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Short-term treatment with a novel HIF-prolyl hydroxylase inhibitor (GSK1278863) failed to improve measures of performance in subjects with claudication-limited peripheral artery disease
- Source :
- Vascular Medicine. 19:473-482
- Publication Year :
- 2014
- Publisher :
- SAGE Publications, 2014.
-
Abstract
- Hypoxia inducible factor (HIF) stabilization by HIF-prolyl hydroxylase (PHD) inhibitors may improve ischemic conditions such as peripheral artery disease (PAD). This multicenter, randomized, placebo-controlled study evaluated the safety and efficacy of GSK1278863 (an oral PHD inhibitor) in subjects with PAD. The study assessed two active treatment paradigms: single dosing and subchronic daily dosing (300 mg single dose and 15 mg daily for 14 days, respectively). Neither regimen improved exercise performance compared with placebo (change from baseline in the 6-minute walk test (6MWT; feet), (GSK1278863, placebo): single dose (–46, –44), p=0.96; repeat dose (9, 8), p=0.99; change in number of contractions to onset of claudication (goniometry): single dose (4, –1), p=0.053; repeat dose (–2, 1), p=0.08). A calf-muscle biopsy substudy showed no increases in mRNA or protein levels of HIF target genes. More subjects receiving GSK1278863 than placebo experienced adverse events, particularly following the 300 mg single dose. Thus, assessing the safety of GSK1278863 in this setting would require a larger population exposed to the agent for a longer duration. These data do not support a benefit of GSK1278863 in PAD using the regimens tested. ClinicalTrials.gov Identifier: NCT01673555
- Subjects :
- Adult
Male
medicine.medical_specialty
Time Factors
Population
Urology
Walking
Placebo
Peripheral Arterial Disease
medicine
Humans
Dosing
Muscle, Skeletal
education
Adverse effect
Aged
Aged, 80 and over
education.field_of_study
business.industry
Prolyl-Hydroxylase Inhibitors
HIF prolyl-hydroxylase inhibitor
Intermittent Claudication
Middle Aged
Surgery
Regimen
Treatment Outcome
Hypoxia-inducible factors
Exercise Test
Quality of Life
Female
medicine.symptom
Cardiology and Cardiovascular Medicine
Claudication
business
Subjects
Details
- ISSN :
- 14770377 and 1358863X
- Volume :
- 19
- Database :
- OpenAIRE
- Journal :
- Vascular Medicine
- Accession number :
- edsair.doi.dedup.....55d22d721b9f7b58d1eeaa2e32ad7802