Safety and Efficacy of Albiglutide + Insulin Glargine Versus Insulin Lispro + Insulin Glargine Subjects With Type 2 Diabetes Mellitus

Phase 3

Completed

Conditions: Diabetes Mellitus, Type 2

Interventions: Drug: Albiglutide
Drug: Insulin Glargine and Insulin Lispro

Registration Number: NCT02229227

Lead Sponsor: GlaxoSmithKline

Brief Summary: This Phase IIIb, randomized, open-label, parallel group, active control, multicenter, treat to-target study of 26 weeks' treatment duration will evaluate the efficacy and safety of once-weekly albiglutide as replacement of prandial insulin in subjects with type 2 diabetes mellitus (T2DM) failing to achieve adequate glycemic control on their current basal bolus insulin regimen (with or without metformin). Approximately 794 subjects will be randomly assigned in a 1:1 ratio to 1 of 2 treatment groups: albiglutide + insulin glargine (with insulin lispro discontinuation at Week 4) (with or without metformin) or to intensification of insulin glargine + insulin lispro (with or without metformin). The study will comprise 4 study periods : Screening (2 weeks), Standardization (4 weeks), Treatment (26 weeks), and Post treatment Follow up (4 weeks). The total duration of a subject's participation will be approximately 36 weeks.

Detailed Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 814

Inclusion Criteria

Male or female, 18 years of age or older (inclusive at the time of Screening) with T2DM
HbA1c >= 7.0% and <= 9.0% at Screening.
Currently treated with a basal-bolus insulin regimen (with or without metformin) for at least 3 months before Screening. The subject must be taking the following:
Basal insulin (1 or 2 daily injections of neutral protamine Hagedorn insulin, insulin glargine, insulin detemir, or insulin degludec) AND
Bolus insulin (at least 2 injections of regular insulin, insulin glulisine, insulin aspart, or insulin lispro) with a total daily dose of bolus insulin <= 70 units
In addition, the total daily dose of insulin must be <= 140 units
If taking metformin, a stable dose for at least 8 weeks before Screening Note: Subject should not have received any other antidiabetic medication within 30 days before screening (e.g., glucagon-like peptide-1 receptor (GLP-1R) agonist, dipeptidyl peptidase-IV inhibitor, SU, or thiazolidinedione). Subjects receiving commercially available premixed basal and prandial insulin are not eligible for this study.
Fasting C-peptide >= 0.8 nanogram (ng) per milliliter (mL) [>= 0.26 nanomoles per litre (nmol/L)]
Body mass index <= 40 kilogram per square meter( kg/m^2)
Thyroid-stimulating hormone (TSH) level is normal or clinically euthyroid as demonstrated by further thyroid tests (e.g., free T4)
Female subjects of childbearing potential (i.e., not surgically sterile and/or not postmenopausal) must be practicing adequate contraception (as defined in the protocol) for the duration of participation in the study including the 4-week post treatment Follow-up Period..
Willing and able to comply with all study procedures including performance of frequent self-monitored blood glucose (SMBG) profiles according to the protocol
Able and willing to provide written informed consent

