A Clinical Study to Assess the Effects of SRT2104 Upon Immobilization-Induced Skeletal Muscle Atrophy in Healthy Human Volunteers

NCT01039909 | Withdrawn Phase 1

• 3 other identifiers: 113682SRT-2104-003SIR113682
• Study Type: interventional
• Target: N/A
• Locations: 0 countries
• Sites: N/A

Brief Summary

The main purpose of this study is to investigate the effect of SRT2104 upon energy production in muscle (specifically the maximum amount of energy produced with muscle contraction), how much sugar and fat are stored in the muscle, and the size of the muscle after receiving 2.0 g of SRT2104 or placebo given in capsule form once a day for 28 days including a 14 day knee and lower leg immobilisation period during the final 14 days of dosing. Imaging methods, muscle biopsies and exercise tests will be used in the study to see whether the following measurements change after taking SRT2104 for 28 days, including an immobilised knee and lower leg for the final 14 days of dosing. i) energy reaching the muscles ii) muscle strength iii) changes in the structure of the muscle This study will also investigate the pharmacokinetics, safety and tolerability of 2.0 g of SRT2104 administered orally once daily for 28 consecutive days. The investigation of pharmacokinetics of SRT2104 allows us to gather information regarding: i) how long it takes for the drug to be absorbed and detected in the blood ii) how much we can detect iii) how long we can detect it for iv) how often we need to give the drug to maintain a steady amount in the blood. SRT2104 will be given to healthy subjects aged between 18 and 40 years old. Subjects will participate in this single centre study for approximately 79 days. The study consists of 11 outpatient clinic visits and 4 telephone calls (including a prescreen call to determine whether subjects are interested in participating).

Conditions

Healthy Volunteer; Atrophy, Muscular

Outcome Measures

Primary Outcomes (1)

• To investigate the effect of SRT2104 upon muscle metabolism, specifically mitochondrial function using P31 Magnetic Resonance Spectroscopy following a 14 day leg immobilization within a 28 day SRT2104 dosing period.

  Muscle metabolism, specifically mitochondrial function using P31 Magnetic Resonance, will be assessed on Day -1, Day 15 and Day 28.

Secondary Outcomes (6)

• To investigate muscle metabolism, intra-muscular lipid and glycogen following a 14 day leg immobilization within a 28 day SRT2104 dosing period.

  Muscle metabolism, intra-muscular lipid and glycogen will be assessed on Day -1, Day 15, and Day 28.

• To investigate the effect of SRT2104 upon muscle strength following a 14 day leg immobilization within a 28 day SRT2104 dosing period.

  Muscle Strength is assessed on Day -1, Day 15, and Day 28.

• To investigate the effect of SRT2104 upon muscle structure (total muscle volume and muscle structure) following a 14 day leg immobilization within a 28 day SRT2104 dosing period.

  Muscle Structure will be assessed on Day -1, Day 15, and Day 28.

• To characterize the pharmacokinetic profile of SRT2104 after a single dose and after multiple administrations of SRT2104.

  PK samples will be collected on Day1 at pre-dose, 1, 3, 4, 8, and 24hrs post-dose (Day 2). On Day 15 and Day 28, PK samples will be collected at pre-dose, 1, 3, 4, and 24hrs post-dose (Day 16 and Day 29).

• To assess the safety and tolerability of 2.0 g/day SRT2104 administered orally for a 28 day dosing period.

  For the duration of the study AEs and clinically significant abnormal laboratory values will be recorded based upon investigator observation and subject reporting through a subject diary. Safety will be monitored by AEs, VS, physical exam, labs and ECGs.

Study Arms (2)

Placebo

PLACEBO COMPARATOR

The Placebo treatment group will be administered 8 placebo capsules per day. Placebo will be administered orally once daily for twenty-eight consecutive days. During the clinic visits, the subjects will receive placebo approximately 15 minutes following the start of consumption of a standardized meal. During non-clinic days, the subject will self-administer the test material approximately 15 minutes following the start of consumption of a standardized meal. Test material should be administered with approximately 400 mL of water at approximately the same time every dosing day. Subjects must wait at least 2 hours before consuming additional calories.

Drug: Placebo

2.0g SRT2104

ACTIVE COMPARATOR

The 2.0g SRT2104 treatment group will be administered 8 SRT2104 0.25g capsules per day. 2.0g SRT2104 will be administered orally once daily for twenty-eight consecutive days. During the clinic visits, the subjects will receive SRT2104 approximately 15 minutes following the start of consumption of a standardized meal. During non-clinic days, the subject will self-administer the test material approximately 15 minutes following the start of consumption of a standardized meal. Test material should be administered with approximately 400 mL of water at approximately the same time every dosing day. Subjects must wait at least 2 hours before consuming additional calories.

