- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT00097786
Long-term Study of Nateglinide+Valsartan to Prevent or Delay Type II Diabetes Mellitus and Cardiovascular Complications (Navigator)
October 25, 2023 updated by: Novartis Pharmaceuticals
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)
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.
Study Overview
Status
Completed
Conditions
Study Type
Interventional
Enrollment (Actual)
9306
Phase
- Phase 3
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Locations
-
-
-
Investigative Site, Argentina
-
-
-
-
-
Investigative Site, Australia
-
-
-
-
-
Multiple Locations, Austria
-
-
-
-
-
Investigative Site, Belgium
-
-
-
-
-
Investigative Site, Brazil
-
-
-
-
-
Investigative Site, Canada
-
-
-
-
-
Investigative Site, Chile
-
-
-
-
-
Investigative Site, China
-
-
-
-
-
Investigative Site, Colombia
-
-
-
-
-
Investigative Site, Czechia
-
-
-
-
-
Investigative Site, Denmark
-
-
-
-
-
Investigative Site, Ecuador
-
-
-
-
-
Investigative Site, Finland
-
-
-
-
-
Investigative Site, France
-
-
-
-
-
Investigative Site, Germany
-
-
-
-
-
Investigative Site, Greece
-
-
-
-
-
Investigative Site, Guatemala
-
-
-
-
-
Investigative Site, Hong Kong
-
-
-
-
-
Investigative Site, Hungary
-
-
-
-
-
Investigative Site, Italy
-
-
-
-
-
Investigative Site, Malaysia
-
-
-
-
-
Investigative Site, Mexico
-
-
-
-
-
Investigative Site, Netherlands
-
-
-
-
-
Investigative Site, Norway
-
-
-
-
-
Investigative Site, Peru
-
-
-
-
-
Investigative Site, Poland
-
-
-
-
-
Investigative Site, Russian Federation
-
-
-
-
-
Investigative Site, Singapore
-
-
-
-
-
Investigative Site, Slovakia
-
-
-
-
-
Investigative Site, South Africa
-
-
-
-
-
Investigative Site, Spain
-
-
-
-
-
Investigative Site, Sweden
-
-
-
-
-
Investigative Site, Switzerland
-
-
-
-
-
Investigative Site, Taiwan
-
-
-
-
-
Investigative Site, Turkey
-
-
-
-
-
Investigative Site, United Kingdom
-
-
-
-
New Jersey
-
Multiple Locations, New Jersey, United States
-
-
-
-
-
Investigative Site, Uruguay
-
-
Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
50 years and older (Adult, Older Adult)
Accepts Healthy Volunteers
No
Description
Inclusion Criteria:
- Adults
- Impaired glucose tolerance
- Age dependent risk factors
Exclusion Criteria:
- Frank diabetes
For detailed information, call contact person.
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: Prevention
- Allocation: Randomized
- Interventional Model: Factorial Assignment
- Masking: Double
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
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.
|
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).
|
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).
|
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).
|
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.
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Percentage of Patients Reaching the Endpoint: Progression to Diabetes - Valsartan Versus Non-valsartan
Time Frame: Mean patient duration of 4.2 years
|
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.
|
Mean patient duration of 4.2 years
|
Percentage of Patients Reaching the Endpoint: Extended Morbidity and Mortality Event - Valsartan Versus Non-valsartan
Time Frame: Mean patient duration of 5.6 years
|
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.
|
Mean patient duration of 5.6 years
|
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
|
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.
|
Mean patient duration of 5.8 years
|
Percentage of Patients Reaching the Endpoint: Progression to Diabetes - Nateglinide Versus Non-nateglinide
Time Frame: Mean patient duration of 4.2 years
|
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.
|
Mean patient duration of 4.2 years
|
Percentage of Patients Reaching the Endpoint: Extended Morbidity and Mortality Event - Nateglinide Versus Non-nateglinide
Time Frame: Mean patient duration of 5.6 years
|
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.
|
Mean patient duration of 5.6 years
|
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
|
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.
|
Mean patient duration of 5.8 years
|
Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Sponsor
Investigators
- Study Director: Novartis Pharmaceuticals, Novartis Pharmaceuticals
Publications and helpful links
The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.
General Publications
- Harumi Higuchi Dos Santos M, Sharma A, Sun JL, Pieper K, McMurray JJ, Holman RR, Lopes RD. International Variation in Outcomes Among People with Cardiovascular Disease or Cardiovascular Risk Factors and Impaired Glucose Tolerance: Insights from the NAVIGATOR Trial. J Am Heart Assoc. 2017 Jan 13;6(1):e003892. doi: 10.1161/JAHA.116.003892.
- Preiss D, Thomas LE, Wojdyla DM, Haffner SM, Gill JM, Yates T, Davies MJ, Holman RR, McMurray JJ, Califf RM, Kraus WE; NAVIGATOR Investigators. Prospective relationships between body weight and physical activity: an observational analysis from the NAVIGATOR study. BMJ Open. 2015 Aug 14;5(8):e007901. doi: 10.1136/bmjopen-2015-007901.
- Katz M, Califf RM, Sun JL, McMurray JJ, Thomas L, Lopes RD. Venous thromboembolism and cardiovascular risk: results from the NAVIGATOR trial. Am J Med. 2015 Mar;128(3):297-302. doi: 10.1016/j.amjmed.2014.08.022. Epub 2014 Nov 20.
- Preiss D, Haffner SM, Thomas LE, Sun JL, Sattar N, Yates T, J Davies M, McMurray JJ, Holman RR, Califf RM, Kraus WE. Change in levels of physical activity after diagnosis of type 2 diabetes: an observational analysis from the NAVIGATOR study. Diabetes Obes Metab. 2014 Dec;16(12):1265-8. doi: 10.1111/dom.12320. Epub 2014 Jun 19.
