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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.
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
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Placebo | Placebo Comparator | Participants received oral dose of matching placebo capsule to denagliptin (DEN) once daily in the morning, 30 minutes (min) prior to breakfast during the main phase 12-weeks treatment period. Participants who were randomized to placebo in the main phase 12-weeks treatment period received oral dose of DEN 2.5 milligram (mg) once daily in the morning, 30 min prior to breakfast during the extension phase 12-weeks treatment period. Participants were dispensed 3 bottles (bottle A, B and C) and were instructed to take 1 capsule daily from each bottle such that taking 1 capsule from each bottle daily provided the appropriate dose of placebo to the participants. |
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| DEN 2.5 mg | Experimental | Participants received oral dose of DEN 2.5 mg capsule once daily in the morning, 30 min prior to breakfast during the main phase/extension phase 12-weeks treatment period. Participants were dispensed 3 bottles (bottle A, B and C) and were instructed to take 1 capsule daily from each bottle such that taking 1 capsule from each bottle daily provided the appropriate dose of DEN 2.5 mg to the participants. |
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| DEN 7.5 mg | Experimental | Participants received oral dose of DEN 7.5 mg capsule once daily in the morning, 30 min prior to breakfast during the main phase/extension phase 12-weeks treatment period. Participants were dispensed 3 bottles (bottle A, B and C) and were instructed to take 1 capsule daily from each bottle such that taking 1 capsule from each bottle daily provided the appropriate dose of DEN 7.5 mg to the participants. |
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| DEN 15 mg |
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Placebo | Drug | Placebo capsules which were white, opaque capsules with no identifying markings, containing white to off-white beads. |
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| Measure | Description | Time Frame |
|---|---|---|
| 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 |
| Measure | Description | Time Frame |
|---|---|---|
| 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. |
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Inclusion criteria:
Exclusion criteria:
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| Name | Affiliation | Role |
|---|---|---|
| GSK Clinical Trials | GlaxoSmithKline | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| GSK Investigational Site | Long Beach | California | 90806 | United States | ||
| GSK Investigational Site |
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| Label | URL |
|---|---|
| Researchers can use this site to request access to anonymised patient level data and/or supporting documents from clinical studies to conduct further research. | View source |
| ID | Type | URL | Comment |
|---|---|---|---|
| 100925 | Individual Participant Data Set | View IPD |
Patient-level data for this study will be made available through www.clinicalstudydatarequest.com following the timelines and process described on this site.
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A total of 375 participants received denagliptin ([DEN] 2.5, 7.5, 15, 30 or 45 milligram [mg]) or placebo which constituted the Safety Population. A total of 318 entered extension phase of study; 3 participants completed main phase but did not enter extension phase.
The study was conducted from 28 April 2005 to 21 July 2006 across 94 centres from 9 countries.
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| ID | Title | Description |
|---|---|---|
| FG000 | Placebo | Participants received oral dose of matching placebo capsule to DEN once daily in the morning, 30 minutes (min) prior to breakfast during the main phase 12-weeks treatment period. Participants who were randomized to placebo in the main phase 12-weeks treatment period received oral dose of DEN 2.5 mg once daily in the morning, 30 min prior to breakfast during the extension phase 12-weeks treatment period. Participants were dispensed 3 bottles (bottle A, B and C) and were instructed to take 1 capsule daily from each bottle such that taking 1 capsule from each bottle daily provided the appropriate dose of placebo to the participants. |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Period 1: Main Phase (12 Weeks) |
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Participants received oral dose of DEN 15 mg capsule once daily in the morning, 30 min prior to breakfast during the main phase/extension phase 12-weeks treatment period. Participants were dispensed 3 bottles (bottle A, B and C) and were instructed to take 1 capsule daily from each bottle such that taking 1 capsule from each bottle daily provided the appropriate dose of DEN 15 mg to the participants. |
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| DEN 30 mg | Experimental | Participants received oral dose of DEN 30 mg capsule once daily in the morning, 30 min prior to breakfast during the main phase/extension phase 12-weeks treatment period. Participants were dispensed 3 bottles (bottle A, B and C) and were instructed to take 1 capsule daily from each bottle such that taking 1 capsule from each bottle daily provided the appropriate dose of DEN 30 mg to the participants. |
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| DEN 45 mg | Experimental | Participants received oral dose of DEN 45 mg capsule once daily in the morning, 30 min prior to breakfast during the main phase/extension phase 12-weeks treatment period. Participants were dispensed 3 bottles (bottle A, B and C) and were instructed to take 1 capsule daily from each bottle such that taking 1 capsule from each bottle daily provided the appropriate dose of DEN 45 mg to the participants. |
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| DEN 2.5 mg | Drug | DEN 2.5 mg capsules which were white, opaque capsules with no identifying markings, containing white to off-white beads. |
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| DEN 7.5 mg | Drug | DEN 7.5 mg capsules which were white, opaque capsules with no identifying markings, containing white to off-white beads. |
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| DEN 15 mg | Drug | DEN 15 mg capsules which were white, opaque capsules with no identifying markings, containing white to off-white beads. |
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| DEN 30 mg | Drug | DEN 30 mg capsules which were white, opaque capsules with no identifying markings, containing white to off-white beads. |
|
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| DEN 45 mg | Drug | DEN 45 mg capsules which were white, opaque capsules with no identifying markings, containing white to off-white beads. |
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| Baseline (Week 0) up to Week 24 |
| 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 |
| 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 |
| 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 |
| 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 |
| 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 |
| 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 |
| 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 |
| 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 |
| 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 |
| 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 |
| 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 |
| 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 |
| 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 |
| 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 |
| 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) |
| 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) |
| 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 |
| 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 |
| 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 |
| 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 |
| 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 |
| 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) |
| 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) |
| 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 |
| 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 |
| Pasadena |
| California |
| 91105 |
| United States |
| GSK Investigational Site | Denver | Colorado | 80220 | United States |
| GSK Investigational Site | Hollywood | Florida | 33021 | United States |
| GSK Investigational Site | Miami | Florida | 33126 | United States |
| GSK Investigational Site | Atlanta | Georgia | 30308 | United States |
| GSK Investigational Site | Marietta | Georgia | 30066 | United States |
| GSK Investigational Site | Honolulu | Hawaii | 96813 | United States |
| GSK Investigational Site | Chicago | Illinois | 60607 | United States |
| GSK Investigational Site | Indianapolis | Indiana | 46202 | United States |
| GSK Investigational Site | Sunset | Louisiana | 70584 | United States |
| GSK Investigational Site | Oxon Hill | Maryland | 20745 | United States |
| GSK Investigational Site | Las Vegas | Nevada | 89106 | United States |
| GSK Investigational Site | Pahrump | Nevada | 89048 | United States |
| GSK Investigational Site | Albany | New York | 12208 | United States |
| GSK Investigational Site | Buffalo | New York | 14209 | United States |
| GSK Investigational Site | Johnson City | New York | 13790 | United States |
| GSK Investigational Site | Rochester | New York | 14642 | United States |
| GSK Investigational Site | Syracuse | New York | 13210 | United States |
| GSK Investigational Site | Durham | North Carolina | 27710 | United States |
| GSK Investigational Site | Raleigh | North Carolina | 27612 | United States |
| GSK Investigational Site | Cincinnati | Ohio | 45246 | United States |
| GSK Investigational Site | Kettering | Ohio | 45429 | United States |
| GSK Investigational Site | Jefferson Hills | Pennsylvania | 15025 | United States |
| GSK Investigational Site | Sewickley | Pennsylvania | 15143 | United States |
| GSK Investigational Site | Columbia | South Carolina | 29201 | United States |
| GSK Investigational Site | Kingsport | Tennessee | 37660 | United States |
| GSK Investigational Site | Arlington | Texas | 76017 | United States |
| GSK Investigational Site | Dallas | Texas | 75230 | United States |
| GSK Investigational Site | Dallas | Texas | 75246 | United States |
| GSK Investigational Site | San Antonio | Texas | 78237 | United States |
| GSK Investigational Site | Salt Lake City | Utah | 84102 | United States |
| GSK Investigational Site | Burke | Virginia | 22015 | United States |
| GSK Investigational Site | Bellingham | Washington | 98226 | United States |
| GSK Investigational Site | Tacoma | Washington | 98403 | United States |
| GSK Investigational Site | Vancouver | Washington | 98664 | United States |
| GSK Investigational Site | Coquitlam | British Columbia | V3K 3P4 | Canada |
| GSK Investigational Site | Winnipeg | Manitoba | R3E 3P4 | Canada |
| GSK Investigational Site | Bay Roberts | Newfoundland and Labrador | A0G 1G0 | Canada |
| GSK Investigational Site | Brampton | Ontario | L6T 3T1 | Canada |
| GSK Investigational Site | Toronto | Ontario | M4R 2G4 | Canada |
| GSK Investigational Site | Toronto | Ontario | M9W 4L6 | Canada |
| GSK Investigational Site | Waterloo | Ontario | N2J 1C4 | Canada |
| GSK Investigational Site | Gatineau | Quebec | J8Y 6S8 | Canada |
| GSK Investigational Site | Mirabel | Quebec | J7J 2K8 | Canada |
| GSK Investigational Site | Pointe-Claire | Quebec | H9R 4S3 | Canada |
| GSK Investigational Site | Sainte-Foy | Quebec | G1W 4R4 | Canada |
| GSK Investigational Site | Sherbrooke | Quebec | J1H 4J6 | Canada |
| GSK Investigational Site | Brno | 656 51 | Czechia |
| GSK Investigational Site | Cheb | 350 02 | Czechia |
| GSK Investigational Site | České Budějovice | 370 87 | Czechia |
| GSK Investigational Site | Liberec | 46004 | Czechia |
| GSK Investigational Site | Prague | 128 21 | Czechia |
| GSK Investigational Site | Prague | 150 05 | Czechia |
| GSK Investigational Site | Prague | 158 00 | Czechia |
