The Experts below are selected from a list of 1416 Experts worldwide ranked by ideXlab platform
James E. Polli - One of the best experts on this subject based on the ideXlab platform.
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generic lamotrigine versus brand name Lamictal bioequivalence in patients with epilepsy a field test of the fda bioequivalence standard
Epilepsia, 2015Co-Authors: Tricia Ting, Wenlei Jiang, Maureen A. Kane, Jessica Wong, Jace W. Jones, Robert Lionberger, Allan Krumholz, Robert Temple, James E. PolliAbstract:SummaryObjective To test the current U.S. Food and Drug Administration (FDA) bioequivalence standard in a comparison of generic and brand-name drug pharmacokinetic (PK) performance in “generic-brittle” patients with epilepsy under clinical use conditions. Methods This randomized, double-blind, multiple-dose, steady-state, fully replicated bioequivalence study compared generic lamotrigine to brand-name Lamictal in “generic-brittle” patients with epilepsy (n = 34) who were already taking lamotrigine. Patients were repeatedly switched between masked Lamictal and generic lamotrigine. Intensive PK blood sampling at the end of each 2-week treatment period yielded two 12-h PK profiles for brand-name and generic forms for each patient. Steady-state area under the curve (AUC), peak plasma concentration (Cmax), and minimum plasma concentration (Cmin) data were subjected to conventional average bioequivalence (ABE) analysis, reference-scaled ABE analysis, and within-subject variability (WSV) comparisons. In addition, generic-versus-brand comparisons in individual patients were performed. Secondary clinical outcomes included seizure frequency and adverse events. Results Generic demonstrated bioequivalence to brand. The 90% confidence intervals of the mean for steady-state AUC, Cmax, and Cmin for generic-versus-brand were 97.2–101.6%, 98.8–104.5%, and 93.4–101.0%, respectively. The WSV of generic and brand were also similar. Individual patient PK ratios for generic-versus-brand were similar but not identical, in part because brand-versus-brand profiles were not identical, even though subjects were rechallenged with the same product. Few subjects had seizure exacerbations or tolerability issues with product switching. One subject, however, reported 267 focal motor seizures, primarily on generic, although his brand and generic PK profiles were practically identical. Significance Some neurologists question whether bioequivalence in healthy volunteers ensures therapeutic equivalence of brand and generic antiepileptic drugs in patients with epilepsy, who may be at increased risk for problems with brand-to-generic switching. Bioequivalence results in “generic-brittle” patients with epilepsy under clinical conditions support the soundness of the FDA bioequivalence standards. Adverse events on generic were not related to the small, allowable PK differences between generic and brand.
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Generic lamotrigine versus brand‐name Lamictal bioequivalence in patients with epilepsy: A field test of the FDA bioequivalence standard
Epilepsia, 2015Co-Authors: Tricia Ting, Wenlei Jiang, Maureen A. Kane, Jessica Wong, Jace W. Jones, Robert Lionberger, Allan Krumholz, Robert Temple, James E. PolliAbstract:SummaryObjective To test the current U.S. Food and Drug Administration (FDA) bioequivalence standard in a comparison of generic and brand-name drug pharmacokinetic (PK) performance in “generic-brittle” patients with epilepsy under clinical use conditions. Methods This randomized, double-blind, multiple-dose, steady-state, fully replicated bioequivalence study compared generic lamotrigine to brand-name Lamictal in “generic-brittle” patients with epilepsy (n = 34) who were already taking lamotrigine. Patients were repeatedly switched between masked Lamictal and generic lamotrigine. Intensive PK blood sampling at the end of each 2-week treatment period yielded two 12-h PK profiles for brand-name and generic forms for each patient. Steady-state area under the curve (AUC), peak plasma concentration (Cmax), and minimum plasma concentration (Cmin) data were subjected to conventional average bioequivalence (ABE) analysis, reference-scaled ABE analysis, and within-subject variability (WSV) comparisons. In addition, generic-versus-brand comparisons in individual patients were performed. Secondary clinical outcomes included seizure frequency and adverse events. Results Generic demonstrated bioequivalence to brand. The 90% confidence intervals of the mean for steady-state AUC, Cmax, and Cmin for generic-versus-brand were 97.2–101.6%, 98.8–104.5%, and 93.4–101.0%, respectively. The WSV of generic and brand were also similar. Individual patient PK ratios for generic-versus-brand were similar but not identical, in part because brand-versus-brand profiles were not identical, even though subjects were rechallenged with the same product. Few subjects had seizure exacerbations or tolerability issues with product switching. One subject, however, reported 267 focal motor seizures, primarily on generic, although his brand and generic PK profiles were practically identical. Significance Some neurologists question whether bioequivalence in healthy volunteers ensures therapeutic equivalence of brand and generic antiepileptic drugs in patients with epilepsy, who may be at increased risk for problems with brand-to-generic switching. Bioequivalence results in “generic-brittle” patients with epilepsy under clinical conditions support the soundness of the FDA bioequivalence standards. Adverse events on generic were not related to the small, allowable PK differences between generic and brand.
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Biopharmaceutic Risk Assessment of Brand and Generic Lamotrigine Tablets.
Molecular Pharmaceutics, 2015Co-Authors: Soundarya Vaithianathan, Siddarth Raman, Wenlei Jiang, Tricia Ting, Maureen A. Kane, James E. PolliAbstract:The therapeutic equivalence of generic and brand name antiepileptic drugs has been questioned by neurologists and the epilepsy community. A potential contributor to such concerns is pharmaceutical quality. The objective was to assess the biopharmaceutic risk of brand name Lamictal 100 mg tablets and generic lamotrigine 100 mg tablets from several manufacturers. Lamotrigine was characterized in terms of the Biopharmaceutics Classification System (BCS), including aqueous solubility and Caco-2 permeability. A panel of pharmaceutical quality tests was also performed on three batches of Lamictal, three batches of Teva generic, and one batch of each of four other generics: appearance, identity, assay, impurity, uniformity of dosage units, disintegration, dissolution, friability, and loss on drying. These market surveillance results indicate that all brand name and generic lamotrigine 100 mg tablets passed all tests and showed acceptable pharmaceutical quality and low biopharmaceutic risk. Lamotrigine was classi...
