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A Phase III Study of BMS-512148 (Dapagliflozin) in Patients With Type 2 Diabetes Who Are Not Well Controlled on Metformin Alone

30 septembre 2015 mis à jour par: AstraZeneca

A Multicenter, Randomized, Double-Blind, Placebo-Controlled, Parallel Group, Phase 3 Trial to Evaluate the Safety and Efficacy of Dapagliflozin in Combination With Metformin in Subjects With Type 2 Diabetes Who Have Inadequate Glycemic Control on Metformin Alone

The purpose of this clinical research study is to learn whether dapagliflozin can help reduce blood sugar levels in participants with Type 2 diabetes that is not well controlled on metformin 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)

915

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

  • Argentine
      • Buenos Aires, Argentine, 1431
        • Local Institution
      • Cordoba, Argentine, 5000
        • Local Institution
    • Buenos Aires
      • Capital Federal, Buenos Aires, Argentine, 1034
        • Local Institution
      • Capital Federal, Buenos Aires, Argentine, 1429
        • Local Institution
      • Capital Federal, Buenos Aires, Argentine, C1056ABJ
        • Local Institution
      • Capital Federal, Buenos Aires, Argentine, C1425AGC
        • Local Institution
      • Ciudad Auton, Buenos Aires, Argentine, C1408INH
        • Local Institution
      • Ciudad Auton., Buenos Aires, Argentine, C1505CWB
        • Local Institution
      • Mar Del Plata, Buenos Aires, Argentine, 7600
        • Local Institution
      • Zarate, Buenos Aires, Argentine, 2800
        • Local Institution
    • Cordoba
      • Villa Carlos Paz, Cordoba, Argentine, 5152
        • Local Institution
  • Brésil
      • Rio De Janeiro, Brésil, 20211
        • Local Institution
    • Ceara
      • Fortaleza, Ceara, Brésil, 60021
        • Local Institution
    • Minas Gerais
      • Itajuba, Minas Gerais, Brésil, 37502
        • Local Institution
    • Para
      • Belem, Para, Brésil, 66073
        • Local Institution
    • Rio Grande Do Sul
      • Caxias Do Sul, Rio Grande Do Sul, Brésil, 95070
        • Local Institution
      • Porto Alegre, Rio Grande Do Sul, Brésil, 90020090
        • Local Institution
      • Porto Alegre, Rio Grande Do Sul, Brésil, 90035
        • Local Institution
    • Sao Paulo
      • Marilia, Sao Paulo, Brésil, 17519
        • Local Institution
  • Canada
    • Alberta
      • Calgary, Alberta, Canada, T2R 0X7
        • Local Institution
    • British Columbia
      • Kelowna, British Columbia, Canada, V1Y 2H4
        • Local Institution
    • Manitoba
      • Winnipeg, Manitoba, Canada, R3E 3P4
        • Local Institution
    • New Brunswick
      • Bathurst, New Brunswick, Canada, E2A 4X7
        • Local Institution
    • Newfoundland and Labrador
      • Mount Pearl, Newfoundland and Labrador, Canada, A1N 1W7
        • Local Institution
      • St-John, Newfoundland and Labrador, Canada, A1E 2E2
        • Local Institution
    • Ontario
      • Sarnia, Ontario, Canada, N7T 4X3
        • Local Institution
      • Thornhill, Ontario, Canada, L4J 8L7
        • Local Institution
      • Toronto, Ontario, Canada, M4R 2G4
        • Local Institution
      • Toronto, Ontario, Canada, M9W 4L6
        • Local Institution
    • Prince Edward Island
      • Charlottetown, Prince Edward Island, Canada, C1A 5Y9
        • Local Institution
    • Quebec
      • Drummondville, Quebec, Canada, J2B 7T1
        • Local Institution
      • Granby, Quebec, Canada, J2G 8Z9
        • Local Institution
      • L'Ancienne Lorette, Quebec, Canada, G2E 2X1
        • Local Institution
      • Mirabel, Quebec, Canada, J7J 2K8
        • Local Institution
      • St-Leonard, Quebec, Canada, H1S 3A9
        • Local Institution
    • Saskatchewan
      • Saskatoon, Saskatchewan, Canada, S7K 3H3
        • Local Institution
      • Saskatoon, Saskatchewan, Canada, S7K 7H9
        • Local Institution
