A trial comparing amphetamine-dextroamphetamine with modafinil did not establish non-inferiority on its primary sleepiness endpoint. That statistical result does not, by itself, prove that amphetamine-dextroamphetamine was inferior.
The randomized, fully blinded trial included 44 adults with idiopathic hypersomnia or narcolepsy type 2. Over 12 weeks, medication was individually titrated up to modafinil 200 mg twice daily or amphetamine-dextroamphetamine 20 mg twice daily.
The primary outcome was change on the Epworth Sleepiness Scale. The protocol used a two-point non-inferiority threshold, defining how much worse the experimental comparison could be while still meeting that criterion.
Epworth scores improved by an average of 5.0 points with modafinil and 4.4 points with amphetamine-dextroamphetamine. Non-inferiority was not demonstrated on that primary outcome, with p = 0.11.
Non-inferiority was demonstrated on several secondary measures, including reported severity, sleepiness, sleep inertia and composite symptom questionnaires. Those secondary findings add information but do not replace the unsuccessful primary test.
Failure to establish non-inferiority can reflect uncertainty about the difference as well as the observed estimates. It is not automatically a successful test of superiority for the comparator. Conversely, improvement within both groups does not prove that the treatments are equivalent.
The trial’s modest size and disease-specific sample limit how broadly its comparative estimates can be applied.
Adverse-event discontinuation was numerically more common with modafinil, but that difference was nonsignificant. Anxiety was more common with modafinil and appetite suppression with amphetamine-dextroamphetamine.
The study concerns treatment in defined sleep disorders. It does not establish suitability for healthy enhancement, sleep-deprived driving or an individual with a positive toxicology result. Its main lesson is to preserve the primary hypothesis, secondary outcomes and uncertainty when describing comparative treatment evidence.
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