Investigate the Efficacy and Safety of GSK1070806 in Obese Subjects with T2DMT2DM
Trial overview
Change from Baseline in fasting plasma glucose (FPG) level on Days 29, 57, and 85
Timeframe: Baseline (Day 1) and Days 29, 57, and 85
Change from Baseline in weighted mean glucose area under the concentration-time curve from time zero (pre-dose) to 4 hours (AUC[0 - 4hrs]) post-Mixed Meal Test (MMT) on Days 29, 57, and 85
Timeframe: Baseline (Day 1), Days 29, 57, and 85
Number of participants with any adverse event (AE) and any serious adverse event (SAE)
Timeframe: Up to 210 days
Albumin and total protein values at Screening; Days 1 (pre-dose and 4 hr post-dose), 4, 9, 14, 21, 29 (pre-dose and 4 hr post-dose), 32, 42, 57, 85, 120, and 165; and follow-up
Timeframe: Up to 210 days
Alkaline phosphatase (ALP),Alanine aminotransferase (ALT),aspartate aminotransferase (AST),gamma glutamyl transferase (GGT) values at Screening; Days 1 (pre-dose, 4 hr post-dose),4,9,14,21,29 (pre-dose, 4 hr postdose), 32, 42, 57, 85,120,165, follow up
Timeframe: Up to 210 days
Total bilirubin (TB), direct bilirubin (DB), uric acid, and creatinine values at Screening; Days 1 (pre-dose and 4 hr post-dose), 4, 9, 14, 21, 29 (pre-dose and 4 hr post-dose), 32, 42, 57, 85, 120, and 165; and follow-up
Timeframe: Up to 210 days
Clinical laboratory parameters at Screening; Days 1 (pre-dose on Day 1 and 4 hour post-dose), 4, 9, 14, 21, 29 (pre-dose and 4 hour post-dose), 32, 42, 57, 85, 120, and 165, and at Day 210
Timeframe: Up to 210 days
Total cholesterol/HDL ratio (TC/HDL ratio), HDL/LDL ratio, and triglyceride/HDL ratio (TG/HDL ratio) values at Screening; Days 1 (pre-dose and 4 hr post-dose), 4, 9, 14, 21, 29 (pre-dose and 4 hr post-dose), 32, 42, 57, 85, 120, and 165; and follow-up
Timeframe: Up to 210 days
Glomerular filtration rate (GFR) values at Screening; Days 1 (pre-dose and 4 hr post-dose), 4, 9, 14, 21, 29 (pre-dose and 4 hr post-dose), 32, 42, 57, 85, 120, and 165; and follow-up
Timeframe: Up to 210 days
Hematological parameters at Screening; Days 1 (pre-dose and 4 hr post-dose), 4, 9, 14, 21, 29 (pre-dose and 4 hr post-dose), 32, 42, 57, 85, 120, and 165; and Day 210
Timeframe: Up to 210 days
Hemoglobin and mean corpuscle hemoglobin concentration (MCHC) values at Screening; Days 1 (pre-dose and 4 hr post-dose), 4, 9, 14, 21, 29 (pre-dose and 4 hr post-dose), 32, 42, 57, 85, 120, and 165; and follow-up
Timeframe: Up to 210 Days
Hematocrit values at Screening; Days 1 (pre-dose and 4 hr post-dose), 4, 9, 14, 21, 29 (pre-dose and 4 hr post-dose), 32, 42, 57, 85, 120, and 165; and follow-up
Timeframe: Up to 210 days
Mean corpuscle hemoglobin (MCH) values at Screening; Days 1 (pre-dose and 4 hr post-dose), 4, 9, 14, 21, 29 (pre-dose and 4 hr post-dose), 32, 42, 57, 85, 120, and 165; and follow-up
Timeframe: Up to 210 days
Mean corpuscle volume (MCV) values at Screening; Days 1 (pre-dose and 4 hr post-dose), 4, 9, 14, 21, 29 (pre-dose and 4 hr post-dose), 32, 42, 57, 85, 120, and 165; and follow-up
Timeframe: Up to 210 days
Red blood cell (RBC) count values at Screening; Days 1 (pre-dose and 4 hr post-dose), 4, 9, 14, 21, 29 (pre-dose and 4 hr post-dose), 32, 42, 57, 85, 120, and 165; and follow-up
