AQ109109

15 evidence topics · 3 sources

Objective

Confirmatory pharmacokinetic study requested in the Complete Response Letter

“The FDA issued a Complete Response Letter (CRL) on January 30, 2026, which requested that the Company complete a human factors study addressing packaging and administration, and a confirmatory pharmacokinetic (PK) study of Anaphylm.” (opens the source at this quote in a new tab)

Comparison of self-administration, clinician administration, and manual intramuscular injection

“In addition, using the revised packaging and revised instructions for use, the Company conducted a single PK study in healthy volunteers comparing self-administration to clinician-administered as well as manual intramuscular (IM) administration.” (opens the source at this quote in a new tab)

Location and study date

Topline results reported in August 2026

“08.10.26 at 7:00 AM EDT” (opens the source at this quote in a new tab)
“today announced results from its human factors (HF) validation study and pharmacokinetic (PK) study for Anaphylm™ (dibutepinephrine) sublingual film, conducted in support of the Company’s planned resubmission of its New Drug Application (NDA) to the U.S. Food and Drug Administration (FDA) for the treatment of Type 1 allergic reactions, including anaphylaxis.” (opens the source at this quote in a new tab)

Study design

Study arms, including a purposely misplaced administration arm

“The FDA also requested that Aquestive include a PK arm studying purposely misplaced administration of Anaphylm on top of the tongue or on the roof of the mouth, intended to demonstrate the impact of incorrect placement on PK and PD measures and tolerability.” (opens the source at this quote in a new tab)

Alignment with the FDA on the design before conduct

“Aquestive provided the proposed PK study design to the FDA prior to the Type A meeting and received preliminary comments in advance of the meeting. Most of the preliminary comments provided by the FDA were focused on ensuring consistency between past PK studies conducted by the Company and the proposed current design.” (opens the source at this quote in a new tab)

Eligibility criteria

Healthy volunteers

“Table 1: Clinical PK Study in Healthy Subjects Comparing Anaphylm Self-Administration to Clinician-Administered and Epinephrine IM Administration (Study AQ109109)*” (opens the source at this quote in a new tab)

Treatment

Revised packaging and instructions for use with an intramuscular comparator

“The Company also completed a confirmatory PK study in healthy volunteers using the revised packaging and revised instructions for use, which evaluated self-administration and clinician administration of Anaphylm and included manual intramuscular epinephrine as a comparator.” (opens the source at this quote in a new tab)

Study outcomes

Rationale for using geometric mean cmax and median tmax as the primary endpoints

Comparison of self-administered with clinician-administered exposure

“Self-administration pharmacokinetic (PK) results were comparable to clinician-administered PK results” (opens the source at this quote in a new tab)

Pharmacodynamic assessment of incorrect film placement

“Top-of-tongue PK arm showed clinically meaningful pharmacodynamic (PD) results” (opens the source at this quote in a new tab)

Statistical analysis description

Number of participants (Planned and analyzed)

No evidence found.

Description of analysis sets

No evidence found.

Results

Participant disposition

No administration errors in the self-administration arm

“No administration errors were observed in the self-administration arm of the PK study.” (opens the source at this quote in a new tab)

Use errors reported at resubmission

“No protocol-defined use errors were observed in the self-administration arm of the PK study.” (opens the source at this quote in a new tab)

Baseline characteristics

No evidence found.

Efficacy results

Pharmacokinetic results by administration route

Description	Anaphylm self-administered	Anaphylm clinician-administered	Manual IM clinician-administered
Geometric mean Cmax (pg/mL)	“391.7”	“357.6”	“334.5”
Median Tmax (minutes)	“12”	“12”	“45”

Pharmacokinetics and pharmacodynamics after top-of-tongue placement

“As expected, compared with prior clinical studies where the film was administered as per the instructions, the geometric mean Cmax is significantly lower and the Tmax significantly longer than with correct placement of our sublingual film. However, top-of-tongue placement resulted in a geometric mean Cmax above 100 pg/mL (baseline unadjusted), a median Tmax of 35 minutes, and clinically meaningful PD results that were comparable to or of greater magnitude than those observed with injectable epinephrine.” (opens the source at this quote in a new tab)

Health-related quality of life and patient-reported outcomes

No evidence found.

Safety results

Adverse events and film retention

“From a tolerability perspective, there were no participants in the HF study and no subjects in the PK study who prematurely removed the film. In the PK study there were no serious adverse events, no serious events, and no events that led to study drug discontinuation.” (opens the source at this quote in a new tab)

Study limitations

Summary: study limitations

Results are available only from a company topline announcement and a regulatory update, so the number of participants, the analysis sets, the statistical methods, and the confidence intervals around the reported geometric mean Cmax and median Tmax values have not been reported. The study was conducted in healthy volunteers rather than during allergic reactions, and the pharmacodynamic comparison for the top-of-tongue arm was described as a cross-study comparison against results from study AQ109301 rather than a within-study randomized comparison. No peer-reviewed publication or registry record for the study was located.