Exclusion Criteria

Type 1 diabetes mellitus
History of cancer that has not been in full remission for at least 3 years before Screening. (A history of squamous cell or basal cell carcinoma of the skin or treated cervical intra-epithelial neoplasia I or II is allowed)
Personal or family history of medullary thyroid carcinoma or multiple endocrine neoplasia type 2
Current symptomatic biliary disease or history of acute or chronic pancreatitis
Severe gastroparesis, i.e., requiring regular therapy within 6 months before Screening
History of significant GI surgery that in the opinion of the investigator is likely to significantly affect upper GI or pancreatic function [e.g., gastric bypass and banding, antrectomy, Roux-en-Y bypass, gastric vagotomy, small bowel resection, or surgeries thought to significantly affect upper GI function]
History of severe hypoglycemia unawareness
Diabetic complications (e.g., active proliferative retinopathy or severe diabetic neuropathy) or any other clinically significant abnormality (including a psychiatric disorder) that, in the opinion of the investigator, may pose additional risk in administering the investigational product
Clinically significant CV and/or cerebrovascular disease within 3 months before Screening including, but not limited to, the following:
Stroke or transient ischemic attack
Acute coronary syndrome (myocardial infarction [MI] or unstable angina not responsive to nitroglycerin)
Cardiac surgery or percutaneous coronary procedure
Current or history of heart failure (New York Heart Association class III or IV)
Alanine aminotransferase (ALT) >2.5 × upper limit of normal (ULN) or bilirubin >1.5 × ULN (isolated bilirubin >1.5 × ULN is acceptable if bilirubin is fractionated and direct bilirubin <35%)
Unstable liver disease (as defined by the presence of ascites, encephalopathy, coagulopathy, hypoalbuminemia, esophageal or gastric varices, or persistent jaundice), cirrhosis, known biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones). (Chronic stable hepatitis B and C are acceptable if subject otherwise meets entry criteria and is not on active antiviral treatment [e.g., presence of hepatitis B surface antigen or positive hepatitis C test result within 3 months of Screening])
Hemoglobin <11 gram (g) per (dL) [<110 g/L] for male subjects and <10 g/dL (<100 g/L) for female subjects at Screening
Estimated glomerular filtration rate (eGFR) <= 30 millilitre per minute per 1.73 square meters (mL/min/1.73 m^2) (calculated using the Modification of Diet in Renal Disease [MDRD] formula) at Screening Note: As the use of metformin in subjects with varying degrees of renal function may differ from country to country, use of metformin should be in accordance with the metformin product label within the participating country.
Fasting triglyceride level >750 mg/dL at Screening
Hemoglobinopathy that may affect proper interpretation of HbA1c
Known allergy to albiglutide or any product components (including yeast and human albumin), any other GLP-1 analogue, insulin, or other study medication's excipients OR other contraindications (per the prescribing information) for the use of potential study medications (e.g., insulin glargine, insulin lispro)
Use of oral or systemically injected glucocorticoids within the 3 months before randomization or high likelihood of a requirement for prolonged treatment (>1 week) in the 6 months following randomization. However, short courses of oral steroids (single dose or multiple doses for up to 7 days) may be permitted provided these cases are discussed with the medical monitor. Inhaled, intra-articular, epidural, and topical corticosteroids are allowed
Female subject is pregnant (confirmed by laboratory testing) or lactating
Receipt of any investigational drug within the 30 days or 5 half-lives, whichever is longer, before Screening, a history of receipt of an investigational antidiabetic drug within the 3 months before randomization, or receipt of albiglutide in previous studies

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Albiglutide + Insulin Glargine Arm	Albiglutide	During standardization period, subjects will transit from basal bolus regimen received during screening period to insulin glargine plus insulin lispro. During treatment period, subject will receive Albiglutide 30 milligrams (mg) weekly subcutaneous (SC) injection and insulin lispro dose will be downtitrated to half that used in the standardization period. At Week 4, Albiglutide will be uptitrated to 50 mg weekly SC injection and insulin lispro will be stopped for the remainder of the treatment Period. Insulin lispro may be re-introduced after Week 8 according to pre-defined hyperglycemia thresholds. Insulin will be adjusted according to protocol-defined insulin titration algorithms
Insulin Glargine + Insulin Lispro Arm	Insulin Glargine and Insulin Lispro	During standardization period, subjects will transit from basal bolus regimen received during screening period to insulin glargine plus insulin lispro. During treatment period, subject will continue with the same doses as at the end of the standardization period and doses will be adjusted according to protocol-defined insulin titration algorithms

Primary Outcome Measures

Name	Time	Method
Change From Baseline in Glycosylated Hemoglobin (HbA1c) at Week 26	Baseline (Day -1) and Week 26	HbA1c is glycosylated hemoglobin. It was measured at Baseline and at Week 26. The analysis was conducted using mixed-effect model with repeated measures (MMRM). The model included HbA1c change from Baseline as the dependent variable; treatment, region, age category, current metformin use, visit week, treatment-by-week interaction, and Baseline HbA1c-by-week interaction as fixed effects; Baseline HbA1c as a continuous covariate; and participant as a random effect. The Baseline value was the last available non-missing value prior to the first dose of the randomized treatment, thus Baseline was Day -1. Change from Baseline is defined as the post-Baseline value minus the Baseline value.

Secondary Outcome Measures

Name	Time	Method
Number of Participants Who Met Prespecified Criteria for Severe, Persistent Hyperglycemia at Week 26	Week 26	Meeting prespecified criteria for severe, persistent hyperglycemia was defined operationally as being withdrawn due to lack of efficacy as recorded on the Treatment Discontinuation and Study Conclusion electronic case report form pages. Number of participants who met prespecified criteria for severe, persistent hyperglycemia at Week 26 are presented.
Total Daily Insulin Dose at Week 26	Week 26	Insulin dose at Week 26 was defined as the prescribed insulin dose at Week 25. Based on MMRM model, prescribed total daily basal insulin dose was equal to Baseline prescribed total daily basal insulin dose + treatment + Baseline HbA1c category + region + age category + current use of metformin + visit week + treatment-by-visit week interaction + Baseline prescribed total daily basal insulin dose-by-visit week interaction. Total daily insulin dose at Week 26 is presented. Only those participants available at the specified time points were analyzed.
Number of Participants Achieving HbA1c <7.0% at Week 26	Week 26	HbA1c is glycosylated hemoglobin. Number of participants achieving a HbA1c \<7.0% at Week 26 are presented.
Number of Participants Achieving a HbA1c <6.5% up to Week 26	Up to Week 26	Number of participants achieving a HbA1c \<6.5% up to Week 26 are presented.
Number of Participants Meeting Prespecified Criteria for Severe, Persistent Hyperglycemia up to Week 26	Up to Week 26	Meeting prespecified criteria for severe, persistent hyperglycemia was defined operationally as being withdrawn due to lack of efficacy as recorded on the Treatment Discontinuation and Study Conclusion electronic case report form pages. Number of participants meeting prespecified criteria for severe, persistent hyperglycemia up to Week 26 are presented.
Number of Participants With Other AE of Special Interest	Up to Week 26	AE is any untoward medical occurrence in a participant or clinical investigation participant, temporally associated with use of a MP, whether or not considered related to MP. AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with use of MP. AE of special interest included hypoglycemic events, cardiovascular events, gastrointestinal events, injection site reactions, potential systemic allergic reactions, pancreatitis, pancreatic cancer, malignant neoplasms following treatment with insulin, diabetic retinopathy events, appendicitis, liver events, pneumonia, and atrial fibrillation/flutter.
Number of Participants With Hypoglycemic Events (in Total and by Each Category as Defined by the American Diabetes Association Criteria)	Up to Week 26	The American Diabetes Association has categorized hypoglycemic events as follows: Severe, documented symptomatic, asymptomatic, probably symptomatic and pseudohypoglycemia. Number of participants with hypoglycemic events in total are also presented.
