Trial Outcomes & Findings for Tecfidera Slow-Titration Study (NCT NCT02428231)
NCT ID: NCT02428231
Last Updated: 2017-05-05
Results Overview
The GSRS is a weekly recall scale to rate the severity of GI symptoms in participants. It was modified for daily recall in this study. GSRS is a rating scale consisting of 15 items for assessment of GI symptoms (see Appendix 1). Items are scored for intensity on a 7-grade Likert scale, defined by descriptive anchors such that 0 = none, 1 = minor, 2 = mild, 3 =moderate, 4 = moderately severe, 5 = severe, and 6 = very severe discomfort. The overall GSRS score is the mean of these 15 items, varying from 0 to 6; a score of 0 indicates that no symptoms are present, and a score of 6 indicates the worst possible degree of all symptoms. A higher score relative to Baseline indicates worsening of severity.
TERMINATED
PHASE3
62 participants
from Week 2 (Baseline) to Week 14
2017-05-05
Participant Flow
Participant milestones
| Measure |
Standard Treatment (One-Week Titration)
Following a 2-week placebo run-in baseline period, 120 mg dimethyl fumarate (DMF) twice daily for 1 week, then 240 mg (as 2 120-mg capsules) DMF twice daily for 11 weeks.
|
Slow Up-Titration (Six-Week Titration)
Following a 2-week placebo run-in baseline period, 120 mg DMF once daily (morning dose) and placebo once daily (evening dose) for 2 weeks, then 120 mg DMF twice daily for 2 weeks, then 240 mg (as 2 120-mg capsules) DMF in the morning and 120 mg in the evening for 2 weeks, then 240 mg (as two 120-mg capsules) DMF twice daily for 6 weeks.
|
|---|---|---|
|
Overall Study
STARTED
|
30
|
32
|
|
Overall Study
COMPLETED
|
17
|
15
|
|
Overall Study
NOT COMPLETED
|
13
|
17
|
Reasons for withdrawal
| Measure |
Standard Treatment (One-Week Titration)
Following a 2-week placebo run-in baseline period, 120 mg dimethyl fumarate (DMF) twice daily for 1 week, then 240 mg (as 2 120-mg capsules) DMF twice daily for 11 weeks.
|
Slow Up-Titration (Six-Week Titration)
Following a 2-week placebo run-in baseline period, 120 mg DMF once daily (morning dose) and placebo once daily (evening dose) for 2 weeks, then 120 mg DMF twice daily for 2 weeks, then 240 mg (as 2 120-mg capsules) DMF in the morning and 120 mg in the evening for 2 weeks, then 240 mg (as two 120-mg capsules) DMF twice daily for 6 weeks.
|
|---|---|---|
|
Overall Study
Other
|
10
|
16
|
|
Overall Study
Required Symptomatic Therapy
|
0
|
1
|
|
Overall Study
Adverse Event
|
3
|
0
|
Baseline Characteristics
Tecfidera Slow-Titration Study
Baseline characteristics by cohort
| Measure |
Standard Treatment (One-Week Titration)
n=30 Participants
Following a 2-week placebo run-in baseline period, 120 mg DMF twice daily for 1 week, then 240 mg (as 2 120-mg capsules) DMF twice daily for 11 weeks.
|
Slow Up-Titration (Six-Week Titration)
n=32 Participants
Following a 2-week placebo run-in baseline period, 120 mg DMF once daily (morning dose) and placebo once daily (evening dose) for 2 weeks, then 120 mg DMF twice daily for 2 weeks, then 240 mg (as 2 120-mg capsules) DMF in the morning and 120 mg in the evening for 2 weeks, then 240 mg (as two 120-mg capsules) DMF twice daily for 6 weeks.
|
Total
n=62 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
45.5 years
STANDARD_DEVIATION 11.77 • n=5 Participants
|
42.5 years
STANDARD_DEVIATION 11.12 • n=7 Participants
|
44.0 years
STANDARD_DEVIATION 11.45 • n=5 Participants
|
|
Sex: Female, Male
Female
|
22 Participants
n=5 Participants
|
21 Participants
n=7 Participants
|
43 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
8 Participants
n=5 Participants
|
11 Participants
n=7 Participants
|
19 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: from Week 2 (Baseline) to Week 14Population: The limited number of participants enrolled and the early termination of the study resulted in efficacy data not collected, and efficacy outcomes not analyzed, as per the pre-specified plan of analysis.
