Hypertension, Diabetes
Conditions
Keywords
Drug Therapy, Hypertension and Diabetes
Brief summary
The purpose of this study was to evaluate the antihypertensive and antiglycemic effects, as well as the safety and tolerability of TAK-491 (azilsartan medoxomil), once daily (QD), in stage 1 hypertensive, type 2 diabetes mellitus (T2DM) participants whose glycemic control was inadequate on metformin alone.
Detailed description
The study included a Screening Period of up to 4 weeks, which coincided with a 2-week single-blind, placebo Run-in Period, a 24 week Treatment Period, and a 2-week Follow-up Period. The duration of the study was approximately 30 weeks. The planned number of participants (n=450) was not reached; actual enrollment consisted of 105 particpants. Due to low enrollment this study was terminated early by Takeda.
Interventions
DRUGPlacebo
Sponsors
Takeda
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 No maximum
Healthy volunteers
No
Inclusion criteria
1. Was male or female and ≥18 years. 2. Had type 2 diabetes mellitus with HbA1c of ≥7.5 to ≤9.5% at Screening. 3. Was treated with metformin alone (no treatment with any antidiabetic agents other than metformin within the 3 months prior to Screening) and was experiencing inadequate glycemic control. The participant should have received metformin monotherapy for ≥8 weeks prior to Screening at a stable dose ≥1500 mg). Participants with a maximum tolerated dose (MTD) that was documented to be less than 1500 mg of metformin could also be enrolled if this dose had been stable for 8 weeks prior to Screening. 4. Was treated with antihypertensive therapy and had a mean, trough, sitting clinic systolic blood pressure (SBP) ≥135 and \< 160 mm Hg on Day -1 (after washout of prior antihypertensive therapy) or the participant had not received antihypertensive treatment within 28 days before Screening and had a mean sitting clinic SBP ≥135 and \< 160 mm Hg at the Screening Visit and on Day -1. 5. Had clinical laboratory evaluations (including clinical chemistry, hematology, and complete urinalysis) within the reference range for the testing laboratory or results that were deemed not clinically significant in this participant population for inclusion in this study, by the investigator.
Exclusion criteria
1. Had a mean, trough, sitting clinic diastolic blood pressure (DBP) ≥ 100 mm Hg at Day -1. 2. Had type 1 or poorly controlled type 2 diabetes mellitus (HbA1c \>9.5%) at Screening. 3. Was taking or expected to take an excluded medication. 4. Had a history of myocardial infarction, heart failure, unstable angina, coronary artery bypass graft, percutaneous coronary intervention, hypertensive encephalopathy, cerebrovascular accident, or transient ischemic attack. 5. Had clinically significant cardiac conduction defects (for example, 3rd degree atrioventricular block, left bundle branch block, sick sinus syndrome, atrial fibrillation). 6. Had hemodynamically significant left ventricular outflow obstruction due to aortic valvular disease. 7. Had secondary hypertension of any etiology (e.g., renovascular disease, pheochromocytoma, Cushing's syndrome). 8. Had renal dysfunction defined as estimated glomerular filtration rate (eGFR) \<60 mL/min/1.73 m2 at Screening. 9. Had albuminuria defined as \>200 mg/g at Screening. 10. Had known or suspected unilateral or bilateral renal artery stenosis. 11. Had unexplained microhematuria ≥3 RBCs/HPF or macrohematuria at Screening and confirmed on repeat testing. 12. Treatment with antidiabetic agents (sulfonylureas, glucagon-like peptide-1 (GLP-1) analogues, dipeptidyl peptidase-4 (DPP-4) inhibitors, glinides, thiazolidinediones (TZDs), and/or insulin) other than metformin during the 3 months prior to Screening. 13. Had hyperkalemia as defined by central laboratory normal reference range at Screening.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Trough Sitting Clinic Systolic Blood Pressure | Baseline and Week 8 | The change in trough systolic blood pressure measured at week 8 relative to baseline. The trough is the average of the non-missing values of the 3 serial trough sitting systolic blood pressure measurements. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Trough Sitting Clinic Diastolic Blood Pressure | Baseline and Week 8 | The change in trough diastolic blood pressure measured at week 8 relative to baseline. The trough is the average of the non-missing values of the 3 serial trough sitting diastolic blood pressure measurements. |
| Change From Baseline in the 24-hour Mean Systolic Blood Pressure, as Measured by Ambulatory Blood Pressure Monitoring | Baseline and Week 8 | The change in 24-hour mean systolic blood pressure measured at week 8 relative to baseline. Ambulatory blood pressure monitoring measures blood pressure at regular intervals throughout the day and night. The 24-hour mean is the average of all measurements recorded for 24 hours after dosing. |
| Change From Baseline in the 24-hour Mean Diastolic Blood Pressure, as Measured by Ambulatory Blood Pressure Monitoring | Baseline and Week 8 | The change in 24-hour mean diastolic blood pressure measured at week 8 relative to baseline. Ambulatory blood pressure monitoring measures blood pressure at regular intervals throughout the day and night. The 24-hour mean is the average of all measurements recorded for 24 hours after dosing. |
| Change From Baseline in the Mean Daytime (6 AM to 10 PM) Systolic Blood Pressure, as Measured by Ambulatory Blood Pressure Monitoring | Baseline and Week 8 | The change in daytime (6am to 10pm) mean systolic blood pressure measured week 8 relative to baseline. Ambulatory blood pressure monitoring measures blood pressure at regular intervals throughout the day and night. Daytime mean is the average of all measurements recorded between the hours of 6 am and 10 pm. |
| Change From Baseline in the Mean Daytime (6 AM to 10 PM) Diastolic Blood Pressure, as Measured by Ambulatory Blood Pressure Monitoring | Baseline and Week 8 | The change in daytime (6am to 10pm) mean diastolic blood pressure measured at week 8 relative to baseline. Ambulatory blood pressure monitoring measures blood pressure at regular intervals throughout the day and night. Daytime mean is the average of all measurements recorded between the hours of 6 am and 10 pm. |
| Change From Baseline in the Mean Nighttime (12 AM to 6 AM) Systolic Blood Pressure, as Measured by Ambulatory Blood Pressure Monitoring | Baseline and Week 8 | The change in nighttime (12am to 6am) mean systolic blood pressure measured at week 8 relative to baseline. Ambulatory blood pressure monitoring measures blood pressure at regular intervals throughout the day and night. Nighttime mean is the average of all measurements recorded between the hours of 12 am and 6 am. |
