Dose-Ranging Study In Subjects With Type 2 Diabetes Mellitus Who Are Treatment-Naive

Diabetes Mellitus, Type 2 Clinical Trial

Official title:

A Once-Daily Dose-Ranging Study of GSK189075 Versus Placebo In The Treatment of Type 2 Diabetes Mellitus in Treatment-Naïve Subjects

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00495469
• Other study ID #: KG2110375
• Status: Completed
• Phase: Phase 2
• First received: June 29, 2007
• Last updated: September 26, 2017
• Start date: August 17, 2007
• Est. completion date: June 5, 2008

Study information

• Verified date: September 2017
• Source: GlaxoSmithKline
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This is a dose-ranging study to evaluate the efficacy, safety and tolerability of a range of doses of GSK189075 (an SGLT2 inhibitor) compared to placebo, administered over 12 weeks in treatment-naive subjects with type 2 diabetes mellitus

Recruitment information / eligibility

• Status: Completed
• Enrollment: 250
• Est. completion date: June 5, 2008
• Est. primary completion date: June 5, 2008
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 70 Years

Eligibility

Inclusion Criteria:

• Subjects with a documented diagnosis of T2DM and HbA1c =7.0% and =9.5% measured by the central laboratory at Visit 1.

• Note: Subjects with HbA1c <7.5% must have a fasting fingerstick glucose =7 mmol/L (126 mg/dL) at Week 0, prior to randomization.

• Note: The proportion of subjects who are randomized with an HbA1c <7.5% will be limited to be no more than 20% (approximately 51 subjects)

• Subjects who are treatment-naïve, and have not taken insulin, or any oral or injectable anti-diabetic medication in the past 3 months and have not taken a glucose lowering agent for =4 weeks at any time in the past, or subjects who are newly diagnosed and treated with diet and exercise for a minimum of 6 weeks

• Subjects who are 18 to 70 years of age inclusive at the time of Screening.

• Females of childbearing and non-childbearing and potential are eligible to participate as follows:

• Women of childbearing potential must be willing to use one of the following contraception methods: intrauterine device, condom or occlusive cap (diaphragm or cervical/vault caps) plus spermicidal agent for at least 30 days prior to the start of study medication, throughout the study and the follow-up visit. Note: use of oral contraceptives is not permitted.

• Women of non-child bearing potential are defined as follows: females regardless of age, with functioning ovaries who have a current documented tubal ligation, or who are surgically sterile (i.e. documented total hysterectomy or bilateral oophorectomy), or females who are post-menopausal.

All females must have a negative urine pregnancy test on the day of, and prior to randomization.

• Informed Consent: a signed and dated written consent must be obtained from the subject before any procedures are performed.

Exclusion Criteria:

• Metabolic Disease

• Diagnosis of Type 1 diabetes mellitus

• History of ketoacidosis which has required hospitalization

• Thyroid disorder

• TSH <0.4 MIU/L (<0.4 MCIU/mL) or >5.5 mIU/L (>5.5 MCIU/mL) at Screening

• BMI of <22 kg/m2 or >43 kg/m2

• Significant weight gain or loss (as defined as >5% of total body weight) in the 3 months prior to Screening

• Diabetic Medication

• Has taken insulin, or any oral or injectable anti-diabetic medication within 3 months of screening

• Has taken insulin or any oral or injectable anti-diabetic medication =4 weeks at any time in the past

• Cardiovascular Disease

Recent history or presence of clinically significant acute cardiovascular disease including:

• Documented myocardial infarction in the 6 months prior to Screening.

• Coronary revascularization including percutaneous transluminal coronary angioplasty (PTCA) or coronary artery bypass graft (CABG) surgery either planned and/or occurred in the 6 months prior to Screening.

• Unstable angina in the 6 months prior to Screening.

• Clinically significant supraventricular arrhythmias requiring medical therapy, or history of nonsustained or sustained ventricular tachycardia. Symptomatic valvular heart disease or valvular heart disease requiring therapy other than endocarditis prophylaxis.

• Congestive heart failure (CHF, New York Heart Association (NYHA) Class II to IV) requiring pharmacologic treatment or the NYHA Class criteria in accordance with the local prescribing information for pioglitazone.

