Diabetes Mellitus, Type 2Phase 1NCT01018628
A Clinical Study to Assess the Safety and Pharmacokinetics of SRT2379 in Normal Healthy Male Volunteers
A Phase 1 study testing SRT2379 in people with Diabetes Mellitus, Type 2, run by GlaxoSmithKline at 1 site in United Kingdom.
Trial summary
The main purpose of this study is to assess the safety and pharmacokinetics of SRT2379 (25, 75, 250, 500, 1000, 2000, and 3000 mg/day [fasted] and 500 mg/day [fed]) in healthy male volunteers. Read more about this study
- Who is it for?
- Ages 18 to 55 years, men onlyHealthy volunteers can take part
- Conditions the study is for
- Diabetes Mellitus, Type 2
- What is being tested?
- SRT2379
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 64 participants
- Where
- 1 siteUnited Kingdom
- Study dates
- 7 Dec 2009to 6 Aug 2010
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 55 years
- Men only
- Healthy volunteers accepted
- Adult
Who may be able to join
- Be male within the age range of 18 to 55 years.
- Voluntarily sign an Independent Review Board/Research Ethics Committee (IRB/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 by the Principal Investigator to be exclusionary) and performed within 21 days of receiving first dose of test material. In addition, the Principal Investigator will discuss any out-of-range electrolyte values with Sirtris' medical monitor for assessment of clinical significance.
- Have a BMI (Body Mass Index) ≥18.0 and ≤30.0 kg/m^2.
- Be clear of any history of HIV 1 and 2 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.
Show all 9Show fewer
- Have a normal 12-lead ECG or an ECG with abnormality considered to be clinically insignificant. Specifically, the QTcB must be ≤ 450 msec, and no evidence of bundle branch block must be present.
- Have the ability to communicate with the investigative site staff in a manner sufficient to carry out all protocol procedures as described.
- Subject and his 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.
Who cannot join
- 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 clinically significant findings on Screening 24 hour 12-lead Holter.
- 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 has a history of smoking, within 3 months, or is currently a smoker.
Show all 13Show fewer
- Subject has a history of alcoholism, and/or is currently drinking more than three drinks per day on a regular basis [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.
- 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 and dietary supplements or prescription drug therapy for which 5 times the half-life is longer than 21 days (i.e., the Screening period) prior to enrollment into the study. Please note: subjects must refrain from taking herbal or dietary supplements for the duration of the study.
- Unwillingness or inability to follow the procedures outlined in the protocol.
- Subject is mentally or legally incapacitated.
Trial locations and contacts
1 site in 1 country.
United Kingdom1 site
GSK Investigational Site
Merthyr Tydfill, Glamorgan, CF48 4DR
About this study
Official title: A Phase I Randomized, Placebo-Controlled, Single-Blind, Multiple-Dose, Dose-Escalation Clinical Study to Assess the Safety and Pharmacokinetics of SRT2379 in Normal Healthy Male Volunteers
The main purpose of this study is to assess the safety and pharmacokinetics of SRT2379 (25, 75, 250, 500, 1000, 2000, and 3000 mg/day [fasted] and 500 mg/day [fed]) in healthy male volunteers.
The purpose is also to explore the effect of SRT2379 on plasma concentrations of Fibroblast Growth Factor 21 (FGF21) and to identify other possible biomarkers suitable for future clinical assessment of oral SIRT1 activators.
Read the detailed description
Prospective, single center, clinical study of SRT2379 administered orally. Randomized, placebo-controlled, single-blind, multiple-dose, dose-escalation inpatient/outpatient study to assess the safety and pharmacokinetics (PK) of SRT2379 in healthy male volunteers. Approximately sixty-four (64) subjects aged 18-55, who fulfill the inclusion/exclusion criteria, will be enrolled in this study. Eight cohorts of eight subjects each will be examined. Subjects within each cohort will be randomized 6:2 to receive SRT2379 at one of seven escalating doses (A, B, C, D, E, F or G), likely to be 25, 75, 250, 500, 1000, 2000, and 3000 mg/day or placebo. All cohorts will be administered SRT2379 in the fasted state, with the exception of one cohort that will receive one of the stated doses of SRT2379 in the fed state (the dose of SRT2379 administered to subjects in the fed state is planned to be 500 mg, however this may be modified upwards or downwards following evaluation of safety and pharmacokinetic data from earlier cohorts. The fed cohort will be the final cohort dosed in the study.). Two subjects will be dosed on Day 1 of the single dose period with one subject receiving active treatment and one subject receiving placebo. The remainder of subjects within each cohort will be dosed on Day 2 of the single dose period with five subjects receiving active treatment and one subject receiving placebo, assuming that no safety issues arise in the two subjects dosed on Day 1. Subjects will remain on a fixed dose of test material for all dosing days in the study.
