Clinical trial NCT00938275: A Clinical Study to Assess the Effect of Food and Gender on the Pharmacokinetics of SRT2104 Administered as an Oral Suspension or Capsule Formulation to Normal Healthy Volunteers
Official title: Gender vs. Fed/Fasted State vs. Capsule/Liquid Suspension Formulation Study
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Diabetes Mellitus, Type 2
Lead sponsor: GlaxoSmithKline
Sponsor class: INDUSTRY
Collaborators: name: GlaxoSmithKline
First posted: 2009-07-13
Enrollment: 20
Sex: ALL
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: BASIC_SCIENCE

Brief summary: The primary objective of this study is to assess the pharmacokinetic profile of a single 500 mg dose of SRT2104 administered as an oral suspension and a capsule formulation to normal healthy male and female volunteers in both the fed and fasted state.

The secondary objective is to assess the safety and tolerance of SRT2104 administered as an oral suspension and as a capsule formulation to healthy male and female volunteers in both the fed and fasted state.


Eligibility criteria: Inclusion Criteria:

* Be a healthy male or female within the age range of 18 to 55 years.
* Voluntarily sign a Research Ethics Committee (REC)-approved informed consent form to participate in the study after all relevant aspects of the study have been explained and discussed with the subject.
* Have Hematology, Coagulation, Clinical Chemistry and Urinalysis test results that are within normal, allowable limits (if out-of-range, must be considered clinically significant to be exclusionary) and performed within 21 days of receiving first dose of test material.
* Have a BMI (Body Mass Index) between 18.0 and 30.0 kg/m\^2.
* Be clear of any history of HIV and hepatitis B and C.
* Have no significant disease or clinically significant abnormal laboratory value as deemed by the investigator on the laboratory evaluations, medical history, or physical exam.
* Have a normal 12-lead ECG or an ECG with abnormality considered to be clinically insignificant.
* Have the ability to communicate with the investigative site staff in a manner sufficient to carry out all protocol procedures as described.
* All subjects and their partner must agree to use an acceptable double barrier method for birth control from the Screening visit through 3 months after the last dose of test material.
* All female subjects must be of non-childbearing potential. For the purposes of this study, this is defined as the subject being amenorrheic for at least 12 consecutive months or at least 6 weeks post-surgical bilateral oophorectomy with or without hysterectomy. (Menopausal status will be confirmed by demonstrating levels of follicle stimulating hormone (FSH) of 20 - 138 mIU/ml and oestradiol \< 20 pg/ml at entry. In the event a subject's menopause status has been clearly established (for example, the subject indicates she has been amenorrheic for 10 years), but FSH and/or oestradiol levels are not consistent with a post-menopausal condition, determination of subject eligibility will be at the discretion of the principal investigator following consultation with the sponsor.
* Subject agrees to refrain from consumption of grapefruits and/or grapefruit juice from 7 days prior to day -1 of treatment visit 1 through to the end of subject's final study visit.

Exclusion Criteria:

* Subject has had a major illness in the past three months or any significant ongoing chronic medical illness that the Investigator would deem unfavorable for enrollment.
* Subject has renal or liver impairment.
* Subject has a history of gastro-intestinal surgery or has a current gastrointestinal disease which may influence drug absorption.
* Subject has a history, within 3 years, of drug abuse (including Benzodiazepines, opioids, amphetamine, cocaine, and THC) or a positive drug result at Screening.
* Subject smokes more than 5 cigarettes a day.
* Subject has a history of alcoholism, and/or is currently drinking more than three drinks per day \[one drink is equal to one unit of alcohol (one glass of wine, half a pint of beer, one measure of a spirit)\].
* Subject has participated in a clinical trial within the past three months (defined as three months from the date of last dose of an investigational medicinal product).
* Subject has a history of difficulty in donating blood or accessibility of veins in left or right arm.
* Subject has donated blood (one unit or 350 mL) within three months prior to receiving test material.
* Subject is taking herbal products, over-the-counter medication or prescription drug therapy (with the exception of hormone replacement therapy for female subjects) for which 5 times the half-life is longer than 21 days (i.e., the Screening period) prior to enrollment into the study.

Primary outcomes:
measure: Characterize and compare the pharmacokinetic profile of a single 500 mg dose of SRT2104 administered as an oral suspension and as a capsule formulation.
timeFrame: PK time points: pre-dose (0 hrs); 0.25, 0.5, 0.75, 1.0, 1.5, 2.0, 2.5, 3.0, 4.0, 5.0. 6.0, 8.0, 10, 12, 15, 24, 36, 48, 72 hours post dose.
Secondary outcomes:
measure: Assess the safety and tolerance of SRT2104.
timeFrame: AEs, concomitant medications (as applicable), vital signs, physical examinations, laboratory parameters, and ECG parameters will be collected for the duration of the study.
Other outcomes:
Locations:
city: Merthyr Tydfill
country: United Kingdom
facility: GSK Investigational Site
state: Glamorgan
Study officials:
affiliation: GlaxoSmithKline
name: GSK Clinical Trials
role: STUDY_DIRECTOR
References:
citation: Hoffmann E, Wald J, Lavu S, Roberts J, Beaumont C, Haddad J, Elliott P, Westphal C, Jacobson E. Pharmacokinetics and tolerability of SRT2104, a first-in-class small molecule activator of SIRT1, after single and repeated oral administration in man. Br J Clin Pharmacol. 2013 Jan;75(1):186-96. doi: 10.1111/j.1365-2125.2012.04340.x.