A New Oral Treatment For Type II Diabetes Mellitus

Diabetes Mellitus, Type 2 Clinical Trial

Official title:

A 12-Week, Parallel-Group, Double-Blind, Randomized, Placebo-Controlled, Multicenter, Dose Ranging Study to Evaluate the Efficacy, Safety and Tolerability of Denagliptin, Administered Orally, Once Daily, as Monotherapy in Subjects With Type 2 Diabetes Mellitus Followed by a 12-week Active Treatment Extension

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00111800
• Other study ID #: DPB100925
• Status: Completed
• Phase: Phase 2
• First received: May 25, 2005
• Last updated: March 19, 2018
• Start date: April 28, 2005
• Est. completion date: July 21, 2006

Study information

• Verified date: March 2018
• Source: GlaxoSmithKline
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This is a 24-week study investigating the safety and efficacy of several dosages of a potential new oral medicine for Type II diabetes mellitus.

Description:

A 12-Week, Parallel-Group, Double-Blind, Randomized, Placebo-Controlled, Multicenter, Dose Ranging Study to Evaluate the Efficacy, Safety and Tolerability of GW823093, Administered Orally, Once Daily, as Monotherapy in Subjects With Type 2 Diabetes Mellitus followed by a 12-week Active Treatment Extension

Recruitment information / eligibility

• Status: Completed
• Enrollment: 375
• Est. completion date: July 21, 2006
• Est. primary completion date: July 1, 2006
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

Inclusion criteria:

• Women must not be pregnant and must not be breastfeeding.

• Have Type II diabetes.

• Not taking any medicine for diabetes, or taking one oral medicine for their diabetes.

Exclusion criteria:

• Have any underlying or significant active disease that would prevent the subject from safely participating in the trial by the judgement of the study doctor.

Related Conditions & MeSH terms

• Diabetes Mellitus
• Diabetes Mellitus, Type 2

Intervention

Drug:
• Placebo
Placebo capsules which were white, opaque capsules with no identifying markings, containing white to off-white beads.
• DEN 2.5 mg
DEN 2.5 mg capsules which were white, opaque capsules with no identifying markings, containing white to off-white beads.
• DEN 7.5 mg
DEN 7.5 mg capsules which were white, opaque capsules with no identifying markings, containing white to off-white beads.
• DEN 15 mg
DEN 15 mg capsules which were white, opaque capsules with no identifying markings, containing white to off-white beads.
• DEN 30 mg
DEN 30 mg capsules which were white, opaque capsules with no identifying markings, containing white to off-white beads.
• DEN 45 mg
DEN 45 mg capsules which were white, opaque capsules with no identifying markings, containing white to off-white beads.

