Clinical Study to Assess the Effects of SRT2104 and Prednisolone on Biomarkers in Blood in Healthy Volunteers

This study has been completed.
Sponsor:
Information provided by:
GlaxoSmithKline
ClinicalTrials.gov Identifier:
NCT00920660
First received: June 12, 2009
Last updated: February 17, 2011
Last verified: February 2011
  Purpose

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.


Condition Intervention Phase
Pulmonary Disease, Chronic Obstructive
Healthy Volunteer
Drug: Placebo
Drug: 0.25g SRT2104
Drug: Prednisolone
Drug: 0.5g SRT2104
Drug: 1g SRT2104
Drug: 2g SRT2104
Phase 1

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Pharmacokinetics/Dynamics Study
Intervention Model: Crossover Assignment
Masking: Double Blind (Subject, Caregiver, Investigator)
Primary Purpose: Basic Science
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

Resource links provided by NLM:


Further study details as provided by GlaxoSmithKline:

Primary Outcome Measures:
  • 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. [ Time Frame: Duration of treatment periods. ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • 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. [ Time Frame: Duration of treatment periods. ] [ Designated as safety issue: No ]
  • 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. [ Time Frame: Duration of treatment periods. ] [ Designated as safety issue: No ]
  • 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. [ Time Frame: Duration of treatment periods. ] [ Designated as safety issue: No ]

Enrollment: 20
Study Start Date: April 2009
Study Completion Date: June 2009
Primary Completion Date: June 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Treatment Group

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. At approximately the same time every morning, subjects will consume a standard, non-high-fat meal (approximately 650 kcal with 30% of calories derived from fat). Test material (per treatment) will be administered within 15-30 minutes following the meal. 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 treatments in the form of 8 capsules: 0.25g SRT2104, 0.5g SRT2104, 1g SRT2104, 2g SRT2104, or placebo.

During the last treatment visit, subjects will receive 30 mg of open-label prednisolone tablets.

Drug: Placebo
Matching placebo is supplied containing microcrystalline cellulose (Avicel PH 105). Placebo will be administered as eight matched capsules.
Drug: 0.25g SRT2104
SRT2104 will be supplied as hard gelatin capsules, with each containing 250 mg. The 0.25g SRT2104 treatment visit will be administered as one SRT2104 capsule with 7 placebo capsules. Dosing will take place during one of the 6 treatment visits.
Drug: Prednisolone
During the last treatment period, subjects will receive 30 mg open-label prednisolone.
Drug: 0.5g SRT2104
SRT2104 will be supplied as hard gelatin capsules, with each containing 250 mg. The 0.5g SRT2104 treatment visit will be administered as two SRT2104 capsules with 6 placebo capsules. Dosing will take place during one of the 6 treatment visits.
Drug: 1g SRT2104
SRT2104 will be supplied as hard gelatin capsules, with each containing 250 mg. The 1g SRT2104 treatment visit will be administered as four SRT2104 capsules with four placebo capsules. Dosing will take place during one of the 6 treatment visits.
Drug: 2g SRT2104
SRT2104 will be supplied as hard gelatin capsules, with each containing 250 mg. The 2g SRT2104 treatment visit will be administered as eight SRT2104 capsules. Dosing will take place during one of the 6 treatment visits.

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

Ages Eligible for Study:   18 Years to 60 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
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].
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00920660

Locations
United Kingdom
GSK Investigational Site
Merthyr Tydfill, Glamorgan, United Kingdom, CF48 4DR
Sponsors and Collaborators
GlaxoSmithKline
Investigators
Study Director: GSK Clinical Trials GlaxoSmithKline
  More Information

No publications provided

Responsible Party: Cheri Hudson; Clinical Disclosure Advisor, GSK Clinical Disclosure
ClinicalTrials.gov Identifier: NCT00920660     History of Changes
Other Study ID Numbers: 113161
Study First Received: June 12, 2009
Last Updated: February 17, 2011
Health Authority: United Kingdom: Medicines and Healthcare Products Regulatory Agency

Additional relevant MeSH terms:
Chronic Disease
Lung Diseases
Pulmonary Disease, Chronic Obstructive
Disease Attributes
Pathologic Processes
Respiratory Tract Diseases
Lung Diseases, Obstructive
Methylprednisolone acetate
Prednisolone acetate
Prednisolone
Methylprednisolone
Methylprednisolone Hemisuccinate
Prednisolone hemisuccinate
Prednisolone phosphate
Anti-Inflammatory Agents
Therapeutic Uses
Pharmacologic Actions
Glucocorticoids
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Antineoplastic Agents, Hormonal
Antineoplastic Agents
Antiemetics
Autonomic Agents
Peripheral Nervous System Agents
Central Nervous System Agents
Gastrointestinal Agents
Neuroprotective Agents
Protective Agents

ClinicalTrials.gov processed this record on August 26, 2014