Trial Outcomes & Findings for Efficacy and Safety of Azilsartan Medoxomil Used in Combination With Metformin in Participants With Hypertension and Diabetes (NCT NCT01496430)

Last Updated: 2015-05-06

Results Overview

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.

Recruitment status

TERMINATED

Study phase

PHASE3

Target enrollment

105 participants

Primary outcome timeframe

Baseline and Week 8

Results posted on

2015-05-06

Participant Flow

Participants took part in the study at 41 investigative sites in the United States from 09 January 2012 to 30 May 2013.

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.

Participant milestones

Participant milestones
Measure	Placebo QD Azilsartan medoxomil placebo-matching tablets, orally, once daily for up to 24 weeks.	Azilsartan Medoxomil 40 mg QD Azilsartan medoxomil 40 mg, tablets, orally, once daily for up to 24 weeks.	Azilsartan Medoxomil 80 mg QD Azilsartan medoxomil 80 mg, tablets, orally, once daily for up to 24 weeks.
Overall Study STARTED	35	35	35
Overall Study COMPLETED	29	30	25
Overall Study NOT COMPLETED	6	5	10

Reasons for withdrawal

Reasons for withdrawal
Measure	Placebo QD Azilsartan medoxomil placebo-matching tablets, orally, once daily for up to 24 weeks.	Azilsartan Medoxomil 40 mg QD Azilsartan medoxomil 40 mg, tablets, orally, once daily for up to 24 weeks.	Azilsartan Medoxomil 80 mg QD Azilsartan medoxomil 80 mg, tablets, orally, once daily for up to 24 weeks.
Overall Study Adverse Event	0	0	1
Overall Study Major Protocol Deviation	0	0	1
Overall Study Lost to Follow-up	2	3	1
Overall Study Voluntary Withdrawal	2	1	6
Overall Study Principal Investigator Discretion	0	1	1
Overall Study Other	2	0	0

Baseline Characteristics

Efficacy and Safety of Azilsartan Medoxomil Used in Combination With Metformin in Participants With Hypertension and Diabetes