| GSK Investigational Site | Třebíč | 674 01 | Czechia |
| GSK Investigational Site | Helsinki | 00260 | Finland |
| GSK Investigational Site | Kuopio | 70210 | Finland |
| GSK Investigational Site | Oulu | 90100 | Finland |
| GSK Investigational Site | Bammental | Baden-Wurttemberg | 69245 | Germany |
| GSK Investigational Site | Deggingen | Baden-Wurttemberg | 73326 | Germany |
| GSK Investigational Site | Heidelberg | Baden-Wurttemberg | 69120 | Germany |
| GSK Investigational Site | Kippenheim | Baden-Wurttemberg | 77971 | Germany |
| GSK Investigational Site | Königsfeld im Schwarzwald | Baden-Wurttemberg | 78126 | Germany |
| GSK Investigational Site | Offenburg | Baden-Wurttemberg | 77654 | Germany |
| GSK Investigational Site | Sinsheim | Baden-Wurttemberg | 74889 | Germany |
| GSK Investigational Site | Stockach | Baden-Wurttemberg | 78333 | Germany |
| GSK Investigational Site | Weinheim | Baden-Wurttemberg | 69469 | Germany |
| GSK Investigational Site | Haag | Bavaria | 83527 | Germany |
| GSK Investigational Site | Höhenkirchen-Siegertsbrunn | Bavaria | 85635 | Germany |
| GSK Investigational Site | Bad Kreuznach | Hesse | 55545 | Germany |
| GSK Investigational Site | Hirschhorn | Hesse | 69434 | Germany |
| GSK Investigational Site | Kelkheim | Hesse | 65779 | Germany |
| GSK Investigational Site | Offenbach | Hesse | 63067 | Germany |
| GSK Investigational Site | Offenbach | Hesse | 63073 | Germany |
| GSK Investigational Site | Bad Lauterberg im Harz | Lower Saxony | 37431 | Germany |
| GSK Investigational Site | Lüneburg | Lower Saxony | 21335 | Germany |
| GSK Investigational Site | Tostedt | Lower Saxony | 21255 | Germany |
| GSK Investigational Site | Ingelheim | Rhineland-Palatinate | 55218 | Germany |
| GSK Investigational Site | Mainz | Rhineland-Palatinate | 55116 | Germany |
| GSK Investigational Site | Rhaunen | Rhineland-Palatinate | 55624 | Germany |
| GSK Investigational Site | Speyer | Rhineland-Palatinate | 67346 | Germany |
| GSK Investigational Site | Dresden | Saxony | 01129 | Germany |
| GSK Investigational Site | Dresden | Saxony | 01219 | Germany |
| GSK Investigational Site | Freital | Saxony | 01705 | Germany |
| GSK Investigational Site | Pirna | Saxony | 01796 | Germany |
| GSK Investigational Site | Schmiedeberg | Saxony | 01762 | Germany |
| GSK Investigational Site | Athens | 115 26 | Greece |
| GSK Investigational Site | Heraklion, Crete | 71409 | Greece |
| GSK Investigational Site | Lávrio | 19500 | Greece |
| GSK Investigational Site | Melíssia | 15127 | Greece |
| GSK Investigational Site | Thessaloniki | 546 42 | Greece |
| GSK Investigational Site | Thessaloniki | 551 32 | Greece |
| GSK Investigational Site | Thessaloniki | 564 29 | Greece |
| GSK Investigational Site | Thessaloniki | 564 34 | Greece |
| GSK Investigational Site | Jelgava | LV 3001 | Latvia |
| GSK Investigational Site | Ogre | LV 5001 | Latvia |
| GSK Investigational Site | Riga | LV 1002 | Latvia |
| GSK Investigational Site | Riga | LV1002 | Latvia |
| GSK Investigational Site | Riga | LV1079 | Latvia |
| GSK Investigational Site | Talsi | LV 3201 | Latvia |
| GSK Investigational Site | Valmiera | LV 4201 | Latvia |
| GSK Investigational Site | Ponce | 00716 | Puerto Rico |
| GSK Investigational Site | Brasov | 500366 | Romania |
| GSK Investigational Site | Bucharest | 020045 | Romania |
| GSK Investigational Site | Bucharest | 020475 | Romania |
| GSK Investigational Site | Gothenburg | SE-413 45 | Sweden |
| GSK Investigational Site | Malmö | SE-205 02 | Sweden |
| GSK Investigational Site | Stockholm | SE-182 88 | Sweden |
For additional information about this study please refer to the GSK Clinical Study Register |
| 100925 | Clinical Study Report | View IPD | For additional information about this study please refer to the GSK Clinical Study Register |
| 100925 | Dataset Specification | View IPD | For additional information about this study please refer to the GSK Clinical Study Register |
| 100925 | Informed Consent Form | View IPD | For additional information about this study please refer to the GSK Clinical Study Register |
| 100925 | Annotated Case Report Form | View IPD | For additional information about this study please refer to the GSK Clinical Study Register |
| 100925 | Study Protocol | View IPD | For additional information about this study please refer to the GSK Clinical Study Register |
| 100925 | Statistical Analysis Plan | View IPD | For additional information about this study please refer to the GSK Clinical Study Register |
| FG001 | DEN 2.5 mg | Participants received oral dose of DEN 2.5 mg capsule once daily in the morning, 30 min prior to breakfast during the main phase/extension phase 12-weeks treatment period. Participants were dispensed 3 bottles (bottle A, B and C) and were instructed to take 1 capsule daily from each bottle such that taking 1 capsule from each bottle daily provided the appropriate dose of DEN 2.5 mg to the participants. |
| FG002 | DEN 7.5 mg | Participants received oral dose of DEN 7.5 mg capsule once daily in the morning, 30 min prior to breakfast during the main phase/extension phase 12-weeks treatment period. Participants were dispensed 3 bottles (bottle A, B and C) and were instructed to take 1 capsule daily from each bottle such that taking 1 capsule from each bottle daily provided the appropriate dose of DEN 7.5 mg to the participants. |
| FG003 | DEN 15 mg | Participants received oral dose of DEN 15 mg capsule once daily in the morning, 30 min prior to breakfast during the main phase/extension phase 12-weeks treatment period. Participants were dispensed 3 bottles (bottle A, B and C) and were instructed to take 1 capsule daily from each bottle such that taking 1 capsule from each bottle daily provided the appropriate dose of DEN 15 mg to the participants. |
| FG004 | DEN 30 mg | Participants received oral dose of DEN 30 mg capsule once daily in the morning, 30 min prior to breakfast during the main phase/extension phase 12-weeks treatment period. Participants were dispensed 3 bottles (bottle A, B and C) and were instructed to take 1 capsule daily from each bottle such that taking 1 capsule from each bottle daily provided the appropriate dose of DEN 30 mg to the participants. |
| FG005 | DEN 45 mg | Participants received oral dose of DEN 45 mg capsule once daily in the morning, 30 min prior to breakfast during the main phase/extension phase 12-weeks treatment period. Participants were dispensed 3 bottles (bottle A, B and C) and were instructed to take 1 capsule daily from each bottle such that taking 1 capsule from each bottle daily provided the appropriate dose of DEN 45 mg to the participants. |
| COMPLETED |
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| NOT COMPLETED |
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| Period 2: Extension Phase (12 Weeks) |
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Not provided
| ID | Title | Description |
|---|---|---|
| BG000 | Placebo | Participants received oral dose of matching placebo capsule to DEN once daily in the morning, 30 min prior to breakfast during the main phase 12-weeks treatment period. Participants who were randomized to placebo in the main phase 12-weeks treatment period received oral dose of DEN 2.5 mg once daily in the morning, 30 min prior to breakfast during the extension phase 12-weeks treatment period. Participants were dispensed 3 bottles (bottle A, B and C) and were instructed to take 1 capsule daily from each bottle such that taking 1 capsule from each bottle daily provided the appropriate dose of placebo to the participants. |
| BG001 | DEN 2.5 mg | Participants received oral dose of DEN 2.5 mg capsule once daily in the morning, 30 min prior to breakfast during the main phase/extension phase 12-weeks treatment period. Participants were dispensed 3 bottles (bottle A, B and C) and were instructed to take 1 capsule daily from each bottle such that taking 1 capsule from each bottle daily provided the appropriate dose of DEN 2.5 mg to the participants. |
| BG002 | DEN 7.5 mg | Participants received oral dose of DEN 7.5 mg capsule once daily in the morning, 30 min prior to breakfast during the main phase/extension phase 12-weeks treatment period. Participants were dispensed 3 bottles (bottle A, B and C) and were instructed to take 1 capsule daily from each bottle such that taking 1 capsule from each bottle daily provided the appropriate dose of DEN 7.5 mg to the participants. |
| BG003 | DEN 15 mg | Participants received oral dose of DEN 15 mg capsule once daily in the morning, 30 min prior to breakfast during the main phase/extension phase 12-weeks treatment period. Participants were dispensed 3 bottles (bottle A, B and C) and were instructed to take 1 capsule daily from each bottle such that taking 1 capsule from each bottle daily provided the appropriate dose of DEN 15 mg to the participants. |
| BG004 | DEN 30 mg | Participants received oral dose of DEN 30 mg capsule once daily in the morning, 30 min prior to breakfast during the main phase/extension phase 12-weeks treatment period. Participants were dispensed 3 bottles (bottle A, B and C) and were instructed to take 1 capsule daily from each bottle such that taking 1 capsule from each bottle daily provided the appropriate dose of DEN 30 mg to the participants. |
| BG005 | DEN 45 mg | Participants received oral dose of DEN 45 mg capsule once daily in the morning, 30 min prior to breakfast during the main phase/extension phase 12-weeks treatment period. Participants were dispensed 3 bottles (bottle A, B and C) and were instructed to take 1 capsule daily from each bottle such that taking 1 capsule from each bottle daily provided the appropriate dose of DEN 45 mg to the participants. |
| BG006 | Total | Total of all reporting groups |
| Units | Counts |
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| Participants |
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| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||
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| Age, Continuous | Mean | Standard Deviation | Years |
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| Sex: Female, Male | Count of Participants | Participants |
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| Race (NIH/OMB) | Count of Participants | Participants |
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| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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| 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. | Intent-to Treat (ITT) Population was defined as all randomized participants who received at least one dose of randomized study medication, had a Baseline assessment and had at least one corresponding on-therapy (scheduled or unscheduled) efficacy assessment. Only those participants available at the specified time points were analyzed. | Posted | Least Squares Mean | Standard Error | Percentage of HbA1c | Baseline (Week 0) and Week 12 |
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| 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. | ITT Population with LOCF dataset was used. Only those participants available at the specified time points were analyzed. | Posted | Mean | Standard Deviation | Percentage of HbA1c | Baseline (Week 0) up to Week 24 |
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| 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. | ITT Population with LOCF dataset was used. Only those participants available at the specified time points were analyzed. | Posted | Least Squares Mean | Standard Error | Millimole per liter (mmol/L) | Baseline (Week 0) and Week 12 |
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| 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. | ITT Population with LOCF dataset was used. Only those participants available at the specified time points were analyzed. | Posted | Mean | Standard Deviation | mmol/L | Baseline (Week 0) up to Week 24 |
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| 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. | ITT Population with LOCF dataset was used. Only those participants available at the specified time points were analyzed. | Posted | Count of Participants | Participants | Week 12 |