Each cohort of subjects will be dosed sequentially approximately three weeks apart for the single dose period, and return to the study unit approximately two weeks after their single dose administration to receive 7 consecutive days of dosing for the multiple-dose period. Each cohort of subjects in the multiple-dose period will be dosed sequentially, approximately, two weeks apart (from multiple dose period Day 7 of preceding cohort to multiple dose period Day 1 dose of the subsequent cohort), allowing for a comprehensive safety assessment prior to initiation of an escalated dose in a subsequent cohort.
Subjects will sign the informed consent form at the Screening Visit. If eligible and willing to participate, subjects will enter into the study. Subjects will have fasted for at least 10 hours overnight and be randomized to receive SRT2379 or placebo (test material). The subject cohort assigned to the fed dose will consume a standardized meal before receiving test material; all other subjects will receive test material in a fasted state. Subjects will be required to stay overnight at the study unit for two nights during the single dose period of the study and subsequently, for the duration of the seven-day multiple-dose period (8 consecutive overnight stays) to assess safety and to gather required PK samples. Subjects will be asked to return to the study center for an End of Study safety assessment approximately 1 week after the last administration of study drug during the multiple-dose period.
Dose escalation will be dependent on safety parameters (physical examination findings, vital signs, ECG studies, adverse events and laboratory values) and PK data.
- Conditions
- Diabetes Mellitus, Type 2
- Being tested
- SRT2379, Placebo
- Medical subject headings
- Diabetes Mellitus, Type 2
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
SRT2379Drug
SRT2379 will be supplied as hard gelatin capsules, with each containing 25 mg or 250 mg of SRT2379 free base equivalent (31 or 310 mg of SRT2379 monosuccinate) without any additive.
PlaceboDrug
For placebo product, the SRT2379 drug substance will be replaced by Microcrystalline Cellulose (Avicel® PH 200) to match the SRT2379 investigational product.
| Study group | Role | What they receive |
|---|---|---|
| Cohort 1 - Dose Level A (25 mg/day) | Active comparator | Cohort 1 will be administered at approximately the same time every dosing day after fasting for 10hrs. Two subjects will be dosed on Day 1 of the single dose period with one subject receiving 25 mg SRT2379 and one subject receiving placebo. The remainder of subjects in this cohort will be dosed on Day 2 of the single dose period with five subjects receiving 25 mg SRT2379 and one subject receiving placebo, assuming that no significant safety issues arise in the two subjects dosed on Day 1. Subjects will remain on a fixed dose of test material for all dosing days in the study. The other cohorts will be dosed sequentially allowing for a comprehensive safety assessment prior to initiation of an escalated dose in a subsequent cohort. Receives: Drug: SRT2379; Drug: Placebo |
| Cohort 2 - Dose Level B (75 mg/day) | Active comparator | Cohort 2 will be administered at approximately the same time every dosing day after fasting for 10hrs. Two subjects will be dosed on Day 1 of the single dose period with one subject receiving 75 mg SRT2379 and one subject receiving placebo. The remainder of subjects in this cohort will be dosed on Day 2 of the single dose period with five subjects receiving 75 mg SRT2379 and one subject receiving placebo, assuming that no significant safety issues arise in the two subjects dosed on Day 1. Subjects will remain on a fixed dose of test material for all dosing days in the study. The other cohorts will be dosed sequentially allowing for a comprehensive safety assessment prior to initiation of an escalated dose in a subsequent cohort. Receives: Drug: SRT2379; Drug: Placebo |
| Cohort 3 - Dose Level C (250 mg/day) | Active comparator | Cohort 3 will be administered at approximately the same time every dosing day after fasting for 10hrs. Two subjects will be dosed on Day 1 of the single dose period with one subject receiving 250 mg SRT2379 and one subject receiving placebo. The remainder of subjects in this cohort will be dosed on Day 2 of the single dose period with five subjects receiving 250 mg SRT2379 and one subject receiving placebo, assuming that no significant safety issues arise in the two subjects dosed on Day 1. Subjects will remain on a fixed dose of test material for all dosing days in the study. The other cohorts will be dosed sequentially allowing for a comprehensive safety assessment prior to initiation of an escalated dose in a subsequent cohort. Receives: Drug: SRT2379; Drug: Placebo |
