New study supports switching between Daybue liquid and powder forms
Results show comparable drug exposure for Rett treatment formulations
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Daybue Stix (trofinetide), a powder formulation of Daybue (trofinetide) approved to treat adults and children ages 2 and older with Rett syndrome, may be used interchangeably with the original strawberry-flavored, ready-to-use liquid formulation.
That’s according to results from a Phase 1 study showing that a single 12,000 mg dose of trofinetide, administered either as 60 mL of liquid Daybue or as Daybue Stix powder mixed with 60 mL of water, delivered comparable drug exposure in the body. This means the two formulations met established criteria for bioequivalence and were considered interchangeable in the study.
Powder formulation matches liquid version in study tests
Bioequivalence criteria were also met when the same dose was prepared as Daybue Stix mixed in a reduced volume of 25 mL of water. This indicates that reducing the preparation volume did not meaningfully affect bioavailability — the extent or rate at which the drug is absorbed into the bloodstream.
Both formulations were generally well tolerated, and no serious or unexpected adverse events were reported.
“The bioequivalence demonstrated in this study supports the clinical interchangeability of [Daybue Stix] and [Daybue] and shows that [Daybue Stix] can be constituted using adjustable volumes of water without affecting bioavailability,” the researchers wrote.
The study, “A Phase 1, Randomized, Open-Label Study to Assess the Bioequivalence of Trofinetide as a Ready-to-Use Oral Solution and Constituted Powder for Oral Solution in Healthy Adults,” was published in Advances in Therapy. The study was funded by Acadia Pharmaceuticals, the company that markets Daybue and Daybue Stix.
Daybue, given twice daily as a liquid, was approved in the U.S. in 2023 as the first treatment for adults and children at least 2 years old with Rett syndrome. It’s thought to reduce inflammation and support connections between nerve cells that are affected in Rett, which are linked to symptoms. Doses are tailored to patients’ body weight to ensure consistent drug exposure, ranging from 5,000 to 12,000 mg per dose.
People with Rett syndrome, however, may experience difficulty swallowing. These challenges can make taking oral medications difficult, particularly when larger volumes of liquid are required. As a result, a powder formulation that can be mixed with varying amounts of liquid has been highly desired by patients and caregivers.
Daybue Stix, which won FDA approval last December, was developed to address this need. Unlike the original liquid, the single-dose powder comes in packets that need to be mixed with water or other beverages — including juice, tea, lemonade, limeade, or liquid hydration drinks — before administration. The volume can be adjusted based on patient preference, offering greater flexibility in taste and the amount of liquid used for dosing.
Study confirms changes in formulation do not affect drug behavior
Because the powder formulation removes certain inactive ingredients — including preservatives and dyes — and allows for different preparation volumes, regulators required evidence that these differences would not affect how the drug is absorbed and processed in the body.
To address this, researchers at Acadia conducted a Phase 1 bioequivalence study involving 38 healthy adults at a single center in the U.S. Participants had a mean age of 34.6, and most were men (84%). Overall, 52.6% were White, 42.1% were Black or African American, 2.6% were Asian, and 2.6% identified as more than one race.
Each participant received a single 12,000 mg dose of trofinetide in three forms: 60 mL of liquid Daybue, Daybue Stix mixed in 60 mL of water, and Daybue Stix mixed in a reduced volume of 25 mL. Participants received the three treatments in one of two sequences, allowing each person to serve as their own comparison.
The study included three dosing periods separated by washout intervals to allow the drug to clear before the next dose was given. Blood samples were collected for 48 hours after each dose to measure drug levels in the blood. A total of 37 participants completed the study.
The main goal of the study was to determine whether Daybue Stix mixed in 60 mL of water was bioequivalent to the 60 mL liquid Daybue. The researchers also evaluated whether preparing the powder in 25 mL affected drug exposure. Safety and tolerability were also assessed.
Drug absorption and exposure similar across all formulations
After dosing, trofinetide was rapidly absorbed, with peak blood levels reached in about two hours. Measures of how much and how fast the drug entered the bloodstream, as well as how long it remained in the body, were similar across all three dosing conditions.
Regulatory criteria for bioequivalence were met when comparing Daybue Stix mixed in 60 mL of water with the liquid Daybue (60 mL), as well as when comparing the Daybue Stix mixed in 25 mL of water with both Daybue (60 mL) and Daybue Stix mixed in 60 mL of water.
The treatment was generally well tolerated. Rates of side effects were slightly higher with the 25 mL powder preparation (23.7%) compared with the 60 mL powder (15.8%) and liquid formulation (13.2%), though most were mild. The most commonly reported side effect was diarrhea, followed by nausea and headache. No serious adverse events were reported, although one severe headache occurred that was not considered related to the treatment and resolved.
“This bioequivalence study demonstrates that the new [Daybue Stix] formulation can be used interchangeably with the current commercially available [Daybue] formulation,” the researchers concluded. They added that the ability to prepare the powder in a significantly reduced volume without affecting bioavailability “allows a more tailored approach to suit individual preferences.”
