The bioequivalence of standard sumatriptan tablets and two encapsulated forms of sumatriptan

Milton, KA; Kleinermans, Diane; Scott, Nicholas R; Cooper, Jackie

doi:10.2165/00124363-200102000-00010

Cited by 6 publications

(5 citation statements)

References 12 publications

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“…The encapsulated sumatriptan was demonstrated to be equivalent to the commercial tablet based on in vitro dissolution conducted in deionized water (data on file). In vivo pharmacokinetic comparison of encapsulated sumatriptan and sumatriptan standard tablets performed by Milton et al (11) showed equivalence of encapsulated sumatriptan. Patients treated three migraine attacks during a study period of 3 months per patient.…”

Section: Methodsmentioning

confidence: 97%

Placebo-Controlled Comparison of Effervescent Acetylsalicylic Acid, Sumatriptan and Ibuprofen in the Treatment of Migraine Attacks

Bussone

Liaño

et al. 2004

Cephalalgia

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Acetylsalicylic acid (ASA) in combination with metoclopramide has been frequently used in clinical trials in the acute treatment of migraine attacks. Recently the efficacy of a new high buffered formulation of 1000 mg effervescent ASA without metoclopramide compared to placebo has been shown. To further confirm the efficacy of this new formulation in comparison with a triptan and a nonsteroidal anti-inflammatory drug (ibuprofen) a three-fold crossover, double-blind, randomized trial with 312 patients was conducted in Germany, Italy and Spain. Effervescent ASA (1000 mg) was compared to encapsulated sumatriptan (50 mg), ibuprofen (400 mg) and placebo. The percentage of patients with reduction in headache severity from moderate or severe to mild or no pain (primary endpoint) was 52.5% for ASA, 60.2% for ibuprofen, 55.8% for sumatriptan and 30.6% for placebo. All active treatments were superior to placebo (P < 0.0001), whereas active treatments were not statistically different. The number of patients who were pain-free at 2 h was 27.1%, 33.2%, 37.1% and 12.6% for those treated with ASA, ibuprofen, sumatriptan or placebo, respectively. The difference between ASA and sumatriptan was statistically significant (P = 0.025). With respect to other secondary efficacy criteria and accompanying symptoms no statistically significant differences between ASA and ibuprofen or sumatriptan were found. Drug-related adverse events were reported in 4.1%, 5.7%, 6.6% and 4.5% of patients treated with ASA, ibuprofen sumatriptan or placebo. This study showed that 1000 mg effervescent ASA is as effective as 50 mg sumatriptan and 400 mg ibuprofen in the treatment of migraine attacks regarding headache relief from moderate/severe to mild/no pain at 2 h. Regarding pain-free at 2 h sumatriptan was most effective.

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Section: Methodsmentioning

confidence: 97%

Placebo-Controlled Comparison of Effervescent Acetylsalicylic Acid, Sumatriptan and Ibuprofen in the Treatment of Migraine Attacks

Bussone

Liaño

et al. 2004

Cephalalgia

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“…Each study used a randomized, placebo‐controlled, parallel‐group, double‐dummy design in which the double‐blind was maintained by matching plain white film‐coated tablets of eletriptan to placebo tablets, and gelatin capsules containing sumatriptan to matching placebo capsules. The blinded sumatriptan was demonstrated to be both bioequivalent and clinically equivalent to the commercial tablet based on five categories of data: (i) an in vitro dissolution study conducted in deionized water (Milton et al , 2001), (ii) an in vivo gamma scintigraphy study showing dissolution (Wilding et al. , 2003), (iii) bioequivalence studies meeting standard regulatory criteria for equivalent AUC and C max values (Milton et al , 2001); (iv) a pooled analysis of three bioequivalence studies confirming early bioequivalence at the 2‐h time point (AUC 0−2h ; data on file, Pfizer Inc.); and (v) a post hoc comparison of the therapeutic gain for headache response at 2 h. In the current pooled analysis, encapsulated sumatriptan showed a 2‐h headache response (and therapeutic gain) of 57.5% (31.2%), which is equivalent to what has been reported across all available placebo‐controlled studies of the 100‐mg dose of sumatriptan, 59% (29%) (Ferrari et al.…”

Section: Methodsmentioning

confidence: 99%

The 40‐mg dose of eletriptan: comparative efficacy and tolerability versus sumatriptan 100 mg