Number of Participants With Hematology Values of Clinical Concern	Up to 30 weeks	Hematology parameters included basophils, eosinophils, hematocrit, hemoglobin, lymphocytes, monocytes, neutrophils, neutrophil bands, platelets, red blood cell (RBC) count, segmented neutrophils and white blood cell (WBC) count. The potential clinical concern values were: Hematocrit \>0.05 below lower limit of normal (LLN) and \>0.04 above upper limit of normal (ULN), hemoglobin: \>20 grams cells per Liter (g/L) below LLN and \>10 g/L above ULN, lymphocytes: \<0.5 x LLN, neutrophils: \<1 giga cells per liter (GI/L), platelets: \<80 GI/L and \>500 GI/L, segmented neutrophils: \<0.5 x LLN, RBC count: \>1 GI/L below LLN and \>5 GI/L above ULN and none for basophils, eosinophils, monocytes, neutrophil bands and RBC count. Only those parameters for which at least one value of potential clinical concern was reported are summarized.
Total Daily Bolus Insulin (Insulin Lispro) at Week 4, 10, 18, and 26 Visits	Weeks 4, 10, 18, and 26	Based on MMRM model, prescribed total daily basal insulin dose was equal to Baseline prescribed total daily basal insulin dose + treatment + Baseline HbA1c category + region + age category + current use of metformin + visit week + treatment-by-visit week interaction + Baseline prescribed total daily basal insulin dose-by-visit week interaction. Total daily bolus insulin (insulin lispro) at Week 4, 10, 18, and 26 visits is presented. Only those participants available at the specified time points were analyzed represented by n=X,X in the category titles.
Total Number of Weekly Insulin Injections to Achieve Glycemic Control at Baseline/Randomization and Week 4, 10, 18, and 26	Baseline (Day -1) and Weeks 4, 10, 18 and 26	Total number of weekly insulin injections (7 days) to achieve glycemic control at Baseline/Randomization and Week 4, 10, 18, and 26 are presented. Only those participants available at the specified time points were analyzed represented by n=X,X in category titles.
Percentage of Participants Achieving HbA1c <7.0% Without Severe or Documented Symptomatic Hypoglycemia at Week 26	Week 26	Percentage of participants achieving HbA1c \<7.0% without severe or documented symptomatic hypoglycemia are presented.
Percentage of Participants Achieving HbA1c <7.0% Without Weight Gain and Without Severe or Documented Hypoglycemia at Week 26	Week 26	Percentage of participants achieving HbA1c \<7.0% without weight gain and without severe or documented hypoglycemia are presented.
Number of Participants With Vital Signs of Clinical Concern	Up to 30 weeks	Vital signs included systolic blood pressure (SBP), diastolic blood pressure (DBP) and pulse rate values. Assessment of vitals were performed with the participant in a semi recumbent or seated position having rested in this position for at least 5 minutes before each reading. The potential clinical concern values were: SBP: \<100 millimeters of mercury (mmHg) and \>170 mmHg, DBP: \<50 mmHg and \>110 mmHg and pulse rate: \<50 beats per minute (bpm) and \> 120 bpm. Number of participants with vital signs of clinical concern are presented.
Percentage of Participants With Severe or Documented Symptomatic Hypoglycemia Through Week 26	Up to Week 26	Severe hypoglycemia was considered as an event requiring assistance of another person to actively administer carbohydrates, glucagon, or take other corrective actions. Plasma glucose concentrations may not be available during an event, but neurological recovery following the return of plasma glucose to normal was considered sufficient evidence that the event was induced by a low plasma glucose concentration. Documented symptomatic hypoglycemia was an event during which typical symptoms of hypoglycemia are accompanied by a measured plasma glucose concentration \<=70 milligrams per deciliters (mg/dL) (\<=3.9 millimoles per liters \[mmol/L\]).
Change From Baseline in Body Weight at Week 26	Baseline (Day -1) and Week 26	Body weight was measured to the nearest 0.1 kilogram on a standard calibrated scale. Participants dressed in light indoor clothes (no coat, jacket, etc.) without shoes and with a voided bladder. The same equipment was used wherever possible. The Baseline value was the last available non-missing value prior to the first dose of the randomized treatment, thus Baseline was Day -1. Change from Baseline is defined as the post-Baseline value minus the Baseline value.
