Trial Outcomes & Findings for Effectiveness of Long-Term Versus Short-Term Treatment of Generalized Anxiety Disorder With Venlafaxine XR (NCT NCT00183274)
NCT ID: NCT00183274
Last Updated: 2017-01-16
Results Overview
Hamilton Rating Scale for Anxiety - The assessment of anxiety states by rating Each item is scored on a scale of 0 (not present) to 4 (severe), with a total score range of 0-56, where \<17 indicates mild severity, 18-24 mild to moderate severity and 25-30 moderate to severe.
COMPLETED
PHASE4
268 participants
Measured at Months 6 (Open Label), 12 (Double-Blind), and 18 (Double-Blind Relapse)
2017-01-16
Participant Flow
Most patients (n=239) were recruited and seen by Penn research psychiatrists in 4 primary care practices; others (n=95) responded to media advertising (radio \& print ads) at the central clinic at the University of Pennsylvania
7-day washout period of any psychoactive medication;other antidepressants and herbal products. Subject on certain medications, such as monamine oxidase inhibitor, investigational and antipsychotic drugs had to be off these medications for at least 30 days.
Participant milestones
| Measure |
Phase 1: Open-Label
Patients received 75mg - 225 mg of open-label venlafaxine XR for 6 months.
|
Phase 2: Double-Blind Venlafaxine XR
Responders to 6 months of open-label venlafaxine XR treatment were randomized to double-blind treatment in 60:40 ratio of drug to placebo
|
Phase 2: Double-Blind Placebo
Responders to 6 months of open-label venlafaxine XR treatment were randomized to double-blind treatment in a 60:40 ratio of drug to placebo
|
Phase 3: Double-Blind Relapse Phase (Drug After Drug)
Patients administered venlafaxine XR in phase 2 continued to take the drug during phase 3
|
Phase 3: Double-Blind Relapse Phase (Placebo After Drug)
Patients administered venlafaxine XR in Phase 2 were given a placebo in Phase 3
|
Phase 3: Double-Blind Relapse Phase (Placebo After Placebo)
Patients administered placebo in Phase 2 continued to take placebo during Phase 3
|
|---|---|---|---|---|---|---|
|
Phase 1: Open-Label
STARTED
|
268
|
0
|
0
|
0
|
0
|
0
|
|
Phase 1: Open-Label
COMPLETED
|
158
|
0
|
0
|
0
|
0
|
0
|
|
Phase 1: Open-Label
NOT COMPLETED
|
110
|
0
|
0
|
0
|
0
|
0
|
|
Phase 2: Double-Blind
STARTED
|
0
|
82
|
54
|
0
|
0
|
0
|
|
Phase 2: Double-Blind
COMPLETED
|
0
|
56
|
11
|
0
|
0
|
0
|
|
Phase 2: Double-Blind
NOT COMPLETED
|
0
|
26
|
43
|
0
|
0
|
0
|
|
Phase 3: Double-Blind
STARTED
|
0
|
0
|
0
|
15
|
34
|
10
|
|
Phase 3: Double-Blind
COMPLETED
|
0
|
0
|
0
|
13
|
14
|
6
|
|
Phase 3: Double-Blind
NOT COMPLETED
|
0
|
0
|
0
|
2
|
20
|
4
|
Reasons for withdrawal
| Measure |
Phase 1: Open-Label
Patients received 75mg - 225 mg of open-label venlafaxine XR for 6 months.