- Huffman KM, Sun JL, Thomas L, Bales CW, Califf RM, Yates T, Davies MJ, Holman RR, McMurray JJ, Bethel MA, Tuomilehto J, Haffner SM, Kraus WE. Impact of baseline physical activity and diet behavior on metabolic syndrome in a pharmaceutical trial: results from NAVIGATOR. Metabolism. 2014 Apr;63(4):554-61. doi: 10.1016/j.metabol.2014.01.002. Epub 2014 Jan 15.
- Yates T, Haffner SM, Schulte PJ, Thomas L, Huffman KM, Bales CW, Califf RM, Holman RR, McMurray JJ, Bethel MA, Tuomilehto J, Davies MJ, Kraus WE. Association between change in daily ambulatory activity and cardiovascular events in people with impaired glucose tolerance (NAVIGATOR trial): a cohort analysis. Lancet. 2014 Mar 22;383(9922):1059-66. doi: 10.1016/S0140-6736(13)62061-9. Epub 2013 Dec 20.
- Shen L, Shah BR, Reyes EM, Thomas L, Wojdyla D, Diem P, Leiter LA, Charbonnel B, Mareev V, Horton ES, Haffner SM, Soska V, Holman R, Bethel MA, Schaper F, Sun JL, McMurray JJ, Califf RM, Krum H. Role of diuretics, beta blockers, and statins in increasing the risk of diabetes in patients with impaired glucose tolerance: reanalysis of data from the NAVIGATOR study. BMJ. 2013 Dec 9;347:f6745. doi: 10.1136/bmj.f6745. Erratum In: BMJ. 2014;348:f1339.
- 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. doi: 10.1111/j.1755-5922.2010.00146.x. 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. doi: 10.1111/j.1464-5491.2009.02864.x.
- 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. doi: 10.1016/j.ahj.2008.05.018. Epub 2008 Jul 31.
- 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, Tamas G, Tognoni G, Tuomilehto J, Villamil AS, Vozar 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. doi: 10.1056/NEJMoa1001121. Epub 2010 Mar 14. Erratum In: N Engl J Med. 2010 May 6;362(18):1748.
- 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, Tamas G, Tognoni G, Tuomilehto J, Villamil AS, Vozar 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. doi: 10.1056/NEJMoa1001122. Epub 2010 Mar 14. Erratum In: N Engl J Med. 2010 May 6;362(18):1748.
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start
January 1, 2002
Primary Completion (Actual)
October 1, 2009
Study Completion (Actual)
October 1, 2009
Study Registration Dates
First Submitted
November 30, 2004
First Submitted That Met QC Criteria
November 30, 2004
First Posted (Estimated)
December 1, 2004
Study Record Updates
Last Update Posted (Actual)
November 8, 2023
Last Update Submitted That Met QC Criteria
October 25, 2023
Last Verified
October 1, 2023
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
- Glucose Metabolism Disorders
- Metabolic Diseases
- Endocrine System Diseases
- Diabetes Mellitus
- Diabetes Mellitus, Type 2
- Hypoglycemic Agents
- Physiological Effects of Drugs
- Molecular Mechanisms of Pharmacological Action
- Antihypertensive Agents
- Angiotensin II Type 1 Receptor Blockers
- Angiotensin Receptor Antagonists
- Valsartan
- Nateglinide
Other Study ID Numbers
- CDJN608B2302
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
Clinical Trials on Diabetes Mellitus, Type 2
-
SanofiCompletedType 1 Diabetes Mellitus-Type 2 Diabetes MellitusHungary, Russian Federation, Germany, Poland, Japan, United States, Finland
-
Mannkind CorporationTerminatedType 2 Diabetes Mellitus | Type 1 Diabetes MellitusUnited States
-
RWTH Aachen UniversityBoehringer IngelheimCompletedDiabetes Mellitus Type 2 (T2DM)Germany
-
Griffin HospitalCalifornia Walnut CommissionCompletedDIABETES MELLITUS TYPE 2United States
-
University Hospital Inselspital, BerneCompletedType 2 Diabetes MellitusSwitzerland
-
India Diabetes Research Foundation & Dr. A. Ramachandran...CompletedTYpe 2 Diabetes MellitusIndia
-
Scripps Whittier Diabetes InstituteSan Diego State UniversityCompletedType 2 Diabetes Mellitus (T2DM)United States
-
AstraZenecaRecruiting
-
Daewoong Pharmaceutical Co. LTD.Not yet recruitingT2DM (Type 2 Diabetes Mellitus)
-
Zhongda HospitalRecruitingType 2 Diabetes Mellitus (T2DM)China
Clinical Trials on Valsartan 160 mg + nateglinide 60 mg
-
Dexa Medica GroupCompleted
-
NovartisCompletedChronic Heart FailureUnited States
-
Mustafa Kemal UniversityNovartis PharmaceuticalsCompletedHypertension | Left Ventricular HypertrophyTurkey
-
Genencell Co. Ltd.Recruiting
-
HK inno.N CorporationCompletedHypertension With Hyperlipidemia
-
RemeGen Co., Ltd.RecruitingPrimary Sjogren's SyndromeChina
-
Vifor (International) Inc.Labcorp Drug Development IncWithdrawnBeta-ThalassemiaUnited States, Bulgaria, Israel
-
Federation Francophone de Cancerologie DigestiveCompletedColorectal AdenocarcinomaFrance
-
Yuhan CorporationActive, not recruitingNon-Small Cell Lung CancerHungary, Korea, Republic of, Australia, Taiwan, Serbia, Singapore, Thailand, Philippines, Turkey, Malaysia, Russian Federation, Greece, Ukraine