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Placebo QD n=35 Participants Azilsartan medoxomil placebo-matching tablets, orally, once daily for up to 24 weeks.	Azilsartan Medoxomil 40 mg QD n=35 Participants Azilsartan medoxomil 40 mg, tablets, orally, once daily for up to 24 weeks.	Azilsartan Medoxomil 80 mg QD n=35 Participants Azilsartan medoxomil 80 mg, tablets, orally, once daily for up to 24 weeks.	Total n=105 Participants Total of all reporting groups
Age, Continuous	57.1 years STANDARD_DEVIATION 8.66 • n=5 Participants	54.7 years STANDARD_DEVIATION 7.63 • n=7 Participants	55.8 years STANDARD_DEVIATION 7.37 • n=5 Participants	55.9 years STANDARD_DEVIATION 7.89 • n=4 Participants
Age, Customized <45 years	3 participants n=5 Participants	3 participants n=7 Participants	2 participants n=5 Participants	8 participants n=4 Participants
Age, Customized Between 45 and 64 years	25 participants n=5 Participants	29 participants n=7 Participants	30 participants n=5 Participants	84 participants n=4 Participants
Age, Customized ≥65 years	7 participants n=5 Participants	3 participants n=7 Participants	3 participants n=5 Participants	13 participants n=4 Participants
Sex: Female, Male Female	14 Participants n=5 Participants	10 Participants n=7 Participants	18 Participants n=5 Participants	42 Participants n=4 Participants
Sex: Female, Male Male	21 Participants n=5 Participants	25 Participants n=7 Participants	17 Participants n=5 Participants	63 Participants n=4 Participants
Race/Ethnicity, Customized Hispanic or Latino	11 participants n=5 Participants	15 participants n=7 Participants	14 participants n=5 Participants	40 participants n=4 Participants
Race/Ethnicity, Customized Non-Hispanic or Latino	24 participants n=5 Participants	20 participants n=7 Participants	21 participants n=5 Participants	65 participants n=4 Participants
Race/Ethnicity, Customized American Indian or Alaska Native	0 participants n=5 Participants	0 participants n=7 Participants	0 participants n=5 Participants	0 participants n=4 Participants
Race/Ethnicity, Customized Asian	4 participants n=5 Participants	5 participants n=7 Participants	2 participants n=5 Participants	11 participants n=4 Participants
Race/Ethnicity, Customized Black or African American	6 participants n=5 Participants	6 participants n=7 Participants	7 participants n=5 Participants	19 participants n=4 Participants
Race/Ethnicity, Customized Native Hawaiian or Other Pacific Islander	0 participants n=5 Participants	1 participants n=7 Participants	0 participants n=5 Participants	1 participants n=4 Participants
Race/Ethnicity, Customized White	25 participants n=5 Participants	23 participants n=7 Participants	26 participants n=5 Participants	74 participants n=4 Participants
Region of Enrollment United States	35 participants n=5 Participants	35 participants n=7 Participants	35 participants n=5 Participants	105 participants n=4 Participants
Height	169.4 cm STANDARD_DEVIATION 9.81 • n=5 Participants	169.8 cm STANDARD_DEVIATION 9.41 • n=7 Participants	167.0 cm STANDARD_DEVIATION 12.30 • n=5 Participants	168.8 cm STANDARD_DEVIATION 10.56 • n=4 Participants
Weight	93.41 kg STANDARD_DEVIATION 19.165 • n=5 Participants	94.56 kg STANDARD_DEVIATION 20.084 • n=7 Participants	92.33 kg STANDARD_DEVIATION 24.027 • n=5 Participants	93.43 kg STANDARD_DEVIATION 21.012 • n=4 Participants
Body Mass Index (BMI)	32.50 kg/m^2 STANDARD_DEVIATION 5.977 • n=5 Participants	32.58 kg/m^2 STANDARD_DEVIATION 5.475 • n=7 Participants	32.94 kg/m^2 STANDARD_DEVIATION 7.339 • n=5 Participants	32.67 kg/m^2 STANDARD_DEVIATION 6.255 • n=4 Participants
Smoking Classification Never smoked	17 participants n=5 Participants	23 participants n=7 Participants	21 participants n=5 Participants	61 participants n=4 Participants
Smoking Classification Current smoker	11 participants n=5 Participants	2 participants n=7 Participants	3 participants n=5 Participants	16 participants n=4 Participants
Smoking Classification Ex-smoker	7 participants n=5 Participants	10 participants n=7 Participants	11 participants n=5 Participants	28 participants n=4 Participants
Baseline Glycosylated Hemoglobin (HbA1c) ≤8.5%	24 participants n=5 Participants	24 participants n=7 Participants	20 participants n=5 Participants	68 participants n=4 Participants
Baseline Glycosylated Hemoglobin (HbA1c) >8.5%	11 participants n=5 Participants	11 participants n=7 Participants	15 participants n=5 Participants	37 participants n=4 Participants
Estimated Glomerular Filtration Rate (eGFR)	87.86 ml/min/1.73 m^2 STANDARD_DEVIATION 18.068 • n=5 Participants	89.31 ml/min/1.73 m^2 STANDARD_DEVIATION 15.631 • n=7 Participants	89.72 ml/min/1.73 m^2 STANDARD_DEVIATION 18.379 • n=5 Participants	88.96 ml/min/1.73 m^2 STANDARD_DEVIATION 17.253 • n=4 Participants
Estimated Glomerular Filtration Rate (eGFR) Categories 30 - <60 mL/min/1.73 m^2	0 participants n=5 Participants	0 participants n=7 Participants	2 participants n=5 Participants	2 participants n=4 Participants
Estimated Glomerular Filtration Rate (eGFR) Categories 60 - <90 mL/min/1.73 m^2	21 participants n=5 Participants	19 participants n=7 Participants	17 participants n=5 Participants	57 participants n=4 Participants
Estimated Glomerular Filtration Rate (eGFR) Categories ≥90 mL/min/1.73 m^2	14 participants n=5 Participants	16 participants n=7 Participants	16 participants n=5 Participants	46 participants n=4 Participants
Baseline Systolic Blood Pressure (SBP) Hypertension Severity Category SBP <140 mm Hg	16 participants n=5 Participants	6 participants n=7 Participants	13 participants n=5 Participants	35 participants n=4 Participants
Baseline Systolic Blood Pressure (SBP) Hypertension Severity Category 140 ≤SBP <160 mm Hg	19 participants n=5 Participants	23 participants n=7 Participants	16 participants n=5 Participants	58 participants n=4 Participants
Baseline Systolic Blood Pressure (SBP) Hypertension Severity Category 160 ≤SBP <180 mm Hg	0 participants n=5 Participants	6 participants n=7 Participants	5 participants n=5 Participants	11 participants n=4 Participants
Baseline Systolic Blood Pressure (SBP) Hypertension Severity Category SBP ≥ 180 mm Hg	0 participants n=5 Participants	0 participants n=7 Participants	1 participants n=5 Participants	1 participants n=4 Participants
Baseline Diastolic Blood Pressure (DBP) Hypertension Severity Category DBP < 90 mm Hg	25 participants n=5 Participants	18 participants n=7 Participants	25 participants n=5 Participants	68 participants n=4 Participants
Baseline Diastolic Blood Pressure (DBP) Hypertension Severity Category DBP ≥ 90 mm Hg	10 participants n=5 Participants	17 participants n=7 Participants	10 participants n=5 Participants	37 participants n=4 Participants
Antihypertension Medication Within 28 Days Yes	32 participants n=5 Participants	27 participants n=7 Participants	30 participants n=5 Participants	89 participants n=4 Participants
Antihypertension Medication Within 28 Days No	3 participants n=5 Participants	8 participants n=7 Participants	5 participants n=5 Participants	16 participants n=4 Participants
Washout Required 21-Day Washout	27 participants n=5 Participants	24 participants n=7 Participants	25 participants n=5 Participants	76 participants n=4 Participants
Washout Required 4 Week Washout	3 participants n=5 Participants	2 participants n=7 Participants	4 participants n=5 Participants	9 participants n=4 Participants
Washout Required Missing	5 participants n=5 Participants	9 participants n=7 Participants	6 participants n=5 Participants	20 participants n=4 Participants
Female Reproductive Status Postmenopausal	4 participants n=5 Participants	5 participants n=7 Participants	9 participants n=5 Participants	18 participants n=4 Participants
Female Reproductive Status Surgically Sterile	6 participants n=5 Participants	3 participants n=7 Participants	8 participants n=5 Participants	17 participants n=4 Participants
Female Reproductive Status Female of Childbearing Potential	4 participants n=5 Participants	2 participants n=7 Participants	1 participants n=5 Participants	7 participants n=4 Participants
Female Reproductive Status N/A (participant is male)	21 participants n=5 Participants	25 participants n=7 Participants	17 participants n=5 Participants	63 participants n=4 Participants

PRIMARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Placebo QD n=35 Participants Azilsartan medoxomil placebo-matching tablets, orally, once daily for up to 24 weeks.	Azilsartan Medoxomil 40 mg QD n=35 Participants Azilsartan medoxomil 40 mg, tablets, orally, once daily for up to 24 weeks.	Azilsartan Medoxomil 80 mg QD n=34 Participants Azilsartan medoxomil 80 mg, tablets, orally, once daily for up to 24 weeks.
Change From Baseline in Trough Sitting Clinic Systolic Blood Pressure	-3.1 mm Hg Standard Error 2.71	-10.2 mm Hg Standard Error 2.69	-13.6 mm Hg Standard Error 2.70

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure	Placebo QD n=35 Participants Azilsartan medoxomil placebo-matching tablets, orally, once daily for up to 24 weeks.	Azilsartan Medoxomil 40 mg QD n=35 Participants Azilsartan medoxomil 40 mg, tablets, orally, once daily for up to 24 weeks.	Azilsartan Medoxomil 80 mg QD n=33 Participants Azilsartan medoxomil 80 mg, tablets, orally, once daily for up to 24 weeks.
Change From Baseline in Glycosylated Hemoglobin (HbA1c)	0.12 percentage glycosylated hemoglobin Standard Error 0.174	-0.19 percentage glycosylated hemoglobin Standard Error 0.174	0.07 percentage glycosylated hemoglobin Standard Error 0.179

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure	Placebo QD n=35 Participants Azilsartan medoxomil placebo-matching tablets, orally, once daily for up to 24 weeks.	Azilsartan Medoxomil 40 mg QD n=35 Participants Azilsartan medoxomil 40 mg, tablets, orally, once daily for up to 24 weeks.	Azilsartan Medoxomil 80 mg QD n=34 Participants Azilsartan medoxomil 80 mg, tablets, orally, once daily for up to 24 weeks.
Change From Baseline in Trough Sitting Clinic Diastolic Blood Pressure	-0.8 mm Hg Standard Error 1.36	-5.4 mm Hg Standard Error 1.37	-5.8 mm Hg Standard Error 1.37

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure	Placebo QD n=21 Participants Azilsartan medoxomil placebo-matching tablets, orally, once daily for up to 24 weeks.	Azilsartan Medoxomil 40 mg QD n=23 Participants Azilsartan medoxomil 40 mg, tablets, orally, once daily for up to 24 weeks.	Azilsartan Medoxomil 80 mg QD n=20 Participants Azilsartan medoxomil 80 mg, tablets, orally, once daily for up to 24 weeks.
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	-8.3 mm Hg Standard Error 2.15	-11.3 mm Hg Standard Error 2.31

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure	Placebo QD n=21 Participants Azilsartan medoxomil placebo-matching tablets, orally, once daily for up to 24 weeks.	Azilsartan Medoxomil 40 mg QD n=23 Participants Azilsartan medoxomil 40 mg, tablets, orally, once daily for up to 24 weeks.	Azilsartan Medoxomil 80 mg QD n=20 Participants Azilsartan medoxomil 80 mg, tablets, orally, once daily for up to 24 weeks.
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	-4.7 mm Hg Standard Error 1.22	-7.2 mm Hg Standard Error 1.31

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure	Placebo QD n=21 Participants Azilsartan medoxomil placebo-matching tablets, orally, once daily for up to 24 weeks.	Azilsartan Medoxomil 40 mg QD n=23 Participants Azilsartan medoxomil 40 mg, tablets, orally, once daily for up to 24 weeks.	Azilsartan Medoxomil 80 mg QD n=20 Participants Azilsartan medoxomil 80 mg, tablets, orally, once daily for up to 24 weeks.
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	-9.0 mm Hg Standard Error 2.13	-11.7 mm Hg Standard Error 2.28