|
Phase 2: Double-Blind Venlafaxine XR
Responders to 6 months of open-label venlafaxine XR treatment were randomized to double-blind treatment in 60:40 ratio of drug to placebo
|
Phase 2: Double-Blind Placebo
Responders to 6 months of open-label venlafaxine XR treatment were randomized to double-blind treatment in a 60:40 ratio of drug to placebo
|
Phase 3: Double-Blind Relapse Phase (Drug After Drug)
Patients administered venlafaxine XR in phase 2 continued to take the drug during phase 3
|
Phase 3: Double-Blind Relapse Phase (Placebo After Drug)
Patients administered venlafaxine XR in Phase 2 were given a placebo in Phase 3
|
Phase 3: Double-Blind Relapse Phase (Placebo After Placebo)
Patients administered placebo in Phase 2 continued to take placebo during Phase 3
|
|---|---|---|---|---|---|---|
|
Phase 1: Open-Label
Adverse Event
|
31
|
0
|
0
|
0
|
0
|
0
|
|
Phase 1: Open-Label
Lack of Efficacy
|
13
|
0
|
0
|
0
|
0
|
0
|
|
Phase 1: Open-Label
Protocol Violation
|
11
|
0
|
0
|
0
|
0
|
0
|
|
Phase 1: Open-Label
Withdrawal by Subject
|
13
|
0
|
0
|
0
|
0
|
0
|
|
Phase 1: Open-Label
Lost to Follow-up
|
33
|
0
|
0
|
0
|
0
|
0
|
|
Phase 1: Open-Label
Other
|
9
|
0
|
0
|
0
|
0
|
0
|
|
Phase 2: Double-Blind
Relapsed
|
0
|
8
|
29
|
0
|
0
|
0
|
|
Phase 2: Double-Blind
Withdrawal by Subject
|
0
|
18
|
14
|
0
|
0
|
0
|
|
Phase 3: Double-Blind
Withdrawal by Subject
|
0
|
0
|
0
|
1
|
9
|
2
|
|
Phase 3: Double-Blind
Relapsed
|
0
|
0
|
0
|
1
|
11
|
2
|
Baseline Characteristics
Effectiveness of Long-Term Versus Short-Term Treatment of Generalized Anxiety Disorder With Venlafaxine XR
Baseline characteristics by cohort
| Measure |
Venlafaxine XR
n=334 Participants
Venlafaxine XR flexible dose of 75 - 225 mg/d
Venlafaxine XR : All participants will take venlafaxine for 6 months. After this initial 6 months, participants who are not randomized to placebo will continue to take venlafaxine.
|
|---|---|
|
Age, Categorical
<=18 years
|
4 Participants
n=93 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
280 Participants
n=93 Participants
|
|
Age, Categorical
>=65 years
|
50 Participants
n=93 Participants
|
|
Age, Continuous
|
46.11 years
STANDARD_DEVIATION 16.14 • n=93 Participants
|
|
Gender
Female
|
210 Participants
n=93 Participants
|
|
Gender
Male
|
124 Participants
n=93 Participants
|
|
Region of Enrollment
United States
|
334 participants
n=93 Participants
|
PRIMARY outcome
Timeframe: Measured at Months 6 (Open Label), 12 (Double-Blind), and 18 (Double-Blind Relapse)Population: The primary efficacy analytic method was time-to-relapse analyses estimated using a discrete-time Cox proportional hazards model.
Hamilton Rating Scale for Anxiety - The assessment of anxiety states by rating Each item is scored on a scale of 0 (not present) to 4 (severe), with a total score range of 0-56, where \<17 indicates mild severity, 18-24 mild to moderate severity and 25-30 moderate to severe.
Outcome measures
| Measure |
Open-Label: Venlafaxine XR
n=268 Participants
A 6-month open label administration of flexible dose Venlafaxine XR that occurred between months 1 - 6 of study.
|
Double-Blind Venlafaxine XR
n=82 Participants
A 6-month double-blind administration of Venlafaxine XR that occurred between months 7 - 12.
|
Double-Blind Placebo
n=54 Participants
A 6-month double-blind administration of placebo that occurred between months 7 - 12.
|
Double-Blind Relapse Drug After Drug
n=15 Participants
A 6-month double-blind administration of Venlafaxine XR that occurred between months 13 - 18.
|
Double-Blind Relapse Placebo After Drug
n=34 Participants
A 6-month double-blind administration of placebo that occurred between months 13 - 18.
|
Double-Blind Placebo After Placebo
n=10 Participants
A 6-month double-blind administration of placebo that occurred between months 13 - 18.
|
|---|---|---|---|---|---|---|
|
Hamilton Rating Scale for Anxiety
|
4.17 HAM-A Rating Score
Standard Deviation 3.10
|
6.29 HAM-A Rating Score
Standard Deviation 5.44
|
11.35 HAM-A Rating Score
Standard Deviation 5.51
|
5.80 HAM-A Rating Score
Standard Deviation 4.95
|
8.42 HAM-A Rating Score
Standard Deviation 6.12
|
6.19 HAM-A Rating Score
Standard Deviation 5.76
|
SECONDARY outcome
Timeframe: Measured at Months 6 (Open Label), 12 (Double-Blind), 18 (Double-Blind, and 24 (Double-Blind Relapse)Population: The primary efficacy analytic method was time to relapse analyses estimated using a discrete time Cox proportional hazards model.Chisquare analyses were used to contrast relapse or responder rates. In the case of small cell sizes, Fisher exact test replaced chisquare analysis.
