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Safety and Efficacy of Dapagliflozin as Monotherapy in Subjects With Type 2 Diabetes

18 avril 2017 mis à jour par: AstraZeneca

A Multicenter, Randomized, Double-Blind, Placebo Controlled, Parallel Group, Phase III Trial to Evaluate the Safety and Efficacy of Dapagliflozin as Monotherapy in Subjects With Type 2 Diabetes Who Have Inadequate Glycemic Control With Diet and Exercise

The purpose of this clinical research study is to learn if BMS-512148 (Dapagliflozin) can help reduce the blood sugar levels in subjects with Type 2 Diabetes who are not well controlled on diet and exercise alone. The safety of this treatment will also be studied

Aperçu de l'étude

Statut

Complété

Les conditions

Intervention / Traitement

Type d'étude

Interventionnel

Inscription (Réel)

497

Phase

  • Phase 3

Contacts et emplacements

Cette section fournit les coordonnées de ceux qui mènent l'étude et des informations sur le lieu où cette étude est menée.

Lieux d'étude

  • Afrique du Sud
    • Gauteng
      • Benoni, Gauteng, Afrique du Sud, 1501
        • Local Institution
      • Soweto, Gauteng, Afrique du Sud, 1818
        • Local Institution
    • Western Cape
      • Paarl, Western Cape, Afrique du Sud, 7646
        • Local Institution
      • Tygerberg, Western Cape, Afrique du Sud, 7505
        • Local Institution
  • Canada
    • Alberta
      • Calgary, Alberta, Canada, T3C 3P1
        • Local Institution
    • British Columbia
      • Coquitlam, British Columbia, Canada, V3K 3V9
        • Local Institution
    • Manitoba
      • Winnipeg, Manitoba, Canada, R3E 3P4
        • Local Institution
    • New Brunswick
      • Bathurst, New Brunswick, Canada, E2A 4X7
        • Local Institution
    • Ontario
      • Ajax, Ontario, Canada, L1S 7J5
        • Local Institution
      • Toronto, Ontario, Canada, M9W 4L6
        • Local Institution
      • Waterloo, Ontario, Canada, N2T 2Z6
        • Local Institution
    • Quebec
      • Drummondville, Quebec, Canada, J2B 7T1
        • Local Institution
      • L'Ancienne Lorette, Quebec, Canada, G2E 2X1
        • Local Institution
      • St-Leonard, Quebec, Canada, H1S 3A9
        • Local Institution
  • Fédération Russe
      • Kursk, Fédération Russe, 305035
        • Local Institution
      • Saint-Petersburg, Fédération Russe, 191015
        • Local Institution
      • Saratov, Fédération Russe, 410012
        • Local Institution
      • Smolensk, Fédération Russe, 214018
        • Local Institution
      • St. Petersburg, Fédération Russe, 195112
        • Local Institution
      • St. Petersburg, Fédération Russe, 195257
        • Local Institution
      • St. Petersburg, Fédération Russe, 197341
        • Local Institution
      • St.Petersburg, Fédération Russe, 197022
        • Local Institution
  • Inde
      • Ahmedabad, Inde, 380 015
        • Local Institution
      • Bangalore, Inde, 560 043
        • Local Institution
      • Bangalore, Inde, 560 052
        • Local Institution
      • Jaipur, Inde, 302001
        • Local Institution
      • Jaipur, Inde, 302016
        • Local Institution
  • Mexique
      • Durango, Mexique, 34000
        • Local Institution
      • Mexico City, Mexique, 06700
        • Local Institution
      • Veracruz, Mexique, 91910
        • Local Institution
    • Distrito Federal
      • Df, Distrito Federal, Mexique, 11800
        • Local Institution
    • Jalisco
      • Guadalajara, Jalisco, Mexique, 44670
        • Local Institution
    • Nuevo Leon
      • Monterrey, Nuevo Leon, Mexique, 64060
        • Local Institution
    • Yucatan
      • Merida, Yucatan, Mexique, 97070
        • Local Institution
  • Porto Rico
      • Ponce, Porto Rico, 00716
        • Local Institution
      • Ponce, Porto Rico, 00717
        • Local Institution
  • États-Unis
    • Arizona
      • Litchfield Park, Arizona, États-Unis, 85340
        • Dedicated Clinical Research
      • Phoenix, Arizona, États-Unis, 85051
        • 43rd Medical Associates, P.C.
      • Tempe, Arizona, États-Unis, 85282
        • Clinical Research Advantage, Inc.
    • California
      • Fresno, California, États-Unis, 93720
        • Valley Research
      • Lomita, California, États-Unis, 90717
        • Marina Raikhel, Md, Faafp
      • Los Gatos, California, États-Unis, 95032
        • Richard S. Cherlin, MD
      • Tustin, California, États-Unis, 92780
        • Orange County Research Center
    • Colorado
      • Greeley, Colorado, États-Unis, 80634
        • Family Physicians Of Greeley
    • Connecticut
      • New London, Connecticut, États-Unis, 06320
        • Coastal Connecticut Research, LLC
    • Florida
      • Altamonte Springs, Florida, États-Unis, 32701
        • Central Florida Clinical Trials, Inc.
      • Jacksonville, Florida, États-Unis, 32205
        • Westside Center for Clinical Research
      • Marianna, Florida, États-Unis, 32446
        • Panhandle Family Care Associates
    • Georgia
      • Roswell, Georgia, États-Unis, 30076
        • Endocrine Research Solutions, Inc.
    • Mississippi
      • Belzoni, Mississippi, États-Unis, 39038
        • Belzoni Clinical Research
    • New Jersey
      • Hamilton, New Jersey, États-Unis, 08690
        • R-Research
    • New York
      • Syracuse, New York, États-Unis, 13210
        • Internist Associates Of Central New York
      • West Seneca, New York, États-Unis, 14224
        • Southgate Medical Group
    • North Carolina
      • Morehead City, North Carolina, États-Unis, 28557
        • Down East Medical Associates, PA
    • Ohio
      • Akron, Ohio, États-Unis, 44319
        • James J. Brown, Md
    • Oklahoma
      • Oklahoma, Oklahoma, États-Unis, 73170
        • Integris Family Care South
    • South Carolina
      • Taylors, South Carolina, États-Unis, 29687
        • Southeastern Research Associates, Inc.
    • Texas
      • San Antonio, Texas, États-Unis, 78224
        • Abbott Clinical Research Group, Inc
    • Utah
      • Midvale, Utah, États-Unis, 84047
        • Avastra Clinical Trials
      • Salt Lake City, Utah, États-Unis, 84102
        • Optimum Clinical Research, Inc.
    • Washington
      • Olympia, Washington, États-Unis, 98502
        • Capital Clinical Research Center
      • Spokane, Washington, États-Unis, 99216
        • Stephen G. Danley, Do