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure	Placebo QD n=21 Participants Azilsartan medoxomil placebo-matching tablets, orally, once daily for up to 24 weeks.	Azilsartan Medoxomil 40 mg QD n=23 Participants Azilsartan medoxomil 40 mg, tablets, orally, once daily for up to 24 weeks.	Azilsartan Medoxomil 80 mg QD n=20 Participants Azilsartan medoxomil 80 mg, tablets, orally, once daily for up to 24 weeks.
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	-5.1 mm Hg Standard Error 1.20	-7.5 mm Hg Standard Error 1.28

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure	Placebo QD n=21 Participants Azilsartan medoxomil placebo-matching tablets, orally, once daily for up to 24 weeks.	Azilsartan Medoxomil 40 mg QD n=23 Participants Azilsartan medoxomil 40 mg, tablets, orally, once daily for up to 24 weeks.	Azilsartan Medoxomil 80 mg QD n=20 Participants Azilsartan medoxomil 80 mg, tablets, orally, once daily for up to 24 weeks.
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	-6.2 mm Hg Standard Error 2.57	-10.9 mm Hg Standard Error 2.76

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure	Placebo QD n=21 Participants Azilsartan medoxomil placebo-matching tablets, orally, once daily for up to 24 weeks.	Azilsartan Medoxomil 40 mg QD n=23 Participants Azilsartan medoxomil 40 mg, tablets, orally, once daily for up to 24 weeks.	Azilsartan Medoxomil 80 mg QD n=20 Participants Azilsartan medoxomil 80 mg, tablets, orally, once daily for up to 24 weeks.
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	-3.2 mm Hg Standard Error 1.58	-7.2 mm Hg Standard Error 1.69

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure	Placebo QD n=21 Participants Azilsartan medoxomil placebo-matching tablets, orally, once daily for up to 24 weeks.	Azilsartan Medoxomil 40 mg QD n=23 Participants Azilsartan medoxomil 40 mg, tablets, orally, once daily for up to 24 weeks.	Azilsartan Medoxomil 80 mg QD n=20 Participants Azilsartan medoxomil 80 mg, tablets, orally, once daily for up to 24 weeks.
Change From Baseline in the 12-hr Mean Systolic Blood Pressure Measured by Ambulatory Blood Pressure Monitoring	-2.7 mm Hg Standard Error 2.40	-8.6 mm Hg Standard Error 2.29	-12.3 mm Hg Standard Error 2.45

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Placebo QD n=21 Participants Azilsartan medoxomil placebo-matching tablets, orally, once daily for up to 24 weeks.	Azilsartan Medoxomil 40 mg QD n=23 Participants Azilsartan medoxomil 40 mg, tablets, orally, once daily for up to 24 weeks.	Azilsartan Medoxomil 80 mg QD n=20 Participants Azilsartan medoxomil 80 mg, tablets, orally, once daily for up to 24 weeks.
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	-4.7 mm Hg Standard Error 1.31	-8.2 mm Hg Standard Error 1.40

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure	Placebo QD n=21 Participants Azilsartan medoxomil placebo-matching tablets, orally, once daily for up to 24 weeks.	Azilsartan Medoxomil 40 mg QD n=23 Participants Azilsartan medoxomil 40 mg, tablets, orally, once daily for up to 24 weeks.	Azilsartan Medoxomil 80 mg QD n=20 Participants Azilsartan medoxomil 80 mg, tablets, orally, once daily for up to 24 weeks.
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 2.80	-7.6 mm Hg Standard Error 2.67	-7.9 mm Hg Standard Error 2.87

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure	Placebo QD n=21 Participants Azilsartan medoxomil placebo-matching tablets, orally, once daily for up to 24 weeks.	Azilsartan Medoxomil 40 mg QD n=23 Participants Azilsartan medoxomil 40 mg, tablets, orally, once daily for up to 24 weeks.	Azilsartan Medoxomil 80 mg QD n=20 Participants Azilsartan medoxomil 80 mg, tablets, orally, once daily for up to 24 weeks.
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	-6.8 mm Hg Standard Error 1.57	-4.0 mm Hg Standard Error 1.66

SECONDARY outcome

Timeframe: 24 Weeks

Population: The full analysis set included all randomized participants who took at least 1 dose of double-blind study medication.

Percentage of participants requiring rescue glycemic therapy during study.