The GSRS is a weekly recall scale to rate the severity of GI symptoms in participants. It was modified for daily recall in this study. GSRS is a rating scale consisting of 15 items for assessment of GI symptoms (see Appendix 1). Items are scored for intensity on a 7-grade Likert scale, defined by descriptive anchors such that 0 = none, 1 = minor, 2 = mild, 3 =moderate, 4 = moderately severe, 5 = severe, and 6 = very severe discomfort. The overall GSRS score is the mean of these 15 items, varying from 0 to 6; a score of 0 indicates that no symptoms are present, and a score of 6 indicates the worst possible degree of all symptoms. A higher score relative to Baseline indicates worsening of severity.
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: Week 2 (Baseline), Week 14Population: The limited number of participants enrolled and the early termination of the study resulted in efficacy data not collected, and efficacy outcomes not analyzed, as per the pre-specified plan of analysis.
Average change from baseline in GSRS scores over the 12 weeks of DMF treatment as measured by the total change in GSRS scores from baseline divided by the total number of days with GSRS scores recorded. The GSRS is a weekly recall scale to rate the severity of GI symptoms in participants. It was modified for daily recall in this study. GSRS is a rating scale consisting of 15 items for assessment of GI symptoms (see Appendix 1). Items are scored for intensity on a 7-grade Likert scale, defined by descriptive anchors such that 0 = none, 1 = minor, 2 = mild, 3 =moderate, 4 = moderately severe, 5 = severe, and 6 = very severe discomfort. The overall GSRS score is the mean of these 15 items, varying from 0 to 6; a score of 0 indicates that no symptoms are present, and a score of 6 indicates the worst possible degree of all symptoms.
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: Week 2 (Baseline), Week 14Population: The limited number of participants enrolled and the early termination of the study resulted in efficacy data not collected, and efficacy outcomes not analyzed, as per the pre-specified plan of analysis.
The GSRS is a weekly recall scale to rate the severity of GI symptoms in participants. The GSRS is a weekly recall scale to rate the severity of GI symptoms in participants. It was modified for daily recall in this study. GSRS is a rating scale consisting of 15 items for assessment of GI symptoms (see Appendix 1). Items are scored for intensity on a 7-grade Likert scale, defined by descriptive anchors such that 0 = none, 1 = minor, 2 = mild, 3 =moderate, 4 = moderately severe, 5 = severe, and 6 = very severe discomfort. The overall GSRS score is the mean of these 15 items, varying from 0 to 6; a score of 0 indicates that no symptoms are present, and a score of 6 indicates the worst possible degree of all symptoms. A higher score relative to Baseline indicates worsening of severity.
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: Week 2 (Baseline), Week 14Population: The limited number of participants enrolled and the early termination of the study resulted in efficacy data not collected, and efficacy outcomes not analyzed, as per the pre-specified plan of analysis.
The GSRS is a weekly recall scale to rate the severity of GI symptoms in participants. The GSRS is a weekly recall scale to rate the severity of GI symptoms in participants. It was modified for daily recall in this study. GSRS is a rating scale consisting of 15 items for assessment of GI symptoms (see Appendix 1). Items are scored for intensity on a 7-grade Likert scale, defined by descriptive anchors such that 0 = none, 1 = minor, 2 = mild, 3 =moderate, 4 = moderately severe, 5 = severe, and 6 = very severe discomfort. The overall GSRS score is the mean of these 15 items, varying from 0 to 6; a score of 0 indicates that no symptoms are present, and a score of 6 indicates the worst possible degree of all symptoms. A higher score relative to Baseline indicates worsening of severity.
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: Week 2 (Baseline), Weeks 4, 6, 8, 10, 12, 14Population: The limited number of participants enrolled and the early termination of the study resulted in efficacy data not collected, and efficacy outcomes not analyzed, as per the pre-specified plan of analysis.
