3 units on a scale | Standard Deviation 7.76 |
| Pregabalin Low Dose | Change From Baseline in Hamilton Anxiety Scale (HAM-A) for Cohort 2 (3-Month Last Visit) at Discontinuation Week 1 | Baseline | 24.7 units on a scale | Standard Deviation 3.89 |
| Pregabalin Low Dose | Change From Baseline in Hamilton Anxiety Scale (HAM-A) for Cohort 2 (3-Month Last Visit) at Discontinuation Week 1 | Change at Discontinuation Week 1 | -15.3 units on a scale | Standard Deviation 6.71 |
| Lorazepam | Change From Baseline in Hamilton Anxiety Scale (HAM-A) for Cohort 2 (3-Month Last Visit) at Discontinuation Week 1 | Baseline | 24.6 units on a scale | Standard Deviation 4.76 |
| Lorazepam | Change From Baseline in Hamilton Anxiety Scale (HAM-A) for Cohort 2 (3-Month Last Visit) at Discontinuation Week 1 | Change at Discontinuation Week 1 | -15.8 units on a scale | Standard Deviation 7.92 |
Primary
Change From Baseline in Hamilton Anxiety Scale (HAM-A) for Cohort 2 (3-Month Last Visit) at Discontinuation Week 2
HAM-A measures treatment-related changes in generalized anxiety symptoms; 14 item questionnaire scored 0 (not present) to 4 (very severe); total possible range 0 to 56. Lower score indicates less affected.
Time frame: Baseline, Week 2 post-treatment discontinuation (discontinuation occurred from Week 9 to Week 15)
Population: Per-protocol analysis set. Cohort 2: Participants who discontinued study from Week 9 to Week 15 and had at least 1 discontinuation assessment were included in Month 3 last visit analysis. Here, N (Number of Participants Analyzed) signifies those participants who were evaluable for this measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Pregabalin High Dose | Change From Baseline in Hamilton Anxiety Scale (HAM-A) for Cohort 2 (3-Month Last Visit) at Discontinuation Week 2 | -15.6 units on a scale | Standard Deviation 7.42 |
| Pregabalin Low Dose | Change From Baseline in Hamilton Anxiety Scale (HAM-A) for Cohort 2 (3-Month Last Visit) at Discontinuation Week 2 | -14.9 units on a scale | Standard Deviation 7.11 |
| Lorazepam | Change From Baseline in Hamilton Anxiety Scale (HAM-A) for Cohort 2 (3-Month Last Visit) at Discontinuation Week 2 | -16.0 units on a scale | Standard Deviation 7.96 |
Primary
Change From Baseline in Hamilton Anxiety Scale (HAM-A) for Cohort 3 (6-Month Last Visit) at Discontinuation Week 1
HAM-A measures treatment-related changes in generalized anxiety symptoms; 14 item questionnaire scored 0 (not present) to 4 (very severe); total possible range 0 to 56. Lower score indicates less affected.
Time frame: Baseline, Week 1 post-treatment discontinuation (discontinuation occurred after Week 15 to Week 24)
Population: Per-protocol analysis set: all randomized participants who had baseline with at least 1 discontinuation or efficacy visit, and were not major protocol violators. Cohort 3: Participants who discontinued study after Week 15 or completed Week 24 visit and had at least 1 discontinuation assessment were included in Month 6 last visit analysis.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Pregabalin High Dose | Change From Baseline in Hamilton Anxiety Scale (HAM-A) for Cohort 3 (6-Month Last Visit) at Discontinuation Week 1 | Baseline | 25.5 units on a scale | Standard Deviation 3.85 |
| Pregabalin High Dose | Change From Baseline in Hamilton Anxiety Scale (HAM-A) for Cohort 3 (6-Month Last Visit) at Discontinuation Week 1 | Change at Discontinuation Week 1 | -17.6 units on a scale | Standard Deviation 7.25 |
| Pregabalin Low Dose | Change From Baseline in Hamilton Anxiety Scale (HAM-A) for Cohort 3 (6-Month Last Visit) at Discontinuation Week 1 | Baseline | 24.2 units on a scale | Standard Deviation 4.64 |
| Pregabalin Low Dose | Change From Baseline in Hamilton Anxiety Scale (HAM-A) for Cohort 3 (6-Month Last Visit) at Discontinuation Week 1 | Change at Discontinuation Week 1 | -18.7 units on a scale | Standard Deviation 5.36 |
| Lorazepam | Change From Baseline in Hamilton Anxiety Scale (HAM-A) for Cohort 3 (6-Month Last Visit) at Discontinuation Week 1 | Baseline | 24.7 units on a scale | Standard Deviation 3.85 |
| Lorazepam | Change From Baseline in Hamilton Anxiety Scale (HAM-A) for Cohort 3 (6-Month Last Visit) at Discontinuation Week 1 | Change at Discontinuation Week 1 | -18.4 units on a scale | Standard Deviation 6.33 |
| Pregabalin Low Dose, Placebo | Change From Baseline in Hamilton Anxiety Scale (HAM-A) for Cohort 3 (6-Month Last Visit) at Discontinuation Week 1 | Baseline | 24.9 units on a scale | Standard Deviation 3.82 |
| Pregabalin Low Dose, Placebo | Change From Baseline in Hamilton Anxiety Scale (HAM-A) for Cohort 3 (6-Month Last Visit) at Discontinuation Week 1 | Change at Discontinuation Week 1 | -16.5 units on a scale | Standard Deviation 7.25 |
| Lorazepam, Lorazepam | Change From Baseline in Hamilton Anxiety Scale (HAM-A) for Cohort 3 (6-Month Last Visit) at Discontinuation Week 1 | Baseline | 24.6 units on a scale | Standard Deviation 4.36 |
| Lorazepam, Lorazepam | Change From Baseline in Hamilton Anxiety Scale (HAM-A) for Cohort 3 (6-Month Last Visit) at Discontinuation Week 1 | Change at Discontinuation Week 1 | -16.2 units on a scale | Standard Deviation 8.11 |
| Lorazepam, Placebo | Change From Baseline in Hamilton Anxiety Scale (HAM-A) for Cohort 3 (6-Month Last Visit) at Discontinuation Week 1 | Baseline | 24.9 units on a scale | Standard Deviation 3.93 |
| Lorazepam, Placebo | Change From Baseline in Hamilton Anxiety Scale (HAM-A) for Cohort 3 (6-Month Last Visit) at Discontinuation Week 1 | Change at Discontinuation Week 1 | -19.1 units on a scale | Standard Deviation 6.69 |
Primary
Change From Baseline in Hamilton Anxiety Scale (HAM-A) for Cohort 3 (6-Month Last Visit) at Discontinuation Week 2
HAM-A measures treatment-related changes in generalized anxiety symptoms; 14 item questionnaire scored 0 (not present) to 4 (very severe); possible range 0 to 56. Lower score indicates less affected.
Time frame: Baseline, Week 2 post-treatment discontinuation (discontinuation occurred after Week 15 to Week 24)
Population: Per-protocol analysis set. Cohort 3: Participants who discontinued study after Week 15 or completed Week 24 visit and had at least 1 discontinuation assessment were included in Month 6 last visit analysis. Here, N (Number of Participants Analyzed) signifies those participants who were evaluable for this measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Pregabalin High Dose | Change From Baseline in Hamilton Anxiety Scale (HAM-A) for Cohort 3 (6-Month Last Visit) at Discontinuation Week 2 | -16.6 units on a scale | Standard Deviation 8.53 |
| Pregabalin Low Dose | Change From Baseline in Hamilton Anxiety Scale (HAM-A) for Cohort 3 (6-Month Last Visit) at Discontinuation Week 2 | -19.1 units on a scale | Standard Deviation 5.8 |
| Lorazepam | Change From Baseline in Hamilton Anxiety Scale (HAM-A) for Cohort 3 (6-Month Last Visit) at Discontinuation Week 2 | -18.3 units on a scale | Standard Deviation 7.05 |
| Pregabalin Low Dose, Placebo | Change From Baseline in Hamilton Anxiety Scale (HAM-A) for Cohort 3 (6-Month Last Visit) at Discontinuation Week 2 | -16.0 units on a scale | Standard Deviation 8.17 |
| Lorazepam, Lorazepam | Change From Baseline in Hamilton Anxiety Scale (HAM-A) for Cohort 3 (6-Month Last Visit) at Discontinuation Week 2 | -16.7 units on a scale | Standard Deviation 7.52 |
| Lorazepam, Placebo | Change From Baseline in Hamilton Anxiety Scale (HAM-A) for Cohort 3 (6-Month Last Visit) at Discontinuation Week 2 | -18.7 units on a scale | Standard Deviation 7.38 |
Primary
Change From Last Visit on Treatment in Physician's Withdrawal Checklist (PWC) Score for Cohort 1 (Less Than 3-Month Last Visit) at Discontinuation Week 1
PWC: 20 item physician rated interview measuring anxiolytic drug withdrawal-related signs and symptoms (gastrointestinal, mood, sleep, motor, somatic, perception and cognition); range 0 (not present) to 3 (severe); total score range: 0 to 60; higher score = more affected.
Time frame: Last visit on treatment, Week 1 post-treatment discontinuation (discontinuation occurred prior to Week 9)
Population: Per-protocol analysis set. Cohort 1: Participants who discontinued study prior to Week 9 and had at least 1 discontinuation assessment were included in less-than Month 3 last visit analysis. N (Number of Participants Analyzed) = participants evaluable for this measure. 'n' = participants evaluable at given time points for each group respectively.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Pregabalin High Dose | Change From Last Visit on Treatment in Physician's Withdrawal Checklist (PWC) Score for Cohort 1 (Less Than 3-Month Last Visit) at Discontinuation Week 1 | Last visit on treatment (n=15,18,20) | 10.1 units on a scale | Standard Deviation 8.72 |
| Pregabalin High Dose | Change From Last Visit on Treatment in Physician's Withdrawal Checklist (PWC) Score for Cohort 1 (Less Than 3-Month Last Visit) at Discontinuation Week 1 | Change at Discontinuation Week 1 (n=15,18,18) | 0.1 units on a scale | Standard Deviation 9.89 |
| Pregabalin Low Dose | Change From Last Visit on Treatment in Physician's Withdrawal Checklist (PWC) Score for Cohort 1 (Less Than 3-Month Last Visit) at Discontinuation Week 1 | Last visit on treatment (n=15,18,20) | 16.8 units on a scale | Standard Deviation 13.2 |
| Pregabalin Low Dose | Change From Last Visit on Treatment in Physician's Withdrawal Checklist (PWC) Score for Cohort 1 (Less Than 3-Month Last Visit) at Discontinuation Week 1 | Change at Discontinuation Week 1 (n=15,18,18) | -2.8 units on a scale | Standard Deviation 7.99 |
| Lorazepam | Change From Last Visit on Treatment in Physician's Withdrawal Checklist (PWC) Score for Cohort 1 (Less Than 3-Month Last Visit) at Discontinuation Week 1 | Last visit on treatment (n=15,18,20) | 13.1 units on a scale | Standard Deviation 10.75 |
| Lorazepam | Change From Last Visit on Treatment in Physician's Withdrawal Checklist (PWC) Score for Cohort 1 (Less Than 3-Month Last Visit) at Discontinuation Week 1 | Change at Discontinuation Week 1 (n=15,18,18) | -4.2 units on a scale | Standard Deviation 6.12 |
Primary
Change From Last Visit on Treatment in Physician's Withdrawal Checklist (PWC) Score for Cohort 1 (Less Than 3-Month Last Visit) at Discontinuation Week 2
PWC: 20 item physician rated interview measuring anxiolytic drug withdrawal-related signs and symptoms (gastrointestinal, mood, sleep, motor, somatic, perception and cognition); range 0 (not present) to 3 (severe); total score range: 0 to 60; higher score = more affected.
