Drug Development.

Area of Science:

• Pharmacology
• Clinical Pharmacy
• Neuroscience

Background:

• ZUNVEYL (benzgalantamine) is an FDA-approved prodrug of galantamine for mild to moderate Alzheimer's dementia.
• It utilizes a delayed-release (DR) formulation to potentially mitigate gastrointestinal side effects associated with acetylcholinesterase inhibitors.
• The 505(b)(2) pathway approval leveraged existing FDA findings for galantamine hydrobromide products.

Purpose of the Study:

• To assess the dose proportionality of ZUNVEYL DR tablets across a dosage range of 5-15 mg.
• To evaluate the pharmacokinetic profile of ZUNVEYL DR tablets in healthy adults.

Main Methods:

• An open-label, randomized, three-arm, single-dose parallel study was conducted in 42 healthy adult subjects under fasting conditions.
• Subjects received single doses of ZUNVEYL DR tablets at 5 mg, 10 mg, or 15 mg.
• Pharmacokinetic parameters were analyzed to determine dose proportionality.

Main Results:

• The study analyzed plasma concentrations of galantamine derived from ZUNVEYL.
• A single gastrointestinal adverse event was reported at the 15 mg dose, suggesting a potentially lower incidence compared to equivalent doses of galantamine hydrobromide.
• Pharmacokinetic profiles indicated dose proportionality for ZUNVEYL across the studied range.

Conclusions:

• ZUNVEYL was well-tolerated with no serious adverse events observed.
• Statistical analysis confirmed dose proportionality for Cmax, AUC0-t, and AUC0-∞ from 5 mg to 15 mg.
• One 5 mg ZUNVEYL DR tablet is bioequivalent to one 4 mg galantamine hydrobromide immediate-release tablet.