Type 2 Diabetes Mellitus
Conditions
Keywords
type 2 diabetes mellitus, interventional, double blind, phase 2
Brief summary
The hypothesis of this Phase 2, 12-week study, is that DS-8500a will improve glycemic control relative to placebo, based on changes in HbA1c, with acceptable safety and tolerability, in patients with Type 2 Diabetes Mellitus (T2DM) who are treated with metformin.
Interventions
Two sitagliptin 50 mg tablets, over-encapsulated to provide a once-daily dose of 100 mg, for oral administration
DRUGDS-8500a 25mg
DS-8500a 25mg tablet for oral administration
DRUGPlacebo Tablet
Placebo matching DS-8500a tablet for oral administration
DRUGPlacebo Capsule
Placebo matching sitagliptin over-capsule for oral administration
Sponsors
Daiichi Sankyo
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
No
Inclusion criteria
* Able to provide written informed consent and adhere to the study visit schedule and treatment * Diagnosed with Type 2 diabetes mellitus as defined in the American Diabetes Association Standards of Medical Care in Diabetes 2015 * Male or female ≥ 18 and ≤ 70 years of age * Screening fasting C-peptide \> 0.5 ng/mL * Women of child bearing potential (WOCBP) must be willing to use double-barrier contraception for the entire study * WOCBP must have a negative pregnancy test (human chorionic gonadotropin, beta subunit \[βhCG\]) before entering the Lead-in Period * Body mass index ≥ 25 kg/m2 and ≤ 45 kg/m2 at the Screening Visit * On stable (≥ 8 weeks) metformin monotherapy ≥ 1000 mg/day * Screening HbA1c ≥ 7.0% and ≤ 10% * Taking ≥ 80% and ≤ 120% of both dispensed DS-8500a placebo tablets and sitagliptin placebo capsules during the Lead-in Period
Exclusion criteria
* History of type 1 diabetes and/or history of ketoacidosis * History of insulin use for \> 2 weeks within 2 months prior to the Screening Visit * Two or more readings of fasting Self-monitoring of Blood Glucose (SMBG) \> 240 mg/dL or worsening symptoms of hyperglycemia with one SMBG level of \> 240 mg/dL during the second week of Lead-in Period, confirmed by laboratory measurement * Screening hemoglobin \<12 g/dL for males and \<11 g/dL for females * Blood donation within 2 months prior to the Screening Visit or plans to donate blood or blood products during the study * Subjects after bariatric surgery or any gastric bypass * Screening thyroid stimulating hormone (TSH) levels not within normal range (based on reference laboratory values ) * Screening Alanine Aminotransferase (ALT) or Aspartate Aminotransferase (AST) \> 2.0 x upper limit of normal (ULN), and/or total bilirubin \> 1.5 x ULN. If a subject has total bilirubin \> 1.5 ULN, unconjugated and conjugated bilirubin fractions should be analyzed and only subjects documented to have Gilbert's syndrome may be enrolled * Screening Serum creatinine ≥ 1.5 mg/dL for males and ≥ 1.4 mg/dL for females, or creatinine clearance (CrCl) \< 50 mL/min for both males and females * Screening Creatine kinase (CK) \> 3.0 × ULN * History of unstable angina, myocardial infarction, cerebrovascular accident, transient ischemic attack, peripheral arterial event or any revascularization procedure during the 6 months prior to the Screening Visit or planned vascular procedures or surgery during study period * History of congestive heart failure (CHF) * Exclusionary concomitant medications: a. Eight weeks prior to screening and throughout the duration of the study: * Any diabetes medication other than metformin; any prescription or over the counter medication for weight-loss. * Systemic corticosteroids (including nasal and inhaled), with the exception of use of topical and ophthalmic corticosteroids. * Rosuvastatin \> 20 mg daily. b. During treatment periods, additional medications will be prohibited based on potential drug-drug interaction (DDI) (see Section 5.6) * Subjects with anticipated interruption in metformin or study drug use during the course of the clinical trial (e.g., due to an imaging procedure involving iodinated contrast media) * Subjects in whom treatment with sitagliptin 100 mg is contraindicated ( e.g., known hypersensitivity or intolerance to sitagliptin) or may not be medically advisable (e.g., history of pancreatitis) * Abuse of or dependence on prescription medications, illicit drugs, or alcohol within the last 1 year * Any history of a malignancy other than basal cell carcinoma within the past 5 years * Pregnancy or breast-feeding, or intent to become pregnant during the study period * Known (or evidence of) infection with human immunodeficiency virus * Any condition, laboratory abnormality, or concomitant therapy which, in the opinion of the Investigator, might pose a risk to the subject or make participation not in the subject's best interest * Subject is currently enrolled in or has not yet completed at least 30 days since ending another investigational device or drug study or is receiving other investigational agents * A direct or familial relationship with the Sponsor, Investigator, or site personnel affiliated with the study
