Demonstrating Bioequivalence for a Lumacaftor Monosubstance Formulation Versus Orkambi® (Lumacaftor/Ivacaftor) in Healthy Subjects.

BACKGROUND AND

OBJECTIVE

Lumacaftor is an active ingredient in the US Food and Drug Administration-approved combination medication Orkambi®, which is used for treating cystic fibrosis. Experimental evidence suggests that lumacaftor can be used as a monotherapy to improve brain perfusion and memory in heart failure. To clinically assess this therapeutic intervention, a formulation with demonstrated bioequivalence to the currently approved combination product is required.

METHODS

This comparative bioavailability and food-effect study compared lumacaftor pharmacokinetics in healthy patients following: (i) oral administration of lumacaftor (400 mg; Test Product) or Orkambi® (lumacaftor 400 mg/ivacaftor 250 mg; Reference Product) in the fed state and (ii) oral administration of lumacaftor (400 mg; Test Product) in the fasted to fed state. Plasma lumacaftor concentrations were measured with a standard liquid chromatography with tandem mass spectrometry approach.

RESULTS

The "Test-to-Reference ratio" of the geometric least-square means for maximum plasma concentration and area under the curve met the Food and Drug Administration-defined criteria for bioequivalence; median times to maximum plasma concentration values were not statistically different. The "Fed to Fasted ratio" of the geometric least-square means for maximum plasma concentration and area under the curve indicated a clear food effect on bioavailability. Lumacaftor exposure was approximately two times higher when administered with fatty foods than when taken in a fasting state. The monosubstance formulation was well tolerated.

CONCLUSIONS

We conclude that the lumacaftor monosubstance formulation delivers lumacaftor exposure that is not meaningfully different than the currently approved combination product.

CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT05968612.