AQ109301

19 evidence topics · 4 sources

Objective

Comparison of single and repeat doses of AQST-109 with intramuscular epinephrine

“To compare the pharmacokinetics (PK) and pharmacodynamics (PD) of single dose and repeat doses (RD) of AQST-109 with intramuscular epinephrine in healthy adults.” (opens the source at this quote in a new tab)

Primary and secondary objectives stated at study initiation

“The primary objective is to compare the PK of epinephrine following the single administration of Anaphylm to single administration of epinephrine IM injection in healthy adult subjects. The secondary objectives include evaluating PK sustainability following repeat administration and evaluating the safety and tolerability following single and repeat administrations versus epinephrine IM injection and epinephrine autoinjectors.” (opens the source at this quote in a new tab)

Location and study date

Single-center study with first participant dosed in December 2023

“The two-part, Phase 3, single-center, open-label, randomized study is designed to compare the PK and pharmacodynamics (PD) of single and repeat doses of Anaphylm versus single and repeat doses of the epinephrine IM injection and epinephrine autoinjectors (EpiPen® and Auvi-Q®) in healthy adult subjects.” (opens the source at this quote in a new tab)

Topline data reported in March 2024

“today released positive topline clinical data from its Phase 3 pivotal pharmacokinetic (PK) clinical study of Anaphylm™ (epinephrine) Sublingual Film and findings from the FDA Type C meeting.” (opens the source at this quote in a new tab)

Study design

Two-part open-label crossover design with injectable comparators

“In this 2-part, phase 3, open-label study, participants received single dose and RD of AQST-109 and epinephrine via manual syringe, EpiPen, or Auvi-Q autoinjector on different days.” (opens the source at this quote in a new tab)

Structure of Part A and Part B

“Part A of the two-part Phase 3 is designed as a three-period, three-treatment, six sequence, comparative PK study and is expected to enroll up to 36 subjects.” (opens the source at this quote in a new tab)
“Part B is designed as a four-period, four-treatment, four-sequence, comparative PK study and is expected to enroll up to 64 subjects, inclusive of those who participated in Part A.” (opens the source at this quote in a new tab)

Eligibility criteria

Healthy adult participants

“The two-part, Phase 3, single-center, open-label, randomized study was designed to compare the PK and pharmacodynamics (PD) of single and repeat doses of Anaphylm versus single and repeat doses of the epinephrine intra-muscular (IM) injection and epinephrine autoinjectors (EpiPen® and Auvi-Q®) in healthy adult subjects.” (opens the source at this quote in a new tab)

Treatment

Anaphylm 12 mg with bracketing autoinjector and manual intramuscular comparators

“Part A will assess both the PK performance and sustainability of Anaphylm 12mg with the bracketed comparison of an epinephrine autoinjector (EpiPen) and epinephrine manual IM injection.” (opens the source at this quote in a new tab)
“Part B will assess the PK of a single dose of Anaphylm 12mg with the bracketed comparison of two autoinjectors (EpiPen and Auvi-Q) and the manual IM injection.” (opens the source at this quote in a new tab)

Study outcomes

Rationale for using bracketed epinephrine exposure as the primary endpoint

Regulatory basis for bracketing exposure against approved injectable products

“As expected, the FDA reiterated that, as with other epinephrine programs under development, concentrations of epinephrine above known EpiPen levels must be justified from a safety perspective, and PK sustainability remains a focus.” (opens the source at this quote in a new tab)

Bracketing of approved intramuscular products in earlier phase 1 work

“AQST-109 delivered epinephrine with PK and PD results within the bracketed range of approved intramuscular products.” (opens the source at this quote in a new tab)

Endpoint measures and sampling window

“PK and PD parameters were assessed in 360 minutes post-administration; primary end points were maximum serum concentration and partial area under the curve. Additional PK and PD end points including blood pressure and heart rate were also measured.” (opens the source at this quote in a new tab)