The CGI provides an overall clinician-determined summary measure that takes into account a knowledge of the patient's history, psychosocial circumstances, symptoms, behavior, and the impact of the symptoms on the patient's ability to function. The CGI is rated on the following seven-point scale: 1=normal, not at all ill; 2=borderline mentally ill; 3=mildly ill; 4=moderately ill; 5=markedly ill; 6=severely ill; 7=among the most extremely ill patients. Results of the "Placebo After Placebo" group in Phase 3 were not entered due to sample size limitations.
Outcome measures
| Measure |
Open-Label: Venlafaxine XR
n=268 Participants
A 6-month open label administration of flexible dose Venlafaxine XR that occurred between months 1 - 6 of study.
|
Double-Blind Venlafaxine XR
n=82 Participants
A 6-month double-blind administration of Venlafaxine XR that occurred between months 7 - 12.
|
Double-Blind Placebo
n=54 Participants
A 6-month double-blind administration of placebo that occurred between months 7 - 12.
|
Double-Blind Relapse Drug After Drug
n=15 Participants
A 6-month double-blind administration of Venlafaxine XR that occurred between months 13 - 18.
|
Double-Blind Relapse Placebo After Drug
n=34 Participants
A 6-month double-blind administration of placebo that occurred between months 13 - 18.
|
Double-Blind Placebo After Placebo
n=10 Participants
A 6-month double-blind administration of placebo that occurred between months 13 - 18.
|
|---|---|---|---|---|---|---|
|
Clinical Global Impressions, Severity of Illness
|
1.37 Severity Score
Standard Deviation 0.65
|
1.73 Severity Score
Standard Deviation 1.27
|
2.64 Severity Score
Standard Deviation 1.25
|
1.86 Severity Score
Standard Deviation 1.01
|
2.25 Severity Score
Standard Deviation 1.17
|
1.95 Severity Score
Standard Deviation 1.31
|
Adverse Events
Venlafaxine XR
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
Venlafaxine XR
n=268 participants at risk
Adverse events were expected with venlafaxine XR. AEs were reported at least once by at least 5% of the study population for all patients who entered treatment. None of the adverse events that were expected or that occurred were considered serious or life threatening.
|
|---|---|
|
General disorders
Abdominal Pain
|
9.7%
26/268
|
|
Gastrointestinal disorders
Constipation
|
28.7%
77/268
|
|
General disorders
Decreased Orgasm
|
20.5%
55/268
|
|
General disorders
Decreased Sex Drive
|
25.4%
68/268
|
|
General disorders
Delayed Orgasm
|
7.1%
19/268
|
|
Gastrointestinal disorders
Diarrhea
|
13.1%
35/268
|
|
General disorders
Drowsiness
|
41.4%
111/268
|
|
General disorders
Dry mouth
|
48.5%
130/268
|
|
General disorders
Faintness
|
7.8%
21/268
|
|
General disorders
Fatigue
|
28.4%
76/268
|
|
Gastrointestinal disorders
Flatulence
|
24.6%
66/268
|
|
Gastrointestinal disorders
Gas
|
6.7%
18/268
|
|
General disorders
Headache
|
36.2%
97/268
|
|
General disorders
Increased sweating
|
34.0%
91/268
|
|
General disorders
Insomnia
|
30.6%
82/268
|
|
General disorders
Jitteriness
|
27.6%
74/268
|
|
General disorders
Lightheadedness
|
38.8%
104/268
|
|
General disorders
Muscle Aches
|
18.7%
50/268
|
|
General disorders
Nausea
|
33.2%
89/268
|
|
General disorders
Nightmares
|
29.1%
78/268
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place