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Glycated Hemoglobin (HbA1c) at Week 12 | Baseline, Week 12 | Glycated hemoglobin is a form of hemoglobin that is measured primarily to identify the three-month average glucose concentration in the blood. Target HbA1c for Type 2 diabetics was less than 7% at the time of this trial. Negative scores show improvement from baseline. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in LDL-C at Week 12 | Baseline, Week 12 | LDL-C is known as the bad cholesterol, so a lower score (negative change) means improvement. |
| Change From Baseline in HDL-C at Week 12 | Baseline, Week 12 | HDL-C is known as the good cholesterol, so a higher score (positive change) means improvement. |
| Change From Baseline in Non-HDL-C at Week 12 | Baseline, Week 12 | Non-HDL-C is the measure of bad cholesterol in the blood, including triglycerides and LDL-C, so a negative change means improvement. The equation for Non-HDL-C = LDL-C + (triglycerides/5). |
| Change From Baseline in Triglycerides at Week 12 | Baseline, Week 12 | Triglycerides are a type of fat found in the blood. The body uses them for energy. Some triglycerides are needed for good health. But high triglycerides might raise the risk of heart disease. Since Type 2 diabetics tend to have high triglycerides, a negative change means improvement. |
| Change From Baseline in Area-Under-the Curve 0-3 Hours (AUC0-3h) of Plasma Glucose (PG) in Response to the Mixed Meal Tolerance Test (MMTT) at Week 4 | Baseline, Week 4 | The MMTT requires a participant to drink a mixed meal, such as Boost or Ensure, that contains protein, carbohydrates, and fat. The goal of the test is to find out how much insulin the pancreas makes in response to food by measuring the level of glucose in the blood. The lower the level of glucose in the blood during the first three hours after the test (AUC0-3h), the more insulin the body has made in response to the test. This would mean a negative change shows improvement. |
| Change From Baseline in AUC0-3h of PG in Response to the MMTT at Week 12 | Baseline, Week 12 | The MMTT requires a participant to drink a mixed meal, such as Boost or Ensure, that contains protein, carbohydrates, and fat. The goal of the test is to find out how much insulin the pancreas makes in response to food by measuring the level of glucose in the blood. The lower the level of glucose in the blood during the first three hours after the test (AUC0-3h), the more insulin the body has made in response to the test. This would mean a negative change shows improvement. |
| Change From Baseline in Total Cholesterol (TC) at Week 12 | Baseline, Week 12 | Total cholesterol is a measure of the total amount of cholesterol in the blood, including low-density lipoprotein cholesterol (LDL-C) - the bad cholesterol, high-density lipoprotein cholesterol (HDL-C) - the good cholesterol, and triglycerides. The equation to calculate total cholesterol is: LDL + HDL + (triglycerides/5) = total cholesterol. |
| Change From Baseline in Cmax of PG in Response to MMTT at Week 12 | Baseline, Week 12 | Cmax measures the highest amount of glucose in the blood, so a negative change means improvement. |
| Change From Baseline in Fasting Plasma Glucose (FPG) at Week 2 | Baseline, Week 2 | Normal fasting plasma glucose -- or blood sugar -- is between 70 and 100 milligrams per deciliter (mg/dL) for people who do not have diabetes. People with Type 2 diabetes typically have FPG that is too high, so a negative change from baseline means improvement. |
| Change From Baseline in Fasting Plasma Glucose (FPG) at Week 4 | Baseline, Week 4 | Normal fasting plasma glucose -- or blood sugar -- is between 70 and 100 milligrams per deciliter (mg/dL) for people who do not have diabetes. People with Type 2 diabetes typically have FPG that is too high, so a negative change from baseline means improvement. |
| Change From Baseline in Fasting Plasma Glucose (FPG) at Week 8 | Baseline, Week 8 | Normal fasting plasma glucose -- or blood sugar -- is between 70 and 100 milligrams per deciliter (mg/dL) for people who do not have diabetes. People with Type 2 diabetes typically have FPG that is too high, so a negative change from baseline means improvement. |
| Change From Baseline in Fasting Plasma Glucose (FPG) at Week 12 | Baseline, Week 12 | Normal fasting plasma glucose -- or blood sugar -- is between 70 and 100 milligrams per deciliter (mg/dL) for people who do not have diabetes. People with Type 2 diabetes typically have FPG that is too high, so a negative change from baseline means improvement. |
| Count of Participants With HbA1c Less Than 7.0% at Week 12 | Week 12 | HbA1C less than 7% is the success goal for many Type 2 diabetics. |
| Change From Baseline in Maximum Concentration (Cmax) of PG in Response to MMTT at Week 4 | Baseline, Week 4 | Cmax measures the highest amount of glucose in the blood, so a negative change means improvement. |
Countries
Canada, United States
Participant flow
Recruitment details
A total of 654 subjects were recruited at multiple sites in the United States and Canada.
Pre-assignment details
A total of 654 subjects were screened and 297 subjects passed the run-in screening period and were randomized. One subject failed screening but was randomized in error.