Critères de participation

Les chercheurs recherchent des personnes qui correspondent à une certaine description, appelée critères d'éligibilité. Certains exemples de ces critères sont l'état de santé général d'une personne ou des traitements antérieurs.

Critère d'éligibilité

Âges éligibles pour étudier

18 ans à 77 ans (Adulte, Adulte plus âgé)

Accepte les volontaires sains

Non

Sexes éligibles pour l'étude

Tout

La description

Inclusion Criteria:

  • Male and females, ≥18 to ≤77 years old, with type 2 diabetes mellitus
  • Subjects must have central laboratory pre-randomization A1C ≥7.0 and ≤ 10.0%
  • C-peptide ≥ 1.0 ng/mL (0.34 nmol/L)
  • Body Mass Index ≤ 45 kg/m²
  • Must be able to perform self monitoring of blood glucose

Exclusion Criteria:

  • aspartate aminotransferase (AST) and/or alanine aminotransferase (ALT) >3* upper limit of normal (ULN)
  • Serum Total bilirubin >2 mg/dL (34.2 µmol/L)
  • Creatinine kinase >3* ULN
  • Serum creatinine ≥1.50 mg/dL (133 µmol/L) for male subjects, ≥1.40 mg/dL (124 µmol/L) for female subjects
  • Currently unstable or serious cardiovascular, renal, hepatic, hematological, oncological, endocrine, psychiatric, or rheumatic diseases

Plan d'étude

Cette section fournit des détails sur le plan d'étude, y compris la façon dont l'étude est conçue et ce que l'étude mesure.

Comment l'étude est-elle conçue ?

