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Efficacy, safety, and tolerability of imepitoin in dogs with newly diagnosed epilepsy in a randomized controlled clinical study with long-term follow up.

Rundfeldt C, Tipold A, Löscher W - BMC Vet. Res. (2015)

Bottom Line: A treatment with 30 mg/kg BID resulted in a significantly greater reduction in monthly seizure frequency relative to baseline data as compared to the 1 mg/kg dose.An increase to 30 mg/kg BID in the low- dose animals resulted in a significant reduction in generalized and partial seizures, but not cluster seizures.Imepitoin was well tolerated.

View Article: PubMed Central - PubMed

Affiliation: Drug-Consulting Network, 01445, Coswig, Germany. chris.rundfeldt@t-online.de.

ABSTRACT

Background: Imepitoin is a novel antiepileptic drug for the treatment of canine idiopathic epilepsy. The present study was conducted to demonstrate superior antiepileptic activity of a high dose of 30 mg/kg BID over a low dose of 1 mg/kg BID of imepitoin during 12 weeks of treatment under double blind conditions in a field population of dogs with previously untreated epilepsy. In a consecutive 12 weeks open label follow up (phase 2), all animals received 30 mg/kg BID, to evaluate the persistence of the antiepileptic activity, and to evaluate the effect of a dose step up to 30 mg/kg in the former low-dose animals.

Results: A treatment with 30 mg/kg BID resulted in a significantly greater reduction in monthly seizure frequency relative to baseline data as compared to the 1 mg/kg dose. Both generalized and partial seizures but not cluster seizures were significantly less frequent in the high dose group. The antiepileptic activity was maintained during study phase 2 in the high dose group. An increase to 30 mg/kg BID in the low- dose animals resulted in a significant reduction in generalized and partial seizures, but not cluster seizures. At the end of study phase 2, 32.1 and 46.8 % of dogs of the former high and former low-dose groups respectively, remained free of generalized tonic-clonic seizures. Imepitoin was well tolerated. The frequency of dogs with any adverse drug reactions was higher in the 30 mg/kg BID dose (59 % vs. 41 %, p = 0.041), and the main target organ was the central nervous system (CNS). The occurrence of CNS related adverse reactions was transient and findings were mostly restricted to the first weeks of treatment. No hepatic enzyme increase and no other organ toxicity were observed.

Conclusion: The administration of imepitoin twice daily at a dose of 30 mg/kg results in significant and persistent antiepileptic effects in patients with newly diagnosed epilepsy and generalized tonic-clonic seizures, as observed over a study period of up to 6 months. Imepitoin was well tolerated. Most CNS related adverse drug reactions were transient. Both the antiepileptic activity and the safety profile make the drug suitable for long-term clinical use.

No MeSH data available.


Related in: MedlinePlus

Reduction in monthly seizure frequency (MSF) during study phase 1. Displayed are mean ± SD of the difference in MSF prior to start of treatment (retrospective baseline) and during treatment with 1 mg/kg BID (Low dose) or 30 mg/kg BID (high dose). The MSF was significantly more reduced in the high dose group (two-sided two-sample t-test)
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Fig1: Reduction in monthly seizure frequency (MSF) during study phase 1. Displayed are mean ± SD of the difference in MSF prior to start of treatment (retrospective baseline) and during treatment with 1 mg/kg BID (Low dose) or 30 mg/kg BID (high dose). The MSF was significantly more reduced in the high dose group (two-sided two-sample t-test)

Mentions: The evaluation of the baseline seizure frequency of generalized tonic-clonic seizures, cluster seizures or status epilepticus events revealed that, in the high-dose group, despite randomized inclusion, the mean seizure frequency was found to be higher than in the low- dose group. This difference was statistically significant (p = 0.030). In both groups, the mean seizure frequency dropped during the study period, but the drop was more pronounced in the high-dose group, reaching a reduction of 1.7 ± 2.8 seizures per month, while the drop in seizure frequency was only 0.8 ± 2.0 seizures per month in the low-dose group. This mean difference was statistically significant (p = 0.044), indicating that the high dose was superior to the low dose in reducing seizure frequency (Table 2 and Fig. 1). In the high-dose group, 37.5 % of animals (24 of 64) became seizure free, but also in the low-dose group 31.7 % (19 of 60) became seizure free, the difference was not significant. In addition, the total number of different seizure types which occurred during the first study phase was counted and the rate of seizures per dog was calculated. This included also counting of partial and complex partial seizures, in addition to generalized tonic-clonic and cluster seizures (Table 3). Both groups differed significantly (p = 0.035) in the rate of generalized tonic-clonic seizures, but not in cluster seizures. The frequency of partial and complex partial seizures was also significantly lower in the high-dose group (p < 0.001). When all seizures were summed, the total number of seizures was also significantly lower in the high-dose group (p < 0.001).Table 2


Efficacy, safety, and tolerability of imepitoin in dogs with newly diagnosed epilepsy in a randomized controlled clinical study with long-term follow up.