  • Mexique
      • Durango, Mexique, 64710
        • Local Institution
    • Distrito Federal
      • Df, Distrito Federal, Mexique, 11800
        • Local Institution
      • Guadalajara, Distrito Federal, Mexique, 44670
        • Local Institution
      • Zapopan, Distrito Federal, Mexique, 45150
        • Local Institution
    • Jalisco
      • Guadalajara, Jalisco, Mexique, 44650
        • Local Institution
      • Guadalajara, Jalisco, Mexique, 44670
        • Local Institution
    • Nuevo Leon
      • Monterrey, Nuevo Leon, Mexique, 64710
        • Local Institution
      • Monterrey, Nuevo Leon, Mexique, 64460
        • Local Institution
      • Monterrrey, Nuevo Leon, Mexique, 64700
        • Local Institution
    • Tamaulipas
      • Tampico, Tamaulipas, Mexique, 89109
        • Local Institution
  • États-Unis
    • Arizona
      • Tempe, Arizona, États-Unis, 85282
        • Clinical Research Advantage / Desert Clinical Res, Llc
    • California
      • Encino, California, États-Unis, 91436
        • Medical Group of Encino
      • Fresno, California, États-Unis, 93720
        • Valley Research
      • Los Angeles, California, États-Unis, 90023
        • Randall Shue, D.O.
      • Northridge, California, États-Unis, 91325
        • Diabetes Medical Center Of California
      • San Diego, California, États-Unis, 92117
        • Ritchken & First M.D.'S
      • Spring Valley, California, États-Unis, 91978
        • Encompass Clinical Research
      • Torrance, California, États-Unis, 90505
        • Raikhel, Marina
    • Colorado
      • Colorado Springs, Colorado, États-Unis, 80909
        • Express Care Clinical Res
      • Denver, Colorado, États-Unis, 80209
        • Denver Internal Medicine
      • Golden, Colorado, États-Unis, 80401
        • New West Physicians
    • Florida
      • Altamonte Springs, Florida, États-Unis, 32701
        • Central Florida Clinical Trials, Inc.
      • Chipley, Florida, États-Unis, 32428
        • Family Care Associates Of Nw Florida
    • Minnesota
      • Minneapolis, Minnesota, États-Unis, 56440
        • Health Partners Research Foundation
    • Missouri
      • Chesterfield, Missouri, États-Unis, 63017
        • Woodlake Research
    • Nevada
      • Las Vegas, Nevada, États-Unis, 89101
        • Nevada Alliance Against Diabetes
    • North Carolina
      • Morehead City, North Carolina, États-Unis, 28557
        • Diabetes & Endocrinology Consultants, PC
    • Ohio
      • Newark, Ohio, États-Unis, 43055
        • Newark Physician Associates
    • Oklahoma
      • Oklahoma City, Oklahoma, États-Unis, 73159
        • Integris Family Care S. Penn
    • Pennsylvania
      • Carlisle, Pennsylvania, États-Unis, 17013
        • Cumberland Valley Endocrinology Center, Llc
      • Pittsburgh, Pennsylvania, États-Unis, 15216
        • Banksville Medical Pc
    • South Carolina
      • Summerville, South Carolina, États-Unis, 29485
        • Palmetto Clinical Research
      • Taylors, South Carolina, États-Unis, 29687
        • Southeastern Research Assoc
    • Texas
      • Houston, Texas, États-Unis, 77081
        • Texas Center For Drug Development, P.A.
      • San Antonio, Texas, États-Unis, 78229
        • Diabetes & Glandular Disease Research Associates, Inc.
      • San Antonio, Texas, États-Unis, 78229
        • S.A.M. Clinical Research Center
    • Utah
      • Salt Lake City, Utah, États-Unis, 84102
        • Optimum Clinical Research
    • Washington
      • Spokane, Washington, États-Unis, 99216
        • Office Of Dr. Gray

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

Key Inclusion Criteria

  • Males and females, 18 to 77 years old, with type 2 diabetes and inadequate glycemic control
  • Participants who have been receiving metformin at a total daily dose ≥1500 mg per day for at least 8 weeks
  • C-peptide ≥1.0 ng/mL
  • Body mass index ≤45.0 kg/m^2
  • Serum creatinine level <1.50 mg/dL for men or <1.40 mg/dL for women.

