Clinical Study to Assess the Safety and Pharmacokinetics of SRT2104 in Type 2 Diabetic Human Subjects
Trial overview
Number of participants with any adverse event (AE), serious adverse event (SAE), AE related to study medication, AE leading to discontinuation and fatal AE of death
Timeframe: Up to Follow-up (58 days)
Number of participants with AE by intensity of mild, moderate and severe
Timeframe: Up to Follow-up (58 days)
Mean change from Baseline in weight over time
Timeframe: Baseline (Day 1) and up to Day 35
Change from Baseline in vital sign parameter of systolic blood pressure (SBP) and diastolic blood pressure (DBP) over time
Timeframe: Baseline (Day 1, pre-dose) and up to Day 35
Change from Baseline in vital sign parameter of heart rate (HR) over time
Timeframe: Baseline (Day 1, pre-dose) and up to Day 35
Change from Baseline in vital sign parameter of respiratory rate (RR) over time
Timeframe: Baseline (Day 1, pre-dose) and up to Day 35
Change from Baseline in vital sign parameter of temperature over time
Timeframe: Baseline (Day 1, pre-dose) and up to Day 35
Change from Baseline in electrocardiogram (ECG) values over time
Timeframe: Baseline (Day 1, pre-dose) and up to Day 35
Change from Baseline in hematology parameters of basophils, eosinophils, lymphocytes, monocytes, neutrophils, platelet and white blood cell (WBC) count over time
Timeframe: Baseline (Day 1) and up to Day 35
Change from Baseline in hematology parameter of red blood cell (RBC) count over time
Timeframe: Baseline (Day 1) and up to Day 35
Change from Baseline in hematology parameter of hematocrit over time
Timeframe: Baseline (Day 1) and up to Day 35
Change from Baseline in hematology parameter of hemoglobin over time
Timeframe: Baseline (Day 1) and up to Day 35
Change from Baseline in hematology parameter of mean corpuscular hemoglobin over time
Timeframe: Baseline (Day 1) and up to Day 35
Change from Baseline in hematology parameter of mean corpuscular hemoglobin concentration over time
Timeframe: Baseline (Day 1) and up to Day 35
Change from Baseline in hematology parameter of mean corpuscular volume over time
Timeframe: Baseline (Day 1) and up to Day 35
Change from Baseline in coagulation parameters of activated partial thromplastin time (aPTT) and prothrombin time (PT) over time
Timeframe: Baseline (Day 1), Day 28 and Day 35
Change from Baseline in coagulation parameter of international normalized ratio over time
Timeframe: Baseline (Day 1), Day 28 and Day 35
Change from Baseline in chemistry parameters of alanine aminotransferase (ALT), aspartate aminotrasferase (AST), alkaline phosphatase (ALP), creatinine phosphokinase and lactate dehydrogenase (LDH) over time
Timeframe: Baseline (Day 1) and up to Day 35
Change from Baseline in chemistry parameter of bicarbonate, blood urea nitrogen (BUN), calcium, chloride, magnesium, phosphate, potassium and sodium over time
Timeframe: Baseline (Day 1) and up to Day 35
Change from Baseline in chemistry parameter of direct bilirubin, indirect bilirubin, serum creatinine, total bilirubin and uric acid over time
Timeframe: Baseline (Day 1) and up to Day 35
Change from Baseline in chemistry parameter of lipid profile over time
Timeframe: Baseline (Day 1) and up to Day 35
Change from Baseline in chemistry parameter of albumin and total protein over time
Timeframe: Baseline (Day 1) and up to Day 35
Change from Baseline in urinalysis parameter of specific gravity over time
Timeframe: Baseline (Day 1) and up to Day 35
Change from Baseline in urinalysis parameter of pH over time
Timeframe: Baseline (Day 1) and up to Day 35