Time frame: Last visit on treatment, Week 2 post-treatment discontinuation (discontinuation occurred prior to Week 9)
Population: Per-protocol analysis set. Cohort 1: Participants who discontinued study prior to Week 9 and had at least 1 discontinuation assessment were included in less-than Month 3 last visit analysis. Here, N (Number of Participants Analyzed) signifies those participants evaluable for this measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Pregabalin High Dose | Change From Last Visit on Treatment in Physician's Withdrawal Checklist (PWC) Score for Cohort 1 (Less Than 3-Month Last Visit) at Discontinuation Week 2 | -2.0 units on a scale | Standard Deviation 6.39 |
| Pregabalin Low Dose | Change From Last Visit on Treatment in Physician's Withdrawal Checklist (PWC) Score for Cohort 1 (Less Than 3-Month Last Visit) at Discontinuation Week 2 | -2.7 units on a scale | Standard Deviation 9.04 |
| Lorazepam | Change From Last Visit on Treatment in Physician's Withdrawal Checklist (PWC) Score for Cohort 1 (Less Than 3-Month Last Visit) at Discontinuation Week 2 | -3.2 units on a scale | Standard Deviation 6.05 |
Primary
Change From Last Visit on Treatment in Physician's Withdrawal Checklist (PWC) Score for Cohort 2 (3-Month Last Visit) at Discontinuation Week 1
PWC: 20 item physician rated interview measuring anxiolytic drug withdrawal-related signs and symptoms (gastrointestinal, mood, sleep, motor, somatic, perception and cognition); range 0 (not present) to 3 (severe); total score range: 0 to 60; higher score = more affected.
Time frame: Last visit on treatment, Week 1 post-treatment discontinuation (discontinuation occurred from Week 9 to Week 15)
Population: Per-protocol analysis set. Cohort 2: Participants who discontinued study from Week 9 to Week 15 and had at least 1 discontinuation assessment were included in Month 3 last visit analysis. Here, N (Number of Participants Analyzed) signifies those participants who were evaluable for this measure.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Pregabalin High Dose | Change From Last Visit on Treatment in Physician's Withdrawal Checklist (PWC) Score for Cohort 2 (3-Month Last Visit) at Discontinuation Week 1 | Last visit on treatment | 7.2 units on a scale | Standard Deviation 7.32 |
| Pregabalin High Dose | Change From Last Visit on Treatment in Physician's Withdrawal Checklist (PWC) Score for Cohort 2 (3-Month Last Visit) at Discontinuation Week 1 | Change at Discontinuation Week 1 | 1.9 units on a scale | Standard Deviation 7.29 |
| Pregabalin Low Dose | Change From Last Visit on Treatment in Physician's Withdrawal Checklist (PWC) Score for Cohort 2 (3-Month Last Visit) at Discontinuation Week 1 | Last visit on treatment | 6.5 units on a scale | Standard Deviation 6.01 |
| Pregabalin Low Dose | Change From Last Visit on Treatment in Physician's Withdrawal Checklist (PWC) Score for Cohort 2 (3-Month Last Visit) at Discontinuation Week 1 | Change at Discontinuation Week 1 | 1.4 units on a scale | Standard Deviation 4.52 |
| Lorazepam | Change From Last Visit on Treatment in Physician's Withdrawal Checklist (PWC) Score for Cohort 2 (3-Month Last Visit) at Discontinuation Week 1 | Last visit on treatment | 5.0 units on a scale | Standard Deviation 3.8 |
| Lorazepam | Change From Last Visit on Treatment in Physician's Withdrawal Checklist (PWC) Score for Cohort 2 (3-Month Last Visit) at Discontinuation Week 1 | Change at Discontinuation Week 1 | 2.3 units on a scale | Standard Deviation 6.6 |
Primary
Change From Last Visit on Treatment in Physician's Withdrawal Checklist (PWC) Score for Cohort 2 (3-Month Last Visit) at Discontinuation Week 2
PWC: 20 item physician rated interview measuring anxiolytic drug withdrawal-related signs and symptoms (gastrointestinal, mood, sleep, motor, somatic, perception and cognition); range 0 (not present) to 3 (severe); total score range: 0 to 60; higher score = more affected.
Time frame: Last visit on treatment, Week 2 post-treatment discontinuation (discontinuation occurred from Week 9 to Week 15)
Population: Per-protocol analysis set. Cohort 2: Participants who discontinued study from Week 9 to Week 15 and had at least 1 discontinuation assessment were included in Month 3 last visit analysis. Here, N (Number of Participants Analyzed) signifies those participants who were evaluable for this measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Pregabalin High Dose | Change From Last Visit on Treatment in Physician's Withdrawal Checklist (PWC) Score for Cohort 2 (3-Month Last Visit) at Discontinuation Week 2 | 2.1 units on a scale | Standard Deviation 6.11 |
| Pregabalin Low Dose | Change From Last Visit on Treatment in Physician's Withdrawal Checklist (PWC) Score for Cohort 2 (3-Month Last Visit) at Discontinuation Week 2 | 2.0 units on a scale | Standard Deviation 5.51 |
| Lorazepam | Change From Last Visit on Treatment in Physician's Withdrawal Checklist (PWC) Score for Cohort 2 (3-Month Last Visit) at Discontinuation Week 2 | 1.6 units on a scale | Standard Deviation 6.33 |
Primary
Change From Last Visit on Treatment in Physician's Withdrawal Checklist (PWC) Score for Cohort 3 (6-Month Last Visit) at Discontinuation Week 1
PWC: 20 item physician rated interview measuring anxiolytic drug withdrawal-related signs and symptoms (gastrointestinal, mood, sleep, motor, somatic, perception and cognition); range 0 (not present) to 3 (severe); total score range: 0 to 60; higher score = more affected.
Time frame: Last visit on treatment, Week 1 post-treatment discontinuation (discontinuation occurred after Week 15 to Week 24)
Population: Per-protocol analysis set. Cohort 3: Participants who discontinued study after Week 15 or completed Week 24 visit and had at least 1 discontinuation assessment were included in Month 6 last visit analysis. Here, 'N' (Number of Participants Analyzed) signifies those participants who were evaluable for this measure.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Pregabalin High Dose | Change From Last Visit on Treatment in Physician's Withdrawal Checklist (PWC) Score for Cohort 3 (6-Month Last Visit) at Discontinuation Week 1 | Last visit on treatment | 5.2 units on a scale | Standard Deviation 5.62 |
| Pregabalin High Dose | Change From Last Visit on Treatment in Physician's Withdrawal Checklist (PWC) Score for Cohort 3 (6-Month Last Visit) at Discontinuation Week 1 | Change at Discontinuation Week 1 | 1.7 units on a scale | Standard Deviation 4.92 |
| Pregabalin Low Dose | Change From Last Visit on Treatment in Physician's Withdrawal Checklist (PWC) Score for Cohort 3 (6-Month Last Visit) at Discontinuation Week 1 | Last visit on treatment | 4.9 units on a scale | Standard Deviation 7.15 |
| Pregabalin Low Dose | Change From Last Visit on Treatment in Physician's Withdrawal Checklist (PWC) Score for Cohort 3 (6-Month Last Visit) at Discontinuation Week 1 | Change at Discontinuation Week 1 | 0.0 units on a scale | Standard Deviation 2.18 |
| Lorazepam | Change From Last Visit on Treatment in Physician's Withdrawal Checklist (PWC) Score for Cohort 3 (6-Month Last Visit) at Discontinuation Week 1 | Last visit on treatment | 3.9 units on a scale | Standard Deviation 4.14 |
| Lorazepam | Change From Last Visit on Treatment in Physician's Withdrawal Checklist (PWC) Score for Cohort 3 (6-Month Last Visit) at Discontinuation Week 1 | Change at Discontinuation Week 1 | 1.1 units on a scale | Standard Deviation 3.5 |
| Pregabalin Low Dose, Placebo | Change From Last Visit on Treatment in Physician's Withdrawal Checklist (PWC) Score for Cohort 3 (6-Month Last Visit) at Discontinuation Week 1 | Last visit on treatment | 6.5 units on a scale | Standard Deviation 6.72 |
| Pregabalin Low Dose, Placebo | Change From Last Visit on Treatment in Physician's Withdrawal Checklist (PWC) Score for Cohort 3 (6-Month Last Visit) at Discontinuation Week 1 | Change at Discontinuation Week 1 | 1.0 units on a scale | Standard Deviation 4.37 |
| Lorazepam, Lorazepam | Change From Last Visit on Treatment in Physician's Withdrawal Checklist (PWC) Score for Cohort 3 (6-Month Last Visit) at Discontinuation Week 1 | Last visit on treatment | 5.3 units on a scale | Standard Deviation 6.65 |
| Lorazepam, Lorazepam | Change From Last Visit on Treatment in Physician's Withdrawal Checklist (PWC) Score for Cohort 3 (6-Month Last Visit) at Discontinuation Week 1 | Change at Discontinuation Week 1 | 3.0 units on a scale | Standard Deviation 6.79 |
| Lorazepam, Placebo | Change From Last Visit on Treatment in Physician's Withdrawal Checklist (PWC) Score for Cohort 3 (6-Month Last Visit) at Discontinuation Week 1 | Last visit on treatment | 4.7 units on a scale | Standard Deviation 4.5 |
| Lorazepam, Placebo | Change From Last Visit on Treatment in Physician's Withdrawal Checklist (PWC) Score for Cohort 3 (6-Month Last Visit) at Discontinuation Week 1 | Change at Discontinuation Week 1 | -0.1 units on a scale | Standard Deviation 3.22 |
Primary
Change From Last Visit on Treatment in Physician's Withdrawal Checklist (PWC) Score for Cohort 3 (6-Month Last Visit) at Discontinuation Week 2
PWC: 20 item physician rated interview measuring anxiolytic drug withdrawal-related signs and symptoms (gastrointestinal, mood, sleep, motor, somatic, perception and cognition); range 0 (not present) to 3 (severe); total score range: 0 to 60; higher score = more affected.
Time frame: Last visit on treatment, Week 2 post-treatment discontinuation (discontinuation occurred after Week 15 to Week 24)
Population: Per-protocol analysis set. Cohort 3: Participants who discontinued study after Week 15 or completed Week 24 visit and had at least 1 discontinuation assessment were included in Month 6 last visit analysis. Here, N (Number of Participants Analyzed) signifies those participants who were evaluable for this measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Pregabalin High Dose | Change From Last Visit on Treatment in Physician's Withdrawal Checklist (PWC) Score for Cohort 3 (6-Month Last Visit) at Discontinuation Week 2 | 2.8 units on a scale | Standard Deviation 5.99 |
| Pregabalin Low Dose | Change From Last Visit on Treatment in Physician's Withdrawal Checklist (PWC) Score for Cohort 3 (6-Month Last Visit) at Discontinuation Week 2 | -1.0 units on a scale | Standard Deviation 5.65 |
| Lorazepam | Change From Last Visit on Treatment in Physician's Withdrawal Checklist (PWC) Score for Cohort 3 (6-Month Last Visit) at Discontinuation Week 2 | 1.7 units on a scale | Standard Deviation 4.78 |
| Pregabalin Low Dose, Placebo | Change From Last Visit on Treatment in Physician's Withdrawal Checklist (PWC) Score for Cohort 3 (6-Month Last Visit) at Discontinuation Week 2 | 1.8 units on a scale | Standard Deviation 5.14 |
| Lorazepam, Lorazepam | Change From Last Visit on Treatment in Physician's Withdrawal Checklist (PWC) Score for Cohort 3 (6-Month Last Visit) at Discontinuation Week 2 | 2.2 units on a scale | Standard Deviation 6.02 |
| Lorazepam, Placebo | Change From Last Visit on Treatment in Physician's Withdrawal Checklist (PWC) Score for Cohort 3 (6-Month Last Visit) at Discontinuation Week 2 | -0.1 units on a scale | Standard Deviation 3.63 |
Secondary
Change From Baseline in Clinical Global Impression - Severity (CGI-S) Score at Week 12
CGI-S: 7-point clinician rated scale to assess severity of participant's current illness state; range: 1 (normal - not ill at all) to 7 (among the most extremely ill patients). Higher score = more affected.