• Blood pressure (BP) >150/100mmHg. If a subject is receiving permitted antihypertensive therapy, then they must be on stable dose(s) of therapy for at least 4 weeks prior to Screening.

• Based on local readings, the subject has an initial QTc interval (Bazett's)=450msec at Screening, and after two additional ECGs taken 5 minutes apart, the average of the QTC interval from the three ECGs is =450msec.

• Other clinically significant ECG abnormalities which, in the opinion of the Investigator, may affect the interpretation of efficacy or safety data, or which otherwise contraindicates participation in a clinical trial with a new chemical entity.

• Fasting triglycerides =400mg/dL (4.56mmol/L) at Screening. If a subject is receiving permitted lipid-lowering therapy, then they must be on a stable dose(s) of therapy for at least 6 weeks prior to Screening. Niacin and bile acid sequestrants are prohibited.

• Hepatic Disease

Has a diagnosis of active hepatitis (hepatitis B surface antigen or hepatitis C antibody), or clinically significant hepatic enzyme elevation including:

Any one of the following enzymes greater than 2 times the upper limit of the reference range (ULRR) value at Screening.

• alanine aminotransferase (ALT)

• aspartate aminotransferase (AST)

• alkaline phosphatase (AP) Has a total bilirubin level that is >1.5 times the ULRR at Screening with the exception of suspected or confirmed Gilbert's disease.

• Pancreatic Disease

• Secondary causes of diabetes:

• history of chronic or acute pancreatitis

• Renal Disease

Significant renal disease at Screening as manifested by:

• Glomerular filtration rate (GFR) <60mL/min (as calculated by Quest at Visit using the Modification of Diet in Renal Disease (MDRD) equation

•=1+ protein on urine dipstick

• Trace or =1+ leukocyte esterase on urine dipstick

• Trace or =1+ blood on urine dipstick

• Positive nitrite on urine dipstick

• Recurrent genitourinary tract infections defined as =2 episodes of complicated or uncomplicated cystitis or pyelonephritis in the 6 months prior to Screening.

• Concurrent Disease

• Has any concurrent condition or any clinically significant abnormality identified on the screening physical examination, laboratory tests (including blood electrolytes), ECG, including pulmonary, neurological or inflammatory diseases, which, in the opinion of the investigator, may affect the interpretation of efficacy and safety data, or which otherwise contraindicates participation in a clinical trial with a new chemical entity.

• History of significant co-morbid diseases active in the 6 months prior to Screening (e.g., cholecystitis, acute pancreatitis, gastrointestinal disease, chronic diarrhea, etc.).

• History of malignancy within the past 5 years other than superficial squamous cell carcinoma (non-invasive on pathology) or basal cell carcinoma (successfully treated with local excision).

• History of cervical cancer in situ treated definitively at least 6 months prior to Screening.

• Concurrent Medication

Is currently taking or has taken any of the following medications in the 8 weeks prior to Screening:

• Digoxin

• Warfarin and other oral anticoagulants (aspirin and non-steroidal anti-inflammatory drugs are permitted)

• Bile acid sequestrants

• Niacin (excluding routine vitamin supplementation)

• Antiobesity agents (including fat absorption blocking agents)

• Oral or injectable corticosteroids (inhaled, topical and intranasal corticosteroids are permitted)

• Loop diuretics

• Monoamine oxidase inhibitors and tricyclic amines

• Antiretroviral drugs

• St John's Wort

• Oral chromium 9.Breast Feeding 10.Other

• Current smoker who is unable to abstain from smoking while in the clinic at each visit

• Has a history of alcohol or substance abuse within the past year at Screening or alcohol or substance abuse during treatment, as determined by the investigator:

• Unwilling to refrain from the use of illicit drugs and adhere to other protocol-stated restrictions while participating in the study

• Has an average weekly intake of alcohol of >21 units or an average daily intake of >3 units (males) or an average weekly intake of >14 units or an average daily intake of >2 units (females). One unit is equivalent to a half pint of beer or 1 measure of spirits or 1 glass of wine

• Has participated in any study with an investigational or marketed drug in the 3 months prior to Screening.

