A Study to Evaluate the Effect of Ranolazine on Postprandial Glucagon in Subjects With Type 2 Diabetes.

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Gilead Sciences
ClinicalTrials.gov Identifier:
NCT01843127
First received: April 17, 2013
Last updated: March 28, 2014
Last verified: March 2014
  Purpose

To explore the mechanism of action of ranolazine as a potential treatment for type 2 diabetes mellitus (T2DM).


Condition Intervention Phase
Type 2 Diabetes Mellitus
Drug: Ranolazine
Drug: Placebo
Drug: Exenatide
Phase 1

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Crossover Assignment
Masking: Single Blind (Subject)
Primary Purpose: Treatment
Official Title: A Phase 1, Randomized, Single-blind, Placebo-controlled, Multiple-dose, Two-sequence, Cross-over Study to Evaluate the Effect of Ranolazine on Glucagon Secretion in Subjects With Type 2 Diabetes Mellitus, Followed by An Open-label, Single Dose, Exenatide Active-control Period

Resource links provided by NLM:


Further study details as provided by Gilead Sciences:

Primary Outcome Measures:
  • Area under the concentration-time curve (AUC) of plasma glucagon during the standard meal test (SMT) [ Time Frame: Days 5, 10, and 14 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Plasma glucose, serum insulin, and serum C-peptide AUCs during the SMT [ Time Frame: Days 5, 10, and 14 ] [ Designated as safety issue: No ]
  • Collapse under Acetaminophen PK [ Time Frame: Days 5 and 10 ] [ Designated as safety issue: No ]
  • Area under the plasma acetaminophen concentration-time curve from time 0 to 240 min (AUC0-240 min) [ Time Frame: Days 5 and 10 ] [ Designated as safety issue: No ]
  • Collapse all under ranolazine pharmacokinetics (PK) [ Time Frame: Days 5 and 10 ] [ Designated as safety issue: No ]
  • Trough plasma ranolazine concentrations (Ctrough) [ Time Frame: Days 5 and 10 ] [ Designated as safety issue: No ]
  • Average plasma ranolazine concentration during a dosing interval at steady state (Css,ave) [ Time Frame: Days 5 and 10 ] [ Designated as safety issue: No ]
  • Area under the plasma ranolazine concentration-time curve over dosing interval (AUCtau) [ Time Frame: Days 5 and 10 ] [ Designated as safety issue: No ]
  • Apparent elimination half-life (t1/2) of ranolazine [ Time Frame: Days 5 and 10 ] [ Designated as safety issue: No ]
  • Adverse events, physical examinations, clinical laboratory determinations, electrocardiograms (ECG), and vital sign assessments. [ Time Frame: From Screening to 7 days after the final dose ] [ Designated as safety issue: Yes ]

Enrollment: 24
Study Start Date: April 2013
Study Completion Date: September 2013
Primary Completion Date: September 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Placebo, Ranolazine, Exenatide Drug: Ranolazine Drug: Placebo Drug: Exenatide
Active Comparator: Ranolazine, Placebo, Exenatide Drug: Ranolazine Drug: Placebo Drug: Exenatide

  Eligibility

Ages Eligible for Study:   18 Years to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Males and females, 18 to 65 years old, inclusive
  • Documented history of T2DM for ≥5 years
  • Body mass index (BMI) 20.0 to 40.0 kg/m2, inclusive, at Screening
  • Stable treatment (≥ 12 weeks) with metformin alone, a sulfonylurea alone, a meglitinide alone, or a combination of metformin with either a sulfonylurea or a meglitinide
  • HbA1c ≥ 7.0% and ≤ 10.5%, inclusive, at Screening
  • Fasting glucose within specific ranges, at Screening and after 14 +/-2 days of wash-out from prior oral anti-diabetic agents
  • Fasting serum C-peptide ≥0.8 ng/mL, at Screening
  • Estimated glomerular filtration rate (eGFR)≥60 mL/min/1.73 m2
  • Ability and willingness to comply with all study procedures during the course of the study, including washout from oral anti-diabetic (OAD) agents approximately 2 weeks prior to Day -2 admission
  • Females of childbearing potential must have a negative pregnancy test at Screening and on Day -2 admission and must agree to use highly effective contraception methods from Screening throughout study participation and for 14 days following the last dose of study drug.

Exclusion Criteria:

  • History of type 1 diabetes mellitus or secondary forms of diabetes
  • History of acute diabetes complications
  • Recent or significant heart conditions
  • Uncontrolled hypertension
  • QTc interval > 500 msec by ECG at Screening or on Day -2 admission, a personal or family history of QTc prolongation, congenital long QT syndrome, or use of drugs that prolong the QTc interval, such as Class Ia or Class III antiarrhythmic agents, erythromycin, and certain antipsychotics (eg, ziprasidone)
  • History of severe GI disease (e.g., gastroparesis)
  • History of pancreatitis (acute or chronic)
  • Current consumption of > 14 alcoholic drinks per week, or more than 4 alcoholic drinks on any one day
  • Current regular use of tobacco- or nicotine-containing products in excess of 10 cigarettes per day or equivalent
  • History of substance abuse within 12 months prior to Screening
  • Significant hepatic disease, including, but not limited to, chronic active hepatitis and liver cirrhosis (Child-Pugh Class A, B, or C)
  • History of malignancy within 5 years prior to Screening
  • Significant thyroid disease
  • Treatment with selected medications, as indicated in the protocol
  • Prior treatment with open-label ranolazine or known hypersensitivity or intolerance to ranolazine or its excipients
  • Known hypersensitivity or intolerance to GLP-1 mimetics
  • Known hypersensitivity or intolerance to acetaminophen
  • Aspartate aminotransferase (AST) and/or alanine aminotransferase (ALT) > 2.5 X upper limit of normal (ULN)
  • Total Bilirubin (TB) > 2 mg/dL
  • Hemoglobin < 12 g/dL (for males) or < 11 g/dL (for females)
  • Positive for hepatitis B surface antigen
  • Positive for anti-hepatitis C virus antibody
  • Positive for human immunodeficiency virus-1 (HIV-1) antibody
  • Positive urine drug screen
  • Positive alcohol test
  • Donation of blood or blood products to a blood bank, blood transfusion, or participation in a clinical study requiring withdrawal of > 500 mL of blood during the 6 weeks prior to Screening
  • Females who are pregnant or breastfeeding
  • Other condition(s) that, in the opinion of the investigator, would compromise the safety of the subject, would prevent compliance with the study protocol, or would compromise the quality of the clinical study.
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01843127

Locations
United States, California
Profil Institute for Clinical Research, Inc.
Chula Vista, California, United States, 91911
United States, Florida
SeaView Research, Inc
Miami, Florida, United States, 33126
Translational Research Institute-Florida Hospital
Orlando, Florida, United States, 32804
Sponsors and Collaborators
Gilead Sciences
  More Information

No publications provided

Responsible Party: Gilead Sciences
ClinicalTrials.gov Identifier: NCT01843127     History of Changes
Other Study ID Numbers: GS-US-259-0165
Study First Received: April 17, 2013
Last Updated: March 28, 2014
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Diabetes Mellitus
Diabetes Mellitus, Type 2
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
Glucagon
Ranolazine
Exenatide
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Pharmacologic Actions
Gastrointestinal Agents
Therapeutic Uses
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Hypoglycemic Agents

ClinicalTrials.gov processed this record on April 21, 2014