Timeframe: Up to 210 days
Mean systolic blood pressure (SBP) and diastolic blood pressure (DBP) values at Screening; Days 1 (pre-dose and 4 hr post-dose), 4, 9, 14, 21, 29 (pre-dose and 4 hr post-dose), 32, 42, 57, 85, 120, and 165; and follow-up
Timeframe: Up to 210 days
Heart rate (HR) values at Screening; Days 1 (pre-dose and 4 hr post-dose), 4, 9, 14, 21, 29 (pre-dose and 4 hr post-dose), 32, 42, 57, 85, 120, and 165; and Day 210
Timeframe: Up to 210 days
Respiration rate (RR) values at Screening; Days 1 (pre-dose and 4 hr post-dose), 4, 9, 14, 21, 29 (pre-dose and 4 hr post-dose), 32, 42, 57, 85, 120, and 165; and Day 210
Timeframe: Up to 210 days
Body temperature values at Screening; Days 1 (pre-dose and 4 hr post-dose), 4, 9, 14, 21, 29 (pre-dose and 4 hr post-dose), 32, 42, 57, 85, 120, and 165; and Day 210
Timeframe: Up to 210 days
Electrocardiogram (ECG) measurements at Screening, Day 1 (pre-dose and 1 hr and 4 hr post-dose), and Day 29 (pre-dose and 1 hr and 4 hr post-dose)
Timeframe: Screening, Day 1 (pre-dose; 1 and 4 hr post-dose), and Day 29 (pre-dose; 1 hr and 4 hr post-dose)
Change from Baseline in glycohemoglobin A1c (% HbA1c) at Days 29, 57, 85, 120 and follow-up
Timeframe: Baseline (Day 1), Days 29, 57, 85, 120 and follow-up
Change from Baseline in fasting blood insulin from the post-mixed meal test (MMT) at pre-meal and 15, 30, 60, 90, 120, 180, and 250 minutes post-meal at Days 29, 57, and 85
Timeframe: Baseline (pre-dose on Day 1), pre-meal; and 15, 30, 60, 90, 120, 180, and 250 post-meal at Days 29, 57, and 85
Change from Baseline in C-peptide levels from the post-MMT (MMT) at pre-meal and 15, 30, 60, 90, 120, 180, and 250 minutes post-meal at Days 29, 57, and 85
Timeframe: Baseline (pre-dose on Day 1), pre-meal; and 15, 30, 60, 90, 120, 180, and 250 minutes post-meal at Days 29, 57, and 85
Change from Baseline in weighted mean insulin level (AUC[0-4hrs]) post-MMT on Days 29, 57, and 85
Timeframe: Baseline (pre-dose on Day 1), Days 29, 57, and 85
Change from Baseline in weighted mean C-peptide levels (AUC[0-4hrs]) post-MMT on Days 29, 57, and 85
Timeframe: Baseline (pre-dose on Day 1), Days 29, 57, and 85
Change from Baseline in derived measures of insulin sensitivity (homeostasis model assessment [HOMA]-%S) and beta cell function (HOMA-%B) for insulin and C-peptide at Days 29, 57, and 85
Timeframe: Baseline (pre-dose on Day 1), Days 29, 57, and 85
Area under the concentration-time curve over the dosing interval (AUC[0-tau])
Timeframe: Baseline (pre-dose on Day 1), 1 and 4 hours post-dose on Day 1, Days 4 and 14, pre-dose on Day 29, 1 hour, 4 hour post-dose on Day 1, Days 32, 42, 57, 85, 120, and 210.
Maximum observed concentration (Cmax)
Timeframe: Baseline (pre-dose on Day 1), 1 and 4 hours post-dose on Day 1, Days 4 and 14, pre-dose on Day 29, 1 hour, 4 hour post-dose on Day 1, Days 32, 42, 57, 85, 120, and 210.
Time of occurrence of Cmax (Tmax)
Timeframe: Baseline (pre-dose on Day 1), 1 and 4 hours post-dose on Day 1, Days 4 and 14, pre-dose on Day 29, 1 hour, 4 hour post-dose on Day 1, Days 32, 42, 57, 85, 120, and 210.
