A Study of Multiple Oral Doses of JNJ-41443532 in Patients With Type 2 Diabetes Mellitus
17 octobre 2013 mis à jour par: Johnson & Johnson Pharmaceutical Research & Development, L.L.C.
A Double-Blind, Randomized, Placebo- and Active Comparator-Controlled, 4-Week Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of Multiple Oral Doses of JNJ-41443532 in Subjects With Type 2 Diabetes Mellitus
The purpose of this study is to evaluate the safety, tolerability, pharmacokinetics (what the body does to the medication) and pharmacodynamics (what the medication does to the body) of treatment with JNJ-41443532 relative to treatment with placebo in type 2 diabetes mellitus participants.
Aperçu de l'étude
Statut
Complété
Les conditions
Intervention / Traitement
Description détaillée
This is a randomized (the study medication is assigned by chance), double-blind (neither investigator nor participant knows the treatment that the participant receives), multicenter (study conducted at multiple sites), and placebo (an inactive substance that is compared with a medication to test whether the medication has a real effect in a clinical study) and active comparator (an established effective treatment that is compared with a medication to test whether the medication has a real effect in a clinical study) controlled study (placebo or active comparator is compared with the study medication to test whether the study medication has a real effect in clinical study).
The study consists of 4 phases: screening phase (45 days before administration of study medication); pre-dosing run-in phase (a phase before a clinical study is commenced when no treatment is given.
In this study, participant's glucose level will be observed during run-in-phase: days 15 to 1 before administration of study medication); treatment phase, and follow-up phase (7 to 10 days after the last dose of the study medication).
Approximately 88 participants will be enrolled in this study.
All participants will be randomly assigned to 4 treatment arms: JNJ-41443532 250 mg; JNJ-41443532 1000 mg; pioglitazone arm; and placebo.
Safety evaluations will include assessment of adverse events including ocular assessments, clinical laboratory tests, electrocardiogram, vital signs, and physical examination which will be monitored throughout the study.
The maximum study duration for each participant will be approximately 12 weeks.
Type d'étude
Interventionnel
Inscription (Réel)
89
Phase
- Phase 2
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
25 ans à 65 ans (Adulte, Adulte plus âgé)
Accepte les volontaires sains
Non
Sexes éligibles pour l'étude
Tout
La description
Inclusion Criteria:
- Diagnosed Type 2 Diabetes Mellitus (T2DM) for at least 3 months prior screening
- On a stable treatment regimen for at least 2 months prior screening
- Medically stable on the basis of physical examination, medical history, and clinical laboratory tests performed at screening and 2 days before administration of the study medication
- Fasting plasma glucose (FPG) concentrations between 140 mg/dL and 270 mg/dL on 2 days before administration of the study medication
- Agrees to protocol-defined use of effective contraception
Exclusion Criteria:
- History of other types of diabetes and complications or secondary forms of diabetes
- History of eating disorder or recent significant changes in body weight (ie, more or equal to 5 percent over 3 months prior to screening) due to dieting or nutritional treatments
- Taking antihyperglycemic agents (insulin, exenatide, and liraglutide) within 6 months or thiazolidinedione within 3 months of 2 days before administration of the study medication
- Clinically significant abnormal electrocardiogram
- History of, or currently active, significant illness or medical disorders, retinal disease, tuberculosis
- Clinically important serious infection, positive for serology at screening (hepatitis B surface antigen, hepatitis C antibodies or human immunodeficiency virus antibodies)
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: Tripler
Armes et Interventions
Groupe de participants / Bras |
Intervention / Traitement |
|---|---|
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Expérimental: JNJ-41443532 250 mg
Participants will receive JNJ-41443532 250 mg in morning and evening for 28 days.
|
Participants will receive JNJ-41443532 tablet(s) orally in JNJ-41443532 250 mg arm (1 X 250 mg) and JNJ-41443532 1000 mg arm (4 X 250 mg) in morning and evening, for 28 days.
Participants will receive matching placebo tablets of JNJ-41443532 and/or matching placebo tablets of pioglitazone orally as per the assigned arms.
|
|
Expérimental: JNJ-41443532 1000 mg
Participants will receive JNJ-41443532 1000 mg (4 X 250 mg) in morning and evening for 28 days.
|
Participants will receive JNJ-41443532 tablet(s) orally in JNJ-41443532 250 mg arm (1 X 250 mg) and JNJ-41443532 1000 mg arm (4 X 250 mg) in morning and evening, for 28 days.
Participants will receive matching placebo tablets of JNJ-41443532 and/or matching placebo tablets of pioglitazone orally as per the assigned arms.
|
|
Comparateur actif: Pioglitazone
Participants will receive pioglitazone 30 mg in morning for 28 days.
|
Participants will receive matching placebo tablets of JNJ-41443532 and/or matching placebo tablets of pioglitazone orally as per the assigned arms.
Participants will receive tablet pioglitazone 30 mg orally in morning for 28 days.
|
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Comparateur placebo: Placebo
Participants will receive matching placebo for JNJ-41443532 and pioglitazone for 28 days.
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Participants will receive matching placebo tablets of JNJ-41443532 and/or matching placebo tablets of pioglitazone orally as per the assigned arms.
|
Que mesure l'étude ?
Principaux critères de jugement
Mesure des résultats |
Description de la mesure |
Délai |
|---|---|---|
|
Change From Baseline (Day -1) to Day 28 in Twenty-Four-Hour Weighted Average Glucose (24-Hour WAG)
Délai: From baseline (Day -1) to Day 28
|
Difference is calculated as the change in 24-hour WAG in Least Square Mean (LSM) from baseline to Day 28 of each treatment group (pioglitazone, JNJ-41443532 250 mg, JNJ-41443532 1000 mg, and placebo).