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| 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. | ITT Population with LOCF dataset was used. Only those participants available at the specified time points were analyzed. | Posted | Count of Participants | Participants | Week 12 |
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| 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. | ITT Population with LOCF dataset was used. Only those participants available at the specified time points were analyzed. | Posted | Least Squares Mean | Standard Error | Micromole (µmol/L) | Baseline (Week 0) and Week 12 |
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| 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. | ITT Population with LOCF dataset was used. Only those participants available at the specified time points were analyzed. | Posted | Mean | Standard Deviation | µmol/L | Baseline (Week 0) up to Week 24 |
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| 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. | ITT Population with LOCF dataset was used. Only those participants available at the specified time points were analyzed. | Posted | Least Squares Mean | Standard Error | Picomole (pmol)/L | Baseline (Week 0) and Week 12 |
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| 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. | ITT Population with LOCF dataset was used. Only those participants available at the specified time points were analyzed. | Posted | Mean | Standard Deviation | pmol/L | Baseline (Week 0) up to Week 24 |
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| 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. | ITT Population without LOCF dataset was used. Only those participants available at the specified time points were analyzed. | Posted | Mean | Standard Deviation | pmol/L | Baseline (Week 0) up to Week 24 |
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| 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. | ITT Population with LOCF dataset was used. Only those participants available at the specified time points were analyzed. | Posted | Least Squares Mean | Standard Error | Ratio | Baseline (Week 0) and Week 12 |
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| 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. | ITT Population with LOCF dataset was used. Only those participants available at the specified time points were analyzed. | Posted | Mean | Standard Deviation | Ratio | Baseline (Week 0) and Week 4 and 8 |
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| 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. | Safety population was defined as all participants who received at least one dose of study medication. | Posted | Count of Participants | Participants | Up to Week 25 |
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| 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. | Safety Population. | Posted | Count of Participants | Participants | Up to Week 25 |
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| 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. | Safety Population. Only those participants available at the specified time points were analyzed. | Posted | Count of Participants | Participants | Baseline (Week 0) up to Week 24 |
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| 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. | Safety Population. Only those participants available at the specified time points were analyzed. | Posted | Mean | Standard Deviation | Kilogram (kg) | Baseline (Week 0) and Week -5 to 25 (Follow-up) |
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| 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. | Safety Population. Only those participants available at the specified time points were analyzed. | Posted | Mean | Standard Deviation | kg/meter square (m^2) | Baseline (Week 0) and Week -5 to 25 (Follow-up) |
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| 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. | Safety Population. Only those participants available at the specified time points were analyzed. | Posted | Mean | Standard Deviation | Centimeter (cm) | Baseline (Week 0) up to Week 24 |
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| 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. | Safety Population. Only those participants available at the specified time points were analyzed. | Posted | Mean | Standard Deviation | Ratio | Baseline (Week 0) up to Week 24 |
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| 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. | Safety Population. Only those participants available at the specified time points were analyzed. | Posted | Mean | Standard Deviation | Milliseconds (msec) | Baseline (Week 0) up to Week 24 |
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| 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. | Safety Population. Only those participants available at the specified time points were analyzed. | Posted | Count of Participants | Participants | Up to Week 24 |
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| 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. | Safety Population. Only those participants available at the specified time points were analyzed. | Posted | Count of Participants | Participants | Up to Week 24 |
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| 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). | Safety Population. | Posted | Count of Participants | Participants | Up to Follow-up (Week 25) |
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| 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). | Safety Population. | Posted | Count of Participants | Participants | 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. | Sparse PK (PPK) Population comprised of all those participants who were assigned to the sparse (population PK) group. All consenting participants were eligible for inclusion in the sparse PK population except for those participants participating in the serial PK assessment. The data for this outcome measure was not collected. | Posted | 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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| 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. | PPK Population. The data for this outcome measure was not collected. | Posted | 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 |
|
AE's were collected up to Follow-up (up to Week 25)
Safety Population was used.
Not provided
| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Placebo | Participants received oral dose of matching placebo capsule to DEN once daily in the morning, 30 min prior to breakfast during the main phase 12-weeks treatment period. Participants who were randomized to placebo in the main phase 12-weeks treatment period received oral dose of DEN 2.5 mg once daily in the morning, 30 min prior to breakfast during the extension phase 12-weeks treatment period. Participants were dispensed 3 bottles (bottle A, B and C) and were instructed to take 1 capsule daily from each bottle such that taking 1 capsule from each bottle daily provided the appropriate dose of placebo to the participants. | 0 | 64 | 1 | 64 | 6 | 64 |
| EG001 | DEN 2.5 mg | Participants received oral dose of DEN 2.5 mg capsule once daily in the morning, 30 min prior to breakfast during the main phase/extension phase 12-weeks treatment period. Participants were dispensed 3 bottles (bottle A, B and C) and were instructed to take 1 capsule daily from each bottle such that taking 1 capsule from each bottle daily provided the appropriate dose of DEN 2.5 mg to the participants. | 0 | 61 | 1 | 61 | 5 | 61 |
| EG002 | DEN 7.5 mg | Participants received oral dose of DEN 7.5 mg capsule once daily in the morning, 30 min prior to breakfast during the main phase/extension phase 12-weeks treatment period. Participants were dispensed 3 bottles (bottle A, B and C) and were instructed to take 1 capsule daily from each bottle such that taking 1 capsule from each bottle daily provided the appropriate dose of DEN 7.5 mg to the participants. | 0 | 63 | 2 | 63 | 8 | 63 |
| EG003 | DEN 15 mg | Participants received oral dose of DEN 15 mg capsule once daily in the morning, 30 min prior to breakfast during the main phase/extension phase 12-weeks treatment period. Participants were dispensed 3 bottles (bottle A, B and C) and were instructed to take 1 capsule daily from each bottle such that taking 1 capsule from each bottle daily provided the appropriate dose of DEN 15 mg to the participants. | 0 | 66 | 0 | 66 | 11 | 66 |
| EG004 | DEN 30 mg | Participants received oral dose of DEN 30 mg capsule once daily in the morning, 30 min prior to breakfast during the main phase/extension phase 12-weeks treatment period. Participants were dispensed 3 bottles (bottle A, B and C) and were instructed to take 1 capsule daily from each bottle such that taking 1 capsule from each bottle daily provided the appropriate dose of DEN 30 mg to the participants. | 0 | 60 | 4 | 60 | 6 | 60 |
| EG005 | DEN 45 mg | Participants received oral dose of DEN 45 mg capsule once daily in the morning, 30 min prior to breakfast during the main phase/extension phase 12-weeks treatment period. Participants were dispensed 3 bottles (bottle A, B and C) and were instructed to take 1 capsule daily from each bottle such that taking 1 capsule from each bottle daily provided the appropriate dose of DEN 45 mg to the participants. | 0 | 61 | 3 | 61 | 3 | 61 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Gastroenteritis | Infections and infestations | MedDRA 9.0 | Systematic Assessment |
| |
| Laryngitis | Infections and infestations | MedDRA 9.0 | Systematic Assessment |
| |
| Sepsis | Infections and infestations | MedDRA 9.0 | Systematic Assessment |
| |
| Cerebrovascular accident | Nervous system disorders | MedDRA 9.0 | Systematic Assessment |
| |
| Hemiparesis | Nervous system disorders | MedDRA 9.0 | Systematic Assessment |
| |
| Ischaemic stroke | Nervous system disorders | MedDRA 9.0 | Systematic Assessment |
| |
| Acute myocardial infarction | Cardiac disorders | MedDRA 9.0 | Systematic Assessment |
| |
| Cardiac failure congestive | Cardiac disorders | MedDRA 9.0 | Systematic Assessment |
| |
| Vertigo | Ear and labyrinth disorders | MedDRA 9.0 | Systematic Assessment |
| |
| Diverticular perforation | Gastrointestinal disorders | MedDRA 9.0 | Systematic Assessment |
| |
| Dehydration | Metabolism and nutrition disorders | MedDRA 9.0 | Systematic Assessment |
|
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Nasopharyngitis | Infections and infestations | MedDRA 9.0 | Systematic Assessment |
| |
| Nausea | Gastrointestinal disorders | MedDRA 9.0 | Systematic Assessment |
| |
| Diarrhoea | Gastrointestinal disorders | MedDRA 9.0 | Systematic Assessment |
| |
| Back pain | Musculoskeletal and connective tissue disorders | MedDRA 9.0 | Systematic Assessment |
|
GSK agreements may vary with individual investigators, but will not prohibit any investigator from publishing. GSK supports the publication of results from all centers of a multi-center trial but requests that reports based on single-site data not precede the primary publication of the entire clinical trial.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| GSK Response Center | GlaxoSmithKline | 866-435-7343 |
| ID | Term |
|---|---|
| D003924 | Diabetes Mellitus, Type 2 |
| ID | Term |
|---|---|
| D003920 | Diabetes Mellitus |
| D044882 | Glucose Metabolism Disorders |
| D008659 | Metabolic Diseases |
| D009750 | Nutritional and Metabolic Diseases |
| D004700 | Endocrine System Diseases |
Not provided
Not provided
| Protocol Violation |
|
| Withdrawal by Subject |
|
| Lack of Efficacy |
|
| Insufficient therapeutic effect |
|
| Lack of Glycaemic Control |
|
| Electrocardiogram (ECG) results |
|
| Participant received metformin |
|
| Male |
|
| Asian |
|
| Native Hawaiian or Other Pacific Islander |
|
| Black or African American |
|
| White |
|
| More than one race |
|
| Unknown or Not Reported |
|
| OG004 | DEN 30 mg | Participants received oral dose of DEN 30 mg capsule once daily in the morning, 30 min prior to breakfast during the main phase/extension phase 12-weeks treatment period. Participants were dispensed 3 bottles (bottle A, B and C) and were instructed to take 1 capsule daily from each bottle such that taking 1 capsule from each bottle daily provided the appropriate dose of DEN 30 mg to the participants. |
| OG005 | DEN 45 mg | Participants received oral dose of DEN 45 mg capsule once daily in the morning, 30 min prior to breakfast during the main phase/extension phase 12-weeks treatment period. Participants were dispensed 3 bottles (bottle A, B and C) and were instructed to take 1 capsule daily from each bottle such that taking 1 capsule from each bottle daily provided the appropriate dose of DEN 45 mg to the participants. |
|
A closed test procedure was used, in an hierarchical manner, that is, test was applied sequentially where testing does not proceed to the next step unless the previous test was found to be significant. |
| ANCOVA |
| <0.001 |
| Mean Difference (Net) |
| -0.53 |
| 2-Sided |
| 95 |
| -0.82 |
| -0.24 |
The point estimate was calculated as least square mean difference (net values) of placebo and DEN 7.5 mg. |
| Superiority |
| A closed test procedure was used, in an hierarchical manner, that is, test was applied sequentially where testing does not proceed to the next step unless the previous test was found to be significant. | ANCOVA | 0.002 | Mean Difference (Net) | -0.45 | 2-Sided | 95 | -0.74 | -0.16 | The point estimate was calculated as least square mean difference (net values) of placebo and DEN 15 mg. | Superiority |
| A closed test procedure was used, in an hierarchical manner, that is, test was applied sequentially where testing does not proceed to the next step unless the previous test was found to be significant. | ANCOVA | <0.001 | Mean Difference (Net) | -0.80 | 2-Sided | 95 | -1.09 | -0.50 | The point estimate was calculated as least square mean difference (net values) of placebo and DEN 30 mg. | Superiority |
| A closed test procedure was used, in an hierarchical manner, that is, test was applied sequentially where testing does not proceed to the next step unless the previous test was found to be significant. | ANCOVA | <0.001 | Mean Difference (Net) | -0.84 | 2-Sided | 95 | -1.13 | -0.55 | The point estimate was calculated as least square mean difference (net values) of placebo and DEN 45 mg. | Superiority |
Participants received oral dose of DEN 2.5 mg capsule once daily in the morning, 30 min prior to breakfast during the main phase/extension phase 12-weeks treatment period. Participants were dispensed 3 bottles (bottle A, B and C) and were instructed to take 1 capsule daily from each bottle such that taking 1 capsule from each bottle daily provided the appropriate dose of DEN 2.5 mg to the participants. |
| OG002 | DEN 7.5 mg | Participants received oral dose of DEN 7.5 mg capsule once daily in the morning, 30 min prior to breakfast during the main phase/extension phase 12-weeks treatment period. Participants were dispensed 3 bottles (bottle A, B and C) and were instructed to take 1 capsule daily from each bottle such that taking 1 capsule from each bottle daily provided the appropriate dose of DEN 7.5 mg to the participants. |
| OG003 | DEN 15 mg | Participants received oral dose of DEN 15 mg capsule once daily in the morning, 30 min prior to breakfast during the main phase/extension phase 12-weeks treatment period. Participants were dispensed 3 bottles (bottle A, B and C) and were instructed to take 1 capsule daily from each bottle such that taking 1 capsule from each bottle daily provided the appropriate dose of DEN 15 mg to the participants. |
| OG004 | DEN 30 mg | Participants received oral dose of DEN 30 mg capsule once daily in the morning, 30 min prior to breakfast during the main phase/extension phase 12-weeks treatment period. Participants were dispensed 3 bottles (bottle A, B and C) and were instructed to take 1 capsule daily from each bottle such that taking 1 capsule from each bottle daily provided the appropriate dose of DEN 30 mg to the participants. |
| OG005 | DEN 45 mg | Participants received oral dose of DEN 45 mg capsule once daily in the morning, 30 min prior to breakfast during the main phase/extension phase 12-weeks treatment period. Participants were dispensed 3 bottles (bottle A, B and C) and were instructed to take 1 capsule daily from each bottle such that taking 1 capsule from each bottle daily provided the appropriate dose of DEN 45 mg to the participants. |
|
|
| DEN 2.5 mg |
Participants received oral dose of DEN 2.5 mg capsule once daily in the morning, 30 min prior to breakfast during the main phase/extension phase 12-weeks treatment period. Participants were dispensed 3 bottles (bottle A, B and C) and were instructed to take 1 capsule daily from each bottle such that taking 1 capsule from each bottle daily provided the appropriate dose of DEN 2.5 mg to the participants. |
| OG002 | DEN 7.5 mg | Participants received oral dose of DEN 7.5 mg capsule once daily in the morning, 30 min prior to breakfast during the main phase/extension phase 12-weeks treatment period. Participants were dispensed 3 bottles (bottle A, B and C) and were instructed to take 1 capsule daily from each bottle such that taking 1 capsule from each bottle daily provided the appropriate dose of DEN 7.5 mg to the participants. |
| OG003 | DEN 15 mg | Participants received oral dose of DEN 15 mg capsule once daily in the morning, 30 min prior to breakfast during the main phase/extension phase 12-weeks treatment period. Participants were dispensed 3 bottles (bottle A, B and C) and were instructed to take 1 capsule daily from each bottle such that taking 1 capsule from each bottle daily provided the appropriate dose of DEN 15 mg to the participants. |
| OG004 | DEN 30 mg | Participants received oral dose of DEN 30 mg capsule once daily in the morning, 30 min prior to breakfast during the main phase/extension phase 12-weeks treatment period. Participants were dispensed 3 bottles (bottle A, B and C) and were instructed to take 1 capsule daily from each bottle such that taking 1 capsule from each bottle daily provided the appropriate dose of DEN 30 mg to the participants. |
| OG005 | DEN 45 mg | Participants received oral dose of DEN 45 mg capsule once daily in the morning, 30 min prior to breakfast during the main phase/extension phase 12-weeks treatment period. Participants were dispensed 3 bottles (bottle A, B and C) and were instructed to take 1 capsule daily from each bottle such that taking 1 capsule from each bottle daily provided the appropriate dose of DEN 45 mg to the participants. |
|
|
|
| DEN 2.5 mg |
Participants received oral dose of DEN 2.5 mg capsule once daily in the morning, 30 min prior to breakfast during the main phase/extension phase 12-weeks treatment period. Participants were dispensed 3 bottles (bottle A, B and C) and were instructed to take 1 capsule daily from each bottle such that taking 1 capsule from each bottle daily provided the appropriate dose of DEN 2.5 mg to the participants. |
| OG002 | DEN 7.5 mg | Participants received oral dose of DEN 7.5 mg capsule once daily in the morning, 30 min prior to breakfast during the main phase/extension phase 12-weeks treatment period. Participants were dispensed 3 bottles (bottle A, B and C) and were instructed to take 1 capsule daily from each bottle such that taking 1 capsule from each bottle daily provided the appropriate dose of DEN 7.5 mg to the participants. |
| OG003 | DEN 15 mg | Participants received oral dose of DEN 15 mg capsule once daily in the morning, 30 min prior to breakfast during the main phase/extension phase 12-weeks treatment period. Participants were dispensed 3 bottles (bottle A, B and C) and were instructed to take 1 capsule daily from each bottle such that taking 1 capsule from each bottle daily provided the appropriate dose of DEN 15 mg to the participants. |
| OG004 | DEN 30 mg | Participants received oral dose of DEN 30 mg capsule once daily in the morning, 30 min prior to breakfast during the main phase/extension phase 12-weeks treatment period. Participants were dispensed 3 bottles (bottle A, B and C) and were instructed to take 1 capsule daily from each bottle such that taking 1 capsule from each bottle daily provided the appropriate dose of DEN 30 mg to the participants. |
| OG005 | DEN 45 mg | Participants received oral dose of DEN 45 mg capsule once daily in the morning, 30 min prior to breakfast during the main phase/extension phase 12-weeks treatment period. Participants were dispensed 3 bottles (bottle A, B and C) and were instructed to take 1 capsule daily from each bottle such that taking 1 capsule from each bottle daily provided the appropriate dose of DEN 45 mg to the participants. |
|
|
| OG002 | DEN 7.5 mg | Participants received oral dose of DEN 7.5 mg capsule once daily in the morning, 30 min prior to breakfast during the main phase/extension phase 12-weeks treatment period. Participants were dispensed 3 bottles (bottle A, B and C) and were instructed to take 1 capsule daily from each bottle such that taking 1 capsule from each bottle daily provided the appropriate dose of DEN 7.5 mg to the participants. |
| OG003 | DEN 15 mg | Participants received oral dose of DEN 15 mg capsule once daily in the morning, 30 min prior to breakfast during the main phase/extension phase 12-weeks treatment period. Participants were dispensed 3 bottles (bottle A, B and C) and were instructed to take 1 capsule daily from each bottle such that taking 1 capsule from each bottle daily provided the appropriate dose of DEN 15 mg to the participants. |
| OG004 | DEN 30 mg | Participants received oral dose of DEN 30 mg capsule once daily in the morning, 30 min prior to breakfast during the main phase/extension phase 12-weeks treatment period. Participants were dispensed 3 bottles (bottle A, B and C) and were instructed to take 1 capsule daily from each bottle such that taking 1 capsule from each bottle daily provided the appropriate dose of DEN 30 mg to the participants. |
| OG005 | DEN 45 mg | Participants received oral dose of DEN 45 mg capsule once daily in the morning, 30 min prior to breakfast during the main phase/extension phase 12-weeks treatment period. Participants were dispensed 3 bottles (bottle A, B and C) and were instructed to take 1 capsule daily from each bottle such that taking 1 capsule from each bottle daily provided the appropriate dose of DEN 45 mg to the participants. |
|
|
|
| OG002 | DEN 7.5 mg | Participants received oral dose of DEN 7.5 mg capsule once daily in the morning, 30 min prior to breakfast during the main phase/extension phase 12-weeks treatment period. Participants were dispensed 3 bottles (bottle A, B and C) and were instructed to take 1 capsule daily from each bottle such that taking 1 capsule from each bottle daily provided the appropriate dose of DEN 7.5 mg to the participants. |
| OG003 | DEN 15 mg | Participants received oral dose of DEN 15 mg capsule once daily in the morning, 30 min prior to breakfast during the main phase/extension phase 12-weeks treatment period. Participants were dispensed 3 bottles (bottle A, B and C) and were instructed to take 1 capsule daily from each bottle such that taking 1 capsule from each bottle daily provided the appropriate dose of DEN 15 mg to the participants. |
| OG004 | DEN 30 mg | Participants received oral dose of DEN 30 mg capsule once daily in the morning, 30 min prior to breakfast during the main phase/extension phase 12-weeks treatment period. Participants were dispensed 3 bottles (bottle A, B and C) and were instructed to take 1 capsule daily from each bottle such that taking 1 capsule from each bottle daily provided the appropriate dose of DEN 30 mg to the participants. |
| OG005 | DEN 45 mg | Participants received oral dose of DEN 45 mg capsule once daily in the morning, 30 min prior to breakfast during the main phase/extension phase 12-weeks treatment period. Participants were dispensed 3 bottles (bottle A, B and C) and were instructed to take 1 capsule daily from each bottle such that taking 1 capsule from each bottle daily provided the appropriate dose of DEN 45 mg to the participants. |
|
|
|
Participants received oral dose of DEN 2.5 mg capsule once daily in the morning, 30 min prior to breakfast during the main phase/extension phase 12-weeks treatment period. Participants were dispensed 3 bottles (bottle A, B and C) and were instructed to take 1 capsule daily from each bottle such that taking 1 capsule from each bottle daily provided the appropriate dose of DEN 2.5 mg to the participants.
| OG002 | DEN 7.5 mg | Participants received oral dose of DEN 7.5 mg capsule once daily in the morning, 30 min prior to breakfast during the main phase/extension phase 12-weeks treatment period. Participants were dispensed 3 bottles (bottle A, B and C) and were instructed to take 1 capsule daily from each bottle such that taking 1 capsule from each bottle daily provided the appropriate dose of DEN 7.5 mg to the participants. |
| OG003 | DEN 15 mg | Participants received oral dose of DEN 15 mg capsule once daily in the morning, 30 min prior to breakfast during the main phase/extension phase 12-weeks treatment period. Participants were dispensed 3 bottles (bottle A, B and C) and were instructed to take 1 capsule daily from each bottle such that taking 1 capsule from each bottle daily provided the appropriate dose of DEN 15 mg to the participants. |
| OG004 | DEN 30 mg | Participants received oral dose of DEN 30 mg capsule once daily in the morning, 30 min prior to breakfast during the main phase/extension phase 12-weeks treatment period. Participants were dispensed 3 bottles (bottle A, B and C) and were instructed to take 1 capsule daily from each bottle such that taking 1 capsule from each bottle daily provided the appropriate dose of DEN 30 mg to the participants. |
| OG005 | DEN 45 mg | Participants received oral dose of DEN 45 mg capsule once daily in the morning, 30 min prior to breakfast during the main phase/extension phase 12-weeks treatment period. Participants were dispensed 3 bottles (bottle A, B and C) and were instructed to take 1 capsule daily from each bottle such that taking 1 capsule from each bottle daily provided the appropriate dose of DEN 45 mg to the participants. |
|
|
|
| OG002 | DEN 7.5 mg | Participants received oral dose of DEN 7.5 mg capsule once daily in the morning, 30 min prior to breakfast during the main phase/extension phase 12-weeks treatment period. Participants were dispensed 3 bottles (bottle A, B and C) and were instructed to take 1 capsule daily from each bottle such that taking 1 capsule from each bottle daily provided the appropriate dose of DEN 7.5 mg to the participants. |
| OG003 | DEN 15 mg | Participants received oral dose of DEN 15 mg capsule once daily in the morning, 30 min prior to breakfast during the main phase/extension phase 12-weeks treatment period. Participants were dispensed 3 bottles (bottle A, B and C) and were instructed to take 1 capsule daily from each bottle such that taking 1 capsule from each bottle daily provided the appropriate dose of DEN 15 mg to the participants. |
| OG004 | DEN 30 mg | Participants received oral dose of DEN 30 mg capsule once daily in the morning, 30 min prior to breakfast during the main phase/extension phase 12-weeks treatment period. Participants were dispensed 3 bottles (bottle A, B and C) and were instructed to take 1 capsule daily from each bottle such that taking 1 capsule from each bottle daily provided the appropriate dose of DEN 30 mg to the participants. |
| OG005 | DEN 45 mg | Participants received oral dose of DEN 45 mg capsule once daily in the morning, 30 min prior to breakfast during the main phase/extension phase 12-weeks treatment period. Participants were dispensed 3 bottles (bottle A, B and C) and were instructed to take 1 capsule daily from each bottle such that taking 1 capsule from each bottle daily provided the appropriate dose of DEN 45 mg to the participants. |
|
|
| OG001 |
| DEN 2.5 mg |
Participants received oral dose of DEN 2.5 mg capsule once daily in the morning, 30 min prior to breakfast during the main phase/extension phase 12-weeks treatment period. Participants were dispensed 3 bottles (bottle A, B and C) and were instructed to take 1 capsule daily from each bottle such that taking 1 capsule from each bottle daily provided the appropriate dose of DEN 2.5 mg to the participants. |
| OG002 | DEN 7.5 mg | Participants received oral dose of DEN 7.5 mg capsule once daily in the morning, 30 min prior to breakfast during the main phase/extension phase 12-weeks treatment period. Participants were dispensed 3 bottles (bottle A, B and C) and were instructed to take 1 capsule daily from each bottle such that taking 1 capsule from each bottle daily provided the appropriate dose of DEN 7.5 mg to the participants. |
| OG003 | DEN 15 mg | Participants received oral dose of DEN 15 mg capsule once daily in the morning, 30 min prior to breakfast during the main phase/extension phase 12-weeks treatment period. Participants were dispensed 3 bottles (bottle A, B and C) and were instructed to take 1 capsule daily from each bottle such that taking 1 capsule from each bottle daily provided the appropriate dose of DEN 15 mg to the participants. |
| OG004 | DEN 30 mg | Participants received oral dose of DEN 30 mg capsule once daily in the morning, 30 min prior to breakfast during the main phase/extension phase 12-weeks treatment period. Participants were dispensed 3 bottles (bottle A, B and C) and were instructed to take 1 capsule daily from each bottle such that taking 1 capsule from each bottle daily provided the appropriate dose of DEN 30 mg to the participants. |
| OG005 | DEN 45 mg | Participants received oral dose of DEN 45 mg capsule once daily in the morning, 30 min prior to breakfast during the main phase/extension phase 12-weeks treatment period. Participants were dispensed 3 bottles (bottle A, B and C) and were instructed to take 1 capsule daily from each bottle such that taking 1 capsule from each bottle daily provided the appropriate dose of DEN 45 mg to the participants. |
|
|
|
| DEN 2.5 mg |
Participants received oral dose of DEN 2.5 mg capsule once daily in the morning, 30 min prior to breakfast during the main phase/extension phase 12-weeks treatment period. Participants were dispensed 3 bottles (bottle A, B and C) and were instructed to take 1 capsule daily from each bottle such that taking 1 capsule from each bottle daily provided the appropriate dose of DEN 2.5 mg to the participants. |
| OG002 | DEN 7.5 mg | Participants received oral dose of DEN 7.5 mg capsule once daily in the morning, 30 min prior to breakfast during the main phase/extension phase 12-weeks treatment period. Participants were dispensed 3 bottles (bottle A, B and C) and were instructed to take 1 capsule daily from each bottle such that taking 1 capsule from each bottle daily provided the appropriate dose of DEN 7.5 mg to the participants. |
| OG003 | DEN 15 mg | Participants received oral dose of DEN 15 mg capsule once daily in the morning, 30 min prior to breakfast during the main phase/extension phase 12-weeks treatment period. Participants were dispensed 3 bottles (bottle A, B and C) and were instructed to take 1 capsule daily from each bottle such that taking 1 capsule from each bottle daily provided the appropriate dose of DEN 15 mg to the participants. |
| OG004 | DEN 30 mg | Participants received oral dose of DEN 30 mg capsule once daily in the morning, 30 min prior to breakfast during the main phase/extension phase 12-weeks treatment period. Participants were dispensed 3 bottles (bottle A, B and C) and were instructed to take 1 capsule daily from each bottle such that taking 1 capsule from each bottle daily provided the appropriate dose of DEN 30 mg to the participants. |
| OG005 | DEN 45 mg | Participants received oral dose of DEN 45 mg capsule once daily in the morning, 30 min prior to breakfast during the main phase/extension phase 12-weeks treatment period. Participants were dispensed 3 bottles (bottle A, B and C) and were instructed to take 1 capsule daily from each bottle such that taking 1 capsule from each bottle daily provided the appropriate dose of DEN 45 mg to the participants. |
|
|
| OG002 | DEN 7.5 mg | Participants received oral dose of DEN 7.5 mg capsule once daily in the morning, 30 min prior to breakfast during the main phase/extension phase 12-weeks treatment period. Participants were dispensed 3 bottles (bottle A, B and C) and were instructed to take 1 capsule daily from each bottle such that taking 1 capsule from each bottle daily provided the appropriate dose of DEN 7.5 mg to the participants. |
| OG003 | DEN 15 mg | Participants received oral dose of DEN 15 mg capsule once daily in the morning, 30 min prior to breakfast during the main phase/extension phase 12-weeks treatment period. Participants were dispensed 3 bottles (bottle A, B and C) and were instructed to take 1 capsule daily from each bottle such that taking 1 capsule from each bottle daily provided the appropriate dose of DEN 15 mg to the participants. |
| OG004 | DEN 30 mg | Participants received oral dose of DEN 30 mg capsule once daily in the morning, 30 min prior to breakfast during the main phase/extension phase 12-weeks treatment period. Participants were dispensed 3 bottles (bottle A, B and C) and were instructed to take 1 capsule daily from each bottle such that taking 1 capsule from each bottle daily provided the appropriate dose of DEN 30 mg to the participants. |
| OG005 | DEN 45 mg | Participants received oral dose of DEN 45 mg capsule once daily in the morning, 30 min prior to breakfast during the main phase/extension phase 12-weeks treatment period. Participants were dispensed 3 bottles (bottle A, B and C) and were instructed to take 1 capsule daily from each bottle such that taking 1 capsule from each bottle daily provided the appropriate dose of DEN 45 mg to the participants. |
|
|
Participants received oral dose of DEN 2.5 mg capsule once daily in the morning, 30 min prior to breakfast during the main phase/extension phase 12-weeks treatment period. Participants were dispensed 3 bottles (bottle A, B and C) and were instructed to take 1 capsule daily from each bottle such that taking 1 capsule from each bottle daily provided the appropriate dose of DEN 2.5 mg to the participants.