| Change From Baseline in the Mean Nighttime (12 AM to 6 AM) Diastolic Blood Pressure, as Measured by Ambulatory Blood Pressure Monitoring | Baseline and Week 8 | The change in nighttime (12am to 6am) mean diastolic blood pressure measured at week 8 relative to baseline. Ambulatory blood pressure monitoring measures blood pressure at regular intervals throughout the day and night. Nighttime mean is the average of all measurements recorded between the hours of 12 am and 6 am. |
| Change From Baseline in the 12-hr Mean Systolic Blood Pressure Measured by Ambulatory Blood Pressure Monitoring | Baseline and Week 8 | The change in 12-hour mean systolic blood pressure measured at week 8 relative to baseline. Ambulatory blood pressure monitoring measures blood pressure at regular intervals throughout the day and night. The 12-hour mean is the average of all measurements recorded during the first 12 hours after dosing. |
| Change From Baseline in the 12-hr Mean Diastolic Blood Pressure Measured by Ambulatory Blood Pressure Monitoring | Baseline and Week 8 | The change in 12-hour mean systolic blood pressure measured at week 8 relative to baseline. Ambulatory blood pressure monitoring measures blood pressure at regular intervals throughout the day and night. The 12-hour mean is the average of all measurements recorded during the first 12 hours after dosing. |
| Change From Baseline in the Trough (22 to 24 Hours After Dosing) Systolic Blood Pressure as Measured by Ambulatory Blood Pressure Monitoring | Baseline and Week 8 | The change in trough systolic blood pressure measured at week 8 relative to baseline. Ambulatory blood pressure monitoring measures blood pressure at regular intervals throughout the day and night. The trough is the average of all measurements recorded from 22 to 24 hours after dosing. |
| Change From Baseline in Glycosylated Hemoglobin (HbA1c) | Baseline and Week 24 | The change in the value of glycosylated hemoglobin (the concentration of glucose bound to hemoglobin as a percent of the absolute maximum that can be bound) collected at week 24 relative to baseline. |
| Percentage of Participants Requiring Rescue Glycemic Therapy | 24 Weeks | Percentage of participants requiring rescue glycemic therapy during study. |
| Time to First Glycemic Rescue | 24 Weeks | The time to the first instance of participants requiring glycemic rescue during study. |
| Change From Baseline in HbA1c | Baseline and Weeks 2, 4, 6, 8, 12, 16 and 20 | The change in the value of glycosylated hemoglobin (the concentration of glucose bound to hemoglobin as a percent of the absolute maximum that can be bound) collected at each week indicated relative to baseline. |
| Change From Baseline in Fasting Plasma Glucose | Baseline and Weeks 2, 4, 6, 8, 12, 16, 20, and 24 | The change between the fasting plasma glucose value collected at each week indicated relative to baseline. |
| Change From Baseline to Week 6 and Week 24 in 2h Glucose During Oral Glucose Tolerance Testing (OGTT) | Baseline and Weeks 6 and 24 | The change between the glucose value collected at weeks 6 and 24 relative to baseline. Oral glucose tolerance test measures glucose, insulin, C-peptide, insulin/glucose ratio, and glucagon through blood samples drawn at 0, 30, 60, and 120 minutes following consumption of a 75 g glucose beverage. |
| Change From Baseline to Week 6 and Week 24 in the Area Under the Plasma Concentration-time Curve (AUC) for Glucose During OGTT | Baseline and Weeks 6 and 24 | The change between the AUC for glucose at weeks 6 and 24 relative to baseline. AUC will be calculated based on measurements at 0, 30, 60 and 120 minutes. Oral glucose tolerance test measures glucose, insulin, C-peptide, insulin/glucose ratio, and glucagon through blood samples drawn at 0, 30, 60, and 120 minutes following consumption of a 75 g glucose beverage. |
| Change From Baseline to Week 6 and Week 24 in AUC for Insulin During OGTT | Baseline and Weeks 6 and 24 | The change between the AUC for insulin at weeks 6 and 24 relative to baseline. AUC will be calculated based on measurements at 0, 30, 60 and 120 minutes. Oral glucose tolerance test measures glucose, insulin, C-peptide, insulin/glucose ratio, and glucagon through blood samples drawn at 0, 30, 60, and 120 minutes following consumption of a 75 g glucose beverage. |
| Change From Baseline to Week 6 and Week 24 in AUC for C-peptide During OGTT | Baseline and Weeks 6 and 24 | The change between the AUC for C-peptide at weeks 6 and 24 relative to baseline. AUC will be calculated based on measurements at 0, 30, 60 and 120 minutes. Oral glucose tolerance test measures glucose, insulin, C-peptide, insulin/glucose ratio, and glucagon through blood samples drawn at 0, 30, 60, and 120 minutes following consumption of a 75 g glucose beverage. |
| Change From Baseline to Week 6 and Week 24 in AUC for Insulin/Glucose Ratio During OGTT | Baseline and Weeks 6 and 24 | The change between the AUC for insulin/glucose ratio at weeks 6 and 24 relative to baseline. AUC will be calculated based on measurements at 0, 30, 60 and 120 minutes. Oral glucose tolerance test measures glucose, insulin, C-peptide, insulin/glucose ratio, and glucagon through blood samples drawn at 0, 30, 60, and 120 minutes following consumption of a 75 g glucose beverage. |
| Change From Baseline to Week 6 and Week 24 in AUC for Glucagon During OGTT | Baseline and Weeks 6 and 24 | The change between the AUC for glucagon at weeks 6 and 24 relative to baseline. AUC will be calculated based on measurements at 0, 30, 60 and 120 minutes. Oral glucose tolerance test measures glucose, insulin, C-peptide, insulin/glucose ratio, and glucagon through blood samples drawn at 0, 30, 60, and 120 minutes following consumption of a 75 g glucose beverage. |
| Change From Baseline in the Trough (22 to 24 Hours After Dosing) Diastolic Blood Pressure as Measured by Ambulatory Blood Pressure Monitoring | Baseline and Week 8 | The change in trough diastolic blood pressure measured at week 8 relative to baseline. Ambulatory blood pressure monitoring measures blood pressure at regular intervals throughout the day and night. The trough is the average of all measurements recorded from 22 to 24 hours after dosing. |
Countries
United States
Participant flow
Recruitment details
Participants took part in the study at 41 investigative sites in the United States from 09 January 2012 to 30 May 2013.
Pre-assignment details
Participants with a diagnosis of stage 1 essential hypertension and type 2 diabetes mellitus uncontrolled on metformin were enrolled equally in 1 of 3 treatment groups, once a day placebo, 40 mg or 80 mg TAK-491.
Participants by arm
| Arm | Count |
|---|---|
| Placebo QD Azilsartan medoxomil placebo-matching tablets, orally, once daily for up to 24 weeks. | 35 |
| Azilsartan Medoxomil 40 mg QD Azilsartan medoxomil 40 mg, tablets, orally, once daily for up to 24 weeks. | 35 |
| Azilsartan Medoxomil 80 mg QD Azilsartan medoxomil 80 mg, tablets, orally, once daily for up to 24 weeks. | 35 |
| Total | 105 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Adverse Event | 0 | 0 | 1 |
| Overall Study | Lost to Follow-up | 2 | 3 | 1 |
| Overall Study | Major Protocol Deviation | 0 | 0 | 1 |
| Overall Study | Other | 2 | 0 | 0 |
| Overall Study | Principal Investigator Discretion | 0 | 1 | 1 |
| Overall Study | Voluntary Withdrawal | 2 | 1 | 6 |
Baseline characteristics
| Characteristic | Placebo QD | Azilsartan Medoxomil 40 mg QD | Azilsartan Medoxomil 80 mg QD | Total |
|---|---|---|---|---|
| Age, Continuous | 57.1 years STANDARD_DEVIATION 8.66 | 54.7 years STANDARD_DEVIATION 7.63 | 55.8 years STANDARD_DEVIATION 7.37 | 55.9 years STANDARD_DEVIATION 7.89 |
| Age, Customized <45 years | 3 participants | 3 participants | 2 participants | 8 participants |
| Age, Customized ≥65 years | 7 participants | 3 participants | 3 participants | 13 participants |
| Age, Customized Between 45 and 64 years | 25 participants | 29 participants | 30 participants | 84 participants |
| Antihypertension Medication Within 28 Days No | 3 participants | 8 participants | 5 participants | 16 participants |
| Antihypertension Medication Within 28 Days Yes | 32 participants | 27 participants | 30 participants | 89 participants |
| Baseline Diastolic Blood Pressure (DBP) Hypertension Severity Category DBP < 90 mm Hg | 25 participants | 18 participants | 25 participants | 68 participants |
| Baseline Diastolic Blood Pressure (DBP) Hypertension Severity Category DBP ≥ 90 mm Hg | 10 participants | 17 participants | 10 participants | 37 participants |
| Baseline Glycosylated Hemoglobin (HbA1c) ≤8.5% | 24 participants | 24 participants | 20 participants | 68 participants |
| Baseline Glycosylated Hemoglobin (HbA1c) >8.5% | 11 participants | 11 participants | 15 participants | 37 participants |
| Baseline Systolic Blood Pressure (SBP) Hypertension Severity Category 140 ≤SBP <160 mm Hg | 19 participants | 23 participants | 16 participants | 58 participants |
| Baseline Systolic Blood Pressure (SBP) Hypertension Severity Category 160 ≤SBP <180 mm Hg | 0 participants | 6 participants | 5 participants | 11 participants |
| Baseline Systolic Blood Pressure (SBP) Hypertension Severity Category SBP <140 mm Hg | 16 participants | 6 participants | 13 participants | 35 participants |
| Baseline Systolic Blood Pressure (SBP) Hypertension Severity Category SBP ≥ 180 mm Hg | 0 participants | 0 participants | 1 participants | 1 participants |
| Body Mass Index (BMI) | 32.50 kg/m^2 STANDARD_DEVIATION 5.977 | 32.58 kg/m^2 STANDARD_DEVIATION 5.475 | 32.94 kg/m^2 STANDARD_DEVIATION 7.339 | 32.67 kg/m^2 STANDARD_DEVIATION 6.255 |
| Estimated Glomerular Filtration Rate (eGFR) | 87.86 ml/min/1.73 m^2 STANDARD_DEVIATION 18.068 | 89.31 ml/min/1.73 m^2 STANDARD_DEVIATION 15.631 | 89.72 ml/min/1.73 m^2 STANDARD_DEVIATION 18.379 | 88.96 ml/min/1.73 m^2 STANDARD_DEVIATION 17.253 |
| Estimated Glomerular Filtration Rate (eGFR) Categories 30 - <60 mL/min/1.73 m^2 | 0 participants | 0 participants | 2 participants | 2 participants |
| Estimated Glomerular Filtration Rate (eGFR) Categories 60 - <90 mL/min/1.73 m^2 | 21 participants | 19 participants | 17 participants | 57 participants |
| Estimated Glomerular Filtration Rate (eGFR) Categories ≥90 mL/min/1.73 m^2 | 14 participants | 16 participants | 16 participants | 46 participants |
| Female Reproductive Status Female of Childbearing Potential | 4 participants | 2 participants | 1 participants | 7 participants |
| Female Reproductive Status N/A (participant is male) | 21 participants | 25 participants | 17 participants | 63 participants |
| Female Reproductive Status Postmenopausal | 4 participants | 5 participants | 9 participants | 18 participants |
| Female Reproductive Status Surgically Sterile | 6 participants | 3 participants | 8 participants | 17 participants |
| Height | 169.4 cm STANDARD_DEVIATION 9.81 | 169.8 cm STANDARD_DEVIATION 9.41 | 167.0 cm STANDARD_DEVIATION 12.3 | 168.8 cm STANDARD_DEVIATION 10.56 |
| Race/Ethnicity, Customized American Indian or Alaska Native | 0 participants | 0 participants | 0 participants | 0 participants |
| Race/Ethnicity, Customized Asian | 4 participants | 5 participants | 2 participants | 11 participants |
| Race/Ethnicity, Customized Black or African American | 6 participants | 6 participants | 7 participants | 19 participants |
| Race/Ethnicity, Customized Hispanic or Latino | 11 participants | 15 participants | 14 participants | 40 participants |
| Race/Ethnicity, Customized Native Hawaiian or Other Pacific Islander | 0 participants | 1 participants | 0 participants | 1 participants |
| Race/Ethnicity, Customized Non-Hispanic or Latino | 24 participants | 20 participants | 21 participants | 65 participants |
| Race/Ethnicity, Customized White | 25 participants | 23 participants | 26 participants | 74 participants |
| Region of Enrollment United States | 35 participants | 35 participants | 35 participants | 105 participants |
| Sex: Female, Male Female | 14 Participants | 10 Participants | 18 Participants | 42 Participants |
| Sex: Female, Male Male | 21 Participants | 25 Participants | 17 Participants | 63 Participants |
| Smoking Classification Current smoker | 11 participants | 2 participants | 3 participants | 16 participants |
| Smoking Classification Ex-smoker | 7 participants | 10 participants | 11 participants | 28 participants |
| Smoking Classification Never smoked | 17 participants | 23 participants | 21 participants | 61 participants |
| Washout Required 21-Day Washout | 27 participants | 24 participants | 25 participants | 76 participants |
| Washout Required 4 Week Washout | 3 participants | 2 participants | 4 participants | 9 participants |
| Washout Required Missing | 5 participants | 9 participants | 6 participants | 20 participants |
| Weight | 93.41 kg STANDARD_DEVIATION 19.165 | 94.56 kg STANDARD_DEVIATION 20.084 | 92.33 kg STANDARD_DEVIATION 24.027 | 93.43 kg STANDARD_DEVIATION 21.012 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 10 / 35 | 10 / 35 | 8 / 35 |
| serious Total, serious adverse events | 0 / 35 | 1 / 35 | 0 / 35 |
Outcome results
Primary
Change From Baseline in Trough Sitting Clinic Systolic Blood Pressure
The change in trough systolic blood pressure measured at week 8 relative to baseline. The trough is the average of the non-missing values of the 3 serial trough sitting systolic blood pressure measurements.
Time frame: Baseline and Week 8
Population: The full analysis set included all randomized participants who took at least 1 dose of double-blind study medication. Missing values were imputed using last observation carried forward.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo QD | Change From Baseline in Trough Sitting Clinic Systolic Blood Pressure | -3.1 mm Hg | Standard Error 2.71 |
| Azilsartan Medoxomil 40 mg QD | Change From Baseline in Trough Sitting Clinic Systolic Blood Pressure | -10.2 mm Hg | Standard Error 2.69 |
| Azilsartan Medoxomil 80 mg QD | Change From Baseline in Trough Sitting Clinic Systolic Blood Pressure | -13.6 mm Hg | Standard Error 2.7 |
p-value: 0.007ANCOVA
p-value: 0.067ANCOVA
Secondary
Change From Baseline in Fasting Plasma Glucose
The change between the fasting plasma glucose value collected at each week indicated relative to baseline.
Time frame: Baseline and Weeks 2, 4, 6, 8, 12, 16, 20, and 24
Population: The full analysis set included all randomized participants who took at least 1 dose of double-blind study medication. Missing values were imputed using last observation carried forward.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo QD | Change From Baseline in Fasting Plasma Glucose | Week 24 (n=35, 35, 34) | 0.76 mmol/L | Standard Error 0.459 |
| Placebo QD | Change From Baseline in Fasting Plasma Glucose | Week 2 (n=34, 35, 34) | 0.16 mmol/L | Standard Error 0.435 |
| Placebo QD | Change From Baseline in Fasting Plasma Glucose | Week 8 (n=35, 35, 34) | 0.39 mmol/L | Standard Error 0.368 |
| Placebo QD | Change From Baseline in Fasting Plasma Glucose | Week 20 (n=35, 35, 34) | 0.94 mmol/L | Standard Error 0.438 |
| Placebo QD | Change From Baseline in Fasting Plasma Glucose | Week 4 (n=35, 35, 34) | 0.96 mmol/L | Standard Error 0.464 |
| Placebo QD | Change From Baseline in Fasting Plasma Glucose | Week 12 (n=35, 35, 34) | 0.76 mmol/L | Standard Error 0.417 |
| Placebo QD | Change From Baseline in Fasting Plasma Glucose | Week 6 (n=35, 35, 34) | 0.71 mmol/L | Standard Error 0.445 |
| Placebo QD | Change From Baseline in Fasting Plasma Glucose | Week 16 (n=35, 35, 34) | 0.36 mmol/L | Standard Error 0.379 |
| Azilsartan Medoxomil 40 mg QD | Change From Baseline in Fasting Plasma Glucose | Week 4 (n=35, 35, 34) | 0.45 mmol/L | Standard Error 0.464 |
| Azilsartan Medoxomil 40 mg QD | Change From Baseline in Fasting Plasma Glucose | Week 16 (n=35, 35, 34) | 0.17 mmol/L | Standard Error 0.379 |
| Azilsartan Medoxomil 40 mg QD | Change From Baseline in Fasting Plasma Glucose | Week 2 (n=34, 35, 34) | 0.64 mmol/L | Standard Error 0.429 |
| Azilsartan Medoxomil 40 mg QD | Change From Baseline in Fasting Plasma Glucose | Week 20 (n=35, 35, 34) | 0.01 mmol/L | Standard Error 0.438 |
| Azilsartan Medoxomil 40 mg QD | Change From Baseline in Fasting Plasma Glucose | Week 24 (n=35, 35, 34) | -0.15 mmol/L | Standard Error 0.459 |
| Azilsartan Medoxomil 40 mg QD | Change From Baseline in Fasting Plasma Glucose | Week 6 (n=35, 35, 34) | 0.28 mmol/L | Standard Error 0.445 |
| Azilsartan Medoxomil 40 mg QD | Change From Baseline in Fasting Plasma Glucose | Week 8 (n=35, 35, 34) | 0.34 mmol/L | Standard Error 0.368 |
| Azilsartan Medoxomil 40 mg QD | Change From Baseline in Fasting Plasma Glucose | Week 12 (n=35, 35, 34) | 0.09 mmol/L | Standard Error 0.417 |
| Azilsartan Medoxomil 80 mg QD | Change From Baseline in Fasting Plasma Glucose | Week 24 (n=35, 35, 34) | 0.48 mmol/L | Standard Error 0.465 |
| Azilsartan Medoxomil 80 mg QD | Change From Baseline in Fasting Plasma Glucose | Week 2 (n=34, 35, 34) | 1.03 mmol/L | Standard Error 0.435 |
| Azilsartan Medoxomil 80 mg QD | Change From Baseline in Fasting Plasma Glucose | Week 4 (n=35, 35, 34) | 0.81 mmol/L | Standard Error 0.47 |
| Azilsartan Medoxomil 80 mg QD | Change From Baseline in Fasting Plasma Glucose | Week 6 (n=35, 35, 34) | 0.81 mmol/L | Standard Error 0.451 |
| Azilsartan Medoxomil 80 mg QD | Change From Baseline in Fasting Plasma Glucose | Week 8 (n=35, 35, 34) | 0.96 mmol/L | Standard Error 0.373 |
| Azilsartan Medoxomil 80 mg QD | Change From Baseline in Fasting Plasma Glucose | Week 12 (n=35, 35, 34) | 0.94 mmol/L | Standard Error 0.423 |
| Azilsartan Medoxomil 80 mg QD | Change From Baseline in Fasting Plasma Glucose | Week 16 (n=35, 35, 34) | 0.49 mmol/L | Standard Error 0.384 |
| Azilsartan Medoxomil 80 mg QD | Change From Baseline in Fasting Plasma Glucose | Week 20 (n=35, 35, 34) | 0.86 mmol/L | Standard Error 0.444 |
Secondary
Change From Baseline in Glycosylated Hemoglobin (HbA1c)
The change in the value of glycosylated hemoglobin (the concentration of glucose bound to hemoglobin as a percent of the absolute maximum that can be bound) collected at week 24 relative to baseline.
Time frame: Baseline and Week 24
Population: The full analysis set included all randomized participants who took at least 1 dose of double-blind study medication. Missing values were imputed using last observation carried forward.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo QD | Change From Baseline in Glycosylated Hemoglobin (HbA1c) | 0.12 percentage glycosylated hemoglobin | Standard Error 0.174 |
| Azilsartan Medoxomil 40 mg QD | Change From Baseline in Glycosylated Hemoglobin (HbA1c) | -0.19 percentage glycosylated hemoglobin | Standard Error 0.174 |
| Azilsartan Medoxomil 80 mg QD | Change From Baseline in Glycosylated Hemoglobin (HbA1c) | 0.07 percentage glycosylated hemoglobin | Standard Error 0.179 |
p-value: 0.86ANCOVA
p-value: 0.21ANCOVA
Secondary
Change From Baseline in HbA1c
The change in the value of glycosylated hemoglobin (the concentration of glucose bound to hemoglobin as a percent of the absolute maximum that can be bound) collected at each week indicated relative to baseline.