Area under plasma concentration curve from time 0 to last measurable time point (AUC 0-t), from time 0 to infinity (AUC 0-infinity) and from time 0 to trough concentration (AUC 0-τ) of SRT2104 on Day 1 and Day 28
Timeframe: Day 1 (pre-dose, 15 and 30 minutes, 1, 2, 3, 4, 8 and 12 hour post-dose), Day 2 (24 hour post-Day 1 dose), Day 8, 15 and 22 (pre-dose), Day 28 (pre-dose, and 15 and 30 minutes, 1, 2, 3, 4, 8 and 12 hour post-dose) and Day 29 (24 hour post-Day 28)
Observed maximum plasma concentration (Cmax) of SRT2104 at Day 1 and Day 28
Timeframe: Day 1 (pre-dose, 15 and 30 minutes, 1, 2, 3, 4, 8 and 12 hour post-dose), Day 2 (24 hour post-Day 1 dose), Day 8, 15 and 22 (pre-dose), Day 28 (pre-dose, and 15 and 30 minutes, 1, 2, 3, 4, 8 and 12 hour post-dose) and Day 29 (24 hour post-Day 28 dose)
Time to Cmax (Tmax) at Day 1 and Day 28
Timeframe: Day 1 (pre-dose, 15 and 30 minutes, 1, 2, 3, 4, 8 and 12 hour post-dose), Day 2 (24 hour post-Day 1 dose), Day 8, 15 and 22 (pre-dose), Day 28 (pre-dose, and 15 and 30 minutes, 1, 2, 3, 4, 8 and 12 hour post-dose) and Day 29 (24 hour post-Day 28 dose)
Terminal elimination half life (T1/2) of SRT2104 at Day 1 and Day 28
Timeframe: Day 1 (pre-dose, 15 and 30 minutes, 1, 2, 3, 4, 8 and 12 hour post-dose), Day 2 (24 hour post-Day 1 dose), Day 8, 15 and 22 (pre-dose), Day 28 (pre-dose, and 15 and 30 minutes, 1, 2, 3, 4, 8 and 12 hour post-dose) and Day 29 (24 hour post-Day 28 dose)
Apparent total clearance of SRT2104 from plasma after oral administration (CL/F) on Day 1 and Day 28
Timeframe: Day 1 (pre-dose, 15 and 30 minutes, 1, 2, 3, 4, 8 and 12 hour post-dose), Day 2 (24 hour post-Day 1 dose), Day 8, 15 and 22 (pre-dose), Day 28 (pre-dose, and 15 and 30 minutes, 1, 2, 3, 4, 8 and 12 hour post-dose) and Day 29 (24 hour post-Day 28 dose)
Apparent volume of distribution after oral administration (Vd/F) at Day 1 and Day 28
Timeframe: Day 1 (pre-dose, 15 and 30 minutes, 1, 2, 3, 4, 8 and 12 hour post-dose), Day 2 (24 hour post-Day 1 dose), Day 8, 15 and 22 (pre-dose), Day 28 (pre-dose, and 15 and 30 minutes, 1, 2, 3, 4, 8 and 12 hour post-dose) and Day 29 (24 hour post-Day 28 dose)
Mean fasting plasma glucose (FPG) levels over time
Timeframe: Up to Day 35
Change from Baseline in FPG levels over time
Timeframe: Baseline (Day 1) and up to Day 35
Mean fasting plasma insulin (FPI) levels over time
Timeframe: Up to Day 35
Change from Baseline in FPI over time
Timeframe: Baseline (Day 1) and up to Day 35
Mean post-prandial glucose (PPG) and post-prandial insulin (PPI) levels at Day 28
Timeframe: Day 28
Change from Baseline in PPG and PPI levels at Day 28
Timeframe: Baseline (Day 1) and Day 28
Mean glycosylated hemoglobin A (HbA1c) levels on Day 28
Timeframe: Day 28
Change from Baseline in HbA1c levels at Day 28
Timeframe: Baseline (Day 1) and Day 28
AUC from time 0 to 1 h (AUC 0-1) and AUC from time 0 to 2 h (AUC 0-2) for PPG and PPI at Day 1 and Day 28
Timeframe: Day 1 (30 minutes, 60 minutes and 2 hour) and Day 28 (30 minutes, 60 minutes and 2 hour)
Mean fructosamine levels at Day 1 and Day 28
Timeframe: Day 1 and Day 28
Change from Baseline in fructosamine levels at Day 28
Timeframe: Baseline (Day 1) and Day 28
Mean homeostatic model assessment-insulin resistance (HOMA-IR) at Day 1 and Day 28
Timeframe: Day 1 and Day 28
Change from Baseline in HOMA-IR at Day 28
Timeframe: Baseline (Day 1) and Day 28
Mean HOMA-percentage cell beta function at Day 1 and Day 28
Timeframe: Day 1 and Day 28
Change from Baseline in HOMA-percentage of beta cell function at Day 28
Timeframe: Baseline (Day 1) and Day 28
Participation criteria
- 1. Subjects of any race and gender within the age range of 30 to 70 years.