| OG002 | DEN 7.5 mg | Participants received oral dose of DEN 7.5 mg capsule once daily in the morning, 30 min prior to breakfast during the main phase/extension phase 12-weeks treatment period. Participants were dispensed 3 bottles (bottle A, B and C) and were instructed to take 1 capsule daily from each bottle such that taking 1 capsule from each bottle daily provided the appropriate dose of DEN 7.5 mg to the participants. |
| OG003 | DEN 15 mg | Participants received oral dose of DEN 15 mg capsule once daily in the morning, 30 min prior to breakfast during the main phase/extension phase 12-weeks treatment period. Participants were dispensed 3 bottles (bottle A, B and C) and were instructed to take 1 capsule daily from each bottle such that taking 1 capsule from each bottle daily provided the appropriate dose of DEN 15 mg to the participants. |
| OG004 | DEN 30 mg | Participants received oral dose of DEN 30 mg capsule once daily in the morning, 30 min prior to breakfast during the main phase/extension phase 12-weeks treatment period. Participants were dispensed 3 bottles (bottle A, B and C) and were instructed to take 1 capsule daily from each bottle such that taking 1 capsule from each bottle daily provided the appropriate dose of DEN 30 mg to the participants. |
| OG005 | DEN 45 mg | Participants received oral dose of DEN 45 mg capsule once daily in the morning, 30 min prior to breakfast during the main phase/extension phase 12-weeks treatment period. Participants were dispensed 3 bottles (bottle A, B and C) and were instructed to take 1 capsule daily from each bottle such that taking 1 capsule from each bottle daily provided the appropriate dose of DEN 45 mg to the participants. |
|
|
|
Participants received oral dose of DEN 2.5 mg capsule once daily in the morning, 30 min prior to breakfast during the main phase/extension phase 12-weeks treatment period. Participants were dispensed 3 bottles (bottle A, B and C) and were instructed to take 1 capsule daily from each bottle such that taking 1 capsule from each bottle daily provided the appropriate dose of DEN 2.5 mg to the participants.
| OG002 | DEN 7.5 mg | Participants received oral dose of DEN 7.5 mg capsule once daily in the morning, 30 min prior to breakfast during the main phase/extension phase 12-weeks treatment period. Participants were dispensed 3 bottles (bottle A, B and C) and were instructed to take 1 capsule daily from each bottle such that taking 1 capsule from each bottle daily provided the appropriate dose of DEN 7.5 mg to the participants. |
| OG003 | DEN 15 mg | Participants received oral dose of DEN 15 mg capsule once daily in the morning, 30 min prior to breakfast during the main phase/extension phase 12-weeks treatment period. Participants were dispensed 3 bottles (bottle A, B and C) and were instructed to take 1 capsule daily from each bottle such that taking 1 capsule from each bottle daily provided the appropriate dose of DEN 15 mg to the participants. |
| OG004 | DEN 30 mg | Participants received oral dose of DEN 30 mg capsule once daily in the morning, 30 min prior to breakfast during the main phase/extension phase 12-weeks treatment period. Participants were dispensed 3 bottles (bottle A, B and C) and were instructed to take 1 capsule daily from each bottle such that taking 1 capsule from each bottle daily provided the appropriate dose of DEN 30 mg to the participants. |
| OG005 | DEN 45 mg | Participants received oral dose of DEN 45 mg capsule once daily in the morning, 30 min prior to breakfast during the main phase/extension phase 12-weeks treatment period. Participants were dispensed 3 bottles (bottle A, B and C) and were instructed to take 1 capsule daily from each bottle such that taking 1 capsule from each bottle daily provided the appropriate dose of DEN 45 mg to the participants. |
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| OG001 | DEN 2.5 mg | Participants received oral dose of DEN 2.5 mg capsule once daily in the morning, 30 min prior to breakfast during the main phase/extension phase 12-weeks treatment period. Participants were dispensed 3 bottles (bottle A, B and C) and were instructed to take 1 capsule daily from each bottle such that taking 1 capsule from each bottle daily provided the appropriate dose of DEN 2.5 mg to the participants. |
| OG002 | DEN 7.5 mg | Participants received oral dose of DEN 7.5 mg capsule once daily in the morning, 30 min prior to breakfast during the main phase/extension phase 12-weeks treatment period. Participants were dispensed 3 bottles (bottle A, B and C) and were instructed to take 1 capsule daily from each bottle such that taking 1 capsule from each bottle daily provided the appropriate dose of DEN 7.5 mg to the participants. |
| OG003 | DEN 15 mg | Participants received oral dose of DEN 15 mg capsule once daily in the morning, 30 min prior to breakfast during the main phase/extension phase 12-weeks treatment period. Participants were dispensed 3 bottles (bottle A, B and C) and were instructed to take 1 capsule daily from each bottle such that taking 1 capsule from each bottle daily provided the appropriate dose of DEN 15 mg to the participants. |
| OG004 | DEN 30 mg | Participants received oral dose of DEN 30 mg capsule once daily in the morning, 30 min prior to breakfast during the main phase/extension phase 12-weeks treatment period. Participants were dispensed 3 bottles (bottle A, B and C) and were instructed to take 1 capsule daily from each bottle such that taking 1 capsule from each bottle daily provided the appropriate dose of DEN 30 mg to the participants. |
| OG005 | DEN 45 mg | Participants received oral dose of DEN 45 mg capsule once daily in the morning, 30 min prior to breakfast during the main phase/extension phase 12-weeks treatment period. Participants were dispensed 3 bottles (bottle A, B and C) and were instructed to take 1 capsule daily from each bottle such that taking 1 capsule from each bottle daily provided the appropriate dose of DEN 45 mg to the participants. |
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| OG001 | DEN 2.5 mg | Participants received oral dose of DEN 2.5 mg capsule once daily in the morning, 30 min prior to breakfast during the main phase/extension phase 12-weeks treatment period. Participants were dispensed 3 bottles (bottle A, B and C) and were instructed to take 1 capsule daily from each bottle such that taking 1 capsule from each bottle daily provided the appropriate dose of DEN 2.5 mg to the participants. |
| OG002 | DEN 7.5 mg | Participants received oral dose of DEN 7.5 mg capsule once daily in the morning, 30 min prior to breakfast during the main phase/extension phase 12-weeks treatment period. Participants were dispensed 3 bottles (bottle A, B and C) and were instructed to take 1 capsule daily from each bottle such that taking 1 capsule from each bottle daily provided the appropriate dose of DEN 7.5 mg to the participants. |
| OG003 | DEN 15 mg | Participants received oral dose of DEN 15 mg capsule once daily in the morning, 30 min prior to breakfast during the main phase/extension phase 12-weeks treatment period. Participants were dispensed 3 bottles (bottle A, B and C) and were instructed to take 1 capsule daily from each bottle such that taking 1 capsule from each bottle daily provided the appropriate dose of DEN 15 mg to the participants. |
| OG004 | DEN 30 mg | Participants received oral dose of DEN 30 mg capsule once daily in the morning, 30 min prior to breakfast during the main phase/extension phase 12-weeks treatment period. Participants were dispensed 3 bottles (bottle A, B and C) and were instructed to take 1 capsule daily from each bottle such that taking 1 capsule from each bottle daily provided the appropriate dose of DEN 30 mg to the participants. |
| OG005 | DEN 45 mg | Participants received oral dose of DEN 45 mg capsule once daily in the morning, 30 min prior to breakfast during the main phase/extension phase 12-weeks treatment period. Participants were dispensed 3 bottles (bottle A, B and C) and were instructed to take 1 capsule daily from each bottle such that taking 1 capsule from each bottle daily provided the appropriate dose of DEN 45 mg to the participants. |
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| OG001 | DEN 2.5 mg | Participants received oral dose of DEN 2.5 mg capsule once daily in the morning, 30 min prior to breakfast during the main phase/extension phase 12-weeks treatment period. Participants were dispensed 3 bottles (bottle A, B and C) and were instructed to take 1 capsule daily from each bottle such that taking 1 capsule from each bottle daily provided the appropriate dose of DEN 2.5 mg to the participants. |
| OG002 | DEN 7.5 mg | Participants received oral dose of DEN 7.5 mg capsule once daily in the morning, 30 min prior to breakfast during the main phase/extension phase 12-weeks treatment period. Participants were dispensed 3 bottles (bottle A, B and C) and were instructed to take 1 capsule daily from each bottle such that taking 1 capsule from each bottle daily provided the appropriate dose of DEN 7.5 mg to the participants. |
| OG003 | DEN 30 mg | Participants received oral dose of DEN 15 mg capsule once daily in the morning, 30 min prior to breakfast during the main phase/extension phase 12-weeks treatment period. Participants were dispensed 3 bottles (bottle A, B and C) and were instructed to take 1 capsule daily from each bottle such that taking 1 capsule from each bottle daily provided the appropriate dose of DEN 15 mg to the participants. |
| OG004 | DEN 15 mg | Participants received oral dose of DEN 30 mg capsule once daily in the morning, 30 min prior to breakfast during the main phase/extension phase 12-weeks treatment period. Participants were dispensed 3 bottles (bottle A, B and C) and were instructed to take 1 capsule daily from each bottle such that taking 1 capsule from each bottle daily provided the appropriate dose of DEN 30 mg to the participants. |
| OG005 | DEN 45 mg | Participants received oral dose of DEN 45 mg capsule once daily in the morning, 30 min prior to breakfast during the main phase/extension phase 12-weeks treatment period. Participants were dispensed 3 bottles (bottle A, B and C) and were instructed to take 1 capsule daily from each bottle such that taking 1 capsule from each bottle daily provided the appropriate dose of DEN 45 mg to the participants. |
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| DEN 2.5 mg |
Participants received oral dose of matching placebo capsule to DEN once daily in the morning, 30 min prior to breakfast during the main phase 12-weeks treatment period. Participants who were randomized to placebo in the main phase 12-weeks treatment period received oral dose of DEN 2.5 mg once daily in the morning, 30 min prior to breakfast during the extension phase 12-weeks treatment period. Participants were dispensed 3 bottles (bottle A, B and C) and were instructed to take 1 capsule daily from each bottle such that taking 1 capsule from each bottle daily provided the appropriate dose of placebo to the participants. |
| OG002 | DEN 7.5 mg | Participants received oral dose of DEN 7.5 mg capsule once daily in the morning, 30 min prior to breakfast during the main phase/extension phase 12-weeks treatment period. Participants were dispensed 3 bottles (bottle A, B and C) and were instructed to take 1 capsule daily from each bottle such that taking 1 capsule from each bottle daily provided the appropriate dose of DEN 7.5 mg to the participants. |
| OG003 | DEN 15 mg | Participants received oral dose of DEN 15 mg capsule once daily in the morning, 30 min prior to breakfast during the main phase/extension phase 12-weeks treatment period. Participants were dispensed 3 bottles (bottle A, B and C) and were instructed to take 1 capsule daily from each bottle such that taking 1 capsule from each bottle daily provided the appropriate dose of DEN 15 mg to the participants. |