Time frame: Baseline and Weeks 2, 4, 6, 8, 12, 16 and 20
Population: The full analysis set included all randomized participants who took at least 1 dose of double-blind study medication. Missing values were imputed using last observation carried forward.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo QD | Change From Baseline in HbA1c | Week 4 (n=35, 35, 33) | -0.02 percentage glycosylated hemoglobin | Standard Error 0.093 |
| Placebo QD | Change From Baseline in HbA1c | Week 12 (n=35, 35, 33) | 0.00 percentage glycosylated hemoglobin | Standard Error 0.171 |
| Placebo QD | Change From Baseline in HbA1c | Week 8 (n=35, 35, 33) | 0.05 percentage glycosylated hemoglobin | Standard Error 0.137 |
| Placebo QD | Change From Baseline in HbA1c | Week 2 (n=34, 35, 32) | -0.01 percentage glycosylated hemoglobin | Standard Error 0.072 |
| Placebo QD | Change From Baseline in HbA1c | Week 20 (n=35, 35, 33) | 0.14 percentage glycosylated hemoglobin | Standard Error 0.167 |
| Placebo QD | Change From Baseline in HbA1c | Week 16 (n=35, 35, 33) | 0.09 percentage glycosylated hemoglobin | Standard Error 0.171 |
| Placebo QD | Change From Baseline in HbA1c | Week 6 (n=35, 35, 33) | 0.06 percentage glycosylated hemoglobin | Standard Error 0.123 |
| Azilsartan Medoxomil 40 mg QD | Change From Baseline in HbA1c | Week 8 (n=35, 35, 33) | -0.03 percentage glycosylated hemoglobin | Standard Error 0.138 |
| Azilsartan Medoxomil 40 mg QD | Change From Baseline in HbA1c | Week 2 (n=34, 35, 32) | 0.05 percentage glycosylated hemoglobin | Standard Error 0.071 |
| Azilsartan Medoxomil 40 mg QD | Change From Baseline in HbA1c | Week 4 (n=35, 35, 33) | -0.02 percentage glycosylated hemoglobin | Standard Error 0.093 |
| Azilsartan Medoxomil 40 mg QD | Change From Baseline in HbA1c | Week 6 (n=35, 35, 33) | -0.02 percentage glycosylated hemoglobin | Standard Error 0.123 |
| Azilsartan Medoxomil 40 mg QD | Change From Baseline in HbA1c | Week 12 (n=35, 35, 33) | -0.05 percentage glycosylated hemoglobin | Standard Error 0.171 |
| Azilsartan Medoxomil 40 mg QD | Change From Baseline in HbA1c | Week 16 (n=35, 35, 33) | -0.06 percentage glycosylated hemoglobin | Standard Error 0.171 |
| Azilsartan Medoxomil 40 mg QD | Change From Baseline in HbA1c | Week 20 (n=35, 35, 33) | -0.13 percentage glycosylated hemoglobin | Standard Error 0.168 |
| Azilsartan Medoxomil 80 mg QD | Change From Baseline in HbA1c | Week 12 (n=35, 35, 33) | 0.29 percentage glycosylated hemoglobin | Standard Error 0.176 |
| Azilsartan Medoxomil 80 mg QD | Change From Baseline in HbA1c | Week 4 (n=35, 35, 33) | 0.29 percentage glycosylated hemoglobin | Standard Error 0.096 |
| Azilsartan Medoxomil 80 mg QD | Change From Baseline in HbA1c | Week 20 (n=35, 35, 33) | 0.09 percentage glycosylated hemoglobin | Standard Error 0.172 |
| Azilsartan Medoxomil 80 mg QD | Change From Baseline in HbA1c | Week 16 (n=35, 35, 33) | 0.16 percentage glycosylated hemoglobin | Standard Error 0.176 |
| Azilsartan Medoxomil 80 mg QD | Change From Baseline in HbA1c | Week 8 (n=35, 35, 33) | 0.23 percentage glycosylated hemoglobin | Standard Error 0.141 |
| Azilsartan Medoxomil 80 mg QD | Change From Baseline in HbA1c | Week 6 (n=35, 35, 33) | 0.24 percentage glycosylated hemoglobin | Standard Error 0.127 |
| Azilsartan Medoxomil 80 mg QD | Change From Baseline in HbA1c | Week 2 (n=34, 35, 32) | -0.06 percentage glycosylated hemoglobin | Standard Error 0.074 |
Secondary
Change From Baseline in the 12-hr Mean Diastolic Blood Pressure Measured by Ambulatory Blood Pressure Monitoring
The change in 12-hour mean systolic blood pressure measured at week 8 relative to baseline. Ambulatory blood pressure monitoring measures blood pressure at regular intervals throughout the day and night. The 12-hour mean is the average of all measurements recorded during the first 12 hours after dosing.
Time frame: Baseline and Week 8
Population: The full analysis set included all randomized participants who took at least 1 dose of double-blind study medication. Observed cases.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo QD | Change From Baseline in the 12-hr Mean Diastolic Blood Pressure Measured by Ambulatory Blood Pressure Monitoring | -1.9 mm Hg | Standard Error 1.37 |
| Azilsartan Medoxomil 40 mg QD | Change From Baseline in the 12-hr Mean Diastolic Blood Pressure Measured by Ambulatory Blood Pressure Monitoring | -4.7 mm Hg | Standard Error 1.31 |
| Azilsartan Medoxomil 80 mg QD | Change From Baseline in the 12-hr Mean Diastolic Blood Pressure Measured by Ambulatory Blood Pressure Monitoring | -8.2 mm Hg | Standard Error 1.4 |
Secondary
Change From Baseline in the 12-hr Mean Systolic Blood Pressure Measured by Ambulatory Blood Pressure Monitoring
The change in 12-hour mean systolic blood pressure measured at week 8 relative to baseline. Ambulatory blood pressure monitoring measures blood pressure at regular intervals throughout the day and night. The 12-hour mean is the average of all measurements recorded during the first 12 hours after dosing.
Time frame: Baseline and Week 8
Population: The full analysis set included all randomized participants who took at least 1 dose of double-blind study medication. Observed cases.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo QD | Change From Baseline in the 12-hr Mean Systolic Blood Pressure Measured by Ambulatory Blood Pressure Monitoring | -2.7 mm Hg | Standard Error 2.4 |
| Azilsartan Medoxomil 40 mg QD | Change From Baseline in the 12-hr Mean Systolic Blood Pressure Measured by Ambulatory Blood Pressure Monitoring | -8.6 mm Hg | Standard Error 2.29 |
| Azilsartan Medoxomil 80 mg QD | Change From Baseline in the 12-hr Mean Systolic Blood Pressure Measured by Ambulatory Blood Pressure Monitoring | -12.3 mm Hg | Standard Error 2.45 |
Secondary
Change From Baseline in the 24-hour Mean Diastolic Blood Pressure, as Measured by Ambulatory Blood Pressure Monitoring
The change in 24-hour mean diastolic blood pressure measured at week 8 relative to baseline. Ambulatory blood pressure monitoring measures blood pressure at regular intervals throughout the day and night. The 24-hour mean is the average of all measurements recorded for 24 hours after dosing.
Time frame: Baseline and Week 8
Population: The full analysis set included all randomized participants who took at least 1 dose of double-blind study medication. Observed cases.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo QD | Change From Baseline in the 24-hour Mean Diastolic Blood Pressure, as Measured by Ambulatory Blood Pressure Monitoring | -1.0 mm Hg | Standard Error 1.28 |
| Azilsartan Medoxomil 40 mg QD | Change From Baseline in the 24-hour Mean Diastolic Blood Pressure, as Measured by Ambulatory Blood Pressure Monitoring | -4.7 mm Hg | Standard Error 1.22 |
| Azilsartan Medoxomil 80 mg QD | Change From Baseline in the 24-hour Mean Diastolic Blood Pressure, as Measured by Ambulatory Blood Pressure Monitoring | -7.2 mm Hg | Standard Error 1.31 |
Secondary
Change From Baseline in the 24-hour Mean Systolic Blood Pressure, as Measured by Ambulatory Blood Pressure Monitoring
The change in 24-hour mean systolic blood pressure measured at week 8 relative to baseline. Ambulatory blood pressure monitoring measures blood pressure at regular intervals throughout the day and night. The 24-hour mean is the average of all measurements recorded for 24 hours after dosing.
Time frame: Baseline and Week 8
Population: The full analysis set included all randomized participants who took at least 1 dose of double-blind study medication. Observed cases.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo QD | Change From Baseline in the 24-hour Mean Systolic Blood Pressure, as Measured by Ambulatory Blood Pressure Monitoring | -1.6 mm Hg | Standard Error 2.25 |
| Azilsartan Medoxomil 40 mg QD | Change From Baseline in the 24-hour Mean Systolic Blood Pressure, as Measured by Ambulatory Blood Pressure Monitoring | -8.3 mm Hg | Standard Error 2.15 |
| Azilsartan Medoxomil 80 mg QD | Change From Baseline in the 24-hour Mean Systolic Blood Pressure, as Measured by Ambulatory Blood Pressure Monitoring | -11.3 mm Hg | Standard Error 2.31 |
Secondary
Change From Baseline in the Mean Daytime (6 AM to 10 PM) Diastolic Blood Pressure, as Measured by Ambulatory Blood Pressure Monitoring
The change in daytime (6am to 10pm) mean diastolic blood pressure measured at week 8 relative to baseline. Ambulatory blood pressure monitoring measures blood pressure at regular intervals throughout the day and night. Daytime mean is the average of all measurements recorded between the hours of 6 am and 10 pm.