Drug: SRT2104

Interventions

Placebo DRUG

For the placebo product, SRT2104 drug substance will be replaced by microcrystalline cellulose (Avicel® PH 105) to match the SRT2104 investigational product. Eight size 00 Swedish orange opaque hard gelatin capsules containing placebo are stored in a dosing bottle and provided to all participating subjects for oral ingestion.

Placebo

SRT2104 DRUG

SRT2104 investigational product is a size 00 Swedish Orange opaque hard gelatin capsule containing 0.25 g of SRT2104, a new chemical entity which is supplied as a micronized, yellowish/amber powder. Eight SRT2104 capsules are stored in a dosing bottle and provided to all participating subjects for oral ingestion.

2.0g SRT2104

Eligibility Criteria

• Age: 18 Years - 40 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Subjects may be of any race and gender within the age range of 18 to 40 years inclusive
• 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, or women who underwent tubal ligation. For women in menopause, menopausal status will be confirmed by demonstrating levels of follicle stimulating hormone (FSH) 40 - 138 mIU/ml and oestradiol \< 20 pg/ml at entry, unless this information is available in the subject's medical record. 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 and Medical Monitor
• All male subjects and their partners must agree to use double-barrier birth control or abstinence while participating in the study and for 12 weeks following the last dose of study drug
• Comprehension of the nature and purpose of the study and compliance with the requirement of the entire protocol
• Willingness and ability to provide written informed consent to participate in the study
• Subject is not taking any concomitant medications which may be associated with thrombosis (e.g., estrogens)
• Have a normal 12-lead ECG or one with changes considered to be clinically insignificant on medical review. QTc must be ≤430msec for males and ≤450msec for females
• No prior history of disease markers for hepatitis B and C virus
• Body Mass Index (BMI) 18-32 kg/m\^2 (inclusive)
• Non-smoking status as verified by urinary cotinine levels below 500ng/mL at the screening visit. This can include ex-smokers who have given up smoking for \>5 years.
• Absence of significant disease or clinically significant abnormal laboratory values on the laboratory evaluations, medical history or physical examination during screening; normal end organ function, as determined by the Principal Investigator
• Ability to communicate in person and by telephone in a manner that allows all protocol procedures to be carried out safely and reliably in the opinion of the investigative site staff
• Ability to swallow 8 capsules of study medication with 400 mL of water

You may not qualify if:

• Any major illness in the past three months or any ongoing chronic medical illness which in the opinion of the PI or Medical Monitor could risk subject safety or interpretation of the results
• History of congenital or acquired coagulopathy, including a history of prior venous thrombophlebitis/thromboembolism
• Family history of hypercoagulable state
• History of bleeding diathesis
• Use of anti-platelet agents other than low dose aspirin, (81 mg per day or equivalent) and/or anti-coagulant medications
• Any condition leading to venous stasis, such as varicose veins or congestive heart failure
• Any surgery of the lower extremity during the last 6 months, except for simple excisions of skin lesions
• Air or other confined travel in excess of two hours within the week prior to enrolment or anticipated at anytime during the study
• History of cancer except non-metastatic, non-melanoma skin cancer or carcinoma-in-situ
• History of renal or liver impairment, including nephrotic syndrome
• Presence of pedal edema
• History of gastro-intestinal surgery or has a current gastrointestinal disease which may influence drug absorption
• History, within 3 years, of drug abuse (including benzodiazepines, opioids, amphetamine, cocaine, and THC) or a positive drug result at the screening visit
• A positive pre-study Hepatitis B surface antigen or positive Hepatitis C antibody result within 3 months of Screening
• A positive test for HIV antibody

Sponsors & Collaborators

• GlaxoSmithKline: lead

MeSH Terms

Conditions

Muscular Atrophy

Interventions

SRT2104

Condition Hierarchy (Ancestors)

Neuromuscular Manifestations; Neurologic Manifestations; Nervous System Diseases; Atrophy; Pathological Conditions, Anatomical; Pathological Conditions, Signs and Symptoms; Signs and Symptoms

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: PARALLEL
• Sponsor Type: INDUSTRY

Study Record Dates

• First Submitted: December 23, 2009
• First Posted: December 25, 2009
• Study Start: January 1, 2011
• Primary Completion: February 1, 2011
• Study Completion: February 1, 2011
• Last Updated: April 17, 2015

Record last verified: 2015-04