Trial Outcomes & Findings for Evaluation of Patient Reported Outcomes in RRMS Patients Candidates for MS Therapy Change and Transitioned to Fingolimod 0.5 mg (EPOC) (NCT NCT01534182)
NCT ID: NCT01534182
Last Updated: 2014-08-08
Results Overview
The Treatment Satisfaction Questionnaire for Medication (TSQM) contains 14 items assessing the following 4 domains: effectiveness (items 1 - 3), side effects (items 4 - 8), convenience (items 9 - 11) and global satisfaction (items 12 - 14). The primary outcome was measured on the global satisfaction domain. Item 12 scored as 1 (not at all confident) to 5 (extremely confident); item 13 scored as 1 (not at all certain) to 5 (extremely certain); and item 14 scored as 1 (extremely dissatisfied) to 7 (extremely satisfied). Responses to items were summed and transformed: specifically, TSQM v 1.4 domain scale scores were computed by adding the items loading on each domain. The lowest possible score was subtracted from the composite score and divided by the greatest possible score range. This provided a transformed score between 0 and 1 that was then multiplied by 100. The final transformed score ranges from 0 to 100, with higher scores indicating better treatment satisfaction.
COMPLETED
PHASE4
298 participants
Baseline, 6 months
2014-08-08
Participant Flow
Participants at screening received standard DMT with either interferon beta-1a or glatiramer acetate from day -30 to day -1.
Eligible participants were then randomized in a 3:1 ratio to fingolimod or a standard DMT. For participants who were randomized to the standard DMT group, those who received IFN during screening were switched to GA at randomization and those who received GA during screening were switched to IFN at randomization.
Participant milestones
| Measure |
Fingolimod
Participants received 0.5 mg orally once a day.
|
Standard Disease Modifying Therapy (DMT)
Participants received interferon beta-1a (IFN), 44 mcg subcutaneously 3 times a week or glatiramer acetate (GA), 20 mg subcutaneously once a day.
|
|---|---|---|
|
Overall Study
STARTED
|
230
|
68
|
|
Overall Study
Safety Set
|
230
|
64
|
|
Overall Study
Full Analysis Set
|
229
|
62
|
|
Overall Study
COMPLETED
|
218
|
58
|
|
Overall Study
NOT COMPLETED
|
12
|
10
|
Reasons for withdrawal
| Measure |
Fingolimod
Participants received 0.5 mg orally once a day.
|
Standard Disease Modifying Therapy (DMT)
Participants received interferon beta-1a (IFN), 44 mcg subcutaneously 3 times a week or glatiramer acetate (GA), 20 mg subcutaneously once a day.
|
|---|---|---|
|
Overall Study
Administrative problems
|
1
|
0
|
|
Overall Study
Withdrawal by Subject
|
4
|
7
|
|
Overall Study
Adverse Event
|
7
|
3
|
Baseline Characteristics
Evaluation of Patient Reported Outcomes in RRMS Patients Candidates for MS Therapy Change and Transitioned to Fingolimod 0.5 mg (EPOC)
Baseline characteristics by cohort
| Measure |
Fingolimod
n=230 Participants
Participants received 0.5 mg orally once a day.
|
Standard Disease Modifying Therapy (DMT)
n=68 Participants
Participants received interferon beta-1a (IFN), 44 mcg subcutaneously 3 times a week or glatiramer acetate (GA), 20 mg subcutaneously once a day.
|
Total
n=298 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
35.4 Years
STANDARD_DEVIATION 9.9 • n=5 Participants
|
36.4 Years
STANDARD_DEVIATION 9.3 • n=7 Participants
|
35.6 Years
STANDARD_DEVIATION 9.8 • n=5 Participants
|
|
Sex: Female, Male
Female
|
162 Participants
n=5 Participants
|
50 Participants
n=7 Participants
|
212 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
68 Participants
n=5 Participants
|
18 Participants
n=7 Participants
|
86 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: Baseline, 6 monthsPopulation: Full Analysis Set (FAS): This set included all randomized participants who had taken at least one dose of study medication and had at least one post-baseline assessment of the TSQM. The last observation carried forward (LOCF) method was applied.