Time frame: Baseline, Week 12
Population: Per-protocol analysis set: all randomized participants who had baseline with at least 1 discontinuation or efficacy visit, and were not major protocol violators. Here, 'N' (Number of Participants Analyzed) signifies those participants who were evaluable for this measure. LOCF method was used to impute missing values.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Pregabalin High Dose | Change From Baseline in Clinical Global Impression - Severity (CGI-S) Score at Week 12 | -2.3 units on a scale | Standard Deviation 1.13 |
| Pregabalin Low Dose | Change From Baseline in Clinical Global Impression - Severity (CGI-S) Score at Week 12 | -2.1 units on a scale | Standard Deviation 1.13 |
| Lorazepam | Change From Baseline in Clinical Global Impression - Severity (CGI-S) Score at Week 12 | -2.1 units on a scale | Standard Deviation 1.17 |
Secondary
Change From Baseline in Clinical Global Impression - Severity (CGI-S) Score at Week 24
CGI-S: 7-point clinician rated scale to assess severity of participant's current illness state; range: 1 (normal - not ill at all) to 7 (among the most extremely ill patients). Higher score = more affected
Time frame: Baseline, Week 24
Population: Per-protocol analysis set: all randomized participants who had baseline with at least 1 discontinuation or efficacy visit, and were not major protocol violators. LOCF method was used to impute missing values.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Pregabalin High Dose | Change From Baseline in Clinical Global Impression - Severity (CGI-S) Score at Week 24 | -2.4 units on a scale | Standard Deviation 1.13 |
| Pregabalin Low Dose | Change From Baseline in Clinical Global Impression - Severity (CGI-S) Score at Week 24 | -2.3 units on a scale | Standard Deviation 1.24 |
| Lorazepam | Change From Baseline in Clinical Global Impression - Severity (CGI-S) Score at Week 24 | -2.4 units on a scale | Standard Deviation 1.04 |
| Pregabalin Low Dose, Placebo | Change From Baseline in Clinical Global Impression - Severity (CGI-S) Score at Week 24 | -2.0 units on a scale | Standard Deviation 1.27 |
| Lorazepam, Lorazepam | Change From Baseline in Clinical Global Impression - Severity (CGI-S) Score at Week 24 | -2.5 units on a scale | Standard Deviation 1.11 |
| Lorazepam, Placebo | Change From Baseline in Clinical Global Impression - Severity (CGI-S) Score at Week 24 | -2.2 units on a scale | Standard Deviation 1.17 |
Secondary
Change From Baseline in Hamilton Anxiety Scale (HAM-A) Score at Week 12
HAM-A measures treatment-related changes in generalized anxiety symptoms; 14 item questionnaire scored 0 (not present) to 4 (very severe); total possible range 0 to 56. Lower score indicates less affected.
Time frame: Baseline, Week 12
Population: Per-protocol analysis set: all randomized participants who had baseline with at least 1 discontinuation or efficacy visit, and were not major protocol violators. LOCF method was used to impute missing values. Here, N (Number of Participants Analyzed) signifies those participants who were evaluable for this measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Pregabalin High Dose | Change From Baseline in Hamilton Anxiety Scale (HAM-A) Score at Week 12 | -17.4 units on a scale | Standard Deviation 7.39 |
| Pregabalin Low Dose | Change From Baseline in Hamilton Anxiety Scale (HAM-A) Score at Week 12 | -16.0 units on a scale | Standard Deviation 7.45 |
| Lorazepam | Change From Baseline in Hamilton Anxiety Scale (HAM-A) Score at Week 12 | -16.7 units on a scale | Standard Deviation 7.92 |
Secondary
Change From Baseline in Hamilton Anxiety Scale (HAM-A) Score at Week 24
HAM-A measures treatment-related changes in generalized anxiety symptoms; 14 item questionnaire scored 0 (not present) to 4 (very severe); total possible range 0 to 56. Lower score indicates less affected.
Time frame: Baseline, Week 24
Population: Per-protocol analysis set: all randomized participants who had baseline with at least 1 discontinuation or efficacy visit, and were not major protocol violators. LOCF method was used to impute missing values.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Pregabalin High Dose | Change From Baseline in Hamilton Anxiety Scale (HAM-A) Score at Week 24 | -18.7 units on a scale | Standard Deviation 7.33 |
| Pregabalin Low Dose | Change From Baseline in Hamilton Anxiety Scale (HAM-A) Score at Week 24 | -17.5 units on a scale | Standard Deviation 6.89 |
| Lorazepam | Change From Baseline in Hamilton Anxiety Scale (HAM-A) Score at Week 24 | -18.2 units on a scale | Standard Deviation 6.59 |
| Pregabalin Low Dose, Placebo | Change From Baseline in Hamilton Anxiety Scale (HAM-A) Score at Week 24 | -14.9 units on a scale | Standard Deviation 7.85 |
| Lorazepam, Lorazepam | Change From Baseline in Hamilton Anxiety Scale (HAM-A) Score at Week 24 | -19.0 units on a scale | Standard Deviation 7.24 |
| Lorazepam, Placebo | Change From Baseline in Hamilton Anxiety Scale (HAM-A) Score at Week 24 | -17.5 units on a scale | Standard Deviation 8.34 |
Secondary
Change From Baseline in Physician's Withdrawal Checklist (PWC) Score for Cohort 1 (Less Than 3-Month Last Visit) at Discontinuation Week 1 and 2
PWC: 20 item physician rated interview measuring anxiolytic drug withdrawal-related signs and symptoms (gastrointestinal, mood, sleep, motor, somatic, perception and cognition); range 0 (not present) to 3 (severe); total score range: 0 to 60; higher score = more affected.
Time frame: Baseline, Week 1, 2 post-treatment discontinuation (discontinuation occurred prior to Week 9)
Population: Per-protocol analysis set. Cohort 1: Participants who discontinued study prior to Week 9 and had at least 1 discontinuation assessment were included in less-than Month 3 last visit analysis. N (Number of Participants Analyzed) = participants evaluable for this measure. 'n' = participants evaluable at given time points for each group respectively.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Pregabalin High Dose | Change From Baseline in Physician's Withdrawal Checklist (PWC) Score for Cohort 1 (Less Than 3-Month Last Visit) at Discontinuation Week 1 and 2 | Change at Discontinuation Week 1 (n=14,19,18) | -3.4 units on a scale | Standard Deviation 11.91 |
| Pregabalin High Dose | Change From Baseline in Physician's Withdrawal Checklist (PWC) Score for Cohort 1 (Less Than 3-Month Last Visit) at Discontinuation Week 1 and 2 | Baseline (n=14,19,21) | 13.6 units on a scale | Standard Deviation 8.19 |
| Pregabalin High Dose | Change From Baseline in Physician's Withdrawal Checklist (PWC) Score for Cohort 1 (Less Than 3-Month Last Visit) at Discontinuation Week 1 and 2 | Change at Discontinuation Week 2 (n=13,15,16) | -4.7 units on a scale | Standard Deviation 10.62 |
| Pregabalin Low Dose | Change From Baseline in Physician's Withdrawal Checklist (PWC) Score for Cohort 1 (Less Than 3-Month Last Visit) at Discontinuation Week 1 and 2 | Change at Discontinuation Week 1 (n=14,19,18) | -3.3 units on a scale | Standard Deviation 9.12 |
| Pregabalin Low Dose | Change From Baseline in Physician's Withdrawal Checklist (PWC) Score for Cohort 1 (Less Than 3-Month Last Visit) at Discontinuation Week 1 and 2 | Baseline (n=14,19,21) | 17.6 units on a scale | Standard Deviation 10.68 |
| Pregabalin Low Dose | Change From Baseline in Physician's Withdrawal Checklist (PWC) Score for Cohort 1 (Less Than 3-Month Last Visit) at Discontinuation Week 1 and 2 | Change at Discontinuation Week 2 (n=13,15,16) | -2.7 units on a scale | Standard Deviation 8.2 |
| Lorazepam | Change From Baseline in Physician's Withdrawal Checklist (PWC) Score for Cohort 1 (Less Than 3-Month Last Visit) at Discontinuation Week 1 and 2 | Baseline (n=14,19,21) | 16.4 units on a scale | Standard Deviation 8.62 |
| Lorazepam | Change From Baseline in Physician's Withdrawal Checklist (PWC) Score for Cohort 1 (Less Than 3-Month Last Visit) at Discontinuation Week 1 and 2 | Change at Discontinuation Week 2 (n=13,15,16) | -5.4 units on a scale | Standard Deviation 8.34 |
| Lorazepam | Change From Baseline in Physician's Withdrawal Checklist (PWC) Score for Cohort 1 (Less Than 3-Month Last Visit) at Discontinuation Week 1 and 2 | Change at Discontinuation Week 1 (n=14,19,18) | -5.9 units on a scale | Standard Deviation 7.43 |
Secondary
Change From Baseline in Physician's Withdrawal Checklist (PWC) Score for Cohort 2 (3-Month Last Visit) at Discontinuation Week 1 and 2
PWC: 20 item physician rated interview measuring anxiolytic drug withdrawal-related signs and symptoms (gastrointestinal, mood, sleep, motor, somatic, perception and cognition); range 0 (not present) to 3 (severe); total score range: 0 to 60; higher score = more affected.
Time frame: Baseline, Week 1, 2 post-treatment discontinuation (discontinuation occurred from Week 9 to Week 15)
Population: Per-protocol analysis set. Cohort 2: Participants who discontinued study from Week 9 to Week 15 and had at least 1 discontinuation assessment were included in Month 3 last visit analysis. N (Number of Participants Analyzed) = participants evaluable for this measure. 'n' = participants evaluable at given time points for each group respectively.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Pregabalin High Dose | Change From Baseline in Physician's Withdrawal Checklist (PWC) Score for Cohort 2 (3-Month Last Visit) at Discontinuation Week 1 and 2 | Change at Discontinuation Week 1 (n=57,51,49) | -8.5 units on a scale | Standard Deviation 9.4 |
| Pregabalin High Dose | Change From Baseline in Physician's Withdrawal Checklist (PWC) Score for Cohort 2 (3-Month Last Visit) at Discontinuation Week 1 and 2 | Baseline (n=57,51,52) | 17.4 units on a scale | Standard Deviation 7.81 |
| Pregabalin High Dose | Change From Baseline in Physician's Withdrawal Checklist (PWC) Score for Cohort 2 (3-Month Last Visit) at Discontinuation Week 1 and 2 | Change at Discontinuation Week 2 (n=53,48,44) | -8.3 units on a scale | Standard Deviation 9.53 |
| Pregabalin Low Dose | Change From Baseline in Physician's Withdrawal Checklist (PWC) Score for Cohort 2 (3-Month Last Visit) at Discontinuation Week 1 and 2 | Change at Discontinuation Week 1 (n=57,51,49) | -9.3 units on a scale | Standard Deviation 9.48 |
| Pregabalin Low Dose | Change From Baseline in Physician's Withdrawal Checklist (PWC) Score for Cohort 2 (3-Month Last Visit) at Discontinuation Week 1 and 2 | Baseline (n=57,51,52) | 17.1 units on a scale | Standard Deviation 9.84 |
| Pregabalin Low Dose | Change From Baseline in Physician's Withdrawal Checklist (PWC) Score for Cohort 2 (3-Month Last Visit) at Discontinuation Week 1 and 2 | Change at Discontinuation Week 2 (n=53,48,44) | -8.7 units on a scale | Standard Deviation 9.68 |
| Lorazepam | Change From Baseline in Physician's Withdrawal Checklist (PWC) Score for Cohort 2 (3-Month Last Visit) at Discontinuation Week 1 and 2 | Baseline (n=57,51,52) | 14.8 units on a scale | Standard Deviation 7.86 |
| Lorazepam | Change From Baseline in Physician's Withdrawal Checklist (PWC) Score for Cohort 2 (3-Month Last Visit) at Discontinuation Week 1 and 2 | Change at Discontinuation Week 2 (n=53,48,44) | -8.0 units on a scale | Standard Deviation 9.7 |
| Lorazepam | Change From Baseline in Physician's Withdrawal Checklist (PWC) Score for Cohort 2 (3-Month Last Visit) at Discontinuation Week 1 and 2 | Change at Discontinuation Week 1 (n=57,51,49) | -7.6 units on a scale | Standard Deviation 9.53 |
Secondary
Change From Baseline in Physician's Withdrawal Checklist (PWC) Score for Cohort 3 (6-Month Last Visit) at Discontinuation Week 1 and 2
PWC: 20 item physician rated interview measuring anxiolytic drug withdrawal-related signs and symptoms (gastrointestinal, mood, sleep, motor, somatic, perception and cognition); range 0 (not present) to 3 (severe); total score range: 0 to 60; higher score = more affected.
