Azilsaltan Tablets (Azilva Tablets) Special Drug Use Surveillance "Hypertension Complicated by Diabetes "

• Sponsor: Takeda (Industry)
• Overall Status: Completed
• CT.gov ID: NCT02100319
• Collaborator: (none)
• Enrollment: 387
• Locations: 2
• Actual Duration (Months): 23.9
• Patients Per Site: 193.5
• Patients Per Site Per Month: 8.1

Study Details

Study Description

Brief Summary

The purpose of this study is to evaluate the efficacy of azilsartan tablets (Azilva Tablets) in patients with hypertension complicated by diabetes mellitus whose blood pressure cannot be sufficiently reduced by monotherapy with angiotensin II receptor blockers (ARBs) other than azilsartan, in routine clinical practice

Condition or Disease	Intervention/Treatment	Phase
Hypertension	Drug: Azilsartan

Detailed Description

This study was designed to evaluate the efficacy of azilsartan tablets (Azilva Tablets) in patients with hypertension complicated by diabetes mellitus whose blood pressure cannot be sufficiently reduced by monotherapy with ARBs, other than azilsartan, in daily medical practice.

Patient enrollment will be started on April 1, 2014. The usual dosage for adults is 20 mg of azilsartan administered orally once daily. The dose can be adjusted according to the participant's age and condition. The maximum daily dose is 40 mg.

Study Design

• Study Type: Observational
• Actual Enrollment: 387 participants
• Observational Model: Cohort
• Time Perspective: Prospective
• Official Title: Azilva Tablets Special Drug Use Surveillance "Hypertension Complicated by Diabetes "
• Actual Study Start Date: Mar 3, 2014
• Actual Primary Completion Date: Feb 29, 2016
• Actual Study Completion Date: Feb 29, 2016

Arms and Interventions

Arm	Intervention/Treatment
Azilsartan at a dose of 20 to 40 mg, orally, once daily Azilsartan tablets	Drug: Azilsartan; Azilsartan tablets; Other Names: Azilva Tablets

Outcome Measures

Primary Outcome Measures

1. Changes From Baseline in Blood Pressure on Final Assessment Point (up to Week 24) Measured at the Medical Institution [From baseline up to final assessment point (up to Week 24)]

   Reported data were changes from baseline in blood pressure (systolic blood pressure [SBP] and diastolic blood pressure [DBP]) measured at the medical institution.

2. Changes From Baseline in Home Blood Pressure on Final Assessment Point (up to Week 24) [From baseline up to final assessment point (up to Week 24)]

   Reported data were changes from baseline in blood pressure (SBP and DBP) measured at home right after waking up and at bedtime.

Secondary Outcome Measures

1. Changes From Baseline in Pulse Rate on Final Assessment Point (up to Week 24) at the Medical Institution [From baseline up to final assessment point (up to Week 24)]

   Reported data were changes from baseline in pulse rate measured at the medical institution.

2. Changes From Baseline in Hemoglobin A1c (HbA1c) on Final Assessment Point (up to Week 24) at the Medical Institution [From baseline up to final assessment point (up to Week 24)]

   Reported data were changes from baseline in HbA1c (National glycohemoglobin standardization program [NGSP] value) measured at the Medical Institution.

3. Changes From Baseline in Creatinine-adjusted Urinary Albumin Level on Final Assessment Point (up to Week 24) at the Medical Institution [From baseline up to final assessment point (up to Week 24)]

   Reported data were changes from baseline in creatinine-adjusted urinary albumin level (that is calculated from urinary albumin level divided by creatinine level) measured at the medical institution. Here "mg/gCr" is Milligrams per Gram of Creatinine.