Terminal half life (t1/2)
Timeframe: Baseline (pre-dose on Day 1), 1 and 4 hours post-dose on Day 1, Days 4 and 14, pre-dose on Day 29, 1 hour, 4 hour post-dose on Day 1, Days 32, 42, 57, 85, 120, and 210.
Change from Baseline in adiponectin and high-sensitivity C-reactive protein (hsCRP) levels at Days 29, 57, and 85
Timeframe: Baseline (pre-dose on Day 1), Day 29, 57, and 85
Change from Baseline in HDL cholesterol, LDL cholesterol at Days 1 (4 hr post-dose), 4, 9, 14, 21, 29 (pre-dose and 4 hr post-dose), 32, 42, 57, 85, 120, and 165
Timeframe: Baseline, Days 1 (4 hr post-dose), 4, 9, 14, 21, 29 (pre-dose and 4 hr post dose), 32, 42, 57, 85, 120,and 165; and follow-up (up to Study Day 210) for HDL, LDL
Change from Baseline in non-esterified fatty acid levels on Days 29, 57, and 85
Timeframe: Baseline and Days 29, 57, and 85
Change from Baseline in fructosamine level at Days 29, 57, and 85
Timeframe: Baseline (pre-dose on Day 1), Day 29, 57, and 85
Change from Baseline in glomerular filtration rate (GFR) at Days 1 (4 hr post-dose), 4, 9, 14, 21, 29 (pre-dose and 4 hr post-dose), 32, 42, 57, 85, 120, and 165; and follow-up
Timeframe: Baseline (pre-dose on Day 1), Days 1 (4 hr post-dose), 4, 9, 14, 21, 29 (pre-dose and 4 hr post-dose), 32, 42, 57, 85, 120, and 165; and follow-up (up to Study Day 210)
Change from Baseline in interleukin-6 (IL-6), inducible protein-10 (IP-10), matrix metalloproteinase-9 (MMP-9), intercellular adhesion molecule-1 (IAM-1), and plasminogen activator inhibitor-1 (PAI-1) levels at Days 29, 57, and 85
Timeframe: Baseline (pre-dose on Day 1), Day 29, 57, and 85
Change from Baseline in lymphocytes biomarker levels at Days 1 (4 hr post-dose), 4, 9, 14, 21, 29 (pre-dose and 4 hr post-dose), 32, 42, 57, 85, 120, and 165; and follow-up
Timeframe: Baseline; Days 1 (4 hr post-dose), 4, 9, 14, 21, 29 (pre-dose and 4 hr post-dose), 32, 42, 57, 85, 120, and 165; and follow-up (up to Study Day 210)
Change from Baseline in resistin biomarker levels at Days 29, 57, and 85
Timeframe: Baseline (pre-dose on Day 1), Day 29, 57, and 85
Change from Baseline in change from Baseline in HDL/LDL Ratio over 210 days (follow-up period)
Timeframe: Baseline (pre-dose on Day 1) and Days 1 (4 hr post-dose), 4, 9, 14, 21, 29 (pre-dose and 4 hr post-dose), 32, 42, 57, 85, 120, and 165; and 210 days
Change from Baseline in Albumin/Creatinine Ratio and MCP1/Creatinine Ratio
Timeframe: Baseline (pre-dose on Day 1), Day 29, 57, and 85 for Albumin/Creatinine Ratio and MCP1/Creatinine Ratio
Change from Baseline in waist circumference at Day 85
Timeframe: Baseline (pre-dose on Day 1) and Day 85
Number of participants with detectable levels of anti-GSK1070806 antibodies
Timeframe: Up to 210 days
Change from Baseline (pre-dose on Day 1) in body mass index (BMI) at Day 85
Timeframe: Baseline (pre-dose on Day 1) and Day 85
Participation criteria
- 1. A diagnosis of T2DM as determined by a responsible physician based on a medical evaluation including medical history, physical examination, and laboratory tests, with onset at least 6 months prior to Screening.
- 2. Male or female between 18 and 70 years of age inclusive, at the time of signing the informed consent.
- 1. Current evidence, or history within the last 7 days, of an influenza-like illness as defined by fever (>38°C) and two or more of the following symptoms: cough, sore throat, runny nose, sneezing, limb / joint pain, headache, vomiting / diarrhoea in the absence of a known cause, other than influenza.