The statistical analyses shows the treatment differences (ie, each study medication group minus placebo) in the LSM change.
24-hour WAG is defined as the area under the plasma glucose concentration time curve over 0 to 24 hours, divided by 24.
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From baseline (Day -1) to Day 28
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Mesures de résultats secondaires
Mesure des résultats |
Description de la mesure |
Délai |
|---|---|---|
|
Change From Baseline to Day 28 in Fasting Plasma Glucose (FPG)
Délai: From baseline to Day 28
|
Difference is calculated as the change in FPG in Least Square Mean (LSM) from baseline to Day 28 of each treatment group (pioglitazone, JNJ-41443532 250 mg, JNJ-41443532 1000 mg, and placebo).
The statistical analyses shows the treatment differences (ie, each study medication group minus placebo) in the LSM change.
|
From baseline to Day 28
|
|
Change From Baseline to Day 28 in Insulin Secretion
Délai: From baseline to Day 28
|
Difference is calculated as the change in insulin secretion in Least Square Mean (LSM) from baseline to Day 28 of each treatment group (pioglitazone, JNJ-41443532 250 mg, JNJ-41443532 1000 mg, and placebo).
The statistical analyses shows the treatment differences (ie, each study medication group minus placebo) in the LSM change.
Insulin secretion is measured by the absolute change in Homeostasis Model Assessment of steady state islet beta cell (HOMA-%B).
HOMA-%B calculated as: (360 multiplied by Insulin [pmol/L]) divided by ([Glucose {mg/dL} minus 63] multiplied by 6.945).
Higher value is better (signifies improvement relative to baseline).
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From baseline to Day 28
|
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Change From Baseline to Day 28 in Insulin Resistance
Délai: From baseline to Day 28
|
Difference is calculated as the change in insulin resistance in Least Square Mean (LSM) from baseline to Day 28 of each treatment group (pioglitazone, JNJ-41443532 250 mg, JNJ-41443532 1000 mg, and placebo).
The statistical analyses shows the treatment differences (ie, each study medication group minus placebo) in the LSM change.
Insuline sensitivity is measured by absolute change in Homeostasis Model Assessment of insulin resistance (HOMA-IR).
Insulin sensitivity is HOMA-%S and HOMA-IR is the reciprocal of HOMA-%S.
HOMA-IR calculated as: (Glucose [mg/dL]) multiplied by Insulin [pmol/L]) divided by (405 multiplied by 6.945).
Lower value is better (signifies improvement relative to baseline).
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From baseline to Day 28
|
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Change From Baseline to Day 28 in Systemic Levels of Interleukin 6 (IL-6)
Délai: From baseline to Day 28
|
Difference is calculated as the geometric mean change in IL-6 from baseline to Day 28 of each treatment group (JNJ-41443532 250 mg, JNJ-41443532 1000 mg, and placebo).
The statistical analyses shows the treatment differences (ie, each study medication group minus placebo) in the geometric mean change.
IL-6 is a systemic inflammatory markers and is an independent predictors of insulin resistance and progression to type 2 diabetes mellitus.
IL-6 was not measured for pioglitazone guoup.
The unit of IL-6 is picograms per milliliter (pg/mL).
|
From baseline to Day 28
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Change From Baseline to Day 28 in Systemic Levels of Interleukin 18 (IL-18)
Délai: From baseline to Day 28
|
Difference is calculated as the geometric mean change in IL-18 from baseline to Day 28 of each treatment group (JNJ-41443532 250 mg, JNJ-41443532 1000 mg, and placebo).
The statistical analyses shows the treatment differences (ie, each study medication group minus placebo) in the geometric mean change.
IL-18 was not measured for pioglitazone group.
The unit of IL-18 is picograms per milliliter (pg/mL)
|
From baseline to Day 28
|
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Change From Baseline to Day 28 in Systemic Levels of C-Reactive Protein (CRP)
Délai: From baseline to Day 28
|
Difference is calculated as the geometric mean change in CRP from baseline to Day 28 of each treatment group (JNJ-41443532 250 mg, JNJ-41443532 1000 mg, and placebo).
The statistical analyses shows the treatment differences (ie, each study medication group minus placebo) in the geometric mean change.
CRP was not measured for pioglitazone group.
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From baseline to Day 28
|
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Change From Baseline to Day 29 in Body Weight
Délai: From baseline to Day 29
|
Difference is calculated as the change in body weight in Least Square Mean (LSM) from baseline to Day 29 of each treatment group (pioglitazone, JNJ-41443532 250 mg, JNJ-41443532 1000 mg, and placebo).
The statistical analyses shows the treatment differences (ie, each study medication group minus placebo) in the LSM change.
|
From baseline to Day 29
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Collaborateurs et enquêteurs
C'est ici que vous trouverez les personnes et les organisations impliquées dans cette étude.
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 décembre 2010
Achèvement primaire (Réel)
1 juin 2011
Achèvement de l'étude (Réel)
1 juin 2011
Dates d'inscription aux études
Première soumission
22 octobre 2010
Première soumission répondant aux critères de contrôle qualité
28 octobre 2010
Première publication (Estimation)
29 octobre 2010
Mises à jour des dossiers d'étude
Dernière mise à jour publiée (Estimation)
11 décembre 2013
Dernière mise à jour soumise répondant aux critères de contrôle qualité
17 octobre 2013
Dernière vérification
1 octobre 2013
Plus d'information
Termes liés à cette étude
Termes MeSH pertinents supplémentaires
Autres numéros d'identification d'étude
- CR017401
- 41443532EDI2001 (Autre identifiant: Johnson & Johnson Pharmaceutical Research & Development, L.L.C.)
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