Long-term Study of Nateglinide+Valsartan to Prevent or Delay Type II Diabetes Mellitus and Cardiovascular Complications - Full Text View

Sponsor:	Novartis Pharmaceuticals
Information provided by:	Novartis
ClinicalTrials.gov Identifier:	NCT00097786

Purpose

This study is a test of the safety and effectiveness of two drugs, one for diabetes and one for hypertension, in keeping patients with high lab values of glucose from progressing to frank diabetes and developing cardiovascular complications. People in this study cannot have frank diabetes but are considered "borderline" based on blood tests. People in the study take none, one or both of the drugs and do not know which one(s) they are taking.

Condition	Intervention	Phase
Diabetes Mellitus, Type 2	Drug: Valsartan 160 mg + nateglinide 60 mg Drug: Valsartan 160 mg + nateglinide placebo Drug: Nateglinide 60 mg + valsartan placebo Drug: Valsartan placebo + nateglinide placebo	Phase III

Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Efficacy Study Intervention Model: Factorial Assignment Masking: Double Blind (Subject, Investigator) Primary Purpose: Prevention
Official Title:	A Multinational, Randomized, Double-blind, Placebo-controlled, Forced-titration, 2 x 2 Factorial Design Study of the Efficacy and Safety of Long-term Administration of Nateglinide and Valsartan in the Prevention of Diabetes and Cardiovascular Outcomes in Subjects With Impaired Glucose Tolerance (IGT)

Resource links provided by NLM:

Genetics Home Reference related topics: 6q24-related transient neonatal diabetes mellitus

MedlinePlus related topics: Diabetes Diabetes Type 2

Drug Information available for: A 4166 Valsartan

U.S. FDA Resources

Further study details as provided by Novartis:

Primary Outcome Measures:

Percentage of Patients Reaching the Endpoint: Progression to Diabetes - Valsartan Versus Non-valsartan [ Time Frame: Mean patient duration of 4.2 years ] [ Designated as safety issue: No ]
Progression to diabetes was determined by (a) an algorithm based on central laboratory measurements of fasting plasma glucose and/or a 2 hour oral glucose tolerance test or (b) adjudication by the Diabetes Endpoint Adjudication Committee.
Percentage of Patients Reaching the Endpoint: Extended Morbidity and Mortality Event - Valsartan Versus Non-valsartan [ Time Frame: Mean patient duration of 5.6 years ] [ Designated as safety issue: No ]
The extended cardiovascular endpoint was defined as a cardiovascular morbidity/mortality event including cardiovascular death, non-fatal myocardial infarction, non-fatal stroke, revascularization procedure, hospitalization for congestive heart failure, and hospitalization for unstable angina.
Percentage of Patients Reaching the Endpoint: Core Cardiovascular Morbidity and Mortality Event - Valsartan Versus Non-valsartan [ Time Frame: Mean patient duration of 5.8 years ] [ Designated as safety issue: No ]
The core cardiovascular endpoint was defined as a cardiovascular morbidity/mortality event including cardiovascular death, non-fatal myocardial infarction, non-fatal stroke and hospitalization for congestive heart failure.
Percentage of Patients Reaching the Endpoint: Progression to Diabetes - Nateglinide Versus Non-nateglinide [ Time Frame: Mean patient duration of 4.2 years ] [ Designated as safety issue: No ]
Progression to diabetes was determined by (a) an algorithm based on central laboratory measurements of fasting plasma glucose and/or a 2 hour oral glucose tolerance test or (b) adjudication by the Diabetes Endpoint Adjudication Committee.
Percentage of Patients Reaching the Endpoint: Extended Morbidity and Mortality Event - Nateglinide Versus Non-nateglinide [ Time Frame: Mean patient duration of 5.6 years ] [ Designated as safety issue: No ]
The extended cardiovascular endpoint was defined as a cardiovascular morbidity/mortality event including cardiovascular death, non-fatal myocardial infarction, non-fatal stroke, revascularization procedure, hospitalization for congestive heart failure, and hospitalization for unstable angina.
Percentage of Patients Reaching the Endpoint: Core Cardiovascular Morbidity and Mortality Event - Nateglinide Versus Non-nateglinide [ Time Frame: Mean patient duration of 5.8 years ] [ Designated as safety issue: No ]
The core cardiovascular endpoint was defined as a cardiovascular morbidity/mortality event including cardiovascular death, non-fatal myocardial infarction, non-fatal stroke and hospitalization for congestive heart failure.