Time frame: Baseline, Week 1, 2 post-treatment discontinuation (discontinuation [DC] occurred after Week 15 to Week 24)
Population: Per-protocol analysis set. Cohort 3: Participants who discontinued study after Week 15 or completed Week 24 visit and had at least 1 discontinuation assessment were included. N (Number of Participants Analyzed) = participants evaluable for this measure. 'n'=participants evaluable at given time points for each group respectively.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Pregabalin High Dose | Change From Baseline in Physician's Withdrawal Checklist (PWC) Score for Cohort 3 (6-Month Last Visit) at Discontinuation Week 1 and 2 | Change at DC Week 1 (n=109,30,94,29,99,30) | -11.0 units on a scale | Standard Deviation 9.48 |
| Pregabalin High Dose | Change From Baseline in Physician's Withdrawal Checklist (PWC) Score for Cohort 3 (6-Month Last Visit) at Discontinuation Week 1 and 2 | Baseline (n=109,30,94,29,99,30) | 17.8 units on a scale | Standard Deviation 8.36 |
| Pregabalin High Dose | Change From Baseline in Physician's Withdrawal Checklist (PWC) Score for Cohort 3 (6-Month Last Visit) at Discontinuation Week 1 and 2 | Change at DC Week 2 (n=106,29,84,26,92,30) | -9.8 units on a scale | Standard Deviation 10.32 |
| Pregabalin Low Dose | Change From Baseline in Physician's Withdrawal Checklist (PWC) Score for Cohort 3 (6-Month Last Visit) at Discontinuation Week 1 and 2 | Change at DC Week 1 (n=109,30,94,29,99,30) | -12.9 units on a scale | Standard Deviation 7.89 |
| Pregabalin Low Dose | Change From Baseline in Physician's Withdrawal Checklist (PWC) Score for Cohort 3 (6-Month Last Visit) at Discontinuation Week 1 and 2 | Baseline (n=109,30,94,29,99,30) | 17.8 units on a scale | Standard Deviation 7.79 |
| Pregabalin Low Dose | Change From Baseline in Physician's Withdrawal Checklist (PWC) Score for Cohort 3 (6-Month Last Visit) at Discontinuation Week 1 and 2 | Change at DC Week 2 (n=106,29,84,26,92,30) | -13.8 units on a scale | Standard Deviation 8.32 |
| Lorazepam | Change From Baseline in Physician's Withdrawal Checklist (PWC) Score for Cohort 3 (6-Month Last Visit) at Discontinuation Week 1 and 2 | Change at DC Week 1 (n=109,30,94,29,99,30) | -11.0 units on a scale | Standard Deviation 8.08 |
| Lorazepam | Change From Baseline in Physician's Withdrawal Checklist (PWC) Score for Cohort 3 (6-Month Last Visit) at Discontinuation Week 1 and 2 | Baseline (n=109,30,94,29,99,30) | 16.1 units on a scale | Standard Deviation 7.52 |
| Lorazepam | Change From Baseline in Physician's Withdrawal Checklist (PWC) Score for Cohort 3 (6-Month Last Visit) at Discontinuation Week 1 and 2 | Change at DC Week 2 (n=106,29,84,26,92,30) | -10.8 units on a scale | Standard Deviation 8.42 |
| Pregabalin Low Dose, Placebo | Change From Baseline in Physician's Withdrawal Checklist (PWC) Score for Cohort 3 (6-Month Last Visit) at Discontinuation Week 1 and 2 | Change at DC Week 1 (n=109,30,94,29,99,30) | -9.9 units on a scale | Standard Deviation 10.98 |
| Pregabalin Low Dose, Placebo | Change From Baseline in Physician's Withdrawal Checklist (PWC) Score for Cohort 3 (6-Month Last Visit) at Discontinuation Week 1 and 2 | Baseline (n=109,30,94,29,99,30) | 17.4 units on a scale | Standard Deviation 9.28 |
| Pregabalin Low Dose, Placebo | Change From Baseline in Physician's Withdrawal Checklist (PWC) Score for Cohort 3 (6-Month Last Visit) at Discontinuation Week 1 and 2 | Change at DC Week 2 (n=106,29,84,26,92,30) | -10.2 units on a scale | Standard Deviation 8.56 |
| Lorazepam, Lorazepam | Change From Baseline in Physician's Withdrawal Checklist (PWC) Score for Cohort 3 (6-Month Last Visit) at Discontinuation Week 1 and 2 | Change at DC Week 1 (n=109,30,94,29,99,30) | -8.7 units on a scale | Standard Deviation 10.77 |
| Lorazepam, Lorazepam | Change From Baseline in Physician's Withdrawal Checklist (PWC) Score for Cohort 3 (6-Month Last Visit) at Discontinuation Week 1 and 2 | Baseline (n=109,30,94,29,99,30) | 16.8 units on a scale | Standard Deviation 8.85 |
| Lorazepam, Lorazepam | Change From Baseline in Physician's Withdrawal Checklist (PWC) Score for Cohort 3 (6-Month Last Visit) at Discontinuation Week 1 and 2 | Change at DC Week 2 (n=106,29,84,26,92,30) | -9.6 units on a scale | Standard Deviation 9.7 |
| Lorazepam, Placebo | Change From Baseline in Physician's Withdrawal Checklist (PWC) Score for Cohort 3 (6-Month Last Visit) at Discontinuation Week 1 and 2 | Baseline (n=109,30,94,29,99,30) | 14.9 units on a scale | Standard Deviation 7.61 |
| Lorazepam, Placebo | Change From Baseline in Physician's Withdrawal Checklist (PWC) Score for Cohort 3 (6-Month Last Visit) at Discontinuation Week 1 and 2 | Change at DC Week 2 (n=106,29,84,26,92,30) | -10.3 units on a scale | Standard Deviation 7.5 |
| Lorazepam, Placebo | Change From Baseline in Physician's Withdrawal Checklist (PWC) Score for Cohort 3 (6-Month Last Visit) at Discontinuation Week 1 and 2 | Change at DC Week 1 (n=109,30,94,29,99,30) | -10.4 units on a scale | Standard Deviation 7.58 |
Secondary
Change From Last Visit of Treatment in Hamilton Anxiety Scale (HAM-A) for Cohort 1 (Less Than 3-Month Last Visit) at Discontinuation Week 1 and 2
HAM-A measures treatment-related changes in generalized anxiety symptoms; 14 item questionnaire scored 0 (not present) to 4 (very severe); total possible range 0 to 56. Lower score indicates less affected.
Time frame: Last visit on treatment, Week 1, 2 post-treatment discontinuation (discontinuation occurred prior to Week 9)
Population: Per-protocol analysis set. Cohort 1: Participants who discontinued study prior to Week 9 and had at least 1 discontinuation assessment were included in less-than Month 3 last visit analysis. N (Number of Participants Analyzed) = participants evaluable for this measure. 'n' = participants evaluable at given time points for each group respectively.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Pregabalin High Dose | Change From Last Visit of Treatment in Hamilton Anxiety Scale (HAM-A) for Cohort 1 (Less Than 3-Month Last Visit) at Discontinuation Week 1 and 2 | Change at Discontinuation Week 1 (n=15,18,18) | 2.0 units on a scale | Standard Deviation 11.45 |
| Pregabalin High Dose | Change From Last Visit of Treatment in Hamilton Anxiety Scale (HAM-A) for Cohort 1 (Less Than 3-Month Last Visit) at Discontinuation Week 1 and 2 | Last visit on treatment (n=15,18,20) | 16.1 units on a scale | Standard Deviation 8.46 |
| Pregabalin High Dose | Change From Last Visit of Treatment in Hamilton Anxiety Scale (HAM-A) for Cohort 1 (Less Than 3-Month Last Visit) at Discontinuation Week 1 and 2 | Change at Discontinuation Week 2 (n=14,15,16) | -2.3 units on a scale | Standard Deviation 9.47 |
| Pregabalin Low Dose | Change From Last Visit of Treatment in Hamilton Anxiety Scale (HAM-A) for Cohort 1 (Less Than 3-Month Last Visit) at Discontinuation Week 1 and 2 | Change at Discontinuation Week 1 (n=15,18,18) | -2.3 units on a scale | Standard Deviation 4.63 |
| Pregabalin Low Dose | Change From Last Visit of Treatment in Hamilton Anxiety Scale (HAM-A) for Cohort 1 (Less Than 3-Month Last Visit) at Discontinuation Week 1 and 2 | Last visit on treatment (n=15,18,20) | 21.6 units on a scale | Standard Deviation 6.18 |
| Pregabalin Low Dose | Change From Last Visit of Treatment in Hamilton Anxiety Scale (HAM-A) for Cohort 1 (Less Than 3-Month Last Visit) at Discontinuation Week 1 and 2 | Change at Discontinuation Week 2 (n=14,15,16) | -3.5 units on a scale | Standard Deviation 5.34 |
| Lorazepam | Change From Last Visit of Treatment in Hamilton Anxiety Scale (HAM-A) for Cohort 1 (Less Than 3-Month Last Visit) at Discontinuation Week 1 and 2 | Last visit on treatment (n=15,18,20) | 16.1 units on a scale | Standard Deviation 10.11 |
| Lorazepam | Change From Last Visit of Treatment in Hamilton Anxiety Scale (HAM-A) for Cohort 1 (Less Than 3-Month Last Visit) at Discontinuation Week 1 and 2 | Change at Discontinuation Week 2 (n=14,15,16) | -2.2 units on a scale | Standard Deviation 4.18 |
| Lorazepam | Change From Last Visit of Treatment in Hamilton Anxiety Scale (HAM-A) for Cohort 1 (Less Than 3-Month Last Visit) at Discontinuation Week 1 and 2 | Change at Discontinuation Week 1 (n=15,18,18) | -2.4 units on a scale | Standard Deviation 3.31 |
Secondary
Change From Last Visit of Treatment in Hamilton Anxiety Scale (HAM-A) for Cohort 2 (3-Month Last Visit) at Discontinuation Week 1 and 2
HAM-A measures treatment-related changes in generalized anxiety symptoms; 14 item questionnaire scored 0 (not present) to 4 (very severe); possible range 0 to 56. Lower score indicates less affected.
Time frame: Last visit on treatment, Week 1, 2 post-treatment discontinuation (discontinuation occurred from Week 9 to Week 15)
Population: Per-protocol analysis set. Cohort 2: Participants who discontinued study from Week 9 to Week 15 and had at least 1 discontinuation assessment were included in Month 3 last visit analysis. N (Number of Participants Analyzed) = participants evaluable for this measure. 'n' = participants evaluable at given time points for each group respectively.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Pregabalin High Dose | Change From Last Visit of Treatment in Hamilton Anxiety Scale (HAM-A) for Cohort 2 (3-Month Last Visit) at Discontinuation Week 1 and 2 | Change at Discontinuation Week 1 (n=58,52,48) | 1.7 units on a scale | Standard Deviation 6.69 |
| Pregabalin High Dose | Change From Last Visit of Treatment in Hamilton Anxiety Scale (HAM-A) for Cohort 2 (3-Month Last Visit) at Discontinuation Week 1 and 2 | Last visit on treatment (n=58,52,50) | 8.0 units on a scale | Standard Deviation 6.57 |
| Pregabalin High Dose | Change From Last Visit of Treatment in Hamilton Anxiety Scale (HAM-A) for Cohort 2 (3-Month Last Visit) at Discontinuation Week 1 and 2 | Change at Discontinuation Week 2 (n=54,49,44) | 1.5 units on a scale | Standard Deviation 5.55 |
| Pregabalin Low Dose | Change From Last Visit of Treatment in Hamilton Anxiety Scale (HAM-A) for Cohort 2 (3-Month Last Visit) at Discontinuation Week 1 and 2 | Change at Discontinuation Week 1 (n=58,52,48) | 0.9 units on a scale | Standard Deviation 4.03 |
| Pregabalin Low Dose | Change From Last Visit of Treatment in Hamilton Anxiety Scale (HAM-A) for Cohort 2 (3-Month Last Visit) at Discontinuation Week 1 and 2 | Last visit on treatment (n=58,52,50) | 8.5 units on a scale | Standard Deviation 6.5 |
| Pregabalin Low Dose | Change From Last Visit of Treatment in Hamilton Anxiety Scale (HAM-A) for Cohort 2 (3-Month Last Visit) at Discontinuation Week 1 and 2 | Change at Discontinuation Week 2 (n=54,49,44) | 1.5 units on a scale | Standard Deviation 6.43 |
| Lorazepam | Change From Last Visit of Treatment in Hamilton Anxiety Scale (HAM-A) for Cohort 2 (3-Month Last Visit) at Discontinuation Week 1 and 2 | Last visit on treatment (n=58,52,50) | 6.7 units on a scale | Standard Deviation 4.29 |
| Lorazepam | Change From Last Visit of Treatment in Hamilton Anxiety Scale (HAM-A) for Cohort 2 (3-Month Last Visit) at Discontinuation Week 1 and 2 | Change at Discontinuation Week 2 (n=54,49,44) | 1.5 units on a scale | Standard Deviation 5.37 |
| Lorazepam | Change From Last Visit of Treatment in Hamilton Anxiety Scale (HAM-A) for Cohort 2 (3-Month Last Visit) at Discontinuation Week 1 and 2 | Change at Discontinuation Week 1 (n=58,52,48) | 2.3 units on a scale | Standard Deviation 5.74 |
Secondary
Change From Last Visit of Treatment in Hamilton Anxiety Scale (HAM-A) for Cohort 3 (6-Month Last Visit) at Discontinuation Week 1 and 2
HAM-A measures treatment-related changes in generalized anxiety symptoms; 14 item questionnaire scored 0 (not present) to 4 (very severe); total possible range 0 to 56. Lower score indicates less affected.