4. Percentage of Participants Who Had One or More Adverse Events [Up to Week 24]

Eligibility Criteria

Criteria

• Ages Eligible for Study: N/A and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Patients with hypertension who meet all the following criteria will be enrolled:

1. Patients who has complications of diabetes mellitus

2. Patients who is on monotherapy with ARBs (other than azilsartan) as antihypertensive treatment (Patients who have continued monotherapy with the same ARB product for at least 8 weeks at the time of Step-1* of participant enrollment and will continue such treatment until the first administration of Azilsartan Tablets)

3. Patients who has a systolic blood pressure of ≥ 130 millimeter of mercury (mmHg) and/or diastolic blood pressure of 80 ≥ mmHg at the examination performed at the medical institution

4. Patients who is an outpatient

5. Patient who keeps a regular lifestyle and whose usual waking time is between 4 a.m. and 9:30 a.m.

*For this surveillance, participant enrollment will be performed in two divided steps: Step-1 (at hospital visit before prescription of Azilsartan Tablets) and Step-2 (at the time of prescription of Azilsartan Tablets).

Exclusion Criteria:

• Patients with contraindications to azilsartan

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1		Osaka		Japan
2		Tokyo		Japan

Sponsors and Collaborators

• Takeda

Investigators

• Study Director: Study Director, Takeda

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Takeda
• ClinicalTrials.gov Identifier: NCT02100319
• Other Study ID Numbers: 279-012; JapicCTI-142466
• First Posted: Mar 31, 2014
• Last Update Posted: Mar 21, 2019
• Last Verified: Dec 1, 2018

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by Takeda: Pharmacological therapy
• Additional relevant MeSH terms: Hypertension; Azilsartan medoxomil

Study Results

Participant Flow

Recruitment Details	Participants took part in the study at 146 investigative sites in Japan, from 03 March 2014 to 29 February 2016.
Pre-assignment Detail	Participants with a historical diagnosis of both hypertension and type 2 diabetes mellitus were enrolled. Participants received interventions as part of routine medical care.

Arm/Group Title	Azilsartan 20 to 40 mg
Arm/Group Description	Azilsartan 20 mg - 40 mg, tablet, orally, once daily for up to 24 weeks in participants based upon the disease severity. Participants received interventions as part of routine medical care.
Period Title: Overall Study
STARTED	387
COMPLETED	371
NOT COMPLETED	16

Baseline Characteristics

Arm/Group Title	Azilsartan 20 to 40 mg
Arm/Group Description	Azilsartan 20 mg - 40 mg, tablet, orally, once daily for up to 24 weeks in participants based upon the disease severity. Participants received interventions as part of routine medical care.
Overall Participants	371
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]	66.8 (11.74)
Sex: Female, Male (Count of Participants)
Female	150 40.4%
Male	221 59.6%
Race and Ethnicity Not Collected (Count of Participants)
Region of Enrollment (Number) [Number]
Japan	371 100%
Type of Diabetes Mellitus (Count of Participants)
Type 1 Diabetes Mellitus	2 0.5%
Type 2 Diabetes Mellitus	369 99.5%
Predisposition to Hypersensitivity (Count of Participants)
Had No Predisposition to Hypersensitivity	345 93%
Had Predisposition to Hypersensitivity	11 3%
Unknown	15 4%
Medical Complications (Count of Participants)
Had No Presence of Medical Complications	77 20.8%
Had Presence of Medical Complications	294 79.2%
Estimated Glomerular Filtration Rate (eGFR) (Count of Participants)
>= 15 mL/min/1.73m^2 and < 30 mL/min/1.73m^2	4 1.1%
>= 30 mL/min/1.73m^2 and < 45 mL/min/1.73m^2	24 6.5%
>= 45 mL/min/1.73m^2 and < 60 mL/min/1.73m^2	57 15.4%
>= 60 mL/min/1.73m^2 and < 90 mL/min/1.73m^2	145 39.1%
>= 90 mL/min/1.73m^2	47 12.7%
BMI (kg/m^2) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [kg/m^2]	25.91 (4.667)
Smoking Classification (Count of Participants)
Never Smoked	173 46.6%
Current Smoker	48 12.9%
Ex-Smoker	94 25.3%
Unknown	56 15.1%
Drinking Habits (Count of Participants)
Yes	73 19.7%
No	241 65%
Unknown	57 15.4%
Pre-treatment ARB before Study Start (Count of Participants)
Losartan	32 8.6%
Candesartan	88 23.7%
Valsartan	58 15.6%
Telmisartan	89 24%
Olmesartan	66 17.8%
Irbesartan	38 10.2%

