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Controlled Clinical Trial
. 2008 Jul;64(7):651-61.
doi: 10.1007/s00228-008-0462-1. Epub 2008 Mar 5.

Efficacy and safety of disodium ascorbyl phytostanol phosphates in men with moderate dyslipidemia

Maud N Vissers  1 , Mieke D Trip, P Haydn Pritchard, Patrick Tam, Tatjana Lukic, Monique G de Sain-van der Velden, Martina de Barse, John J P Kastelein
Affiliations
Controlled Clinical Trial

Efficacy and safety of disodium ascorbyl phytostanol phosphates in men with moderate dyslipidemia

Maud N Vissers et al. Eur J Clin Pharmacol. 2008 Jul.

Abstract

Objective: This study investigated the efficacy, safety, tolerability, and pharmacokinetics of a novel cholesterol absorption inhibitor, FM-VP4, comprising disodium ascorbyl sitostanol phosphate (DASP) and disodium ascorbyl campestanol phosphate (DACP).

Methods: In phase 1, 30 men received a single dose of 100, 200, 400, 800, 1,600, or 2,000 mg FM-VP4 or placebo. In phase 2, 100 men were treated with 100, 200, 400, or 800 mg/day of FM-VP4 or placebo for 4 weeks.

Results: The drug was well tolerated at each single or multiple dose level. After 4 weeks of treatment, low-density lipoprotein cholesterol (LDL-C) levels changed by 2.7% in the placebo group and by 2.9%, -4.2%, and -4.6% in the 100, 200, and 800 mg/day groups, respectively, which was not statistically significant. However, 400 mg/day of FM-VP4 significantly decreased LDL-C by 6.5% (p=0.02). Phase 1 showed that DACP and DASP were absorbed into plasma with a median t(max) of 12 h for both components, and clearance was slow with a mean t(1/2lambda) of 57 h. During 4 weeks of treatment, steady state was reached by approximately 8 days.

Conclusion: This study demonstrated that up to 800 mg/day of FM-VP4 is safe and well tolerated for at least 4 weeks. Furthermore, the higher doses significantly reduced LDL-C by 7% compared with baseline or by 10% compared with placebo, with the maximum effect reached at 400 mg/day.

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Figures

Fig. 1
Fig. 1
Chemical structure of FM-VP4, composed of disodium ascorbyl campestanol phosphate (R=CH3) and disodium ascorbyl sitostanol phosphate (R=C2H5)
Fig. 2
Fig. 2
Mean low-density lipoprotein cholesterol levels during 28 days of treatment with placebo or 100, 200, 400, and 800 mg/day FM-VP4 (disodium ascorbyl campestanol phosphate and disodium ascorbyl sitostanol phosphate) and after 14 days of follow-up
Fig. 3
Fig. 3
Mean trough concentrations of disodium ascorbyl sitostanol phosphate (DASP) and disodium ascorbyl campestanol phosphate (DACP) during 28 days of dosing and 14 days postdosing follow-up. The dots of days 2–5 represent the 16 hospitalized subjects on FM-VP4 (DACP and DASP), whereas the dots of days 8, 28, and 42 represent all 80 subjects on FM-VP4. DASP and DACP were not present in plasma at day 1 (baseline), and DACP concentrations were mostly below detection limit during the first 5 days of intake in the 100-mg group. The mean levels of DASP in the 100-mg group and DACP in the 200-mg group were below the lower limit of quantification (LLOQ) because some of the subjects had levels below the LLOQ, which were regarded as 0 ng/ml
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Comment in

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