Time frame: Baseline and Week 8
Population: The full analysis set included all randomized participants who took at least 1 dose of double-blind study medication. Observed cases.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo QD | Change From Baseline in the Mean Daytime (6 AM to 10 PM) Diastolic Blood Pressure, as Measured by Ambulatory Blood Pressure Monitoring | -1.4 mm Hg | Standard Error 1.25 |
| Azilsartan Medoxomil 40 mg QD | Change From Baseline in the Mean Daytime (6 AM to 10 PM) Diastolic Blood Pressure, as Measured by Ambulatory Blood Pressure Monitoring | -5.1 mm Hg | Standard Error 1.2 |
| Azilsartan Medoxomil 80 mg QD | Change From Baseline in the Mean Daytime (6 AM to 10 PM) Diastolic Blood Pressure, as Measured by Ambulatory Blood Pressure Monitoring | -7.5 mm Hg | Standard Error 1.28 |
Secondary
Change From Baseline in the Mean Daytime (6 AM to 10 PM) Systolic Blood Pressure, as Measured by Ambulatory Blood Pressure Monitoring
The change in daytime (6am to 10pm) mean systolic blood pressure measured week 8 relative to baseline. Ambulatory blood pressure monitoring measures blood pressure at regular intervals throughout the day and night. Daytime mean is the average of all measurements recorded between the hours of 6 am and 10 pm.
Time frame: Baseline and Week 8
Population: The full analysis set included all randomized participants who took at least 1 dose of double-blind study medication. Observed cases.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo QD | Change From Baseline in the Mean Daytime (6 AM to 10 PM) Systolic Blood Pressure, as Measured by Ambulatory Blood Pressure Monitoring | -2.0 mm Hg | Standard Error 2.23 |
| Azilsartan Medoxomil 40 mg QD | Change From Baseline in the Mean Daytime (6 AM to 10 PM) Systolic Blood Pressure, as Measured by Ambulatory Blood Pressure Monitoring | -9.0 mm Hg | Standard Error 2.13 |
| Azilsartan Medoxomil 80 mg QD | Change From Baseline in the Mean Daytime (6 AM to 10 PM) Systolic Blood Pressure, as Measured by Ambulatory Blood Pressure Monitoring | -11.7 mm Hg | Standard Error 2.28 |
Secondary
Change From Baseline in the Mean Nighttime (12 AM to 6 AM) Diastolic Blood Pressure, as Measured by Ambulatory Blood Pressure Monitoring
The change in nighttime (12am to 6am) mean diastolic blood pressure measured at week 8 relative to baseline. Ambulatory blood pressure monitoring measures blood pressure at regular intervals throughout the day and night. Nighttime mean is the average of all measurements recorded between the hours of 12 am and 6 am.
Time frame: Baseline and Week 8
Population: The full analysis set included all randomized participants who took at least 1 dose of double-blind study medication. Observed cases.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo QD | Change From Baseline in the Mean Nighttime (12 AM to 6 AM) Diastolic Blood Pressure, as Measured by Ambulatory Blood Pressure Monitoring | 0.6 mm Hg | Standard Error 1.65 |
| Azilsartan Medoxomil 40 mg QD | Change From Baseline in the Mean Nighttime (12 AM to 6 AM) Diastolic Blood Pressure, as Measured by Ambulatory Blood Pressure Monitoring | -3.2 mm Hg | Standard Error 1.58 |
| Azilsartan Medoxomil 80 mg QD | Change From Baseline in the Mean Nighttime (12 AM to 6 AM) Diastolic Blood Pressure, as Measured by Ambulatory Blood Pressure Monitoring | -7.2 mm Hg | Standard Error 1.69 |
Secondary
Change From Baseline in the Mean Nighttime (12 AM to 6 AM) Systolic Blood Pressure, as Measured by Ambulatory Blood Pressure Monitoring
The change in nighttime (12am to 6am) mean systolic blood pressure measured at week 8 relative to baseline. Ambulatory blood pressure monitoring measures blood pressure at regular intervals throughout the day and night. Nighttime mean is the average of all measurements recorded between the hours of 12 am and 6 am.
Time frame: Baseline and Week 8
Population: The full analysis set included all randomized participants who took at least 1 dose of double-blind study medication. Observed cases.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo QD | Change From Baseline in the Mean Nighttime (12 AM to 6 AM) Systolic Blood Pressure, as Measured by Ambulatory Blood Pressure Monitoring | 0.4 mm Hg | Standard Error 2.68 |
| Azilsartan Medoxomil 40 mg QD | Change From Baseline in the Mean Nighttime (12 AM to 6 AM) Systolic Blood Pressure, as Measured by Ambulatory Blood Pressure Monitoring | -6.2 mm Hg | Standard Error 2.57 |
| Azilsartan Medoxomil 80 mg QD | Change From Baseline in the Mean Nighttime (12 AM to 6 AM) Systolic Blood Pressure, as Measured by Ambulatory Blood Pressure Monitoring | -10.9 mm Hg | Standard Error 2.76 |
Secondary
Change From Baseline in the Trough (22 to 24 Hours After Dosing) Diastolic Blood Pressure as Measured by Ambulatory Blood Pressure Monitoring
The change in trough diastolic blood pressure measured at week 8 relative to baseline. Ambulatory blood pressure monitoring measures blood pressure at regular intervals throughout the day and night. The trough is the average of all measurements recorded from 22 to 24 hours after dosing.
Time frame: Baseline and Week 8
Population: The full analysis set included all randomized participants who took at least 1 dose of double-blind study medication. Observed cases.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo QD | Change From Baseline in the Trough (22 to 24 Hours After Dosing) Diastolic Blood Pressure as Measured by Ambulatory Blood Pressure Monitoring | 0.2 mm Hg | Standard Error 1.63 |
| Azilsartan Medoxomil 40 mg QD | Change From Baseline in the Trough (22 to 24 Hours After Dosing) Diastolic Blood Pressure as Measured by Ambulatory Blood Pressure Monitoring | -6.8 mm Hg | Standard Error 1.57 |
| Azilsartan Medoxomil 80 mg QD | Change From Baseline in the Trough (22 to 24 Hours After Dosing) Diastolic Blood Pressure as Measured by Ambulatory Blood Pressure Monitoring | -4.0 mm Hg | Standard Error 1.66 |
Secondary
Change From Baseline in the Trough (22 to 24 Hours After Dosing) Systolic Blood Pressure as Measured by Ambulatory Blood Pressure Monitoring
The change in trough systolic blood pressure measured at week 8 relative to baseline. Ambulatory blood pressure monitoring measures blood pressure at regular intervals throughout the day and night. The trough is the average of all measurements recorded from 22 to 24 hours after dosing.
Time frame: Baseline and Week 8
Population: The full analysis set included all randomized participants who took at least 1 dose of double-blind study medication. Observed cases.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo QD | Change From Baseline in the Trough (22 to 24 Hours After Dosing) Systolic Blood Pressure as Measured by Ambulatory Blood Pressure Monitoring | 2.3 mm Hg | Standard Error 2.8 |
| Azilsartan Medoxomil 40 mg QD | Change From Baseline in the Trough (22 to 24 Hours After Dosing) Systolic Blood Pressure as Measured by Ambulatory Blood Pressure Monitoring | -7.6 mm Hg | Standard Error 2.67 |
| Azilsartan Medoxomil 80 mg QD | Change From Baseline in the Trough (22 to 24 Hours After Dosing) Systolic Blood Pressure as Measured by Ambulatory Blood Pressure Monitoring | -7.9 mm Hg | Standard Error 2.87 |
Secondary
Change From Baseline in Trough Sitting Clinic Diastolic Blood Pressure
The change in trough diastolic blood pressure measured at week 8 relative to baseline. The trough is the average of the non-missing values of the 3 serial trough sitting diastolic blood pressure measurements.