| Cohort 4 - Dose Level D (500 mg/day) | Active comparator | Cohort 4 will be administered at approximately the same time every dosing day after fasting for 10hrs. Two subjects will be dosed on Day 1 of the single dose period with one subject receiving 500 mg SRT2379 and one subject receiving placebo. The remainder of subjects in this cohort will be dosed on Day 2 of the single dose period with five subjects receiving 500 mg SRT2379 and one subject receiving placebo, assuming that no significant safety issues arise in the two subjects dosed on Day 1. Subjects will remain on a fixed dose of test material for all dosing days in the study. The other cohorts will be dosed sequentially allowing for a comprehensive safety assessment prior to initiation of an escalated dose in a subsequent cohort. Receives: Drug: SRT2379; Drug: Placebo |
| Cohort 5 - Dose Level E (1000 mg/day) | Active comparator | Cohort 5 will be administered at approximately the same time every dosing day after fasting for 10hrs. Two subjects will be dosed on Day 1 of the single dose period with one subject receiving 1000 mg SRT2379 and one subject receiving placebo. The remainder of subjects in this cohort will be dosed on Day 2 of the single dose period with five subjects receiving 1000 mg SRT2379 and one subject receiving placebo, assuming that no significant safety issues arise in the two subjects dosed on Day 1. Subjects will remain on a fixed dose of test material for all dosing days in the study. The other cohorts will be dosed sequentially allowing for a comprehensive safety assessment prior to initiation of an escalated dose in a subsequent cohort. Receives: Drug: SRT2379; Drug: Placebo |
| Cohort 6 - Dose Level F (2000 mg/day) | Active comparator | Cohort 6 will be administered at approximately the same time every dosing day after fasting for 10hrs. Two subjects will be dosed on Day 1 of the single dose period with one subject receiving 2000 mg SRT2379 and one subject receiving placebo. The remainder of subjects in this cohort will be dosed on Day 2 of the single dose period with five subjects receiving 2000 mg SRT2379 and one subject receiving placebo, assuming that no significant safety issues arise in the two subjects dosed on Day 1. Subjects will remain on a fixed dose of test material for all dosing days in the study. The other cohorts will be dosed sequentially allowing for a comprehensive safety assessment prior to initiation of an escalated dose in a subsequent cohort. Receives: Drug: SRT2379; Drug: Placebo |
| Cohort 7 - Dose Level G (3000 mg/day) | Active comparator | Cohort 7 will be administered at approximately the same time every dosing day after fasting for 10hrs. Two subjects will be dosed on Day 1 of the single dose period with one subject receiving 3000 mg SRT2379 and one subject receiving placebo. The remainder of subjects in this cohort will be dosed on Day 2 of the single dose period with five subjects receiving 3000 mg SRT2379 and one subject receiving placebo, assuming that no significant safety issues arise in the two subjects dosed on Day 1. Subjects will remain on a fixed dose of test material for all dosing days in the study. The other cohorts will be dosed sequentially allowing for a comprehensive safety assessment prior to initiation of an escalated dose in a subsequent cohort. Receives: Drug: SRT2379; Drug: Placebo |
| Cohort 8 - Dose Level H (500 mg/day in fed state) | Active comparator | Cohort 8 will be administered at approximately the same time every dosing day and 30 minutes following the start of consumption of a standardized high-fat meal. Two subjects will be dosed on Day 1 of the single dose period with one subject receiving SRT2379 and one subject receiving placebo. The remainder of subjects in this cohort will be dosed on Day 2 of the single dose period with five subjects receiving SRT2379 and one subject receiving placebo, assuming that no significant safety issues arise in the two subjects dosed on Day 1. Subjects will remain on a fixed dose of test material for all dosing days in the study. The dose of SRT2379 administered to subjects in the fed state is planned to be 500 mg, however this may be modified upwards or downwards following evaluation of safety and pharmacokinetic data from earlier cohorts. The fed cohort will be the final cohort dosed in the study. Receives: Drug: SRT2379; Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
To determine the safety and tolerability of SRT2379 (25, 75, 250, 500, 1000, 2000, 3000 mg/day [fasted] and 500 mg/day [fed]) in healthy male volunteers after single and multiple dose administration in the fasted and fed states.
