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 microalbuminuria associated with type II diabetes, and to evaluate the efficacy and safety of Telmisartan (Micardis®, Gliosartan®, Kinzal®, Kinzalmono®, Predxal®, Pritor®, Samertan®, Telmisartan®) for diabetic nephropathy patients.

Condition	Intervention	Phase
Diabetic Nephropathies	Drug: Placebo  Drug: Telmisartan capsule 40 mg  Drug: Telmisartan capsule 80 mg	Phase IV

Further Study Details: 

Primary Outcomes: Non-transition to overt nephropathy
Secondary Outcomes: - Change in renal parameters; - Composite endpoint
Expected Total Enrollment:  450

A prospective, randomised, double-blind, multicentric and comparative study to investigate, on a long-term basis, the preventive effect on the transition to overt nephropathy and the safety of Telmisartan (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 nephropathy demonstrating microalbuminuria, has the preventive effect on transition from incipient to overt nephropathy.

Comparison(s):

The primary endpoint is defined as the transition from incipient to overt nephropathy, and the non-transition curve will be demonstrated based on the Kaplan-Meier method. The evaluation criteria for the point to transition to overt nephropathy is defined as urinary albumin to creatinine ratios at consecutive 2 measuring points increasing over 300 mg/g-Creatinine and excess 30% increase comparing with the baseline value. The curve of non-transition will be compared with Logrank test. Those in BIBR277 groups are sequentially compared with that in the placebo group by the closed testing procedure.

Ages Eligible for Study:  30 Years   -   74 Years,  Genders Eligible for Study:  Both

Criteria

Inclusion Criteria

Those who satisfy all the following conditions are eligible:

1. Diagnostic classification: outpatients who are able to visit the study site throughout the run-in period
2. Aged >= 30 and <= 74 years
3. Those diagnosed with type II diabetes mellitus
4. Patients having incipient nephropathy 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 level is in the range of 100 to 300 mg/g-Creatinine at 2 measuring points during the run-in period 2) <100 mg/g-Creatinine at either point of Visit 2 or 3, but the level at Visit 3.1 is in the range of 100 to 300 mg/g-Creatinine
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

EXCLUSION CRITERIA

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 1) Post renal transplantation 2) History of non-diabetic renal disease 3) Marked haematuria (>= 20 RBC/HPF) in qualitative tests 4) Complication of urinary tract infection
7. Cardiovascular diseases 1) Patients with unstable angina, myocardial infarction, coronary artery bypass graft surgery or percutaneous transluminal coronary angioplasty within 6 months before signing the informed consent form 2) New York Heart Association (NYHA) class III or IV heart failure 3) Patient with transient cerebral ischemic attack within 6 months before signing the informed consent form 4) Patient who had a stroke within 6 months before signing the informed consent form 5) Atrioventricular conduction disturbance (grade II-III) or atrial fibrillation 6) Serious arrhythmia 7) Known or suspected secondary hypertension (such as primary aldosteronism, melanocytoma)
8. Patients with history of characteristic symptoms of angioedema (such as facial, tongue, pharyngeal and laryngeal swellings with dyspnea) during administration of AT1 antagonists or ACE inhibitors
9. Hypersensitivity to telmisartan or any other AT1 antagonists
10. Patients with history of sudden exacerbation of renal function due to AT1 antagonists or ACE inhibitors
11. Patients with markedly poor bile secretion: direct bilirubin > 2.0 mg/dL
12. Hepatic dysfunction defined by the following laboratory parameters: SGPT (ALT) or SGOT (AST) >= 100 IU/L
13. Serum potassium level < 3.5 mEq/L or >= 5.1 mEq/L
14. Patients unable to discontinue AT1 antagonists or ACE inhibitors

15. Patients who require prolonged administration of any medications* known to affect blood pressure, except diuretics, a-blockers, ß-blockers, and calcium channel blockers

    *: Medications with indication or efficacy for "hypertension" or "hypotension"

