NCT03772314

Modafinil Versus Amphetamines for the Treatment of Narcolepsy Type 2 and Idiopathic Hypersomnia

Completed Phase 2 Results posted Last updated 23 May 2024

What this trial tests

Phase 2 trial testing Modafinil in Idiopathic Hypersomnia in 44 participants. Completed in 4 May 2023.

Timeline

15 April 2019

Primary endpoint
4 May 2023

4 May 2023

Quick facts

Lead sponsor	Emory University
Phase	Phase 2
Status	Completed
Study type	INTERVENTIONAL
Allocation	randomized
Design	parallel
Masking	quadruple
Primary purpose	treatment
Enrollment	44
Start date	15 April 2019
Primary completion	4 May 2023
Estimated completion	4 May 2023
Sites	1 location across United States

Drugs / interventions tested

• Modafinil (modafinil) — full drug profile →
• Amphetamine-Dextroamphetamine

Conditions studied

• Idiopathic Hypersomnia — all drugs for Idiopathic Hypersomnia →
• Narcolepsy Without Cataplexy — all drugs for Narcolepsy Without Cataplexy →

Sponsor

Emory University

Who can join

Adults 18 to 65, any sex, with Idiopathic Hypersomnia or Narcolepsy Without Cataplexy. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Change in Epworth Sleepiness Scale (ESS) Score Primary · Baseline, Week 12

The Epworth Sleepiness Scale (ESS) asks respondents to indicate how likely they are to doze off or fall asleep during daytime situations such as reading or talking to someone. There are 8 items which are answered on a scale of 0 to 4 where 0 = would never doze and 4 = high chance of dozing. Total score can range from 0 to 24, with higher scores indicating more sleepiness. A score of 0 to 5 can be interpreted as "lower normal daytime sleepiness", a score of 6 to 10 is "higher normal daytime sleepiness", score between 11 to 12 are "mild excessive daytime sleepiness, scores of 13 to 15 are "moder

Group	Value	95% CI
Modafinil	5.0	± 2.7
Amphetamine-dextroamphetamine	4.4	± 4.7

Number of Participants Reporting Any Improvement by Patient Global Impression of Change (PGIC) for Overall Disease Severity Score Secondary · Week 12

The PGIC for Overall Severity asks respondents to rate their overall disease compared to baseline. Responses are indicated on a 7-point scale where 1 = "very much improved", 2 = "much improved", 3 = "minimally improved" 4 = "no change", 5 = "minimally worse", 6 = "much worse" and 7 = "very much worse". Responses were dichotomized into groups of participants who were treatment responders having any level of improvement (responses of "minimally improved", "much improved", or "very much improved") and treatment non-responders (responses of "no change" to "very much worse"). The number of particip

Group	Value	95% CI
Modafinil	18
Amphetamine-dextroamphetamine	16

Number of Participants Reporting Much or Very Much Improvement by Patient Global Impression of Change (PGIC) for Overall Disease Severity Score Secondary · Week 12

The PGIC for Overall Severity asks respondents to rate their overall disease compared to baseline. Responses are indicated on a scale of 1 to 7 where 1 = "very much improved", 2 = "much improved", 3 = "minimally improved" 4 = "no change", 5 = "minimally worse", 6 = "much worse" and 7 = "very much worse". The number of participants reporting "much improved" or "very much improved" at the Week 12 assessment compared to how they felt right before starting the study medication was examined.

Group	Value	95% CI
Modafinil	13
Amphetamine-dextroamphetamine	10

Number of Participants Reporting Any Improvement From Baseline on Patient Global Impression of Change (PGIC) for Sleepiness Score Secondary · Week 12

The PGIC for Sleepiness asks respondents to rate their sleepiness compared to baseline. Responses are indicated on a 7-point scale where 1 = "very much improved", 2 = "much improved", 3 = "minimally improved" 4 = "no change", 5 = "minimally worse", 6 = "much worse" and 7 = "very much worse". Responses were dichotomized into groups of participants who were treatment responders having any level of improvement (responses of "minimally improved", "much improved", or "very much improved") and treatment non-responders (responses of "no change" to "very much worse"). The number of participants report