Participants by arm
| Arm | Count |
|---|---|
| DS-8500a 25mg One DS-8500a 25 mg tablet, 2 placebo tablets, and one placebo capsule in a once-daily oral dose | 46 |
| DS-8500a 50 mg Two DS-8500a 25 mg tablets, 1 placebo tablet, and one placebo capsule in a once-daily oral dose | 46 |
| DS-8500a 75 mg Three DS-8500a 25 mg tablets and one placebo capsule in a once-daily oral dose | 69 |
| Sitagliptin 100 mg Three placebo tablets and one sitagliptin 100 mg over-capsule in a once-daily oral dose | 68 |
| Placebo Three placebo tablets and one placebo capsule in a once-daily oral dose | 69 |
| Total | 298 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 |
|---|---|---|---|---|---|---|
| Overall Study | Adverse Event | 0 | 1 | 3 | 2 | 1 |
| Overall Study | Develop anemia | 1 | 0 | 0 | 0 | 0 |
| Overall Study | Disposition Missing Due to Fire at Site | 2 | 3 | 4 | 3 | 4 |
| Overall Study | Lack of Efficacy | 0 | 0 | 0 | 1 | 0 |
| Overall Study | Lost to Follow-up | 1 | 1 | 0 | 0 | 0 |
| Overall Study | Persistent hyperglycemia | 0 | 1 | 1 | 1 | 1 |
| Overall Study | Protocol Violation | 0 | 0 | 3 | 0 | 0 |
| Overall Study | Reason not provided | 0 | 0 | 1 | 0 | 2 |
| Overall Study | Study terminated by sponsor | 1 | 1 | 1 | 1 | 2 |
| Overall Study | Withdrawal by Subject | 7 | 4 | 2 | 2 | 7 |
Baseline characteristics
| Characteristic | Total | DS-8500a 25mg | DS-8500a 50 mg | DS-8500a 75 mg | Sitagliptin 100 mg | Placebo |
|---|---|---|---|---|---|---|
| 1. Glycated Hemoglobin | 7.93 mmol/mol STANDARD_DEVIATION 0.852 | 7.94 mmol/mol STANDARD_DEVIATION 0.939 | 8.09 mmol/mol STANDARD_DEVIATION 0.91 | 7.99 mmol/mol STANDARD_DEVIATION 0.9 | 7.78 mmol/mol STANDARD_DEVIATION 0.79 | 7.92 mmol/mol STANDARD_DEVIATION 0.699 |
| 2. Total Cholesterol | 178.1 mg/dL STANDARD_DEVIATION 41.7 | 177.1 mg/dL STANDARD_DEVIATION 36.72 | 180.3 mg/dL STANDARD_DEVIATION 32.21 | 178.0 mg/dL STANDARD_DEVIATION 37.38 | 172.6 mg/dL STANDARD_DEVIATION 55.25 | 182.8 mg/dL STANDARD_DEVIATION 43.11 |
| 3. Low Density Lipoprotein-C | 97.0 mg/dL STANDARD_DEVIATION 34.51 | 96.6 mg/dL STANDARD_DEVIATION 33.58 | 96.9 mg/dL STANDARD_DEVIATION 30.53 | 96.6 mg/dL STANDARD_DEVIATION 32.84 | 95.1 mg/dL STANDARD_DEVIATION 37.93 | 99.8 mg/dL STANDARD_DEVIATION 37.14 |
| 4. High Density Lipoprotein-C | 46.87 mg/dL STANDARD_DEVIATION 12.19 | 49.5 mg/dL STANDARD_DEVIATION 12.8 | 49.3 mg/dL STANDARD_DEVIATION 13.2 | 46.4 mg/dL STANDARD_DEVIATION 11.77 | 44.3 mg/dL STANDARD_DEVIATION 12.17 | 46.7 mg/dL STANDARD_DEVIATION 10.93 |
| 5. Non-High Density Lipoprotein-C | 131.21 mg/dL STANDARD_DEVIATION 38.56 | 127.6 mg/dL STANDARD_DEVIATION 38.13 | 131.0 mg/dL STANDARD_DEVIATION 32.54 | 131.6 mg/dL STANDARD_DEVIATION 35.93 | 128.4 mg/dL STANDARD_DEVIATION 44.46 | 136.1 mg/dL STANDARD_DEVIATION 40.69 |
| 6. Triglycerides | 175.5 mg/dL STANDARD_DEVIATION 94.54 | 165.3 mg/dL STANDARD_DEVIATION 114.5 | 174.9 mg/dL STANDARD_DEVIATION 95.55 | 179.6 mg/dL STANDARD_DEVIATION 83.39 | 169.8 mg/dL STANDARD_DEVIATION 84.9 | 184.2 mg/dL STANDARD_DEVIATION 91.02 |
| Age, Continuous | 56.7 years STANDARD_DEVIATION 8.56 | 56.4 years STANDARD_DEVIATION 9.3 | 57.0 years STANDARD_DEVIATION 8.95 | 57.0 years STANDARD_DEVIATION 9.41 | 57.4 years STANDARD_DEVIATION 7.77 | 55.6 years STANDARD_DEVIATION 7.72 |
| Race (NIH/OMB) American Indian or Alaska Native | 4 Participants | 1 Participants | 0 Participants | 2 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Asian | 26 Participants | 3 Participants | 3 Participants | 3 Participants | 4 Participants | 13 Participants |
| Race (NIH/OMB) Black or African American | 44 Participants | 7 Participants | 7 Participants | 10 Participants | 10 Participants | 10 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 2 Participants | 1 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) White | 222 Participants | 34 Participants | 36 Participants | 54 Participants | 53 Participants | 45 Participants |
| Region of Enrollment Canada | 47 Participants | 7 Participants | 6 Participants | 7 Participants | 12 Participants | 15 Participants |
| Region of Enrollment United States | 251 Participants | 39 Participants | 40 Participants | 62 Participants | 56 Participants | 54 Participants |
| Sex: Female, Male Female | 140 Participants | 22 Participants | 22 Participants | 38 Participants | 28 Participants | 30 Participants |
| Sex: Female, Male Male | 158 Participants | 24 Participants | 24 Participants | 31 Participants | 40 Participants | 39 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk |
|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 43 | 0 / 44 | 0 / 68 | 0 / 68 | 0 / 69 |
| other Total, other adverse events | 7 / 43 | 2 / 44 | 11 / 68 | 6 / 68 | 7 / 69 |
| serious Total, serious adverse events | 1 / 43 | 0 / 44 | 1 / 68 | 1 / 68 | 0 / 69 |
Outcome results
Primary
Change From Baseline in Glycated Hemoglobin (HbA1c) at Week 12
Glycated hemoglobin is a form of hemoglobin that is measured primarily to identify the three-month average glucose concentration in the blood. Target HbA1c for Type 2 diabetics was less than 7% at the time of this trial. Negative scores show improvement from baseline.