Outcome measures

Outcome measures
Measure	Placebo QD n=35 Participants Azilsartan medoxomil placebo-matching tablets, orally, once daily for up to 24 weeks.	Azilsartan Medoxomil 40 mg QD n=35 Participants Azilsartan medoxomil 40 mg, tablets, orally, once daily for up to 24 weeks.	Azilsartan Medoxomil 80 mg QD n=35 Participants Azilsartan medoxomil 80 mg, tablets, orally, once daily for up to 24 weeks.
Percentage of Participants Requiring Rescue Glycemic Therapy	25.7 percentage of participants	25.7 percentage of participants	25.7 percentage of participants

SECONDARY outcome

Timeframe: 24 Weeks

Population: The full analysis set included all randomized participants who took at least 1 dose of double-blind study medication.

The time to the first instance of participants requiring glycemic rescue during study.

Outcome measures

Outcome measures
Measure	Placebo QD n=35 Participants Azilsartan medoxomil placebo-matching tablets, orally, once daily for up to 24 weeks.	Azilsartan Medoxomil 40 mg QD n=35 Participants Azilsartan medoxomil 40 mg, tablets, orally, once daily for up to 24 weeks.	Azilsartan Medoxomil 80 mg QD n=35 Participants Azilsartan medoxomil 80 mg, tablets, orally, once daily for up to 24 weeks.
Time to First Glycemic Rescue	NA Days Interval 21.57 to Median and third quartile times to glycemic rescue were not observed.	NA Days Interval 22.57 to Median and third quartile times to glycemic rescue were not observed.	NA Days Interval 17.14 to Median and third quartile times to glycemic rescue were not observed.

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure	Placebo QD n=35 Participants Azilsartan medoxomil placebo-matching tablets, orally, once daily for up to 24 weeks.	Azilsartan Medoxomil 40 mg QD n=35 Participants Azilsartan medoxomil 40 mg, tablets, orally, once daily for up to 24 weeks.	Azilsartan Medoxomil 80 mg QD n=33 Participants Azilsartan medoxomil 80 mg, tablets, orally, once daily for up to 24 weeks.
Change From Baseline in HbA1c Week 2 (n=34, 35, 32)	-0.01 percentage glycosylated hemoglobin Standard Error 0.072	0.05 percentage glycosylated hemoglobin Standard Error 0.071	-0.06 percentage glycosylated hemoglobin Standard Error 0.074
Change From Baseline in HbA1c Week 4 (n=35, 35, 33)	-0.02 percentage glycosylated hemoglobin Standard Error 0.093	-0.02 percentage glycosylated hemoglobin Standard Error 0.093	0.29 percentage glycosylated hemoglobin Standard Error 0.096
Change From Baseline in HbA1c Week 6 (n=35, 35, 33)	0.06 percentage glycosylated hemoglobin Standard Error 0.123	-0.02 percentage glycosylated hemoglobin Standard Error 0.123	0.24 percentage glycosylated hemoglobin Standard Error 0.127
Change From Baseline in HbA1c Week 8 (n=35, 35, 33)	0.05 percentage glycosylated hemoglobin Standard Error 0.137	-0.03 percentage glycosylated hemoglobin Standard Error 0.138	0.23 percentage glycosylated hemoglobin Standard Error 0.141
Change From Baseline in HbA1c Week 12 (n=35, 35, 33)	0.00 percentage glycosylated hemoglobin Standard Error 0.171	-0.05 percentage glycosylated hemoglobin Standard Error 0.171	0.29 percentage glycosylated hemoglobin Standard Error 0.176
Change From Baseline in HbA1c Week 16 (n=35, 35, 33)	0.09 percentage glycosylated hemoglobin Standard Error 0.171	-0.06 percentage glycosylated hemoglobin Standard Error 0.171	0.16 percentage glycosylated hemoglobin Standard Error 0.176
Change From Baseline in HbA1c Week 20 (n=35, 35, 33)	0.14 percentage glycosylated hemoglobin Standard Error 0.167	-0.13 percentage glycosylated hemoglobin Standard Error 0.168	0.09 percentage glycosylated hemoglobin Standard Error 0.172

SECONDARY outcome

Timeframe: 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.

The change between the fasting plasma glucose value collected at each week indicated relative to baseline.

