ADDM Study - Amtrel and Co-Diovan in Type 2 Diabetes Mellitus Hypertension Patients With Microalbuminuria

• ClinicalTrials.gov Identifier: NCT01375322
• Recruitment Status: Completed
• First Posted: June 17, 2011
• Last Update Posted: June 17, 2011
• Sponsor: TSH Biopharm Corporation Limited
• Information provided by: TSH Biopharm Corporation Limited

Tracking Information

• First Submitted Date: June 15, 2011
• First Posted Date: June 17, 2011
• Last Update Posted Date: June 17, 2011
• Study Start Date: June 2007
• Actual Primary Completion Date: June 2010 (Final data collection date for primary outcome measure)
• Current Primary Outcome Measures (submitted: June 16, 2011): To compare the change from baseline in blood pressures (DBP/SBP) to 16-week regimen between Amtrel® and Co-Diovan® [ Time Frame: 16-week ]
• Original Primary Outcome Measures: Same as current
• Change History: No Changes Posted
• Current Secondary Outcome Measures (submitted: June 16, 2011): To compare the response rate (defined as SBP < 130 mmHg and DBP < 80 mmHg) at the end of study [ Time Frame: 16-week ]
• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: ADDM Study - Amtrel and Co-Diovan in Type 2 Diabetes Mellitus Hypertension Patients With Microalbuminuria
• Official Title: Efficacy and Safety of Two Fixed-combination Antihypertensive Regimens, Amtrel® and Co-Diovan® in Type 2 Diabetes Hypertension Patients With Microalbuminuria

Brief Summary

The purpose of the study is to compare the change from baseline in blood pressures (DBP/SBP) to 16-week regimen between Amtrel® and Co-Diovan®. The secondary objectives were listed as the following.

• To compare the response rate (defined as SBP < 130 mmHg and DBP < 80 mmHg) at the end of study
• To evaluate the change from baseline in albumin-to-creatinine ratio with antihypertensive medications in whole group (combined treatment groups) and each treatment group (Amtrel®, Co-Diovan®) at Week 16
• The change from baseline in glycosylated hemoglobin (HbA1c) at Week 16
• The change from baseline in fasting plasma glucose (FPG) at Week 16
• The change from baseline in fasting lipid profiles (triglyceride, total cholesterol, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol) at Week 16
• The change from baseline in arteriosclerosis marker (brachial-ankle pulse-wave velocity (ba-PWV) and ankle-brachial pressure index (ABI), using Colin-VP1000) at Week 16
• The change from baseline on the body mass index (BMI) and waist-hip ratio (WHR) at each specified study time point
• To ascertain the safety and tolerability of Amtrel® versus Co-Diovan® including AE/SAE, and laboratory examinations

Detailed Description

At the screening visit, patients who fulfilled the entrance criteria and had given written informed consent entered a placebo running period where they discontinued antihypertensive medication for two weeks. During that period, Adalat 5mg could be given for emergency. At the end of placebo running period those patients became hypertensive (i.e., SBP between 130-180mmHg or DBP between 80-110mmHg) were randomized into either treatment group. For those patients remaining normotensive continued to be on placebo run-in for another two weeks (10 - 14 days). After the two-week (10 - 14 days) placebo run-in period those patients became hypertensive were randomized into either treatment group. However for those patients remaining normotensive were excluded from the study. After randomization into either arm, patients entered four months treatment period. The dosage adjustment were proceed in order to reach the best effect. During the treatment period there was a monthly visit to assess the response of the patients.

The starting dose of Amtrel® was 1 capsule (contains 1/2 tablet) (amlodipine / benazepril hydrochloride 2.5 mg/ 5 mg) every morning and could be adjusted up to 2 capsules (contains 1 tablet per capsule) (amlodipine / benazepril hydrochloride 10 mg/ 20 mg) every morning if patients did not achieve the criteria of SBP<130 mmHg and DBP< 80 mmHg during treatment period.

The starting dose of Co-Diovan® was 1 capsule (contains 1/2 tablet) (valsartan/ hydrochlorothiazide 40 mg/ 6.25 mg) every morning and could be adjusted up to 2 capsules (contains 1 tablet per capsule) (valsartan/ hydrochlorothiazide 160 mg/ 25.0 mg) every morning if patients did not achieve the criteria of SBP<130 mmHg and DBP< 80 mmHg during treatment period.

All randomized patients attended monthly clinic visits for the 16-week treatment period. At week 4 (Visit 3), all patients were force-titrated to 1 capsule (1 tablet per capsule) for 4 weeks. Subsequently, those patients did not achieve the target blood pressure (SBP<130 mmHg and DBP<80 mmHg) were titrated monthly to next dose level (2 capsule per day).

• Study Type: Interventional
• Study Phase: Phase 4
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor); Primary Purpose: Treatment

Condition

• Hypertension
• Diabetes Mellitus, Type 2
• Albuminuria

Intervention

• Drug: Amlodipine+Benazepril
  Amlodipine besylate 5 mg + Benazepril hydrochloride 10 mg, daily use and forced titrate till 16-week end
  Other Name: Amtrel®
• Drug: Valsartan+Hydrochlorothiazide
  Valsartan 80 mg + Hydrochlorothiazide 12.5 mg, daily use and forced titrate till 16-week end
  Other Name: Co-Diovan®

Study Arms

• Active Comparator: Co-Diovan® Group
  The starting dose of Co-Diovan® was 1 capsule (contains 1/2 tablet) (valsartan/ hydrochlorothiazide 40 mg/ 6.25 mg) every morning and could be adjusted up to 2 capsules (contains 1 tablet per capsule) (valsartan/ hydrochlorothiazide 160 mg/ 25.0 mg) every morning if patients did not achieve the criteria of SBP<130 mmHg and DBP< 80 mmHg during treatment period
  Intervention: Drug: Valsartan+Hydrochlorothiazide
• Experimental: Amtrel® Group
  The starting dose of Amtrel® was 1 capsule (contains 1/2 tablet) (amlodipine / benazepril hydrochloride 2.5 mg/ 5 mg) every morning and could be adjusted up to 2 capsules (contains 1 tablet per capsule) (amlodipine / benazepril hydrochloride 10 mg/ 20 mg) every morning if patients did not achieve the criteria of SBP<130 mmHg and DBP< 80 mmHg during treatment period
  Intervention: Drug: Amlodipine+Benazepril

• Publications *: Lee IT, Hung YJ, Chen JF, Wang CY, Lee WJ, Sheu WH. Comparison of the efficacy and safety profiles of two fixed-dose combinations of antihypertensive agents, amlodipine/benazepril versus valsartan/hydrochlorothiazide, in patients with type 2 diabetes mellitus and hypertension: a 16-week, multicenter, randomized, double-blind, noninferiority study. Clin Ther. 2012 Aug;34(8):1735-50. doi: 10.1016/j.clinthera.2012.06.014. Epub 2012 Jul 10.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: June 16, 2011): 226
• Original Actual Enrollment: Same as current
• Actual Study Completion Date: June 2010
• Actual Primary Completion Date: June 2010 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• type 2 diabetes with stable controlled (HbA1c between 6.5-10%)
• SBP between 130-180mmHg or DBP between 80-110mmHg
• microalbuminuria (UAE 30-300mg/24hrs or creatinine 30-300mg/g)

Exclusion Criteria:

• IDDM or secondary forms of diabetes
• hepatic and/or renal dysfunction
• serum potassium level > 5.5mmol/L
• severe renal disease
• Chronic Heart Failure (NYHA class III or IV)
• unstable CV disease
• PTCA within 3 months

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 20 Years to 80 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Taiwan

Administrative Information

• NCT Number: NCT01375322
• Other Study ID Numbers: TTY-ABM-0601
• Has Data Monitoring Committee: No
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Responsible Party: Owen Chen/Clinical Research Manager, TSH Biopharm Corporation Limited
• Study Sponsor: TSH Biopharm Corporation Limited
• Collaborators: Not Provided

Investigators

• Principal Investigator: Wayne H-H Sheu; Taichung Veterans General Hospital

• PRS Account: TSH Biopharm Corporation Limited
• Verification Date: June 2011