A Phase 1/2 interventional study of Flumazenil in Hypersomnia, Primary Hypersomnia and Idiopathic Hypersomnia, sponsored by Lynn Marie Trotti. Completed at 1 site in United States. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2017-12-12.
Sponsored by Lynn Marie Trotti · Phase 1/2, Interventional, and Treatment
Among 30 studies in Idiopathic Hypersomnia with a site in United States — 12 open to participants now, 13 under way, 4 of them phase 3. Idiopathic Hypersomnia · United States.
Among the 30 studies in Idiopathic Hypersomnia with a site in United States, this one is the 26th largest by enrollment of the 27 interventional ones, is one of 3 that started in 2010, is the only one in phase 1/2, and was the 2nd registered.
52 studies on the registry are indexed under Idiopathic Hypersomnia; 23 are open to participants now.
This study's enrollment of 10 is below the median of 82 across 40 interventional studies indexed under Idiopathic Hypersomnia.
Browse Idiopathic Hypersomnia studies →12 of the 30 studies in Idiopathic Hypersomnia with a site in United States are open now, in 12 countries. Each count lists the studies.
Of the 17 Idiopathic Hypersomnia studies recruiting now, 4 (24%) set no upper age limit and 12 (71%) stop at 75 or younger; 2 take children under 18; 4 take healthy volunteers.
This study: 18 Years and older · all sexes · no healthy volunteers.
The full table on the hub →30 studies; the count open now beside each. This study's row is marked.
First in 2010; this study’s year is marked. 3 started in 2010.
Median enrollment 100 across the 27 interventional studies, 100 across the 3 observational. Of the 16 that completed or were terminated, 9 (56%) have results posted.
18 of 30 have an industry lead sponsor. The 10 most frequent:
Lynn Marie Trotti is the lead sponsor of 2 studies on the registry; none are open to participants now.
Lynn Marie Trotti has 2 studies filed under Idiopathic Hypersomnia — fewer than ten, so there is no comparison to draw.
5 of the studies in Idiopathic Hypersomnia with a site in United States that are under way reach primary completion within a year, 1 of them phase 3. Phase 3 first, then by date:
| Study | Primary completion |
|---|---|
| NCT07500090Phase 3Harmony Biosciences Management, Inc.A Phase 3 Efficacy and Safety Study of HBS-301 in Participants With Idiopathic Hypersomnia (IH) | 2027-10 |
| NCT06843590Alkermes, Inc.A Study to Evaluate the Safety and Effectiveness of ALKS 2680 in Subjects With Idiopathic Hypersomnia | 2026-11 |
| NCT06812078TakedaA Study of TAK-360 in Adults With Idiopathic Hypersomnia | 2026-11-30 |
| NCT06752668Centessa Pharmaceuticals (UK) LimitedA Study of ORX750 in Participants With Narcolepsy and Idiopathic Hypersomnia | 2026-12 |
| NCT05837091Mayo ClinicLow Sodium Oxybate in Patients With Idiopathic Hypersomnia | 2027-01-29 |
Among the 30 studies in Idiopathic Hypersomnia with a site in United States, from their registry updates:
The term 'hypersomnia' describes a group of symptoms that includes severe daytime sleepiness and sleeping long periods of time (more than 10 hours per night). Sometimes, hypersomnia is caused by a problem with the quality of sleep occurring at night, for instance when nighttime sleep is disrupted by frequent breathing pauses. In other cases, however, hypersomnia occurs even when nighttime sleep is of good quality. These cases of hypersomnia are presumed to be a symptom of brain dysfunction, and so are referred to as hypersomnias of central (i.e., brain) origin, or primary hypersomnias.
The causes of most of these primary hypersomnias are not known. However, our group has recently identified a problem with the major brain chemical responsible for sedation, known as GABA. In a subset of our hypersomnia patients, there is a naturally-occurring substance that causes the GABA receptor to be hyperactive. In essence, it is as though these patients are chronically medicated with Valium (or Xanax or alcohol, all substances that act through the GABA system), even though they do not take these medications.
Current treatment of central hypersomnias is limited. For the fraction of cases with narcolepsy, there are FDA-approved, available treatments. However, for the remainder of patients, there are no treatments approved by the FDA. They are usually treated with medications approved for narcolepsy, but sleep experts agree that these medications are often not effective for this group of patients.