Enrollment:	9306
Study Start Date:	January 2002
Study Completion Date:	October 2009
Primary Completion Date:	October 2009 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: Valsartan 160 mg + nateglinide 60 mg For the first 2 weeks of treatment, patients took the combination of nateglinide 30 mg (3 times daily, ante cibum [ac] before meals) and valsartan 80 mg (once daily [od] in the morning). After 2 weeks, patients were up-titrated to nateglinide 60 mg ac and valsartan 160 mg od.	Drug: Valsartan 160 mg + nateglinide 60 mg The double-blinding of the randomized study medication was maintained by the use of identical placebo and active tablets and capsules for nateglinide and valsartan, respectively. Patients were instructed not to take the morning dose of either medication nor to eat breakfast on the day of a scheduled study visit, but to wait until after the visit was completed. Patients not tolerating the higher dose (Level 2) were down-titrated to receive Level 1. Patients not tolerating the lower dose (Level 1) had a treatment interruption. Starting at Week 2 and throughout the study, attempts were to be made to reach the highest dose level (Level 2), if medically acceptable. Following each change in dose level or re-initiation of treatment, tolerability was assessed after 2 weeks of exposure.
Experimental: Valsartan 160 mg + nateglinide placebo For the first 2 weeks of treatment, patients took valsartan 80 mg capsules (once daily [od] in the morning). After 2 weeks, patients were up-titrated to 160 mg valsartan od. Patients also received nateglinide placebo tablets (3 times daily, ante cibum [ac] before meals).	Drug: Valsartan 160 mg + nateglinide placebo The double-blinding of the randomized study medication was maintained by the use of identical placebo and active tablets and capsules for nateglinide and valsartan, respectively. Patients were instructed not to take the morning dose of either medication nor to eat breakfast on the day of a scheduled study visit, but to wait until after the visit was completed. Patients not tolerating the higher dose (Level 2) were down-titrated to receive Level 1. Patients not tolerating the lower dose (Level 1) had a treatment interruption. Starting at Week 2 and throughout the study, attempts were to be made to reach the highest dose level (Level 2), if medically acceptable. Following each change in dose level or re-initiation of treatment, tolerability was assessed after 2 weeks of exposure.
Experimental: Nateglinide 60 mg + valsartan placebo For the first 2 weeks of treatment, patients took nateglinide 30 mg tablets (3 times daily, ante cibum [ac] before meals). After 2 weeks, patients were uptitrated to 60 mg nateglinide ac. Patients also received valsartan placebo capsules (once daily [od] in the morning).	Drug: Nateglinide 60 mg + valsartan placebo The double-blinding of the randomized study medication was maintained by the use of identical placebo and active tablets and capsules for nateglinide and valsartan, respectively. Patients were instructed not to take the morning dose of either medication nor to eat breakfast on the day of a scheduled study visit, but to wait until after the visit was completed. Patients not tolerating the higher dose (Level 2) were down-titrated to receive Level 1. Patients not tolerating the lower dose (Level 1) had a treatment interruption. Starting at Week 2 and throughout the study, attempts were to be made to reach the highest dose level (Level 2), if medically acceptable. Following each change in dose level or re-initiation of treatment, tolerability was assessed after 2 weeks of exposure.
Placebo Comparator: Placebo Patients took 3 nateglinide placebo tablets (3 times daily, ante cibum [ac] before meals) and 1 valsartan placebo capsule (once daily [od] in the morning).	Drug: Valsartan placebo + nateglinide placebo The double-blinding of the randomized study medication was maintained by the use of identical placebo and active tablets and capsules for nateglinide and valsartan, respectively. Patients were instructed not to take the morning dose of either medication nor to eat breakfast on the day of a scheduled study visit, but to wait until after the visit was completed. Patients not tolerating the higher dose (Level 2) were down-titrated to receive Level 1. Patients not tolerating the lower dose (Level 1) had a treatment interruption. Starting at Week 2 and throughout the study, attempts were to be made to reach the highest dose level (Level 2), if medically acceptable. Following each change in dose level or re-initiation of treatment, tolerability was assessed after 2 weeks of exposure.