Locations

Country	Name	City	State
Canada	GSK Investigational Site	Bay Roberts	Newfoundland and Labrador
Canada	GSK Investigational Site	Brampton	Ontario
Canada	GSK Investigational Site	Coquitlam	British Columbia
Canada	GSK Investigational Site	Gatineau	Quebec
Canada	GSK Investigational Site	Mirabel	Quebec
Canada	GSK Investigational Site	Pointe-Claire	Quebec
Canada	GSK Investigational Site	Sainte-Foy	Quebec
Canada	GSK Investigational Site	Sherbrooke	Quebec
Canada	GSK Investigational Site	Toronto	Ontario
Canada	GSK Investigational Site	Toronto	Ontario
Canada	GSK Investigational Site	Waterloo	Ontario
Canada	GSK Investigational Site	Winnipeg	Manitoba
Czechia	GSK Investigational Site	Brno
Czechia	GSK Investigational Site	Ceske Budejovice
Czechia	GSK Investigational Site	Cheb
Czechia	GSK Investigational Site	Liberec
Czechia	GSK Investigational Site	Praha 2
Czechia	GSK Investigational Site	Praha 5
Czechia	GSK Investigational Site	Praha 5
Czechia	GSK Investigational Site	Trebic
Finland	GSK Investigational Site	Helsinki
Finland	GSK Investigational Site	Kuopio
Finland	GSK Investigational Site	Oulu
Germany	GSK Investigational Site	Bad Kreuznach	Hessen
Germany	GSK Investigational Site	Bad Lauterberg	Niedersachsen
Germany	GSK Investigational Site	Bammental	Baden-Wuerttemberg
Germany	GSK Investigational Site	Deggingen	Baden-Wuerttemberg
Germany	GSK Investigational Site	Dresden	Sachsen
Germany	GSK Investigational Site	Dresden	Sachsen
Germany	GSK Investigational Site	Freital	Sachsen
Germany	GSK Investigational Site	Haag	Bayern
Germany	GSK Investigational Site	Heidelberg	Baden-Wuerttemberg
Germany	GSK Investigational Site	Hirschhorn	Hessen
Germany	GSK Investigational Site	Hoehenkirchen-Siegertsbrunn	Bayern
Germany	GSK Investigational Site	Ingelheim	Rheinland-Pfalz
Germany	GSK Investigational Site	Kelkheim	Hessen
Germany	GSK Investigational Site	Kippenheim	Baden-Wuerttemberg
Germany	GSK Investigational Site	Koenigsfeld	Baden-Wuerttemberg
Germany	GSK Investigational Site	Lueneburg	Niedersachsen
Germany	GSK Investigational Site	Mainz	Rheinland-Pfalz
Germany	GSK Investigational Site	Offenbach	Hessen
Germany	GSK Investigational Site	Offenbach	Hessen
Germany	GSK Investigational Site	Offenburg	Baden-Wuerttemberg
Germany	GSK Investigational Site	Pirna	Sachsen
Germany	GSK Investigational Site	Rhaunen	Rheinland-Pfalz
Germany	GSK Investigational Site	Schmiedeberg	Sachsen
Germany	GSK Investigational Site	Sinsheim	Baden-Wuerttemberg
Germany	GSK Investigational Site	Speyer	Rheinland-Pfalz
Germany	GSK Investigational Site	Stockach	Baden-Wuerttemberg
Germany	GSK Investigational Site	Tostedt	Niedersachsen
Germany	GSK Investigational Site	Weinheim	Baden-Wuerttemberg
Greece	GSK Investigational Site	Athens
Greece	GSK Investigational Site	Heraklion, Crete
Greece	GSK Investigational Site	Lavrio
Greece	GSK Investigational Site	Melissia
Greece	GSK Investigational Site	Thessaloniki
Greece	GSK Investigational Site	Thessaloniki
Greece	GSK Investigational Site	Thessaloniki
Greece	GSK Investigational Site	Thessaloniki
Latvia	GSK Investigational Site	Jelgava
Latvia	GSK Investigational Site	Ogre
Latvia	GSK Investigational Site	Riga
Latvia	GSK Investigational Site	Riga
Latvia	GSK Investigational Site	Riga
Latvia	GSK Investigational Site	Talsi
Latvia	GSK Investigational Site	Valmiera
Puerto Rico	GSK Investigational Site	Ponce
Romania	GSK Investigational Site	Brasov
Romania	GSK Investigational Site	Bucharest
Romania	GSK Investigational Site	Bucharest
Sweden	GSK Investigational Site	Göteborg
Sweden	GSK Investigational Site	Malmö
Sweden	GSK Investigational Site	Stockholm
United States	GSK Investigational Site	Albany	New York
United States	GSK Investigational Site	Arlington	Texas
United States	GSK Investigational Site	Atlanta	Georgia
United States	GSK Investigational Site	Bellingham	Washington
United States	GSK Investigational Site	Buffalo	New York
United States	GSK Investigational Site	Burke	Virginia
United States	GSK Investigational Site	Chicago	Illinois
United States	GSK Investigational Site	Cincinnati	Ohio
United States	GSK Investigational Site	Columbia	South Carolina
United States	GSK Investigational Site	Dallas	Texas
United States	GSK Investigational Site	Dallas	Texas
United States	GSK Investigational Site	Denver	Colorado
United States	GSK Investigational Site	Durham	North Carolina
United States	GSK Investigational Site	Hollywood	Florida
United States	GSK Investigational Site	Honolulu	Hawaii
United States	GSK Investigational Site	Indianapolis	Indiana
United States	GSK Investigational Site	Jefferson Hills	Pennsylvania
United States	GSK Investigational Site	Johnson City	New York
United States	GSK Investigational Site	Kettering	Ohio
United States	GSK Investigational Site	Kingsport	Tennessee
United States	GSK Investigational Site	Las Vegas	Nevada
United States	GSK Investigational Site	Long Beach	California
United States	GSK Investigational Site	Marietta	Georgia
United States	GSK Investigational Site	Miami	Florida
United States	GSK Investigational Site	Oxon Hill	Maryland
United States	GSK Investigational Site	Pahrump	Nevada
United States	GSK Investigational Site	Pasadena	California
United States	GSK Investigational Site	Raleigh	North Carolina
United States	GSK Investigational Site	Rochester	New York
United States	GSK Investigational Site	Salt Lake City	Utah
United States	GSK Investigational Site	San Antonio	Texas
United States	GSK Investigational Site	Sewickley	Pennsylvania
United States	GSK Investigational Site	Sunset	Louisiana
United States	GSK Investigational Site	Syracuse	New York
United States	GSK Investigational Site	Tacoma	Washington
United States	GSK Investigational Site	Vancouver	Washington

Sponsors (1)

Lead Sponsor	Collaborator
GlaxoSmithKline

Countries where clinical trial is conducted

United States,  Canada,  Czechia,  Finland,  Germany,  Greece,  Latvia,  Puerto Rico,  Romania,  Sweden, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change From Baseline in Glycosylated Hemoglobin (HbA1c) at Week 12	HbA1c is used to show in participants with diabetes, how well their diabetes is being controlled. The HbA1c test gives the average blood glucose levels over the pervious two to three months. The sample for HbA1c assessment was collected at Visit 5 (Week 0) and Visit 12 (Week 12). Baseline value was defined as the assessment done at Week 0. The change from Baseline was calculated by subtracting the Baseline value (Week 0) from the individual post-Baseline (Week 12) value. Analysis of covariance (ANCOVA) model for analysis was used with the terms for gender, prior therapy (diet & exercise/monotherapy), treatment, region and Baseline measurement (continuous covariate). Last observation carried forward (LOCF) dataset defined as carrying forward of the last valid observation recorded on-treatment (scheduled or unscheduled) for participants who withdrew from the study to all remaining main phase visits was used. Adjusted mean is reported as least square (LS) mean.	Baseline (Week 0) and Week 12
Secondary	Change From Baseline in HbA1c at Week 4, 8, 16, 20 and 24	HbA1c is use d to show in participants with diabetes, how well their diabetes is being controlled. The HbA1c test gives the average blood glucose levels over the pervious two to three months. The sample for HbA1c assessment was collected at Visit 5 (Week 0), Visit 9 (Week 4), Visit 11 (Week 8), Visit 16 (Week 16), Visit 17 (Week 20) and Visit 18 (Week 24). Baseline value was defined as the assessment done at Week 0. The change from Baseline was calculated by subtracting the Baseline value (Week 0) from the individual post-Baseline (Week 4, Week 8, Week 16, Week 20 and Week 24) values.	Baseline (Week 0) up to Week 24
Secondary	Change From Baseline in FPG at Week 12	The glycemic assessment of FPG measures a participant's blood sugar level after fasting or not eating anything for at least eight hours (h). The samples of FPG was collected was collected at Visit 5 (Week 0) and Visit 12 (Week 12). Baseline value was defined as the assessment done at Week 0. The change from Baseline was calculated by subtracting the Baseline value (Week 0) from the individual post-Baseline (Week 12) value. ANCOVA model for analysis was used with the terms for gender, prior therapy (diet & exercise/monotherapy), treatment, region and Baseline measurement (continuous covariate). Adjusted mean is reported as LS mean.	Baseline (Week 0) and Week 12
Secondary	Change From Baseline in FPG at Week 1, 2, 3, 4, 6, 8, 13, 14, 15, 16, 20 and 24	The glycemic assessment of FPG measures a participant's blood sugar level after fasting or not eating anything for at least eight h. The sample for FPG assessment was collected at Visit 5 (Week 0), Visit 6 (Week 1), Visit 7 (Week 2), Visit 8 (Week 3), Visit 9 (Week 4), Visit 10 (Week 6), Visit 11 (Week 8), Visit 13 (Week 13), Visit 14 (Week 14), Visit 15 (Week 15), Visit 16 (Week 16), Visit 17 (Week 20) and Visit 18 (Week 24). Baseline value was defined as the assessment done at Week 0. The change from Baseline was calculated by subtracting the Baseline value (Week 0) from the individual post-Baseline (Week 1, 2, 3, 4, 6, 8, 13, 14, 15, 16, 20 and 24) values.	Baseline (Week 0) up to Week 24
Secondary	Number of Participants Who Were HbA1c Responders at Week 12	HbA1c is used to show in participants with diabetes, how well their diabetes is being controlled. The HbA1c test gives the average blood glucose levels over the pervious two to three months. The responders were defined as HbA1c values of <=6.5%, <7% and HbA1c reduction of >=0.7%. Analysis was done based on a logistic regression model with terms included for treatment, gender, prior therapy and Baseline measurement.	Week 12
Secondary	Number of Participants of FPG Responders at Week 12	The glycemic assessment of FPG measures a participant's blood sugar level after fasting or not eating anything for at least eight h. The responders were defined as FPG value of <7 mmol/L and FPG reduction value of >=1.7 mmol/L. Analysis was done based on a logistic regression model with terms included for treatment, gender, prior therapy and Baseline measurement.	Week 12
Secondary	Change From Baseline in Fructosamine at Week 12	The sample for fructosamine (total and corrected protein) assessment was collected at Visit 5 (Week 0) and Visit 12 (Week 12). Baseline value was defined as the assessment done at Week 0. The change from Baseline was calculated by subtracting the Baseline value (Week 0) from the individual post-Baseline (Week 12) value. ANCOVA model for analysis was used with the terms for gender, prior therapy (diet & exercise/monotherapy), treatment, region and Baseline measurement (continuous covariate). Adjusted mean is reported as LS mean.	Baseline (Week 0) and Week 12
Secondary	Change From Baseline in Fructosamine at Weeks 4, 8, 16, 20 and 24	The sample for fructosamine (total and corrected protein) assessment was collected at Visit 5 (Week 0), Visit 9 (Week 4), Visit 11 (Week 8), Visit 16 (Week 16), Visit 17 (Week 20) and Visit 18 (Week 24). Baseline value was defined as the assessment done at Week 0. The change from Baseline was calculated by subtracting the Baseline value (Week 0) from the individual post-Baseline (Week 4, 8, 16, 20 and 24) values.	Baseline (Week 0) up to Week 24
Secondary	Change From Baseline in Fasting Serum Insulin and Pro-insulin at Week 12	The assessment of fasting serum insulin measures a participant's serum insulin level after fasting or not eating anything for at least eight h. The sample for fasting serum insulin and pro-insulin was collected at Visit 5 (Week 0) and Visit 12 (Week 12). Baseline value was defined as the assessment done at Week 0. The change from Baseline was calculated by subtracting the Baseline value (Week 0) from the individual post-Baseline (Week 12) value. ANCOVA model for analysis was used with the terms for gender, prior therapy (diet & exercise/monotherapy), treatment, region and baseline measurement (continuous covariate). Adjusted mean is reported as LS mean.	Baseline (Week 0) and Week 12
Secondary	Change From Baseline in Fasting Serum Insulin at Weeks 4, 8, 16, 20, 24 and Pro-insulin at Weeks 4 and 8	The assessment of fasting serum insulin measures a participant's serum insulin level after fasting or not eating anything for at least eight h. The sample for fasting serum insulin was collected at Visit 5 (Week 0) Visit 9 (Week 4), Visit 11 (Week 8), Visit 16 (Week 16), Visit 17 (Week 20) and Visit 18 (Week 24). The sample for pro-insulin was collected at Visit 5 (Week 0), Visit 9 (Week 4) and Visit 11 (Week 8). Baseline value was defined as the assessment done at Week 0. The change from Baseline was calculated by subtracting the Baseline value (Week 0) from the individual post-Baseline (Week 4, 8, 16, 20 and 24) values.	Baseline (Week 0) up to Week 24
Secondary	Change From Baseline in Pro-insulin at Week 16, 20 and 24.	The sample for pro-insulin was collected at Visit 5 (Week 0), Visit 16 (Week 16), Visit 17 (Week 20) and Visit 18 (Week 24). Baseline value was defined as the assessment done at Week 0. The change from Baseline was calculated by subtracting the Baseline value (Week 0) from the individual post-Baseline (Week 16, 20 and 24) values.	Baseline (Week 0) up to Week 24