Key Exclusion Criteria

  • Aspartate aminotransferase and/or alanine aminotransferase level >3.0 times the upper limit of normal
  • Serum total bilirubin level >2 mg/dL
  • Creatinine kinase level >3 times upper limit of normal
  • Symptoms of severely uncontrolled diabetes
  • Serum creatinine level ≥1.50 mg/dL for men or ≥1.40 mg/dL for women
  • Currently unstable or serious cardiovascular, renal, hepatic, hematologic, oncologic, 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
Comparateur placebo: Placebo + Metformin
Participants received dapagliflozin-matching placebo once daily plus open-label metformin ≥1500 mg per day for up to 102 weeks
Médicament: Placebo
Dapagliflozin-matching placebo administered as tablets orally once daily for up to 102 weeks
Médicament: Metformin
Open-label metformin administered as ≥1500 mg per day for up to 102 weeks
Expérimental: Dapagliflozin, 2.5 mg + Metformin
Participants received dapagliflozin, 2.5 mg, once daily plus open-label metformin ≥1500 mg per day for up to 102 weeks
Médicament: Metformin
Open-label metformin administered as ≥1500 mg per day for up to 102 weeks
Médicament: Dapagliflozin
Tablets administered orally as a 2.5-, 5-, or 10-mg dose once daily for up to 102 weeks
Autres noms:
  • BMS-512148
Expérimental: Dapagliflozin, 5 mg + Metformin
Participants received dapagliflozin, 5 mg, once daily plus open-label metformin ≥1500 mg per day for up to 102 weeks
Médicament: Metformin
Open-label metformin administered as ≥1500 mg per day for up to 102 weeks
Médicament: Dapagliflozin
Tablets administered orally as a 2.5-, 5-, or 10-mg dose once daily for up to 102 weeks
Autres noms:
  • BMS-512148
Expérimental: Dapagliflozin, 10 mg + Metformin
Participants received dapagliflozin, 10 mg, once daily plus open-label metformin ≥1500 mg per day for up to 102 weeks
Médicament: Placebo
Dapagliflozin-matching placebo administered as tablets orally once daily for up to 102 weeks
Médicament: Metformin
Open-label metformin administered as ≥1500 mg per day for up to 102 weeks
Médicament: Dapagliflozin
Tablets administered orally as a 2.5-, 5-, or 10-mg dose once daily for up to 102 weeks
Autres noms:
  • BMS-512148

Que mesure l'étude ?

Principaux critères de jugement

Mesure des résultats
Description de la mesure
Délai
Changement moyen ajusté par rapport au départ de l'hémoglobine A1C (HbA1c) à la semaine 24 (dernière observation reportée [LOCF])
Délai: De la ligne de base à la semaine 24
L'HbA1c a été mesurée en pourcentage de l'hémoglobine par un laboratoire central. Les données après traitement de secours ont été exclues de cette analyse. La ligne de base a été définie comme la dernière évaluation avant la date et l'heure de début de la première dose du médicament à l'étude en double aveugle. Dans les cas où l'heure de la première dose ou l'heure de l'évaluation n'était pas disponible, la ligne de base était définie comme la dernière évaluation à ou avant la date de la première dose du médicament à l'étude en double aveugle. Les mesures de l'HbA1c ont été obtenues pendant les périodes de qualification et d'introduction et le jour 1 et les semaines 4, 8, 12, 16, 20 et 24 de la période en double aveugle.
De la ligne de base à la semaine 24