Eligibility

Ages Eligible for Study:	50 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

Adults
Impaired glucose tolerance
Age dependent risk factors

Exclusion Criteria:

Frank diabetes

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Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00097786

Show 38 Study Locations

Sponsors and Collaborators

Novartis Pharmaceuticals

Investigators

Study Director:

Novartis Pharmaceuticals

More Information

No publications provided by Novartis

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

NAVIGATOR Study Group; McMurray JJ, Holman RR, Haffner SM, Bethel MA, Holzhauer B, Hua TA, Belenkov Y, Boolell M, Buse JB, Buckley BM, Chacra AR, Chiang FT, Charbonnel B, Chow CC, Davies MJ, Deedwania P, Diem P, Einhorn D, Fonseca V, Fulcher GR, Gaciong Z, Gaztambide S, Giles T, Horton E, Ilkova H, Jenssen T, Kahn SE, Krum H, Laakso M, Leiter LA, Levitt NS, Mareev V, Martinez F, Masson C, Mazzone T, Meaney E, Nesto R, Pan C, Prager R, Raptis SA, Rutten GE, Sandstroem H, Schaper F, Scheen A, Schmitz O, Sinay I, Soska V, Stender S, Tamás G, Tognoni G, Tuomilehto J, Villamil AS, Vozár J, Califf RM. Effect of valsartan on the incidence of diabetes and cardiovascular events. N Engl J Med. 2010 Apr 22;362(16):1477-90. Epub 2010 Mar 14.

NAVIGATOR Study Group; Holman RR, Haffner SM, McMurray JJ, Bethel MA, Holzhauer B, Hua TA, Belenkov Y, Boolell M, Buse JB, Buckley BM, Chacra AR, Chiang FT, Charbonnel B, Chow CC, Davies MJ, Deedwania P, Diem P, Einhorn D, Fonseca V, Fulcher GR, Gaciong Z, Gaztambide S, Giles T, Horton E, Ilkova H, Jenssen T, Kahn SE, Krum H, Laakso M, Leiter LA, Levitt NS, Mareev V, Martinez F, Masson C, Mazzone T, Meaney E, Nesto R, Pan C, Prager R, Raptis SA, Rutten GE, Sandstroem H, Schaper F, Scheen A, Schmitz O, Sinay I, Soska V, Stender S, Tamás G, Tognoni G, Tuomilehto J, Villamil AS, Vozár J, Califf RM. Effect of nateglinide on the incidence of diabetes and cardiovascular events. N Engl J Med. 2010 Apr 22;362(16):1463-76. Epub 2010 Mar 14.

Krum H, McMurray JJ, Horton E, Gerlock T, Holzhauer B, Zuurman L, Haffner SM, Bethel MA, Holman RR, Califf RM. Baseline Characteristics of the Nateglinide and Valsartan Impaired Glucose Tolerance Outcomes Research (NAVIGATOR) trial population: comparison with other diabetes prevention trials. Cardiovasc Ther. 2010 Apr;28(2):124-32. Epub 2010 Feb 23.

Bethel MA, Deedwania P, Levitt NS, Schmitz O, Huntsman-Labed A, Califf RM, Haffner SM, Diem P; NAVIGATOR Study Group. Metabolic syndrome and alanine aminotransferase: a global perspective from the NAVIGATOR screening population. Diabet Med. 2009 Dec;26(12):1204-11.

Bethel MA, Holman R, Haffner SM, Califf RM, Huntsman-Labed A, Hua TA, McMurray J. Determining the most appropriate components for a composite clinical trial outcome. Am Heart J. 2008 Oct;156(4):633-40. Epub 2008 Jul 31.

Responsible Party:	Study Director, Novartis Pharmaceuticals
ClinicalTrials.gov Identifier:	NCT00097786 History of Changes
Other Study ID Numbers:	CDJN608B2302
Study First Received:	November 30, 2004
Results First Received:	January 14, 2011
Last Updated:	June 27, 2011
Health Authority:	United States: Food and Drug Administration

Keywords provided by Novartis:

Prevention
Diabetes type 2
valsartan
nateglinide

Additional relevant MeSH terms:

Diabetes Mellitus
Diabetes Mellitus, Type 2
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
Nateglinide
Valsartan
Hypoglycemic Agents

Physiological Effects of Drugs
Pharmacologic Actions
Angiotensin II Type 1 Receptor Blockers
Angiotensin Receptor Antagonists
Molecular Mechanisms of Pharmacological Action
Antihypertensive Agents
Cardiovascular Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on February 09, 2012