Secondary	Change From Baseline in Pro-insulin to Insulin Ratio at Week 12	The samples for pro-insulin and insulin was collected at Visit 5 (Week 0) and Visit 12 (Week 12). Baseline value was defined as the assessment done at Week 0. The change from Baseline was calculated by subtracting the Baseline value (Week 0) from the individual post-Baseline (Week 12) value. ANCOVA model for analysis was used with the terms for gender, prior therapy (diet & exercise/monotherapy), treatment, region and baseline measurement (continuous covariate). Adjusted mean is reported as LS mean.	Baseline (Week 0) and Week 12
Secondary	Change From Baseline in Pro-insulin to Insulin Ratio at Week 4 and 8	The samples for pro-insulin and insulin was collected at Visit 5 (Week 0), Visit 9 (Week 4) and Visit 11 (Week 8). Baseline value was defined as the assessment done at Week 0. The change from Baseline was calculated by subtracting the Baseline value (Week 0) from the individual post-Baseline (Week 4 and 8) values. ANCOVA model for analysis was used with the terms for gender, prior therapy (diet & exercise/monotherapy), treatment, region and baseline measurement (continuous covariate). Adjusted mean is reported as LS mean.	Baseline (Week 0) and Week 4 and 8
Secondary	Number of Participants With Any Adverse Events (AE) or Serious Adverse Events (SAE) and Events of Hypoglycaemia	An AE is defined as any untoward medical occurrence in a participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. An SAE is defined as any untoward medical occurrence that, at any dose, results in death, is life-threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, or is a congenital anomaly/birth defect, may jeopardize the participant or may require medical or surgical intervention to prevent one of the other outcomes listed in this definition. Medications that lowered blood glucose were capable of producing hypoglycemia or symptoms of hypoglycemia. Participants were provided with a hypoglycemic symptoms log at each visit and were asked to record symptoms of hypoglycemia.	Up to Week 25
Secondary	Number of Participants With AE and Event of Hypoglycaemia of Mild, Moderate and Severe	An AE is defined as any untoward medical occurrence in a participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. Medications that lowered blood glucose were capable of producing hypoglycemia or symptoms of hypoglycemia. Participants were provided with a hypoglycemic symptoms log at each visit and were asked to record symptoms of hypoglycemia. The assessment of severity was done by the investigator. A mild AE was defined as an event that was easily tolerated by the participant, causing minimal discomfort and not interfering with everyday activities. A moderate AE was defined as an event that was sufficiently discomforting to interfere with normal everyday activities. A severe AE was defined as an event that prevents normal everyday activities.	Up to Week 25
Secondary	Number of Participants With Change From Baseline Value of Potential Clinical Concern (PCC) in Vital Signs at Any Time During Therapy	The vital sign assessments include systolic blood pressure (SBP), diastolic blood pressure (DBP) and heart rate (HR). The assessments were done pre-dose at Visit 5 (Week 0), Visit 6 (Week 1), Visit 7 (Week 2), Visit 8 (Week 3), Visit 9 (Week 4), Visit 10 (Week 6), Visit 11 (Week 8), Visit 12 (Week 12), Visit 13 (Week 13), Visit 14 (Week 14), Visit 15 (Week 15), Visit 16 (Week 16), Visit 17 (Week 20) and Visit 18 (Week 24). Baseline value was defined as the assessment done at Week 0. The change from Baseline was calculated by subtracting the Baseline value (Week 0) from the individual post-Baseline (Week 1 to 24) values. The criteria for PCC included: HR increase or decrease from Baseline >30 beats per minute (bpm) and <50 or >120 bpm; SBP increase or decrease from Baseline >30 millimeter of mercury (mmHg) in the same posture and >170 or <100 mmHg; increase or decrease from Baseline >20 mmHg in same posture and >110 or <50 mmHg.	Baseline (Week 0) up to Week 24
Secondary	Change From Baseline in Body Weight Over Time	The assessment of body weight was done during the run-in phase, randomized treatment phase and Follow-up at Visit 2 (Week -5), Visit 3 (Week -4), Visit 4 (Week -2), Visit 5 (Week 0), Visit 6 (Week 1), Visit 7 (Week 2), Visit 8 (Week 3), Visit 9 (Week 4), Visit 10 (Week 6), Visit 11 (Week 8), Visit 12 (Week 12), Visit 13 (Week 13), Visit 14 (Week 14), Visit 15 (Week 15), Visit 16 (Week 16), Visit 17 (Week 20), Visit 12 (Week 12), Visit 18 (Week 24) and Visit 19 (Week 25). Baseline value was defined as the assessment done at Week 0. The change from Baseline was calculated by subtracting the Baseline value (Week 0) from the individual post-Baseline (Week -5 to 24) values.	Baseline (Week 0) and Week -5 to 25 (Follow-up)
Secondary	Change From Baseline in Body Mass Index (BMI) Over Time	BMI is an estimated the body fat of the participants, based on body weight divided by height squared. Height was assessed at Screening (Visit 2, Week -5) and confirmed at Baseline (Visit 5, Week 0). Weight was assessed at all Visits (Visit -5 to Visit 19). BMI was calculated during the run-in phase, randomized treatment phase and Follow-up at Visit 2 (Week -5), Visit 3 (Week -4), Visit 4 (Week -2), Visit 5 (Week 0), Visit 6 (Week 1), Visit 7 (Week 2), Visit 8 (Week 3), Visit 9 (Week 4), Visit 10 (Week 6), Visit 11 (Week 8), Visit 12 (Week 12), Visit 13 (Week 13), Visit 14 (Week 14), Visit 15 (Week 15), Visit 16 (Week 16), Visit 17 (Week 20), Visit 12 (Week 12), Visit 18 (Week 24) and Visit 19 (Week 25). Baseline value was defined as the assessment done at Week 0. The change from Baseline was calculated by subtracting the Baseline value (Week 0) from the individual post-Baseline (Week -5 to 24) values.	Baseline (Week 0) and Week -5 to 25 (Follow-up)
Secondary	Change From Baseline in Waist Circumference and Hip Circumference Over Time	Waist and hip measurements were done at Screening (Visit 2, Week -5), Visit 5 (Week 0), Visit 12 (Week 12) and Visit 18 (Week 24). Baseline value was defined as the assessment done at Week 0. The change from Baseline was calculated by subtracting the Baseline value (Week 0) from the individual post-Baseline (Week -5 to 24) values.	Baseline (Week 0) up to Week 24
Secondary	Mean Change From Baseline in Waist to Hip Ratio Over Time	Waist to hip ratio calculation from the waist and hip measurements were done at Screening (Visit 2, Week -5), Visit 5 (Week 0), Visit 12 (Week 12) and Visit 18 (Week 24). Baseline value was defined as the assessment done at Week 0. The change from Baseline was calculated by subtracting the Baseline value (Week 0) from the individual post-Baseline (Week -5 to 24) values.	Baseline (Week 0) up to Week 24
Secondary	Change From Baseline in 12-lead ECG Over Time	12-lead ECGs were obtained during the study using an ECG machine that automatically calculated the HR and measured PR, QRS, RR, QT, and QTc intervals. The mean PR interval, RR interval, QRS duration, uncorrected QT interval (UncQT) and QTcB (QT corrected by Bazett's formula) and QTcF (corrected by Friedericia's formula) was calculated from automated ECG readings. ECG was read centrally and locally at Visit 2 (Week -5), Visit 5 (Week 0), Visit 9 (Week 4), Visit 12 (Week 12), Visit 16 (Week 16) and Visit 18 (Week 24). Baseline value was defined as the assessment done at Week 0. The change from Baseline was calculated by subtracting the Baseline value (Week 0) from the individual post-Baseline (Week -5 to 24) values.	Baseline (Week 0) up to Week 24