| OG004 | DEN 30 mg | Participants received oral dose of DEN 30 mg capsule once daily in the morning, 30 min prior to breakfast during the main phase/extension phase 12-weeks treatment period. Participants were dispensed 3 bottles (bottle A, B and C) and were instructed to take 1 capsule daily from each bottle such that taking 1 capsule from each bottle daily provided the appropriate dose of DEN 30 mg to the participants. |
| OG005 | DEN 45 mg | Participants received oral dose of DEN 45 mg capsule once daily in the morning, 30 min prior to breakfast during the main phase/extension phase 12-weeks treatment period. Participants were dispensed 3 bottles (bottle A, B and C) and were instructed to take 1 capsule daily from each bottle such that taking 1 capsule from each bottle daily provided the appropriate dose of DEN 45 mg to the participants. |
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| OG001 | DEN 2.5 mg | Participants received oral dose of DEN 2.5 mg capsule once daily in the morning, 30 min prior to breakfast during the main phase/extension phase 12-weeks treatment period. Participants were dispensed 3 bottles (bottle A, B and C) and were instructed to take 1 capsule daily from each bottle such that taking 1 capsule from each bottle daily provided the appropriate dose of DEN 2.5 mg to the participants. |
| OG002 | DEN 7.5 mg | Participants received oral dose of DEN 7.5 mg capsule once daily in the morning, 30 min prior to breakfast during the main phase/extension phase 12-weeks treatment period. Participants were dispensed 3 bottles (bottle A, B and C) and were instructed to take 1 capsule daily from each bottle such that taking 1 capsule from each bottle daily provided the appropriate dose of DEN 7.5 mg to the participants. |
| OG003 | DEN 15 mg | Participants received oral dose of DEN 15 mg capsule once daily in the morning, 30 min prior to breakfast during the main phase/extension phase 12-weeks treatment period. Participants were dispensed 3 bottles (bottle A, B and C) and were instructed to take 1 capsule daily from each bottle such that taking 1 capsule from each bottle daily provided the appropriate dose of DEN 15 mg to the participants. |
| OG004 | DEN 30 mg | Participants received oral dose of DEN 30 mg capsule once daily in the morning, 30 min prior to breakfast during the main phase/extension phase 12-weeks treatment period. Participants were dispensed 3 bottles (bottle A, B and C) and were instructed to take 1 capsule daily from each bottle such that taking 1 capsule from each bottle daily provided the appropriate dose of DEN 30 mg to the participants. |
| OG005 | DEN 45 mg | Participants received oral dose of DEN 45 mg capsule once daily in the morning, 30 min prior to breakfast during the main phase/extension phase 12-weeks treatment period. Participants were dispensed 3 bottles (bottle A, B and C) and were instructed to take 1 capsule daily from each bottle such that taking 1 capsule from each bottle daily provided the appropriate dose of DEN 45 mg to the participants. |
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| OG002 | DEN 7.5 mg | Participants received oral dose of DEN 7.5 mg capsule once daily in the morning, 30 min prior to breakfast during the main phase/extension phase 12-weeks treatment period. Participants were dispensed 3 bottles (bottle A, B and C) and were instructed to take 1 capsule daily from each bottle such that taking 1 capsule from each bottle daily provided the appropriate dose of DEN 7.5 mg to the participants. |
| OG003 | DEN 15 mg | Participants received oral dose of DEN 15 mg capsule once daily in the morning, 30 min prior to breakfast during the main phase/extension phase 12-weeks treatment period. Participants were dispensed 3 bottles (bottle A, B and C) and were instructed to take 1 capsule daily from each bottle such that taking 1 capsule from each bottle daily provided the appropriate dose of DEN 15 mg to the participants. |
| OG004 | DEN 30 mg | Participants received oral dose of DEN 30 mg capsule once daily in the morning, 30 min prior to breakfast during the main phase/extension phase 12-weeks treatment period. Participants were dispensed 3 bottles (bottle A, B and C) and were instructed to take 1 capsule daily from each bottle such that taking 1 capsule from each bottle daily provided the appropriate dose of DEN 30 mg to the participants. |
| OG005 | DEN 45 mg | Participants received oral dose of DEN 45 mg capsule once daily in the morning, 30 min prior to breakfast during the main phase/extension phase 12-weeks treatment period. Participants were dispensed 3 bottles (bottle A, B and C) and were instructed to take 1 capsule daily from each bottle such that taking 1 capsule from each bottle daily provided the appropriate dose of DEN 45 mg to the participants. |
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| OG002 | DEN 7.5 mg | Participants received oral dose of DEN 7.5 mg capsule once daily in the morning, 30 min prior to breakfast during the main phase/extension phase 12-weeks treatment period. Participants were dispensed 3 bottles (bottle A, B and C) and were instructed to take 1 capsule daily from each bottle such that taking 1 capsule from each bottle daily provided the appropriate dose of DEN 7.5 mg to the participants. |
| OG003 | DEN 15 mg | Participants received oral dose of DEN 15 mg capsule once daily in the morning, 30 min prior to breakfast during the main phase/extension phase 12-weeks treatment period. Participants were dispensed 3 bottles (bottle A, B and C) and were instructed to take 1 capsule daily from each bottle such that taking 1 capsule from each bottle daily provided the appropriate dose of DEN 15 mg to the participants. |
| OG004 | DEN 30 mg | Participants received oral dose of DEN 30 mg capsule once daily in the morning, 30 min prior to breakfast during the main phase/extension phase 12-weeks treatment period. Participants were dispensed 3 bottles (bottle A, B and C) and were instructed to take 1 capsule daily from each bottle such that taking 1 capsule from each bottle daily provided the appropriate dose of DEN 30 mg to the participants. |
| OG005 | DEN 45 mg | Participants received oral dose of DEN 45 mg capsule once daily in the morning, 30 min prior to breakfast during the main phase/extension phase 12-weeks treatment period. Participants were dispensed 3 bottles (bottle A, B and C) and were instructed to take 1 capsule daily from each bottle such that taking 1 capsule from each bottle daily provided the appropriate dose of DEN 45 mg to the participants. |
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| OG001 |
| DEN 2.5 mg |
Participants received oral dose of DEN 2.5 mg capsule once daily in the morning, 30 min prior to breakfast during the main phase/extension phase 12-weeks treatment period. Participants were dispensed 3 bottles (bottle A, B and C) and were instructed to take 1 capsule daily from each bottle such that taking 1 capsule from each bottle daily provided the appropriate dose of DEN 2.5 mg to the participants. |
| OG002 | DEN 7.5 mg | Participants received oral dose of DEN 7.5 mg capsule once daily in the morning, 30 min prior to breakfast during the main phase/extension phase 12-weeks treatment period. Participants were dispensed 3 bottles (bottle A, B and C) and were instructed to take 1 capsule daily from each bottle such that taking 1 capsule from each bottle daily provided the appropriate dose of DEN 7.5 mg to the participants. |
| OG003 | DEN 15 mg | Participants received oral dose of DEN 15 mg capsule once daily in the morning, 30 min prior to breakfast during the main phase/extension phase 12-weeks treatment period. Participants were dispensed 3 bottles (bottle A, B and C) and were instructed to take 1 capsule daily from each bottle such that taking 1 capsule from each bottle daily provided the appropriate dose of DEN 15 mg to the participants. |
| OG004 | DEN 30 mg | Participants received oral dose of DEN 30 mg capsule once daily in the morning, 30 min prior to breakfast during the main phase/extension phase 12-weeks treatment period. Participants were dispensed 3 bottles (bottle A, B and C) and were instructed to take 1 capsule daily from each bottle such that taking 1 capsule from each bottle daily provided the appropriate dose of DEN 30 mg to the participants. |
| OG005 | DEN 45 mg | Participants received oral dose of DEN 45 mg capsule once daily in the morning, 30 min prior to breakfast during the main phase/extension phase 12-weeks treatment period. Participants were dispensed 3 bottles (bottle A, B and C) and were instructed to take 1 capsule daily from each bottle such that taking 1 capsule from each bottle daily provided the appropriate dose of DEN 45 mg to the participants. |
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| OG001 | DEN 2.5 mg | Participants received oral dose of DEN 2.5 mg capsule once daily in the morning, 30 min prior to breakfast during the main phase/extension phase 12-weeks treatment period. Participants were dispensed 3 bottles (bottle A, B and C) and were instructed to take 1 capsule daily from each bottle such that taking 1 capsule from each bottle daily provided the appropriate dose of DEN 2.5 mg to the participants. |
| OG002 | DEN 7.5 mg | Participants received oral dose of DEN 7.5 mg capsule once daily in the morning, 30 min prior to breakfast during the main phase/extension phase 12-weeks treatment period. Participants were dispensed 3 bottles (bottle A, B and C) and were instructed to take 1 capsule daily from each bottle such that taking 1 capsule from each bottle daily provided the appropriate dose of DEN 7.5 mg to the participants. |
| OG003 | DEN 15 mg | Participants received oral dose of DEN 15 mg capsule once daily in the morning, 30 min prior to breakfast during the main phase/extension phase 12-weeks treatment period. Participants were dispensed 3 bottles (bottle A, B and C) and were instructed to take 1 capsule daily from each bottle such that taking 1 capsule from each bottle daily provided the appropriate dose of DEN 15 mg to the participants. |
| OG004 | DEN 30 mg | Participants received oral dose of DEN 30 mg capsule once daily in the morning, 30 min prior to breakfast during the main phase/extension phase 12-weeks treatment period. Participants were dispensed 3 bottles (bottle A, B and C) and were instructed to take 1 capsule daily from each bottle such that taking 1 capsule from each bottle daily provided the appropriate dose of DEN 30 mg to the participants. |
| OG005 | DEN 45 mg | Participants received oral dose of DEN 45 mg capsule once daily in the morning, 30 min prior to breakfast during the main phase/extension phase 12-weeks treatment period. Participants were dispensed 3 bottles (bottle A, B and C) and were instructed to take 1 capsule daily from each bottle such that taking 1 capsule from each bottle daily provided the appropriate dose of DEN 45 mg to the participants. |
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|
Participants received oral dose of matching placebo capsule to DEN once daily in the morning, 30 min prior to breakfast during the main phase 12-weeks treatment period. Participants who were randomized to placebo in the main phase 12-weeks treatment period received oral dose of DEN 2.5 mg once daily in the morning, 30 min prior to breakfast during the extension phase 12-weeks treatment period. Participants were dispensed 3 bottles (bottle A, B and C) and were instructed to take 1 capsule daily from each bottle such that taking 1 capsule from each bottle daily provided the appropriate dose of placebo to the participants.