Measured: Single Dose Period PK samples will be collected on Day1 at 0h, 15min, 30min, 1, 2, 4, 8, 12 and 24hrs post-dose. Multiple Dose Period PK samples will be collected on Days1-6 at 0h only, and on Day7 at 0h, 15min, 30min, 1, 2, 4, 8, 12 and 24hrs post-dose.
To determine the pharmacokinetic profile of SRT2379 (25, 75, 250, 500, 1000, 2000, 3000 mg/day [fasted] and 500 mg/day [fed]) in healthy male volunteers after single and multiple dose administration in the fasted and fed states.
Measured: AEs and clinically significant abnormal lab values will be recorded based upon Investigator observation and subject reporting. Safety will be monitored by AEs, VS, physical exam, labs and ECGs during the study.
Secondary outcomes (2)
To explore the effect of SRT2379 (25, 75, 250, 500, 1000, 2000, and 3000 mg/day [fasted] and 500 mg/day [fed]) on plasma concentrations of Fibroblast Growth Factor 21 (FGF21).
Measured: Biomarker samples for plasma FGF-21 analysis will be collected on Day1 (single dose period) and Day7 (multiple dose period) at 0h, 1h, 4h, 8h post-dose and 24hrs post-dose on Days2 (single dose period) and 8 (multiple dose period).
To identify other possible biomarkers suitable for future clinical assessment of oral SIRT1 activators.
Measured: Blood samples for analysis of exploratory biomarkers will be collected on Day1 (single dose period) and Day7 (multiple dose period) at 0h, 1h, 4h, 8h post-dose and 24hrs post-dose on Days2 (single dose period) and 8 (multiple dose period).
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted23 Nov 2009 (estimated)
- Study start7 Dec 2009
- Primary completion6 Aug 2010
- Study completion6 Aug 2010
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Diabetes Mellitus, Type 2Studies of the same condition, open and under way.
- More trials run by GlaxoSmithKlineThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind
- Who is masked
- Participant
- Enrolment
- 64 participants (actual)
Sponsor and investigators
- Lead sponsor
- GlaxoSmithKline
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- GSK Clinical Trials, Study director, GlaxoSmithKline
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01018628
- Sponsor's protocol ID
- 114011
- Status last verified
- Jun 2017
- First submitted
- 19 Nov 2009
- Last updated
- 9 Jun 2017
- Results posted
- No
- Data monitoring committee
- No
- Individual data sharing
- Yes: Patient-level data for this study will be made available through www.clinicalstudydatarequest.com following the timelines and process described on this site.
Publications
GSK has concluded that it is not feasible to publish this study in a peer-reviewed scientific journal because the nature of the study is unlikely to be of interest to a journal. GSK is providing a results summary with a conclusion.