Time frame: Last visit on treatment, Week 1, 2 post-treatment discontinuation (discontinuation [DC] occurred after Week 15 to Week 24)
Population: Per-protocol analysis set. Cohort 3: Participants who discontinued study after Week 15 or completed Week 24 visit and had at least 1 discontinuation assessment were included. N(Number of Participants Analyzed) = participants evaluable for this measure. 'n' = participants evaluable at given time points for each group respectively.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Pregabalin High Dose | Change From Last Visit of Treatment in Hamilton Anxiety Scale (HAM-A) for Cohort 3 (6-Month Last Visit) at Discontinuation Week 1 and 2 | Change at DC Week 1 (n=109,30,93,28,99,30) | 1.6 units on a scale | Standard Deviation 4.37 |
| Pregabalin High Dose | Change From Last Visit of Treatment in Hamilton Anxiety Scale (HAM-A) for Cohort 3 (6-Month Last Visit) at Discontinuation Week 1 and 2 | Last visit on treatment (n=109,30,93,29,100,30) | 6.3 units on a scale | Standard Deviation 5.89 |
| Pregabalin High Dose | Change From Last Visit of Treatment in Hamilton Anxiety Scale (HAM-A) for Cohort 3 (6-Month Last Visit) at Discontinuation Week 1 and 2 | Change at DC Week 2 (n=107,29,84,26,94,30) | 2.5 units on a scale | Standard Deviation 5.74 |
| Pregabalin Low Dose | Change From Last Visit of Treatment in Hamilton Anxiety Scale (HAM-A) for Cohort 3 (6-Month Last Visit) at Discontinuation Week 1 and 2 | Change at DC Week 1 (n=109,30,93,28,99,30) | -0.0 units on a scale | Standard Deviation 2.3 |
| Pregabalin Low Dose | Change From Last Visit of Treatment in Hamilton Anxiety Scale (HAM-A) for Cohort 3 (6-Month Last Visit) at Discontinuation Week 1 and 2 | Last visit on treatment (n=109,30,93,29,100,30) | 5.5 units on a scale | Standard Deviation 6.12 |
| Pregabalin Low Dose | Change From Last Visit of Treatment in Hamilton Anxiety Scale (HAM-A) for Cohort 3 (6-Month Last Visit) at Discontinuation Week 1 and 2 | Change at DC Week 2 (n=107,29,84,26,94,30) | -0.8 units on a scale | Standard Deviation 5.33 |
| Lorazepam | Change From Last Visit of Treatment in Hamilton Anxiety Scale (HAM-A) for Cohort 3 (6-Month Last Visit) at Discontinuation Week 1 and 2 | Change at DC Week 1 (n=109,30,93,28,99,30) | 0.7 units on a scale | Standard Deviation 3.08 |
| Lorazepam | Change From Last Visit of Treatment in Hamilton Anxiety Scale (HAM-A) for Cohort 3 (6-Month Last Visit) at Discontinuation Week 1 and 2 | Last visit on treatment (n=109,30,93,29,100,30) | 5.6 units on a scale | Standard Deviation 5.02 |
| Lorazepam | Change From Last Visit of Treatment in Hamilton Anxiety Scale (HAM-A) for Cohort 3 (6-Month Last Visit) at Discontinuation Week 1 and 2 | Change at DC Week 2 (n=107,29,84,26,94,30) | 1.2 units on a scale | Standard Deviation 3.9 |
| Pregabalin Low Dose, Placebo | Change From Last Visit of Treatment in Hamilton Anxiety Scale (HAM-A) for Cohort 3 (6-Month Last Visit) at Discontinuation Week 1 and 2 | Change at DC Week 1 (n=109,30,93,28,99,30) | 0.6 units on a scale | Standard Deviation 2.69 |
| Pregabalin Low Dose, Placebo | Change From Last Visit of Treatment in Hamilton Anxiety Scale (HAM-A) for Cohort 3 (6-Month Last Visit) at Discontinuation Week 1 and 2 | Last visit on treatment (n=109,30,93,29,100,30) | 8.3 units on a scale | Standard Deviation 6.49 |
| Pregabalin Low Dose, Placebo | Change From Last Visit of Treatment in Hamilton Anxiety Scale (HAM-A) for Cohort 3 (6-Month Last Visit) at Discontinuation Week 1 and 2 | Change at DC Week 2 (n=107,29,84,26,94,30) | 1.5 units on a scale | Standard Deviation 5.08 |
| Lorazepam, Lorazepam | Change From Last Visit of Treatment in Hamilton Anxiety Scale (HAM-A) for Cohort 3 (6-Month Last Visit) at Discontinuation Week 1 and 2 | Change at DC Week 1 (n=109,30,93,28,99,30) | 3.0 units on a scale | Standard Deviation 5.73 |
| Lorazepam, Lorazepam | Change From Last Visit of Treatment in Hamilton Anxiety Scale (HAM-A) for Cohort 3 (6-Month Last Visit) at Discontinuation Week 1 and 2 | Last visit on treatment (n=109,30,93,29,100,30) | 5.6 units on a scale | Standard Deviation 6.17 |
| Lorazepam, Lorazepam | Change From Last Visit of Treatment in Hamilton Anxiety Scale (HAM-A) for Cohort 3 (6-Month Last Visit) at Discontinuation Week 1 and 2 | Change at DC Week 2 (n=107,29,84,26,94,30) | 2.2 units on a scale | Standard Deviation 5.39 |
| Lorazepam, Placebo | Change From Last Visit of Treatment in Hamilton Anxiety Scale (HAM-A) for Cohort 3 (6-Month Last Visit) at Discontinuation Week 1 and 2 | Last visit on treatment (n=109,30,93,29,100,30) | 5.5 units on a scale | Standard Deviation 4.66 |
| Lorazepam, Placebo | Change From Last Visit of Treatment in Hamilton Anxiety Scale (HAM-A) for Cohort 3 (6-Month Last Visit) at Discontinuation Week 1 and 2 | Change at DC Week 2 (n=107,29,84,26,94,30) | 0.6 units on a scale | Standard Deviation 3.76 |
| Lorazepam, Placebo | Change From Last Visit of Treatment in Hamilton Anxiety Scale (HAM-A) for Cohort 3 (6-Month Last Visit) at Discontinuation Week 1 and 2 | Change at DC Week 1 (n=109,30,93,28,99,30) | 0.3 units on a scale | Standard Deviation 3.01 |
Secondary
Clinical Global Impression - Improvement (CGI-I) Score at the End of Period 1
CGI-I: 7-point clinician rated scale ranging from 1 (very much improved) to 7 (very much worse). Improvement is defined as a score of 1 (very much improved), 2 (much improved), or 3 (minimally improved) on the scale.
Time frame: Week 12
Population: Per-protocol analysis set: all randomized participants who had baseline with at least 1 discontinuation or efficacy visit, and were not major protocol violators. LOCF method was used to impute missing values.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Pregabalin High Dose | Clinical Global Impression - Improvement (CGI-I) Score at the End of Period 1 | 1.9 units on a scale | Standard Deviation 1.13 |
| Pregabalin Low Dose | Clinical Global Impression - Improvement (CGI-I) Score at the End of Period 1 | 1.9 units on a scale | Standard Deviation 1.01 |
| Lorazepam | Clinical Global Impression - Improvement (CGI-I) Score at the End of Period 1 | 1.9 units on a scale | Standard Deviation 1.17 |
Secondary
Clinical Global Impression - Improvement (CGI-I) Score at the End of Period 2
CGI-I: 7-point clinician rated scale ranging from 1 (very much improved) to 7 (very much worse). Improvement is defined as a score of 1 (very much improved), 2 (much improved), or 3 (minimally improved) on the scale.
Time frame: Week 24
Population: Per-protocol analysis set: all randomized participants who had baseline with at least 1 discontinuation or efficacy visit, and were not major protocol violators. LOCF method was used to impute missing values.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Pregabalin High Dose | Clinical Global Impression - Improvement (CGI-I) Score at the End of Period 2 | 1.7 units on a scale | Standard Deviation 0.99 |
| Pregabalin Low Dose | Clinical Global Impression - Improvement (CGI-I) Score at the End of Period 2 | 1.9 units on a scale | Standard Deviation 1.15 |
| Lorazepam | Clinical Global Impression - Improvement (CGI-I) Score at the End of Period 2 | 1.6 units on a scale | Standard Deviation 0.75 |
| Pregabalin Low Dose, Placebo | Clinical Global Impression - Improvement (CGI-I) Score at the End of Period 2 | 2.3 units on a scale | Standard Deviation 1.53 |
| Lorazepam, Lorazepam | Clinical Global Impression - Improvement (CGI-I) Score at the End of Period 2 | 1.5 units on a scale | Standard Deviation 0.91 |
| Lorazepam, Placebo | Clinical Global Impression - Improvement (CGI-I) Score at the End of Period 2 | 2.0 units on a scale | Standard Deviation 1.07 |
Secondary
Clinical Global Impression - Severity (CGI-S) Score for Period 1
CGI-S: 7-point clinician rated scale to assess severity of participant's current illness state; range: 1 (normal - not ill at all) to 7 (among the most extremely ill patients). Higher score = more affected.