Change From Baseline to Week 26 in Body Weight	Baseline (Day -1) to Week 26	Body weight was measured to the nearest 0.1 kilogram on a standard calibrated scale. Participants dressed in light indoor clothes (no coat, jacket, etc.) without shoes and with a voided bladder. The same equipment was used wherever possible. The Baseline value was the last available non-missing value prior to the first dose of the randomized treatment, thus Baseline was Day -1. Change from Baseline is defined as the post-Baseline value minus the Baseline value. Change from Baseline to Week 26 in body weight are presented. FA Population was analyzed. Only those participants available at the specified time points were analyzed represented by n=X,X in the category titles.
Change From Baseline to Week 26 in HbA1c	Baseline to Week 26	HbA1c is glycosylated hemoglobin and was measured up to Week 26. The Baseline value was the last available non-missing value prior to the first dose of the randomized treatment, thus Baseline was Day -1. Change from Baseline is defined as the post-Baseline value minus the Baseline value. Only those participants available at the specified time points were analyzed represented by n=X,X in the category titles.
Change From Baseline in Fasting Plasma Glucose (FPG) at Week 26	Baseline and Week 26	FPG was measured at Baseline (Day -1). FPG values for all participants at Week 26 were not collected due to an error in the protocol and were imputed with the fasting serum glucose (FSG) values at this time point. The imputation of the FPG at Week 26 from the FSG values was deemed acceptable from the results of the analysis of the correlation between FPG and FSG at the screening visit. The Baseline value was the last available non-missing value prior to the first dose of the randomized treatment, thus Baseline was Day -1. Change from Baseline is defined as the post-Baseline value minus the Baseline value.
Number of Participants Achieving HbA1c <7.0% up to Week 26	Up to Week 26	HbA1c is glycosylated hemoglobin. Number of participants achieving a HbA1c \<7.0% up to Week 26 are presented.
Number of Participants Achieving a HbA1c <6.5% at Week 26	Week 26	Number of participants achieving a HbA1c \<6.5% at Week 26 are presented.
Total Daily Insulin Dose at Week 4, Week 10 and Week 18	Weeks 4, 10, and 18	Based on MMRM model, prescribed total daily basal insulin dose was equal to Baseline prescribed total daily basal insulin dose + treatment + Baseline HbA1c category + region + age category + current use of metformin + visit week + treatment-by-visit week interaction + Baseline prescribed total daily basal insulin dose-by-visit week interaction. Total daily insulin dose at Week 4, Week 10 and Week 18 is presented. Only those participants available at the specified time points were analyzed represented by n=X,X in the category titles.
Percentage of Participants Achieving HbA1c <7.0% Without Weight Gain at Week 26	Week 26	Percentage of participants achieving HbA1c \<7.0% without weight gain are presented.
Number of Participants With Daytime and Nocturnal Hypoglycemia	Up to Week 26	Daytime hypoglycemia was defined as hypoglycemic events with an onset between 06:00 hours and 00:00 hours (inclusive), and nocturnal hypoglycemia (in total and by category), defined as hypoglycemic events with an onset between 00:01 hours and 05:59 hours (inclusive). Number of participants with daytime and nocturnal hypoglycemia (in total and by category) are presented.
Number of Participants Treated With Once-weekly Albiglutide That Were Able to Discontinue Insulin Lispro at Week 4 and Did Not Meet Prespecified Criteria for Severe, Persistent Hyperglycemia Through Week 26	Up to Week 26	Participants who did not meet prespecified criteria for severe, persistent hyperglycemia through Week 26 were those participants treated with once-weekly albiglutide that were able to replace prandial insulin without lispro re-introduction through Week 26. Number of participants treated with once-weekly albiglutide that were able to discontinue insulin lispro at Week 4 and did not meet prespecified criteria for severe, persistent hyperglycemia through Week 26 have been presented.