Rundfeldt C, Tipold A, Löscher W - BMC Vet. Res. (2015)

Reduction in monthly seizure frequency (MSF) during study phase 1. Displayed are mean ± SD of the difference in MSF prior to start of treatment (retrospective baseline) and during treatment with 1 mg/kg BID (Low dose) or 30 mg/kg BID (high dose). The MSF was significantly more reduced in the high dose group (two-sided two-sample t-test)
© Copyright Policy - OpenAccess
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4556053&req=5

Fig1: Reduction in monthly seizure frequency (MSF) during study phase 1. Displayed are mean ± SD of the difference in MSF prior to start of treatment (retrospective baseline) and during treatment with 1 mg/kg BID (Low dose) or 30 mg/kg BID (high dose). The MSF was significantly more reduced in the high dose group (two-sided two-sample t-test)
Mentions: The evaluation of the baseline seizure frequency of generalized tonic-clonic seizures, cluster seizures or status epilepticus events revealed that, in the high-dose group, despite randomized inclusion, the mean seizure frequency was found to be higher than in the low- dose group. This difference was statistically significant (p = 0.030). In both groups, the mean seizure frequency dropped during the study period, but the drop was more pronounced in the high-dose group, reaching a reduction of 1.7 ± 2.8 seizures per month, while the drop in seizure frequency was only 0.8 ± 2.0 seizures per month in the low-dose group. This mean difference was statistically significant (p = 0.044), indicating that the high dose was superior to the low dose in reducing seizure frequency (Table 2 and Fig. 1). In the high-dose group, 37.5 % of animals (24 of 64) became seizure free, but also in the low-dose group 31.7 % (19 of 60) became seizure free, the difference was not significant. In addition, the total number of different seizure types which occurred during the first study phase was counted and the rate of seizures per dog was calculated. This included also counting of partial and complex partial seizures, in addition to generalized tonic-clonic and cluster seizures (Table 3). Both groups differed significantly (p = 0.035) in the rate of generalized tonic-clonic seizures, but not in cluster seizures. The frequency of partial and complex partial seizures was also significantly lower in the high-dose group (p < 0.001). When all seizures were summed, the total number of seizures was also significantly lower in the high-dose group (p < 0.001).Table 2

Bottom Line: A treatment with 30 mg/kg BID resulted in a significantly greater reduction in monthly seizure frequency relative to baseline data as compared to the 1 mg/kg dose.An increase to 30 mg/kg BID in the low- dose animals resulted in a significant reduction in generalized and partial seizures, but not cluster seizures.Imepitoin was well tolerated.

View Article: PubMed Central - PubMed

Affiliation: Drug-Consulting Network, 01445, Coswig, Germany. chris.rundfeldt@t-online.de.

ABSTRACT

Background: Imepitoin is a novel antiepileptic drug for the treatment of canine idiopathic epilepsy. The present study was conducted to demonstrate superior antiepileptic activity of a high dose of 30 mg/kg BID over a low dose of 1 mg/kg BID of imepitoin during 12 weeks of treatment under double blind conditions in a field population of dogs with previously untreated epilepsy. In a consecutive 12 weeks open label follow up (phase 2), all animals received 30 mg/kg BID, to evaluate the persistence of the antiepileptic activity, and to evaluate the effect of a dose step up to 30 mg/kg in the former low-dose animals.

Results: A treatment with 30 mg/kg BID resulted in a significantly greater reduction in monthly seizure frequency relative to baseline data as compared to the 1 mg/kg dose. Both generalized and partial seizures but not cluster seizures were significantly less frequent in the high dose group. The antiepileptic activity was maintained during study phase 2 in the high dose group. An increase to 30 mg/kg BID in the low- dose animals resulted in a significant reduction in generalized and partial seizures, but not cluster seizures. At the end of study phase 2, 32.1 and 46.8 % of dogs of the former high and former low-dose groups respectively, remained free of generalized tonic-clonic seizures. Imepitoin was well tolerated. The frequency of dogs with any adverse drug reactions was higher in the 30 mg/kg BID dose (59 % vs. 41 %, p = 0.041), and the main target organ was the central nervous system (CNS). The occurrence of CNS related adverse reactions was transient and findings were mostly restricted to the first weeks of treatment. No hepatic enzyme increase and no other organ toxicity were observed.

Conclusion: The administration of imepitoin twice daily at a dose of 30 mg/kg results in significant and persistent antiepileptic effects in patients with newly diagnosed epilepsy and generalized tonic-clonic seizures, as observed over a study period of up to 6 months. Imepitoin was well tolerated. Most CNS related adverse drug reactions were transient. Both the antiepileptic activity and the safety profile make the drug suitable for long-term clinical use.

No MeSH data available.


Related in: MedlinePlus