Time frame: Baseline, Week 12
Population: Modified Intent to Treat (mITT) Set, defined as all participants in the Safety Set who have a baseline measurement and at least 1 post-baseline measurement. mITT was used for analysis because one of the sites had a fire so 16 participants who were included in the baseline population were not included in analyses.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| DS-8500a 25mg | Change From Baseline in Glycated Hemoglobin (HbA1c) at Week 12 | -0.24 percent of HbA1c | Standard Deviation 1.019 |
| DS-8500a 50 mg | Change From Baseline in Glycated Hemoglobin (HbA1c) at Week 12 | -0.16 percent of HbA1c | Standard Deviation 0.798 |
| DS-8500a 75 mg | Change From Baseline in Glycated Hemoglobin (HbA1c) at Week 12 | -0.35 percent of HbA1c | Standard Deviation 0.791 |
| Sitagliptin 100 mg | Change From Baseline in Glycated Hemoglobin (HbA1c) at Week 12 | -0.66 percent of HbA1c | Standard Deviation 0.623 |
| Placebo | Change From Baseline in Glycated Hemoglobin (HbA1c) at Week 12 | -0.23 percent of HbA1c | Standard Deviation 0.657 |
Comparison: Difference in change at week 12p-value: 0.75590% CI: [-0.211, 0.309]Mixed Model Repeated Measure
Comparison: Difference in change at week 12p-value: 0.51290% CI: [-0.16, 0.371]Mixed Model Repeated Measure
Comparison: Difference in change at week 12p-value: 0.56690% CI: [-0.312, 0.151]Mixed Model Repeated Measure
Comparison: Difference in change at week 12p-value: 0.00290% CI: [-0.655, -0.197]Mixed Model Repeated Measure
Secondary
Change From Baseline in Area-Under-the Curve 0-3 Hours (AUC0-3h) of Plasma Glucose (PG) in Response to the Mixed Meal Tolerance Test (MMTT) at Week 4
The MMTT requires a participant to drink a mixed meal, such as Boost or Ensure, that contains protein, carbohydrates, and fat. The goal of the test is to find out how much insulin the pancreas makes in response to food by measuring the level of glucose in the blood. The lower the level of glucose in the blood during the first three hours after the test (AUC0-3h), the more insulin the body has made in response to the test. This would mean a negative change shows improvement.
Time frame: Baseline, Week 4
Population: mITT with a measurement at baseline and Week 4
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| DS-8500a 25mg | Change From Baseline in Area-Under-the Curve 0-3 Hours (AUC0-3h) of Plasma Glucose (PG) in Response to the Mixed Meal Tolerance Test (MMTT) at Week 4 | -4.32 (mg/dL)*hr | Standard Deviation 71.235 |
| DS-8500a 50 mg | Change From Baseline in Area-Under-the Curve 0-3 Hours (AUC0-3h) of Plasma Glucose (PG) in Response to the Mixed Meal Tolerance Test (MMTT) at Week 4 | 1.36 (mg/dL)*hr | Standard Deviation 67.661 |
| DS-8500a 75 mg | Change From Baseline in Area-Under-the Curve 0-3 Hours (AUC0-3h) of Plasma Glucose (PG) in Response to the Mixed Meal Tolerance Test (MMTT) at Week 4 | -6.32 (mg/dL)*hr | Standard Deviation 83.597 |
| Sitagliptin 100 mg | Change From Baseline in Area-Under-the Curve 0-3 Hours (AUC0-3h) of Plasma Glucose (PG) in Response to the Mixed Meal Tolerance Test (MMTT) at Week 4 | -41.61 (mg/dL)*hr | Standard Deviation 73.971 |
| Placebo | Change From Baseline in Area-Under-the Curve 0-3 Hours (AUC0-3h) of Plasma Glucose (PG) in Response to the Mixed Meal Tolerance Test (MMTT) at Week 4 | -3.97 (mg/dL)*hr | Standard Deviation 87.625 |
Comparison: Difference in change at week 4p-value: 0.72890% CI: [-19.932, 30.566]Mixed Model Repeated Measure
Comparison: Difference in change at week 4p-value: 0.83790% CI: [-29.446, 22.914]Mixed Model Repeated Measure
Comparison: Difference in change at week 4p-value: 0.79190% CI: [-26.352, 19.051]Mixed Model Repeated Measure
Comparison: Difference in change at week 4p-value: 0.00390% CI: [-62.283, -17.787]Mixed Model Repeated Measure
Secondary
Change From Baseline in AUC0-3h of PG in Response to the MMTT at Week 12
The MMTT requires a participant to drink a mixed meal, such as Boost or Ensure, that contains protein, carbohydrates, and fat. The goal of the test is to find out how much insulin the pancreas makes in response to food by measuring the level of glucose in the blood. The lower the level of glucose in the blood during the first three hours after the test (AUC0-3h), the more insulin the body has made in response to the test. This would mean a negative change shows improvement.