The Treatment Satisfaction Questionnaire for Medication (TSQM) contains 14 items assessing the following 4 domains: effectiveness (items 1 - 3), side effects (items 4 - 8), convenience (items 9 - 11) and global satisfaction (items 12 - 14). The primary outcome was measured on the global satisfaction domain. Item 12 scored as 1 (not at all confident) to 5 (extremely confident); item 13 scored as 1 (not at all certain) to 5 (extremely certain); and item 14 scored as 1 (extremely dissatisfied) to 7 (extremely satisfied). Responses to items were summed and transformed: specifically, TSQM v 1.4 domain scale scores were computed by adding the items loading on each domain. The lowest possible score was subtracted from the composite score and divided by the greatest possible score range. This provided a transformed score between 0 and 1 that was then multiplied by 100. The final transformed score ranges from 0 to 100, with higher scores indicating better treatment satisfaction.
Outcome measures
| Measure |
Fingolimod
n=229 Participants
Participants received 0.5 mg orally once a day.
|
Standard Disease Modifying Therapy (DMT)
n=62 Participants
Participants received interferon beta-1a (IFN), 44 mcg subcutaneously 3 times a week or glatiramer acetate (GA), 20 mg subcutaneously once a day.
|
|---|---|---|
|
Change in Patient-reported Treatment Satisfaction
|
22.69 scores on a scale
Standard Deviation 28.12
|
13.92 scores on a scale
Standard Deviation 30.63
|
SECONDARY outcome
Timeframe: 6 monthsPopulation: Safety Set: This set included all randomized participants who received at least one dose of study medication.
Participants were monitored for adverse events, serious adverse events and death throughout the study.
Outcome measures
| Measure |
Fingolimod
n=230 Participants
Participants received 0.5 mg orally once a day.
|
Standard Disease Modifying Therapy (DMT)
n=64 Participants
Participants received interferon beta-1a (IFN), 44 mcg subcutaneously 3 times a week or glatiramer acetate (GA), 20 mg subcutaneously once a day.
|
|---|---|---|
|
Number of Patients Who Experienced Adverse Events, Serious Adverse Events and Death
Adverse events (serious and non-serious)
|
73 Participants
|
26 Participants
|
|
Number of Patients Who Experienced Adverse Events, Serious Adverse Events and Death
Serious adverse events
|
2 Participants
|
0 Participants
|
|
Number of Patients Who Experienced Adverse Events, Serious Adverse Events and Death
Deaths
|
0 Participants
|
0 Participants
|
SECONDARY outcome
Timeframe: Baseline, 6 monthsPopulation: FAS: The LOCF method was applied.
TSQM v 1.4 domains for effectiveness, side effects and convenience were used to evaluate this outcome. The effectiveness domain for items 1 - 3 was scored as: 1 (extremely dissatisfied) to 7 (extremely satisfied). For the side effects domain, item 4 scored as 0(no) or 1(yes); item 5 scored as 1 (extremely bothersome) to 5 (not at all bothersome); and items 6 - 8 scored as 1 (a great deal) to 5 (not at all). For the convenience domain, items 9 and 10 scored as 1(extremely difficult) to 7 (extremely easy), and item 11 scored as 1 (extremely inconvenient) to 7 (extremely convenient). For each domain, scale scores were computed by adding the items loading on each domain. The lowest possible score was subtracted from the composite score and divided by the greatest possible score range. This provided a transformed score between 0 and 1 that was then multiplied by 100. The final transformed score ranges from 0 to 100, with higher scores indicating better treatment satisfaction.
Outcome measures
| Measure |
Fingolimod
n=229 Participants
Participants received 0.5 mg orally once a day.
|
Standard Disease Modifying Therapy (DMT)
n=62 Participants
Participants received interferon beta-1a (IFN), 44 mcg subcutaneously 3 times a week or glatiramer acetate (GA), 20 mg subcutaneously once a day.
|
|---|---|---|
|
Changes in Patient-reported Effectiveness, Side Effects and Convenience
Effectiveness
|
21.57 scores on a scale
Standard Deviation 24.01
|
11.56 scores on a scale
Standard Deviation 20.70
|
|
Changes in Patient-reported Effectiveness, Side Effects and Convenience
Side effects
|
26.75 scores on a scale
Standard Deviation 35.83
|
13.07 scores on a scale
Standard Deviation 40.19
|
|
Changes in Patient-reported Effectiveness, Side Effects and Convenience
Convenience
|
25.38 scores on a scale
Standard Deviation 20.72
|
10.57 scores on a scale
Standard Deviation 20.93
|
SECONDARY outcome
Timeframe: Baseline, 6 monthsPopulation: FAS: The LOCF method was applied.
