Ignite Creation Date:
2025-12-26 @ 10:56 AM
Ignite Modification Date:
2025-12-29 @ 12:11 PM
Study NCT ID:
NCT01031108
Status:
COMPLETED
Last Update Posted:
2017-06-20
First Post:
2009-12-10
Is Gene Therapy:
True
Has Adverse Events:
False
Brief Title:
A Clinical Trial to Assess the Safety of Oral SRT2104 and Its Effects on Vascular Dysfunction in Otherwise Healthy Cigarette Smokers and Subjects With Type 2 Diabetes Mellitus
Sponsor:
Sirtris, a GSK Company
Organization:
Study Overview
Official Title:
A Phase I, Randomized, Placebo-Controlled, Crossover Clinical Trial to Assess the Safety of Oral SRT2104 and Its Effects on Vascular Dysfunction in Otherwise Healthy Cigarette Smokers and Subjects With Type 2 Diabetes Mellitus
Status:
COMPLETED
Status Verified Date:
2017-06
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
The primary purpose of this study is to evaluate the safety and tolerability of SRT2104 (2.0 g administered once daily for 28 days) and to examine the effects of SRT2104 (2.0 g administered once daily for 28 days) on reversing vasomotor and fibrinolytic dysfunction in both type 2 diabetes mellitus patients and otherwise healthy cigarette smokers in a fed state.
This study will investigate the effects of SRT2104 on the reduction of platelet activation markers (platelet-monocyte aggregates), and to evaluate the effects of SRT2104 on platelet and monocyte surface markers (P-selectin, CD11b), inflammatory markers (high sensitivity CRP, IL-6, SAA, TNF-α and sCD40L), and markers of oxidative stress (urinary and plasma F2-isoprostanes and nitrotyrosine).
Further goals of this study is to characterize the pharmacokinetic profile of SRT2104 after a single dose and multiple administrations in both type 2 diabetes mellitus patients and otherwise healthy cigarette smokers in a fed state, and to explore the effects of SRT2104 on potential biomarkers of activity for glucose control (HbA1c, glycated albumin and fructosamine) and/or Sirt1 activation.
This study will investigate the effects of SRT2104 on the reduction of platelet activation markers (platelet-monocyte aggregates), and to evaluate the effects of SRT2104 on platelet and monocyte surface markers (P-selectin, CD11b), inflammatory markers (high sensitivity CRP, IL-6, SAA, TNF-α and sCD40L), and markers of oxidative stress (urinary and plasma F2-isoprostanes and nitrotyrosine).
Further goals of this study is to characterize the pharmacokinetic profile of SRT2104 after a single dose and multiple administrations in both type 2 diabetes mellitus patients and otherwise healthy cigarette smokers in a fed state, and to explore the effects of SRT2104 on potential biomarkers of activity for glucose control (HbA1c, glycated albumin and fructosamine) and/or Sirt1 activation.
Detailed Description:
Single-center, randomized, double-blind, placebo-controlled, crossover, safety, activity, and pharmacokinetic (PK) study of 2.0 g of SRT2104 administered orally once daily for 28 consecutive days to two different populations: type 2 diabetic (T2D) subjects on an existing, stable, hypoglycemic regimen and otherwise healthy cigarette smokers (≥ 10cigarettes/day for at least 1 year). Approximately 24 subjects with T2D and 24 otherwise healthy cigarette smokers, aged 18-60 years, who fulfill the inclusion/exclusion criteria, will be enrolled in this study to ensure at least 20 evaluable subjects per population are enrolled. Subjects will be evenly stratified and randomized to receive SRT2104 2.0 g/day or placebo once daily for 28 days. After 28 days, subjects will cross over to receive the other test article for another 28 days of dosing, bringing the total dosing period to 56 days.
Subjects will sign the informed consent form at the screening visit (to occur within 21 days of first dose of test article), and will undergo screening assessments to verify eligibility for the study. If eligible and willing to participate, subjects will return to the clinic on Days -1 and 1 for safety assessments, hematology and biochemistry measurements, platelet monocyte aggregation (PMA) assessment, forearm venous occlusion plethysmography, pulse wave analysis (PWA), pulse wave velocity (PWV) and PK sampling. The first dose of test article will occur on Day 1 after eligibility has been confirmed. After each 28 day dosing period, subjects will return on Day 28 and Day 56 for safety assessments, hematology and biochemistry measurements, forearm plethysmography, PWA, PWV, and PK sampling. Subjects will return to the clinic on Days 2, 15, 29, 43, and 57 for safety assessments and additional PK sampling. Subjects will be asked to complete a study drug diary on a daily basis for compliance and adverse event (AE) monitoring (diabetic subjects will be required to monitor and record their fasting blood glucose in the diary also). An End of Study visit will occur 14 days following the final dose of SRT2104 or placebo on Day 70. A followup safety call will be made to each subject 30 days following their final dose of SRT2104 or placebo (Day 86).
Subjects will sign the informed consent form at the screening visit (to occur within 21 days of first dose of test article), and will undergo screening assessments to verify eligibility for the study. If eligible and willing to participate, subjects will return to the clinic on Days -1 and 1 for safety assessments, hematology and biochemistry measurements, platelet monocyte aggregation (PMA) assessment, forearm venous occlusion plethysmography, pulse wave analysis (PWA), pulse wave velocity (PWV) and PK sampling. The first dose of test article will occur on Day 1 after eligibility has been confirmed. After each 28 day dosing period, subjects will return on Day 28 and Day 56 for safety assessments, hematology and biochemistry measurements, forearm plethysmography, PWA, PWV, and PK sampling. Subjects will return to the clinic on Days 2, 15, 29, 43, and 57 for safety assessments and additional PK sampling. Subjects will be asked to complete a study drug diary on a daily basis for compliance and adverse event (AE) monitoring (diabetic subjects will be required to monitor and record their fasting blood glucose in the diary also). An End of Study visit will occur 14 days following the final dose of SRT2104 or placebo on Day 70. A followup safety call will be made to each subject 30 days following their final dose of SRT2104 or placebo (Day 86).
Study Oversight
Has Oversight DMC:
False
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?: