Phase 2
Completed N=53
To Investigate the Safety, Tolerability and Pharmacodynamics of GSK2890457 in Healthy Volunteers and Subjects With Type 2 Diabetes
Source: ClinicalTrials.gov NCT01725126 ↗Enrolled (actual)
53
Serious AEs
0.0%
Results posted
Oct 2017
Primary outcomePrimary: Number of Participants With Any Adverse Event (AE), Serious Adverse Event (SAE) or Death During Part A — 3; 10; 0; 0 Participants
Summary
This study is the first administration of GSK2890457 in humans. The study will be conducted in 3 parts: - Part A (conducted at a single investigative site) will determine the safety and tolerability of GSK2890457 alone in healthy subjects during six weeks of dosing, as well as evaluating the potential for a pharmacokinetic interaction with metformin. Part A consists of Screening, Treatment (6 weeks) and Follow-up periods. - Part B (conducted at multiple sites) will determine safety, tolerability, and pharmacodynamics (PD) in subjects with Type 2 diabetes (T2D) when co-dosed for six weeks with liraglutide (Victoza). Part B consists of Screening, Run-in (1 week), Stabilization (12 weeks), Treatment (6 weeks) and Follow-up periods. - Part C (conducted at multiple sites) will determine safety, tolerability, and PD in subjects with T2D when co-dosed for 6 weeks with metformin. Part C consists of Screening, Run-in (1 week), Stabilization (12 weeks), Treatment (6 weeks) and Follow-up periods.
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Number of Participants With Any Adverse Event (AE), Serious Adverse Event (SAE) or Death During Part A |
3; 10; 0; 0; 0; 0 | — |
| PRIMARY Number of Participants With Any AE, SAE or Death During Part B and Part C |
1; 3; 3; 3; 0; 0 | — |
| PRIMARY Number of Participants With Any Hypoglycemic Events During Part A |
0; 0 | — |
| PRIMARY Number of Participants With Any Hypoglycemic Events During Part B and Part C |
0; 0; 0; 0 | — |
| PRIMARY Change From Baseline in Clinical Chemistry Parameters of Alkaline Phosphatase (ALP), ALT, Aspartate Aminotransferase (AST) and Gamma Glutamyltransferase (GGT) During Double-blind Treatment Period of Part A |
-6.0; -3.8; -1.3; -1.4; 0.0; -1.8 | — |
| PRIMARY Change From Baseline in Clinical Chemistry Parameters of ALP, ALT, AST and GGT During the Double-blind Treatment Period of Part B and C |
5.3; 5.5; 1.8; -2.2; 5.2; 1.8 | — |
| PRIMARY Change From Baseline in Clinical Chemistry Parameters of Electrolytes, Glucose Phosphorus Inorganic and Urea/Blood Urea Nitrogen (BUN) During the Double-blind Treatment Period of Part A |
-0.025; -0.023; 0.056; -0.023; 0.056; -0.010 | — |
| PRIMARY Change From Baseline in Clinical Chemistry Parameters of Electrolytes, Glucose Phosphorus Inorganic, BUN and Cholesterol During the Double-blind Treatment Period of Part B and C |
0.083; 0.053; 0.025; -0.004; 0.050; 0.041 | — |
| PRIMARY Change From Baseline in Clinical Chemistry Parameters of Direct Bilirubin, Total Bilirubin, Creatinine and Uric Acid During the Double-blind Treatment Period of Part A |
0.000; -0.311; 0.428; -0.466; -0.428; -0.855 | — |
| PRIMARY Change From Baseline in Clinical Chemistry Parameters of Direct Bilirubin, Total Bilirubin, Creatinine and Uric Acid During the Double-blind Treatment Period of Part B and C |
0.542; -0.208; -0.513; -0.200; 0.314; -0.305 | — |
| PRIMARY Change From Baseline in Clinical Chemistry Parameters of Albumin and Total Protein During the Double-blind Treatment Period of Part A |
0.0; -0.3; 2.0; 0.4; 2.5; 0.4 | — |
| PRIMARY Change From Baseline in Clinical Chemistry Parameters of Albumin and Total Protein During the Double-blind Treatment Period of Part B and C |
2.0; 3.1; 1.3; 0.5; 2.7; 2.6 | — |
| PRIMARY Change From Baseline in Clinical Chemistry Parameters of Insulin During the Double-blind Treatment Period of Part A |
-1.256; 12.516; 8.072; 1.973; -11.659; 8.969 | — |
| PRIMARY Change From Baseline in Clinical Chemistry Parameters of Insulin During the Double-blind Treatment Period of Part B and C |