Time frame: Baseline, Week 12
Population: mITT with a measurement at baseline and Week 12
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| DS-8500a 25mg | Change From Baseline in AUC0-3h of PG in Response to the MMTT at Week 12 | -18.77 (mg/dL)*hr | Standard Deviation 96.472 |
| DS-8500a 50 mg | Change From Baseline in AUC0-3h of PG in Response to the MMTT at Week 12 | 13.81 (mg/dL)*hr | Standard Deviation 67.025 |
| DS-8500a 75 mg | Change From Baseline in AUC0-3h of PG in Response to the MMTT at Week 12 | -5.51 (mg/dL)*hr | Standard Deviation 104.992 |
| Sitagliptin 100 mg | Change From Baseline in AUC0-3h of PG in Response to the MMTT at Week 12 | -53.40 (mg/dL)*hr | Standard Deviation 74.803 |
| Placebo | Change From Baseline in AUC0-3h of PG in Response to the MMTT at Week 12 | -24.16 (mg/dL)*hr | Standard Deviation 101.016 |
Comparison: Difference in change at week 12p-value: 0.8390% CI: [-29.312, 38.087]Mixed Model Repeated Measure
Comparison: Difference in change at week 12p-value: 0.23590% CI: [-9.354, 57.848]Mixed Model Repeated Measure
Comparison: Difference in change at week 12p-value: 0.33190% CI: [-12.03, 46.529]Mixed Model Repeated Measure
Comparison: Difference in change at week 12p-value: 0.09190% CI: [-58.254, -0.775]Mixed Model Repeated Measure
Secondary
Change From Baseline in Cmax of PG in Response to MMTT at Week 12
Cmax measures the highest amount of glucose in the blood, so a negative change means improvement.
Time frame: Baseline, Week 12
Population: mITT with a measurement at baseline and Week 12
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| DS-8500a 25mg | Change From Baseline in Cmax of PG in Response to MMTT at Week 12 | -5.93 mg/dL | Standard Deviation 47.53 |
| DS-8500a 50 mg | Change From Baseline in Cmax of PG in Response to MMTT at Week 12 | -1.10 mg/dL | Standard Deviation 53.045 |
| DS-8500a 75 mg | Change From Baseline in Cmax of PG in Response to MMTT at Week 12 | -4.43 mg/dL | Standard Deviation 60.957 |
| Sitagliptin 100 mg | Change From Baseline in Cmax of PG in Response to MMTT at Week 12 | -28.29 mg/dL | Standard Deviation 42.184 |
| Placebo | Change From Baseline in Cmax of PG in Response to MMTT at Week 12 | 1.11 mg/dL | Standard Deviation 58.731 |
Comparison: Difference in change at week 12p-value: 0.52790% CI: [-27.441, 12.221]Mixed Model Repeated Measure
Comparison: Difference in change at week 12p-value: 0.53290% CI: [-26.927, 12.138]Mixed Model Repeated Measure
Comparison: Difference in change at week 12p-value: 0.67290% CI: [-21.635, 12.807]Mixed Model Repeated Measure
Comparison: Difference in change at week 12p-value: 0.00290% CI: [-48.482, -14.676]Mixed Model Repeated Measure
Secondary
Change From Baseline in Fasting Plasma Glucose (FPG) at Week 12
Normal fasting plasma glucose -- or blood sugar -- is between 70 and 100 milligrams per deciliter (mg/dL) for people who do not have diabetes. People with Type 2 diabetes typically have FPG that is too high, so a negative change from baseline means improvement.
Time frame: Baseline, Week 12
Population: mITT with a measurement at baseline and Week 12
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| DS-8500a 25mg | Change From Baseline in Fasting Plasma Glucose (FPG) at Week 12 | 0.0 mg/dL | Standard Deviation 25.67 |
| DS-8500a 50 mg | Change From Baseline in Fasting Plasma Glucose (FPG) at Week 12 | -9.1 mg/dL | Standard Deviation 34.89 |
| DS-8500a 75 mg | Change From Baseline in Fasting Plasma Glucose (FPG) at Week 12 | -5.8 mg/dL | Standard Deviation 35.27 |
| Sitagliptin 100 mg | Change From Baseline in Fasting Plasma Glucose (FPG) at Week 12 | -5.7 mg/dL | Standard Deviation 46.29 |
| Placebo | Change From Baseline in Fasting Plasma Glucose (FPG) at Week 12 | 8.1 mg/dL | Standard Deviation 32.72 |
Comparison: Difference in change at week 12p-value: 0.28590% CI: [-22.09, 4.7]Mixed Model Repeated Measure
Comparison: Difference in change at week 12p-value: 0.0290% CI: [-31.73, -5.49]Mixed Model Repeated Measure
Comparison: Difference in change at week 12p-value: 0.06790% CI: [-24.6, -1.35]Mixed Model Repeated Measure
Comparison: Difference in change at week 12p-value: 0.01290% CI: [-28.76, -6.03]Mixed Model Repeated Measure
Secondary
Change From Baseline in Fasting Plasma Glucose (FPG) at Week 2
Normal fasting plasma glucose -- or blood sugar -- is between 70 and 100 milligrams per deciliter (mg/dL) for people who do not have diabetes. People with Type 2 diabetes typically have FPG that is too high, so a negative change from baseline means improvement.