Outcome measures

Outcome measures
Measure	Placebo QD n=35 Participants Azilsartan medoxomil placebo-matching tablets, orally, once daily for up to 24 weeks.	Azilsartan Medoxomil 40 mg QD n=35 Participants Azilsartan medoxomil 40 mg, tablets, orally, once daily for up to 24 weeks.	Azilsartan Medoxomil 80 mg QD n=34 Participants Azilsartan medoxomil 80 mg, tablets, orally, once daily for up to 24 weeks.
Change From Baseline in Fasting Plasma Glucose Week 24 (n=35, 35, 34)	0.76 mmol/L Standard Error 0.459	-0.15 mmol/L Standard Error 0.459	0.48 mmol/L Standard Error 0.465
Change From Baseline in Fasting Plasma Glucose Week 2 (n=34, 35, 34)	0.16 mmol/L Standard Error 0.435	0.64 mmol/L Standard Error 0.429	1.03 mmol/L Standard Error 0.435
Change From Baseline in Fasting Plasma Glucose Week 4 (n=35, 35, 34)	0.96 mmol/L Standard Error 0.464	0.45 mmol/L Standard Error 0.464	0.81 mmol/L Standard Error 0.470
Change From Baseline in Fasting Plasma Glucose Week 6 (n=35, 35, 34)	0.71 mmol/L Standard Error 0.445	0.28 mmol/L Standard Error 0.445	0.81 mmol/L Standard Error 0.451
Change From Baseline in Fasting Plasma Glucose Week 8 (n=35, 35, 34)	0.39 mmol/L Standard Error 0.368	0.34 mmol/L Standard Error 0.368	0.96 mmol/L Standard Error 0.373
Change From Baseline in Fasting Plasma Glucose Week 12 (n=35, 35, 34)	0.76 mmol/L Standard Error 0.417	0.09 mmol/L Standard Error 0.417	0.94 mmol/L Standard Error 0.423
Change From Baseline in Fasting Plasma Glucose Week 16 (n=35, 35, 34)	0.36 mmol/L Standard Error 0.379	0.17 mmol/L Standard Error 0.379	0.49 mmol/L Standard Error 0.384
Change From Baseline in Fasting Plasma Glucose Week 20 (n=35, 35, 34)	0.94 mmol/L Standard Error 0.438	0.01 mmol/L Standard Error 0.438	0.86 mmol/L Standard Error 0.444

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure	Placebo QD n=32 Participants Azilsartan medoxomil placebo-matching tablets, orally, once daily for up to 24 weeks.	Azilsartan Medoxomil 40 mg QD n=31 Participants Azilsartan medoxomil 40 mg, tablets, orally, once daily for up to 24 weeks.	Azilsartan Medoxomil 80 mg QD n=29 Participants Azilsartan medoxomil 80 mg, tablets, orally, once daily for up to 24 weeks.
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	-0.46 mmol/L Standard Error 0.556	-0.09 mmol/L Standard Error 0.565
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	-1.66 mmol/L Standard Error 0.811	-3.94 mmol/L Standard Error 0.949

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure	Placebo QD n=30 Participants Azilsartan medoxomil placebo-matching tablets, orally, once daily for up to 24 weeks.	Azilsartan Medoxomil 40 mg QD n=31 Participants Azilsartan medoxomil 40 mg, tablets, orally, once daily for up to 24 weeks.	Azilsartan Medoxomil 80 mg QD n=29 Participants Azilsartan medoxomil 80 mg, tablets, orally, once daily for up to 24 weeks.
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	-1.01 mmol*hours/L Standard Error 1.148	1.04 mmol*hours/L Standard Error 1.140
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	-1.13 mmol*hours/L Standard Error 1.308	-5.52 mmol*hours/L Standard Error 1.471

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure	Placebo QD n=29 Participants Azilsartan medoxomil placebo-matching tablets, orally, once daily for up to 24 weeks.	Azilsartan Medoxomil 40 mg QD n=32 Participants Azilsartan medoxomil 40 mg, tablets, orally, once daily for up to 24 weeks.	Azilsartan Medoxomil 80 mg QD n=28 Participants Azilsartan medoxomil 80 mg, tablets, orally, once daily for up to 24 weeks.
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 74.80	-26.1 pmol*hours/L Standard Error 71.42	19.5 pmol*hours/L Standard Error 74.78
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	80.1 pmol*hours/L Standard Error 149.88	477.0 pmol*hours/L Standard Error 169.22

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure	Placebo QD n=29 Participants Azilsartan medoxomil placebo-matching tablets, orally, once daily for up to 24 weeks.	Azilsartan Medoxomil 40 mg QD n=32 Participants Azilsartan medoxomil 40 mg, tablets, orally, once daily for up to 24 weeks.	Azilsartan Medoxomil 80 mg QD n=28 Participants Azilsartan medoxomil 80 mg, tablets, orally, once daily for up to 24 weeks.
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	-0.091 nmol*hours/L Standard Error 0.1696	-0.138 nmol*hours/L Standard Error 0.1780
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	0.182 nmol*hours/L Standard Error 0.2138	0.155 nmol*hours/L Standard Error 0.2444

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure	Placebo QD n=28 Participants Azilsartan medoxomil placebo-matching tablets, orally, once daily for up to 24 weeks.	Azilsartan Medoxomil 40 mg QD n=31 Participants Azilsartan medoxomil 40 mg, tablets, orally, once daily for up to 24 weeks.	Azilsartan Medoxomil 80 mg QD n=28 Participants Azilsartan medoxomil 80 mg, tablets, orally, once daily for up to 24 weeks.
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	1.73 pmol*hr/mmol Standard Error 5.578	-0.75 pmol*hr/mmol Standard Error 5.663
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	1.05 pmol*hr/mmol Standard Error 13.883	52.68 pmol*hr/mmol Standard Error 14.976

