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ZUNVEYL (benzgalantamine, galantamine benzoate gluconate), is a pharmacologically inactive prodrug of galantamine. ZUNVEYL was FDA approved in 2024 for BID dosing for the treatment of mild to moderate Alzheimer's dementia, via the 505(b)(2) regulatory pathway, relying on FDA's previous finding of safety and efficacy for the listed drugs (LDs) Razadyne® (galantamine hydrobromide tablets), and Razadyne® ER (galantamine hydrobromide extended-release capsules). When dosed as a delayed-release (DR) tablet, ZUNVEZYL bypasses the stomach and, is absorbed in the small intestine potentially reducing the gastrointestinal side effects common for acetylcholinesterase inhibitors. Consequently, ZUNVEYL may offer advantages over the other acetylcholinesterase inhibitors by reducing gastrointestinal adverse effects which limit compliance. Here we describe the outcomes of two studies designed to assess the relative bioavailability of ZUNVEYL DR tablets to galantamine hydrobromide immediate release (IR) tablets under fed and fasting conditions. The studies were open-label, balanced, randomized, single-dose, two-treatment, two-period, two-way crossover designs to evaluate the relative bioavailability of ZUNVEYL DR 5 mg tablet compared to galantamine hydrobromide 4 mg IR tablet, in healthy adult subjects under fed (Study ALPHA-1062-01; N=34) and fasting (Study ALPHA-1062-02; N=34) conditions. Study protocols underwent ethics review and were conducted to GCP standards. Table 1 documents plasma pharmacokinetic parameters calculated from the analysis of galantamine (from ZUNVEYL) and galantamine hydrobromide IR. ZUNVEYL (prodrug) was inconsistently detected in plasma and represented approximately 1% of total circulating drug. The low percentage of circulating prodrug provides a greater margin of safety. ZUNVEYL was well-tolerated with no serious adverse events noted. Bioequivalence assessment demonstrated that ZUNVEYL was bioequivalent to galantamine hydrobromide IR for AUC0-t and AUC0-∞, under fed and fasting conditions, and for Cmax under fed conditions. These results combined with those of a steady state study [abstract # 107147], established a scientific bridge to the LDs and the approval of ZUNVEYL, relying on FDA's previous finding of safety and efficacy of the LDs.

ZUNVEYL (benzgalantamine, galantamine benzoate gluconate), is a pharmacologically inactive prodrug of galantamine. ZUNVEYL was FDA approved in 2024 for BID dosing for the treatment of mild to moderate Alzheimer's dementia, via the 505(b)(2) regulatory pathway, relying on FDA's previous finding of safety and efficacy for the listed drugs (LDs) Razadyne® (galantamine hydrobromide tablets), and Razadyne® ER (galantamine hydrobromide extended-release capsules). When dosed as a delayed-release (DR) tablet, ZUNVEYL bypasses the stomach and, is absorbed in the small intestine potentially reducing the gastrointestinal side effects common for acetylcholinesterase inhibitors. Consequently, ZUNVEYL may offer advantages over the other acetylcholinesterase inhibitors by reducing gastrointestinal adverse effects which limit patient compliance. Here we report the outcome of a study designed to assess the dose proportionality of ZUNVEYL DR tablets over a dosage range of 5-15 milligrams. This was an open-label, balanced, randomized, three-arm, three-treatment, single-dose parallel study to evaluate the pharmacokinetics and dose proportionality of ZUNVEYL DR tablets of 5, 10 and 15 mg strength in healthy adult subjects (N=42), under fasting conditions. The study protocol underwent ethics review and was conducted under GCP conditions. The dose proportionality of ZUNVEYL based on the plasma analysis of galantamine derived from ZUNVEYL (Table 1), and the pharmacokinetic profiles of all three doses (Figure 1) are presented below. Fifteen milligrams of ZUNVEYL administered to drug naïve subjects, provoked one gastrointestinal adverse event (1/14), a lower incidence than that expected with an equivalent dose of Galantamine hydrobromide. ZUNVEYL was well-tolerated, no serious adverse events were observed. Statistical analysis confirmed the dose proportionality for Cmax, AUC0-t, & AUC0-∞ over the entire 5 mg to 15 mg dose range for ZUNVEYL. The studies demonstrating bioequivalence, under fed and fasted (abstract #107030), and steady state (abstract #107147) conditions, and dose proportionality studies, lead to the conclusion that one ZUNVEYL 5 mg DR tablet is equivalent to one galantamine hydrobromide 4 mg immediate release tablet.