Time frame: Baseline, Week 12
Population: Per-protocol analysis set: all randomized participants who had baseline with at least 1 discontinuation or efficacy visit, and were not major protocol violators. LOCF method was used to impute missing values.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Pregabalin High Dose | Clinical Global Impression - Severity (CGI-S) Score for Period 1 | Baseline | 4.6 units on a scale | Standard Deviation 0.68 |
| Pregabalin High Dose | Clinical Global Impression - Severity (CGI-S) Score for Period 1 | Week 12 | 2.3 units on a scale | Standard Deviation 1.06 |
| Pregabalin Low Dose | Clinical Global Impression - Severity (CGI-S) Score for Period 1 | Baseline | 4.5 units on a scale | Standard Deviation 0.71 |
| Pregabalin Low Dose | Clinical Global Impression - Severity (CGI-S) Score for Period 1 | Week 12 | 2.5 units on a scale | Standard Deviation 1.17 |
| Lorazepam | Clinical Global Impression - Severity (CGI-S) Score for Period 1 | Baseline | 4.4 units on a scale | Standard Deviation 0.65 |
| Lorazepam | Clinical Global Impression - Severity (CGI-S) Score for Period 1 | Week 12 | 2.3 units on a scale | Standard Deviation 1 |
Secondary
Clinical Global Impression - Severity (CGI-S) Score for Period 2
CGI-S: 7-point clinician rated scale to assess severity of participant's current illness state; range: 1 (normal - not ill at all) to 7 (among the most extremely ill patients). Higher score = more affected
Time frame: Baseline, Week 24
Population: Per-protocol analysis set: all randomized participants who had baseline with at least 1 discontinuation or efficacy visit, and were not major protocol violators. LOCF method was used to impute missing values.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Pregabalin High Dose | Clinical Global Impression - Severity (CGI-S) Score for Period 2 | Baseline | 4.7 units on a scale | Standard Deviation 0.65 |
| Pregabalin High Dose | Clinical Global Impression - Severity (CGI-S) Score for Period 2 | Week 24 | 2.3 units on a scale | Standard Deviation 1.08 |
| Pregabalin Low Dose | Clinical Global Impression - Severity (CGI-S) Score for Period 2 | Baseline | 4.5 units on a scale | Standard Deviation 0.69 |
| Pregabalin Low Dose | Clinical Global Impression - Severity (CGI-S) Score for Period 2 | Week 24 | 2.2 units on a scale | Standard Deviation 1.16 |
| Lorazepam | Clinical Global Impression - Severity (CGI-S) Score for Period 2 | Baseline | 4.5 units on a scale | Standard Deviation 0.71 |
| Lorazepam | Clinical Global Impression - Severity (CGI-S) Score for Period 2 | Week 24 | 2.1 units on a scale | Standard Deviation 0.97 |
| Pregabalin Low Dose, Placebo | Clinical Global Impression - Severity (CGI-S) Score for Period 2 | Baseline | 4.5 units on a scale | Standard Deviation 0.73 |
| Pregabalin Low Dose, Placebo | Clinical Global Impression - Severity (CGI-S) Score for Period 2 | Week 24 | 2.5 units on a scale | Standard Deviation 1.24 |
| Lorazepam, Lorazepam | Clinical Global Impression - Severity (CGI-S) Score for Period 2 | Baseline | 4.4 units on a scale | Standard Deviation 0.68 |
| Lorazepam, Lorazepam | Clinical Global Impression - Severity (CGI-S) Score for Period 2 | Week 24 | 1.9 units on a scale | Standard Deviation 0.9 |
| Lorazepam, Placebo | Clinical Global Impression - Severity (CGI-S) Score for Period 2 | Baseline | 4.5 units on a scale | Standard Deviation 0.56 |
| Lorazepam, Placebo | Clinical Global Impression - Severity (CGI-S) Score for Period 2 | Week 24 | 2.4 units on a scale | Standard Deviation 0.98 |
Secondary
Hamilton Anxiety Scale (HAM-A) for Cohort 1 (Less Than 3-Month Last Visit)
HAM-A measures treatment-related changes in generalized anxiety symptoms; 14 item questionnaire scored 0 (not present) to 4 (very severe); total possible range 0 to 56. Lower score indicates less affected.
Time frame: Week 1, 2 post-treatment discontinuation (discontinuation occurred prior to Week 9)
Population: Per-protocol analysis set. Cohort 1: Participants who discontinued study prior to Week 9 and had at least 1 discontinuation assessment were included in less-than Month 3 last visit analysis. N (Number of Participants Analyzed) = participants evaluable for this measure. 'n' = participants evaluable at given time points for each group respectively.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Pregabalin High Dose | Hamilton Anxiety Scale (HAM-A) for Cohort 1 (Less Than 3-Month Last Visit) | Discontinuation Week 1 (n=15,19,18) | 18.1 units on a scale | Standard Deviation 7.11 |
| Pregabalin High Dose | Hamilton Anxiety Scale (HAM-A) for Cohort 1 (Less Than 3-Month Last Visit) | Discontinuation Week 2 (n=14,15,16) | 13.9 units on a scale | Standard Deviation 7.33 |
| Pregabalin Low Dose | Hamilton Anxiety Scale (HAM-A) for Cohort 1 (Less Than 3-Month Last Visit) | Discontinuation Week 1 (n=15,19,18) | 19.0 units on a scale | Standard Deviation 7.61 |
| Pregabalin Low Dose | Hamilton Anxiety Scale (HAM-A) for Cohort 1 (Less Than 3-Month Last Visit) | Discontinuation Week 2 (n=14,15,16) | 18.6 units on a scale | Standard Deviation 6.15 |
| Lorazepam | Hamilton Anxiety Scale (HAM-A) for Cohort 1 (Less Than 3-Month Last Visit) | Discontinuation Week 1 (n=15,19,18) | 14.1 units on a scale | Standard Deviation 10.31 |
| Lorazepam | Hamilton Anxiety Scale (HAM-A) for Cohort 1 (Less Than 3-Month Last Visit) | Discontinuation Week 2 (n=14,15,16) | 14.6 units on a scale | Standard Deviation 10.41 |
Secondary
Hamilton Anxiety Scale (HAM-A) for Cohort 2 (3-Month Last Visit)
HAM-A measures treatment-related changes in generalized anxiety symptoms; 14 item questionnaire scored 0 (not present) to 4 (very severe); possible range 0 to 56. Lower score indicates less affected.
Time frame: Week 1, 2 post-treatment discontinuation (discontinuation occurred from Week 9 to Week 15)
Population: Per-protocol analysis set. Cohort 2: Participants who discontinued study from Week 9 to Week 15 and had at least 1 discontinuation assessment were included in Month 3 last visit analysis. N (Number of Participants Analyzed) = participants evaluable for this measure. 'n' = participants evaluable at given time points for each group respectively.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Pregabalin High Dose | Hamilton Anxiety Scale (HAM-A) for Cohort 2 (3-Month Last Visit) | Discontinuation Week 1 (n=58,52,48) | 9.6 units on a scale | Standard Deviation 6.38 |
| Pregabalin High Dose | Hamilton Anxiety Scale (HAM-A) for Cohort 2 (3-Month Last Visit) | Discontinuation Week 2 (n=54,49,44) | 9.0 units on a scale | Standard Deviation 6.44 |
| Pregabalin Low Dose | Hamilton Anxiety Scale (HAM-A) for Cohort 2 (3-Month Last Visit) | Discontinuation Week 1 (n=58,52,48) | 9.4 units on a scale | Standard Deviation 6.6 |
| Pregabalin Low Dose | Hamilton Anxiety Scale (HAM-A) for Cohort 2 (3-Month Last Visit) | Discontinuation Week 2 (n=54,49,44) | 9.9 units on a scale | Standard Deviation 7.04 |
| Lorazepam | Hamilton Anxiety Scale (HAM-A) for Cohort 2 (3-Month Last Visit) | Discontinuation Week 1 (n=58,52,48) | 8.8 units on a scale | Standard Deviation 5.88 |
| Lorazepam | Hamilton Anxiety Scale (HAM-A) for Cohort 2 (3-Month Last Visit) | Discontinuation Week 2 (n=54,49,44) | 8.3 units on a scale | Standard Deviation 6.48 |
Secondary
Hamilton Anxiety Scale (HAM-A) Score for Cohort 3 (6-Month Last Visit)
HAM-A measures treatment-related changes in generalized anxiety symptoms; 14 item questionnaire scored 0 (not present) to 4 (very severe); total possible range 0 to 56. Lower score indicates less affected.
Time frame: Week 1, 2 post-treatment discontinuation (discontinuation [DC] occurred after Week 15 to Week 24)
Population: Per-protocol analysis set. Cohort 3: Participants who discontinued study after Week 15 or completed Week 24 visit and had at least 1 discontinuation assessment were included. N (Number of Participants Analyzed) = participants evaluable for this measure. 'n' = participants evaluable at given time points for each group respectively.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Pregabalin High Dose | Hamilton Anxiety Scale (HAM-A) Score for Cohort 3 (6-Month Last Visit) | Discontinuation Week 1 (n=109,30,94,28,99,30) | 7.9 units on a scale | Standard Deviation 6.34 |
| Pregabalin High Dose | Hamilton Anxiety Scale (HAM-A) Score for Cohort 3 (6-Month Last Visit) | Discontinuation Week 2 (n=107,29,84,26,94,30) | 8.9 units on a scale | Standard Deviation 7.6 |
| Pregabalin Low Dose | Hamilton Anxiety Scale (HAM-A) Score for Cohort 3 (6-Month Last Visit) | Discontinuation Week 1 (n=109,30,94,28,99,30) | 5.5 units on a scale | Standard Deviation 4.85 |
| Pregabalin Low Dose | Hamilton Anxiety Scale (HAM-A) Score for Cohort 3 (6-Month Last Visit) | Discontinuation Week 2 (n=107,29,84,26,94,30) | 5.0 units on a scale | Standard Deviation 4.32 |
| Lorazepam | Hamilton Anxiety Scale (HAM-A) Score for Cohort 3 (6-Month Last Visit) | Discontinuation Week 1 (n=109,30,94,28,99,30) | 6.3 units on a scale | Standard Deviation 5.48 |
| Lorazepam | Hamilton Anxiety Scale (HAM-A) Score for Cohort 3 (6-Month Last Visit) | Discontinuation Week 2 (n=107,29,84,26,94,30) | 6.5 units on a scale | Standard Deviation 6.36 |
| Pregabalin Low Dose, Placebo | Hamilton Anxiety Scale (HAM-A) Score for Cohort 3 (6-Month Last Visit) | Discontinuation Week 1 (n=109,30,94,28,99,30) | 8.4 units on a scale | Standard Deviation 6.67 |
| Pregabalin Low Dose, Placebo | Hamilton Anxiety Scale (HAM-A) Score for Cohort 3 (6-Month Last Visit) | Discontinuation Week 2 (n=107,29,84,26,94,30) | 9.2 units on a scale | Standard Deviation 8.28 |
| Lorazepam, Lorazepam | Hamilton Anxiety Scale (HAM-A) Score for Cohort 3 (6-Month Last Visit) | Discontinuation Week 1 (n=109,30,94,28,99,30) | 8.4 units on a scale | Standard Deviation 7.07 |
| Lorazepam, Lorazepam | Hamilton Anxiety Scale (HAM-A) Score for Cohort 3 (6-Month Last Visit) | Discontinuation Week 2 (n=107,29,84,26,94,30) | 7.9 units on a scale | Standard Deviation 6.27 |
| Lorazepam, Placebo | Hamilton Anxiety Scale (HAM-A) Score for Cohort 3 (6-Month Last Visit) | Discontinuation Week 1 (n=109,30,94,28,99,30) | 7.07 units on a scale | Standard Deviation 4.92 |
| Lorazepam, Placebo | Hamilton Anxiety Scale (HAM-A) Score for Cohort 3 (6-Month Last Visit) | Discontinuation Week 2 (n=107,29,84,26,94,30) | 6.1 units on a scale | Standard Deviation 6 |
Secondary
Hamilton Anxiety Scale (HAM-A) Score for Period 1
HAM-A measures treatment-related changes in generalized anxiety symptoms; 14 item questionnaire scored 0 (not present) to 4 (very severe); total possible range 0 to 56. Lower score indicates less affected.
Time frame: Baseline, Week 12
Population: Per-protocol analysis set: all randomized participants who had baseline with at least 1 discontinuation or efficacy visit, and were not major protocol violators. Last observation carried forward (LOCF) method was used to impute missing values.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Pregabalin High Dose | Hamilton Anxiety Scale (HAM-A) Score for Period 1 | Baseline | 25.3 units on a scale | Standard Deviation 4.39 |
| Pregabalin High Dose | Hamilton Anxiety Scale (HAM-A) Score for Period 1 | Week 12 | 8.0 units on a scale | Standard Deviation 6.23 |
| Pregabalin Low Dose | Hamilton Anxiety Scale (HAM-A) Score for Period 1 | Baseline | 24.9 units on a scale | Standard Deviation 3.87 |
| Pregabalin Low Dose | Hamilton Anxiety Scale (HAM-A) Score for Period 1 | Week 12 | 8.9 units on a scale | Standard Deviation 7.19 |
| Lorazepam | Hamilton Anxiety Scale (HAM-A) Score for Period 1 | Baseline | 24.5 units on a scale | Standard Deviation 4.39 |
| Lorazepam | Hamilton Anxiety Scale (HAM-A) Score for Period 1 | Week 12 | 7.9 units on a scale | Standard Deviation 6.7 |
Secondary
Hamilton Anxiety Scale (HAM-A) Score for Period 2
HAM-A measures treatment-related changes in generalized anxiety symptoms; 14 item questionnaire scored 0 (not present) to 4 (very severe); total possible range 0 to 56. Lower score indicates less affected.