Détails de conception

  • Objectif principal: Traitement
  • Répartition: Randomisé
  • Modèle interventionnel: Affectation parallèle
  • Masquage: Double

Armes et Interventions

Groupe de participants / Bras
Intervention / Traitement
Expérimental: Dapagliflozin 1 mg
Dapagliflozin: 1 mg
Médicament: Dapagliflozin
Tablets, Oral, Once Daily, Up to 24 weeks
Autres noms:
  • BMS-512148
  • Farxiga™
Expérimental: Dapagliflozin 2.5 mg
Dapagliflozin: 2.5 mg
Médicament: Dapagliflozin
Tablets, Oral, Once Daily, Up to 24 weeks
Autres noms:
  • BMS-512148
  • Farxiga™
Expérimental: Dapagliflozin 5 mg
Dapagliflozin: 5 mg
Médicament: Dapagliflozin
Tablets, Oral, Once Daily, Up to 24 weeks
Autres noms:
  • BMS-512148
  • Farxiga™
Comparateur placebo: Placebo
Placebo: 0 mg
Médicament: Placebo
Tablets, Oral, Once Daily, Up to 24 weeks

Que mesure l'étude ?

Principaux critères de jugement

Mesure des résultats
Description de la mesure
Délai
Adjusted Mean Change From Baseline in Hemoglobin A1c (HbA1c) at Week 24 Last Observation Carried Forward (LOCF) - All Randomized Participants
Délai: Baseline (Day 1), Week 24
Adjusted mean change in HbA1c from baseline at Week 24, or the last post-baseline measurement prior to Week 24 if no Week 24 assessment was available was determined(LOCF). HbA1c was measured as percent of hemoglobin by a central laboratory. Data after rescue medication (metformin) was excluded from this analysis. Baseline was defined as the last assessment prior to the start date and time of the first dose of the double-blind study medication. In cases where time of the first dose or time of the assessment was not available, baseline was defined as the last assessment on or prior to the date of the first dose of the double-blind study medication. HbA1c values were obtained at enrollment, lead-in, and at Day 1, Weeks 4, 8, 12, 16, 20, and 24 in the double-blind period.
Baseline (Day 1), Week 24