16. Untreated sodium depletion
17. Pre-menopausal females who meet any one of the following 1) - 3) 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. Patient having malignant tumour or other diseases requiring oral or injection immunosuppressants
19. Patients with compliance of < 70% or >= 120% of placebo taken for the run-in period
20. Patients with history of drug or alcohol abuse
21. Patients who participated in other clinical studies within 3 months before signing the informed consent form
22. Any other clinical conditions that study investigators or subinvestigators judge as ineligible

Japan
      Boehringer Ingelheim Investigational Site, Isehara, Kanagawa,  Japan
      Boehringer Ingelheim Investigational Site, Shinjyuku-ku, Tokyo,  Japan
      Boehringer Ingelheim Investigational Site, Okayama, Okayama,  Japan
      Boehringer Ingelheim Investigational Site, Sagamihara, Kanagawa,  Japan
      Boehringer Ingelheim Investigational Site, Sapporo, Hokkaido,  Japan
      Boehringer Ingelheim Investigational Site, Chitose, Hokkaido,  Japan
      Boehringer Ingelheim Investigational Site, Sapporo, Hokkaido,  Japan
      Boehringer Ingelheim Investigational Site, Sapporo, Hokkaido,  Japan
      Boehringer Ingelheim Investigational Site, Sapporo, Hokkaido,  Japan
      Boehringer Ingelheim Investigational Site, Sapporo, Hokkaido,  Japan
      Boehringer Ingelheim Investigational Site, Sapporo, Hokkaido,  Japan
      Boehringer Ingelheim Investigational Site, Shibetsu, Hokkaido,  Japan
      Boehringer Ingelheim Investigational Site, Koriyama,Fukushima,  Japan
      Boehringer Ingelheim Investigational Site, Tsuchiura,Ibaraki,  Japan
      Boehringer Ingelheim Investigational Site, Toride, Ibaraki,  Japan
      Boehringer Ingelheim Investigational Site, Kawagoe, Saitama,  Japan
      Boehringer Ingelheim Investigational Site, Funabashi, Chiba,  Japan
      Boehringer Ingelheim Investigational Site, Shinjuku-ku, Tokyo,  Japan
      Boehringer Ingelheim Investigational Site, Shinjuku-ku, Tokyo,  Japan
      Boehringer Ingelheim Investigational Site, Katsushika-ku, Tokyo,  Japan
      Boehringer Ingelheim Investigational Site, Adachi-ku, Tokyo,  Japan
      Boehringer Ingelheim Investigational Site, Kita-ku, Tokyo,  Japan
      Boehringer Ingelheim Investigational Site, Yokohama, Kanagawa,  Japan
      Boehringer Ingelheim Investigational Site, Yokohama, Kanagawa,  Japan
      Boehringer Ingelheim Investigational Site, Ebina, Kanagawa,  Japan
      Boehringer Ingelheim Investigational Site, Kawasaki, Kanagawa,  Japan
      Boehringer Ingelheim Investigational Site, Yokohama, Kanagawa,  Japan
      Boehringer Ingelheim Investigational Site, Kamakura, Kanagawa,  Japan
      Boehringer Ingelheim Investigational Site, Kamakura, Kanagawa,  Japan
      Boehringer Ingelheim Investigational Site, Odawara, Kanagawa,  Japan
      Boehringer Ingelheim Investigational Site, Yokohama, Kanagawa,  Japan
      Boehringer Ingelheim Investigational Site, Chisagata-gun, Nagano,  Japan
      Boehringer Ingelheim Investigational Site, Chisagata-gun, Nagano,  Japan
      Boehringer Ingelheim Investigational Site, Nagoya, Aichi,  Japan
      Boehringer Ingelheim Investigational Site, Nagoya, Aichi,  Japan
