AQST-109 first-in-human phase 1 single-ascending-dose study

13 evidence topics · 1 source

Objective

Safety, tolerability, pharmacokinetic, and pharmacodynamic profiling of four formulations

“The Phase 1 randomized, single-ascending dose (SAD) study was performed with AQST-109 in order to assess safety, tolerability, PK, and PD profiles.” (opens the source at this quote in a new tab)

Location and study date

Conducted in Canada with topline results reported in October 2021

“10.25.21 at 8:31 AM EDT” (opens the source at this quote in a new tab)
“The study was conducted in Canada pursuant to a clinical trial application approved by Health Canada.” (opens the source at this quote in a new tab)

Study design

Randomized single-ascending-dose design across four formulations

“Subjects participating in the trial received, in ascending fashion, sublingually administered doses of AQST-109 across four different formulations. The four formulation compositions were varied to assess critical absorption factors including drug loading and the use of inventive excipients designed to influence absorption, stability, and the conversion of the prodrug.” (opens the source at this quote in a new tab)

Eligibility criteria

Healthy volunteers

“The changes observed suggest a comparable effect for AQST-109 when compared to autoinjectors in healthy volunteers.” (opens the source at this quote in a new tab)

Treatment

Dose strengths of the target formulation

“In addition, the target formulation had similar median Tmax values at lower dose strengths (15 minutes and 17.5 minutes for the 6 mg and 9 mg doses, respectively, included in the study).” (opens the source at this quote in a new tab)

Study outcomes

Rationale for using maximum epinephrine concentration and time to maximum concentration as the primary endpoints

Comparability measures chosen against approved autoinjectors

“Key clinical measures for comparability to existing autoinjectors (Cmax, Tmax, and area under the curve, or AUC) were within expected ranges for formulations 1, 2 (target), and 4” (opens the source at this quote in a new tab)

Pharmacodynamic markers measured

“The PD markers measured changes from baseline in heart rate, systolic blood pressure, and diastolic blood pressure.” (opens the source at this quote in a new tab)

Statistical analysis description

Number of participants (Planned and analyzed)

Doses administered per formulation

Film formulation	Dosings (n)
1	“6”
2 (target)	“8”
3	“6”
4	“7”

Description of analysis sets

No evidence found.

Results

Participant disposition

No evidence found.

Baseline characteristics

No evidence found.

Efficacy results

Pharmacokinetics of the target formulation

“This study indicated that AQST-109 was absorbed and rapidly converted to epinephrine with an observed median Tmax of 15 minutes and an observed geometric mean Cmax of 762 pg/mL for the target formulation.” (opens the source at this quote in a new tab)

Pharmacokinetic parameters across the four formulations

Parameter	Formulation 1	Formulation 2 (target)	Formulation 3	Formulation 4
Cmax (pg/mL)	“552”	“762”	“164”	“307”
AUC 0-t (hr*pg/mL)	“634”	“603”	“329”	“303”
Median Tmax (minutes)	“15”	“15”	“20”	“10”
Tmax range (minutes)	“15-25”	“10-35”	“20-50”	“5-50”

Pharmacodynamic comparability with autoinjectors

“Observed PD values were comparable to existing data for autoinjectors” (opens the source at this quote in a new tab)

Health-related quality of life and patient-reported outcomes

No evidence found.

Safety results

Treatment-emergent adverse events and absence of serious adverse events

“Safety data indicated that AQST-109 was generally well tolerated with no serious adverse events (SAE’s), significant medical events, or treatment-related severe adverse events reported within the trial. All treatment-emergent adverse events (TEAEs) deemed at least possibly related were mild to moderate in nature across cohorts.” (opens the source at this quote in a new tab)

Study limitations

Summary: study limitations

The study was a first-in-human single-ascending-dose evaluation in healthy volunteers with 6 to 8 dosings per formulation, so estimates of Cmax, Tmax, and area under the curve rest on very small numbers. It included no randomized injectable comparator arm; comparisons with EpiPen and Auvi-Q were drawn from previous and published studies rather than measured in the same participants. Two of the four formulations, including the formulation later taken forward, differed from the final commercial configuration, and no registry record or peer-reviewed publication of this individual study was located.