-20.21; -20.05; 45.11; -29.59; -21.65; -9.62 | — |
| PRIMARY Change From Baseline in Clinical Chemistry Parameters of Amylase and Lipase the Double-blind Treatment Period of Part B of Study |
6.0; 9.2; 7.5; 18.8 | — |
| PRIMARY Change From Baseline in Clinical Chemistry Parameter of Triiodothyronine (T3) Uptake During the Double-blind Treatment Period of Part B and C |
-0.018; -0.009; 0.002; -0.001 | — |
| PRIMARY Change From Baseline in Clinical Chemistry Parameters of Total Thyroxine and Total T3 During the Double-blind Treatment Period of Part B and C |
0.8578; 1.0891; -5.1478; -2.3597; -0.3; 0.1 | — |
| PRIMARY Change From Baseline in Clinical Chemistry Parameters of Thyroid Stimulating Hormone During the Double-blind Treatment Period of Part B and C |
-5.790; 0.137; -0.067; -0.187; 0.149 | — |
| PRIMARY Change From Baseline in Hematology Parameters of Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils, Platelet Count, White Blood Cell (WBC) Count During the Double-blind Treatment Period of Part A |
0.00; 0.00; -0.03; 0.01; 0.00; 0.00 | — |
| PRIMARY Change From Baseline in Hematology Parameters of Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils, Platelet Count, WBC Count During the Double-blind Treatment Period of Part B and C |
0.0270; 0.0047; 0.0047; -0.0078; 0.0037; 0.0041 | — |
| PRIMARY Change From Baseline in Hematology Parameters of Hemoglobin and Mean Corpuscle Hemoglobin Concentration (MCHC) During the Double-blind Treatment Period of Part A |
0.8; -2.0; 4.0; -0.9; 11.3; 0.5 | — |
| PRIMARY Change From Baseline in Hematology Parameters of Hemoglobin and MCHC During the Double-blind Treatment Period of Part B and C |
0.2; -1.0; -4.3; -3.4; 0.2; -1.1 | — |
| PRIMARY Change From Baseline in Hematology Parameters of Red Blood Cell (RBC) Count and Reticulocytes During the Double-blind Treatment Period of Part A |
-0.008; -0.116; 0.090; -0.084; 0.258; -0.045 | — |
| PRIMARY Change From Baseline in Hematology Parameters of RBC Count and Reticulocytes During the Double-blind Treatment Period of Part B and C |
0.018; 0.004; -0.107; -0.085; -0.030; -0.011 | — |
| PRIMARY Change From Baseline in Hematology Parameter of Hematocrit During the Double-blind Treatment Period of Part A |
0.0000; -0.0128; 0.0128; -0.0026; 0.0228; -0.0066 | — |
| PRIMARY Change From Baseline in Hematology Parameter of Hematocrit During the Double-blind Treatment Period of Part B and C |
0.0032; 0.0019; -0.0082; -0.0072; -0.0028; 0.0011 | — |
| PRIMARY Change From Baseline in Hematology Parameter of Mean Corpuscle Hemoglobin (MCH) During the Double-blind Treatment Period of Part A |
0.25; 0.31; 0.27; 0.32; 0.70; 0.37 | — |
| PRIMARY Change From Baseline in Hematology Parameter of MCH During the Double-blind Treatment Period of Part B and C |
-0.02; -0.21; -0.23; -0.18; 0.18; -0.10 | — |
| PRIMARY Change From Baseline in Hematology Parameter of Mean Corpuscle Volume (MCV) During the Double-blind Treatment Period of Part A |
0.15; -0.55; 0.85; 0.95; -0.30; -0.62 | — |
| PRIMARY Change From Baseline in Hematology Parameter of MCV During the Double-blind Treatment Period of Part B and C |
0.35; 0.39; 0.40; 0.25; 0.02; 0.54 | — |
| PRIMARY Number of Participants With Abnormal Urinalyisis Dipstick and Microscopic Results During the Double-blind Treatment Period of Part A |
1; 3; 0; 2; 0; 1 | — |
| PRIMARY Number of Participants With Abnormal Urinalyisis Dipstick and Microscopic Results During the Double-blind Treatment Period of Part B |
1; 0; 0; 1; 0; 1 | — |
| PRIMARY Number of Participants With Abnormal Urinalyisis Dipstick and Microscopic Results During the Double-blind Treatment Period of Part C |
0; 1; 0; 2; 1; 1 | — |
| PRIMARY Mean Specific Gravity Values of Urine During the Double-blind Treatment Period of Part A |
1.0193; 1.0175; 1.0133; 1.0165; 1.0153; 1.0152 | — |
