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

NCT00920660 | Completed Phase 1

• 1 other identifier: 113161
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Pulmonary Disease, Chronic Obstructive

Outcome Measures

Primary Outcomes (1)

• 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.

  Duration of treatment periods.

Secondary Outcomes (3)

• 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.

  Duration of treatment periods.

• 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.

  Duration of treatment periods.

• 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.

  Duration of treatment periods.

Study Arms (1)

Treatment Group

EXPERIMENTAL

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; Drug: 0.25g SRT2104; Drug: Prednisolone; Drug: 0.5g SRT2104; Drug: 1g SRT2104; Drug: 2g SRT2104

Interventions

Placebo DRUG

Matching placebo is supplied containing microcrystalline cellulose (Avicel PH 105). Placebo will be administered as eight matched capsules.

Treatment Group

0.25g SRT2104 DRUG

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.

Treatment Group

Prednisolone DRUG

During the last treatment period, subjects will receive 30 mg open-label prednisolone.

Treatment Group

0.5g SRT2104 DRUG

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.

Treatment Group

1g SRT2104 DRUG

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.

Treatment Group

2g SRT2104 DRUG

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.

Treatment Group

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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\].

Sponsors & Collaborators

• GlaxoSmithKline: lead

Study Sites (1)

GSK Investigational Site

Merthyr Tydfill, Glamorgan, CF48 4DR, United Kingdom

Location

Related Links

• Researchers can use this site to request access to anonymised patient level data and/or supporting documents from clinical studies to conduct further research.
• Results for study 113161 can be found on the GSK Clinical Study Register.

MeSH Terms

Conditions

Pulmonary Disease, Chronic Obstructive

Interventions

SRT2104; Prednisolone

Condition Hierarchy (Ancestors)

Lung Diseases, Obstructive; Lung Diseases; Respiratory Tract Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds

Study Officials

• GSK Clinical Trials

  GlaxoSmithKline

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: BASIC SCIENCE
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 12, 2009
• First Posted: June 15, 2009
• Study Start: April 6, 2009
• Primary Completion: June 12, 2009
• Study Completion: June 12, 2009
• Last Updated: July 7, 2017

Record last verified: 2017-07

Data Sharing

• IPD Sharing: Will share

Locations

GB (1)