Primary and secondary endpoints as reported with topline data

“The primary endpoint was to compare the PK of epinephrine following the single administration of Anaphylm to the single administration of Adrenalin (epinephrine IM injection) and autoinjectors in healthy adult subjects. The secondary endpoints included evaluating PK sustainability following repeat administration and the safety and tolerability following single and repeat administrations versus epinephrine IM injection and epinephrine autoinjectors.” (opens the source at this quote in a new tab)

Statistical analysis description

Number of participants (Planned and analyzed)

Participants enrolled in the single-dose and repeat-dose parts

“The single dose part of the Phase 3 study was designed as a four-period, four-treatment, four-sequence, comparative PK study with 64 enrolled adult subjects.” (opens the source at this quote in a new tab)
“The repeat dosing part of the Phase 3 study was designed as a three-period, three-treatment, six sequence, comparative PK study with 36 enrolled adult subjects.” (opens the source at this quote in a new tab)

Description of analysis sets

No evidence found.

Results

Participant disposition

No evidence found.

Baseline characteristics

No evidence found.

Efficacy results

Single-dose pharmacokinetics and pharmacodynamics

“Achieved a geometric mean Cmax of 470 pg/mL bracketed by epinephrine autoinjectors AUVI-Q at 521 pg/mL and EpiPen at 469 pg/mL,” (opens the source at this quote in a new tab)
“Generated partial AUCs between (bracketed) autoinjectors and Adrenalin manual IM injection from 5 to 60 minutes” (opens the source at this quote in a new tab)
“Maintained a median Tmax of 12 minutes compared to 20 minutes for EpiPen, 30 minutes for AUVI-Q, and 50 minutes for Adrenalin,” (opens the source at this quote in a new tab)
“Produced a meaningful change from baseline pharmacodynamic measures of blood pressure and heart rate at the first tracked time point of 2 minutes, and” (opens the source at this quote in a new tab)

Repeat-dose pharmacokinetics and pharmacodynamics

“Maintains epinephrine plasma concentrations equal to or greater than existing injection products at all but 1 timepoint out to 2 hours,” (opens the source at this quote in a new tab)
“Demonstrated a median Tmax of 10 minutes after administration of the second dose,” (opens the source at this quote in a new tab)
“Exhibited consistent pharmacodynamics, and” (opens the source at this quote in a new tab)

Published single-dose and repeat-dose results

“After single dose AQST-109 administration, area under the curve and maximum serum concentration met the primary end point of PK bracketing of 60 minutes, exceeding that of manual intramuscular injection, equaling EpiPen, but lower than that of Auvi-Q.” (opens the source at this quote in a new tab)
“AQST-109 had a median time-to-maximum plasma concentration of 12 minutes, exceeding that of EpiPen (20 minutes), Auvi-Q (30 minutes), and intramuscular injection (50 minutes); there was also more consistency (narrower IQR) than the comparators.” (opens the source at this quote in a new tab)
“AQST-109 demonstrated more rapid and larger increases in blood pressure and heart rate than the comparators. RD AQST-109 had greater than dose-proportional increases in PK and PD parameters, exceeding the comparators.” (opens the source at this quote in a new tab)

Health-related quality of life and patient-reported outcomes

No evidence found.

Safety results

No serious adverse events in either part of the study

“Was consistently well tolerated with no SAEs.” (opens the source at this quote in a new tab)

Safety outcome reported in the publication

“No serious adverse events were reported.” (opens the source at this quote in a new tab)

Study limitations

Summary: study limitations

The study enrolled healthy adult volunteers rather than participants experiencing an allergic reaction, so epinephrine exposure and hemodynamic response were measured under conditions that differ from an anaphylaxis emergency. It was open label and single center, no clinical efficacy endpoint such as symptom reversal was assessed, and the comparison with approved injectable products rested on pharmacokinetic bracketing rather than on a direct clinical outcome. Enrollment totalled 64 participants in the single-dose part and 36 in the repeat-dose part, and no registry record identifying the trial on ClinicalTrials.gov was located.