| PRIMARY Mean Specific Gravity Values of Urine During the Double-blind Treatment Period of Part B and C |
1.0168; 1.0174; 1.0172; 1.0187; 1.0208; 1.0191 | — |
| PRIMARY Mean pH Values of Urine During the Double-blind Treatment Period of Part A |
5.25; 5.95; 5.88; 5.86; 5.50; 5.91 | — |
| PRIMARY Mean pH Values of Urine During the Double-blind Treatment Period of Part B and C |
5.92; 6.25; 5.67; 5.83; 5.83; 5.89 | — |
| PRIMARY Change From Baseline in Vital Sign Parameter of Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) During the Double-blind Treatment Period of Part A |
0.8; -4.0; -0.5; -3.9; -3.3; -5.5 | — |
| PRIMARY Change From Baseline in Vital Sign Parameter of SBP and DBP During the Double-blind Treatment Period of Part B and C |
1.6; 2.0; 3.2; -3.7; 5.6; 3.6 | — |
| PRIMARY Change From Baseline in Vital Sign Parameter of Heart Rate (HR) During the Double-blind Treatment Period of Part A |
8.0; 4.6; 6.3; 0.6; 5.5; 3.3 | — |
| PRIMARY Change From Baseline in Vital Sign Parameter of HR During the Double-blind Treatment Period of Part B and C |
-3.6; 0.3; 0.1; 1.6; -3.3; 0.4 | — |
| PRIMARY Change From Baseline in Electrocardiogram (ECG) Intervals During Part A |
6.3; 1.1; 9.0; 1.5; 2.2; -2.1 | — |
| PRIMARY Change From Baseline in ECG Intervals During Part B and C |
5.56; 3.08; -6.44; -4.44; -1.11; -3.69 | — |
| PRIMARY Change From Baseline in the Overall Gastrointestinal (GI) Symptoms Rating Scale (GSRS) Score During the Double-blind Treatment Period of Part A |
0.02; 0.08; 0.08; 0.04; 0.02; -0.02 | — |
| PRIMARY Change From Baseline in the Overall GSRS Score During the Double-blind Treatment Period of Part B and C |
0.03; -0.03; 0.24; 0.13; -0.09; 0.05 | — |
| PRIMARY Change From Baseline in In-clinic Body Weight During the Double-blind Treatment Period of Part B and C |
-0.12; 0.20; 0.28; 0.47; 0.37; 0.05 | — |
| PRIMARY Percent Change From Baseline in In-clinic Body Weight During the Double-blind Treatment Period of Part B and C |
-0.16; 0.18; 0.36; 0.59; 0.47; -0.04 | — |
| PRIMARY Change From Baseline in Weighted Mean Glucose Area Under the Curves From Time 0 to 24 Hours (AUC [0-24 Hours]) During the Double-blind Treatment Period of Part B and C |
0.018; -0.164; 1.194; 0.341; -0.613; -0.968 | — |
| PRIMARY Change From Baseline in Fasting Glucose During the Double-blind Treatment Period of Part B and C |
-0.384; -0.230; 0.136; -0.387 | — |
| PRIMARY Change From Baseline in Fasting Insulin and Weighted Mean Insulin AUC (0-4 Hour) and AUC (0-24 Hour) During the Double-blind Treatment Period of Part B and C |
-4.887; 1.133; -11.946; 12.300; 69.635; 14.589 | — |
| PRIMARY Change From Baseline in Glycated Hemoglobin (HbA1c) During the Double-blind Treatment Period of Part B and C |
-0.214; -0.278; 0.018; -0.201 | — |
| PRIMARY Change From Baseline in Homeostasis Model of Assessment-Insulin Resistance (HOMA-IR]) During the Double-blind Treatment Period of Part B and C |
-0.150; 0.017 | — |
| PRIMARY Change From Baseline in Matsuda Index During the Double Blind-treatment Period of Part B and C |
-0.991; -0.602 | — |
| PRIMARY Change From Baseline in Fasting Plasma Glucose (Safety Laboratory) Values During the Double-blind Treatment Period of Part B and C |
-0.278; 0.285; 0.879; -1.665; -0.093; 0.210 | — |
| SECONDARY Area Under Plasma Concentration From Time Zero (Pre-dose) to Last Time of Quantifiable Concentration (AUC [0-t]) of Liraglutide During the Double-blind Treatment Period of Part B |
2210.15; 1268.65; 2505.23; 1265.92 | — |
| SECONDARY Maximum Observed Concentration (Cmax) of Liraglutide During the Double-blind Treatment Period of Part B |
120.00; 72.24; 128.57; 70.86 | — |
| SECONDARY Time of Occurrence of Cmax (Tmax) of Liraglutide During the Double-blind Treatment Period of Part B |
9.74; 8.00; 9.92; 9.98 | — |
| SECONDARY AUC of Metformin From Time 0 to 10 Hours Post-dose (AUC [0-10 Hour]) During the Double-blind Treatment Period of Part A |