- 2. Use of anti-inflammatory drugs including corticosteroids, chronic maintenance therapy with NSAIDs, anti-Tumor Necrosis Factor (anti-TNF) or anti-Interleukin-1 (anti-IL1) within 60 days prior to dosing.
- Non-childbearing potential
- Child-bearing potential and agrees to use an acceptable form of contraception. 10. Male subjects must agree to use one of the contraception methods listed 11. ALT < 2xULN; alkaline phosphatase and bilirubin ≤ 1.5xULN (isolated bilirubin >1.5xULN is acceptable if bilirubin is fractionated and direct bilirubin <35%). 12. Single or Average QTc, QTcB or QTcF < 450 msec; or QTc < 480 msec in subjects with Bundle Branch Block.
1. A diagnosis of T2DM as determined by a responsible physician based on a medical evaluation including medical history, physical examination, and laboratory tests, with onset at least 6 months prior to Screening. 2. Male or female between 18 and 70 years of age inclusive, at the time of signing the informed consent. 3. HbA1c levels ≥ 7.0 % and ≤ 9.5%; at Screening. 4. On a stable dose of monotherapy with metformin for three months prior to screening, and at a total daily dose greater than or equal to 1000 mg for at least 2 months prior to dosing. 5. Fasting plasma glucose level < 13.3 mmol/L (240 mg/dL) at screening. 6. Obese with BMI ≥ 30 kg/m2, and < 40 kg/m2. 7. Presence of microalbuminuria: 30-300mg/L albumin in urine or Albumin Creatinine Ratio (ACR) ≥ 3.5 mg/mmol (female) or ≥2.5 mg/mmol (male) and ≤ 30 mg/mmol (female and male).. 8. The subject is capable of giving written informed consent, which includes compliance with the requirements and restrictions listed in the consent form. 9. A female subject is eligible to participate if she is of:
- 1. Current evidence, or history within the last 7 days, of an influenza-like illness as defined by fever (>38°C) and two or more of the following symptoms: cough, sore throat, runny nose, sneezing, limb / joint pain, headache, vomiting / diarrhoea in the absence of a known cause, other than influenza. 2. Use of anti-inflammatory drugs including corticosteroids, chronic maintenance therapy with NSAIDs, anti-Tumor Necrosis Factor (anti-TNF) or anti-Interleukin-1 (anti-IL1) within 60 days prior to dosing. 3. Current evidence of ongoing or acute infection, history of repeated, chronic or opportunistic infections (e.g. recurrent folliculitis, other cutaneous infections or repeated pneumonia) or history of a serious bacterial infection within 6 months of randomisation. 4. History of malignancy or significant cardiac, pulmonary, metabolic, renal, hepatic, or gastrointestinal conditions. 5. History chronic granulomatous infections, such as of Mycobacterium tuberculosis or any other previous Mycobacterium infection. 6. Creatinine clearance less than 60ml/min 7. Screens positive of Hepatitis B surface antigen, Hepatitis C antibody or Human Immunodeficiency Virus (HIV) 8. History of a severe allergic reaction, anaphylaxis or immunodeficiency. 9. Current or chronic history of liver disease, or known hepatic or biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones). 10. A positive pre-study drug/alcohol screen. 11. History of regular alcohol consumption within 6 months of the study 12. The subject has participated in a clinical trial and has received an investigational product within the following time period prior to the first dosing day in the current study: 30 days, 5 half-lives or twice the duration of the biological effect of the investigational product (whichever is longer). 13. Exposure to more than four new chemical entities within 12 months prior to the first dosing day. 14. Unable to refrain from the use of prescription or non-prescription drugs, including vitamins, herbal and dietary supplements (including St John’s Wort) within 7 days (or 14 days if the drug is a potential enzyme inducer) or 5 half-lives (whichever is longer) prior to the first dose of study medication. 15. History of sensitivity to any of the study medications, or components thereof 16. Where participation in the study would result in donation of blood or blood products in excess of 500 mL within a 56 day period. 17. Pregnant females as determined by positive serum or urine hCG test at screening. 18. Lactating females. 19. Unwillingness or inability to follow the procedures outlined in the protocol. 20. Subject is mentally or legally incapacitated. 21. Subject has received a live attenuated vaccine(s) within 30 days of randomisation or will require vaccination with a live attenuated vaccine prior to the end of the study.
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.