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure	Placebo QD n=30 Participants Azilsartan medoxomil placebo-matching tablets, orally, once daily for up to 24 weeks.	Azilsartan Medoxomil 40 mg QD n=30 Participants Azilsartan medoxomil 40 mg, tablets, orally, once daily for up to 24 weeks.	Azilsartan Medoxomil 80 mg QD n=28 Participants Azilsartan medoxomil 80 mg, tablets, orally, once daily for up to 24 weeks.
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	27.1 ng*hours/L Standard Error 9.39	0.2 ng*hours/L Standard Error 9.32
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	12.0 ng*hours/L Standard Error 8.45	1.0 ng*hours/L Standard Error 9.34

Adverse Events

Placebo QD

Serious events: 0 serious events

Other events: 10 other events

Deaths: 0 deaths

Azilsartan Medoxomil 40 mg QD

Serious events: 1 serious events

Other events: 10 other events

Deaths: 0 deaths

Azilsartan Medoxomil 80 mg QD

Serious events: 0 serious events

Other events: 8 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Placebo QD n=35 participants at risk Azilsartan medoxomil placebo-matching tablets, orally, once daily for up to 24 weeks.	Azilsartan Medoxomil 40 mg QD n=35 participants at risk Azilsartan medoxomil 40 mg, tablets, orally, once daily for up to 24 weeks.	Azilsartan Medoxomil 80 mg QD n=35 participants at risk Azilsartan medoxomil 80 mg, tablets, orally, once daily for up to 24 weeks.
Respiratory, thoracic and mediastinal disorders Chronic obstructive pulmonary disease	0.00% 0/35 • Treatment-emergent adverse events are adverse events that started after the first dose of double-blind study drug and no more than 14 days (or 30 days for a serious adverse event) after the last dose of double-blind study drug, for up to 28 weeks. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	2.9% 1/35 • Treatment-emergent adverse events are adverse events that started after the first dose of double-blind study drug and no more than 14 days (or 30 days for a serious adverse event) after the last dose of double-blind study drug, for up to 28 weeks. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/35 • Treatment-emergent adverse events are adverse events that started after the first dose of double-blind study drug and no more than 14 days (or 30 days for a serious adverse event) after the last dose of double-blind study drug, for up to 28 weeks. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Respiratory, thoracic and mediastinal disorders Hypoxia	0.00% 0/35 • Treatment-emergent adverse events are adverse events that started after the first dose of double-blind study drug and no more than 14 days (or 30 days for a serious adverse event) after the last dose of double-blind study drug, for up to 28 weeks. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	2.9% 1/35 • Treatment-emergent adverse events are adverse events that started after the first dose of double-blind study drug and no more than 14 days (or 30 days for a serious adverse event) after the last dose of double-blind study drug, for up to 28 weeks. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/35 • Treatment-emergent adverse events are adverse events that started after the first dose of double-blind study drug and no more than 14 days (or 30 days for a serious adverse event) after the last dose of double-blind study drug, for up to 28 weeks. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.

