Cette page a été traduite automatiquement et l'exactitude de la traduction n'est pas garantie. Veuillez vous référer au version anglaise pour un texte source.

Multiple Dose Study Of PF-04937319 In Patients With Type 2 Diabetes

6 décembre 2016 mis à jour par: Pfizer

A Phase 1 Placebo-controlled Trial To Assess The Safety, Tolerability, Pharmacokinetics, And Pharmacodynamics Of Multiple Escalating Oral Doses Of Pf-04937319 In Adult Patients With Type 2 Diabetes Mellitus (t2dm)

The purpose of this study is to characterize the safety, tolerability, pharmacokinetics (PK), and pharmacodynamics (PD) of PF-04937319 following multiple (14 days) escalating oral doses in patients with type 2 diabetes.

Aperçu de l'étude

Statut

Complété

Les conditions

Intervention / Traitement

Type d'étude

Interventionnel

Inscription (Réel)

61

Phase

  • La phase 1

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

  • États-Unis
    • Florida
      • Miami, Florida, États-Unis, 33169
        • Elite Research Institute
      • South Miami, Florida, États-Unis, 33143
        • Miami Research Associates
      • South Miami, Florida, États-Unis, 33143
        • MRA Clinical Research
    • Ohio
      • Cincinnati, Ohio, États-Unis, 45212
        • Medpace Clinical Pharmacology Unit

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 70 ans (Adulte, Adulte plus âgé)

Accepte les volontaires sains

Non

Sexes éligibles pour l'étude

Tout

La description

Inclusion Criteria:

  • Patients with type 2 diabetes mellitus who are taking metformin only.
  • Treatment should be stable, where this is defined as no change in the treatment, including dose, over the past 2 months. Regimens may include once daily and twice daily dosing only.
  • Male and/or female patients (females will be women of non childbearing potential)
  • Body Mass Index (BMI) of 18.5 to 45.0 kg/m2; and a total body weight >50 kg (110 lbs).
  • HbA1c between 7.0% and 10.0%.

Exclusion Criteria:

  • Evidence or history of clinically significant hematological, renal, endocrine, pulmonary, gastrointestinal, cardiovascular, hepatic, psychiatric, neurologic, or allergic disease (including drug allergies, but excluding untreated, asymptomatic, seasonal allergies at time of dosing). Patients who have chronic conditions other than T2DM (for example, hypercholesterolemia or hypertension) but are controlled by either diet or stable (for the last 2 months) doses of medications may be included as well (for example, a subject with hypercholesterolemia on appropriate treatment is eligible).
  • Evidence or history of diabetic complications with significant end organ damage, eg, proliferative retinopathy and/or macular edema, creatinine clearance less than 60 mL/min
  • Any condition possibly affecting drug absorption (eg, gastrectomy)
  • History of stroke or transient ischemic attack or myocardial infarction within the past 6 months
  • History of coronary artery bypass graft or stent implantation.
  • Clinically significant peripheral vascular disease (eg, manifested by claudication).
  • Any history or clinical evidence of congestive heart failure, NYHA Classes II to IV.
  • One or more self reported significant/severe/requiring treatment episodes of hypoglycemia within the last 3 months, or two or more self reported significant/severe/requiring treatment episodes of hypoglycaemia within the last 6 months.
  • Current history of angina/unstable angina.
  • Milk or soy allergy

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
Médicament: Placebo
Placebo to match PF-04937319 will be provided. Subjects will be dosed for 14 days. In each cohort 9 subjects will receive PF-04937319 and 3 will receive placebo.
Expérimental: PF-04937319
Médicament: PF-04937319
Subjects will be dosed with PF-04937319 for 14 days. The doses planned are 10, 30, 100 and 300 mg QD. All doses will be administered as tablets (10 and 100 mg strengths). In each Cohort, 9 patients will receive PF 04937319 and 3 will receive placebo. An additional cohort of 12 patients (9 active, 3 placebo) may be performed to explore a QD or BID dose. The dose for this additional cohort could be a dose already studied or a new dose that is within the exposure stopping criteria.

Que mesure l'étude ?