Change From Baseline to Week 26 in FPG	Baseline to Week 26	FPG was measured at Baseline (Day -1) up to Week 26. FPG values for all participants at Week 26 were not collected due to an error in the protocol and were imputed with the FSG values at this time point. The imputation of the FPG at Week 26 from the FSG values was deemed acceptable from the results of the analysis of the correlation between FPG and FSG at the screening visit. The Baseline value was the last available non-missing value prior to the first dose of the randomized treatment, thus Baseline was Day -1. Change from Baseline is defined as the post-Baseline value minus the Baseline value.
Number of Participants With On-therapy Adverse Events (AE) and Serious AE (SAE), and AE Leading to Discontinuation of Randomized Study Medication	Up to Week 26	AE is any untoward medical occurrence in a participant, temporally associated with use of medicinal product (MP), whether or not considered related to MP. AE can be any unfavorable, unintended sign (also an abnormal laboratory finding), symptom, or disease (new/exacerbated) temporally associated with use of MP. SAE is any untoward medical occurrence that, at any dose results in death, is life-threatening, requires hospitalization or prolongation of existing hospitalization, results in disability, or is a congenital anomaly/birth defect or is medically significant or all events of possible drug induced liver injury with hyperbilirubinemia. Safety Population: All participants who received at least 1 dose of randomized study medication. A participant randomized to Albiglutide + Insulin glargine by mistake received Insulin Lispro + Insulin Glargine instead. Since this participant received actual treatment as Insulin Lispro + Insulin Glargine, was summarized as such in Safety Population.
Percentage of Participants With Events of Hypoglycemia With Confirmed Home Blood Glucose Monitoring and/or Third-party Intervention Through Week 26	Up to Week 26	Hypoglycemic events with confirmed home plasma glucose monitoring \<3.9 millimoles per Liter and/or requiring third party intervention were severe, documented symptomatic (DS) and asymptomatic hypoglycemic events. Participants with more than one hypoglycemic event are counted in all categories reported. Any severe, documented symptomatic, and asymptomatic hypoglycemic events in 3-month intervals (i.e., from Day 0 to Week 12, \>Week 12 to Week 26) are presented.
Number of Participants With Hypoglycemia With Blood Glucose <56 Milligrams Per Deciliter (mg/dL) (<3.1 Millimoles Per Liter [mmol/L]), Regardless of Symptoms	Up to Week 26	Number of participants with hypoglycemia with blood glucose \<56 mg/dL (\<3.1 mmol/L), regardless of symptoms are presented.
Number of Participants With Different Number of Erythrocytes in Urine at Week 0 and Week 26	Week 0 and Week 26	Urine samples were collected for analysis of erythrocyte count. Only those participants available at the specified time points were analyzed represented by n=X,X in the category titles. Number of participants with different number of erythrocytes in urine at Week 0 and Week 26 are presented.
Number of Participants With Clinically Significant Change in Electrocardiogram (ECG) Parameters	Up to 30 weeks	A single 12-lead ECG recordings were performed in a participant in semi recumbent position for 10 to 15 minutes before obtaining the ECG. Any clinically significant favorable and unfavorable findings are reported.
Total Daily Basal Insulin (Insulin Glargine) at Week 4, 10, 18, and 26 Visits	Weeks 4, 10, 18, and 26	Based on MMRM model, prescribed total daily basal insulin dose was equal to Baseline prescribed total daily basal insulin dose + treatment + Baseline HbA1c category + region + age category + current use of metformin + visit week + treatment-by-visit week interaction + Baseline prescribed total daily basal insulin dose-by-visit week interaction. Total daily basal insulin (insulin glargine) at Week 4, 10, 18, and 26 visits is presented. Only those participants available at the specified time points were analyzed represented by n=X,X in the category titles.
Mean Albumin at Week 0 and Week 26	Week 0 and Week 26	Urine samples were collected for analysis of albumin. Only those participants available at the specified time points were analyzed represented by n=X,X in the category titles. Mean albumin at Week 0 and Week 26 are presented.