Study at a glance
From the registry record, last updated by the sponsor on 9 Jun 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase I Randomized, Placebo-Controlled, Single-Blind, Multiple-Dose, Dose-Escalation Clinical Study to Assess the Safety and Pharmacokinetics of SRT2379 in Normal Healthy Male Volunteers
- ClinicalTrials.gov ID
- NCT01018628
- Acronym / sponsor ID
- 114011
- Conditions
- Diabetes Mellitus, Type 2
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 64 participants (actual)
- Lead sponsor
- GlaxoSmithKlineIndustry (pharma, biotech, devices)
- Study start
- 7 Dec 2009 (actual)
- Primary completion
- 6 Aug 2010 (actual)
- Study completion
- 6 Aug 2010 (actual)
- First posted
- 23 Nov 2009 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The main purpose of this study is to assess the safety and pharmacokinetics of SRT2379 (25, 75, 250, 500, 1000, 2000, and 3000 mg/day [fasted] and 500 mg/day [fed]) in healthy male volunteers.
The purpose is also to explore the effect of SRT2379 on plasma concentrations of Fibroblast Growth Factor 21 (FGF21) and to identify other possible biomarkers suitable for future clinical assessment of oral SIRT1 activators.
Detailed description
Prospective, single center, clinical study of SRT2379 administered orally. Randomized, placebo-controlled, single-blind, multiple-dose, dose-escalation inpatient/outpatient study to assess the safety and pharmacokinetics (PK) of SRT2379 in healthy male volunteers. Approximately sixty-four (64) subjects aged 18-55, who fulfill the inclusion/exclusion criteria, will be enrolled in this study. Eight cohorts of eight subjects each will be examined. Subjects within each cohort will be randomized 6:2 to receive SRT2379 at one of seven escalating doses (A, B, C, D, E, F or G), likely to be 25, 75, 250, 500, 1000, 2000, and 3000 mg/day or placebo. All cohorts will be administered SRT2379 in the fasted state, with the exception of one cohort that will receive one of the stated doses of SRT2379 in the fed state (the dose of SRT2379 administered to subjects in the fed state is planned to be 500 mg, however this may be modified upwards or downwards following evaluation of safety and pharmacokinetic data from earlier cohorts. The fed cohort will be the final cohort dosed in the study.). Two subjects will be dosed on Day 1 of the single dose period with one subject receiving active treatment and one subject receiving placebo. The remainder of subjects within each cohort will be dosed on Day 2 of the single dose period with five subjects receiving active treatment and one subject receiving placebo, assuming that no safety issues arise in the two subjects dosed on Day 1. Subjects will remain on a fixed dose of test material for all dosing days in the study.
Each cohort of subjects will be dosed sequentially approximately three weeks apart for the single dose period, and return to the study unit approximately two weeks after their single dose administration to receive 7 consecutive days of dosing for the multiple-dose period. Each cohort of subjects in the multiple-dose period will be dosed sequentially, approximately, two weeks apart (from multiple dose period Day 7 of preceding cohort to multiple dose period Day 1 dose of the subsequent cohort), allowing for a comprehensive safety assessment prior to initiation of an escalated dose in a subsequent cohort.
Subjects will sign the informed consent form at the Screening Visit. If eligible and willing to participate, subjects will enter into the study. Subjects will have fasted for at least 10 hours overnight and be randomized to receive SRT2379 or placebo (test material). The subject cohort assigned to the fed dose will consume a standardized meal before receiving test material; all other subjects will receive test material in a fasted state. Subjects will be required to stay overnight at the study unit for two nights during the single dose period of the study and subsequently, for the duration of the seven-day multiple-dose period (8 consecutive overnight stays) to assess safety and to gather required PK samples. Subjects will be asked to return to the study center for an End of Study safety assessment approximately 1 week after the last administration of study drug during the multiple-dose period.
Dose escalation will be dependent on safety parameters (physical examination findings, vital signs, ECG studies, adverse events and laboratory values) and PK data.