      Boehringer Ingelheim Investigational Site, Nagoya, Aichi,  Japan
      Boehringer Ingelheim Investigational Site, Ichinomiya, Aichi,  Japan
      Boehringer Ingelheim Investigational Site, Nagoya, Aichi,  Japan
      Boehringer Ingelheim Investigational Site, Gobo, Wakayama,  Japan
      Boehringer Ingelheim Investigational Site, Kobe, Hyogo,  Japan
      Boehringer Ingelheim Investigational Site, Fukuoka, Fukuoka,  Japan
      Boehringer Ingelheim Investigational Site, Chikugo, Fukuoka,  Japan
      Boehringer Ingelheim Investigational Site, Tosu, Saga,  Japan
      Boehringer Ingelheim Investigational Site, Sapporo, Hokkaido,  Japan
      Boehringer Ingelheim Investigational Site, Obihiro, Hokkaido,  Japan
      Boehringer Ingelheim Investigational Site, Sendai, Miyagi,  Japan
      Boehringer Ingelheim Investigational Site, Tsuchiura, Ibaraki,  Japan
      Boehringer Ingelheim Investigational Site, Shibuya-ku, Tokyo,  Japan
      Boehringer Ingelheim Investigational Site, Minato-ku, Tokyo,  Japan
      Boehringer Ingelheim Investigational Site, Minato-ku, Tokyo,  Japan
      Boehringer Ingelheim Investigational Site, Yokohama, Kanagawa,  Japan
      Boehringer Ingelheim Investigational Site, Yokohama, Kanagawa,  Japan
      Boehringer Ingelheim Investigational Site, Atsugi,Kanagawa,  Japan
      Boehringer Ingelheim Investigational Site, Toyohashi, Aichi,  Japan
      Boehringer Ingelheim Investigational Site, Nagoya, Aichi,  Japan
      Boehringer Ingelheim Investigational Site, Uji, Kyoto,  Japan
      Boehringer Ingelheim Investigational Site, Hirakata, Osaka,  Japan
      Boehringer Ingelheim Investigational Site, Osaka, Osaka,  Japan
      Boehringer Ingelheim Investigational Site, Nishinomiya, Hyogo,  Japan
      Boehringer Ingelheim Investigational Site, Fukuyama, Hiroshima,  Japan
      Boehringer Ingelheim Investigational Site, Fukuoka, Fukuoka,  Japan
      Boehringer Ingelheim Investigational Site, Hitachiota, Ibaragi,  Japan
      Boehringer Ingelheim Investigational Site, Tsukuba, Ibaragi,  Japan
      Boehringer Ingelheim Investigational Site, Arakawa-ku, Tokyo,  Japan
      Boehringer Ingelheim Investigational Site, Nakano-ku, Tokyo,  Japan
      Boehringer Ingelheim Investigational Site, Yokohama, Kanagawa,  Japan
      Boehringer Ingelheim Investigational Site, Kounan, Aichi,  Japan
      Boehringer Ingelheim Investigational Site, Ikeda, Osaka,  Japan
      Boehringer Ingelheim Investigational Site, Nishinomiya, Hyogo,  Japan
      Boehringer Ingelheim Investigational Site, Iida, Nagano,  Japan
      Boehringer Ingelheim Investigational Site, Kyoto, Kyoto,  Japan
      Boehringer Ingelheim Investigational Site, Amagasaki, Hyogo,  Japan
      Boehringer Ingelheim Investigational Site, Nishinomiya, Hyogo,  Japan
      Boehringer Ingelheim Investigational Site, Matsuyama, Ehime,  Japan
      Boehringer Ingelheim Investigational Site, Minato-ku, Tokyo,  Japan
      Boehringer Ingelheim Investigational Site, Osaka-sayama, Osaka,  Japan
      Boehringer Ingelheim Investigational Site, Uwajima, Ehime,  Japan
      Boehringer Ingelheim Investigational Site, Noda, Chiba,  Japan
      Boehringer Ingelheim Investigational Site, Kawasaki, Kanagawa,  Japan