Time frame: Baseline, Week 2
Population: mITT with a measurement at baseline and Week 2
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| DS-8500a 25mg | Change From Baseline in Fasting Plasma Glucose (FPG) at Week 2 | 4.3 mg/dL | Standard Deviation 25.98 |
| DS-8500a 50 mg | Change From Baseline in Fasting Plasma Glucose (FPG) at Week 2 | -8.1 mg/dL | Standard Deviation 25.24 |
| DS-8500a 75 mg | Change From Baseline in Fasting Plasma Glucose (FPG) at Week 2 | 0.0 mg/dL | Standard Deviation 31.52 |
| Sitagliptin 100 mg | Change From Baseline in Fasting Plasma Glucose (FPG) at Week 2 | -16.2 mg/dL | Standard Deviation 26.11 |
| Placebo | Change From Baseline in Fasting Plasma Glucose (FPG) at Week 2 | 10.7 mg/dL | Standard Deviation 32.38 |
Comparison: Difference in change at week 2p-value: 0.29890% CI: [-15.9, 3.6]Mixed Model Repeated Measure
Comparison: Difference in change at week 2p-value: 0.00890% CI: [-26.37, -6.27]Mixed Model Repeated Measure
Comparison: Difference in change at week 2p-value: 0.07490% CI: [-18.31, -0.75]Mixed Model Repeated Measure
Comparison: Difference in change at week 2p-value: <0.00190% CI: [-35.96, -18.38]Mixed Model Repeated Measure
Secondary
Change From Baseline in Fasting Plasma Glucose (FPG) at Week 4
Normal fasting plasma glucose -- or blood sugar -- is between 70 and 100 milligrams per deciliter (mg/dL) for people who do not have diabetes. People with Type 2 diabetes typically have FPG that is too high, so a negative change from baseline means improvement.
Time frame: Baseline, Week 4
Population: mITT with a measurement at baseline and Week 4
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| DS-8500a 25mg | Change From Baseline in Fasting Plasma Glucose (FPG) at Week 4 | 0.04 mg/dL | Standard Deviation 18.71 |
| DS-8500a 50 mg | Change From Baseline in Fasting Plasma Glucose (FPG) at Week 4 | -12.7 mg/dL | Standard Deviation 30.82 |
| DS-8500a 75 mg | Change From Baseline in Fasting Plasma Glucose (FPG) at Week 4 | -5.9 mg/dL | Standard Deviation 35.17 |
| Sitagliptin 100 mg | Change From Baseline in Fasting Plasma Glucose (FPG) at Week 4 | -11.1 mg/dL | Standard Deviation 31.81 |
| Placebo | Change From Baseline in Fasting Plasma Glucose (FPG) at Week 4 | 2.4 mg/dL | Standard Deviation 32.01 |
Comparison: Difference in change at week 4p-value: 0.8490% CI: [-11.04, 8.63]Mixed Model Repeated Measure
Comparison: Difference in change at week 4p-value: 0.0590% CI: [-21.94, -1.91]Mixed Model Repeated Measure
Comparison: Difference in change at week 4p-value: 0.22790% CI: [-15.21, 2.33]Mixed Model Repeated Measure
Comparison: Difference in change at week 4p-value: 0.1390% CI: [-21.83, -4.43]Mixed Model Repeated Measure
Secondary
Change From Baseline in Fasting Plasma Glucose (FPG) at Week 8
Normal fasting plasma glucose -- or blood sugar -- is between 70 and 100 milligrams per deciliter (mg/dL) for people who do not have diabetes. People with Type 2 diabetes typically have FPG that is too high, so a negative change from baseline means improvement.
Time frame: Baseline, Week 8
Population: mITT with a measurement at baseline and Week 8
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| DS-8500a 25mg | Change From Baseline in Fasting Plasma Glucose (FPG) at Week 8 | 2.3 mg/dL | Standard Deviation 27.57 |
| DS-8500a 50 mg | Change From Baseline in Fasting Plasma Glucose (FPG) at Week 8 | -5.9 mg/dL | Standard Deviation 27.9 |
| DS-8500a 75 mg | Change From Baseline in Fasting Plasma Glucose (FPG) at Week 8 | -7.1 mg/dL | Standard Deviation 37.51 |
| Sitagliptin 100 mg | Change From Baseline in Fasting Plasma Glucose (FPG) at Week 8 | -16.6 mg/dL | Standard Deviation 32.96 |
| Placebo | Change From Baseline in Fasting Plasma Glucose (FPG) at Week 8 | -1.0 mg/dL | Standard Deviation 31.63 |
Comparison: Difference in change at week 8p-value: 0.64290% CI: [-7.77, 13.88]Mixed Model Repeated Measure
Comparison: Difference in change at week 8p-value: 0.51290% CI: [-15.52, 6.68]Mixed Model Repeated Measure
Comparison: Difference in change at week 8p-value: 0.48690% CI: [-13.66, 5.54]Mixed Model Repeated Measure
Comparison: Difference in change at week 8p-value: 0.00490% CI: [-26.31, -7.16]Mixed Model Repeated Measure
Secondary
Change From Baseline in HDL-C at Week 12
HDL-C is known as the good cholesterol, so a higher score (positive change) means improvement.