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Generic versus brand-name lamotrigine bioequivalence in generic-sensitive epilepsy patients: a field test of the public bioequivalence standard (S31.003)
Neurology, 2015Co-Authors: Tricia Ting, Wenlei Jiang, Maureen A. Kane, Jessica Wong, Jace W. Jones, Allan Krumholz, James E. PolliAbstract:OBJECTIVE: The primary outcome of the BioEquivalence in Epilepsy Patients (BEEP) study (1, 2) was the average bioequivalence (ABE) assessment of generic versus brand lamotrigine in “generic brittle” epilepsy patients under clinical use conditions. Secondary outcomes were seizure frequency and adverse events with generic and brand product switching BACKGROUND: The bioequivalence (BE) testing standard for generic drug approval typically relies on healthy volunteers and has been questioned for assuring therapeutic equivalence in epilepsy patients who may be at increased risk for problems with antiepileptic drug (AED) brand-to-generic switching. DESIGN/METHODS: This randomized, double-blind, multiple-dose, steady-state, replicate-design BE study compared the most common generic lamotrigine to brand Lamictal in “generic-brittle” epilepsy patients, who are considered potentially sensitive to poor outcomes with generic switching. The most common generic immediate-release lamotrigine (manufactured by Teva) was compared to Lamictal, employing 100mg tablets at the patient’s usual dose (e.g. 100mg BID, 200mg BID, or 300mg BID). RESULTS: Generic was BE on average to the brand (n=34 completed per-protocol patients). Cmax 90[percnt] CI was 98.8-104.5[percnt]. AUC 90[percnt] CI was 97.2-101.6[percnt]. All patient pharmacokinetic (PK) ratios for generic vs brand were within +/-25[percnt], supporting the ABE public standard. No patient characteristic explained the small differences observed across individuals, and small differences were not associated with worsened seizures or side effects for the vast majority of generic-brittle patients. Even when subjects were re-challenged with identical product, individual patient PK ratios for each generic and brand were not identical to self. CONCLUSIONS: Results support the soundness of the ABE public standard, including its use of healthy volunteers rather than patients. No patient sub-population reacted poorly to generic or brand, much less one product but not the other. Generic and brand product passed ABE testing standards with observed efficacy and tolerability even in at-risk generic-brittle epilepsy patients under clinical use conditions. Disclosure: Dr. Ting has nothing to disclose. Dr. Jiang has nothing to disclose. Dr. Wong has nothing to disclose. Dr. Jones has nothing to disclose. Dr. Krumholz has nothing to disclose. Dr. Kane has nothing to disclose. Dr. Polli has nothing to disclose.
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Quantification of lamotrigine in patient plasma using a fast liquid chromatography-tandem mass spectrometry method with backflush technology.
Therapeutic Drug Monitoring, 2015Co-Authors: Jessica Wong, Wenlei Jiang, James E. Polli, Jace W. Jones, Maureen A. KaneAbstract:Background:Recent concerns have been raised by neurologists and patients with epilepsy regarding the bioequivalence of generic lamotrigine to the brand Lamictal. Bioequivalence studies require the quantification of lamotrigine in human plasma, including in the presence of other drugs, for studies th
Maureen A. Kane - One of the best experts on this subject based on the ideXlab platform.
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generic lamotrigine versus brand name Lamictal bioequivalence in patients with epilepsy a field test of the fda bioequivalence standard
Epilepsia, 2015Co-Authors: Tricia Ting, Wenlei Jiang, Maureen A. Kane, Jessica Wong, Jace W. Jones, Robert Lionberger, Allan Krumholz, Robert Temple, James E. PolliAbstract:SummaryObjective To test the current U.S. Food and Drug Administration (FDA) bioequivalence standard in a comparison of generic and brand-name drug pharmacokinetic (PK) performance in “generic-brittle” patients with epilepsy under clinical use conditions. Methods This randomized, double-blind, multiple-dose, steady-state, fully replicated bioequivalence study compared generic lamotrigine to brand-name Lamictal in “generic-brittle” patients with epilepsy (n = 34) who were already taking lamotrigine. Patients were repeatedly switched between masked Lamictal and generic lamotrigine. Intensive PK blood sampling at the end of each 2-week treatment period yielded two 12-h PK profiles for brand-name and generic forms for each patient. Steady-state area under the curve (AUC), peak plasma concentration (Cmax), and minimum plasma concentration (Cmin) data were subjected to conventional average bioequivalence (ABE) analysis, reference-scaled ABE analysis, and within-subject variability (WSV) comparisons. In addition, generic-versus-brand comparisons in individual patients were performed. Secondary clinical outcomes included seizure frequency and adverse events. Results Generic demonstrated bioequivalence to brand. The 90% confidence intervals of the mean for steady-state AUC, Cmax, and Cmin for generic-versus-brand were 97.2–101.6%, 98.8–104.5%, and 93.4–101.0%, respectively. The WSV of generic and brand were also similar. Individual patient PK ratios for generic-versus-brand were similar but not identical, in part because brand-versus-brand profiles were not identical, even though subjects were rechallenged with the same product. Few subjects had seizure exacerbations or tolerability issues with product switching. One subject, however, reported 267 focal motor seizures, primarily on generic, although his brand and generic PK profiles were practically identical. Significance Some neurologists question whether bioequivalence in healthy volunteers ensures therapeutic equivalence of brand and generic antiepileptic drugs in patients with epilepsy, who may be at increased risk for problems with brand-to-generic switching. Bioequivalence results in “generic-brittle” patients with epilepsy under clinical conditions support the soundness of the FDA bioequivalence standards. Adverse events on generic were not related to the small, allowable PK differences between generic and brand.