      Boehringer Ingelheim Investigational Site, Asaguchi-gun, Okayama,  Japan
      Boehringer Ingelheim Investigational Site, Kochi, Kochi,  Japan
      Boehringer Ingelheim Investigational Site, Nagoya, Aichi,  Japan
      Boehringer Ingelheim Investigational Site, Osaka,  Japan
      Boehringer Ingelheim Investigational Site, Hachioji, Tokyo,  Japan
      Boehringer Ingelheim Investigational Site, Sagamihara, Kanagawa,  Japan
      Boehringer Ingelheim Investigational Site, Takasaki, Gunma,  Japan
      Boehringer Ingelheim Investigational Site, Koriyama, Fukushima,  Japan
      Boehringer Ingelheim Investigational Site, Kawasaki, Kanagawa,  Japan
      Boehringer Ingelheim Investigational Site, Sakai, Osaka,  Japan
      Boehringer Ingelheim Investigational Site, Sakai, Osaka,  Japan
      Boehringer Ingelheim Investigational Site, Hakodate, Hokkaido,  Japan
      Boehringer Ingelheim Investigational Site, Hanamaki, Iwate,  Japan
      Boehringer Ingelheim Investigational Site, Isezaki, Gunma,  Japan
      Boehringer Ingelheim Investigational Site, Kita-katushika-gun, Saitama,  Japan
      Boehringer Ingelheim Investigational Site, Kisarazu, Chiba,  Japan
      Boehringer Ingelheim Investigational Site, Chiyoda-ku, Tokyo,  Japan
      Boehringer Ingelheim Investigational Site, Chiyoda-ku, Tokyo,  Japan
      Boehringer Ingelheim Investigational Site, Musashino, Tokyo,  Japan
      Boehringer Ingelheim Investigational Site, Atami, Shizuoka,  Japan
      Boehringer Ingelheim Investigational Site, Komaki, Aichi,  Japan
      Boehringer Ingelheim Investigational Site, Takarazuka, Hyogo,  Japan
      Boehringer Ingelheim Investigational Site, Itami, Hyogo,  Japan
      Boehringer Ingelheim Investigational Site, Kobe, Hyogo,  Japan
      Boehringer Ingelheim Investigational Site, Okayama, Okayama,  Japan
      Boehringer Ingelheim Investigational Site, Kurashiki, Okayama,  Japan
      Boehringer Ingelheim Investigational Site, Kurashiki, Okayama,  Japan
      Boehringer Ingelheim Investigational Site, Okayama, Okayama,  Japan
      Boehringer Ingelheim Investigational Site, Hatsukaichi, Hiroshima,  Japan
      Boehringer Ingelheim Investigational Site, Asahikwa, Hokkaido,  Japan
      Boehringer Ingelheim Investigational Site, Otaru, Hokkaido,  Japan
      Boehringer Ingelheim Investigational Site, Sapporo, Hokkaido,  Japan
      Boehringer Ingelheim Investigational Site, Sapporo, Hokkaido,  Japan
      Boehringer Ingelheim Investigational Site, Furukawa, Miyagi,  Japan
      Boehringer Ingelheim Investigational Site, Sendai, Miyagi,  Japan
      Boehringer Ingelheim Investigational Site, Koriyama, Fukushima,  Japan
      Boehringer Ingelheim Investigational Site, Inashiki-gun, Ibaragi,  Japan
      Boehringer Ingelheim Investigational Site, Asahi, Chiba,  Japan
      Boehringer Ingelheim Investigational Site, Kamogawa, Chiba,  Japan
      Boehringer Ingelheim Investigational Site, Kumagaya, Saitama,  Japan
      Boehringer Ingelheim Investigational Site, Kodaira, Tokyo,  Japan
      Boehringer Ingelheim Investigational Site, Seto, Aichi,  Japan
      Boehringer Ingelheim Investigational Site, Nangoku, Kochi,  Japan
      Boehringer Ingelheim Investigational Site, Oita, Oita,  Japan