Time frame: Baseline, Week 24
Population: Per-protocol analysis set: all randomized participants who had baseline with at least 1 discontinuation or efficacy visit, and were not major protocol violators. LOCF method was used to impute missing values.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Pregabalin High Dose | Hamilton Anxiety Scale (HAM-A) Score for Period 2 | Baseline | 25.6 units on a scale | Standard Deviation 3.82 |
| Pregabalin High Dose | Hamilton Anxiety Scale (HAM-A) Score for Period 2 | Week 24 | 7.0 units on a scale | Standard Deviation 6.53 |
| Pregabalin Low Dose | Hamilton Anxiety Scale (HAM-A) Score for Period 2 | Baseline | 24.6 units on a scale | Standard Deviation 4.66 |
| Pregabalin Low Dose | Hamilton Anxiety Scale (HAM-A) Score for Period 2 | Week 24 | 7.1 units on a scale | Standard Deviation 7.09 |
| Lorazepam | Hamilton Anxiety Scale (HAM-A) Score for Period 2 | Baseline | 24.8 units on a scale | Standard Deviation 3.77 |
| Lorazepam | Hamilton Anxiety Scale (HAM-A) Score for Period 2 | Week 24 | 6.5 units on a scale | Standard Deviation 5.98 |
| Pregabalin Low Dose, Placebo | Hamilton Anxiety Scale (HAM-A) Score for Period 2 | Baseline | 25.1 units on a scale | Standard Deviation 3.92 |
| Pregabalin Low Dose, Placebo | Hamilton Anxiety Scale (HAM-A) Score for Period 2 | Week 24 | 10.2 units on a scale | Standard Deviation 7.49 |
| Lorazepam, Lorazepam | Hamilton Anxiety Scale (HAM-A) Score for Period 2 | Baseline | 24.7 units on a scale | Standard Deviation 4.41 |
| Lorazepam, Lorazepam | Hamilton Anxiety Scale (HAM-A) Score for Period 2 | Week 24 | 5.7 units on a scale | Standard Deviation 6.06 |
| Lorazepam, Placebo | Hamilton Anxiety Scale (HAM-A) Score for Period 2 | Baseline | 24.1 units on a scale | Standard Deviation 4.03 |
| Lorazepam, Placebo | Hamilton Anxiety Scale (HAM-A) Score for Period 2 | Week 24 | 6.6 units on a scale | Standard Deviation 6.33 |
Secondary
Number of Participants With Discontinuation-Emergent Signs and Symptoms (DESS) for Cohort 1 (Less Than 3-Month Last Visit)
DESS adverse events, a subset of Treatment Emergent Signs and Symptoms (TESS), were defined as those spontaneously reported adverse events that developed or existed prior to but worsened during Discontinuation Week 1 and 2.
Time frame: 2 weeks post-treatment discontinuation (discontinuation occurred prior to Week 9)
Population: Per-protocol analysis set. Cohort 1: Participants who discontinued study prior to Week 9 and had at least 1 discontinuation assessment were included in less-than Month 3 last visit analysis.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Pregabalin High Dose | Number of Participants With Discontinuation-Emergent Signs and Symptoms (DESS) for Cohort 1 (Less Than 3-Month Last Visit) | Newly developed DESS | 6 participants |
| Pregabalin High Dose | Number of Participants With Discontinuation-Emergent Signs and Symptoms (DESS) for Cohort 1 (Less Than 3-Month Last Visit) | Worsened DESS | 0 participants |
| Pregabalin Low Dose | Number of Participants With Discontinuation-Emergent Signs and Symptoms (DESS) for Cohort 1 (Less Than 3-Month Last Visit) | Newly developed DESS | 0 participants |
| Pregabalin Low Dose | Number of Participants With Discontinuation-Emergent Signs and Symptoms (DESS) for Cohort 1 (Less Than 3-Month Last Visit) | Worsened DESS | 0 participants |
| Lorazepam | Number of Participants With Discontinuation-Emergent Signs and Symptoms (DESS) for Cohort 1 (Less Than 3-Month Last Visit) | Newly developed DESS | 3 participants |
| Lorazepam | Number of Participants With Discontinuation-Emergent Signs and Symptoms (DESS) for Cohort 1 (Less Than 3-Month Last Visit) | Worsened DESS | 0 participants |
Secondary
Number of Participants With Discontinuation-Emergent Signs and Symptoms (DESS) for Cohort 2 (3-Month Last Visit)
DESS adverse events, a subset of Treatment Emergent Signs and Symptoms (TESS), were defined as those spontaneously reported adverse events that developed or existed prior to but worsened during Discontinuation Week 1 and 2.
Time frame: 2 weeks post-treatment discontinuation (discontinuation occurred from Week 9 to Week 15)
Population: Per-protocol analysis set. Cohort 1: Participants who discontinued study from Week 9 to Week 15 and had at least 1 discontinuation assessment were included in Month 3 last visit analysis.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Pregabalin High Dose | Number of Participants With Discontinuation-Emergent Signs and Symptoms (DESS) for Cohort 2 (3-Month Last Visit) | Newly developed DESS | 40 participants |
| Pregabalin High Dose | Number of Participants With Discontinuation-Emergent Signs and Symptoms (DESS) for Cohort 2 (3-Month Last Visit) | Worsened DESS | 1 participants |
| Pregabalin Low Dose | Number of Participants With Discontinuation-Emergent Signs and Symptoms (DESS) for Cohort 2 (3-Month Last Visit) | Newly developed DESS | 38 participants |
| Pregabalin Low Dose | Number of Participants With Discontinuation-Emergent Signs and Symptoms (DESS) for Cohort 2 (3-Month Last Visit) | Worsened DESS | 2 participants |
| Lorazepam | Number of Participants With Discontinuation-Emergent Signs and Symptoms (DESS) for Cohort 2 (3-Month Last Visit) | Newly developed DESS | 36 participants |
| Lorazepam | Number of Participants With Discontinuation-Emergent Signs and Symptoms (DESS) for Cohort 2 (3-Month Last Visit) | Worsened DESS | 1 participants |
Secondary
Number of Participants With Discontinuation-Emergent Signs and Symptoms (DESS) for Cohort 3 (6-Month Last Visit)
DESS adverse events, a subset of Treatment Emergent Signs and Symptoms (TESS), were defined as those spontaneously reported adverse events that developed or existed prior to but worsened during Discontinuation Week 1 and 2.
Time frame: 2 weeks post-treatment discontinuation (discontinuation occurred after Week 15 to Week 24)
Population: Per-protocol analysis set. Cohort 3: Participants who discontinued study after Week 15 or completed Week 24 visit and had at least 1 discontinuation assessment were included in Month 6 last visit analysis.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Pregabalin High Dose | Number of Participants With Discontinuation-Emergent Signs and Symptoms (DESS) for Cohort 3 (6-Month Last Visit) | Newly developed DESS | 78 participants |
| Pregabalin High Dose | Number of Participants With Discontinuation-Emergent Signs and Symptoms (DESS) for Cohort 3 (6-Month Last Visit) | Worsened DESS | 2 participants |
| Pregabalin Low Dose | Number of Participants With Discontinuation-Emergent Signs and Symptoms (DESS) for Cohort 3 (6-Month Last Visit) | Newly developed DESS | 5 participants |
| Pregabalin Low Dose | Number of Participants With Discontinuation-Emergent Signs and Symptoms (DESS) for Cohort 3 (6-Month Last Visit) | Worsened DESS | 0 participants |
| Lorazepam | Number of Participants With Discontinuation-Emergent Signs and Symptoms (DESS) for Cohort 3 (6-Month Last Visit) | Newly developed DESS | 35 participants |
| Lorazepam | Number of Participants With Discontinuation-Emergent Signs and Symptoms (DESS) for Cohort 3 (6-Month Last Visit) | Worsened DESS | 2 participants |
| Pregabalin Low Dose, Placebo | Number of Participants With Discontinuation-Emergent Signs and Symptoms (DESS) for Cohort 3 (6-Month Last Visit) | Worsened DESS | 1 participants |
| Pregabalin Low Dose, Placebo | Number of Participants With Discontinuation-Emergent Signs and Symptoms (DESS) for Cohort 3 (6-Month Last Visit) | Newly developed DESS | 17 participants |
| Lorazepam, Lorazepam | Number of Participants With Discontinuation-Emergent Signs and Symptoms (DESS) for Cohort 3 (6-Month Last Visit) | Newly developed DESS | 50 participants |
| Lorazepam, Lorazepam | Number of Participants With Discontinuation-Emergent Signs and Symptoms (DESS) for Cohort 3 (6-Month Last Visit) | Worsened DESS | 5 participants |
| Lorazepam, Placebo | Number of Participants With Discontinuation-Emergent Signs and Symptoms (DESS) for Cohort 3 (6-Month Last Visit) | Worsened DESS | 0 participants |
| Lorazepam, Placebo | Number of Participants With Discontinuation-Emergent Signs and Symptoms (DESS) for Cohort 3 (6-Month Last Visit) | Newly developed DESS | 7 participants |
Secondary
Number of Participants With Rebound Anxiety for Cohort 1 (Less Than 3-Month Last Visit)
Rebound anxiety was defined as a rapid return of the participant's original symptoms following drug discontinuation, that were worse compared to baseline. This was characterized by a HAM-A score at the Discontinuation Week 1 or Week 2 greater than or equal to the baseline value.
Time frame: 2 weeks post-treatment discontinuation (discontinuation occurred prior to Week 9)
Population: Per-protocol analysis set. Cohort 1: Participants who discontinued study prior to Week 9 and had at least 1 discontinuation assessment were included in less-than Month 3 last visit analysis. Here, N (Number of Participants Analyzed) signifies those participants who were evaluable for this measure.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Pregabalin High Dose | Number of Participants With Rebound Anxiety for Cohort 1 (Less Than 3-Month Last Visit) | 1 participants |
| Pregabalin Low Dose | Number of Participants With Rebound Anxiety for Cohort 1 (Less Than 3-Month Last Visit) | 5 participants |
| Lorazepam | Number of Participants With Rebound Anxiety for Cohort 1 (Less Than 3-Month Last Visit) | 1 participants |
Secondary
Number of Participants With Rebound Anxiety for Cohort 2 (3-Month Last Visit)
Rebound anxiety was defined as a rapid return of the participant's original symptoms following drug discontinuation, that were worse compared to baseline. This was characterized by a HAM-A score at the Discontinuation Week 1 or Week 2 greater than or equal to the baseline value.
Time frame: 2 weeks post-treatment discontinuation (discontinuation occurred from Week 9 to Week 15)
Population: Per-protocol analysis set. Cohort 2: Participants who discontinued study from Week 9 to Week 15 and had at least 1 discontinuation assessment were included in Month 3 last visit analysis. Here, N (Number of Participants Analyzed) signifies those participants who were evaluable for this measure.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Pregabalin High Dose | Number of Participants With Rebound Anxiety for Cohort 2 (3-Month Last Visit) | 3 participants |
| Pregabalin Low Dose | Number of Participants With Rebound Anxiety for Cohort 2 (3-Month Last Visit) | 1 participants |
| Lorazepam | Number of Participants With Rebound Anxiety for Cohort 2 (3-Month Last Visit) | 2 participants |
Secondary
Number of Participants With Rebound Anxiety for Cohort 3 (6-Month Last Visit)
Rebound anxiety was defined as a rapid return of the participant's original symptoms following drug discontinuation, that were worse compared to baseline. This was characterized by a HAM-A score at the Discontinuation Week 1 or Week 2 greater than or equal to the baseline value.
