In a randomized dose-finding study aimed at determining the optimum dose of linaprazan glurate, a total of 248 patients with either moderate (Los Angeles [LA] grade A or B) or severe (LA grade C or D) esophagitis were randomly assigned to linaprazan glurate (25 mg, 50 mg, 75 mg, or 100 mg twice a day) or lansoprazole (30 mg once a day) for a 4-week double-blind treatment period. After the initial 4 weeks, an endoscopy was performed to assess healing. All patients then entered a 4-week open-label treatment period with lansoprazole 30 mg daily, ensuring that each patient received a full 8-week course of therapy.
The primary outcome was the healing rate of erosive esophagitis. The results indicated a 4-week healing rate of 73.7% (linaprazan glurate 25 mg) up to a maximum of 78.0% (linaprazan glurate 75 mg), which surpassed the healing rates seen with lansoprazole (60.6%). According to the per-protocol analysis, the healing rates at 4 weeks peaked at 90.5% for the 75-mg dose compared with 59.1% for lansoprazole.
In the subgroup of patients with severe esophagitis, a healing rate gradient from 58.3% (linaprazan glurate 25 mg) to 85.0% (linaprazan glurate 75 mg) was seen, dropping to 50.0% for the 100-mg dose. All these percentages were higher than the healing rate of 33.3% with lansoprazole.
Secondary objectives included patient-reported outcomes, particularly the number of heartburn-free days. Across the various doses, the number of heartburn-free days was comparable, although slightly higher for the 100-mg dose. Overall, the safety profile was comparable to that of lansoprazole, and no deaths or adverse events of special interest were reported.
Healing, symptom control, and safety data support dose selection and further development of linaprazan glurate in phase 3 studies. The drug showed high rates of erosive esophagitis healing and low symptom burden. Linaprazan glurate was well tolerated with no dose-related increase in adverse events.
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