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Generic lamotrigine versus brand‐name Lamictal bioequivalence in patients with epilepsy: A field test of the FDA bioequivalence standard
Epilepsia, 2015Co-Authors: Tricia Ting, Wenlei Jiang, Maureen A. Kane, Jessica Wong, Jace W. Jones, Robert Lionberger, Allan Krumholz, Robert Temple, James E. PolliAbstract:SummaryObjective To test the current U.S. Food and Drug Administration (FDA) bioequivalence standard in a comparison of generic and brand-name drug pharmacokinetic (PK) performance in “generic-brittle” patients with epilepsy under clinical use conditions. Methods This randomized, double-blind, multiple-dose, steady-state, fully replicated bioequivalence study compared generic lamotrigine to brand-name Lamictal in “generic-brittle” patients with epilepsy (n = 34) who were already taking lamotrigine. Patients were repeatedly switched between masked Lamictal and generic lamotrigine. Intensive PK blood sampling at the end of each 2-week treatment period yielded two 12-h PK profiles for brand-name and generic forms for each patient. Steady-state area under the curve (AUC), peak plasma concentration (Cmax), and minimum plasma concentration (Cmin) data were subjected to conventional average bioequivalence (ABE) analysis, reference-scaled ABE analysis, and within-subject variability (WSV) comparisons. In addition, generic-versus-brand comparisons in individual patients were performed. Secondary clinical outcomes included seizure frequency and adverse events. Results Generic demonstrated bioequivalence to brand. The 90% confidence intervals of the mean for steady-state AUC, Cmax, and Cmin for generic-versus-brand were 97.2–101.6%, 98.8–104.5%, and 93.4–101.0%, respectively. The WSV of generic and brand were also similar. Individual patient PK ratios for generic-versus-brand were similar but not identical, in part because brand-versus-brand profiles were not identical, even though subjects were rechallenged with the same product. Few subjects had seizure exacerbations or tolerability issues with product switching. One subject, however, reported 267 focal motor seizures, primarily on generic, although his brand and generic PK profiles were practically identical. Significance Some neurologists question whether bioequivalence in healthy volunteers ensures therapeutic equivalence of brand and generic antiepileptic drugs in patients with epilepsy, who may be at increased risk for problems with brand-to-generic switching. Bioequivalence results in “generic-brittle” patients with epilepsy under clinical conditions support the soundness of the FDA bioequivalence standards. Adverse events on generic were not related to the small, allowable PK differences between generic and brand.
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Biopharmaceutic Risk Assessment of Brand and Generic Lamotrigine Tablets.
Molecular Pharmaceutics, 2015Co-Authors: Soundarya Vaithianathan, Siddarth Raman, Wenlei Jiang, Tricia Ting, Maureen A. Kane, James E. PolliAbstract:The therapeutic equivalence of generic and brand name antiepileptic drugs has been questioned by neurologists and the epilepsy community. A potential contributor to such concerns is pharmaceutical quality. The objective was to assess the biopharmaceutic risk of brand name Lamictal 100 mg tablets and generic lamotrigine 100 mg tablets from several manufacturers. Lamotrigine was characterized in terms of the Biopharmaceutics Classification System (BCS), including aqueous solubility and Caco-2 permeability. A panel of pharmaceutical quality tests was also performed on three batches of Lamictal, three batches of Teva generic, and one batch of each of four other generics: appearance, identity, assay, impurity, uniformity of dosage units, disintegration, dissolution, friability, and loss on drying. These market surveillance results indicate that all brand name and generic lamotrigine 100 mg tablets passed all tests and showed acceptable pharmaceutical quality and low biopharmaceutic risk. Lamotrigine was classi...
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Generic versus brand-name lamotrigine bioequivalence in generic-sensitive epilepsy patients: a field test of the public bioequivalence standard (S31.003)
Neurology, 2015Co-Authors: Tricia Ting, Wenlei Jiang, Maureen A. Kane, Jessica Wong, Jace W. Jones, Allan Krumholz, James E. PolliAbstract:OBJECTIVE: The primary outcome of the BioEquivalence in Epilepsy Patients (BEEP) study (1, 2) was the average bioequivalence (ABE) assessment of generic versus brand lamotrigine in “generic brittle” epilepsy patients under clinical use conditions. Secondary outcomes were seizure frequency and adverse events with generic and brand product switching BACKGROUND: The bioequivalence (BE) testing standard for generic drug approval typically relies on healthy volunteers and has been questioned for assuring therapeutic equivalence in epilepsy patients who may be at increased risk for problems with antiepileptic drug (AED) brand-to-generic switching. DESIGN/METHODS: This randomized, double-blind, multiple-dose, steady-state, replicate-design BE study compared the most common generic lamotrigine to brand Lamictal in “generic-brittle” epilepsy patients, who are considered potentially sensitive to poor outcomes with generic switching. The most common generic immediate-release lamotrigine (manufactured by Teva) was compared to Lamictal, employing 100mg tablets at the patient’s usual dose (e.g. 100mg BID, 200mg BID, or 300mg BID). RESULTS: Generic was BE on average to the brand (n=34 completed per-protocol patients). Cmax 90[percnt] CI was 98.8-104.5[percnt]. AUC 90[percnt] CI was 97.2-101.6[percnt]. All patient pharmacokinetic (PK) ratios for generic vs brand were within +/-25[percnt], supporting the ABE public standard. No patient characteristic explained the small differences observed across individuals, and small differences were not associated with worsened seizures or side effects for the vast majority of generic-brittle patients. Even when subjects were re-challenged with identical product, individual patient PK ratios for each generic and brand were not identical to self. CONCLUSIONS: Results support the soundness of the ABE public standard, including its use of healthy volunteers rather than patients. No patient sub-population reacted poorly to generic or brand, much less one product but not the other. Generic and brand product passed ABE testing standards with observed efficacy and tolerability even in at-risk generic-brittle epilepsy patients under clinical use conditions. Disclosure: Dr. Ting has nothing to disclose. Dr. Jiang has nothing to disclose. Dr. Wong has nothing to disclose. Dr. Jones has nothing to disclose. Dr. Krumholz has nothing to disclose. Dr. Kane has nothing to disclose. Dr. Polli has nothing to disclose.