Time frame: 2 weeks post-treatment discontinuation (discontinuation occurred after Week 15 to Week 24)
Population: Per-protocol analysis set. Cohort 3: Participants who discontinued study after Week 15 or completed Week 24 visit and had at least 1 discontinuation assessment were included in Month 6 last visit analysis. Here, N (Number of Participants Analyzed) signifies those participants who were evaluable for this measure.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Pregabalin High Dose | Number of Participants With Rebound Anxiety for Cohort 3 (6-Month Last Visit) | 4 participants |
| Pregabalin Low Dose | Number of Participants With Rebound Anxiety for Cohort 3 (6-Month Last Visit) | 0 participants |
| Lorazepam | Number of Participants With Rebound Anxiety for Cohort 3 (6-Month Last Visit) | 0 participants |
| Pregabalin Low Dose, Placebo | Number of Participants With Rebound Anxiety for Cohort 3 (6-Month Last Visit) | 1 participants |
| Lorazepam, Lorazepam | Number of Participants With Rebound Anxiety for Cohort 3 (6-Month Last Visit) | 6 participants |
| Lorazepam, Placebo | Number of Participants With Rebound Anxiety for Cohort 3 (6-Month Last Visit) | 0 participants |
Secondary
Physician's Withdrawal Checklist (PWC) Score for Cohort 1 (Less Than 3-Month Last Visit)
PWC: 20 item physician rated interview measuring anxiolytic drug withdrawal-related signs and symptoms (gastrointestinal, mood, sleep, motor, somatic, perception and cognition); range 0 (not present) to 3 (severe); total score range: 0 to 60; higher score = more affected.
Time frame: Week 1, 2 post-treatment discontinuation (discontinuation occurred prior to Week 9)
Population: Per-protocol analysis set. Cohort 1: Participants who discontinued study prior to Week 9 and had at least 1 discontinuation assessment were included in less-than Month 3 last visit analysis. N (Number of Participants Analyzed) = participants evaluable for this measure. 'n' = participants evaluable at given time points for each group respectively.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Pregabalin High Dose | Physician's Withdrawal Checklist (PWC) Score for Cohort 1 (Less Than 3-Month Last Visit) | Discontinuation Week 1 (n=15,19,18) | 10.2 units on a scale | Standard Deviation 7.97 |
| Pregabalin High Dose | Physician's Withdrawal Checklist (PWC) Score for Cohort 1 (Less Than 3-Month Last Visit) | Discontinuation Week 2 (n=14,15,16) | 8.2 units on a scale | Standard Deviation 6.7 |
| Pregabalin Low Dose | Physician's Withdrawal Checklist (PWC) Score for Cohort 1 (Less Than 3-Month Last Visit) | Discontinuation Week 1 (n=15,19,18) | 14.3 units on a scale | Standard Deviation 10.04 |
| Pregabalin Low Dose | Physician's Withdrawal Checklist (PWC) Score for Cohort 1 (Less Than 3-Month Last Visit) | Discontinuation Week 2 (n=14,15,16) | 14.1 units on a scale | Standard Deviation 9.16 |
| Lorazepam | Physician's Withdrawal Checklist (PWC) Score for Cohort 1 (Less Than 3-Month Last Visit) | Discontinuation Week 1 (n=15,19,18) | 9.1 units on a scale | Standard Deviation 9.25 |
| Lorazepam | Physician's Withdrawal Checklist (PWC) Score for Cohort 1 (Less Than 3-Month Last Visit) | Discontinuation Week 2 (n=14,15,16) | 10.6 units on a scale | Standard Deviation 9.39 |
Secondary
Physician's Withdrawal Checklist (PWC) Score for Cohort 2 (3-Month Last Visit)
PWC: 20 item physician rated interview measuring anxiolytic drug withdrawal-related signs and symptoms (gastrointestinal, mood, sleep, motor, somatic, perception and cognition); range 0 (not present) to 3 (severe); total score range: 0 to 60; higher score = more affected.
Time frame: Week 1, 2 post-treatment discontinuation (discontinuation occurred from Week 9 to Week 15)
Population: Per-protocol analysis set. Cohort 2: Participants who discontinued study from Week 9 to Week 15 and had at least 1 discontinuation assessment were included in Month 3 last visit analysis. N (Number of Participants Analyzed) = participants evaluable for this measure. 'n' = participants evaluable at given time points for each group respectively.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Pregabalin High Dose | Physician's Withdrawal Checklist (PWC) Score for Cohort 2 (3-Month Last Visit) | Discontinuation Week 1 (n=58,52,49) | 9.1 units on a scale | Standard Deviation 6.82 |
| Pregabalin High Dose | Physician's Withdrawal Checklist (PWC) Score for Cohort 2 (3-Month Last Visit) | Discontinuation Week 2 (n=54,49,44) | 8.9 units on a scale | Standard Deviation 7.28 |
| Pregabalin Low Dose | Physician's Withdrawal Checklist (PWC) Score for Cohort 2 (3-Month Last Visit) | Discontinuation Week 1 (n=58,52,49) | 8.0 units on a scale | Standard Deviation 6.19 |
| Pregabalin Low Dose | Physician's Withdrawal Checklist (PWC) Score for Cohort 2 (3-Month Last Visit) | Discontinuation Week 2 (n=54,49,44) | 8.3 units on a scale | Standard Deviation 6.32 |
| Lorazepam | Physician's Withdrawal Checklist (PWC) Score for Cohort 2 (3-Month Last Visit) | Discontinuation Week 1 (n=58,52,49) | 7.3 units on a scale | Standard Deviation 6.69 |
| Lorazepam | Physician's Withdrawal Checklist (PWC) Score for Cohort 2 (3-Month Last Visit) | Discontinuation Week 2 (n=54,49,44) | 6.9 units on a scale | Standard Deviation 6.38 |
Secondary
Physician's Withdrawal Checklist (PWC) Score for Cohort 3 (6-Month Last Visit)
PWC: 20 item physician rated interview measuring anxiolytic drug withdrawal-related signs and symptoms (gastrointestinal, mood, sleep, motor, somatic, perception and cognition); range 0 (not present) to 3 (severe); total score range: 0 to 60; higher score = more affected.
Time frame: Week 1, 2 post-treatment discontinuation (discontinuation occurred after Week 15 to Week 24)
Population: Per-protocol analysis set. Cohort 3: Participants who discontinued study after Week 15 or completed Week 24 visit and had at least 1 discontinuation assessment were included. N (Number of Participants Analyzed) = participants evaluable for this measure. 'n' = participants evaluable at given time points for each group respectively.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Pregabalin High Dose | Physician's Withdrawal Checklist (PWC) Score for Cohort 3 (6-Month Last Visit) | Discontinuation Week 1 (n=109,30,94,29,99,30) | 6.8 units on a scale | Standard Deviation 6.56 |
| Pregabalin High Dose | Physician's Withdrawal Checklist (PWC) Score for Cohort 3 (6-Month Last Visit) | Discontinuation Week 2 (n=106,29,84,26,93,30) | 7.9 units on a scale | Standard Deviation 7.59 |
| Pregabalin Low Dose | Physician's Withdrawal Checklist (PWC) Score for Cohort 3 (6-Month Last Visit) | Discontinuation Week 1 (n=109,30,94,29,99,30) | 4.9 units on a scale | Standard Deviation 5.73 |
| Pregabalin Low Dose | Physician's Withdrawal Checklist (PWC) Score for Cohort 3 (6-Month Last Visit) | Discontinuation Week 2 (n=106,29,84,26,93,30) | 4.1 units on a scale | Standard Deviation 4.17 |
| Lorazepam | Physician's Withdrawal Checklist (PWC) Score for Cohort 3 (6-Month Last Visit) | Discontinuation Week 1 (n=109,30,94,29,99,30) | 5.1 units on a scale | Standard Deviation 4.45 |
| Lorazepam | Physician's Withdrawal Checklist (PWC) Score for Cohort 3 (6-Month Last Visit) | Discontinuation Week 2 (n=106,29,84,26,93,30) | 5.7 units on a scale | Standard Deviation 6.11 |
| Pregabalin Low Dose, Placebo | Physician's Withdrawal Checklist (PWC) Score for Cohort 3 (6-Month Last Visit) | Discontinuation Week 1 (n=109,30,94,29,99,30) | 7.4 units on a scale | Standard Deviation 6.43 |
| Pregabalin Low Dose, Placebo | Physician's Withdrawal Checklist (PWC) Score for Cohort 3 (6-Month Last Visit) | Discontinuation Week 2 (n=106,29,84,26,93,30) | 7.1 units on a scale | Standard Deviation 8.65 |
| Lorazepam, Lorazepam | Physician's Withdrawal Checklist (PWC) Score for Cohort 3 (6-Month Last Visit) | Discontinuation Week 1 (n=109,30,94,29,99,30) | 8.0 units on a scale | Standard Deviation 7.45 |
| Lorazepam, Lorazepam | Physician's Withdrawal Checklist (PWC) Score for Cohort 3 (6-Month Last Visit) | Discontinuation Week 2 (n=106,29,84,26,93,30) | 7.1 units on a scale | Standard Deviation 6.64 |
| Lorazepam, Placebo | Physician's Withdrawal Checklist (PWC) Score for Cohort 3 (6-Month Last Visit) | Discontinuation Week 1 (n=109,30,94,29,99,30) | 4.6 units on a scale | Standard Deviation 4.22 |
| Lorazepam, Placebo | Physician's Withdrawal Checklist (PWC) Score for Cohort 3 (6-Month Last Visit) | Discontinuation Week 2 (n=106,29,84,26,93,30) | 4.6 units on a scale | Standard Deviation 4.67 |
Other Pre-specified
Number of Participants With Treatment-Emergent Adverse Events (AEs)
An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. Treatment-emergent are events between first dose of study drug and Week 12, for period 1, and between Week 13 and Week 24, for period 2, that were absent before treatment or that worsened relative to pretreatment state.
Time frame: Baseline up to Week 12 (period 1), Week 13 up to Week 24 (period 2)
Population: Safety analysis set: all randomized participants who received at least 1 dose of study medication. Here, 'n' signifies those participants who were evaluable for this measure during each specified period, for each group respectively.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Pregabalin High Dose | Number of Participants With Treatment-Emergent Adverse Events (AEs) | Period 1 (n=154,52,154,52,153,50) | 103 participants |
| Pregabalin High Dose | Number of Participants With Treatment-Emergent Adverse Events (AEs) | Period 2 (n=121,39,112,38,114,39) | 62 participants |
| Pregabalin Low Dose | Number of Participants With Treatment-Emergent Adverse Events (AEs) | Period 1 (n=154,52,154,52,153,50) | 37 participants |
| Pregabalin Low Dose | Number of Participants With Treatment-Emergent Adverse Events (AEs) | Period 2 (n=121,39,112,38,114,39) | 26 participants |
| Lorazepam | Number of Participants With Treatment-Emergent Adverse Events (AEs) | Period 1 (n=154,52,154,52,153,50) | 100 participants |
| Lorazepam | Number of Participants With Treatment-Emergent Adverse Events (AEs) | Period 2 (n=121,39,112,38,114,39) | 62 participants |
| Pregabalin Low Dose, Placebo | Number of Participants With Treatment-Emergent Adverse Events (AEs) | Period 1 (n=154,52,154,52,153,50) | 40 participants |
| Pregabalin Low Dose, Placebo | Number of Participants With Treatment-Emergent Adverse Events (AEs) | Period 2 (n=121,39,112,38,114,39) | 18 participants |
| Lorazepam, Lorazepam | Number of Participants With Treatment-Emergent Adverse Events (AEs) | Period 1 (n=154,52,154,52,153,50) | 95 participants |
| Lorazepam, Lorazepam | Number of Participants With Treatment-Emergent Adverse Events (AEs) | Period 2 (n=121,39,112,38,114,39) | 52 participants |
| Lorazepam, Placebo | Number of Participants With Treatment-Emergent Adverse Events (AEs) | Period 1 (n=154,52,154,52,153,50) | 35 participants |
| Lorazepam, Placebo | Number of Participants With Treatment-Emergent Adverse Events (AEs) | Period 2 (n=121,39,112,38,114,39) | 20 participants |
Other Pre-specified
Sheehan-Suicidality Tracking Scale (S-STS) Score
Sheehan-Suicidality Tracking Scale (S-STS): an 8-item prospective rating scale that tracked treatment-emergent suicidal ideation and behaviors. Items 1a, 2-6, 7a, and 8 were scored on a 5-point Likert scale (ranging from 0= not at all to 4=extremely). Items 1, 1b, and 7 required yes or no responses. Total score ranged from 0 to 35, higher score indicated higher suicidal tendency.
Time frame: Baseline up to Week 24
Population: Data was not statistically summarized but was available in individual participant listings and mapped to Columbia Classification Algorithm of Suicide Assessment (C-CASA) due to change in planned analysis.