Abstract
A monocentric, open, randomised, single-dose, six-period crossover trial was carried
out in healthy volunteers under fasting conditions to establish the most appropriate
study design for a pivotal bioequivalence trial with acarbose (CAS 56180-94-0) regarding
a) dosage of the drug, b) type of carbohydrate load, c) type of primary endpoint,
and d) sample size. 50 g sucrose or 50 g starch were used as carbohydrate load. Acarbose
was administered in doses of 50 and 200 mg. Blood glucose and breath hydrogen were
evaluated as endpoints. Both acarbose doses reduced the effect of carbohydrate load.
Blood glucose: no statistically significant difference could be noted between the
overall effect of 50 mg and that of 200 mg acarbose irrespective of the type of carbohydrate
load. Breath hydrogen: an influence could be shown only for sucrose as carbohydrate
load. Practically no effect was observed with starch. The overall increase of effect
is by more than 200% with sucrose when the dose of acarbose increases from 50 to 200
mg. This difference between the effects of both doses of acarbose on breath hydrogen
is statistically significant. For a pivotal trial, sucrose is the most appropriate
type of carbohydrate load, baseline adjusted area under the breath hydrogen response
is the most appropriate primary endpoint, and a dose of 100 mg acarbose is the most
appropriate dosage. A total number of 100 subjects will be needed for proving pharmacodynamic
equivalence between two acarbose products in a pivotal trial.
Key words
Acarbose - Blood glucose - Breath hydrogen - Carbohydrate load - CAS 56180-94-0 -
Starch - Sucrose