Time frame: Baseline and Week 8
Population: The full analysis set included all randomized participants who took at least 1 dose of double-blind study medication. Missing values were imputed using last observation carried forward.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo QD | Change From Baseline in Trough Sitting Clinic Diastolic Blood Pressure | -0.8 mm Hg | Standard Error 1.36 |
| Azilsartan Medoxomil 40 mg QD | Change From Baseline in Trough Sitting Clinic Diastolic Blood Pressure | -5.4 mm Hg | Standard Error 1.37 |
| Azilsartan Medoxomil 80 mg QD | Change From Baseline in Trough Sitting Clinic Diastolic Blood Pressure | -5.8 mm Hg | Standard Error 1.37 |
Secondary
Change From Baseline to Week 6 and Week 24 in 2h Glucose During Oral Glucose Tolerance Testing (OGTT)
The change between the glucose value collected at weeks 6 and 24 relative to baseline. Oral glucose tolerance test measures glucose, insulin, C-peptide, insulin/glucose ratio, and glucagon through blood samples drawn at 0, 30, 60, and 120 minutes following consumption of a 75 g glucose beverage.
Time frame: Baseline and Weeks 6 and 24
Population: The full analysis set included all randomized participants who took at least 1 dose of double-blind study medication. Observed cases.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo QD | Change From Baseline to Week 6 and Week 24 in 2h Glucose During Oral Glucose Tolerance Testing (OGTT) | Week 24 (n=25, 26, 19) | -0.44 mmol/L | Standard Error 0.824 |
| Placebo QD | Change From Baseline to Week 6 and Week 24 in 2h Glucose During Oral Glucose Tolerance Testing (OGTT) | Week 6 (n=30, 30, 29) | 1.01 mmol/L | Standard Error 0.555 |
| Azilsartan Medoxomil 40 mg QD | Change From Baseline to Week 6 and Week 24 in 2h Glucose During Oral Glucose Tolerance Testing (OGTT) | Week 6 (n=30, 30, 29) | -0.46 mmol/L | Standard Error 0.556 |
| Azilsartan Medoxomil 40 mg QD | Change From Baseline to Week 6 and Week 24 in 2h Glucose During Oral Glucose Tolerance Testing (OGTT) | Week 24 (n=25, 26, 19) | -1.66 mmol/L | Standard Error 0.811 |
| Azilsartan Medoxomil 80 mg QD | Change From Baseline to Week 6 and Week 24 in 2h Glucose During Oral Glucose Tolerance Testing (OGTT) | Week 6 (n=30, 30, 29) | -0.09 mmol/L | Standard Error 0.565 |
| Azilsartan Medoxomil 80 mg QD | Change From Baseline to Week 6 and Week 24 in 2h Glucose During Oral Glucose Tolerance Testing (OGTT) | Week 24 (n=25, 26, 19) | -3.94 mmol/L | Standard Error 0.949 |
Secondary
Change From Baseline to Week 6 and Week 24 in AUC for C-peptide During OGTT
The change between the AUC for C-peptide at weeks 6 and 24 relative to baseline. AUC will be calculated based on measurements at 0, 30, 60 and 120 minutes. Oral glucose tolerance test measures glucose, insulin, C-peptide, insulin/glucose ratio, and glucagon through blood samples drawn at 0, 30, 60, and 120 minutes following consumption of a 75 g glucose beverage.
Time frame: Baseline and Weeks 6 and 24
Population: The full analysis set included all randomized participants who took at least 1 dose of double-blind study medication. Observed cases.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo QD | Change From Baseline to Week 6 and Week 24 in AUC for C-peptide During OGTT | Week 6 (n=28, 31, 28) | 0.051 nmol*hours/L | Standard Error 0.1779 |
| Placebo QD | Change From Baseline to Week 6 and Week 24 in AUC for C-peptide During OGTT | Week 24 (n=21, 25, 19) | -0.449 nmol*hours/L | Standard Error 0.2323 |
| Azilsartan Medoxomil 40 mg QD | Change From Baseline to Week 6 and Week 24 in AUC for C-peptide During OGTT | Week 6 (n=28, 31, 28) | -0.091 nmol*hours/L | Standard Error 0.1696 |
| Azilsartan Medoxomil 40 mg QD | Change From Baseline to Week 6 and Week 24 in AUC for C-peptide During OGTT | Week 24 (n=21, 25, 19) | 0.182 nmol*hours/L | Standard Error 0.2138 |
| Azilsartan Medoxomil 80 mg QD | Change From Baseline to Week 6 and Week 24 in AUC for C-peptide During OGTT | Week 6 (n=28, 31, 28) | -0.138 nmol*hours/L | Standard Error 0.178 |
| Azilsartan Medoxomil 80 mg QD | Change From Baseline to Week 6 and Week 24 in AUC for C-peptide During OGTT | Week 24 (n=21, 25, 19) | 0.155 nmol*hours/L | Standard Error 0.2444 |
Secondary
Change From Baseline to Week 6 and Week 24 in AUC for Glucagon During OGTT
The change between the AUC for glucagon at weeks 6 and 24 relative to baseline. AUC will be calculated based on measurements at 0, 30, 60 and 120 minutes. Oral glucose tolerance test measures glucose, insulin, C-peptide, insulin/glucose ratio, and glucagon through blood samples drawn at 0, 30, 60, and 120 minutes following consumption of a 75 g glucose beverage.
Time frame: Baseline and Weeks 6 and 24
Population: The full analysis set included all randomized participants who took at least 1 dose of double-blind study medication. Observed cases.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo QD | Change From Baseline to Week 6 and Week 24 in AUC for Glucagon During OGTT | Week 24 (n=22, 23, 19) | 2.7 ng*hours/L | Standard Error 8.51 |
| Placebo QD | Change From Baseline to Week 6 and Week 24 in AUC for Glucagon During OGTT | Week 6 (n=27, 27, 27) | -5.8 ng*hours/L | Standard Error 9.34 |
| Azilsartan Medoxomil 40 mg QD | Change From Baseline to Week 6 and Week 24 in AUC for Glucagon During OGTT | Week 6 (n=27, 27, 27) | 27.1 ng*hours/L | Standard Error 9.39 |
| Azilsartan Medoxomil 40 mg QD | Change From Baseline to Week 6 and Week 24 in AUC for Glucagon During OGTT | Week 24 (n=22, 23, 19) | 12.0 ng*hours/L | Standard Error 8.45 |
| Azilsartan Medoxomil 80 mg QD | Change From Baseline to Week 6 and Week 24 in AUC for Glucagon During OGTT | Week 6 (n=27, 27, 27) | 0.2 ng*hours/L | Standard Error 9.32 |
| Azilsartan Medoxomil 80 mg QD | Change From Baseline to Week 6 and Week 24 in AUC for Glucagon During OGTT | Week 24 (n=22, 23, 19) | 1.0 ng*hours/L | Standard Error 9.34 |
Secondary
Change From Baseline to Week 6 and Week 24 in AUC for Insulin During OGTT
The change between the AUC for insulin at weeks 6 and 24 relative to baseline. AUC will be calculated based on measurements at 0, 30, 60 and 120 minutes. Oral glucose tolerance test measures glucose, insulin, C-peptide, insulin/glucose ratio, and glucagon through blood samples drawn at 0, 30, 60, and 120 minutes following consumption of a 75 g glucose beverage.