• In the opinion of the investigator has a risk of non-compliance with study procedures, or cannot read, understand, or complete study related materials, particularly the informed consent.

• Known allergy to any of the tablet or capsule excipients, or history of drug or other allergy, which, in the opinion of the responsible study physician, contraindicates participation.

Related Conditions & MeSH terms

• Diabetes Mellitus
• Diabetes Mellitus, Type 2

Intervention

Drug:
• GSK189075
GSK189075 is available as a white, capsule-shaped tablet dosage form containing 50mg, 125mg, 250mg or 500mg of GSK189075 per tablet
• Placebo
Available as Placebo matching tablet to GSK189075

Locations

Country	Name	City	State
Canada	GSK Investigational Site	Bathurst	New Brunswick
Canada	GSK Investigational Site	Bay Roberts	Newfoundland and Labrador
Canada	GSK Investigational Site	Brampton	Ontario
Canada	GSK Investigational Site	L'ancienne-Lorette	Quebec
Canada	GSK Investigational Site	Langley	British Columbia
Canada	GSK Investigational Site	Mississauga	Ontario
Canada	GSK Investigational Site	Oakville	Ontario
Canada	GSK Investigational Site	Ottawa	Ontario
Canada	GSK Investigational Site	Québec
Canada	GSK Investigational Site	Thornhill	Ontario
Canada	GSK Investigational Site	Toronto	Ontario
Canada	GSK Investigational Site	Toronto	Ontario
Czechia	GSK Investigational Site	Brno
Czechia	GSK Investigational Site	Brno
Czechia	GSK Investigational Site	Praha 10
Czechia	GSK Investigational Site	Praha 5
Estonia	GSK Investigational Site	Parnu
Estonia	GSK Investigational Site	Tallin
Estonia	GSK Investigational Site	Tallinn
Estonia	GSK Investigational Site	Tartu
Germany	GSK Investigational Site	Allmendingen	Baden-Wuerttemberg
Germany	GSK Investigational Site	Berlin
Germany	GSK Investigational Site	Berlin
Germany	GSK Investigational Site	Berlin
Germany	GSK Investigational Site	Berlin
Germany	GSK Investigational Site	Brinkum/Stuhr	Niedersachsen
Germany	GSK Investigational Site	Dresden	Sachsen
Germany	GSK Investigational Site	Einbeck	Niedersachsen
Germany	GSK Investigational Site	Falkensee	Brandenburg
Germany	GSK Investigational Site	Freital	Sachsen
Germany	GSK Investigational Site	Grossheirath	Bayern
Germany	GSK Investigational Site	Hannover	Niedersachsen
Germany	GSK Investigational Site	Hassloch	Rheinland-Pfalz
Germany	GSK Investigational Site	Hohenau	Bayern
Germany	GSK Investigational Site	Ingelheim	Rheinland-Pfalz
Germany	GSK Investigational Site	Kuenzing	Bayern
Germany	GSK Investigational Site	Luebeck	Schleswig-Holstein
Germany	GSK Investigational Site	Lueneburg	Niedersachsen
Germany	GSK Investigational Site	Muenchen	Bayern
Germany	GSK Investigational Site	Muenchen	Bayern
Germany	GSK Investigational Site	Parsberg	Bayern
Germany	GSK Investigational Site	Ruhmannsfelden	Bayern
Germany	GSK Investigational Site	Schmiedeberg	Sachsen
Germany	GSK Investigational Site	Sulzbach-Rosenberg	Bayern
Germany	GSK Investigational Site	Tostedt	Niedersachsen
Germany	GSK Investigational Site	Wangen	Baden-Wuerttemberg
Germany	GSK Investigational Site	Wolmirstedt	Sachsen-Anhalt
Greece	GSK Investigational Site	Athens
Greece	GSK Investigational Site	Athens
Greece	GSK Investigational Site	Thessaloniki
Greece	GSK Investigational Site	Thessaloniki,
India	GSK Investigational Site	Bangalore
India	GSK Investigational Site	Bangalore
India	GSK Investigational Site	Chennai
India	GSK Investigational Site	Mumbai
India	GSK Investigational Site	Pune
Lithuania	GSK Investigational Site	Kaunas
Lithuania	GSK Investigational Site	Kaunas
Lithuania	GSK Investigational Site	Kaunas
Lithuania	GSK Investigational Site	Vilnius
Mexico	GSK Investigational Site	Cuernavaca	Morelos
Mexico	GSK Investigational Site	Durango
Mexico	GSK Investigational Site	Guadalajara	Jalisco
Mexico	GSK Investigational Site	Mérida	Yucatán
New Zealand	GSK Investigational Site	Rotorua
Poland	GSK Investigational Site	Bydgoszcz
Poland	GSK Investigational Site	Porabka
Poland	GSK Investigational Site	Siemianowice Slaskie
Poland	GSK Investigational Site	Wroclaw
Puerto Rico	GSK Investigational Site	Aibonito/Puerto Rico
Puerto Rico	GSK Investigational Site	Caguas
Puerto Rico	GSK Investigational Site	Carolina
Puerto Rico	GSK Investigational Site	Ponce
Puerto Rico	GSK Investigational Site	Rio Piedras
Puerto Rico	GSK Investigational Site	Trujillo Alto/Puerto Rico
Romania	GSK Investigational Site	Arad
Romania	GSK Investigational Site	Brasov
Romania	GSK Investigational Site	Sfantu Gheorghe
Romania	GSK Investigational Site	Timisoara
Russian Federation	GSK Investigational Site	Moscow
Russian Federation	GSK Investigational Site	Saint-Peterburgh
Russian Federation	GSK Investigational Site	St.Petersburg
Russian Federation	GSK Investigational Site	Tomsk
Russian Federation	GSK Investigational Site	Tumen
South Africa	GSK Investigational Site	Bellville
South Africa	GSK Investigational Site	Gauteng
South Africa	GSK Investigational Site	Lenasia South	Gauteng
South Africa	GSK Investigational Site	Parow
South Africa	GSK Investigational Site	Roodepoort
Ukraine	GSK Investigational Site	Dnipropetrovsk
Ukraine	GSK Investigational Site	Kyiv
Ukraine	GSK Investigational Site	Vinnitsa
United States	GSK Investigational Site	Albuquerque	New Mexico
United States	GSK Investigational Site	Artesia	California
United States	GSK Investigational Site	Asheboro/North Carolina	North Carolina
United States	GSK Investigational Site	Athens/Tennessee	Tennessee
United States	GSK Investigational Site	Atlanta	Georgia
United States	GSK Investigational Site	Atlanta	Georgia
United States	GSK Investigational Site	Bellevue	Washington
United States	GSK Investigational Site	Bensalem/Pennsylvania	Pennsylvania
United States	GSK Investigational Site	Bloomingdale	Illinois
United States	GSK Investigational Site	Boston	Massachusetts
United States	GSK Investigational Site	Buena Park	California
United States	GSK Investigational Site	Burke	Virginia
United States	GSK Investigational Site	Canal Fulton	Ohio
United States	GSK Investigational Site	Chesterfield	Missouri
United States	GSK Investigational Site	Chicago	Illinois
United States	GSK Investigational Site	Clifton	New Jersey
United States	GSK Investigational Site	Commack	New York
United States	GSK Investigational Site	Corpus Christi	Texas
United States	GSK Investigational Site	Dallas	Texas
United States	GSK Investigational Site	Dallas	Texas
United States	GSK Investigational Site	Deland/Florida	Florida
United States	GSK Investigational Site	Fresno	California
United States	GSK Investigational Site	Greenbrae	California
United States	GSK Investigational Site	Gulfport	Mississippi
United States	GSK Investigational Site	Harlingen/Texas	Texas
United States	GSK Investigational Site	Henderson	Nevada
United States	GSK Investigational Site	Hollywood	Florida
United States	GSK Investigational Site	Houston	Texas
United States	GSK Investigational Site	Houston	Texas
United States	GSK Investigational Site	Houston	Texas
United States	GSK Investigational Site	Ithaca	New York
United States	GSK Investigational Site	Jackson	Mississippi
United States	GSK Investigational Site	Jacksonville/Florida	Florida
United States	GSK Investigational Site	Kosciusko	Mississippi
United States	GSK Investigational Site	La Jolla	California
United States	GSK Investigational Site	Lafayette	Louisiana
United States	GSK Investigational Site	Lake Charles	Louisiana
United States	GSK Investigational Site	Las Vegas	Nevada
United States	GSK Investigational Site	Las Vegas	Nevada
United States	GSK Investigational Site	Las Vegas	Nevada
United States	GSK Investigational Site	Las Vegas	Nevada
United States	GSK Investigational Site	Manning	South Carolina
United States	GSK Investigational Site	Mesa	Arizona
United States	GSK Investigational Site	Miami	Florida
United States	GSK Investigational Site	Miami	Florida
United States	GSK Investigational Site	Midland	Texas
United States	GSK Investigational Site	New York	New York
United States	GSK Investigational Site	Norwalk	California
United States	GSK Investigational Site	Oak Brook	Illinois
United States	GSK Investigational Site	Ocoee/Florida	Florida
United States	GSK Investigational Site	Oxon Hill	Maryland
United States	GSK Investigational Site	Petaluma	California
United States	GSK Investigational Site	Rolling Fork	Mississippi
United States	GSK Investigational Site	Sacramento	California
United States	GSK Investigational Site	Saint Cloud	Florida
United States	GSK Investigational Site	San Anonio	Texas
United States	GSK Investigational Site	San Antonio	Texas
United States	GSK Investigational Site	San Mateo	California
United States	GSK Investigational Site	Santa Ana	California
United States	GSK Investigational Site	Simpsonville	South Carolina
United States	GSK Investigational Site	South Bend	Indiana
United States	GSK Investigational Site	St. Louis/Missouri	Missouri
United States	GSK Investigational Site	Tarzana	California
United States	GSK Investigational Site	Torrance	California
United States	GSK Investigational Site	West Chester	Pennsylvania

Sponsors (1)

Lead Sponsor	Collaborator
GlaxoSmithKline

Countries where clinical trial is conducted

United States,  Canada,  Czechia,  Estonia,  Germany,  Greece,  India,  Lithuania,  Mexico,  New Zealand,  Poland,  Puerto Rico,  Romania,  Russian Federation,  South Africa,  Ukraine, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Mean Change From Baseline in Hemoglobin A1c (Glycosylated Hemoglobin) (HbA1c) at Week 12	The blood samples were collected at Baseline, Week 4, Week 8 and at Week 12 (or early withdrawal). Baseline was defined as the period immediately preceding treatment with study medication (Week 0). For participants with missing Baseline assessment, the last pre-therapy value prior to the Baseline visit was used as the Baseline value. Change from Baseline was the value at Week 12 minus Baseline value. The primary analysis was performed on the Intent-to-Treat (ITT) Population with Last observation carried forward (LOCF). Adjusted mean is presented as least square (LS) mean.	Baseline (Week 0) and at Week 12
Secondary	Mean Change From Baseline in HbA1c at Weeks 4 and 8	The blood samples were collected at Baseline, Week 4, Week 8 and at Week 12 (or early withdrawal). Baseline was defined as the period immediately preceding treatment with study medication (Week 0). For participants with missing Baseline assessment, the last pre-therapy value prior to the Baseline visit was used as the Baseline value. Change from Baseline was the value at Week 4 and 8 minus Baseline value. The primary analysis was performed on the ITT Population with LOCF.	Baseline (Week 0) and at Week 4 nad 8
Secondary	Mean Change From Baseline to Week 12 in Fasting Plasma Glucose (FPG)	The samples were collected at Baseline, Week 2, Week 4, Week 8, Week 12 and Week 14 (follow up). Participants were asked to be on fast for at least 8 hours prior to each study visits and collection of lab samples. Baseline was defined as the period immediately preceding treatment with study medication (Week 0). For participants with missing Baseline assessment, the last pre-therapy value prior to the Baseline visit was used as the Baseline value. Change from Baseline was the value at Week 12 minus Baseline value. The primary analysis was performed on the ITT Population with LOCF. Adjusted mean is presented as LS mean.	Baseline (Week 0) and at Week 12
Secondary	Mean Change From Baseline to Week 12 in Fructosamine (Corrected)	The blood samples were collected at Baseline, Week 2, Week 4, Week 8, Week 12 and Week 14 (follow up). Participants were asked to be on fast for at least 8 hours prior to each study visits and collection of lab samples. Baseline was defined as the period immediately preceding treatment with study medication (Week 0). For participants with missing Baseline assessment, the last pre-therapy value prior to the Baseline visit was used as the Baseline value. Change from Baseline was the value at Week 12 minus Baseline value. The primary analysis was performed on the ITT Population with LOCF. Adjusted mean is presented as LS mean.	Baseline (Week 0) and at Week 12
Secondary	Number of Participants Who Were HbA1c Responders at Week 12	Differences between treatment groups in the proportion of participants who achieved HbA1c targets of <=6.5% and <7% at Week 12 in the ITT population with LOCF were assessed based on a logistic regression model with terms included for treatment and Baseline HbA1c. Differences between treatment groups in the proportion of participants who achieved a clinically meaningful decreases from Baseline in HbA1c (>=0.7%) at Week 12 were assessed in the same manner.	Week 12
