Trial Outcomes & Findings for Dimethyl Fumarate for Obstructive Sleep Apnea (NCT NCT02438137)

Last Updated: 2017-05-31

Results Overview

For the 50 participants who had interpretable month 4 polysomnography (PSG) data available, mean change in sleep apnea severity, as measured by the mean change in respiratory disturbance index (RDI) between baseline (Month 0) PSG and Month 4 PSG, was calculated. The RDI represents the total number of apneas, hypopneas and respiratory-related arousals per hour of sleep.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

65 participants

Primary outcome timeframe

Month 0 to Month 4

Results posted on

2017-05-31

Participant Flow

Participant milestones

Participant milestones
Measure	Dimethyl Fumarate (Tecfidera®) Capsules The starting dose for dimethyl fumarate was 120 mg twice a day orally. After 7 days, the dose was increased to the maintenance dose of 240 mg twice a day. Slower dose escalations were allowed to increase tolerability, if necessary. Participants randomized to dimethyl fumarate were instructed to take this medication twice a day with breakfast and dinner for a period of 4 months. Dimethyl fumarate: Dimethyl fumarate capsules were dispensed at routine study appointments. 120 mg tablets were dispensed to facilitate dose titrations. Drug was dispensed in 1 month supply, so that compliance could be reconciled at follow-up visits, and recorded in accountability logs. Participants were instructed to take medication with food, (morning and at dinnertime). If participants missed a dose, they were instructed to resume their normal dose at the next scheduled time, and not to take an extra dose at their next dosing interval if they previously miss a dose.	Placebo The placebo is an inert product that looks like a pill and is identical to dimethyl fumarate capsules, but it contains no medicine. Participants randomized to placebo were instructed to take placebo twice a day with breakfast and dinner for a period of 4 months. Placebo: Placebo capsules were dispensed during routine study appointments. Placebo were dispensed in 1 month supply, so that compliance could be reconciled at monthly follow-up visits, and recorded in accountability logs. Participants were instructed to take the placebo with food, in the morning and at dinnertime. If participants missed a dose, they were instructed to resume their normal dose at the next scheduled time, and not to take an extra dose at their next dosing interval if they previously missed a dose.
Overall Study STARTED	44	21
Overall Study COMPLETED	36	15
Overall Study NOT COMPLETED	8	6

Reasons for withdrawal

Reasons for withdrawal
Measure	Dimethyl Fumarate (Tecfidera®) Capsules The starting dose for dimethyl fumarate was 120 mg twice a day orally. After 7 days, the dose was increased to the maintenance dose of 240 mg twice a day. Slower dose escalations were allowed to increase tolerability, if necessary. Participants randomized to dimethyl fumarate were instructed to take this medication twice a day with breakfast and dinner for a period of 4 months. Dimethyl fumarate: Dimethyl fumarate capsules were dispensed at routine study appointments. 120 mg tablets were dispensed to facilitate dose titrations. Drug was dispensed in 1 month supply, so that compliance could be reconciled at follow-up visits, and recorded in accountability logs. Participants were instructed to take medication with food, (morning and at dinnertime). If participants missed a dose, they were instructed to resume their normal dose at the next scheduled time, and not to take an extra dose at their next dosing interval if they previously miss a dose.	Placebo The placebo is an inert product that looks like a pill and is identical to dimethyl fumarate capsules, but it contains no medicine. Participants randomized to placebo were instructed to take placebo twice a day with breakfast and dinner for a period of 4 months. Placebo: Placebo capsules were dispensed during routine study appointments. Placebo were dispensed in 1 month supply, so that compliance could be reconciled at monthly follow-up visits, and recorded in accountability logs. Participants were instructed to take the placebo with food, in the morning and at dinnertime. If participants missed a dose, they were instructed to resume their normal dose at the next scheduled time, and not to take an extra dose at their next dosing interval if they previously missed a dose.
Overall Study Lost to Follow-up	3	2
Overall Study Adverse Event	1	0
Overall Study Withdrawal by Subject	4	3
Overall Study Physician Decision	0	1