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Quantification of lamotrigine in patient plasma using a fast liquid chromatography-tandem mass spectrometry method with backflush technology.
Therapeutic Drug Monitoring, 2015Co-Authors: Jessica Wong, Wenlei Jiang, James E. Polli, Jace W. Jones, Maureen A. KaneAbstract:Background:Recent concerns have been raised by neurologists and patients with epilepsy regarding the bioequivalence of generic lamotrigine to the brand Lamictal. Bioequivalence studies require the quantification of lamotrigine in human plasma, including in the presence of other drugs, for studies th
Tricia Ting - One of the best experts on this subject based on the ideXlab platform.
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generic lamotrigine versus brand name Lamictal bioequivalence in patients with epilepsy a field test of the fda bioequivalence standard
Epilepsia, 2015Co-Authors: Tricia Ting, Wenlei Jiang, Maureen A. Kane, Jessica Wong, Jace W. Jones, Robert Lionberger, Allan Krumholz, Robert Temple, James E. PolliAbstract:SummaryObjective To test the current U.S. Food and Drug Administration (FDA) bioequivalence standard in a comparison of generic and brand-name drug pharmacokinetic (PK) performance in “generic-brittle” patients with epilepsy under clinical use conditions. Methods This randomized, double-blind, multiple-dose, steady-state, fully replicated bioequivalence study compared generic lamotrigine to brand-name Lamictal in “generic-brittle” patients with epilepsy (n = 34) who were already taking lamotrigine. Patients were repeatedly switched between masked Lamictal and generic lamotrigine. Intensive PK blood sampling at the end of each 2-week treatment period yielded two 12-h PK profiles for brand-name and generic forms for each patient. Steady-state area under the curve (AUC), peak plasma concentration (Cmax), and minimum plasma concentration (Cmin) data were subjected to conventional average bioequivalence (ABE) analysis, reference-scaled ABE analysis, and within-subject variability (WSV) comparisons. In addition, generic-versus-brand comparisons in individual patients were performed. Secondary clinical outcomes included seizure frequency and adverse events. Results Generic demonstrated bioequivalence to brand. The 90% confidence intervals of the mean for steady-state AUC, Cmax, and Cmin for generic-versus-brand were 97.2–101.6%, 98.8–104.5%, and 93.4–101.0%, respectively. The WSV of generic and brand were also similar. Individual patient PK ratios for generic-versus-brand were similar but not identical, in part because brand-versus-brand profiles were not identical, even though subjects were rechallenged with the same product. Few subjects had seizure exacerbations or tolerability issues with product switching. One subject, however, reported 267 focal motor seizures, primarily on generic, although his brand and generic PK profiles were practically identical. Significance Some neurologists question whether bioequivalence in healthy volunteers ensures therapeutic equivalence of brand and generic antiepileptic drugs in patients with epilepsy, who may be at increased risk for problems with brand-to-generic switching. Bioequivalence results in “generic-brittle” patients with epilepsy under clinical conditions support the soundness of the FDA bioequivalence standards. Adverse events on generic were not related to the small, allowable PK differences between generic and brand.
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Generic lamotrigine versus brand‐name Lamictal bioequivalence in patients with epilepsy: A field test of the FDA bioequivalence standard
Epilepsia, 2015Co-Authors: Tricia Ting, Wenlei Jiang, Maureen A. Kane, Jessica Wong, Jace W. Jones, Robert Lionberger, Allan Krumholz, Robert Temple, James E. PolliAbstract:SummaryObjective To test the current U.S. Food and Drug Administration (FDA) bioequivalence standard in a comparison of generic and brand-name drug pharmacokinetic (PK) performance in “generic-brittle” patients with epilepsy under clinical use conditions. Methods This randomized, double-blind, multiple-dose, steady-state, fully replicated bioequivalence study compared generic lamotrigine to brand-name Lamictal in “generic-brittle” patients with epilepsy (n = 34) who were already taking lamotrigine. Patients were repeatedly switched between masked Lamictal and generic lamotrigine. Intensive PK blood sampling at the end of each 2-week treatment period yielded two 12-h PK profiles for brand-name and generic forms for each patient. Steady-state area under the curve (AUC), peak plasma concentration (Cmax), and minimum plasma concentration (Cmin) data were subjected to conventional average bioequivalence (ABE) analysis, reference-scaled ABE analysis, and within-subject variability (WSV) comparisons. In addition, generic-versus-brand comparisons in individual patients were performed. Secondary clinical outcomes included seizure frequency and adverse events. Results Generic demonstrated bioequivalence to brand. The 90% confidence intervals of the mean for steady-state AUC, Cmax, and Cmin for generic-versus-brand were 97.2–101.6%, 98.8–104.5%, and 93.4–101.0%, respectively. The WSV of generic and brand were also similar. Individual patient PK ratios for generic-versus-brand were similar but not identical, in part because brand-versus-brand profiles were not identical, even though subjects were rechallenged with the same product. Few subjects had seizure exacerbations or tolerability issues with product switching. One subject, however, reported 267 focal motor seizures, primarily on generic, although his brand and generic PK profiles were practically identical. Significance Some neurologists question whether bioequivalence in healthy volunteers ensures therapeutic equivalence of brand and generic antiepileptic drugs in patients with epilepsy, who may be at increased risk for problems with brand-to-generic switching. Bioequivalence results in “generic-brittle” patients with epilepsy under clinical conditions support the soundness of the FDA bioequivalence standards. Adverse events on generic were not related to the small, allowable PK differences between generic and brand.