Secondary	Number of Participants Who Were Fasting Plasma Glucose (FPG) Responders at Week 12	Differences between treatment groups in the proportion of participants who achieved FPG targets of <7.0 millimoles per liter (mmol/L) (126 milligrams per deciliter [mg/dL]) and <7.8 mmol/L (140 mg/dL) at Week 12 in the ITT population with LOCF were assessed based on a logistic regression model with terms included for treatment and Baseline FPG. The proportion of participants who achieved the target of <5.5 mmol/L (100 mg/dL) at Week 12 within each treatment group were summarized only. Differences between treatment groups in the proportion of participants who achieved a clinically meaningful decreases from Baseline in FPG (1.7 mmol/L [>=30 mg/dL]) at Week 12 were assessed in the same manner.	Week 12
Secondary	Mean Change From Baseline to Week 12 in Triglycerides	Samples were collected at Baseline and at Week 12 (or early withdrawal). Baseline was defined as the period immediately preceding treatment with study medication (Week 0). For participants with missing Baseline assessment, the last pre-therapy value prior to the Baseline visit was used as the Baseline value. Change from Baseline was the value at Week 12 minus Baseline value. Adjusted mean is presented as LS mean.	Baseline (Week 0) and at Week 12
Secondary	Mean Change From Baseline to Week 12 in Total Cholesterol	Samples were collected at Baseline and at Week 12 (or early withdrawal). Baseline was defined as the period immediately preceding treatment with study medication (Week 0). For participants with missing Baseline assessment, the last pre-therapy value prior to the Baseline visit was used as the Baseline value. Change from Baseline was the value at Week 12 minus Baseline value. Adjusted mean is presented as LS mean.	Baseline (Week 0) and at Week 12
Secondary	Mean Change From Baseline to Week 12 in Low Density Lipoprotein Cholesterol (LDL-c)	Blood samples were collected at Baseline and at Week 12 (or early withdrawal). Baseline was defined as the period immediately preceding treatment with study medication (Week 0). For participants with missing Baseline assessment, the last pre-therapy value prior to the Baseline visit was used as the Baseline value. Change from Baseline was the value at Week 12 minus Baseline value. Adjusted mean is presented as LS mean.	Baseline (Week 0) and Week 12
Secondary	Mean Change From Baseline to Week 12 in High Density Lipoprotein Cholesterol (HDL-c)	Blood samples were collected at Baseline and at Week 12 (or early withdrawal). Baseline was defined as the period immediately preceding treatment with study medication (Week 0). For participants with missing Baseline assessment, the last pre-therapy value prior to the Baseline visit was used as the Baseline value. Change from Baseline was the value at Week 12 minus Baseline value. Adjusted mean is presented as LS mean.	Baseline (Week 0) and Week 12
Secondary	Mean Change From Baseline to Week 12 in LDL-c/HDL-c Ratio	Blood samples were collected at Baseline and at Week 12 (or early withdrawal). Baseline was defined as the period immediately preceding treatment with study medication (Week 0). For participants with missing Baseline assessment, the last pre-therapy value prior to the Baseline visit was used as the Baseline value. Change from Baseline was the value at Week 12 minus Baseline value. Adjusted mean is presented as LS mean.	Baseline (Week 0) and Week 12