Baseline Characteristics

Dimethyl Fumarate for Obstructive Sleep Apnea

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Dimethyl Fumarate (Tecfidera®) Capsules n=44 Participants The starting dose for dimethyl fumarate was 120 mg twice a day orally. After 7 days, the dose was increased to the maintenance dose of 240 mg twice a day. Slower dose escalations were allowed to increase tolerability, if necessary. Participants randomized to dimethyl fumarate were instructed to take this medication twice a day with breakfast and dinner for a period of 4 months. Dimethyl fumarate: Dimethyl fumarate capsules were dispensed at routine study appointments. 120 mg tablets were dispensed to facilitate dose titrations. Drug was dispensed in 1 month supply, so that compliance could be reconciled at follow-up visits, and recorded in accountability logs. Participants were instructed to take medication with food, (morning and at dinnertime). If participants missed a dose, they were instructed to resume their normal dose at the next scheduled time, and not to take an extra dose at their next dosing interval if they previously miss a dose.	Placebo n=21 Participants The placebo is an inert product that looks like a pill and is identical to dimethyl fumarate capsules, but it contains no medicine. Participants randomized to placebo were instructed to take placebo twice a day with breakfast and dinner for a period of 4 months. Placebo: Placebo capsules were dispensed during routine study appointments. Placebo were dispensed in 1 month supply, so that compliance could be reconciled at monthly follow-up visits, and recorded in accountability logs. Participants were instructed to take the placebo with food, in the morning and at dinnertime. If participants missed a dose, they were instructed to resume their normal dose at the next scheduled time, and not to take an extra dose at their next dosing interval if they previously missed a dose.	Total n=65 Participants Total of all reporting groups
Age, Continuous	49.1 years STANDARD_DEVIATION 11.7 • n=5 Participants	52.5 years STANDARD_DEVIATION 12.4 • n=7 Participants	50.2 years STANDARD_DEVIATION 12 • n=5 Participants
Sex: Female, Male Female	24 Participants n=5 Participants	9 Participants n=7 Participants	33 Participants n=5 Participants
Sex: Female, Male Male	20 Participants n=5 Participants	12 Participants n=7 Participants	32 Participants n=5 Participants
Region of Enrollment United States	44 participants n=5 Participants	21 participants n=7 Participants	65 participants n=5 Participants
Respiratory Disturbance Index (RDI)	36.4 respiratory events/hour STANDARD_DEVIATION 28 • n=5 Participants	29.0 respiratory events/hour STANDARD_DEVIATION 16.9 • n=7 Participants	34 respiratory events/hour STANDARD_DEVIATION 25.1 • n=5 Participants
Baseline cytokine levels (log-transformed values) Interleukin-6	0.406 pg/ml STANDARD_DEVIATION 0.354 • n=5 Participants	0.300 pg/ml STANDARD_DEVIATION 0.249 • n=7 Participants	0.372 pg/ml STANDARD_DEVIATION 0.325 • n=5 Participants
Baseline cytokine levels (log-transformed values) Tissue Necrosis Factor-alpha	0.933 pg/ml STANDARD_DEVIATION 0.195 • n=5 Participants	1.009 pg/ml STANDARD_DEVIATION 0.354 • n=7 Participants	0.957 pg/ml STANDARD_DEVIATION 0.257 • n=5 Participants
Baseline cytokine levels (log-transformed values) Interleukin-10	0.596 pg/ml STANDARD_DEVIATION 0.558 • n=5 Participants	0.392 pg/ml STANDARD_DEVIATION 0.294 • n=7 Participants	0.530 pg/ml STANDARD_DEVIATION 0.496 • n=5 Participants
Baseline cytokine levels (log-transformed values) Monocyte Chemoattractant Protein-1	2.632 pg/ml STANDARD_DEVIATION 0.118 • n=5 Participants	2.593 pg/ml STANDARD_DEVIATION 0.210 • n=7 Participants	2.619 pg/ml STANDARD_DEVIATION 0.153 • n=5 Participants