ZUNVEYL (benzgalantamine, galantamine benzoate gluconate), is a pharmacologically inactive prodrug of galantamine. ZUNVEYL was FDA approved in 2024 for BID dosing for the treatment of mild to moderate Alzheimer's dementia, via the 505(b)(2) regulatory pathway, relying on FDA's previous finding of safety and efficacy for the listed drugs (LDs) Razadyne® (galantamine hydrobromide tablets), and Razadyne® ER (galantamine hydrobromide extended-release capsules). When dosed as a delayed-release (DR) tablet, ZUNVEZYL bypasses the stomach and, is absorbed in the small intestine potentially reducing the gastrointestinal side effects common for acetylcholinesterase inhibitors. Consequently, ZUNVEYL may offer advantages over the other acetylcholinesterase inhibitors by reducing gastrointestinal adverse effects which limit patient compliance. Here we report the outcome of a study designed to assess the relative bioavailability of ZUNVEYL DR tablets to galantamine hydrobromide extended-release (ER) capsules, under steady state conditions. This was an open-label, balanced, randomized, multiple dose, two-treatment, two-arm, two-period, comparative steady state study of ZUNVEYL DR tablets, 5 mg (BID, for 7 days) compared to galantamine hydrobromide ER, 8 mg (QD, for 7 days), in healthy adult subjects (N=40). The study protocol underwent ethics review and was conducted under GCP conditions. Table 1 and Figure 1 describe the pharmacokinetic parameters calculated from the plasma analysis of galantamine derived from ZUNVEYL and galantamine hydrobromide ER. ZUNVEYL represented less than 1% of total circulating drug, which provided further evidence of safety. ZUNVEYL was well-tolerated with no serious adverse event noted. The steady state study established a scientific bridge to the LD, galantamine hydrobromide ER capsules. Although the extent of absorption measured by the AUC[0-24]ss was comparable between ZUNVEYL and the LD, the Cmaxss was slightly higher than the LD. The safety of the higher Cmax of galantamine derived from ZUNVEYL compared to galantamine hydrobromide ER capsules is supported by the lower Cmax of galantamine derived from ZUNVEYL compared to the galantamine hydrobromide immediate release tablets [see abstract # 107030].

Background ZUNVEYL (benzgalantamine, galantamine benzoate gluconate), is a pharmacologically inactive prodrug of galantamine. ZUNVEYL was FDA approved in 2024 for BID dosing for the treatment of mild to moderate Alzheimer’s dementia, via the 505(b)(2) regulatory pathway, relying on FDA’s previous finding of safety and efficacy for the listed drugs (LDs) Razadyne® (galantamine hydrobromide tablets), and Razadyne® ER (galantamine hydrobromide extended‐release capsules). When dosed as a delayed‐release (DR) tablet, ZUNVEZYL bypasses the stomach and, is absorbed in the small intestine potentially reducing the gastrointestinal side effects common for acetylcholinesterase inhibitors. Consequently, ZUNVEYL may offer advantages over the other acetylcholinesterase inhibitors by reducing gastrointestinal adverse effects which limit patient compliance. Here we report the outcome of a study designed to assess the relative bioavailability of ZUNVEYL DR tablets to galantamine hydrobromide extended‐release (ER) capsules, under steady state conditions. Methods This was an open‐label, balanced, randomized, multiple dose, two‐treatment, two‐arm, two‐period, comparative steady state study of ZUNVEYL DR tablets, 5 mg (BID, for 7 days) compared to galantamine hydrobromide ER, 8 mg (QD, for 7 days), in healthy adult subjects (N=40). The study protocol underwent ethics review and was conducted under GCP conditions. Results Table 1 and Figure 1 describe the pharmacokinetic parameters calculated from the plasma analysis of galantamine derived from ZUNVEYL and galantamine hydrobromide ER. ZUNVEYL represented less than 1% of total circulating drug, which provided further evidence of safety. Conclusions ZUNVEYL was well‐tolerated with no serious adverse event noted. The steady state study established a scientific bridge to the LD, galantamine hydrobromide ER capsules. Although the extent of absorption measured by the AUC[0‐24]ss was comparable between ZUNVEYL and the LD, the Cmaxss was slightly higher than the LD. The safety of the higher Cmax of galantamine derived from ZUNVEYL compared to galantamine hydrobromide ER capsules is supported by the lower Cmax of galantamine derived from ZUNVEYL compared to the galantamine hydrobromide immediate release tablets [see # 107030].

Background ZUNVEYL (benzgalantamine, galantamine benzoate gluconate), is a pharmacologically inactive prodrug of galantamine. ZUNVEYL was FDA approved in 2024 for BID dosing for the treatment of mild to moderate Alzheimer’s dementia, via the 505(b)(2) regulatory pathway, relying on FDA’s previous finding of safety and efficacy for the listed drugs (LDs) Razadyne® (galantamine hydrobromide tablets), and Razadyne® ER (galantamine hydrobromide extended‐release capsules). When dosed as a delayed‐release (DR) tablet, ZUNVEZYL bypasses the stomach and, is absorbed in the small intestine potentially reducing the gastrointestinal side effects common for acetylcholinesterase inhibitors. Consequently, ZUNVEYL may offer advantages over the other acetylcholinesterase inhibitors by reducing gastrointestinal adverse effects which limit compliance. Here we describe the outcomes of two studies designed to assess the relative bioavailability of ZUNVEYL DR tablets to galantamine hydrobromide immediate release (IR) tablets under fed and fasting conditions. Methods The studies were open‐label, balanced, randomized, single‐dose, two‐treatment, two‐period, two‐way crossover designs to evaluate the relative bioavailability of ZUNVEYL DR 5 mg tablet compared to galantamine hydrobromide 4 mg IR tablet, in healthy adult subjects under fed (Study ALPHA‐1062‐01; N=34) and fasting (Study ALPHA‐1062‐02; N=34) conditions. Study protocols underwent ethics review and were conducted to GCP standards. Results Table 1 documents plasma pharmacokinetic parameters calculated from the analysis of galantamine (from ZUNVEYL) and galantamine hydrobromide IR. ZUNVEYL (prodrug) was inconsistently detected in plasma and represented approximately 1% of total circulating drug. The low percentage of circulating prodrug provides a greater margin of safety. Conclusions ZUNVEYL was well‐tolerated with no serious adverse events noted. Bioequivalence assessment demonstrated that ZUNVEYL was bioequivalent to galantamine hydrobromide IR for AUC0‐t and AUC0‐∞, under fed and fasting conditions, and for Cmax under fed conditions. These results combined with those of a steady state study [ # 107147], established a scientific bridge to the LDs and the approval of ZUNVEYL, relying on FDA’s previous finding of safety and efficacy of the LDs.