Outcome Measures

1. Primary Outcome

Title	Changes From Baseline in Blood Pressure on Final Assessment Point (up to Week 24) Measured at the Medical Institution
Description	Reported data were changes from baseline in blood pressure (systolic blood pressure [SBP] and diastolic blood pressure [DBP]) measured at the medical institution.
Time Frame	From baseline up to final assessment point (up to Week 24)

Outcome Measure Data

Analysis Population Description

Efficacy assessment population; The efficacy assessment population was defined as participants who completed the study and had efficacy data at baseline and post-baseline time points available. The analyzed numbers were participants who were evaluable for this outcome measure.

Arm/Group Title	Azilsartan 20 to 40 mg
Arm/Group Description	Azilsartan 20 mg - 40 mg, tablet, orally, once daily for up to 24 weeks in participants based upon the disease severity. Participants received interventions as part of routine medical care.
Measure Participants	371
Systolic Blood Pressure (SBP)	-10.5 (18.40)
Diastolic Blood Pressure (DBP)	-5.1 (11.57)

2. Primary Outcome

Title	Changes From Baseline in Home Blood Pressure on Final Assessment Point (up to Week 24)
Description	Reported data were changes from baseline in blood pressure (SBP and DBP) measured at home right after waking up and at bedtime.
Time Frame	From baseline up to final assessment point (up to Week 24)

Outcome Measure Data

Analysis Population Description

Efficacy assessment population; The efficacy assessment population was defined as participants who completed the study and had efficacy data at baseline and post-baseline time points available. The analyzed numbers were participants who were evaluable for this outcome measure.

Arm/Group Title	Azilsartan 20 to 40 mg
Arm/Group Description	Azilsartan 20 mg - 40 mg, tablet, orally, once daily for up to 24 weeks in participants based upon the disease severity. Participants received interventions as part of routine medical care.
Measure Participants	371
SBP Right after Waking-up	-7.9 (14.86)
DBP Right after Waking-up	-4.1 (8.07)
SBP at Bedtime	-7.1 (13.82)
DBP at Bedtime	-4.3 (7.76)

3. Secondary Outcome

Title	Changes From Baseline in Pulse Rate on Final Assessment Point (up to Week 24) at the Medical Institution
Description	Reported data were changes from baseline in pulse rate measured at the medical institution.
Time Frame	From baseline up to final assessment point (up to Week 24)

Outcome Measure Data

Analysis Population Description

Efficacy assessment population; The efficacy assessment population was defined as participants who completed the study and had efficacy data at baseline and post-baseline time points available. The analyzed numbers were participants who were evaluable for this outcome measure.

Arm/Group Title	Azilsartan 20 to 40 mg
Arm/Group Description	Azilsartan 20 mg - 40 mg, tablet, orally, once daily for up to 24 weeks in participants based upon the disease severity. Participants received interventions as part of routine medical care.
Measure Participants	371
Mean (Standard Deviation) [Beat per Minutes (bpm)]	-1.3 (10.22)

4. Secondary Outcome

Title	Changes From Baseline in Hemoglobin A1c (HbA1c) on Final Assessment Point (up to Week 24) at the Medical Institution
Description	Reported data were changes from baseline in HbA1c (National glycohemoglobin standardization program [NGSP] value) measured at the Medical Institution.
Time Frame	From baseline up to final assessment point (up to Week 24)

Outcome Measure Data

Analysis Population Description

Efficacy assessment population; The efficacy assessment population was defined as participants who completed the study and had efficacy data at baseline and post-baseline time points available. The analyzed numbers were participants who were evaluable for this outcome measure.