Time frame: Baseline, Week 12
Population: mITT
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| DS-8500a 25mg | Change From Baseline in HDL-C at Week 12 | 3.0 percent change in HCL-C | Standard Deviation 11.48 |
| DS-8500a 50 mg | Change From Baseline in HDL-C at Week 12 | 1.1 percent change in HCL-C | Standard Deviation 10.18 |
| DS-8500a 75 mg | Change From Baseline in HDL-C at Week 12 | 2.2 percent change in HCL-C | Standard Deviation 11.59 |
| Sitagliptin 100 mg | Change From Baseline in HDL-C at Week 12 | 1.1 percent change in HCL-C | Standard Deviation 13.17 |
| Placebo | Change From Baseline in HDL-C at Week 12 | 1.2 percent change in HCL-C | Standard Deviation 11.41 |
Comparison: Difference in change at week 12p-value: 0.57690% CI: [-2.83, 5.73]Mixed Model Repeated Measure
Comparison: Difference in change at week 12p-value: 0.64690% CI: [-5.53, 3.12]Mixed Model Repeated Measure
Comparison: Difference in change at week 12p-value: 0.90290% CI: [-3.52, 4.08]Mixed Model Repeated Measure
Comparison: Difference in change at week 12p-value: 0.47890% CI: [-5.35, 2.13]Mixed Model Repeated Measure
Secondary
Change From Baseline in LDL-C at Week 12
LDL-C is known as the bad cholesterol, so a lower score (negative change) means improvement.
Time frame: Baseline, Week 12
Population: mITT
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| DS-8500a 25mg | Change From Baseline in LDL-C at Week 12 | -6.7 percent change in LDL-C | Standard Deviation 17.34 |
| DS-8500a 50 mg | Change From Baseline in LDL-C at Week 12 | 2.8 percent change in LDL-C | Standard Deviation 46.18 |
| DS-8500a 75 mg | Change From Baseline in LDL-C at Week 12 | -0.1 percent change in LDL-C | Standard Deviation 22.84 |
| Sitagliptin 100 mg | Change From Baseline in LDL-C at Week 12 | -2.4 percent change in LDL-C | Standard Deviation 23.2 |
| Placebo | Change From Baseline in LDL-C at Week 12 | 0.9 percent change in LDL-C | Standard Deviation 20.12 |
Comparison: Difference in change at week 12p-value: 0.22890% CI: [-15.74, 2.43]Mixed Model Repeated Measure
Comparison: Difference in change at week 12p-value: 0.89490% CI: [-8.36, 9.84]Mixed Model Repeated Measure
Comparison: Difference in change at week 12p-value: 0.84690% CI: [-8.97, 7.08]Mixed Model Repeated Measure
Comparison: Difference in change at week 12p-value: 0.40990% CI: [-11.82, 3.93]Mixed Model Repeated Measure
Secondary
Change From Baseline in Maximum Concentration (Cmax) of PG in Response to MMTT at Week 4
Cmax measures the highest amount of glucose in the blood, so a negative change means improvement.
Time frame: Baseline, Week 4
Population: mITT with a measurement at baseline and Week 4
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| DS-8500a 25mg | Change From Baseline in Maximum Concentration (Cmax) of PG in Response to MMTT at Week 4 | -1.92 mg/dL | Standard Deviation 41.26 |
| DS-8500a 50 mg | Change From Baseline in Maximum Concentration (Cmax) of PG in Response to MMTT at Week 4 | -7.35 mg/dL | Standard Deviation 39.645 |
| DS-8500a 75 mg | Change From Baseline in Maximum Concentration (Cmax) of PG in Response to MMTT at Week 4 | -3.47 mg/dL | Standard Deviation 54.258 |
| Sitagliptin 100 mg | Change From Baseline in Maximum Concentration (Cmax) of PG in Response to MMTT at Week 4 | -28.44 mg/dL | Standard Deviation 45.327 |
| Placebo | Change From Baseline in Maximum Concentration (Cmax) of PG in Response to MMTT at Week 4 | -0.35 mg/dL | Standard Deviation 41.885 |
Comparison: Difference in change at week 4p-value: 0.87390% CI: [-13.835, 16.815]Mixed Model Repeated Measure
Comparison: Difference in change at week 4p-value: 0.39590% CI: [-23.79, 7.604]Mixed Model Repeated Measure
Comparison: Difference in change at week 4p-value: 0.76190% CI: [-16.247, 11.185]Mixed Model Repeated Measure
Comparison: Difference in change at week 4p-value: <0.00190% CI: [-41.22, -14.236]Mixed Model Repeated Measure
Secondary
Change From Baseline in Non-HDL-C at Week 12
Non-HDL-C is the measure of bad cholesterol in the blood, including triglycerides and LDL-C, so a negative change means improvement. The equation for Non-HDL-C = LDL-C + (triglycerides/5).