Principaux critères de jugement

Mesure des résultats
Description de la mesure
Délai
Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)
Délai: Baseline (Day 1) up to 14 days after last dose of study treatment (up to 28 days)
An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. An SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Treatment-emergent are events between first dose of study drug and up to 14 days after last dose that were absent before treatment or that worsened relative to pre-treatment state.
Baseline (Day 1) up to 14 days after last dose of study treatment (up to 28 days)
Maximum Observed Plasma Concentration (Cmax) On Day 1
Délai: 0 (pre-dose), 0.5, 1.5, 3, 5, 8, 12, 16, 24 hours (hrs) post morning dose on Day 1 (fasted condition)
0 (pre-dose), 0.5, 1.5, 3, 5, 8, 12, 16, 24 hours (hrs) post morning dose on Day 1 (fasted condition)
Maximum Observed Plasma Concentration (Cmax) On Day 6
Délai: 0 (pre-dose), 0.5, 1.5, 3, 5, 8 hours post-dose on Day 6 (fed condition)
0 (pre-dose), 0.5, 1.5, 3, 5, 8 hours post-dose on Day 6 (fed condition)
Time to Reach Maximum Observed Plasma Concentration (Tmax) on Day 1
Délai: 0 (pre-dose), 0.5, 1.5, 3, 5, 8, 12, 16, 24 hours post morning dose on Day 1 (fasted condition)
0 (pre-dose), 0.5, 1.5, 3, 5, 8, 12, 16, 24 hours post morning dose on Day 1 (fasted condition)
Time to Reach Maximum Observed Plasma Concentration (Tmax) on Day 6
Délai: 0 (pre-dose), 0.5, 1.5, 3, 5, 8 hours post-dose on Day 6 (fed condition)
0 (pre-dose), 0.5, 1.5, 3, 5, 8 hours post-dose on Day 6 (fed condition)
Area Under the Curve From Time Zero to End of Dosing Interval (AUCtau) on Day 1
Délai: 0 (pre-dose), 0.5, 1.5, 3, 5, 8, 12, 16, 24 hours post morning dose on Day 1 (fasted condition)
AUCtau is the area under the plasma concentration versus time curve from time zero (pre-dose) to the end of the dosing interval (tau), here dosing interval is 24 hours.
0 (pre-dose), 0.5, 1.5, 3, 5, 8, 12, 16, 24 hours post morning dose on Day 1 (fasted condition)
Maximum Observed Plasma Concentration at Steady State (Cmax, ss) On Day 14
Délai: 0 (pre-dose), 0.5, 1.5, 3, 5, 8, 12, 16, 24 hours post morning dose on Day 14 (fasted condition)
0 (pre-dose), 0.5, 1.5, 3, 5, 8, 12, 16, 24 hours post morning dose on Day 14 (fasted condition)
Time to Reach Maximum Observed Plasma Concentration at Steady State (Tmax, ss) on Day 14
Délai: 0 (pre-dose), 0.5, 1.5, 3, 5, 8, 12, 16, 24 hours post morning dose on Day 14 (fasted condition)
0 (pre-dose), 0.5, 1.5, 3, 5, 8, 12, 16, 24 hours post morning dose on Day 14 (fasted condition)
Area Under the Curve From Time Zero to End of Dosing Interval at Steady State (AUCtau, ss) on Day 14
Délai: 0 (pre-dose), 0.5, 1.5, 3, 5, 8, 12, 16, 24 hours post morning dose on Day 14 (fasted condition)
AUCtau, ss = Area under the plasma concentration versus time curve from time zero (pre-dose) to the end of the dosing interval (tau) at steady state, here dosing interval is 24 hours.
0 (pre-dose), 0.5, 1.5, 3, 5, 8, 12, 16, 24 hours post morning dose on Day 14 (fasted condition)
Plasma Decay Half-Life (t1/2) on Day 14
Délai: 0 (pre-dose), 0.5, 1.5, 3, 5, 8, 12, 16, 24, 36, 48 hours post morning dose on Day 14 (fasted condition)
Plasma decay half-life is the time measured for the plasma concentration to decrease by one half.
0 (pre-dose), 0.5, 1.5, 3, 5, 8, 12, 16, 24, 36, 48 hours post morning dose on Day 14 (fasted condition)
Minimum Observed Plasma Trough Concentration at Steady State (Cmin, ss) on Day 14
Délai: 0 (pre-dose), 0.5, 1.5, 3, 5, 8, 12, 16 hours post morning dose on Day 14 (fasted condition)