Study design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (participant)
- Number of arms
- 8
| Arm | Type | Receives |
|---|---|---|
| Cohort 1 - Dose Level A (25 mg/day) | Active comparator | Drug: SRT2379, Drug: PlaceboCohort 1 will be administered at approximately the same time every dosing day after fasting for 10hrs. Two subjects will be dosed on Day 1 of the single dose period with one subject receiving 25 mg SRT2379 and one subject receiving placebo. The remainder of subjects in this cohort will be dosed on Day 2 of the single dose period with five subjects receiving 25 mg SRT2379 and one subject receiving placebo, assuming that no significant safety issues arise in the two subjects dosed on Day 1. Subjects will remain on a fixed dose of test material for all dosing days in the study. The other cohorts will be dosed sequentially allowing for a comprehensive safety assessment prior to initiation of an escalated dose in a subsequent cohort. |
| Cohort 2 - Dose Level B (75 mg/day) | Active comparator | Drug: SRT2379, Drug: PlaceboCohort 2 will be administered at approximately the same time every dosing day after fasting for 10hrs. Two subjects will be dosed on Day 1 of the single dose period with one subject receiving 75 mg SRT2379 and one subject receiving placebo. The remainder of subjects in this cohort will be dosed on Day 2 of the single dose period with five subjects receiving 75 mg SRT2379 and one subject receiving placebo, assuming that no significant safety issues arise in the two subjects dosed on Day 1. Subjects will remain on a fixed dose of test material for all dosing days in the study. The other cohorts will be dosed sequentially allowing for a comprehensive safety assessment prior to initiation of an escalated dose in a subsequent cohort. |
| Cohort 3 - Dose Level C (250 mg/day) | Active comparator | Drug: SRT2379, Drug: PlaceboCohort 3 will be administered at approximately the same time every dosing day after fasting for 10hrs. Two subjects will be dosed on Day 1 of the single dose period with one subject receiving 250 mg SRT2379 and one subject receiving placebo. The remainder of subjects in this cohort will be dosed on Day 2 of the single dose period with five subjects receiving 250 mg SRT2379 and one subject receiving placebo, assuming that no significant safety issues arise in the two subjects dosed on Day 1. Subjects will remain on a fixed dose of test material for all dosing days in the study. The other cohorts will be dosed sequentially allowing for a comprehensive safety assessment prior to initiation of an escalated dose in a subsequent cohort. |
| Cohort 4 - Dose Level D (500 mg/day) | Active comparator | Drug: SRT2379, Drug: PlaceboCohort 4 will be administered at approximately the same time every dosing day after fasting for 10hrs. Two subjects will be dosed on Day 1 of the single dose period with one subject receiving 500 mg SRT2379 and one subject receiving placebo. The remainder of subjects in this cohort will be dosed on Day 2 of the single dose period with five subjects receiving 500 mg SRT2379 and one subject receiving placebo, assuming that no significant safety issues arise in the two subjects dosed on Day 1. Subjects will remain on a fixed dose of test material for all dosing days in the study. The other cohorts will be dosed sequentially allowing for a comprehensive safety assessment prior to initiation of an escalated dose in a subsequent cohort. |
| Cohort 5 - Dose Level E (1000 mg/day) | Active comparator | Drug: SRT2379, Drug: PlaceboCohort 5 will be administered at approximately the same time every dosing day after fasting for 10hrs. Two subjects will be dosed on Day 1 of the single dose period with one subject receiving 1000 mg SRT2379 and one subject receiving placebo. The remainder of subjects in this cohort will be dosed on Day 2 of the single dose period with five subjects receiving 1000 mg SRT2379 and one subject receiving placebo, assuming that no significant safety issues arise in the two subjects dosed on Day 1. Subjects will remain on a fixed dose of test material for all dosing days in the study. The other cohorts will be dosed sequentially allowing for a comprehensive safety assessment prior to initiation of an escalated dose in a subsequent cohort. |