- 2. All female subjects must be of non-child-bearing 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. 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
- 1. Any major illness in the past three months or any significant ongoing chronic medical illness not related to diabetes
- 2. Renal or liver impairment, defined as serum creatinine level of ≥ 1.4 mg/dL for females and ≥ 1.5 mg/dL for males, and greater than two times the upper limit of normal for liver enzymes, respectively.
- 1. Subjects of any race and gender within the age range of 30 to 70 years. 2. All female subjects must be of non-child-bearing 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. 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 3. All male subjects must agree with their partners to use double-barrier birth control or abstinence while participating in the study and for 12 weeks following the last dose of study drug. 4. Willingness to provide written informed consent to participate in the study 5. HbA1c ≥ 7.5 and ≤ 10.5 6. Fasting glucose ≥ 160 and ≤ 240 mg/dL 7. Body Mass Index (BMI) ≥ 25.0 kg/m^2 and ≤ 40.0 kg/m^2 8. On stable metformin medication for at least 3 months (≥ 1.0 g/day) prior to Screening 9. No prior history of HIV 1 or 2 10. Absence of disease markers for hepatitis B & C virus 11. Absence of significant disease or clinically significant abnormal laboratory values on the laboratory evaluations, medical history or physical examination during the screening; normal end organ function 12. Have a normal 12-lead ECG or one with abnormality considered to be clinically insignificant 13. Have a normal chest X-ray (P. A. View) or one with abnormality considered to be clinically insignificant 14. Comprehension of the nature and purpose of the study and compliance with the requirement of the entire protocol
- 1. Any major illness in the past three months or any significant ongoing chronic medical illness not related to diabetes 2. Renal or liver impairment, defined as serum creatinine level of ≥ 1.4 mg/dL for females and ≥ 1.5 mg/dL for males, and greater than two times the upper limit of normal for liver enzymes, respectively. 3. History of or current gastro-intestinal diseases influencing drug absorption, except for appendectomy 4. History, within 3 years, of drug abuse (including Benzodiazepines, opioids, amphetamine, cocaine, and THC) 5. History of alcoholism (more than two years), moderate drinkers (more than three drinks per day) or having consumed alcohol within 48 hrs prior to dosing [one drink is equal to one unit of alcohol (one glass wine, half pint beer, one measure of spirit)] 6. Participation in any clinical trial within the past three months 7. History of difficulty in donating blood or accessibility of veins in left or right arm 8. Donation of blood (one unit or 350 ml) within three months prior to receiving the first dose of test material 9. Use of any prescription drug therapy, with exception of any prescription medication administered at a stable dose for at least 6 weeks prior to Screening, provided the medication is not contraindicated by the metformin label 10. Use of any alternate anti-diabetic therapy, except metformin, within three months of enrollment
Trial location(s)
Study documents
If you wish to request for full study report, please contact - [email protected]
Results overview
Results posted on ClinicalTrials.gov
Plain language summaries
Plain language summaries of clinical trial results for Phase 2-4 clinical trials that were initiated on or after January 2022 will be posted by GSK within one year following study completion.