Secondary	Number of Participants With Laboratory Clinical Chemistry Values of PCC at Any Time on Therapy	The parameters of clinical chemistry included sodium, potassium, chloride, bicarbonate, lactate dehydrogenase ([LDH] if >2x upper limit of reference range, LDH isoenzymes were collected), total protein, albumin, blood urea nitrogen (BUN), creatinine, total bilirubin, direct bilirubin, alkaline phosphatase (ALP), aspartate transaminase (AST), alanine transaminase (ALT), Calcium, phosphorus (inorganic) and uric acid. The assessments were done at Visit 5 (Week 0), Visit 6 (Week 1), Visit 7 (Week 2), Visit 8 (Week 3), Visit 9 (Week 4), Visit 10 (Week 6), Visit 11 (Week 8), Visit 12 (Week 12), Visit 13 (Week 13), Visit 14 (Week 14), Visit 15 (Week 15), Visit 16 (Week 16), Visit 17 (Week 20) and Visit 18 (Week 24). Only those parameters for which at least one value of PCC was reported are summarized.	Up to Week 24
Secondary	Number of Participants With Laboratory Haematology Values of PCC at Any Time on Therapy	The parameters of hematology included red blood cell (RBC) count, hemoglobin, hematocrit, platelet count and total white blood cell (WBC) count. The assessments were done at Visit 5 (Week 0), Visit 6 (Week 1), Visit 7 (Week 2), Visit 8 (Week 3), Visit 9 (Week 4), Visit 10 (Week 6), Visit 11 (Week 8), Visit 12 (Week 12), Visit 13 (Week 13), Visit 14 (Week 14), Visit 15 (Week 15), Visit 16 (Week 16), Visit 17 (Week 20) and Visit 18 (Week 24). Only those parameters for which at least one value of PCC was reported are summarized.	Up to Week 24
Secondary	Number of Participants With Abnormal Urinalysis Dipstick Result	The parameters of dipstick urinalysis included glucose, bilirubin, protein and ketones. The abnormal results of dispstick parameters were categorized for glucose as trace or 1/10 gram (g)/deciliter (dL %), 1+ or ¼ g/dL (%), 2+ or ½ g/dL (%), 3+ or 1 g/dL (%); for ketones as 1+ and trace; for proteins as 1+, 2+, 3+ and trace. The assessments were done at Visit 2 (Week -5), Visit 5 (Week 0), Visit 6 (Week 1), Visit 7 (Week 2), Visit 8 (Week 3), Visit 9 (Week 4), Visit 10 (Week 6), Visit 11 (Week 8), Visit 12 (Week 12), Visit 13 (Week 13), Visit 14 (Week 14), Visit 15 (Week 15), Visit 16 (Week 16), Visit 17 (Week 20), Visit 18 (Week 24) and Visit 19 (Week 25).	Up to Follow-up (Week 25)
Secondary	Number of Participants With Urinalysis Microscopic Result	The parameters of microscopic urinalysis included RBC and WBC. The microscopic urinalysis results for the parameters were categorized as cells of 0-1, 1-3, 3-5, 5-10, 10-15, 15-25, 25-50, 50-100 and innumerable. The assessments were done at Visit 2 (Week -5), Visit 5 (Week 0), Visit 6 (Week 1), Visit 7 (Week 2), Visit 8 (Week 3), Visit 9 (Week 4), Visit 10 (Week 6), Visit 11 (Week 8), Visit 12 (Week 12), Visit 13 (Week 13), Visit 14 (Week 14), Visit 15 (Week 15), Visit 16 (Week 16), Visit 17 (Week 20), Visit 18 (Week 24) and Visit 19 (Week 25).	Up to Follow-up (Week 25)
Secondary	Population Pharmacokinetic (PK) Parameter of Plasma Concentration of DEN	A total of 6 blood samples, 2 milliliter each were planned to be obtained over the course of the study for determination of DEN plasma concentrations. For each PK sampling visit a sampling interval was defined. PK samples were planned to be collected at any time during the defined sampling intervals.	Pre-dose at Week 0, 0.5 to 1.5 h post-dose at Week 4, 12, 16 or 20, 2 to 4 h post-dose at Week 4, 12, 16 or 20 and 6 to 10 h post-dose at Week 4, 12, 16 or 20
Secondary	Descriptive Statistics of Dipeptidyl Peptidase-IV (DPP-IV) Inhibition Performed as Part of the Population PK	A total of 6 blood samples, 2 milliliter each were planned to be obtained over the course of the study for determination of DPP-IV inhibition. For each PK sampling visit a sampling interval was defined. PK samples were planned to be collected at any time during the defined sampling intervals.	Pre-dose at Week 0, 0.5 to 1.5 h post-dose at Week 4, 12, 16 or 20, 2 to 4 h post-dose at Week 4, 12, 16 or 20 and 6 to 10 h post-dose at Week 4, 12, 16 or 20

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