Secondary	Mean Change From Baseline to Week 12 in Total Cholesterol/HDL-c Ratio	Blood samples were collected at Baseline and at Week 12 (or early withdrawal). Baseline was defined as the period immediately preceding treatment with study medication (Week 0). For participants with missing Baseline assessment, the last pre-therapy value prior to the Baseline visit was used as the Baseline value. Change from Baseline was the value at Week 12 minus Baseline value. Adjusted mean is presented as LS mean.	Baseline (Week 0) and Week 12
Secondary	Mean Change From Baseline to Week 12 in Body Weight	Body weight measurement was taken at Baseline, Week 2, Week 4, Week 8, Week 12 and at Week 14 (follow up). Baseline was defined as the period immediately preceding treatment with study medication (Week 0). For participants with missing Baseline assessment, the last pre-therapy value prior to the Baseline visit was used as the Baseline value. Change from Baseline was the value at Week 12 minus Baseline value. Adjusted mean is presented as LS mean.	Baseline (Week 0) and Week 12
Secondary	Number of Participants With Any On-therapy Adverse Events (AEs) and Serious Adverse Events (SAEs)	AE was defined as any untoward medical occurrence in a clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. SAE was defined as any untoward event resulting in death, life threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, congenital anomaly/birth defect or any other situation according to medical or scientific judgment.	Up to Week 12
Secondary	Number of Participants With On-therapy Hypoglycemia	Participants were provided with a Daily Glucose Monitoring Log to record glucose meter readings and to record symptoms of hypoglycemia. A separate electronic case report form (eCRF) page was provided to capture events of hypoglycemia.	Up to Week 12
Secondary	Number of Participants With Vital Signs of Potential Clinical Importance (PCI) at Any Time on Therapy	Systolic blood pressure (SBP), diastolic blood pressure (DBP), heart rate (HR) were measured pre-dose in duplicate, after the participant has been lying quietly for 5 minutes, and then in duplicate 3 minutes after standing up. Participants were asked to refrain from smoking for at least 30 minutes prior to vital sign measurements.	Up to Week 12
Secondary	Number of Participants With Abnormal Electrocardiogram (ECG) Findings at Any Time Post-Baseline	Full 12-lead ECGs were recorded at Randomization (Week 0), Week 4, and Week 12 or early withdrawal. If the QTc was >500 milliseconds on the locally read ECG recording, an additional 2 ECG recordings at 10 minute intervals were made at that visit. If the average QTc for the 3 recordings was >500 milliseconds, the participant was withdrawn from the study.	Up to Week 12
Secondary	Number of Participants With Abnormal Chemistry Value of PCI at Any Time on Therapy	Chemistry parameters: Albumin, Alkaline phosphatase, Alanine animotransferase, Aspartate aminotransferase, Total billirubin, Calcium, Carbon dioxide/Bicarbonate, Glucose, Potassium, Sodium, Phosphorus and Total protein were assessed for abnormal PCI values. Participants were instructed to fast for at least 8 hours prior to all study visits for the collection of laboratory samples. Samples were collected at Baseline, Week 2, Week 4, Week 8, Week 12 and at Week 14 (follow up).	Up to Week 12
Secondary	Number of Participants With Abnormal Hematology Value of PCI at Any Time on Therapy	Hematology parameters: Hemoglobin, Hematocrit, Platelet count and White blood cells were assessed for abnormal PCI values. Participants were instructed to fast for at least 8 hours prior to all study visits for the collection of laboratory samples. Samples were collected at Baseline, Week 2, Week 4, Week 8, Week 12 and at Week 14 (follow up).	Up to Week 12