Time frame: Baseline, Week 12
Population: mITT
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| DS-8500a 25mg | Change From Baseline in Non-HDL-C at Week 12 | -8.9 Percent change in Non-HDL-C | Standard Deviation 14.89 |
| DS-8500a 50 mg | Change From Baseline in Non-HDL-C at Week 12 | -2.5 Percent change in Non-HDL-C | Standard Deviation 31.68 |
| DS-8500a 75 mg | Change From Baseline in Non-HDL-C at Week 12 | -2.9 Percent change in Non-HDL-C | Standard Deviation 16.68 |
| Sitagliptin 100 mg | Change From Baseline in Non-HDL-C at Week 12 | -4.7 Percent change in Non-HDL-C | Standard Deviation 19.1 |
| Placebo | Change From Baseline in Non-HDL-C at Week 12 | -2.5 Percent change in Non-HDL-C | Standard Deviation 17.02 |
Comparison: Difference in change at week 12p-value: 0.07290% CI: [-14.57, -0.64]Mixed Model Repeated Measure
Comparison: Difference in change at week 12p-value: 0.79490% CI: [-8.15, 5.92]Mixed Model Repeated Measure
Comparison: Difference in change at week 12p-value: 0.94690% CI: [-6.45, 5.94]Mixed Model Repeated Measure
Comparison: Difference in change at week 12p-value: 0.43190% CI: [-8.99, 3.18]Mixed Model Repeated Measure
Secondary
Change From Baseline in Total Cholesterol (TC) at Week 12
Total cholesterol is a measure of the total amount of cholesterol in the blood, including low-density lipoprotein cholesterol (LDL-C) - the bad cholesterol, high-density lipoprotein cholesterol (HDL-C) - the good cholesterol, and triglycerides. The equation to calculate total cholesterol is: LDL + HDL + (triglycerides/5) = total cholesterol.
Time frame: Baseline, Week 12
Population: mITT
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| DS-8500a 25mg | Change From Baseline in Total Cholesterol (TC) at Week 12 | -5.6 percent change in TC | Standard Deviation 11.95 |
| DS-8500a 50 mg | Change From Baseline in Total Cholesterol (TC) at Week 12 | -1.7 percent change in TC | Standard Deviation 22.3 |
| DS-8500a 75 mg | Change From Baseline in Total Cholesterol (TC) at Week 12 | -1.8 percent change in TC | Standard Deviation 12.58 |
| Sitagliptin 100 mg | Change From Baseline in Total Cholesterol (TC) at Week 12 | -3.6 percent change in TC | Standard Deviation 14.34 |
| Placebo | Change From Baseline in Total Cholesterol (TC) at Week 12 | -1.7 percent change in TC | Standard Deviation 13.57 |
Comparison: Difference in change at week 12p-value: 0.14490% CI: [-9.76, 0.58]Mixed Model Repeated Measure
Comparison: Difference in change at week 12p-value: 0.77390% CI: [-6.14, 4.31]Mixed Model Repeated Measure
Comparison: Difference in change at week 12p-value: 0.96390% CI: [-4.73, 4.48]Mixed Model Repeated Measure
Comparison: Difference in change at week 12p-value: 0.25890% CI: [-7.64, 1.42]Mixed Model Repeated Measure
Secondary
Change From Baseline in Triglycerides at Week 12
Triglycerides are a type of fat found in the blood. The body uses them for energy. Some triglycerides are needed for good health. But high triglycerides might raise the risk of heart disease. Since Type 2 diabetics tend to have high triglycerides, a negative change means improvement.
Time frame: Baseline, Week 12
Population: mITT
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| DS-8500a 25mg | Change From Baseline in Triglycerides at Week 12 | -12.4 percent change in triglycerides | Standard Deviation 22.35 |
| DS-8500a 50 mg | Change From Baseline in Triglycerides at Week 12 | -1.9 percent change in triglycerides | Standard Deviation 78.27 |
| DS-8500a 75 mg | Change From Baseline in Triglycerides at Week 12 | -5.8 percent change in triglycerides | Standard Deviation 27.71 |
| Sitagliptin 100 mg | Change From Baseline in Triglycerides at Week 12 | -7.0 percent change in triglycerides | Standard Deviation 27.9 |
| Placebo | Change From Baseline in Triglycerides at Week 12 | -3.0 percent change in triglycerides | Standard Deviation 27.76 |
Comparison: Difference in change at week 12p-value: 0.95190% CI: [-13.7, 14.77]Mixed Model Repeated Measure
Comparison: Difference in change at week 12p-value: 0.85290% CI: [-13.96, 11.13]Mixed Model Repeated Measure
Comparison: Difference in change at week 12p-value: 0.22890% CI: [-24.43, 3.78]Mixed Model Repeated Measure
Comparison: Difference in change at week 12p-value: 0.60890% CI: [-16.13, 8.48]Mixed Model Repeated Measure
Secondary
Count of Participants With HbA1c Less Than 7.0% at Week 12
HbA1C less than 7% is the success goal for many Type 2 diabetics.
Time frame: Week 12
Population: mITT
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| DS-8500a 25mg | Count of Participants With HbA1c Less Than 7.0% at Week 12 | 6 Participants |
| DS-8500a 50 mg | Count of Participants With HbA1c Less Than 7.0% at Week 12 | 8 Participants |
| DS-8500a 75 mg | Count of Participants With HbA1c Less Than 7.0% at Week 12 | 15 Participants |
| Sitagliptin 100 mg | Count of Participants With HbA1c Less Than 7.0% at Week 12 | 28 Participants |
| Placebo | Count of Participants With HbA1c Less Than 7.0% at Week 12 | 10 Participants |