| Cohort 6 - Dose Level F (2000 mg/day) | Active comparator | Drug: SRT2379, Drug: PlaceboCohort 6 will be administered at approximately the same time every dosing day after fasting for 10hrs. Two subjects will be dosed on Day 1 of the single dose period with one subject receiving 2000 mg SRT2379 and one subject receiving placebo. The remainder of subjects in this cohort will be dosed on Day 2 of the single dose period with five subjects receiving 2000 mg SRT2379 and one subject receiving placebo, assuming that no significant safety issues arise in the two subjects dosed on Day 1. Subjects will remain on a fixed dose of test material for all dosing days in the study. The other cohorts will be dosed sequentially allowing for a comprehensive safety assessment prior to initiation of an escalated dose in a subsequent cohort. |
| Cohort 7 - Dose Level G (3000 mg/day) | Active comparator | Drug: SRT2379, Drug: PlaceboCohort 7 will be administered at approximately the same time every dosing day after fasting for 10hrs. Two subjects will be dosed on Day 1 of the single dose period with one subject receiving 3000 mg SRT2379 and one subject receiving placebo. The remainder of subjects in this cohort will be dosed on Day 2 of the single dose period with five subjects receiving 3000 mg SRT2379 and one subject receiving placebo, assuming that no significant safety issues arise in the two subjects dosed on Day 1. Subjects will remain on a fixed dose of test material for all dosing days in the study. The other cohorts will be dosed sequentially allowing for a comprehensive safety assessment prior to initiation of an escalated dose in a subsequent cohort. |
| Cohort 8 - Dose Level H (500 mg/day in fed state) | Active comparator | Drug: SRT2379, Drug: PlaceboCohort 8 will be administered at approximately the same time every dosing day and 30 minutes following the start of consumption of a standardized high-fat meal. Two subjects will be dosed on Day 1 of the single dose period with one subject receiving SRT2379 and one subject receiving placebo. The remainder of subjects in this cohort will be dosed on Day 2 of the single dose period with five subjects receiving SRT2379 and one subject receiving placebo, assuming that no significant safety issues arise in the two subjects dosed on Day 1. Subjects will remain on a fixed dose of test material for all dosing days in the study. The dose of SRT2379 administered to subjects in the fed state is planned to be 500 mg, however this may be modified upwards or downwards following evaluation of safety and pharmacokinetic data from earlier cohorts. The fed cohort will be the final cohort dosed in the study. |
Who may qualify
- Ages
- 18 to 55 years
- Sex
- Male only
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (9 listed)
- Be male within the age range of 18 to 55 years.
- Voluntarily sign an Independent Review Board/Research Ethics Committee (IRB/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 by the Principal Investigator to be exclusionary) and performed within 21 days of receiving first dose of test material. In addition, the Principal Investigator will discuss any out-of-range electrolyte values with Sirtris' medical monitor for assessment of clinical significance.
- Have a BMI (Body Mass Index) ≥18.0 and ≤30.0 kg/m^2.
- Be clear of any history of HIV 1 and 2 and hepatitis B and C.
Key exclusion criteria (13 listed)
- 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 clinically significant findings on Screening 24 hour 12-lead Holter.
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| SRT2379SRT2379 will be supplied as hard gelatin capsules, with each containing 25 mg or 250 mg of SRT2379 free base equivalent (31 or 310 mg of SRT2379 monosuccinate) without any additive. | Drug | Cohort 1 - Dose Level A (25 mg/day), Cohort 2 - Dose Level B (75 mg/day), Cohort 3 - Dose Level C (250 mg/day), Cohort 4 - Dose Level D (500 mg/day), Cohort 5 - Dose Level E (1000 mg/day), Cohort 6 - Dose Level F (2000 mg/day), Cohort 7 - Dose Level G (3000 mg/day), Cohort 8 - Dose Level H (500 mg/day in fed state) |
| PlaceboFor placebo product, the SRT2379 drug substance will be replaced by Microcrystalline Cellulose (Avicel® PH 200) to match the SRT2379 investigational product. | Drug | Cohort 1 - Dose Level A (25 mg/day), Cohort 2 - Dose Level B (75 mg/day), Cohort 3 - Dose Level C (250 mg/day), Cohort 4 - Dose Level D (500 mg/day), Cohort 5 - Dose Level E (1000 mg/day), Cohort 6 - Dose Level F (2000 mg/day), Cohort 7 - Dose Level G (3000 mg/day), Cohort 8 - Dose Level H (500 mg/day in fed state) |
Primary outcome
To determine the safety and tolerability of SRT2379 (25, 75, 250, 500, 1000, 2000, 3000 mg/day [fasted] and 500 mg/day [fed]) in healthy male volunteers after single and multiple dose administration in the fasted and fed states.
Time frame: Single Dose Period PK samples will be collected on Day1 at 0h, 15min, 30min, 1, 2, 4, 8, 12 and 24hrs post-dose. Multiple Dose Period PK samples will be collected on Days1-6 at 0h only, and on Day7 at 0h, 15min, 30min, 1, 2, 4, 8, 12 and 24hrs post-dose.