Based on our understanding of the GABA abnormality in these patients, we evaluated whether flumazenil (an medication approved by the FDA for the treatment of overdose of GABA medications or the reversal of GABA-based anesthesia) would reverse the GABA abnormality in our patients. In a test tube model of this disease, flumazenil does in fact return the function of the GABA system to normal. The investigators have treated a few patients with flumazenil and most have felt that their hypersomnia symptoms improved with this treatment.
To determine whether flumazenil is truly beneficial for primary hypersomnia, this study will compare flumazenil to an inactive pill (the placebo). All subjects will receive both flumazenil and the placebo at different times, and their reaction times and symptoms will be compared on these two treatments to determine if one is superior. Currently, flumazenil can only be given through an injection into a vein (i.e., intravenously). This study will evaluate this intravenous dosing as well as a new form of flumazenil, which is taken as a lozenge to be dissolved under the tongue. If this study shows that flumazenil is more effective than placebo in the treatment of hypersomnia, it will identify a potential new therapy for this difficult-to-treat disorder.
52 studies on the registry are indexed under Idiopathic Hypersomnia; 23 are open to participants now.
This study's enrollment of 10 is below the median of 82 across 40 interventional studies indexed under Idiopathic Hypersomnia.
Browse Idiopathic Hypersomnia studies →Lynn Marie Trotti is the lead sponsor of 2 studies on the registry; none are open to participants now.
Compared within Idiopathic Hypersomnia, this study's primary condition as ClinicalTrials.gg classifies it; the registry's first condition term is Disorders of Excessive Somnolence. The counts are of registry records indexed under each term, refreshed daily. How we classify →
Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.
Exclusion Criteria:
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
A reason a treatment, test or procedure should not be given to a particular person, such as an allergy, another illness or a medicine they take.
Contraindication
A reason a treatment, test or procedure should not be given to a particular person, such as an allergy, another illness or a medicine they take.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Subjects in this arm will first receive a day of placebo, then a day of sublingual flumazenil
Drug: Flumazenil
Subjects in this group will first receive a day of sublingual flumazenil, then a day of placebo.
Drug: Flumazenil
Sublingual flumazenil
Change in Psychomotor Vigilance Task (PVT) Median Reaction Time
The PVT measures the reaction time to button press following the presentation of a visual stimulus, reported here as the median reaction time for multiple presentations during the 10 minute task. The measure used was the change in median reaction time from baseline to drug administration, where the median reaction time at each of the time points (below) was averaged to provide a single on-treatment value for median reaction time. The measure was then calculated as baseline value - treatment value, such that higher numbers denote improvement from baseline.
Time frame: 10, 30, 60, 90, 120, and 150 minutes after drug administration (averaged for all time points for each subject)
PVT Additional Measure #1, Change in Lapse Frequency
A PVT lapse is defined as a reaction time exceeding 500 msec following the presentation of a single stimulus, which are then summed for the entire 10 minute PVT testing period. The measure used was the change in the frequency of lapses from baseline to drug administration (calculated as baseline value - average value with study drug, where higher numbers denote improvement from baseline).
Time frame: 10, 30, 60, 90, 120, and 150 minutes after drug administration (averaged for all time points for each subject)
PVT Additional Measure #2, Change in Duration of Lapse Domain
The PVT duration of lapse domain is defined as the reciprocal of the reaction time averaged across the slowest 10% of responses. The measure used was the change in duration of lapse domain from baseline to drug administration (calculated as baseline value - average value with study drug, where lower numbers denote improvement from baseline).
Time frame: 10, 30, 60, 90, 120, and 150 minutes after drug administration (averaged for all time points for each subject)
PVT Additional Measure #3, Change in Optimum Response Times
The optimum response times is defined as the reciprocal of the reaction time averaged across the fastest 10% of responses. The measure used was the change in optimum response time from baseline to following drug administration (calculated as baseline value - average value with study drug, where lower numbers denote improvement from baseline).
Time frame: 10, 30, 60, 90, 120, and 150 minutes after drug administration (averaged for all time points for each subject)
PVT Additional Measure #4, Change in False Response Frequency
The false response frequency is defined as the number of button presses when no stimulus is presented. The measure used was the change in false response frequency from baseline to drug administration (calculated as baseline value - average value with study drug, where higher numbers denote improvement from baseline).
