EPIPHAST II

13 evidence topics · 5 sources

Objective

Comparison of single and repeat doses with EpiPen and manual intramuscular epinephrine

“The EPIPHAST II trial was designed to compare single doses of AQST-109 to EpiPen® 0.3mg and epinephrine 0.3mg intramuscular (IM) injection, as well as repeat doses of AQST-109 to repeat doses of epinephrine 0.3mg IM injection.” (opens the source at this quote in a new tab)

Location and study date

Topline results reported in September 2022

“WARREN, N.J., Sept. 27, 2022 (GLOBE NEWSWIRE) -- Aquestive Therapeutics, Inc. (NASDAQ: AQST), a pharmaceutical company advancing medicines to solve patients’ problems with current standards of care and provide transformative products to improve their lives, today announced positive topline results from the EPIPHAST II trial for its AQST-109 epinephrine sublingual film.” (opens the source at this quote in a new tab)

Study design

Randomized open-label crossover phase 1 design

“Data were integrated from 2 randomized, open-label, phase I crossover trials that evaluated the PK and PD of epinephrine in 54 healthy volunteers.” (opens the source at this quote in a new tab)

Single-dose and repeat-dose comparisons

“Aquestive is conducting its EPIHPHAST II study comparing AQST-109 to epi 0.3mg IM injection (repeat dose) and AQST-109 to EpiPen 0.3mg (single dose).” (opens the source at this quote in a new tab)

Eligibility criteria

Healthy volunteers without other medical conditions

“They had no previous medical conditions and were delivered either AQST-109 12 mg or 0.3 mg EpiPen, 0.3 mg generic EpiPen, 0.3 mg Auvi-Q, and 0.3 mg manual intramuscular injection.” (opens the source at this quote in a new tab)

Treatment

AQST-109 12 mg, EpiPen 0.3 mg, and epinephrine 0.3 mg intramuscular injection

“The EPIPHAST II trial was designed to compare single doses of AQST-109 to EpiPen® 0.3mg and epinephrine 0.3mg intramuscular (IM) injection, as well as repeat doses of AQST-109 to repeat doses of epinephrine 0.3mg IM injection.” (opens the source at this quote in a new tab)

Study outcomes

Rationale for using time to maximum epinephrine concentration as the primary endpoint

Clinical importance of rapid systemic epinephrine delivery

“Speed matters in delivering systemic epinephrine during an anaphylaxis event. Any delay can result in severe bronchospasm, acute respiratory failure and/or cardiovascular collapse, as well as less favorable outcomes and death” (opens the source at this quote in a new tab)

Pharmacodynamic measures assessed alongside pharmacokinetics

“After one dose of AQST-109, maximum mean effects on systolic blood pressure occurred within 5 minutes of dosing compared to 8 minutes for EpiPen. Maximum mean effects in heart rate occurred within 8 minutes of administering AQST-109 compared to an average of 5 minutes within administering EpiPen.” (opens the source at this quote in a new tab)

Statistical analysis description

Number of participants (Planned and analyzed)

Participants across the two integrated phase 1 trials

“Data were integrated from 2 randomized, open-label, phase I crossover trials that evaluated the PK and PD of epinephrine in 54 healthy volunteers.” (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

Time to maximum concentration after a single dose

“Results from the single dose administration showed AQST-109 achieved a significantly faster Tmax (12 minutes), compared to both EpiPen® (22.5 minutes) and epinephrine 0.3mg IM injection (45 minutes).” (opens the source at this quote in a new tab)

Maximum concentration after single and repeat dosing

“AQST-109 repeat dosing provided significantly higher drug plasma concentrations, with a Tmax of 8 minutes after administration, and extensive absorption was observed. The mean maximum concentration (Cmax) of AQST-109 was 465 pg/mL after one dose and 2,958 pg/mL after two doses. In comparison, the epi 0.3mg IM injection Cmax was 489 pg/mL after one dose and 911 pg/mL after two doses. The single dose of EpiPen resulted in a Cmax of 869 pg/mL.” (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 severe or serious adverse events

“Safety results for AQST-109 were in line with expectations, and no severe or serious adverse events were reported.” (opens the source at this quote in a new tab)

Study limitations

Summary: study limitations

The trial was open label and enrolled healthy volunteers, so results describe epinephrine absorption and hemodynamic change in the absence of an allergic reaction. Reported results come from a company announcement and from an integrated analysis that pooled this trial with the earlier EPIPHAST trial, and the individual trial has no registry record and no separate peer-reviewed publication, so the number of participants, the analysis sets, and the variability around the reported Cmax and Tmax values are not available. Repeat dosing produced a mean Cmax of 2,958 pg/mL, well above the 911 pg/mL reported after two intramuscular doses, an exposure difference the FDA later required be justified on safety grounds.