4346.8; 3402.6; 5081.9; 2231.7 | — |
| SECONDARY Cmax of Metformin During the Double-blind Treatment Period of Part A |
681.8; 576.2; 860.1; 374.1 | — |
| SECONDARY Tmax of Metformin During the Double-blind Treatment Period of Part A |
3.010; 2.000; 4.000; 2.000 | — |
| SECONDARY AUC From Time Zero (Pre-dose) to Last Time of Quantifiable Concentration (AUC [0-t]) of Metformin During the Double-blind Treatment Period of Part C |
— | — |
| SECONDARY Cmax of Metformin During the Double-blind Treatment Period of Part C |
— | — |
| SECONDARY Tmax of Metformin During the Double-blind Treatment Period of Part C |
— | — |
Eligibility Criteria
Inclusion Criteria:Part A (Healthy Subjects)
- Subject able to understand and voluntarily provide the consent to participate in the study
- 18 - 70 years of age, inclusive, at the time of signing the informed consent and Body Mass Index (BMI) between 18.0 and 35.0 Kilogram (kg) per m^2, inclusive
- Understands and is willing, able and likely to be compliant with taking study drug and comply with all study procedures and restrictions
- Subject is willing to consume the foods that are part of the standardized breakfast, lunch, and dinner
- In good general health with no clinically significant and relevant abnormalities of medical history or physical examination which includes adequate renal function, alanine transaminase (ALT), alkaline phosphatase and bilirubin 3 months postpartum and who have undergone a surgical sterilization procedure are eligible to participate in consultation with the GSK Medical Monitor
Parts B and C (Type 2 Diabetic Subjects)
- All the criteria mentioned in Part A except Body Mass Index (BMI) should be between 30.0 and 42.0 kg per m^2
- Diagnosis of T2D for at least 3 months, as defined by the American Diabetes Association
- All T2D subjects must meet label recommendations for metformin
- For Part B, subjects must be willing to discontinue metformin and replace it with daily liraglutide administered by subcutaneous injection and they must meet label recommendations
- No personal history or family history of medullary thyroid carcinoma or Multiple Endocrine Neoplasia syndrome type 2
Exclusion Criteria
- History of gastrointestinal disease, current or chronic history of liver disease, history of serious, severe or unstable physical or psychiatric illness , significant cardiovascular disease, surgery for weight loss or gastrointestinal surgery within 3 months of screening, any documented or reported eating disorder, uncontrolled hypertension, as evidenced by systolic pressure>160 or diastolic pressure >90 mmHg
- Positive test for HIV, Hepatitis B, or Hepatitis C at Screening
- Subjects with significant ECG abnormalities
- For subjects in Part C (continuing metformin), history of untreated pernicious anemia or who have laboratory parameters suggestive of subclinical megaloblastic anemia
- Presence of or symptoms of an active infection
- Uncorrected Thyroid Dysfunction
- History of chronic or acute pancreatitis
- Currently dieting to lose weight including, but not limited to, participation in a program designed to alter body weight within the last 60 days and unwilling to maintain relatively consistent exercise patterns throughout the study
- Current or recent history (within one year of screening) of alcohol or other substance abuse
- Unable to refrain from the use of non-prescription drugs
- Current participation in another clinical study or participation in a clinical study involving an investigational drug within 30 days of the screening visit
- History of sensitivity to any of the study medications, or components thereof or a history of drug or other allergy
- An employee of the sponsor or the study site or members of their immediate family.
Data sourced from ClinicalTrials.gov (NCT01725126). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication. Informational only — not medical advice.