Time frame: Baseline and Weeks 6 and 24
Population: The full analysis set included all randomized participants who took at least 1 dose of double-blind study medication. Observed cases.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo QD | Change From Baseline to Week 6 and Week 24 in AUC for Insulin During OGTT | Week 6 (n=28, 31, 28) | 64.4 pmol*hours/L | Standard Error 74.8 |
| Placebo QD | Change From Baseline to Week 6 and Week 24 in AUC for Insulin During OGTT | Week 24 (n=21, 25, 19) | -63.3 pmol*hours/L | Standard Error 162.81 |
| Azilsartan Medoxomil 40 mg QD | Change From Baseline to Week 6 and Week 24 in AUC for Insulin During OGTT | Week 6 (n=28, 31, 28) | -26.1 pmol*hours/L | Standard Error 71.42 |
| Azilsartan Medoxomil 40 mg QD | Change From Baseline to Week 6 and Week 24 in AUC for Insulin During OGTT | Week 24 (n=21, 25, 19) | 80.1 pmol*hours/L | Standard Error 149.88 |
| Azilsartan Medoxomil 80 mg QD | Change From Baseline to Week 6 and Week 24 in AUC for Insulin During OGTT | Week 6 (n=28, 31, 28) | 19.5 pmol*hours/L | Standard Error 74.78 |
| Azilsartan Medoxomil 80 mg QD | Change From Baseline to Week 6 and Week 24 in AUC for Insulin During OGTT | Week 24 (n=21, 25, 19) | 477.0 pmol*hours/L | Standard Error 169.22 |
Secondary
Change From Baseline to Week 6 and Week 24 in AUC for Insulin/Glucose Ratio During OGTT
The change between the AUC for insulin/glucose ratio at weeks 6 and 24 relative to baseline. AUC will be calculated based on measurements at 0, 30, 60 and 120 minutes. Oral glucose tolerance test measures glucose, insulin, C-peptide, insulin/glucose ratio, and glucagon through blood samples drawn at 0, 30, 60, and 120 minutes following consumption of a 75 g glucose beverage.
Time frame: Baseline and Weeks 6 and 24
Population: The full analysis set included all randomized participants who took at least 1 dose of double-blind study medication. Observed cases.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo QD | Change From Baseline to Week 6 and Week 24 in AUC for Insulin/Glucose Ratio During OGTT | Week 6 (n=27, 29, 28) | 4.86 pmol*hr/mmol | Standard Error 5.777 |
| Placebo QD | Change From Baseline to Week 6 and Week 24 in AUC for Insulin/Glucose Ratio During OGTT | Week 24 (n=20, 23, 19) | -5.36 pmol*hr/mmol | Standard Error 14.823 |
| Azilsartan Medoxomil 40 mg QD | Change From Baseline to Week 6 and Week 24 in AUC for Insulin/Glucose Ratio During OGTT | Week 6 (n=27, 29, 28) | 1.73 pmol*hr/mmol | Standard Error 5.578 |
| Azilsartan Medoxomil 40 mg QD | Change From Baseline to Week 6 and Week 24 in AUC for Insulin/Glucose Ratio During OGTT | Week 24 (n=20, 23, 19) | 1.05 pmol*hr/mmol | Standard Error 13.883 |
| Azilsartan Medoxomil 80 mg QD | Change From Baseline to Week 6 and Week 24 in AUC for Insulin/Glucose Ratio During OGTT | Week 6 (n=27, 29, 28) | -0.75 pmol*hr/mmol | Standard Error 5.663 |
| Azilsartan Medoxomil 80 mg QD | Change From Baseline to Week 6 and Week 24 in AUC for Insulin/Glucose Ratio During OGTT | Week 24 (n=20, 23, 19) | 52.68 pmol*hr/mmol | Standard Error 14.976 |
Secondary
Change From Baseline to Week 6 and Week 24 in the Area Under the Plasma Concentration-time Curve (AUC) for Glucose During OGTT
The change between the AUC for glucose at weeks 6 and 24 relative to baseline. AUC will be calculated based on measurements at 0, 30, 60 and 120 minutes. Oral glucose tolerance test measures glucose, insulin, C-peptide, insulin/glucose ratio, and glucagon through blood samples drawn at 0, 30, 60, and 120 minutes following consumption of a 75 g glucose beverage.
Time frame: Baseline and Weeks 6 and 24
Population: The full analysis set included all randomized participants who took at least 1 dose of double-blind study medication. Observed cases.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo QD | Change From Baseline to Week 6 and Week 24 in the Area Under the Plasma Concentration-time Curve (AUC) for Glucose During OGTT | Week 6 (n=28, 29, 29) | 1.60 mmol*hours/L | Standard Error 1.159 |
| Placebo QD | Change From Baseline to Week 6 and Week 24 in the Area Under the Plasma Concentration-time Curve (AUC) for Glucose During OGTT | Week 24 (n=23, 24, 19) | -1.97 mmol*hours/L | Standard Error 1.339 |
| Azilsartan Medoxomil 40 mg QD | Change From Baseline to Week 6 and Week 24 in the Area Under the Plasma Concentration-time Curve (AUC) for Glucose During OGTT | Week 6 (n=28, 29, 29) | -1.01 mmol*hours/L | Standard Error 1.148 |
| Azilsartan Medoxomil 40 mg QD | Change From Baseline to Week 6 and Week 24 in the Area Under the Plasma Concentration-time Curve (AUC) for Glucose During OGTT | Week 24 (n=23, 24, 19) | -1.13 mmol*hours/L | Standard Error 1.308 |
| Azilsartan Medoxomil 80 mg QD | Change From Baseline to Week 6 and Week 24 in the Area Under the Plasma Concentration-time Curve (AUC) for Glucose During OGTT | Week 6 (n=28, 29, 29) | 1.04 mmol*hours/L | Standard Error 1.14 |
| Azilsartan Medoxomil 80 mg QD | Change From Baseline to Week 6 and Week 24 in the Area Under the Plasma Concentration-time Curve (AUC) for Glucose During OGTT | Week 24 (n=23, 24, 19) | -5.52 mmol*hours/L | Standard Error 1.471 |
Secondary
Percentage of Participants Requiring Rescue Glycemic Therapy
Percentage of participants requiring rescue glycemic therapy during study.
Time frame: 24 Weeks
Population: The full analysis set included all randomized participants who took at least 1 dose of double-blind study medication.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo QD | Percentage of Participants Requiring Rescue Glycemic Therapy | 25.7 percentage of participants |
| Azilsartan Medoxomil 40 mg QD | Percentage of Participants Requiring Rescue Glycemic Therapy | 25.7 percentage of participants |
| Azilsartan Medoxomil 80 mg QD | Percentage of Participants Requiring Rescue Glycemic Therapy | 25.7 percentage of participants |
Secondary
Time to First Glycemic Rescue
The time to the first instance of participants requiring glycemic rescue during study.
Time frame: 24 Weeks
Population: The full analysis set included all randomized participants who took at least 1 dose of double-blind study medication.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Placebo QD | Time to First Glycemic Rescue | NA Days |
| Azilsartan Medoxomil 40 mg QD | Time to First Glycemic Rescue | NA Days |
| Azilsartan Medoxomil 80 mg QD | Time to First Glycemic Rescue | NA Days |