Time frame: 10, 30, 60, 90, 120, and 150 minutes after drug administration (averaged for all time points for each subject)
PVT Additional Measure #5, Change in Visual Analog Scale Rating of Sleepiness at the Completion of PVT
At the end of the 10 minute PVT testing period, subjects were asked to rate their current level of sleepiness along a line, which was transformed into a numeric value from 1-10, such that high levels indicated more severe subjective sleepiness. The measure used was the change in this rating from baseline to drug administration (calculated as baseline value - average value with study drug, where higher numbers denote improvement from baseline).
Time frame: 10, 30, 60, 90, 120, and 150 minutes after drug administration (averaged for all time points for each subject)
Change in Stanford Sleepiness Scale
The Stanford Sleepiness Scale (SSS) is a subjective rating of sleepiness, with score ranging from 1 to 7, where higher values reflect more severe sleepiness. The measure used was change in SSS from baseline to drug administration (calculated as baseline value - average value with study drug, where higher numbers denote improvement from baseline).
Time frame: 10, 30, 60, 90, 120, and 150 minutes after drug administration (averaged for all time points for each subject)
Electroencephalogram (EEG) Power
EEG signals reflect the state of excitability of the cerebral cortex and correlate highly with levels of behavioral arousal. This is quantifiable as 'power' of the signal (microvolts squared/signal frequency). The EEG signals will be acquired and stored for off-line power analysis and comparison between treatment conditions.
Time frame: following drug administration
Participants were recruited from the Sleep Center of the Emory Clinic, in Atlanta, Georgia, USA, between December 2010 and October 2011.
| Milestone | Placebo First, Then Flumazenil | Flumazenil First, Then Placebo |
|---|---|---|
| Started | 5 | 5 |
| Completed | 5 | 5 |
| Not completed | 0 | 0 |
| Milestone | Placebo First, Then Flumazenil | Flumazenil First, Then Placebo |
|---|---|---|
| Started | 5 | 5 |
| Completed | 5 | 5 |
| Not completed | 0 | 0 |
| Milestone | Placebo First, Then Flumazenil | Flumazenil First, Then Placebo |
|---|---|---|
| Started | 5 | 5 |
| Completed | 5 | 5 |
| Not completed | 0 | 0 |
The PVT measures the reaction time to button press following the presentation of a visual stimulus, reported here as the median reaction time for multiple presentations during the 10 minute task. The measure used was the change in median reaction time from baseline to drug administration, where the median reaction time at each of the time points (below) was averaged to provide a single on-treatment value for median reaction time. The measure was then calculated as baseline value - treatment value, such that higher numbers denote improvement from baseline.
| msec | Placebo | Sublingual Flumazenil |
|---|---|---|
| Change in Psychomotor Vigilance Task (PVT) Median Reaction Time | -9.86 ± 28.2 | -4.46 ± 63.7 |
A PVT lapse is defined as a reaction time exceeding 500 msec following the presentation of a single stimulus, which are then summed for the entire 10 minute PVT testing period. The measure used was the change in the frequency of lapses from baseline to drug administration (calculated as baseline value - average value with study drug, where higher numbers denote improvement from baseline).
| number of lapses during PVT testing | Placebo | Sublingual Flumazenil |
|---|---|---|
| PVT Additional Measure #1, Change in Lapse Frequency | -3.3 ± 6.9 | -2.6 ± 8.7 |
The PVT duration of lapse domain is defined as the reciprocal of the reaction time averaged across the slowest 10% of responses. The measure used was the change in duration of lapse domain from baseline to drug administration (calculated as baseline value - average value with study drug, where lower numbers denote improvement from baseline).
| 1/msec | Placebo | Sublingual Flumazenil |
|---|---|---|
| PVT Additional Measure #2, Change in Duration of Lapse Domain | 0.18 ± 0.30 | 0.25 ± 0.45 |
The optimum response times is defined as the reciprocal of the reaction time averaged across the fastest 10% of responses. The measure used was the change in optimum response time from baseline to following drug administration (calculated as baseline value - average value with study drug, where lower numbers denote improvement from baseline).