To determine the pharmacokinetic profile of SRT2379 (25, 75, 250, 500, 1000, 2000, 3000 mg/day [fasted] and 500 mg/day [fed]) in healthy male volunteers after single and multiple dose administration in the fasted and fed states.
Time frame: AEs and clinically significant abnormal lab values will be recorded based upon Investigator observation and subject reporting. Safety will be monitored by AEs, VS, physical exam, labs and ECGs during the study.
2 secondary outcomes
To explore the effect of SRT2379 (25, 75, 250, 500, 1000, 2000, and 3000 mg/day [fasted] and 500 mg/day [fed]) on plasma concentrations of Fibroblast Growth Factor 21 (FGF21).
Time frame: Biomarker samples for plasma FGF-21 analysis will be collected on Day1 (single dose period) and Day7 (multiple dose period) at 0h, 1h, 4h, 8h post-dose and 24hrs post-dose on Days2 (single dose period) and 8 (multiple dose period).
To identify other possible biomarkers suitable for future clinical assessment of oral SIRT1 activators.
Time frame: Blood samples for analysis of exploratory biomarkers will be collected on Day1 (single dose period) and Day7 (multiple dose period) at 0h, 1h, 4h, 8h post-dose and 24hrs post-dose on Days2 (single dose period) and 8 (multiple dose period).
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 9 Jun 2017.
- BackgroundGSK has concluded that it is not feasible to publish this study in a peer-reviewed scientific journal because the nature of the study is unlikely to be of interest to a journal. GSK is providing a results summary with a conclusion.
- Results for study 114011 can be found on the GSK Clinical Study Register.Link provided by the sponsor.
- Researchers can use this site to request access to anonymised patient level data and/or supporting documents from clinical studies to conduct further research.Link provided by the sponsor.
- Individual participant dataSharing planned: Yes. Patient-level data for this study will be made available through www.clinicalstudydatarequest.com following the timelines and process described on this site.
Related trials for Diabetes Mellitus, Type 2
Not yet recruitingPhase 3
Efficacy and Safety of Once-Weekly SHR-3167 Compared With Once-Daily Insulin Glargine in Adults With Insulin-Naive Type 2 Diabetes
Type 2 Diabetes
Active, not recruiting
Digital Reinforcement of Motivational Interviewing Micro-Skills Among Primary Care Healthcare Professionals
Hypertension (Without Type 2 Diabetes Mellitus)
Recruiting
Investigating Vascular Properties of HEMI and SPG Signals in Individuals With or at Risk for Chronic Kidney Disease
Chronic Kidney Disease, Hypertension (HTN)
Not yet recruitingPhase 3
A Study to Evaluate the Effectiveness and Safety of the Drug AZD6234 for Managing Weight in Adults Who Are Obese or Overweight. These Participants May or May Not Also Have Type 2 Diabetes
Obesity, Overweight
Not yet recruiting
Impact of Endoscopic Sleeve Gastroplasty (ESG) in Obese Adults With Type 2 Diabetes (T2D)
Type 2 Diabetes Mellitus (T2D), Obesity (BMI>30)
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
GSK Clinical Trials study director
GlaxoSmithKline
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing SRT2379 in people with Diabetes Mellitus, Type 2, run by GlaxoSmithKline at 1 site in United Kingdom.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 9 inclusion and 13 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 9 Jun 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
To determine the safety and tolerability of SRT2379 (25, 75, 250, 500, 1000, 2000, 3000 mg/day [fasted] and 500 mg/day [fed]) in healthy male volunteers after single and multiple dose administration in the fasted and fed states. (time frame: Single Dose Period PK samples will be collected on Day1 at 0h, 15min, 30min, 1, 2, 4, 8, 12 and 24hrs post-dose. Multiple Dose Period PK samples will be collected on Days1-6 at 0h only, and on Day7 at 0h, 15min, 30min, 1, 2, 4, 8, 12 and 24hrs post-dose.). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01018628, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 9 Jun 2017.