Format

Send to

Choose Destination
J Clin Pharmacol. 2016 Apr;56(4):484-91. doi: 10.1002/jcph.610. Epub 2015 Nov 9.

A thorough QTc study demonstrates that olmesartan medoxomil does not prolong the QTc interval.

Author information

1
Daiichi Sankyo Pharma Development, Edison, NJ, USA.
2
Daiichi Sankyo Co., Ltd, Tokyo, Japan.
3
Celerion Pharma Services, Tempe, AZ, USA.

Abstract

Two studies (ROADMAP and ORIENT) evaluating the renoprotective effects of olmesartan medoxomil (OM) in patients with type 2 diabetes suggested OM is associated with increased cardiovascular mortality. We conducted a thorough QTc study to evaluate the effects of OM on cardiac repolarization. A randomized, double-blind, phase 1 study was conducted per E14 Guidance to assess the effects of single doses of OM therapeutic dose (40 mg), OM supratherapeutic dose (160 mg), placebo, or moxifloxacin (MOXI; 400 mg) on QTc in 56 healthy subjects. The primary endpoint was the baseline-adjusted, placebo-corrected QTc interval using Fridericia's formula (ΔΔQTcF) for OM and MOXI. Assay sensitivity was concluded if lower limit of 1-sided 95%CI > 5 milliseconds of ΔΔQTcF for MOXI. No threshold pharmacologic effect for OM was concluded if upper limit of 1-sided 95%CI <10 milliseconds for ΔΔQTcF at any timepoint. Pharmacokinetics, ECGs, and safety were assessed. Assay sensitivity was demonstrated. The largest upper limit of the 1-sided 95%CI for ΔΔQTcF was <5 milliseconds for OM. No clinically significant changes were observed in ECGs. Pharmacokinetics and safety profile were consistent with previous data. Therapeutic and supratherapeutic OM doses had no clinically significant effect on cardiac repolarization and were well tolerated.

KEYWORDS:

QTc interval; angiotensin receptor blocker; cardiac safety; olmesartan

PMID:
26239632
PMCID:
PMC5063153
DOI:
10.1002/jcph.610
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Wiley Icon for PubMed Central
Loading ...
Support Center