| OG002 | DEN 7.5 mg | Participants received oral dose of DEN 7.5 mg capsule once daily in the morning, 30 min prior to breakfast during the main phase/extension phase 12-weeks treatment period. Participants were dispensed 3 bottles (bottle A, B and C) and were instructed to take 1 capsule daily from each bottle such that taking 1 capsule from each bottle daily provided the appropriate dose of DEN 7.5 mg to the participants. |
| OG003 | DEN 15 mg | Participants received oral dose of DEN 15 mg capsule once daily in the morning, 30 min prior to breakfast during the main phase/extension phase 12-weeks treatment period. Participants were dispensed 3 bottles (bottle A, B and C) and were instructed to take 1 capsule daily from each bottle such that taking 1 capsule from each bottle daily provided the appropriate dose of DEN 15 mg to the participants. |
| OG004 | DEN 30 mg | Participants received oral dose of DEN 30 mg capsule once daily in the morning, 30 min prior to breakfast during the main phase/extension phase 12-weeks treatment period. Participants were dispensed 3 bottles (bottle A, B and C) and were instructed to take 1 capsule daily from each bottle such that taking 1 capsule from each bottle daily provided the appropriate dose of DEN 30 mg to the participants. |
| OG005 | DEN 45 mg | Participants received oral dose of DEN 45 mg capsule once daily in the morning, 30 min prior to breakfast during the main phase/extension phase 12-weeks treatment period. Participants were dispensed 3 bottles (bottle A, B and C) and were instructed to take 1 capsule daily from each bottle such that taking 1 capsule from each bottle daily provided the appropriate dose of DEN 45 mg to the participants. |
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Participants received oral dose of DEN 2.5 mg capsule once daily in the morning, 30 min prior to breakfast during the main phase/extension phase 12-weeks treatment period. Participants were dispensed 3 bottles (bottle A, B and C) and were instructed to take 1 capsule daily from each bottle such that taking 1 capsule from each bottle daily provided the appropriate dose of DEN 2.5 mg to the participants.
| OG002 | DEN 7.5 mg | Participants received oral dose of DEN 7.5 mg capsule once daily in the morning, 30 min prior to breakfast during the main phase/extension phase 12-weeks treatment period. Participants were dispensed 3 bottles (bottle A, B and C) and were instructed to take 1 capsule daily from each bottle such that taking 1 capsule from each bottle daily provided the appropriate dose of DEN 7.5 mg to the participants. |
| OG003 | DEN 15 mg | Participants received oral dose of DEN 15 mg capsule once daily in the morning, 30 min prior to breakfast during the main phase/extension phase 12-weeks treatment period. Participants were dispensed 3 bottles (bottle A, B and C) and were instructed to take 1 capsule daily from each bottle such that taking 1 capsule from each bottle daily provided the appropriate dose of DEN 15 mg to the participants. |
| OG004 | DEN 30 mg | Participants received oral dose of DEN 30 mg capsule once daily in the morning, 30 min prior to breakfast during the main phase/extension phase 12-weeks treatment period. Participants were dispensed 3 bottles (bottle A, B and C) and were instructed to take 1 capsule daily from each bottle such that taking 1 capsule from each bottle daily provided the appropriate dose of DEN 30 mg to the participants. |
| OG005 | DEN 45 mg | Participants received oral dose of DEN 45 mg capsule once daily in the morning, 30 min prior to breakfast during the main phase/extension phase 12-weeks treatment period. Participants were dispensed 3 bottles (bottle A, B and C) and were instructed to take 1 capsule daily from each bottle such that taking 1 capsule from each bottle daily provided the appropriate dose of DEN 45 mg to the participants. |
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| OG002 | DEN 7.5 mg | Participants received oral dose of DEN 7.5 mg capsule once daily in the morning, 30 min prior to breakfast during the main phase/extension phase 12-weeks treatment period. Participants were dispensed 3 bottles (bottle A, B and C) and were instructed to take 1 capsule daily from each bottle such that taking 1 capsule from each bottle daily provided the appropriate dose of DEN 7.5 mg to the participants. |
| OG003 | DEN 15 mg | Participants received oral dose of DEN 15 mg capsule once daily in the morning, 30 min prior to breakfast during the main phase/extension phase 12-weeks treatment period. Participants were dispensed 3 bottles (bottle A, B and C) and were instructed to take 1 capsule daily from each bottle such that taking 1 capsule from each bottle daily provided the appropriate dose of DEN 15 mg to the participants. |
| OG004 | DEN 30 mg | Participants received oral dose of DEN 30 mg capsule once daily in the morning, 30 min prior to breakfast during the main phase/extension phase 12-weeks treatment period. Participants were dispensed 3 bottles (bottle A, B and C) and were instructed to take 1 capsule daily from each bottle such that taking 1 capsule from each bottle daily provided the appropriate dose of DEN 30 mg to the participants. |
| OG005 | DEN 45 mg | Participants received oral dose of DEN 45 mg capsule once daily in the morning, 30 min prior to breakfast during the main phase/extension phase 12-weeks treatment period. Participants were dispensed 3 bottles (bottle A, B and C) and were instructed to take 1 capsule daily from each bottle such that taking 1 capsule from each bottle daily provided the appropriate dose of DEN 45 mg to the participants. |
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| OG002 | DEN 15 mg | Participants received oral dose of DEN 15 mg capsule once daily in the morning, 30 min prior to breakfast during the main phase/extension phase 12-weeks treatment period. Participants were dispensed 3 bottles (bottle A, B and C) and were instructed to take 1 capsule daily from each bottle such that taking 1 capsule from each bottle daily provided the appropriate dose of DEN 15 mg to the participants. |
| OG003 | DEN 30 mg | Participants received oral dose of DEN 30 mg capsule once daily in the morning, 30 min prior to breakfast during the main phase/extension phase 12-weeks treatment period. Participants were dispensed 3 bottles (bottle A, B and C) and were instructed to take 1 capsule daily from each bottle such that taking 1 capsule from each bottle daily provided the appropriate dose of DEN 30 mg to the participants. |
| OG004 | DEN 45 mg | Participants received oral dose of DEN 45 mg capsule once daily in the morning, 30 min prior to breakfast during the main phase/extension phase 12-weeks treatment period. Participants were dispensed 3 bottles (bottle A, B and C) and were instructed to take 1 capsule daily from each bottle such that taking 1 capsule from each bottle daily provided the appropriate dose of DEN 45 mg to the participants. |
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| OG002 | DEN 15 mg | Participants received oral dose of DEN 15 mg capsule once daily in the morning, 30 min prior to breakfast during the main phase/extension phase 12-weeks treatment period. Participants were dispensed 3 bottles (bottle A, B and C) and were instructed to take 1 capsule daily from each bottle such that taking 1 capsule from each bottle daily provided the appropriate dose of DEN 15 mg to the participants. |
| OG003 | DEN 30 mg | Participants received oral dose of DEN 30 mg capsule once daily in the morning, 30 min prior to breakfast during the main phase/extension phase 12-weeks treatment period. Participants were dispensed 3 bottles (bottle A, B and C) and were instructed to take 1 capsule daily from each bottle such that taking 1 capsule from each bottle daily provided the appropriate dose of DEN 30 mg to the participants. |
| OG004 | DEN 45 mg | Participants received oral dose of DEN 45 mg capsule once daily in the morning, 30 min prior to breakfast during the main phase/extension phase 12-weeks treatment period. Participants were dispensed 3 bottles (bottle A, B and C) and were instructed to take 1 capsule daily from each bottle such that taking 1 capsule from each bottle daily provided the appropriate dose of DEN 45 mg to the participants. |
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