Arm/Group Title	Azilsartan 20 to 40 mg
Arm/Group Description	Azilsartan 20 mg - 40 mg, tablet, orally, once daily for up to 24 weeks in participants based upon the disease severity. Participants received interventions as part of routine medical care.
Measure Participants	371
Mean (Standard Deviation) [Percent]	6.72 (0.792)

5. Secondary Outcome

Title	Changes From Baseline in Creatinine-adjusted Urinary Albumin Level on Final Assessment Point (up to Week 24) at the Medical Institution
Description	Reported data were changes from baseline in creatinine-adjusted urinary albumin level (that is calculated from urinary albumin level divided by creatinine level) measured at the medical institution. Here "mg/gCr" is Milligrams per Gram of Creatinine.
Time Frame	From baseline up to final assessment point (up to Week 24)

Outcome Measure Data

Analysis Population Description

Efficacy assessment population; The efficacy assessment population was defined as participants who completed the study and had efficacy data at baseline and post-baseline time points available. The analyzed numbers were participants who were evaluable for this outcome measure.

Arm/Group Title	Azilsartan 20 to 40 mg
Arm/Group Description	Azilsartan 20 mg - 40 mg, tablet, orally, once daily for up to 24 weeks in participants based upon the disease severity. Participants received interventions as part of routine medical care.
Measure Participants	371
Mean (Standard Deviation) [mg/gCr]	-44.344 (413.9519)

6. Secondary Outcome

Title	Percentage of Participants Who Had One or More Adverse Events
Time Frame	Up to Week 24

Outcome Measure Data

Analysis Population Description

Safety Analysis Set; The safety analysis set was defined as all participants who completed the study.

Arm/Group Title	Azilsartan 20 to 40 mg
Arm/Group Description	Azilsartan 20 mg - 40 mg, tablet, orally, once daily for up to 24 weeks in participants based upon the disease severity. Participants received interventions as part of routine medical care.
Measure Participants	371
Number [Percentage of Participants]	6.47 1.7%

Adverse Events

Time Frame	Up to Week 24
Adverse Event Reporting Description	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.
Arm/Group Title	Azilsartan 20 to 40 mg
Arm/Group Description	Azilsartan 20 mg - 40 mg, tablet, orally, once daily for up to 24 weeks in participants based upon the disease severity. Participants received interventions as part of routine medical care.
All Cause Mortality
	Azilsartan 20 to 40 mg
	Affected / at Risk (%)	# Events
Total	2/371 (0.5%)
Serious Adverse Events
	Azilsartan 20 to 40 mg
	Affected / at Risk (%)	# Events
Total	5/371 (1.3%)
Cardiac disorders
Cardiac failure	1/371 (0.3%)
Gastrointestinal disorders
Diarrhoea	1/371 (0.3%)
General disorders
Sudden death	1/371 (0.3%)
Infections and infestations
Sepsis	1/371 (0.3%)
Metabolism and nutrition disorders
Hypoglycaemia	1/371 (0.3%)
Musculoskeletal and connective tissue disorders
Intervertebral disc protrusion	1/371 (0.3%)
Respiratory, thoracic and mediastinal disorders
Asthma	1/371 (0.3%)
Dyspnoea	1/371 (0.3%)
Other (Not Including Serious) Adverse Events
	Azilsartan 20 to 40 mg
	Affected / at Risk (%)	# Events
Total	20/371 (5.4%)
Cardiac disorders
Atrial fibrillation	1/371 (0.3%)
Gastrointestinal disorders
Gastrooesophageal reflux disease	1/371 (0.3%)
Stomatitis	1/371 (0.3%)
Large intestine polyp	1/371 (0.3%)
General disorders
Feeling abnormal	1/371 (0.3%)
Oedema peripheral	1/371 (0.3%)
Investigations
Blood pressure increased	2/371 (0.5%)
Blood glucose increased	1/371 (0.3%)
Glycosylated haemoglobin increased	3/371 (0.8%)
Blood creatinine increased	1/371 (0.3%)
Metabolism and nutrition disorders
Diabetes mellitus	7/371 (1.9%)
Diabetes mellitus inadequate control	1/371 (0.3%)
Hyperglycaemia	1/371 (0.3%)
Hypoglycaemia	1/371 (0.3%)
Dyslipidaemia	1/371 (0.3%)
Nervous system disorders
Dizziness postural	1/371 (0.3%)
Sciatica	1/371 (0.3%)
Reproductive system and breast disorders
Vaginal discharge	1/371 (0.3%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

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.