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Biopharmaceutic Risk Assessment of Brand and Generic Lamotrigine Tablets.
Molecular Pharmaceutics, 2015Co-Authors: Soundarya Vaithianathan, Siddarth Raman, Wenlei Jiang, Tricia Ting, Maureen A. Kane, James E. PolliAbstract:The therapeutic equivalence of generic and brand name antiepileptic drugs has been questioned by neurologists and the epilepsy community. A potential contributor to such concerns is pharmaceutical quality. The objective was to assess the biopharmaceutic risk of brand name Lamictal 100 mg tablets and generic lamotrigine 100 mg tablets from several manufacturers. Lamotrigine was characterized in terms of the Biopharmaceutics Classification System (BCS), including aqueous solubility and Caco-2 permeability. A panel of pharmaceutical quality tests was also performed on three batches of Lamictal, three batches of Teva generic, and one batch of each of four other generics: appearance, identity, assay, impurity, uniformity of dosage units, disintegration, dissolution, friability, and loss on drying. These market surveillance results indicate that all brand name and generic lamotrigine 100 mg tablets passed all tests and showed acceptable pharmaceutical quality and low biopharmaceutic risk. Lamotrigine was classi...
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Generic versus brand-name lamotrigine bioequivalence in generic-sensitive epilepsy patients: a field test of the public bioequivalence standard (S31.003)
Neurology, 2015Co-Authors: Tricia Ting, Wenlei Jiang, Maureen A. Kane, Jessica Wong, Jace W. Jones, Allan Krumholz, James E. PolliAbstract:OBJECTIVE: The primary outcome of the BioEquivalence in Epilepsy Patients (BEEP) study (1, 2) was the average bioequivalence (ABE) assessment of generic versus brand lamotrigine in “generic brittle” epilepsy patients under clinical use conditions. Secondary outcomes were seizure frequency and adverse events with generic and brand product switching BACKGROUND: The bioequivalence (BE) testing standard for generic drug approval typically relies on healthy volunteers and has been questioned for assuring therapeutic equivalence in epilepsy patients who may be at increased risk for problems with antiepileptic drug (AED) brand-to-generic switching. DESIGN/METHODS: This randomized, double-blind, multiple-dose, steady-state, replicate-design BE study compared the most common generic lamotrigine to brand Lamictal in “generic-brittle” epilepsy patients, who are considered potentially sensitive to poor outcomes with generic switching. The most common generic immediate-release lamotrigine (manufactured by Teva) was compared to Lamictal, employing 100mg tablets at the patient’s usual dose (e.g. 100mg BID, 200mg BID, or 300mg BID). RESULTS: Generic was BE on average to the brand (n=34 completed per-protocol patients). Cmax 90[percnt] CI was 98.8-104.5[percnt]. AUC 90[percnt] CI was 97.2-101.6[percnt]. All patient pharmacokinetic (PK) ratios for generic vs brand were within +/-25[percnt], supporting the ABE public standard. No patient characteristic explained the small differences observed across individuals, and small differences were not associated with worsened seizures or side effects for the vast majority of generic-brittle patients. Even when subjects were re-challenged with identical product, individual patient PK ratios for each generic and brand were not identical to self. CONCLUSIONS: Results support the soundness of the ABE public standard, including its use of healthy volunteers rather than patients. No patient sub-population reacted poorly to generic or brand, much less one product but not the other. Generic and brand product passed ABE testing standards with observed efficacy and tolerability even in at-risk generic-brittle epilepsy patients under clinical use conditions. Disclosure: Dr. Ting has nothing to disclose. Dr. Jiang has nothing to disclose. Dr. Wong has nothing to disclose. Dr. Jones has nothing to disclose. Dr. Krumholz has nothing to disclose. Dr. Kane has nothing to disclose. Dr. Polli has nothing to disclose.
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Is Generic Drug Quality as Good as Brand? Surveillance Testing of Marketed Lamotrigine Batches and Comparison to Brand (P3.002)
Neurology, 2014Co-Authors: Soundarya Vaithianathan, Siddarth Raman, Wenlei Jiang, Tricia Ting, Maureen A. Kane, James E. PolliAbstract:OBJECTIVE: To assess the pharmaceutical quality of three batches of brand name Lamictal and three batches of generic Teva lamotrigine tablets. BACKGROUND: The therapeutic equivalence of generics and brand name anti-epileptic drugs (AED) has been questioned. A potential concern is pharmaceutical quality. METHODS: The following pharmaceutical quality tests were performed on each batch, which were purchased from a distributor: appearance, identity, assay, impurity, uniformity of dosage units, disintegration, dissolution, friability, and loss on drying. Identity, assay, impurity, uniformity of dosage units, and dissolution were performed as specified in the United States Pharmacopeia (USP) monograph for lamotrigine tablets. Disintegration was performed per USP general chapter . The solubility of lamotrigine was measured at pH 1.2, 4.5, and 6.8. RESULTS: Results indicate that each batch passed each test. Given each batch passed, perhaps the most notable observation was the assay result of Lamictal batch B, which was 94.1%. Additionally, disintegration of generic Teva batch was longer than Lamictal (i.e. over 1 min versus about 20 sec), although dissolution for all batches was complete by 5 min, which is supported by the drug’s solubility profile. CONCLUSION: Overall, these market surveillance results indicate that brand and Teva generic lamotrigine tablets showed acceptable and comparable pharmaceutical quality. Given the role in vitro quality control tests play in assuring on-going product quality of both brand and generic drugs, these results implicate that phenomena other than pharmaceutical tablet quality might contribute to any lamotrigine switchability issues. Disclosure: Dr. Vaithianathan has nothing to disclose. Dr. Raman has nothing to disclose. Dr. Jiang has nothing to disclose. Dr. Ting has nothing to disclose. Dr. Kane has nothing to disclose. Dr. Polli has nothing to disclose.