Mean Creatinine at Week 0 and Week 26	Week 0 and Week 26	Urine samples were collected for analysis of creatinine. Only those participants available at the specified time points were analyzed represented by n=X,X in the category titles. Mean creatinine at Week 0 and Week 26 are presented.
Mean Specific Gravity at Week 0 and Week 26	Week 0 and Week 26	Urine specific gravity is a measure of the concentration of solutes in the urine and provides information on the kidney's ability to concentrate urine. The concentration of the excreted molecules determines the urine's specific gravity. A urinary specific gravity measurement is a routine part of urinalysis. Only those participants available at the specified time points were analyzed represented by n=X,X in the category titles.
Number of Participants With Clinical Chemistry Values of Clinical Concern	Up to 30 weeks	Clinical chemistry parameters and their potential clinical concern values were: albumin (\>5 g/L above ULN or below LLN), alkaline phosphatase(\>3 x ULN), alanine aminotransferase (\>3 x ULN), aspartate aminotransferase (\>3 x ULN), carbon dioxide content (\<16 millimoles per Liter \[mmol/L\] and \> 40 mmol/L), blood urea nitrogen (\>2 x ULN), calcium (\<1.8 mmol/L and \>3.0 mmol/L), chloride (none), creatinine (\>159 micromoles/Liter), direct bilirubin (\>1.35 x ULN), gamma glutamyl transferase (\>3 x ULN), glucose (fasting) (\<3 mmol/L and \>22 mmol/L), magnesium (\<0.411 mmol/L and \>1.644 mmol/L), phosphate (\>0.323 mmol/L above ULN or below LLN), potassium (\>0.5 mmol/L below LLN and \>1.0 mmol/L above ULN), sodium (\>5 mmol/L above ULN or below LLN), triglycerides (\> 9.04 mmol/L), total bilirubin (\>1.5 x ULN), total protein (\>15 g/L above ULN or below LLN) and uric acid (\>654 umol/L). Only those parameters for which at least one value of potential clinical concern was reported are summarized.
Mean Urine Albumin/Creatinine Ratio at Week 0 and Week 26	Week 0 and Week 26	Urine samples were collected for analysis of albumin/creatinine ratio. Only those participants available at the specified time points were analyzed represented by n=X,X in the category titles. Mean urine albumin/creatinine ratio at Week 0 and Week 26 are presented.
Number of Participants With Different Values of Potential of Hydrogen (pH) at Week 0 and Week 26	Week 0 and Week 26	Urine pH is an acid-base measurement. pH is measured on a numeric scale ranging from 0 to 14; values on the scale refer to the degree of alkalinity or acidity. A pH of 7 is neutral. A pH less than 7 is acidic, and a pH greater than 7 is basic. Normal urine has a slightly acid pH (5.0 - 6.0). Safety Population was analyzed. Only those participants available at the specified time points were analyzed represented by n=X,X in the category titles.
Number of Participants With Different Number of Leukocytes in Urine at Week 0 and Week 26	Week 0 and Week 26	Urine samples were collected for analysis of leukocyte count. Only those participants available at the specified time points were analyzed represented by n=X,X in the category titles. Number of participants with different number of leukocytes in urine at Week 0 and Week 26 are presented.
Change From Baseline in Total Cholesterol (TC), Low-density Lipoprotein Cholesterol (LDL-c), High Density Lipoprotein (HDL-c), Triglycerides (TG) and Free Fatty Acids (FFA) at Week 10 and Week 26	Baseline, Week 10 and Week 26	Lipid parameters included TC, LDL-c, HDL-c, TG and FFA. The Baseline value was the last available non-missing value prior to the first dose of the randomized treatment, thus Baseline was Day -1. Change from Baseline is defined as the post-Baseline value minus the Baseline value. LDL-c and FFA were collected as part of the lipid panel and results were reviewed by investigators for individual participants. Change from Baseline at Week 10 and Week 26 was not assessed for these parameters. Analysis of these parameters was not a specific study objective and would not have any impact on study conclusions. Only those parameters with data values have been presented. Only those participants available at the specified time points were analyzed represented by n=X,X in the category titles.