Mesures de résultats secondaires

Mesure des résultats
Description de la mesure
Délai
Adjusted Mean Change From Baseline in Fasting Plasma Glucose at Week 24 (Last Observation Carried Forward [LOCF])
Délai: From Baseline to Week 24
Secondary endpoints were tested using sequential testing procedure and are presented in hierarchical order. Data after rescue medication was excluded from this analysis. Fasting plasma glucose was measured as 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 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.
From Baseline to Week 24
Adjusted Mean Change From Baseline in Total Body Weight at Week 24 (Last Observation Carried Forward [LOCF])
Délai: From Baseline to Week 24
Secondary endpoints were tested using sequential testing procedure and are presented in hierarchical order. Adjusted mean change from baseline in total body weight at Week 24 (or the last postbaseline measurement prior to Week 24 if no Week 24 assessment was available was determined. Data after rescue medication 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 measurements were obtained during the qualification and lead-in periods and on Day 1 and Weeks 1, 2, 3, 4, 6, 8, 12, 16, 20, and 24 of the double-blind period.
From Baseline to Week 24
Percentage of Participants Achieving a Therapeutic Glycemic Response (Hemoglobin A1c [HbA1C]) <7.0% at Week 24 (Last Observation Carried Forward [LOCF])
Délai: From Baseline to Week 24
Secondary endpoints were tested using sequential testing procedure and are presented in hierarchical order. Percent adjusted for baseline HbA1c. Therapeutic glycemic response is defined as HbA1c <7.0%. Data after rescue medication was excluded from this analysis. HbA1c was measured as a percent of hemoglobin.
From Baseline to Week 24
Adjusted Mean Change From Baseline in Hemoglobin A1c (HbA1c) in Participants With Baseline HbA1c ≥9.0% at Week 24 (Last Observation Carried Forward [LOCF])
Délai: From Baseline to Week 24
Secondary endpoints were tested using sequential testing procedure and are presented in hierarchical order. HbA1c was measured as percent of hemoglobin by a central laboratory. The population included those randomized participants who received treatment and had a baseline HbA1c > 9.0%. Data after rescue medication were 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.
From Baseline to Week 24
Adjusted Mean Change From Baseline in Total Body Weight at Week 24 in Participants With Baseline Body Mass Index (BMI) ≥27 kg/m^2 (Last Observation Carried Forward [LOCF])
Délai: From Baseline to Week 24
Secondary endpoints were tested using sequential testing procedure and are presented in hierarchical order. Adjusted mean change from baseline in total body weight at Week 24 (or the last postbaseline measurement prior to Week 24 if no Week 24 assessment was available was determined.) Data after rescue medication 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 measurements were obtained during the qualification and lead-in Periods and on Day 1 and Weeks 1, 2, 3, 4, 6, 8, 12, 16, 20, and 24 of the double-blind period.
From Baseline to Week 24
Adjusted Mean Change From Baseline in Hemoglobin A1c (HbA1c) in Participants With Baseline Body Mass Index (BMI) ≥27 kg/m^2 at Week 24 (Last Observation Carried Forward [LOCF])
Délai: From Baseline to Week 24
Secondary endpoints were tested using sequential testing procedure and are presented in hierarchical order. Adjusted for baseline HbA1c. HbA1c was measured as percent of hemoglobin by a central laboratory. Data after rescue medication were 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.
From Baseline to Week 24
Adjusted Mean Change From Baseline in Fasting Plasma Glucose at Week 1 (Last Observation Carried Forward [LOCF])
Délai: From Baseline to Week 1
Secondary endpoints were tested using sequential testing procedure and are presented in hierarchical order. Data after rescue medication was excluded from this analysis. Fasting plasma glucose was measured by a central laboratory. 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.
From Baseline to Week 1
Adjusted Percentage of Participants Achieving Hemoglobin A1c (HbA1C) ≤6.5% at Week 24 (Last Observation Carried Forward [LOCF])
Délai: From Baseline to Week 24
Secondary endpoints were tested using sequential testing procedure and are presented in hierarchical order. Percent adjusted for baseline HbA1c. Data after rescue medication was excluded from this analysis. HbA1c was measured as a percent of hemoglobin.
From Baseline to Week 24