Wenlei Jiang - One of the best experts on this subject based on the ideXlab platform.
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generic lamotrigine versus brand name Lamictal bioequivalence in patients with epilepsy a field test of the fda bioequivalence standard
Epilepsia, 2015Co-Authors: Tricia Ting, Wenlei Jiang, Maureen A. Kane, Jessica Wong, Jace W. Jones, Robert Lionberger, Allan Krumholz, Robert Temple, James E. PolliAbstract:SummaryObjective To test the current U.S. Food and Drug Administration (FDA) bioequivalence standard in a comparison of generic and brand-name drug pharmacokinetic (PK) performance in “generic-brittle” patients with epilepsy under clinical use conditions. Methods This randomized, double-blind, multiple-dose, steady-state, fully replicated bioequivalence study compared generic lamotrigine to brand-name Lamictal in “generic-brittle” patients with epilepsy (n = 34) who were already taking lamotrigine. Patients were repeatedly switched between masked Lamictal and generic lamotrigine. Intensive PK blood sampling at the end of each 2-week treatment period yielded two 12-h PK profiles for brand-name and generic forms for each patient. Steady-state area under the curve (AUC), peak plasma concentration (Cmax), and minimum plasma concentration (Cmin) data were subjected to conventional average bioequivalence (ABE) analysis, reference-scaled ABE analysis, and within-subject variability (WSV) comparisons. In addition, generic-versus-brand comparisons in individual patients were performed. Secondary clinical outcomes included seizure frequency and adverse events. Results Generic demonstrated bioequivalence to brand. The 90% confidence intervals of the mean for steady-state AUC, Cmax, and Cmin for generic-versus-brand were 97.2–101.6%, 98.8–104.5%, and 93.4–101.0%, respectively. The WSV of generic and brand were also similar. Individual patient PK ratios for generic-versus-brand were similar but not identical, in part because brand-versus-brand profiles were not identical, even though subjects were rechallenged with the same product. Few subjects had seizure exacerbations or tolerability issues with product switching. One subject, however, reported 267 focal motor seizures, primarily on generic, although his brand and generic PK profiles were practically identical. Significance Some neurologists question whether bioequivalence in healthy volunteers ensures therapeutic equivalence of brand and generic antiepileptic drugs in patients with epilepsy, who may be at increased risk for problems with brand-to-generic switching. Bioequivalence results in “generic-brittle” patients with epilepsy under clinical conditions support the soundness of the FDA bioequivalence standards. Adverse events on generic were not related to the small, allowable PK differences between generic and brand.
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Generic lamotrigine versus brand‐name Lamictal bioequivalence in patients with epilepsy: A field test of the FDA bioequivalence standard
Epilepsia, 2015Co-Authors: Tricia Ting, Wenlei Jiang, Maureen A. Kane, Jessica Wong, Jace W. Jones, Robert Lionberger, Allan Krumholz, Robert Temple, James E. PolliAbstract:SummaryObjective To test the current U.S. Food and Drug Administration (FDA) bioequivalence standard in a comparison of generic and brand-name drug pharmacokinetic (PK) performance in “generic-brittle” patients with epilepsy under clinical use conditions. Methods This randomized, double-blind, multiple-dose, steady-state, fully replicated bioequivalence study compared generic lamotrigine to brand-name Lamictal in “generic-brittle” patients with epilepsy (n = 34) who were already taking lamotrigine. Patients were repeatedly switched between masked Lamictal and generic lamotrigine. Intensive PK blood sampling at the end of each 2-week treatment period yielded two 12-h PK profiles for brand-name and generic forms for each patient. Steady-state area under the curve (AUC), peak plasma concentration (Cmax), and minimum plasma concentration (Cmin) data were subjected to conventional average bioequivalence (ABE) analysis, reference-scaled ABE analysis, and within-subject variability (WSV) comparisons. In addition, generic-versus-brand comparisons in individual patients were performed. Secondary clinical outcomes included seizure frequency and adverse events. Results Generic demonstrated bioequivalence to brand. The 90% confidence intervals of the mean for steady-state AUC, Cmax, and Cmin for generic-versus-brand were 97.2–101.6%, 98.8–104.5%, and 93.4–101.0%, respectively. The WSV of generic and brand were also similar. Individual patient PK ratios for generic-versus-brand were similar but not identical, in part because brand-versus-brand profiles were not identical, even though subjects were rechallenged with the same product. Few subjects had seizure exacerbations or tolerability issues with product switching. One subject, however, reported 267 focal motor seizures, primarily on generic, although his brand and generic PK profiles were practically identical. Significance Some neurologists question whether bioequivalence in healthy volunteers ensures therapeutic equivalence of brand and generic antiepileptic drugs in patients with epilepsy, who may be at increased risk for problems with brand-to-generic switching. Bioequivalence results in “generic-brittle” patients with epilepsy under clinical conditions support the soundness of the FDA bioequivalence standards. Adverse events on generic were not related to the small, allowable PK differences between generic and brand.
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Biopharmaceutic Risk Assessment of Brand and Generic Lamotrigine Tablets.
Molecular Pharmaceutics, 2015Co-Authors: Soundarya Vaithianathan, Siddarth Raman, Wenlei Jiang, Tricia Ting, Maureen A. Kane, James E. PolliAbstract:The therapeutic equivalence of generic and brand name antiepileptic drugs has been questioned by neurologists and the epilepsy community. A potential contributor to such concerns is pharmaceutical quality. The objective was to assess the biopharmaceutic risk of brand name Lamictal 100 mg tablets and generic lamotrigine 100 mg tablets from several manufacturers. Lamotrigine was characterized in terms of the Biopharmaceutics Classification System (BCS), including aqueous solubility and Caco-2 permeability. A panel of pharmaceutical quality tests was also performed on three batches of Lamictal, three batches of Teva generic, and one batch of each of four other generics: appearance, identity, assay, impurity, uniformity of dosage units, disintegration, dissolution, friability, and loss on drying. These market surveillance results indicate that all brand name and generic lamotrigine 100 mg tablets passed all tests and showed acceptable pharmaceutical quality and low biopharmaceutic risk. Lamotrigine was classi...
