Clinical Study to Assess the Effects of SRT2104 and Prednisolone on Biomarkers in Blood in Healthy Volunteers
Information source: GlaxoSmithKline
ClinicalTrials.gov processed this data on August 23, 2015 Link to the current ClinicalTrials.gov record.
Condition(s) targeted: Pulmonary Disease, Chronic Obstructive; Healthy Volunteer
Intervention: Placebo (Drug); 0.25g SRT2104 (Drug); Prednisolone (Drug); 0.5g SRT2104 (Drug); 1g SRT2104 (Drug); 2g SRT2104 (Drug)
Phase: Phase 1
Status: Completed
Sponsored by: GlaxoSmithKline Official(s) and/or principal investigator(s): GSK Clinical Trials, Study Director, Affiliation: GlaxoSmithKline
Summary
The primary purpose of this study is to assess the pharmacodynamic effect of single, oral
doses of SRT2104 (250 mg, 500 mg, 1000 mg, 2000 mg) and prednisolone as measured by levels
of ex vivo LPS-induced TNF-alpha production in whole blood of healthy adult subjects.
The secondary purposes of this study are to assess the pharmacodynamic effects of single,
oral doses of SRT2104 (250 mg, 500 mg, 1000 mg, 2000 mg) and prednisolone (30mg) as measured
by levels of IL-6, IL-8 and IL-1beta in whole blood of healthy adult subjects. In addition,
plasma pharmacokinetics, safety and tolerability of SRT2104 following the administration of
single, oral doses of SRT2104 (250 mg, 500 mg, 1000 mg, 2000 mg) in healthy adult subjects
will also be assessed. As exploratory endpoints, transcriptomic profiles, biomarker
exploration, and relationships between plasma SRT2104 levels and ex vivo LPS-induced
TNF-alpha production may also be examined.
Clinical Details
Official title: A Randomised, Double-blind, Placebo-controlled, Multi-way Crossover Study to Assess the Effects of Single Oral Doses of SRT2104 and Prednisolone on Biomarkers in Blood in Healthy Volunteers
Study design: Allocation: Randomized, Endpoint Classification: Pharmacokinetics/Dynamics Study, Intervention Model: Crossover Assignment, Masking: Double Blind (Subject, Caregiver, Investigator), Primary Purpose: Basic Science
Primary outcome: To assess the pharmacodynamic effect of single, oral doses of SRT2104 (250 mg, 500 mg, 1000 mg, and 2000 mg) and prednisolone (30 mg) as measured by levels of ex vivo LPS-induced TNF-alpha production in whole blood of healthy adult subjects.
Secondary outcome: To assess the pharmacodynamic effect of single, oral doses of SRT2104 (250 mg, 500 mg, 1000 mg, and 2000 mg) and prednisolone (30 mg) as measured by levels of IL-6, IL-8 and IL-1beta in whole blood of healthy adult subjects.To assess the plasma pharmacokinetics of SRT2104 following the administration of single, oral doses of SRT2104 (250 mg, 500 mg, 1000 mg, and 2000 mg) in healthy adult subjects. To assess the safety and tolerability of single oral doses of SRT2104 (250 mg, 500 mg, 1000 mg, and 2000 mg) in healthy adult subjects.
Detailed description:
This is a prospective, single center, non-therapeutic clinical study of SRT2104 administered
orally as 250 mg capsules. Randomized, double-blind study to evaluate and compare the
sensitivity of systemic biomarkers, such as ex-vivo LPS-induced TNF-alpha, IL-6, IL-8, and
IL-1beta, to treatment with four-single oral doses of SRT2104 (250 mg, 500 mg, 1000 mg, and
2000 mg), prednisolone (30 mg), and placebo in healthy adult volunteers. Twenty (20)
subjects (males and females of non-childbearing potential) aged 18-60, who fulfill the
inclusion/exclusion criteria, will be enrolled in this study to achieve a minimum of 15
evaluable subjects. Each subject will participate in 6 treatment periods. For each treatment
period subjects will fast for at least 10 hours overnight. After pre-dosing procedures,
subjects will consume a standard, non-high-fat (approximately 650 kcal with approximately
30% of calories derived from fat) meal 15-30 minutes prior to receiving test material.