PRIMARY outcome

Timeframe: Month 0 to Month 4

Population: 65 participants were randomized. 14 participants withdrew from the study or were lost to followup. 51 completed study activities. 50 (35 DMF and 15 placebo) both completed the study and had an interpretable Month 4 PSG. One participant's Month 4 PSG was uninterpretable, thus the RDI from this participant could not be included in the final analysis.

Outcome measures

Outcome measures
Measure	Dimethyl Fumarate (Tecfidera®) Capsules n=35 Participants The starting dose for dimethyl fumarate was 120 mg twice a day orally. After 7 days, the dose was increased to the maintenance dose of 240 mg twice a day. Slower dose escalations were allowed to increase tolerability, if necessary. Participants randomized to dimethyl fumarate were instructed to take this medication twice a day with breakfast and dinner for a period of 4 months. Dimethyl fumarate: Dimethyl fumarate capsules were dispensed at routine study appointments. 120 mg tablets were dispensed to facilitate dose titrations. Drug was dispensed in 1 month supply, so that compliance could be reconciled at follow-up visits, and recorded in accountability logs. Participants were instructed to take medication with food, (morning and at dinnertime). If participants missed a dose, they were instructed to resume their normal dose at the next scheduled time, and not to take an extra dose at their next dosing interval if they previously miss a dose.	Placebo n=15 Participants The placebo is an inert product that looks like a pill and is identical to dimethyl fumarate capsules, but it contains no medicine. Participants randomized to placebo will be instructed to take placebo twice a day with breakfast and dinner for a period of 4 months. Placebo: Placebo capsules were dispensed during routine study appointments. Placebo were dispensed in 1 month supply, so that compliance can be reconciled at monthly follow-up visits, and recorded in accountability logs. Participants were instructed to take the placebo with food, in the morning and at dinnertime. If participants missed a dose, they were instructed to resume their normal dose at the next scheduled time, and not to take an extra dose at their next dosing interval if they previously missed a dose.
Mean Change in Apnea Severity as Measured by the Respiratory Disturbance Index (RDI)	-3.11 respiratory events/hour Standard Deviation 12.9	10.2 respiratory events/hour Standard Deviation 13.1

SECONDARY outcome

Timeframe: Month 0 to Month 4

Population: Cytokine analyses were conducted for those participants who completed the study and had interpretable Month 4 PSG results. Among this group, 3 participants did not have usable Month 4 blood specimens for this analysis. Thus, the mean difference in cytokine levels was calculated for 47 participants.

Levels of markers in the blood known as cytokines (measured in picograms per milliliter) were measured on a monthly basis from Month 0 (baseline) to Month 4. The outcome is the mean difference in cytokine level from baseline to month 4 (mean level at Month 4 - mean level at Baseline). Values were log-transformed for normality, prior to analysis.