Mesures de résultats secondaires

Mesure des résultats
Description de la mesure
Délai
Adjusted Mean Change From Baseline in Total Body Weight at Week 24 (LOCF) - Randomized Participants
Délai: Baseline (Day 1), Week 24
Adjusted mean change in total body weight from baseline at Week 24, or the last post-baseline measurement prior to Week 24 if no Week 24 assessment was available LOCF was determined. Data after rescue medication (metformin) was excluded from this analysis. Baseline was defined as the last assessment prior to the start date and time of the first dose of the double-blind study medication. In cases where time of the first dose or time of the assessment was not available, baseline was defined as the last assessment on or prior to the date of the first dose of the double-blind study medication. Body weight was measured in kilograms (kg) at qualification, lead-in, Day 1, Weeks 1, 2, 4, 8, 12, 16, 20, and 24 during double-blind period.
Baseline (Day 1), Week 24
Adjusted Mean Change From Baseline in Fasting Plasma Glucose at Week 24 (LOCF) - Randomized Participants
Délai: Baseline (Day 1), Week 24
Adjusted mean change in fasting plasma glucose (FPG) from baseline at Week 24 (LOCF) was determined. Data after rescue medication (metformin) was excluded from this analysis. FPG was measured as milligrams per deciliter (mg/dL) by a central laboratory at qualification, lead-in, Day 1, Weeks 1, 2, 4, 8, 12, 16, 20, and 24 during double-blind period. Baseline was defined as the last assessment prior to the start date and time of the first dose of the double-blind study medication. In cases where time of the first dose or time of the assessment was not available, baseline was defined as the last assessment on or prior to the date of the first dose of the double-blind study medication.
Baseline (Day 1), Week 24
Adjusted Mean Change From Baseline in Effect on 2-hour Post Liquid Meal Glucose at Week 24 (LOCF) - Randomized Participants
Délai: Baseline (Day 1), Week 24
Liquid meal tolerance tests (MTTs) were scheduled to occur at Day 1 visit (MTT was to be completed 2 hours prior to first dose of treatment) and at Week 24 / End of treatment visit, or Rescue visit for participants meeting criteria for rescue due to lack of glycemic control. At Week 24, study treatment was given 1 hour before MTT was administered. Participant fasted for at least 10 hours (h) prior to both visits and abstained from tobacco, alcohol, and caffeine for 24 h prior to the MTT. The liquid meal supplement was administered over 10 minutes, starting immediately after Time 0 blood sample was drawn. Blood samples for post-liquid meal Glucose were obtained at 30, 60, 120, and 180 minutes after ingesting the liquid supplement. Glucose was measured in milligrams per deciliter (mg/dL) by a central laboratory. Baseline was defined as the last assessment prior to the start date and time of the first dose of double-blind study medication.
Baseline (Day 1), Week 24
Adjusted Percentage of Participants Achieving a Therapeutic Glycemic Response at Week 24 (LOCF) - Randomized Participants
Délai: Baseline (Day 1), Week 24
Therapeutic glycemic response was defined as HbA1c less than 7.0%. n=Number of participants with HBA1c less than (<) 7 % at Week 24, last observation carried forward (LOCF) while N=number of randomized participants with non-missing baseline and Week 24 (LOCF) values. Percent=n/N and was adjusted for Baseline HbA1c. Data after rescue medication (metformin) was excluded from this analysis. HbA1c was measured as a percent of hemoglobin.
Baseline (Day 1), Week 24
Adjusted Mean Change From Baseline in Waist Circumference at Week 24 (LOCF) - Randomization Participants
Délai: Baseline (Day 1), Week 24
Adjusted mean waist circumference values from baseline to Week 24 (or the last post-baseline measurement prior to Week 24 if no Week 24 assessment was available, last observation carried forward, (LOCF) was determined. Data after rescue medication (metformin) was excluded from this analysis. Waist circumference was measured centimeters (cm) and obtained at lead-in, Day 1, and Week 24 of the double-blind period. Baseline was defined as the last assessment prior to the start date and time of the first dose of the double-blind study medication. In cases where time of the first dose or time of the assessment was not available, baseline was defined as the last assessment on or prior to the date of the first dose of the double-blind study medication.
Baseline (Day 1), Week 24
Number of Participants With Deaths, Serious AEs (SAEs), Adverse Events (AEs), Discontinuation Due to AEs, During the 12 Week Double Blind Period, Including Data After Rescue - All Treated Participants
Délai: Day 1 of Double Blind Period to end of Week 24 Plus 30 days
Medical Dictionary for Regulatory Activities (MedDRA), version 12.1 AE=any new unfavorable symptom, sign, or disease or worsening of a preexisting condition that may not have a causal relationship with treatment. SAE=a medical event that at any dose results in death, persistent or significant disability/incapacity, or drug dependency/abuse; is life-threatening, an important medical event, or a congenital anomaly/birth defect; or requires or prolongs hospitalization. Treatment-related=having certain, probable, possible, or missing relationship to study drug as per the investigator. Baseline to last dose plus 4 days for AEs, plus 30 days for SAEs. Data after rescue included.
Day 1 of Double Blind Period to end of Week 24 Plus 30 days
Number of Participants With Adverse Events of Special Interest During the 12 Week Double Blind Period - All Treated Participants
Délai: Baseline to last dose plus 4 days in 12 Week Double Blind Period
Participants with AEs of hypoglycemia, cardiac/vascular disorders, renal impairment or failure, volume depletion (hypotension/dehydration/hypovolemia), fractures, urinary stones, and other reports suggestive of genital infection or urinary tract infection (UTI) were summarized using MedDRA version 12.1. Data after rescue included for all AEs of special interest except hypoglycemia; hypoglycemia AEs were prior to rescue. Major hypoglycemic episode: symptomatic requiring 3rd party assistance due to severe impairment in consciousness or behavior with a glucose value < 54 mg/dL and prompt recovery after glucose/glucagon; Minor: either symptomatic with glucose measurement < 63 mg/dL, regardless of need for 3rd party assistance, or asymptomatic with glucose < 63 mg/dL that does not qualify as major; Other: suggestive but not meeting criteria for major or minor.
Baseline to last dose plus 4 days in 12 Week Double Blind Period
Mean Change From Baseline in Seated Systolic and Diastolic Blood Pressure at Week 24, Including Data After Rescue - Treated Participants
Délai: Baseline (Day 1), Week 24
Blood pressure values were obtained on Day 1, Weeks 1, 2, 4, 8, 12, 16, 20, and 24 in the double blind period, after the participant was seated for quietly for 5 minutes; the same arm (right or left) was used consistently through out the study. Measurements were taken at least 10 hours after the last ingestion of caffeine, alcohol, or nicotine. Blood pressure was measured in millimeters of mercury (mmHg). Data after rescue were also included. Baseline was defined as the last assessment prior to the start date and time of the first dose of the double-blind study medication. In cases where time of the first dose or time of the assessment was not available, baseline was defined as the last assessment on or prior to the date of the first dose of the double-blind study medication.
Baseline (Day 1), Week 24
Mean Change From Baseline in Seated Heart Rate at Week 24 - Treated Participants
Délai: Baseline (Day 1), Week 24
Heart rate values were obtained after the participant was seated for quietly for 5 minutes; the same arm (right or left) was used consistently through out the study. Measurements were taken at least 10 hours after the last ingestion of caffeine, alcohol, or nicotine. Heart rate was measured in beats per minute (bpm). Data after rescue were also included. Baseline was defined as the last assessment prior to the start date and time of the first dose of the double-blind study medication. In cases where time of the first dose or time of the assessment was not available, baseline was defined as the last assessment on or prior to the date of the first dose of the double-blind study medication.
Baseline (Day 1), Week 24
Number of Participants With Normal or Abnormal Electrocardiogram Summary Tracing at Week 24 (LOCF) - Treated Participants
Délai: Week 24
12-Lead electrocardiograms (ECGs) were performed at Day -14 and Week 24/End of treatment visit (last observation carried forward) on participants who were supine. ECGs were assessed by the investigator. Baseline (BL) was Day -14 for this parameter.
Week 24
Number of Participants With Marked Laboratory Abnormalities in 24 Week Double Blind Treatment Period - Treated Participants
Délai: Baseline to Week 24/end of treatment plus 4 days
Safety laboratory measurements were obtained at Day 1, Weeks 1, 2, 4, 8, 12, 20, and 24 in the double blind Period. Baseline was defined as the last assessment prior to the start of the first dose of the double-blind study medication. Data included from baseline up to and including the last day of treatment plus 4 days. Data after rescue was also included. Abbreviations; Pretreatment (PreRX); grams per deciliter (g/dL); upper limit of normal (ULN); milliequivalent per liter (mEq/L); greater than (>) less than (<); Units per liter (U/L), alanine aminotransferase (ALT); aspartate aminotransferase (AST); alkaline phosphatase (ALP); blood urea nitrogen (BUN). Marked abnormality Low (High) defined: hemoglobin <6 (>18 females or >20 males) g/dL; hematocrit <20% ( >55% females or >60% males); BUN (>60 mg/dL) or Urea >21.4 mmol/L; creatinine (>=1.5*preRX, >=2.5 mg/dL); AST and ALT >3*ULN; bilirubin >1.5*ULN; ALP >1.5*ULN.
Baseline to Week 24/end of treatment plus 4 days