      Boehringer Ingelheim Investigational Site, Sapporo, Hokkaido,  Japan
      Boehringer Ingelheim Investigational Site, Sapporo, Hokkaido,  Japan
      Boehringer Ingelheim Investigational Site, Sendai, Miyagi,  Japan
      Boehringer Ingelheim Investigational Site, Kawaguchi, Saitama,  Japan
      Boehringer Ingelheim Investigational Site, Toyohashi, Aichi,  Japan
      Boehringer Ingelheim Investigational Site, Osaka, Osaka,  Japan
      Boehringer Ingelheim Investigational Site, Fukuoka, Fukuoka,  Japan
      Boehringer Ingelheim Investigational Site, Asahikawa, Hokkaido,  Japan
      Boehringer Ingelheim Investigational Site, Sapporo, Hokkaido,  Japan
      Boehringer Ingelheim Investigational Site, Nagoya, Aichi,  Japan
      Boehringer Ingelheim Investigational Site, Kochi, Kochi,  Japan
      Boehringer Ingelheim Investigational Site, Okawa, Fukuoka,  Japan
      Boehringer Ingelheim Investigational Site, Shinagawa, Tokyo,  Japan
      Boehringer Ingelheim Investigational Site, Osaka, Osaka,  Japan
      Boehringer Ingelheim Investigational Site, Hannan, Osaka,  Japan
      Boehringer Ingelheim Investigational Site, Nomi, Ishikawa,  Japan
      Boehringer Ingelheim Investigational Site, Toyota, Aichi,  Japan
      Boehringer Ingelheim Investigational Site, Sapporo, Hokkaido,  Japan
      Boehringer Ingelheim Investigational Site, Setagaya-ku, Tokyo,  Japan
      Boehringer Ingelheim Investigational Site, Gifu, Gifu,  Japan
      Boehringer Ingelheim Investigational Site, Hashima-gun, Gifu,  Japan
      Boehringer Ingelheim Investigational Site, Kodaira, Tokyo,  Japan
      Boehringer Ingelheim Investigational Site, Tama, Tokyo,  Japan
      Boehringer Ingelheim Investigational Site, Kitami, Hokkaido,  Japan
      Boehringer Ingelheim Investigational Site, Ushiku, Ibaraki,  Japan
      Boehringer Ingelheim Investigational Site, Oyama, Tochigi,  Japan
      Boehringer Ingelheim Investigational Site, Kawasaki, Kanagawa,  Japan
      Boehringer Ingelheim Investigational Site, Kawasaki, Kanagawa,  Japan
      Boehringer Ingelheim Investigational Site, Matsuyama, Ehime,  Japan
      Boehringer Ingelheim Investigational Site, Sapporo, Hokkaido,  Japan
      Boehringer Ingelheim Investigational Site, Chiyoda, Tokyo,  Japan
      Boehringer Ingelheim Investigational Site, Fujisawa, Kanagawa,  Japan
      Boehringer Ingelheim Investigational Site, Shiojiri, Nagano,  Japan
      Boehringer Ingelheim Investigational Site, Takatsuki, Osaka,  Japan
      Boehringer Ingelheim Investigational Site, Izumisano, Osaka,  Japan
      Boehringer Ingelheim Investigational Site, Komatsushima, Tokushima,  Japan
      Boehringer Ingelheim Investigational Site, Takamatsu, Kagawa,  Japan
      Boehringer Ingelheim Investigational Site, Sunagawa, Hokkaido,  Japan
      Boehringer Ingelheim Investigational Site, Kawasaki, Kanagawa,  Japan

Study chairs or principal investigators

Toshiyuki Sumida,  Study Chair,  Nippon Boehringer/Kawanishi   

Study ID Numbers:  502.413
Last Updated:  September 9, 2005
Record first received:  September 9, 2005
ClinicalTrials.gov Identifier:  NCT00153088
Health Authority: Japan: Ministry of Health, Labor and Welfare
ClinicalTrials.gov processed this record on 2005-09-13