Diener

Ryan²,

Sun

et al. 2004

Euro J of Neurology

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Meta-analysis provides valuable information regarding relative efficacies of triptans, but head-to-head comparator studies remain the gold standard. Three similar head-to-head trials comparing eletriptan 40 mg (E40) with sumatriptan 100 mg (S100) provide a rare opportunity and sufficient power, for robust comparisons of efficacy. Data were combined from three double-blind, placebo-controlled, first-dose, first-attack acute migraine treatment studies comparing E40 (n=1132), S100 (n=1129), and placebo (n=645). The primary outcome was headache response at 2 h. Secondary outcomes included headache response at 1 h, pain-free and functional responses, and sustained headache and pain-free responses. Odds ratios were calculated for summary estimates of probability of response. There were higher headache response rates with eletriptan versus sumatriptan at 2 h (67% vs. 57%; P<0.0001) and 1 h (34% vs. 26%; P<0.0001). Eletriptan also had higher 2 h pain-free (35% vs. 25%; P<0.0001) and functional responses (67% vs. 58%; P<0.0001). Sustained headache (42%) and pain-free (22%) response rates were higher for eletriptan versus sumatriptan (34%, P<0.0001; 15%, P<0.0001). The probability of response for eletriptan versus sumatriptan ranged from 36% higher (relief of nausea) to 64% higher (sustained pain-free rate). Combined analysis demonstrates that E40 has superior efficacy versus S100 across all clinically relevant outcomes.

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“…[1] In fact, no relationship of AUC 0-2 with 'therapeutic effect' has been established for sumatriptan. The critique in the above letter is based on a highly selective review of available data and an unusual interpretation of bioequivalence.…”

Section: Replymentioning

confidence: 99%

“…

The bioequivalence of standard sumatriptan tablets and two encapsulated forms of sumatriptan Milton et al reported a study claiming to demonstrate the bioequivalence of sumatriptan tablet versus two variations of encapsulated sumatriptan [1]. Pfizer conducted this bioequivalence study to validate their decision to use encapsulated sumatriptan while not similarly encumbering their own product, eletriptan, in three Pfizer-sponsored comparator trials.

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confidence: 99%

Untitled

McNeal¹,

O’Quinn²,

Scott³

2001

Int J Pharm Med

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The bioequivalence of standard sumatriptan tablets and two encapsulated forms of sumatriptan Milton et al. reported a study claiming to demonstrate the bioequivalence of sumatriptan tablet versus two variations of encapsulated sumatriptan [1]. Pfizer conducted this bioequivalence study to validate their decision to use encapsulated sumatriptan while not similarly encumbering their own product, eletriptan, in three Pfizer-sponsored comparator trials. Sumatriptan efficacy in these three trials was notably lower than the results seen in other comparator trials where sumatriptan was not encapsulated (see Figure 1).It is believed that the speed in which a triptan works is directly related to the ability of the drug to rapidly enter the bloodstream. Although standard bioequivalence testing uses 24-h AUC [AUC 1 ] and C max as comparative parameters, the Food and Drug Administration (FDA) has acknowledged that both direct (e.g. rate constant and profile) and indirect measures of absorption (e.g. C max , T max ) are limited in their ability to assess rate of absorption for some disease states. The measurement of partial area under the concentration-time profile curve (i.e. 2-h AUC [AUC 0-2 ]) may be justified [2]. We believe migraine to be one of these disease states, due in part to migraine-associated gastric stasis, and assert that AUC 1 and C max should not be the sole determinants when comparing acute therapeutic interventions in disease states with unpredictable acute onset.Milton et al. concluded that the two forms of encapsulated sumatriptan were bioequivalent (using AUC 1 and C max ) to commercially available sumatriptan tablets. The authors support this conclusion by providing an out-of-context description of O'Quinn et al.[3] that presents data from two trials conducted to evaluate the absorption of sumatriptan 50 mg tablets versus encapsulated sumatriptan 50 mg tablets in healthy volunteers and in migraineurs during a migraine. Absorption was assessed by calculating the area under the curve 0-2 hours postdose (AUC 0-2 ), and by measuring the time to the first measurable serum concentration (T lag ), time to 10 ng/ml (T 10 ) and 20 ng/ml (T 20 ), and T max . Overall bioequivalence was assessed by AUC 1 and C max . Sumatriptan concentrations during the first 2 h after dosing were lower with the capsule than the tablet, an effect larger in patients during migraine than in healthy volunteers.

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The bioequivalence of standard sumatriptan tablets and two encapsulated forms of sumatriptan

Cited by 6 publications

References 12 publications

Placebo-Controlled Comparison of Effervescent Acetylsalicylic Acid, Sumatriptan and Ibuprofen in the Treatment of Migraine Attacks

Placebo-Controlled Comparison of Effervescent Acetylsalicylic Acid, Sumatriptan and Ibuprofen in the Treatment of Migraine Attacks

The 40‐mg dose of eletriptan: comparative efficacy and tolerability versus sumatriptan 100 mg

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