Outcome measures

Outcome measures
Measure	Dimethyl Fumarate (Tecfidera®) Capsules n=34 Participants The starting dose for dimethyl fumarate was 120 mg twice a day orally. After 7 days, the dose was increased to the maintenance dose of 240 mg twice a day. Slower dose escalations were allowed to increase tolerability, if necessary. Participants randomized to dimethyl fumarate were instructed to take this medication twice a day with breakfast and dinner for a period of 4 months. Dimethyl fumarate: Dimethyl fumarate capsules were dispensed at routine study appointments. 120 mg tablets were dispensed to facilitate dose titrations. Drug was dispensed in 1 month supply, so that compliance could be reconciled at follow-up visits, and recorded in accountability logs. Participants were instructed to take medication with food, (morning and at dinnertime). If participants missed a dose, they were instructed to resume their normal dose at the next scheduled time, and not to take an extra dose at their next dosing interval if they previously miss a dose.	Placebo n=13 Participants The placebo is an inert product that looks like a pill and is identical to dimethyl fumarate capsules, but it contains no medicine. Participants randomized to placebo will be instructed to take placebo twice a day with breakfast and dinner for a period of 4 months. Placebo: Placebo capsules were dispensed during routine study appointments. Placebo were dispensed in 1 month supply, so that compliance can be reconciled at monthly follow-up visits, and recorded in accountability logs. Participants were instructed to take the placebo with food, in the morning and at dinnertime. If participants missed a dose, they were instructed to resume their normal dose at the next scheduled time, and not to take an extra dose at their next dosing interval if they previously missed a dose.
Mean Change in Serum Cytokine Levels (Mean Difference of Log-transformed Values) Interleukin-6	0.038 picograms/milliliter (log-transformed) Standard Deviation 0.249	-0.015 picograms/milliliter (log-transformed) Standard Deviation 0.096
Mean Change in Serum Cytokine Levels (Mean Difference of Log-transformed Values) Tissue necrosis factor-alpha	-0.002 picograms/milliliter (log-transformed) Standard Deviation 0.171	0.003 picograms/milliliter (log-transformed) Standard Deviation 0.257
Mean Change in Serum Cytokine Levels (Mean Difference of Log-transformed Values) Interleukin-10	0.084 picograms/milliliter (log-transformed) Standard Deviation 0.253	-0.036 picograms/milliliter (log-transformed) Standard Deviation 0.170
Mean Change in Serum Cytokine Levels (Mean Difference of Log-transformed Values) Monocyte chemoattractant protein-1	0.005 picograms/milliliter (log-transformed) Standard Deviation 0.136	0.057 picograms/milliliter (log-transformed) Standard Deviation 0.157

Adverse Events

Dimethyl Fumarate (Tecfidera®) Capsules

Serious events: 1 serious events

Other events: 27 other events

Deaths: 0 deaths

Placebo

Serious events: 1 serious events

Other events: 7 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Dimethyl Fumarate (Tecfidera®) Capsules n=44 participants at risk The starting dose for dimethyl fumarate was 120 mg twice a day orally. After 7 days, the dose was increased to the maintenance dose of 240 mg twice a day. Slower dose escalations were allowed to increase tolerability, if necessary. Participants randomized to dimethyl fumarate were instructed to take this medication twice a day with breakfast and dinner for a period of 4 months. Dimethyl fumarate: Dimethyl fumarate capsules were dispensed at routine study appointments. 120 mg tablets were dispensed to facilitate dose titrations. Drug was dispensed in 1 month supply, so that compliance could be reconciled at follow-up visits, and recorded in accountability logs. Participants were instructed to take medication with food, (morning and at dinnertime). If participants missed a dose, they were instructed to resume their normal dose at the next scheduled time, and not to take an extra dose at their next dosing interval if they previously miss a dose.	Placebo n=21 participants at risk The placebo is an inert product that looks like a pill and is identical to dimethyl fumarate capsules, but it contains no medicine. Participants randomized to placebo were instructed to take placebo twice a day with breakfast and dinner for a period of 4 months. Placebo: Placebo capsules were dispensed during routine study appointments. Placebo were dispensed in 1 month supply, so that compliance could be reconciled at monthly follow-up visits, and recorded in accountability logs. Participants were instructed to take the placebo with food, in the morning and at dinnertime. If participants missed a dose, they were instructed to resume their normal dose at the next scheduled time, and not to take an extra dose at their next dosing interval if they previously missed a dose.
Infections and infestations Pneumonia	2.3% 1/44 • Number of events 1 • For each participant, adverse events were captured at each visit beginning with Month 1 visit and ending with the Month 5 follow-up visit.	0.00% 0/21 • For each participant, adverse events were captured at each visit beginning with Month 1 visit and ending with the Month 5 follow-up visit.
Cardiac disorders Myocardial Infarction	0.00% 0/44 • For each participant, adverse events were captured at each visit beginning with Month 1 visit and ending with the Month 5 follow-up visit.	4.8% 1/21 • Number of events 1 • For each participant, adverse events were captured at each visit beginning with Month 1 visit and ending with the Month 5 follow-up visit.