Average change from baseline to end of DMF treatment in the GSRS. The GSRS is a weekly recall scale to rate the severity of GI symptoms in participants. It was modified for daily recall in this study. GSRS is a rating scale consisting of 15 items for assessment of GI symptoms (see Appendix 1). Items are scored for intensity on a 7-grade Likert scale, defined by descriptive anchors such that 0 = none, 1 = minor, 2 = mild, 3 =moderate, 4 = moderately severe, 5 = severe, and 6 = very severe discomfort. The overall GSRS score is the mean of these 15 items, varying from 0 to 6; a score of 0 indicates that no symptoms are present, and a score of 6 indicates the worst possible degree of all symptoms.
Outcome measures
Outcome data not reported
Adverse Events
Standard 1-Week Titration Arm
6-Week Titration Arm
Serious adverse events
| Measure |
Standard 1-Week Titration Arm
n=30 participants at risk
Following a 2-week placebo run-in baseline period, 120 mg DMF twice daily for 1 week, then 240 mg (as 2 120-mg capsules) DMF twice daily for 11 weeks.
|
6-Week Titration Arm
n=32 participants at risk
Following a 2-week placebo run-in baseline period, 120 mg DMF once daily (morning dose) and placebo once daily (evening dose) for 2 weeks, then 120 mg DMF twice daily for 2 weeks, then 240 mg (as 2 120-mg capsules) DMF in the morning and 120 mg in the evening for 2 weeks, then 240 mg (as two 120-mg capsules) DMF twice daily for 6 weeks.
|
|---|---|---|
|
Infections and infestations
Gastrointestinal infection
|
3.3%
1/30 • From start of study through Week 14 plus 2 weeks (±5 days) follow-up. Serious events were collected from time of informed consent and non-serious events were collected from the first dose and throughout the study.
|
0.00%
0/32 • From start of study through Week 14 plus 2 weeks (±5 days) follow-up. Serious events were collected from time of informed consent and non-serious events were collected from the first dose and throughout the study.
|
|
Injury, poisoning and procedural complications
Hip fracture
|
3.3%
1/30 • From start of study through Week 14 plus 2 weeks (±5 days) follow-up. Serious events were collected from time of informed consent and non-serious events were collected from the first dose and throughout the study.
|
0.00%
0/32 • From start of study through Week 14 plus 2 weeks (±5 days) follow-up. Serious events were collected from time of informed consent and non-serious events were collected from the first dose and throughout the study.
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
0.00%
0/30 • From start of study through Week 14 plus 2 weeks (±5 days) follow-up. Serious events were collected from time of informed consent and non-serious events were collected from the first dose and throughout the study.
|
3.1%
1/32 • From start of study through Week 14 plus 2 weeks (±5 days) follow-up. Serious events were collected from time of informed consent and non-serious events were collected from the first dose and throughout the study.
|
|
Musculoskeletal and connective tissue disorders
Osteoarthritis
|
0.00%
0/30 • From start of study through Week 14 plus 2 weeks (±5 days) follow-up. Serious events were collected from time of informed consent and non-serious events were collected from the first dose and throughout the study.
|
3.1%
1/32 • From start of study through Week 14 plus 2 weeks (±5 days) follow-up. Serious events were collected from time of informed consent and non-serious events were collected from the first dose and throughout the study.
|
Other adverse events
| Measure |
Standard 1-Week Titration Arm
n=30 participants at risk
Following a 2-week placebo run-in baseline period, 120 mg DMF twice daily for 1 week, then 240 mg (as 2 120-mg capsules) DMF twice daily for 11 weeks.
|
6-Week Titration Arm
n=32 participants at risk
Following a 2-week placebo run-in baseline period, 120 mg DMF once daily (morning dose) and placebo once daily (evening dose) for 2 weeks, then 120 mg DMF twice daily for 2 weeks, then 240 mg (as 2 120-mg capsules) DMF in the morning and 120 mg in the evening for 2 weeks, then 240 mg (as two 120-mg capsules) DMF twice daily for 6 weeks.
|
|---|---|---|
|
Gastrointestinal disorders
Abdominal pain upper
|
6.7%
2/30 • From start of study through Week 14 plus 2 weeks (±5 days) follow-up. Serious events were collected from time of informed consent and non-serious events were collected from the first dose and throughout the study.
|
0.00%
0/32 • From start of study through Week 14 plus 2 weeks (±5 days) follow-up. Serious events were collected from time of informed consent and non-serious events were collected from the first dose and throughout the study.