Collaborateurs et enquêteurs

C'est ici que vous trouverez les personnes et les organisations impliquées dans cette étude.

Parrainer

AstraZeneca

Collaborateurs

Bristol-Myers Squibb

Publications et liens utiles

La personne responsable de la saisie des informations sur l'étude fournit volontairement ces publications. Il peut s'agir de tout ce qui concerne l'étude.

Publications générales

Dates d'enregistrement des études

Ces dates suivent la progression des dossiers d'étude et des soumissions de résultats sommaires à ClinicalTrials.gov. Les dossiers d'étude et les résultats rapportés sont examinés par la Bibliothèque nationale de médecine (NLM) pour s'assurer qu'ils répondent à des normes de contrôle de qualité spécifiques avant d'être publiés sur le site Web public.

Dates principales de l'étude

Début de l'étude (Réel)

22 septembre 2008

Achèvement primaire (Réel)

29 décembre 2009

Achèvement de l'étude (Réel)

29 décembre 2009

Dates d'inscription aux études

Première soumission

15 août 2008

Première soumission répondant aux critères de contrôle qualité

15 août 2008

Première publication (Estimation)

18 août 2008

Mises à jour des dossiers d'étude

Dernière mise à jour publiée (Réel)

20 avril 2017

Dernière mise à jour soumise répondant aux critères de contrôle qualité

18 avril 2017

Dernière vérification

1 avril 2017

Plus d'information

Termes liés à cette étude

Mots clés

Termes MeSH pertinents supplémentaires

Autres numéros d'identification d'étude

  • MB102-032

Informations sur les médicaments et les dispositifs, documents d'étude

Étudie un produit pharmaceutique réglementé par la FDA américaine

Non

Étudie un produit d'appareil réglementé par la FDA américaine

Non

produit fabriqué et exporté des États-Unis.

Non

Ces informations ont été extraites directement du site Web clinicaltrials.gov sans aucune modification. Si vous avez des demandes de modification, de suppression ou de mise à jour des détails de votre étude, veuillez contacter register@clinicaltrials.gov. Dès qu'un changement est mis en œuvre sur clinicaltrials.gov, il sera également mis à jour automatiquement sur notre site Web .

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