Other adverse events

Other adverse events
Measure	Placebo QD n=35 participants at risk Azilsartan medoxomil placebo-matching tablets, orally, once daily for up to 24 weeks.	Azilsartan Medoxomil 40 mg QD n=35 participants at risk Azilsartan medoxomil 40 mg, tablets, orally, once daily for up to 24 weeks.	Azilsartan Medoxomil 80 mg QD n=35 participants at risk Azilsartan medoxomil 80 mg, tablets, orally, once daily for up to 24 weeks.
Infections and infestations Urinary tract infection	8.6% 3/35 • Treatment-emergent adverse events are adverse events that started after the first dose of double-blind study drug and no more than 14 days (or 30 days for a serious adverse event) after the last dose of double-blind study drug, for up to 28 weeks. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	11.4% 4/35 • Treatment-emergent adverse events are adverse events that started after the first dose of double-blind study drug and no more than 14 days (or 30 days for a serious adverse event) after the last dose of double-blind study drug, for up to 28 weeks. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	8.6% 3/35 • Treatment-emergent adverse events are adverse events that started after the first dose of double-blind study drug and no more than 14 days (or 30 days for a serious adverse event) after the last dose of double-blind study drug, for up to 28 weeks. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Metabolism and nutrition disorders Hyperglycaemia	5.7% 2/35 • Treatment-emergent adverse events are adverse events that started after the first dose of double-blind study drug and no more than 14 days (or 30 days for a serious adverse event) after the last dose of double-blind study drug, for up to 28 weeks. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	5.7% 2/35 • Treatment-emergent adverse events are adverse events that started after the first dose of double-blind study drug and no more than 14 days (or 30 days for a serious adverse event) after the last dose of double-blind study drug, for up to 28 weeks. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	5.7% 2/35 • Treatment-emergent adverse events are adverse events that started after the first dose of double-blind study drug and no more than 14 days (or 30 days for a serious adverse event) after the last dose of double-blind study drug, for up to 28 weeks. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Gastrointestinal disorders Diarrhoea	5.7% 2/35 • Treatment-emergent adverse events are adverse events that started after the first dose of double-blind study drug and no more than 14 days (or 30 days for a serious adverse event) after the last dose of double-blind study drug, for up to 28 weeks. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	2.9% 1/35 • Treatment-emergent adverse events are adverse events that started after the first dose of double-blind study drug and no more than 14 days (or 30 days for a serious adverse event) after the last dose of double-blind study drug, for up to 28 weeks. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	5.7% 2/35 • Treatment-emergent adverse events are adverse events that started after the first dose of double-blind study drug and no more than 14 days (or 30 days for a serious adverse event) after the last dose of double-blind study drug, for up to 28 weeks. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Infections and infestations Upper respiratory tract infection	5.7% 2/35 • Treatment-emergent adverse events are adverse events that started after the first dose of double-blind study drug and no more than 14 days (or 30 days for a serious adverse event) after the last dose of double-blind study drug, for up to 28 weeks. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	2.9% 1/35 • Treatment-emergent adverse events are adverse events that started after the first dose of double-blind study drug and no more than 14 days (or 30 days for a serious adverse event) after the last dose of double-blind study drug, for up to 28 weeks. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	5.7% 2/35 • Treatment-emergent adverse events are adverse events that started after the first dose of double-blind study drug and no more than 14 days (or 30 days for a serious adverse event) after the last dose of double-blind study drug, for up to 28 weeks. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Gastrointestinal disorders Constipation	5.7% 2/35 • Treatment-emergent adverse events are adverse events that started after the first dose of double-blind study drug and no more than 14 days (or 30 days for a serious adverse event) after the last dose of double-blind study drug, for up to 28 weeks. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	2.9% 1/35 • Treatment-emergent adverse events are adverse events that started after the first dose of double-blind study drug and no more than 14 days (or 30 days for a serious adverse event) after the last dose of double-blind study drug, for up to 28 weeks. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	2.9% 1/35 • Treatment-emergent adverse events are adverse events that started after the first dose of double-blind study drug and no more than 14 days (or 30 days for a serious adverse event) after the last dose of double-blind study drug, for up to 28 weeks. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Hepatobiliary disorders Cholelithiasis	0.00% 0/35 • Treatment-emergent adverse events are adverse events that started after the first dose of double-blind study drug and no more than 14 days (or 30 days for a serious adverse event) after the last dose of double-blind study drug, for up to 28 weeks. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	5.7% 2/35 • Treatment-emergent adverse events are adverse events that started after the first dose of double-blind study drug and no more than 14 days (or 30 days for a serious adverse event) after the last dose of double-blind study drug, for up to 28 weeks. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/35 • Treatment-emergent adverse events are adverse events that started after the first dose of double-blind study drug and no more than 14 days (or 30 days for a serious adverse event) after the last dose of double-blind study drug, for up to 28 weeks. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Respiratory, thoracic and mediastinal disorders Cough	0.00% 0/35 • Treatment-emergent adverse events are adverse events that started after the first dose of double-blind study drug and no more than 14 days (or 30 days for a serious adverse event) after the last dose of double-blind study drug, for up to 28 weeks. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	5.7% 2/35 • Treatment-emergent adverse events are adverse events that started after the first dose of double-blind study drug and no more than 14 days (or 30 days for a serious adverse event) after the last dose of double-blind study drug, for up to 28 weeks. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/35 • Treatment-emergent adverse events are adverse events that started after the first dose of double-blind study drug and no more than 14 days (or 30 days for a serious adverse event) after the last dose of double-blind study drug, for up to 28 weeks. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Renal and urinary disorders Proteinuria	5.7% 2/35 • Treatment-emergent adverse events are adverse events that started after the first dose of double-blind study drug and no more than 14 days (or 30 days for a serious adverse event) after the last dose of double-blind study drug, for up to 28 weeks. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/35 • Treatment-emergent adverse events are adverse events that started after the first dose of double-blind study drug and no more than 14 days (or 30 days for a serious adverse event) after the last dose of double-blind study drug, for up to 28 weeks. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/35 • Treatment-emergent adverse events are adverse events that started after the first dose of double-blind study drug and no more than 14 days (or 30 days for a serious adverse event) after the last dose of double-blind study drug, for up to 28 weeks. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.

Additional Information

Medical Director; Clinical Science

Takeda

Phone: 800-778-2860

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee The first study related publication will be a multi-center publication submitted within 24 months after conclusion or termination of a study at all sites. After such multi site publication, all proposed site publications and presentations will be submitted to sponsor for review 60 days in advance of publication. Site will remove Sponsor confidential information unrelated to study results. Sponsor can delay a proposed publication for another 60 days to preserve intellectual property.
Publication restrictions are in place

Restriction type: OTHER