|
|
Infections and infestations
Cystitis
|
6.7%
2/30 • From start of study through Week 14 plus 2 weeks (±5 days) follow-up. Serious events were collected from time of informed consent and non-serious events were collected from the first dose and throughout the study.
|
6.2%
2/32 • From start of study through Week 14 plus 2 weeks (±5 days) follow-up. Serious events were collected from time of informed consent and non-serious events were collected from the first dose and throughout the study.
|
|
Infections and infestations
Gastroenteritis viral
|
3.3%
1/30 • From start of study through Week 14 plus 2 weeks (±5 days) follow-up. Serious events were collected from time of informed consent and non-serious events were collected from the first dose and throughout the study.
|
9.4%
3/32 • From start of study through Week 14 plus 2 weeks (±5 days) follow-up. Serious events were collected from time of informed consent and non-serious events were collected from the first dose and throughout the study.
|
|
Infections and infestations
Nasopharyngitis
|
10.0%
3/30 • From start of study through Week 14 plus 2 weeks (±5 days) follow-up. Serious events were collected from time of informed consent and non-serious events were collected from the first dose and throughout the study.
|
9.4%
3/32 • From start of study through Week 14 plus 2 weeks (±5 days) follow-up. Serious events were collected from time of informed consent and non-serious events were collected from the first dose and throughout the study.
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
3.3%
1/30 • From start of study through Week 14 plus 2 weeks (±5 days) follow-up. Serious events were collected from time of informed consent and non-serious events were collected from the first dose and throughout the study.
|
6.2%
2/32 • From start of study through Week 14 plus 2 weeks (±5 days) follow-up. Serious events were collected from time of informed consent and non-serious events were collected from the first dose and throughout the study.
|
|
Nervous system disorders
Headache
|
6.7%
2/30 • From start of study through Week 14 plus 2 weeks (±5 days) follow-up. Serious events were collected from time of informed consent and non-serious events were collected from the first dose and throughout the study.
|
12.5%
4/32 • From start of study through Week 14 plus 2 weeks (±5 days) follow-up. Serious events were collected from time of informed consent and non-serious events were collected from the first dose and throughout the study.
|
|
Nervous system disorders
Multiple sclerosis relapse
|
10.0%
3/30 • From start of study through Week 14 plus 2 weeks (±5 days) follow-up. Serious events were collected from time of informed consent and non-serious events were collected from the first dose and throughout the study.
|
3.1%
1/32 • From start of study through Week 14 plus 2 weeks (±5 days) follow-up. Serious events were collected from time of informed consent and non-serious events were collected from the first dose and throughout the study.
|
|
Skin and subcutaneous tissue disorders
Pruritus
|
6.7%
2/30 • From start of study through Week 14 plus 2 weeks (±5 days) follow-up. Serious events were collected from time of informed consent and non-serious events were collected from the first dose and throughout the study.
|
3.1%
1/32 • From start of study through Week 14 plus 2 weeks (±5 days) follow-up. Serious events were collected from time of informed consent and non-serious events were collected from the first dose and throughout the study.
|
|
Skin and subcutaneous tissue disorders
Rash
|
10.0%
3/30 • From start of study through Week 14 plus 2 weeks (±5 days) follow-up. Serious events were collected from time of informed consent and non-serious events were collected from the first dose and throughout the study.
|
3.1%
1/32 • From start of study through Week 14 plus 2 weeks (±5 days) follow-up. Serious events were collected from time of informed consent and non-serious events were collected from the first dose and throughout the study.
|
|
Vascular disorders
Flushing
|
23.3%
7/30 • From start of study through Week 14 plus 2 weeks (±5 days) follow-up. Serious events were collected from time of informed consent and non-serious events were collected from the first dose and throughout the study.
|
18.8%
6/32 • From start of study through Week 14 plus 2 weeks (±5 days) follow-up. Serious events were collected from time of informed consent and non-serious events were collected from the first dose and throughout the study.
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee Our agreement is subject to confidentiality but generally the PI can publish, for noncommercial purposes only, results and methods of the trial, but no other Sponsor Confidential Information. PI must give Sponsor no less than 60 days to review any manuscript for a proposed publication and must delay publication for up to an additional 90 days thereafter if Sponsor needs to file any patent application to protect any of Sponsor's intellectual property contained in the proposed publication.
- Publication restrictions are in place
Restriction type: OTHER