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Generic versus brand-name lamotrigine bioequivalence in generic-sensitive epilepsy patients: a field test of the public bioequivalence standard (S31.003)
Neurology, 2015Co-Authors: Tricia Ting, Wenlei Jiang, Maureen A. Kane, Jessica Wong, Jace W. Jones, Allan Krumholz, James E. PolliAbstract:OBJECTIVE: The primary outcome of the BioEquivalence in Epilepsy Patients (BEEP) study (1, 2) was the average bioequivalence (ABE) assessment of generic versus brand lamotrigine in “generic brittle” epilepsy patients under clinical use conditions. Secondary outcomes were seizure frequency and adverse events with generic and brand product switching BACKGROUND: The bioequivalence (BE) testing standard for generic drug approval typically relies on healthy volunteers and has been questioned for assuring therapeutic equivalence in epilepsy patients who may be at increased risk for problems with antiepileptic drug (AED) brand-to-generic switching. DESIGN/METHODS: This randomized, double-blind, multiple-dose, steady-state, replicate-design BE study compared the most common generic lamotrigine to brand Lamictal in “generic-brittle” epilepsy patients, who are considered potentially sensitive to poor outcomes with generic switching. The most common generic immediate-release lamotrigine (manufactured by Teva) was compared to Lamictal, employing 100mg tablets at the patient’s usual dose (e.g. 100mg BID, 200mg BID, or 300mg BID). RESULTS: Generic was BE on average to the brand (n=34 completed per-protocol patients). Cmax 90[percnt] CI was 98.8-104.5[percnt]. AUC 90[percnt] CI was 97.2-101.6[percnt]. All patient pharmacokinetic (PK) ratios for generic vs brand were within +/-25[percnt], supporting the ABE public standard. No patient characteristic explained the small differences observed across individuals, and small differences were not associated with worsened seizures or side effects for the vast majority of generic-brittle patients. Even when subjects were re-challenged with identical product, individual patient PK ratios for each generic and brand were not identical to self. CONCLUSIONS: Results support the soundness of the ABE public standard, including its use of healthy volunteers rather than patients. No patient sub-population reacted poorly to generic or brand, much less one product but not the other. Generic and brand product passed ABE testing standards with observed efficacy and tolerability even in at-risk generic-brittle epilepsy patients under clinical use conditions. Disclosure: Dr. Ting has nothing to disclose. Dr. Jiang has nothing to disclose. Dr. Wong has nothing to disclose. Dr. Jones has nothing to disclose. Dr. Krumholz has nothing to disclose. Dr. Kane has nothing to disclose. Dr. Polli has nothing to disclose.
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Quantification of lamotrigine in patient plasma using a fast liquid chromatography-tandem mass spectrometry method with backflush technology.
Therapeutic Drug Monitoring, 2015Co-Authors: Jessica Wong, Wenlei Jiang, James E. Polli, Jace W. Jones, Maureen A. KaneAbstract:Background:Recent concerns have been raised by neurologists and patients with epilepsy regarding the bioequivalence of generic lamotrigine to the brand Lamictal. Bioequivalence studies require the quantification of lamotrigine in human plasma, including in the presence of other drugs, for studies th
Jessica Wong - One of the best experts on this subject based on the ideXlab platform.
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generic lamotrigine versus brand name Lamictal bioequivalence in patients with epilepsy a field test of the fda bioequivalence standard
Epilepsia, 2015Co-Authors: Tricia Ting, Wenlei Jiang, Maureen A. Kane, Jessica Wong, Jace W. Jones, Robert Lionberger, Allan Krumholz, Robert Temple, James E. PolliAbstract:SummaryObjective To test the current U.S. Food and Drug Administration (FDA) bioequivalence standard in a comparison of generic and brand-name drug pharmacokinetic (PK) performance in “generic-brittle” patients with epilepsy under clinical use conditions. Methods This randomized, double-blind, multiple-dose, steady-state, fully replicated bioequivalence study compared generic lamotrigine to brand-name Lamictal in “generic-brittle” patients with epilepsy (n = 34) who were already taking lamotrigine. Patients were repeatedly switched between masked Lamictal and generic lamotrigine. Intensive PK blood sampling at the end of each 2-week treatment period yielded two 12-h PK profiles for brand-name and generic forms for each patient. Steady-state area under the curve (AUC), peak plasma concentration (Cmax), and minimum plasma concentration (Cmin) data were subjected to conventional average bioequivalence (ABE) analysis, reference-scaled ABE analysis, and within-subject variability (WSV) comparisons. In addition, generic-versus-brand comparisons in individual patients were performed. Secondary clinical outcomes included seizure frequency and adverse events. Results Generic demonstrated bioequivalence to brand. The 90% confidence intervals of the mean for steady-state AUC, Cmax, and Cmin for generic-versus-brand were 97.2–101.6%, 98.8–104.5%, and 93.4–101.0%, respectively. The WSV of generic and brand were also similar. Individual patient PK ratios for generic-versus-brand were similar but not identical, in part because brand-versus-brand profiles were not identical, even though subjects were rechallenged with the same product. Few subjects had seizure exacerbations or tolerability issues with product switching. One subject, however, reported 267 focal motor seizures, primarily on generic, although his brand and generic PK profiles were practically identical. Significance Some neurologists question whether bioequivalence in healthy volunteers ensures therapeutic equivalence of brand and generic antiepileptic drugs in patients with epilepsy, who may be at increased risk for problems with brand-to-generic switching. Bioequivalence results in “generic-brittle” patients with epilepsy under clinical conditions support the soundness of the FDA bioequivalence standards. Adverse events on generic were not related to the small, allowable PK differences between generic and brand.