During the first five treatment periods, subjects will receive a single dose of SRT2104 or
matched placebo; during the last treatment period, subjects will receive 30 mg open-label
prednisolone. Assessments will be performed until 24 hours post dose in each treatment
period.
Subjects will be asked to sign the informed consent form(s) at the screening visit. If
eligible and willing to participate, subjects will enter into the study. Subjects will be
required to attend the research unit in a fasted state (at least 10 hours without food) on
six separate occasions (treatment visits) during the study. There will be at least a 7-day
washout period between treatment visits.
During the first five treatment visits, subjects will receive one of the following five
treatments:
A. 250 mg SRT2104 administered as eight oral capsules (one active SRT2104 250 mg capsule +
seven placebo capsules) B. 500 mg SRT2104 administered as eight oral capsules (two active
SRT2104 250 mg capsules + six placebo capsules) C. 1000 mg SRT2104 administered as eight
oral capsules (four active SRT2104 250 mg capsules + four placebo capsules) D. 2000 mg
SRT2104 administered as eight oral capsules (eight active SRT2104 250 mg capsules + zero
placebo capsules) E. Eight placebo capsules
During the last treatment visit, subjects will receive 30 mg of open-label prednisolone
tablets.
Subjects will be required to return to the research unit 24 hours after dosing in each
treatment period in order to gather the required PK and PD samples. Subjects will be asked
to return to the study center for an End of Study safety assessment 7 to 10 days after the
last treatment visit.
Eligibility
Minimum age: 18 Years.
Maximum age: 60 Years.
Gender(s): Both.
Criteria:
Inclusion Criteria:
- The study is open to healthy male and female volunteers, 18 to 60 years of age, with
hematology, clinical chemistry, electrolytes, serology, and urinalysis tests within
normal, allowable limits using normal laboratory values (if out-of-range values
result, they must be considered clinically significant by the Investigator to be
exclusionary) and performed within 21 days to 1 day of receiving the first dose of
test material.
- All male subjects and their female partners must be willing and able to use an
acceptable form of double-barrier birth control (hormonal or double barrier method of
birth control [condom and occlusive cap (diaphragm or cervical/vault caps) with
spermicidal foam, gel, film, cream, or suppository]; true abstinence) for at least 12
weeks after the last treatment dose.
- All female subjects must be of non-childbearing potential. For the purposes of this
study, non-childbearing potential is defined as pre-menopausal females with a
documented tubal ligation or hysterectomy; or postmenopausal defined as 12 months of
spontaneous amenorrhea [in questionable cases a blood sample with simultaneous
follicle stimulating hormone (FSH) > 40 MlU/ml and estradiol < 40 pg/ml (<140 pmol/L)
is confirmatory]. [Females on hormone replacement therapy (HRT) and whose menopausal
status is in doubt will be required to use adequate contraception (hormonal or double
barrier method of birth control [condom and occlusive cap (diaphragm or
cervical/vault caps) with spermicidal foam, gel, film, cream, or suppository]; true
abstinence) for the duration of the study dosing and for at least 12 weeks after the
last treatment dose, if they wish to continue their HRT during the study. Otherwise,
they must discontinue HRT to allow confirmation of post-menopausal status prior to
study enrollment. For most forms of HRT, at least 2-4 weeks will elapse between the
cessation of therapy and the blood draw; this interval depends on the type and dosage
of HRT. Following confirmation of their post-menopausal status, they can resume use
of HRT during the study without use of a contraceptive method].
Locations and Contacts
GSK Investigational Site, Merthyr Tydfill, Glamorgan CF48 4DR, United Kingdom
Additional Information
Starting date: April 2009
Last updated: February 17, 2011
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