Other adverse events

Other adverse events
Measure	Dimethyl Fumarate (Tecfidera®) Capsules n=44 participants at risk The starting dose for dimethyl fumarate was 120 mg twice a day orally. After 7 days, the dose was increased to the maintenance dose of 240 mg twice a day. Slower dose escalations were allowed to increase tolerability, if necessary. Participants randomized to dimethyl fumarate were instructed to take this medication twice a day with breakfast and dinner for a period of 4 months. Dimethyl fumarate: Dimethyl fumarate capsules were dispensed at routine study appointments. 120 mg tablets were dispensed to facilitate dose titrations. Drug was dispensed in 1 month supply, so that compliance could be reconciled at follow-up visits, and recorded in accountability logs. Participants were instructed to take medication with food, (morning and at dinnertime). If participants missed a dose, they were instructed to resume their normal dose at the next scheduled time, and not to take an extra dose at their next dosing interval if they previously miss a dose.	Placebo n=21 participants at risk The placebo is an inert product that looks like a pill and is identical to dimethyl fumarate capsules, but it contains no medicine. Participants randomized to placebo were instructed to take placebo twice a day with breakfast and dinner for a period of 4 months. Placebo: Placebo capsules were dispensed during routine study appointments. Placebo were dispensed in 1 month supply, so that compliance could be reconciled at monthly follow-up visits, and recorded in accountability logs. Participants were instructed to take the placebo with food, in the morning and at dinnertime. If participants missed a dose, they were instructed to resume their normal dose at the next scheduled time, and not to take an extra dose at their next dosing interval if they previously missed a dose.
Skin and subcutaneous tissue disorders Flushing	52.3% 23/44 • Number of events 27 • For each participant, adverse events were captured at each visit beginning with Month 1 visit and ending with the Month 5 follow-up visit.	0.00% 0/21 • For each participant, adverse events were captured at each visit beginning with Month 1 visit and ending with the Month 5 follow-up visit.
Gastrointestinal disorders Indigestion	4.5% 2/44 • Number of events 3 • For each participant, adverse events were captured at each visit beginning with Month 1 visit and ending with the Month 5 follow-up visit.	14.3% 3/21 • Number of events 3 • For each participant, adverse events were captured at each visit beginning with Month 1 visit and ending with the Month 5 follow-up visit.
Gastrointestinal disorders Nausea	9.1% 4/44 • Number of events 5 • For each participant, adverse events were captured at each visit beginning with Month 1 visit and ending with the Month 5 follow-up visit.	0.00% 0/21 • For each participant, adverse events were captured at each visit beginning with Month 1 visit and ending with the Month 5 follow-up visit.
Infections and infestations Cold	6.8% 3/44 • Number of events 4 • For each participant, adverse events were captured at each visit beginning with Month 1 visit and ending with the Month 5 follow-up visit.	14.3% 3/21 • Number of events 3 • For each participant, adverse events were captured at each visit beginning with Month 1 visit and ending with the Month 5 follow-up visit.
Infections and infestations Sinus Infection	0.00% 0/44 • For each participant, adverse events were captured at each visit beginning with Month 1 visit and ending with the Month 5 follow-up visit.	9.5% 2/21 • Number of events 2 • For each participant, adverse events were captured at each visit beginning with Month 1 visit and ending with the Month 5 follow-up visit.

Additional Information

Tiffany Braley, M.D., M.S.

UMichigan

Phone: 734-232-1147

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place