Clinical Studies

ZUNVEYL Bioequivalence Studies

ZUNVEYL was approved by the FDA via the 505(b)(2) regulatory pathway, based on the previously established safety and efficacy for galantamine hydrobromide5

  • The efficacy of ZUNVEYL is based upon 3 studies demonstrating bioequivalence in healthy adults comparing galantamine immediate-release (IR) tablets and galantamine extended-release (ER) capsules with ZUNVEYL.1,5
    • 5 mg delayed-release tablet of ZUNVEYL was shown to be equivalent to one 4 mg tablet of galantamine hydrobromide IR
    • 5 mg delayed-release tablet of ZUNVEYL, administered twice daily, was shown to be equivalent to one 8 mg galantamine hydrobromide ER capsule administered once daily

A dose proportionality study was conducted that confirmed ZUNVEYL exhibits linear pharmacokinetics equivalent to galantamine.5

BID=twice daily; FDA=U.S. Food and Drug Administration; QD=once daily.

In the 4 studies above, the most common adverse events were increased alanine transaminases (n=4), diarrhea (n=2), and vomiting (n=1).6-9

Bioequivalence Results Support Pharmacokinetic Consistency

Results from the ZUNVEYL comparative bioequivalence studies

  • Reaches bioequivalence without initial peak.5
  • Narrow confidence intervals for consistent delivery (90% CI, 88.9-95.2).5
  • Bioequivalent at 48 hours.5

Improvement in Cognition, Behavior and Daily Living

Co-Primary Clinical Endpoints: ADAS-cog and CIBIC-plus

In a 21-week study of 978 patients with mild to moderate Alzheimer's disease, galantamine (the active ingredient of ZUNVEYL) showed sustained cognitive benefits through ADAS-cog scores.1,10

Patients treated with galantamine (the active ingredient of ZUNVEYL) showed significant gains or sustainment in CIBIC-plus scores, demonstrating its impact across cognition, behavior, and daily living activities.1

Improvement in Behavioral Symptoms

Secondary Clinical Endpoint: Neuropsychiatric Inventory

Among patients treated with galantamine (the active ingredient in ZUNVEYL), the results of the Neuropsychiatric Inventory (NPI) indicate a significant benefit of galantamine on behavioral symptoms compared to placebo.10

The NPI assesses the frequency and severity of symptoms in 10 behavioral domains (delusions, hallucinations, agitation/aggression, dysphoria, anxiety, euphoria, apathy, disinhibition, irritability/lability, and aberrant motor behavior). These assessments were performed at baseline, at weeks 4 and 13, and at 5 months.10

Pooled safety profile of oral galantamine in Phase 3 placebo-controlled trials

Adverse Reactions Reported by ≥1% of Galantamine-Treated Patients in 8 Placebo-Controlled, Double-Blind Clinical Trials1




INDICATION AND USAGE

ZUNVEYL is a cholinesterase inhibitor indicated for the treatment of mild to moderate dementia of the Alzheimer's type in adults.

IMPORTANT SAFETY INFORMATION

CONTRAINDICATIONS

ZUNVEYL is contraindicated in patients with known hypersensitivity to benzgalantamine, galantamine, or to any inactive ingredients in ZUNVEYL. Serious skin reactions have occurred.

WARNINGS AND PRECAUTIONS

Serious Skin Reactions: Serious skin reactions (Stevens-Johnson syndrome and acute generalized exanthematous pustulosis) have been reported in patients receiving galantamine (the active metabolite of ZUNVEYL tablets). If signs or symptoms suggest a serious skin reaction, use of this drug should not be resumed, and alternative therapy should be considered.

Anesthesia: See Drug Interactions Section

Cardiovascular Conditions: Cholinesterase inhibitors, including ZUNVEYL, have vagotonic effects on the sinoatrial and atrioventricular nodes, leading to bradycardia and AV block. Bradycardia and all types of heart block have been reported in patients taking cholinesterase inhibitors, both with and without known underlying cardiac conduction abnormalities. Therefore, all patients should be considered at risk for adverse effects on cardiac conduction.

Patients treated with galantamine up to 24 mg/day using the recommended dosing schedule showed a dose-related increase in risk of syncope.

Gastrointestinal Conditions: Cholinesterase inhibitors, including ZUNVEYL, may increase gastric acid secretion. Patients should be monitored closely for active or occult gastrointestinal bleeding, especially those with a history of ulcer disease or those receiving concurrent nonsteroidal anti-inflammatory drugs (NSAIDs). Clinical studies of galantamine have shown no increase, relative to placebo, in the incidence of either peptic ulcer disease or gastrointestinal bleeding.

Galantamine has been shown to produce nausea, vomiting, diarrhea, anorexia, and weight loss. Monitor the patient's weight during therapy with ZUNVEYL.

Genitourinary Conditions: Although this was not observed in clinical trials with galantamine, cholinesterase inhibitors, including ZUNVEYL, may cause bladder outflow obstruction.

Neurological Conditions: Cholinesterase inhibitors are believed to have some potential to cause generalized convulsions. Seizure activity may also be a manifestation of Alzheimer's disease. Patients with Alzheimer's disease should be monitored closely for seizures while taking ZUNVEYL.

Pulmonary Conditions: Cholinesterase inhibitors, including ZUNVEYL, should be prescribed with care to patients with a history of severe asthma or obstructive pulmonary disease. Monitor for respiratory adverse reactions.

ADVERSE REACTIONS

The most common adverse reactions with galantamine tablets (≥5%) were nausea, vomiting, diarrhea, dizziness, headache, and decreased appetite.

DRUG INTERACTIONS

Use with Anticholinergics: Galantamine has the potential to interfere with the activity of anticholinergic medications.

Use with Cholinomimetics and Other Cholinesterase Inhibitors: A synergistic effect is expected when cholinesterase inhibitors are given concurrently with succinylcholine, other cholinesterase inhibitors, similar neuromuscular blocking agents or cholinergic agonists such as bethanechol.

USE IN SPECIFIC POPULATIONS

Pregnancy: Based on animal data may cause fetal harm.

Hepatic Impairment: In patients with moderate hepatic impairment, a decrease in clearance of galantamine was observed; therefore, a dosage adjustment is recommended. Use of ZUNVEYL in patients with severe hepatic impairment is not recommended.

Renal Impairment: In patients with a creatinine clearance of 9 to 59 mL/min, an increase in exposure of galantamine was observed; therefore, a dosage adjustment is recommended. Use of ZUNVEYL in patients with creatinine clearance less than 9 mL/min is not recommended.

For more information about ZUNVEYL, please see the full Prescribing Information here.