| 1/msec | Placebo | Sublingual Flumazenil |
|---|---|---|
| PVT Additional Measure #3, Change in Optimum Response Times | -0.02 ± 0.27 | -0.04 ± 0.63 |
The false response frequency is defined as the number of button presses when no stimulus is presented. The measure used was the change in false response frequency from baseline to drug administration (calculated as baseline value - average value with study drug, where higher numbers denote improvement from baseline).
| number of false starts | Placebo | Sublingual Flumazenil |
|---|---|---|
| PVT Additional Measure #4, Change in False Response Frequency | 0.09 ± 0.56 | -0.38 ± 0.45 |
At the end of the 10 minute PVT testing period, subjects were asked to rate their current level of sleepiness along a line, which was transformed into a numeric value from 1-10, such that high levels indicated more severe subjective sleepiness. The measure used was the change in this rating from baseline to drug administration (calculated as baseline value - average value with study drug, where higher numbers denote improvement from baseline).
| units on a scale | Placebo | Sublingual Flumazenil |
|---|---|---|
| PVT Additional Measure #5, Change in Visual Analog Scale Rating of Sleepiness at the Completion of PVT | 1.23 ± 1.49 | 1.01 ± 2.0 |
The Stanford Sleepiness Scale (SSS) is a subjective rating of sleepiness, with score ranging from 1 to 7, where higher values reflect more severe sleepiness. The measure used was change in SSS from baseline to drug administration (calculated as baseline value - average value with study drug, where higher numbers denote improvement from baseline).
| units on a scale | Placebo | Sublingual Flumazenil |
|---|---|---|
| Change in Stanford Sleepiness Scale | 0.84 ± 1.68 | 0.26 ± 1.36 |
EEG signals reflect the state of excitability of the cerebral cortex and correlate highly with levels of behavioral arousal. This is quantifiable as 'power' of the signal (microvolts squared/signal frequency). The EEG signals will be acquired and stored for off-line power analysis and comparison between treatment conditions.
No measurements were reported for this outcome.
Collected over Symptoms experienced within 24 hours of drug administration. Non-serious events are listed at a 5% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| Placebo | — | 0/10 (0%) | 4/10 (40%) |
| Sublingual Flumazenil | — | 0/10 (0%) | 9/10 (90%) |
| Event | Placebo | Sublingual Flumazenil |
|---|---|---|
| feeling "dizzy", "lightheaded", or "spacey"Nervous system disorders | 4/10 | 3/10 |
| headache (during or following drug administration)Nervous system disorders | 0/10 | 4/10 |
| feeling "jittery"Nervous system disorders | 0/10 | 1/10 |
| feeling of "panic", "anxiety", or "uneasy"Psychiatric disorders | 1/10 | 1/10 |
| back painMusculoskeletal and connective tissue disorders | 0/10 | 1/10 |
| feeling "giggly" or "high"Psychiatric disorders | 0/10 | 1/10 |
| feeling dysphoria or "drugged"Psychiatric disorders | 0/10 | 1/10 |
| Age, Categorical(Participants) | Placebo First, Then Flumazenil | Flumazenil First, Then Placebo | Total |
|---|---|---|---|
| <=18 years | 0 | 0 | 0 |
| Between 18 and 65 years | 5 | 5 | 10 |
| >=65 years | 0 | 0 | 0 |
| Age, Continuous(years) | Placebo First, Then Flumazenil | Flumazenil First, Then Placebo | Total |
|---|---|---|---|
| Mean | 33.6 ± 13.3 | 41.8 ± 18.1 | 37.7 ± 15.6 |
| Sex: Female, Male(Participants) | Placebo First, Then Flumazenil | Flumazenil First, Then Placebo | Total |
|---|---|---|---|
| Female | 5 | 5 | 10 |
| Male | 0 | 0 | 0 |
| Region of Enrollment(participants) | Placebo First, Then Flumazenil | Flumazenil First, Then Placebo | Total |
|---|---|---|---|
| United States | 5 | 5 | 10 |
The record gives a start of Sep 2010, a primary completion of Jan 2012 and a completion of Jan 2012. It does not say whether these dates are actual or estimated.
Results were first posted in Mar 2013, 1 year 2 months after primary completion.
How these figures are worked out, and which studies are left out of them.
This study is completed, as verified in Nov 2017. You cannot join it, but the record below documents what was studied.
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Studies of the drug tested here: Flumazenil
Lynn Marie Trotti