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Generic lamotrigine versus brand‐name Lamictal bioequivalence in patients with epilepsy: A field test of the FDA bioequivalence standard
Epilepsia, 2015Co-Authors: Tricia Ting, Wenlei Jiang, Maureen A. Kane, Jessica Wong, Jace W. Jones, Robert Lionberger, Allan Krumholz, Robert Temple, James E. PolliAbstract:SummaryObjective To test the current U.S. Food and Drug Administration (FDA) bioequivalence standard in a comparison of generic and brand-name drug pharmacokinetic (PK) performance in “generic-brittle” patients with epilepsy under clinical use conditions. Methods This randomized, double-blind, multiple-dose, steady-state, fully replicated bioequivalence study compared generic lamotrigine to brand-name Lamictal in “generic-brittle” patients with epilepsy (n = 34) who were already taking lamotrigine. Patients were repeatedly switched between masked Lamictal and generic lamotrigine. Intensive PK blood sampling at the end of each 2-week treatment period yielded two 12-h PK profiles for brand-name and generic forms for each patient. Steady-state area under the curve (AUC), peak plasma concentration (Cmax), and minimum plasma concentration (Cmin) data were subjected to conventional average bioequivalence (ABE) analysis, reference-scaled ABE analysis, and within-subject variability (WSV) comparisons. In addition, generic-versus-brand comparisons in individual patients were performed. Secondary clinical outcomes included seizure frequency and adverse events. Results Generic demonstrated bioequivalence to brand. The 90% confidence intervals of the mean for steady-state AUC, Cmax, and Cmin for generic-versus-brand were 97.2–101.6%, 98.8–104.5%, and 93.4–101.0%, respectively. The WSV of generic and brand were also similar. Individual patient PK ratios for generic-versus-brand were similar but not identical, in part because brand-versus-brand profiles were not identical, even though subjects were rechallenged with the same product. Few subjects had seizure exacerbations or tolerability issues with product switching. One subject, however, reported 267 focal motor seizures, primarily on generic, although his brand and generic PK profiles were practically identical. Significance Some neurologists question whether bioequivalence in healthy volunteers ensures therapeutic equivalence of brand and generic antiepileptic drugs in patients with epilepsy, who may be at increased risk for problems with brand-to-generic switching. Bioequivalence results in “generic-brittle” patients with epilepsy under clinical conditions support the soundness of the FDA bioequivalence standards. Adverse events on generic were not related to the small, allowable PK differences between generic and brand.
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Generic versus brand-name lamotrigine bioequivalence in generic-sensitive epilepsy patients: a field test of the public bioequivalence standard (S31.003)
Neurology, 2015Co-Authors: Tricia Ting, Wenlei Jiang, Maureen A. Kane, Jessica Wong, Jace W. Jones, Allan Krumholz, James E. PolliAbstract:OBJECTIVE: The primary outcome of the BioEquivalence in Epilepsy Patients (BEEP) study (1, 2) was the average bioequivalence (ABE) assessment of generic versus brand lamotrigine in “generic brittle” epilepsy patients under clinical use conditions. Secondary outcomes were seizure frequency and adverse events with generic and brand product switching BACKGROUND: The bioequivalence (BE) testing standard for generic drug approval typically relies on healthy volunteers and has been questioned for assuring therapeutic equivalence in epilepsy patients who may be at increased risk for problems with antiepileptic drug (AED) brand-to-generic switching. DESIGN/METHODS: This randomized, double-blind, multiple-dose, steady-state, replicate-design BE study compared the most common generic lamotrigine to brand Lamictal in “generic-brittle” epilepsy patients, who are considered potentially sensitive to poor outcomes with generic switching. The most common generic immediate-release lamotrigine (manufactured by Teva) was compared to Lamictal, employing 100mg tablets at the patient’s usual dose (e.g. 100mg BID, 200mg BID, or 300mg BID). RESULTS: Generic was BE on average to the brand (n=34 completed per-protocol patients). Cmax 90[percnt] CI was 98.8-104.5[percnt]. AUC 90[percnt] CI was 97.2-101.6[percnt]. All patient pharmacokinetic (PK) ratios for generic vs brand were within +/-25[percnt], supporting the ABE public standard. No patient characteristic explained the small differences observed across individuals, and small differences were not associated with worsened seizures or side effects for the vast majority of generic-brittle patients. Even when subjects were re-challenged with identical product, individual patient PK ratios for each generic and brand were not identical to self. CONCLUSIONS: Results support the soundness of the ABE public standard, including its use of healthy volunteers rather than patients. No patient sub-population reacted poorly to generic or brand, much less one product but not the other. Generic and brand product passed ABE testing standards with observed efficacy and tolerability even in at-risk generic-brittle epilepsy patients under clinical use conditions. Disclosure: Dr. Ting has nothing to disclose. Dr. Jiang has nothing to disclose. Dr. Wong has nothing to disclose. Dr. Jones has nothing to disclose. Dr. Krumholz has nothing to disclose. Dr. Kane has nothing to disclose. Dr. Polli has nothing to disclose.
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Quantification of lamotrigine in patient plasma using a fast liquid chromatography-tandem mass spectrometry method with backflush technology.
Therapeutic Drug Monitoring, 2015Co-Authors: Jessica Wong, Wenlei Jiang, James E. Polli, Jace W. Jones, Maureen A. KaneAbstract:Background:Recent concerns have been raised by neurologists and patients with epilepsy regarding the bioequivalence of generic lamotrigine to the brand Lamictal. Bioequivalence studies require the quantification of lamotrigine in human plasma, including in the presence of other drugs, for studies th