0 (pre-dose), 0.5, 1.5, 3, 5, 8, 12, 16 hours post morning dose on Day 14 (fasted condition)
Percentage of Unchanged Drug Excreted in the Urine Over Dosing Interval (Ae[%]) on Day 14
Délai: 0 hour (pre-dose) through 24 hours post-dose on Day 14
Percentage of drug excreted unchanged in urine calculated as overall amount of unchanged drug excreted in the urine over the dosing interval (24 hours) divided by total daily dose multiplied by 100.
0 hour (pre-dose) through 24 hours post-dose on Day 14
Apparent Oral Clearance (CL/F) on Day 14
Délai: 0 (pre-dose), 0.5, 1.5, 3, 5, 8, 12, 16, 24 hours post morning dose on Day 14 (fasted condition)
Drug clearance is a quantitative measure of the rate at which a drug substance is removed from the blood.
0 (pre-dose), 0.5, 1.5, 3, 5, 8, 12, 16, 24 hours post morning dose on Day 14 (fasted condition)
Apparent Volume of Distribution (Vz/F) on Day 14
Délai: 0 (pre-dose), 0.5, 1.5, 3, 5, 8, 12, 16, 24 hours post morning dose on Day 14 (fasted condition)
Volume of distribution is defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired plasma concentration of a drug.
0 (pre-dose), 0.5, 1.5, 3, 5, 8, 12, 16, 24 hours post morning dose on Day 14 (fasted condition)
Observed Accumulation Ratio for AUCtau (Rac)
Délai: 0 (pre-dose), 0.5, 1.5, 3, 5, 8, 12, 16, 24 hours post morning dose on Day 1 and Day 14 (fasted condition)
Accumulation ratio for AUCtau (Rac) was calculated as area under the curve from time zero to end of dosing interval (AUCtau) on Day 14 divided by area under the curve from time zero to end of dosing interval (AUCtau) on Day 1. Dosing interval = 24 hours.
0 (pre-dose), 0.5, 1.5, 3, 5, 8, 12, 16, 24 hours post morning dose on Day 1 and Day 14 (fasted condition)
Observed Accumulation Ratio for Cmax (Rac, Cmax)
Délai: 0 (pre-dose), 0.5, 1.5, 3, 5, 8, 12, 16, 24 hours post morning dose on Day 1 and Day 14 (fasted condition)
Accumulation ratio for Cmax (Rac, Cmax) was calculated as maximum observed plasma concentration (Cmax) on Day 14 divided by maximum observed plasma concentration (Cmax) on Day 1.
0 (pre-dose), 0.5, 1.5, 3, 5, 8, 12, 16, 24 hours post morning dose on Day 1 and Day 14 (fasted condition)
Percent Change From Baseline in Glucose Area Under the Curve From Time 2 to 6 Hours (AUC [2-6]) After a Mixed Meal Tolerance Test (MMTT) at Day 1
Délai: -46, -45.75, -45.5, -45, -44.5, -44, -43, -42 hrs pre-dose on Day -1; 2, 2.25, 2.5, 3, 3.5, 4, 5, 6 hrs post-dose on Day 1 (fasted condition)
Percent change from baseline in area under the plasma glucose concentration-time curve as determined by standardized MMTT. Linear trapezoidal method was used to compute AUC. Baseline value was the AUC (2-6) calculated on Day -1.
-46, -45.75, -45.5, -45, -44.5, -44, -43, -42 hrs pre-dose on Day -1; 2, 2.25, 2.5, 3, 3.5, 4, 5, 6 hrs post-dose on Day 1 (fasted condition)
Percent Change From Baseline in Glucose Area Under the Curve From Time 2 to 6 Hours (AUC [2-6]) After a Mixed Meal Tolerance Test (MMTT) at Day 14
Délai: -46, -45.75, -45.5, -45, -44.5, -44, -43, -42 hrs pre-dose on Day -1; 2, 2.25, 2.5, 3, 3.5, 4, 5, 6 hrs post-dose on Day 14 (fasted condition)
Percent change from baseline in area under the plasma glucose concentration-time curve as determined by standardized MMTT. Linear trapezoidal method was used to compute AUC. Baseline value was the AUC (2-6) calculated on Day -1.
-46, -45.75, -45.5, -45, -44.5, -44, -43, -42 hrs pre-dose on Day -1; 2, 2.25, 2.5, 3, 3.5, 4, 5, 6 hrs post-dose on Day 14 (fasted condition)