Group	Value	95% CI
Modafinil	19
Amphetamine-dextroamphetamine	16

Number of Participants Reporting Much or Very Much Improvement From Baseline on Patient Global Impression of Change (PGIC) for Sleepiness Score Secondary · Week 12

The PGIC for Sleepiness asks respondents to rate their sleepiness compared to baseline. Responses are indicated on a 7-point scale where 1 = "very much improved", 2 = "much improved", 3 = "minimally improved" 4 = "no change", 5 = "minimally worse", 6 = "much worse" and 7 = "very much worse". The number of participants reporting "much improved" or "very much improved" at the Week 12 assessment compared to how they felt right before starting the study medication was examined.

Group	Value	95% CI
Modafinil	14
Amphetamine-dextroamphetamine	10

Number of Participants Reporting Any Improvement With Patient Global Impression of Change (PGIC) for Cognitive Dysfunction Score Secondary · Week 12

The PGIC for Cognitive Dysfunction asks respondents to rate their cognitive dysfunction compared to baseline. Cognitive dysfunction is defined for participants as "difficulty with thinking, problems with attention or concentration, and/or brain fog". Responses are indicated on a scale of 1 to 7 where where 1 = "very much improved", 2 = "much improved", 3 = "minimally improved" 4 = "no change", 5 = "minimally worse", 6 = "much worse" and 7 = "very much worse". Responses were dichotomized into groups of participants who were treatment responders having any level of improvement (responses of "min

Group	Value	95% CI
Modafinil	16
Amphetamine-dextroamphetamine	13

Number of Participants Reporting Much or Very Much Improvement With Patient Global Impression of Change (PGIC) for Cognitive Dysfunction Score Secondary · Week 12

The PGIC for Cognitive Dysfunction asks respondents to rate their cognitive dysfunction compared to baseline. Cognitive dysfunction is defined for participants as "difficulty with thinking, problems with attention or concentration, and/or brain fog". Responses are indicated on a scale of 1 to 7 where 1 = "very much improved", 2 = "much improved", 3 = "minimally improved" 4 = "no change", 5 = "minimally worse", 6 = "much worse" and 7 = "very much worse". The number of participants reporting "much improved" or "very much improved" at the Week 12 assessment compared to how they felt right before

Group	Value	95% CI
Modafinil	5
Amphetamine-dextroamphetamine	10

Number of Participants Reporting Any Improvement by Patient Global Impression of Change (PGIC) for Sleep Inertia Score Secondary · Week 12

The PGIC for Sleep Inertia asks respondents to rate their sleep inertia compared to baseline. Sleep inertia is defined for participants as "difficulty waking up and getting out of bed in the morning because of sleepiness". Responses are indicated on a scale of 1 to 7 where 1 = "very much improved", 2 = "much improved", 3 = "minimally improved" 4 = "no change", 5 = "minimally worse", 6 = "much worse" and 7 = "very much worse". Responses were dichotomized into groups of participants who were treatment responders having any level of improvement (responses of "minimally improved", "much improved",

Group	Value	95% CI
Modafinil	11
Amphetamine-dextroamphetamine	11

Number of Participants Reporting Much or Very Much Improvement by Patient Global Impression of Change (PGIC) for Sleep Inertia Score Secondary · Week 12

The PGIC for Sleep Inertia asks respondents to rate their sleep inertia compared to baseline. Sleep inertia is defined for participants as "difficulty waking up and getting out of bed in the morning because of sleepiness". Responses are indicated on a scale of 1 to 7 where 1 = "very much improved", 2 = "much improved", 3 = "minimally improved" 4 = "no change", 5 = "minimally worse", 6 = "much worse" and 7 = "very much worse". The number of participants reporting "much improved" or "very much improved" at the Week 12 assessment compared to how they felt right before starting the study medicatio

Group	Value	95% CI
Modafinil	4
Amphetamine-dextroamphetamine	4

Change in Hypersomnia Severity Index (HSI) From Baseline Secondary · Baseline, Week 12

The HSI is a 9-item instrument assessing the severity of excessive sleepiness (hypersomnolence). Items are scored on a Likert scale where 0 = not at all and 4 = very much. Total scores range from 0 to 36 and higher scores indicate greater severity of symptoms of hypersomnia. The change in HSI score is obtained by subtracting the total score at week 12 from the baseline score. Scores above 0 signify that the mean score at Week 12 was lower than the mean score at Baseline, indicating reduced severity of hypersomnia symptoms.