The Beck Depression Inventory (BDI-I) scale was used to measure this outcome. The scale consists of 21 items to assess the intensity of depression in clinical and normal patients. Each item is a list of four statements arranged in increasing severity about a particular symptom of depression. Each item was scored from 0 - 3. If more than one score was provided for an item, the maximum score was considered the item score. The total score was calculated as the sum of all individual items and then compared to a key to determine the depression's severity. The standard key ranges were: 0 - 9 indicated minimal depression; 10 - 18 indicated mild depression; 19 - 29 indicated moderate depression and 30 - 63 indicated severe depression. Higher total scores indicate more severe depressive symptoms.
Outcome measures
| Measure |
Fingolimod
n=229 Participants
Participants received 0.5 mg orally once a day.
|
Standard Disease Modifying Therapy (DMT)
n=62 Participants
Participants received interferon beta-1a (IFN), 44 mcg subcutaneously 3 times a week or glatiramer acetate (GA), 20 mg subcutaneously once a day.
|
|---|---|---|
|
Change in Patient-reported Depression
|
-2.88 scores on a scale
Standard Deviation 6.80
|
-1.86 scores on a scale
Standard Deviation 8.04
|
SECONDARY outcome
Timeframe: Baseline, 6 monthsPopulation: Participants from the full analysis set were considered for this analysis. However, for a given time frame, participants analyzed had both baseline and 6 month asssessment values.
The SF-36 is a health-related quality of life instrument used in numerous disease states, including MS (Brazier et al 1992). It is a self-administered survey that measures 8 domains of health including: physical functioning, role limitations due to physical health, bodily pain, general health perceptions, vitality, social functioning, role limitations due to emotional problems and general mental health. Two summary scale scores can be calculated: the Physical Component Summary (PCS) and the Mental Component Summary (MCS). Each domain was scored by adding the individual items from the domain and transforming the resulting scores into a 0 to 100 scale with higher scores indicating better health status or functioning.
Outcome measures
| Measure |
Fingolimod
n=229 Participants
Participants received 0.5 mg orally once a day.
|
Standard Disease Modifying Therapy (DMT)
n=62 Participants
Participants received interferon beta-1a (IFN), 44 mcg subcutaneously 3 times a week or glatiramer acetate (GA), 20 mg subcutaneously once a day.
|
|---|---|---|
|
Change in Patient-reported Health-related Quality-of-life Using the Short Form Health Survey v2 Acute (SF-36 v2 Acute)
Physical functioning (n=225,61)
|
3.62 scores on scale
Standard Deviation 16.23
|
1.39 scores on scale
Standard Deviation 14.23
|
|
Change in Patient-reported Health-related Quality-of-life Using the Short Form Health Survey v2 Acute (SF-36 v2 Acute)
Role limitations due to physical health (n=226,61)
|
6.50 scores on scale
Standard Deviation 21.99
|
4.30 scores on scale
Standard Deviation 27.52
|
|
Change in Patient-reported Health-related Quality-of-life Using the Short Form Health Survey v2 Acute (SF-36 v2 Acute)
Bodily pain (n=225,61)
|
5.24 scores on scale
Standard Deviation 23.79
|
0.93 scores on scale
Standard Deviation 22.95
|
|
Change in Patient-reported Health-related Quality-of-life Using the Short Form Health Survey v2 Acute (SF-36 v2 Acute)
General health (n=226,61)
|
4.28 scores on scale
Standard Deviation 17.72
|
4.43 scores on scale
Standard Deviation 22.57
|
|
Change in Patient-reported Health-related Quality-of-life Using the Short Form Health Survey v2 Acute (SF-36 v2 Acute)
Vitality (n=226,61)
|
7.72 scores on scale
Standard Deviation 18.61
