INNOVATION Study - Telmisartan (Micardis?) in Incipient Diabetic Nephropathy

Condition(s) targeted: Diabetic Nephropathies

Intervention: Telmisartan capsule 40 mg (Drug); Placebo (Drug); Telmisartan capsule 80 mg (Drug)

Phase: Phase 4

Status: Completed

Sponsored by: Boehringer Ingelheim Pharmaceuticals

Official(s) and/or principal investigator(s):
Boehringer Ingelheim Study Coordinator, Study Chair, Affiliation: Nippon Boehringer Ingelheim Co., Ltd.

The aim of this study is to compare the preventive effect of Telmisartan (Micardis?) versus placebo control on the transition to overt nephropathy in patients with diabetic nephropathy manifesting mic roalbuminuria associated with type II diabetes, and to evaluate the efficacy and safety of Telmisart an (Micardis?, Gliosartan?, Kinzal?, Kinzalmono?, Predxal?, Pritor?, Samertan?, Telmisartan?) for di abetic nephropathy patients.

Official title: A Randomised, Double-Blind, Placebo-Controlled, Multicenter Trial to Investigate the Preventive Effect of BIBR277 (Telmisartan) in Diabetic Nephropathy on Transition From Incipient to Overt Nephropathy - Incipient to Overt : Angiotensin 2 Receptor Blocker, Telmisartan, Investigation on Type 2 Diabet

Study design: Treatment, Randomized, Double-Blind, Dose Comparison, Parallel Assignment, Efficacy Study

Primary outcome: Non-transition to overt nephropathy

Secondary outcome: Change in renal parameters Composite endpoint

Detailed description: A prospective, randomised, double-blind, multicentric and comparative study to investigate, on a lon g-term basis, the preventive effect on the transition to overt nephropathy and the safety of Telmisa rtan (Micardis?) against placebo in patients with diabetic nephropathy, manifesting microalbuminuria associated with type II diabetes

Study Hypothesis:

The hypothesis is that Telmisartan (Micardis?) at 40 mg or 80 mg versus placebo control in patients with concurrent type II diabetic mellitus or diabetic nephro pathy demonstrating microalbuminuria, has the preventive effect on transition fr om incipient to overt nephropathy.

Comparison(s):

The primary endpoint is defined as the transition from incipient to overt nephro pathy, and the non-transition curve will be demonstrated based on the Kaplan-Mei er method. The evaluation criteria for the point to transition to overt nephropa thy is defined as urinary albumin to creatinine ratios at consecutive 2 measurin g points increasing over 300 mg/g-Creatinine and excess 30% increase comparing w ith the baseline value. The curve of non-transition will be compared with Logran k test. Those in BIBR277 groups are sequentially compared with that in the place bo group by the closed testing procedure.

Minimum age: 30 Years. Maximum age: 74 Years. Gender(s): Both.

Criteria:

Those who satisfy all the following conditions are eligible:

1. Outpatients who are able to visit the study site throughout the run-in period

2. Aged ? 30 and ? 74 years

3. Type II diabetes mellitus

4. Patients with urinary albumin to creatinine ratios within the following ranges at 2 measuring points during the run-in period 1) the first-morning voided urine, iin the range of 100 to 300 mg/g?Creatinine 2) <100 mg/g?Creatinine at either point of Visit 2 or 3, but iin the range of 100 to 300 mg/g?Creatinine at follow-up

5. Serum creatinine level of < 1. 5 mg/dL in male and < 1. 3 mg/dL in female

6. Normotensive or hypertensive patients

7. Patients taking AT1 antagonists or ACE inhibitors at screening, but are able to stop those drugs during the study

8. Patients who are able to provide written informed consent in accordance with the Good Clinical Practice (GCP) and other relevant laws such as the Pharmaceutical Affairs Law

Patients who do not fall under any one of the following are eligible:

1. Age of onset of type 2 diabetes is < 30 years

2. Type I diabetes

3. Urinary albumin to creatinine ratio of > 300 mg/g?Creatinine

4. HbA1c ? 9%

5. Seated SBP ? 180 mmHg or DBP ? 110 mmHg

6. Findings suggesting a renal disease other than diabetic nephropathy; such as ' Post renal transplantation', 'History of non-diabetic renal disease', 'Marked haematuria', 'Complication of urinary tract infection'

7. Cardiovascular diseases 1) Patients with unstable angina, myocardial infarction, CABG, PTCA within 6 months before, 2) CHF with NYHA III-IV, 3) TIA within 6 months, 4) Stroke within 6 months, 5) AV block (grade II-III) or AF, 6) Serious arrhythmia, 7) Known or suspected secondary HT

8. History of angioedema during administration of ARB/ACE-i

9. Hypersensitivity

10. History of sudden exacerbation of renal function due to ARB/ACE-i

11. Markedly poor bile secretion

12. Hepatic dysfunction: SGPT (ALT) or SGOT (AST) ? 100 IU/L

13. Serum potassium level < 3. 5 mEq/L or ? 5. 1 mEq/L

14. Unable to discontinue ARB/ACE-i

15. Require prolonged administration of any medications affecting blood pressure, except diuretics, ?- or ?-blockers, and CCB

16. Untreated sodium depletion

17. Pre-menopausal females who meet any one of the; 1) Pregnant or possibly pregnant, 2) Breast-feeding, 3) Hope to be pregnant during the study period Even when a patient is confirmed not to meet the above criteria at the start of the study, a female patient who has the potential to be pregnant during the study is to undergo pregnancy tests. If the result turns positive, the study medication should be discontinued.

18. Malignant tumour or other diseases requiring oral or injection immunosuppressants

19. Non-compliance

20. History of drug or alcohol abuse

21. Participated in other clinical studies within 3 months

22. Any other conditions investigators judged as ineligible

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Ending date: November 2005
Last updated: April 3, 2008