Group	Value	95% CI
Modafinil	8.0	± 5.6
Amphetamine-dextroamphetamine	10.4	± 6.8

Change in Sleep Inertia Questionnaire (SIQ) Score From Baseline Secondary · Baseline, Week 12

The SIQ is an instrument with 21 items with responses on a 5-point scale where 1 = "not at all" and 5 = "all the time". Two additional questions relate to how much time it takes for the respondent to wake up in the morning. For these analyses, a total score for the 21 items was generated. The change in SIQ score is obtained by subtracting the total score at week 12 from the baseline score. Scores above 0 signify that the mean score at Week 12 was lower than the mean score at Baseline, indicating reduced difficulty awakening.

Group	Value	95% CI
Modafinil	19.0	± 15.9
Amphetamine-dextroamphetamine	18.2	± 18.4

Adverse events — posted to ClinicalTrials.gov

Time frame: Information on adverse events was collected once participants began taking the study medication and continued through the final assessment at Week 12.. Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Modafinil

Serious: 1/22 (5%)

Deaths: 0/22

Amphetamine-dextroamphetamine

Serious: 0/22 (0%)

Deaths: 0/22

Serious adverse events (1 terms)

Reaction	System	Modafinil	Amphetamine-dextroamphetam…
Hospitalization due to suicidal ideation	Psychiatric disorders	—	—

Other adverse events (11 terms — click to expand)

Reaction	System	Modafinil	Amphetamine-dextroamphetam…
Reduced appetite	General disorders	—	—
Headache	General disorders	—	—
Insomnia	General disorders	—	—
Anxiety symptoms	Psychiatric disorders	—	—
Dizziness	General disorders	—	—
Depressive symptoms	Psychiatric disorders	—	—
Nausea	General disorders	—	—
Dry mouth	General disorders	—	—
Elevated heart rate/palpitations	Cardiac disorders	—	—
Jitteriness	General disorders	—	—
Elevated blood pressure	Vascular disorders	—	—

Most-reported serious reactions: Hospitalization due to suicidal ideation.

Data from ClinicalTrials.gov NCT03772314 adverse events section.

Sponsor's own description

For diseases that cause excessive daytime sleepiness (such as narcolepsy and idiopathic hypersomnia), there are several medications that can be used to treat sleepiness. However, it can be difficult to decide which medication to use for a particular individual for several reasons: 1) there are very few studies that directly compare two medications to see which works best; 2) there are very few studies that include people with a disorder of sleepiness called idiopathic hypersomnia.

To address this gap in knowledge, the researchers propose a randomized clinical trial comparing modafinil and amphetamine salts in patients with narcolepsy type 2 or idiopathic hypersomnia. All participants will either receive modafinil or amphetamine salts - no participant will receive placebo.

This study will evaluate which medication works better to improve sleepiness. The researchers will also see which medication is better for other symptoms including difficulty waking up and difficulty thinking, as well as seeing which medication causes fewer side effects. Finally, this study will see if any information about patients (such as age or sleep study features) predicts responding better to one medication or the other.

Publications & conference data

2 peer-reviewed publications reference this trial (live from Europe PMC):

1. Medications for daytime sleepiness in individuals with idiopathic hypersomnia.
   Trotti LM, Becker LA, Friederich Murray C, Hoque R. · · 2021 · cited 7× · PMID 34031871 · DOI 10.1002/14651858.cd012714.pub2
2. Modafinil Versus Amphetamine-Dextroamphetamine For Idiopathic Hypersomnia and Narcolepsy Type 2: A Randomized, Blinded, Non-inferiority Trial.
   Trotti LM, Blake T, Hoque R, Rye DB, et al · · 2024 · cited 3× · PMID 39306601 · DOI 10.1007/s40263-024-01122-y