|
1.95 scores on scale
Standard Deviation 21.97
|
|
Change in Patient-reported Health-related Quality-of-life Using the Short Form Health Survey v2 Acute (SF-36 v2 Acute)
Social functioning (n=226,61)
|
5.59 scores on scale
Standard Deviation 23.36
|
1.64 scores on scale
Standard Deviation 23.77
|
|
Change in Patient-reported Health-related Quality-of-life Using the Short Form Health Survey v2 Acute (SF-36 v2 Acute)
Role limit. due to emotional problems (n=224,61)
|
7.18 scores on scale
Standard Deviation 25.98
|
5.33 scores on scale
Standard Deviation 27.00
|
|
Change in Patient-reported Health-related Quality-of-life Using the Short Form Health Survey v2 Acute (SF-36 v2 Acute)
Mental health (n=226,61)
|
5.60 scores on scale
Standard Deviation 18.55
|
2.79 scores on scale
Standard Deviation 22.09
|
|
Change in Patient-reported Health-related Quality-of-life Using the Short Form Health Survey v2 Acute (SF-36 v2 Acute)
Physical component summary (n=222,61)
|
1.51 scores on scale
Standard Deviation 5.69
|
0.68 scores on scale
Standard Deviation 6.57
|
|
Change in Patient-reported Health-related Quality-of-life Using the Short Form Health Survey v2 Acute (SF-36 v2 Acute)
Mental component summary (n=222,61)
|
3.16 scores on scale
Standard Deviation 9.66
|
1.68 scores on scale
Standard Deviation 11.31
|
Adverse Events
Fingolimod
Standard Disease Modifying Therapy (DMT): Interferon Beta-1a
Standard Disease Modifying Therapy: Glatiramer Acetate
Serious adverse events
| Measure |
Fingolimod
n=230 participants at risk
Participants received 0.5 mg orally once a day.
|
Standard Disease Modifying Therapy (DMT): Interferon Beta-1a
n=28 participants at risk
Participants received interferon beta-1a (IFN), 44 mcg subcutaneously 3 times a week
|
Standard Disease Modifying Therapy: Glatiramer Acetate
n=36 participants at risk
Patients who received glatiramer acetate (GA), 20 mg subcutaneously once a day.
|
|---|---|---|---|
|
Injury, poisoning and procedural complications
Foot Fracture
|
0.43%
1/230
|
0.00%
0/28
|
0.00%
0/36
|
|
Renal and urinary disorders
Renal colic
|
0.43%
1/230
|
0.00%
0/28
|
0.00%
0/36
|
Other adverse events
| Measure |
Fingolimod
n=230 participants at risk
Participants received 0.5 mg orally once a day.
|
Standard Disease Modifying Therapy (DMT): Interferon Beta-1a
n=28 participants at risk
Participants received interferon beta-1a (IFN), 44 mcg subcutaneously 3 times a week
|
Standard Disease Modifying Therapy: Glatiramer Acetate
n=36 participants at risk
Patients who received glatiramer acetate (GA), 20 mg subcutaneously once a day.
|
|---|---|---|---|
|
Blood and lymphatic system disorders
Lymphopenia
|
11.7%
27/230
|
0.00%
0/28
|
5.6%
2/36
|
|
Investigations
Gamma-Glutamyltransferase increased
|
5.7%
13/230
|
3.6%
1/28
|
0.00%
0/36
|
|
Investigations
Alanine aminotransferase increased
|
4.8%
11/230
|
7.1%
2/28
|
0.00%
0/36
|
|
General disorders
Influenza like illness
|
0.00%
0/230
|
35.7%
10/28
|
0.00%
0/36
|
|
General disorders
Injection site pain
|
0.00%
0/230
|
3.6%
1/28
|
16.7%
6/36
|
|
General disorders
Injection site erythema
|
0.00%
0/230
|
0.00%
0/28
|
8.3%
3/36
|
|
General disorders
Injection site extravasation
|
0.00%
0/230
|
0.00%
0/28
|
5.6%
2/36
|
Additional Information
Study Director
Novartis
Results disclosure agreements
- Principal investigator is a sponsor employee The terms and conditions of Novartis' agreements with its investigators may vary. However, Novartis does not prohibit any investigator from publishing. Any publications from a single-site are postponed until the publication of the pooled data (i.e., data from all sites) in the clinical trial or disclosure of trial results in their entirety.
- Publication restrictions are in place
Restriction type: OTHER