Autres mesures de résultats

Mesure des résultats
Description de la mesure
Délai
Number of Participants With Adverse Events (AEs), Hypoglycemia Events, Related AEs, Death as Outcome, Serious AEs (SAEs), Related SAEs, SAEs Leading to Discontinuation, AEs Leading to Discontinuation, and Hypoglycemia Events Leading to Discontinuation
Délai: From Baseline to end of Long-term Period (Week 102)
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. Related=having certain, probable, possible, or missing relationship to study drug. Events captured from baseline to last dose plus 4 days for AEs and plus 30 days for SAEs during the double-blind 12-week period. Data after rescue included.
From Baseline to end of Long-term Period (Week 102)
Number of Participants With Laboratory Test Results Meeting the Criteria for Laboratory Abnormality
Délai: Day 1 to Week 102
BUN=blood urea nitrogen; preRX=pretreatment; ULN=upper limit of normal; AST=aspartate aminotransferase; ALT=alanine aminotransferase; ALP=alkaline phosphatase. Phosphorus, inorganic (low): ages 17-65 years, ≤1.8 mg/dL; ages≥66 years, ≤2.1 mg/dL. Phosphorus, inorganic (high): ages 17-65 years, ≥5.6 mg/dL; ages≥66 years, ≥5.6 mg/dL. Phosphorus, inorganic (low) ≤1.8 mg/dL if age 17-65 or ≤2.1 mg/dL if age ≥66. Calcium, total (high): ≥1 mg/dL from ULN and ≥0.5 mg/dL from preRx value.
Day 1 to Week 102
Number of Participants With Changes in Baseline in Electrocardiogram Findings at Week 102 (Last Observation Carried Forward [LOCF])
Délai: Baseline to Week 102
12-Lead electrocardiograms (ECGs) were performed at entry into lead-in period Day -7 visit and Week 24/dnd of treatment visit (LOCF) on participants who were supine. ECGs were assessed by the investigator. Baseline was Day -7 for this parameter. Data after rescue included.The Week 102 value is the last observation, regardless of rescue prior to Week 102 if no Week 102 measurement was available.
Baseline to Week 102
Mean Changes From Baseline in Seated Systolic Blood Pressure
Délai: From Baseline to Week 102
Blood pressure values were obtained after the participant was seated quietly for 5 minutes; at least 8 hours after the last ingestion of caffeine, alcohol, or nicotine; and in the same arm (right or left) consistently through out the study. 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.
From Baseline to Week 102
Mean Changes From Baseline in Seated Diastolic Blood Pressure
Délai: From Baseline to Week 102
Blood pressure values were obtained after the participant was seated quietly for 5 minutes; at least 8 hours after the last ingestion of caffeine, alcohol, or nicotine; and in the same arm (right or left) consistently through out the study. 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.
From Baseline to Week 102
Number of Participants With Orthostatic Hypotension
Délai: From Baseline to Week 102
Orthostatic hypotension was defined as a decrease from supine to standing blood pressure of >20 mm Hg in systolic blood pressure or >10 mm Hg in diastolic blood pressure.
From Baseline to Week 102

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

1 septembre 2007

Achèvement primaire (Réel)

1 novembre 2008

Achèvement de l'étude (Réel)

1 mai 2010

Dates d'inscription aux études

Première soumission

11 septembre 2007

Première soumission répondant aux critères de contrôle qualité

11 septembre 2007

Première publication (Estimation)

12 septembre 2007

Mises à jour des dossiers d'étude

Dernière mise à jour publiée (Estimation)

20 octobre 2015

Dernière mise à jour soumise répondant aux critères de contrôle qualité

30 septembre 2015

Dernière vérification

1 septembre 2015

Plus d'information

Termes liés à cette étude

Mots clés

Termes MeSH pertinents supplémentaires

Autres numéros d'identification d'étude

  • MB102-014 LT
  • MB102-014 (Autre identifiant: Other Study ID Numbers:)

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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