Background ZUNVEYL (benzgalantamine, galantamine benzoate gluconate), is a pharmacologically inactive prodrug of galantamine. ZUNVEYL was FDA approved in 2024 for BID dosing for the treatment of mild to moderate Alzheimer’s dementia, via the 505(b)(2) regulatory pathway, relying on FDA’s previous finding of safety and efficacy for the listed drugs (LDs) Razadyne® (galantamine hydrobromide tablets), and Razadyne® ER (galantamine hydrobromide extended‐release capsules). When dosed as a delayed‐release (DR) tablet, ZUNVEYL bypasses the stomach and, is absorbed in the small intestine potentially reducing the gastrointestinal side effects common for acetylcholinesterase inhibitors. Consequently, ZUNVEYL may offer advantages over the other acetylcholinesterase inhibitors by reducing gastrointestinal adverse effects which limit patient compliance. Here we report the outcome of a study designed to assess the dose proportionality of ZUNVEYL DR tablets over a dosage range of 5‐15 milligrams. Methods This was an open‐label, balanced, randomized, three‐arm, three‐treatment, single‐dose parallel study to evaluate the pharmacokinetics and dose proportionality of ZUNVEYL DR tablets of 5, 10 and 15 mg strength in healthy adult subjects (N=42), under fasting conditions. The study protocol underwent ethics review and was conducted under GCP conditions. Results The dose proportionality of ZUNVEYL based on the plasma analysis of galantamine derived from ZUNVEYL (Table 1), and the pharmacokinetic profiles of all three doses (Figure 1) are presented below. Fifteen milligrams of ZUNVEYL administered to drug naïve subjects, provoked one gastrointestinal adverse event (1/14), a lower incidence than that expected with an equivalent dose of Galantamine hydrobromide. Conclusions ZUNVEYL was well‐tolerated, no serious adverse events were observed. Statistical analysis confirmed the dose proportionality for Cmax, AUC0‐t, & AUC0‐∞ over the entire 5 mg to 15 mg dose range for ZUNVEYL. The studies demonstrating bioequivalence, under fed and fasted ( #107030), and steady state ( #107147) conditions, and dose proportionality studies, lead to the conclusion that one ZUNVEYL 5 mg DR tablet is equivalent to one galantamine hydrobromide 4 mg immediate release tablet.

Transfusional iron overload is a potentially fatal complication of the treatment of thalassaemia. We aimed to investigate short-term efficacy, pharmacokinetic/pharma-codynamic (PK/PD) relations, and safety of ICL670, a novel, tridentate, orally active iron chelator. We enrolled 24 patients and divided them into three cohorts consisting of a minimum of seven individuals. Patients were admitted to a metabolic unit and consumed a diet with a defined content of iron. Two patients in each cohort were randomly allocated placebo. Five or more patients received one daily dose of ICL670 at 10, 20, or 40 mg kg−1 day−1, from day 1 to 12. Net iron excretion (NIE) was measured between days 1 and 12. Primary objectives included assessment of safety and tolerability (measured by adverse events and clinical laboratory monitoring), pharmacokinetics (measured as drug and drug-iron complex), and cumulative net iron excretion (measured by faecal and urine output minus food input). Analysis was for efficacy. ICL670 was absorbed promptly and was detectable in the blood for 24 h. Exposure (area under the curve of plasma concentration) to ICL670 at pharmacokinetic steady state was proportional to dose. All three doses resulted in positive NIE. The NIE achieved at 20 mg kg−1day−1 would prevent net iron accumulation in most patients transfused with 12–15 mL packed red-blood-cells kg−1 month−1, equivalent to 0·3–0·5 mg iron kg−1 day−1. A linear relation (PK/PD) was recorded between exposure to ICL670 and total iron excretion, by contrast with placebo (r2=0·54, p<0·0001). Skin rashes were noted in four patients treated at 20 and 40 mg kg−1 day−1, and one patient also developed grade 2 transaminitis. ICL670 given once daily at 20 mg/kg seems to be an effective orally active iron chelator and is reasonably well tolerated. Long-term studies are now necessary to establish the practical contribution of this drug.