Mesures de résultats secondaires

Mesure des résultats
Description de la mesure
Délai
Percent Change From Baseline in Insulin Area Under the Curve From Time 2 to 6 Hours (AUC [2-6]) After a Mixed Meal Tolerance Test (MMTT) at Day 1 and 14
Délai: -46, -45.75, -45.5, -45, -44.5, -44, -43, -42 hrs pre-dose on Day -1; 2, 2.25, 2.5, 3, 3.5, 4, 5, 6 hrs post-dose on Day 1 and 14 (fasted condition)
Percent change from baseline in area under the plasma insulin concentration-time curve as determined by standardized MMTT. Linear trapezoidal method was used to compute AUC. Baseline value was the AUC (2-6) calculated on Day -1.
-46, -45.75, -45.5, -45, -44.5, -44, -43, -42 hrs pre-dose on Day -1; 2, 2.25, 2.5, 3, 3.5, 4, 5, 6 hrs post-dose on Day 1 and 14 (fasted condition)
Percent Change From Baseline in C-peptide Area Under the Curve From Time 2 to 6 Hours (AUC [2-6]) After a Mixed Meal Tolerance Test (MMTT) at Day 1 and 14
Délai: -46, -45.75, -45.5, -45, -44.5, -44, -43, -42 hrs pre-dose on Day -1; 2, 2.25, 2.5, 3, 3.5, 4, 5, 6 hrs post-dose on Day 1 and 14 (fasted condition)
Percent change from baseline in area under the plasma C-peptide concentration-time curve as determined by standardized MMTT. Linear trapezoidal method was used to compute AUC. Baseline value was the AUC (2-6) calculated on Day -1.
-46, -45.75, -45.5, -45, -44.5, -44, -43, -42 hrs pre-dose on Day -1; 2, 2.25, 2.5, 3, 3.5, 4, 5, 6 hrs post-dose on Day 1 and 14 (fasted condition)
Change From Baseline in Average Plasma Glucose at Day 1, 6, 14
Délai: -46, -44, -42, -40, -38, -36, -30, -27 hrs pre-dose on Day -1; 2, 6, 8, 10, 12,18,21 hrs post-dose on Day 1, 6 and 14; additional 0 hr (pre-dose) on Day 6 and 4 hr post-dose on Day 1 and 14
Glucometer testing performed by finger-stick at 8 time points per day to measure glucose levels. Average plasma glucose was calculated as area under the plasma glucose concentration-time curve from 0 to 24 hours (AUC [0-24]) divided by 24.
-46, -44, -42, -40, -38, -36, -30, -27 hrs pre-dose on Day -1; 2, 6, 8, 10, 12,18,21 hrs post-dose on Day 1, 6 and 14; additional 0 hr (pre-dose) on Day 6 and 4 hr post-dose on Day 1 and 14
Change From Baseline in Fasting Plasma Glucose at Day 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14 and 15
Délai: Baseline (Pre-dose on Day 1), Day 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15
Baseline (Pre-dose on Day 1), Day 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15
Change From Baseline in Triglyceride (TG) Level at Day 3, 6, 10, 14, 16 and Follow-up
Délai: Baseline (Day -2), Day 3, 6, 10, 14, 16 and Follow-up (7 to 14 days after last dose of study medication)
Blood sample for lipid biomarker was taken following 12-hours fasting. Baseline value was collected on Day -2 for lipids.
Baseline (Day -2), Day 3, 6, 10, 14, 16 and Follow-up (7 to 14 days after last dose of study medication)
Change From Baseline in Total Cholesterol (TC) Level at Day 3, 6, 10, 14, 16 and Follow-up
Délai: Baseline (Day -2), Day 3, 6, 10, 14, 16 and Follow-up (7 to 14 days after last dose of study medication)
Blood sample for lipid biomarker was taken following 12-hours fasting. Baseline value was collected on Day -2 for lipids.
Baseline (Day -2), Day 3, 6, 10, 14, 16 and Follow-up (7 to 14 days after last dose of study medication)
Change From Baseline in Low Density Lipoprotein-Cholesterol (LDL-C) Level at Day 3, 6, 10, 14, 16 and Follow-up
Délai: Baseline (Day -2), Day 3, 6, 10, 14, 16 and Follow-up (7 to 14 days after last dose of study medication)
Blood sample for lipid biomarker was taken following 12-hours fasting. Baseline value was collected on Day -2 for lipids.
Baseline (Day -2), Day 3, 6, 10, 14, 16 and Follow-up (7 to 14 days after last dose of study medication)
Change From Baseline in High Density Lipoprotein-Cholesterol (HDL-C) Level at Day 3, 6, 10, 14, 16 and Follow-up
Délai: Baseline (Day -2), Day 3, 6, 10, 14, 16 and Follow-up (7 to 14 days after last dose of study medication)
Blood sample for lipid biomarker was taken following 12-hours fasting. Baseline value was collected on Day -2 for lipids.
Baseline (Day -2), Day 3, 6, 10, 14, 16 and Follow-up (7 to 14 days after last dose of study medication)
Change From Baseline in Lactate Level at Day 6 and 14
Délai: Baseline (Day 1), Day 6 and 14
Baseline value was collected at 0 hour on Day 1 for lactate.
Baseline (Day 1), Day 6 and 14

Collaborateurs et enquêteurs

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

Parrainer

Pfizer

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

Liens utiles

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 février 2011

Achèvement primaire (Réel)

1 juillet 2011

Achèvement de l'étude (Réel)

1 juillet 2011

Dates d'inscription aux études

Première soumission

6 janvier 2011

Première soumission répondant aux critères de contrôle qualité

6 janvier 2011

Première publication (Estimation)

10 janvier 2011

Mises à jour des dossiers d'étude

Dernière mise à jour publiée (Estimation)

1 février 2017

Dernière mise à jour soumise répondant aux critères de contrôle qualité

6 décembre 2016

Dernière vérification

1 octobre 2016

Plus d'information

Termes liés à cette étude

Mots clés

Termes MeSH pertinents supplémentaires

Autres numéros d'identification d'étude

  • B1621003

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 .

S'abonner