Attached files
| file | filename |
|---|---|
| 8-K - 8-K - Aquestive Therapeutics, Inc. | brhc10015485_8k.htm |
| EX-99.3 - EXHIBIT 99.3 - Aquestive Therapeutics, Inc. | brhc10015485_ex99-3.htm |
| EX-99.1 - EXHIBIT 99.1 - Aquestive Therapeutics, Inc. | brhc10015485_ex99-1.htm |
Exhibit 99.2
September 2020 Libervant Complete Response Letter Update
The Libervant development program has fully characterized the behavior of buccally-administered
diazepam Study Description Study Number Comparative bioavailability profile to Diastat in healthy volunteers Study 1899Study 1900Study 162021Study 162022Study 172018 Dose proportionality/ Linear pharmacokinetic (PK) behavior of
Libervant Study 162013 Effect of Seizure State on Libervant PK Study 160326 Comparative bioavailability profile to Diastat in patients Study 180323 Long term safety profile, >1100 exposures Study 42-1703 2
The Libervant Complete Response Letter (CRL) is focused solely on Study 180323 3 While the FDA
acknowledged that the overall Cmax geometric mean ratio (GMR) of Libervant versus Diastat in Study 180323 was comparable, some patients in two weight groups showed lower Cmax levels when compared to Diastat:51-62 kg (n=6) (12.5 mg Libervant/
15.0 mg Diastat)76-87 kg (n=7) (15.0 mg Libervant / 17.5 mg Diastat)The FDA is concerned that the Cmax for patients in those weight groups are too low The FDA also noted that, also in Study 180323, 4 subjects in the weight groups noted above
and 1 additional subject in the 63-75 kg weight group had a median Cmax level that was approximately half of the median Diastat level (180 ng/mL vs. 375 ng/mL respectively)The FDA also noted protocol deviations on a small number of blood
draws in a limited number of subjects for timepoints at 3 days or laterNo other concerns were cited in the CRL Aquestive plans to request a Type A meeting early in Q4
4 Study 180323: A Randomized, Open-Label Crossover Study to Evaluate the Pharmacokinetics of Single
Doses of Diazepam Buccal Film (DBF) Compared with Diastat Rectal Gel in Adult Subjects on a Concomitant Regimen of Antiepileptic Drugs (AED) for the Treatment of Epilepsy Libervant demonstrates consistent PK performance, while staying within
the observed range of the RLD, across the weight groups N=6 N=4 N=7 N=11
The linear PK profile allows the prescriber to adjust dose with predictable impact (Cmax) 5 Figure
14.2.2-38a, Study 162013 Mean (+/-SD) Cmax vs. Dose for Diazepam