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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT01843127
Recruitment Status : Completed
First Posted : April 30, 2013
Last Update Posted : March 31, 2014
Information provided by (Responsible Party):
Gilead Sciences

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

Condition or disease Intervention/treatment Phase
Type 2 Diabetes Mellitus Drug: Ranolazine Drug: Placebo Drug: Exenatide Phase 1

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 24 participants
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Single (Participant)
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
Study Start Date : April 2013
Actual Primary Completion Date : September 2013
Actual Study Completion Date : September 2013

Resource links provided by the National Library of Medicine

U.S. FDA Resources

Arm Intervention/treatment
Active Comparator: Placebo, Ranolazine, Exenatide Drug: Ranolazine Drug: Placebo Drug: Exenatide
Active Comparator: Ranolazine, Placebo, Exenatide Drug: Ranolazine Drug: Placebo Drug: Exenatide

Primary Outcome Measures :
  1. Area under the concentration-time curve (AUC) of plasma glucagon during the standard meal test (SMT) [ Time Frame: Days 5, 10, and 14 ]

Secondary Outcome Measures :
  1. Plasma glucose, serum insulin, and serum C-peptide AUCs during the SMT [ Time Frame: Days 5, 10, and 14 ]
  2. Collapse under Acetaminophen PK [ Time Frame: Days 5 and 10 ]
  3. Area under the plasma acetaminophen concentration-time curve from time 0 to 240 min (AUC0-240 min) [ Time Frame: Days 5 and 10 ]
  4. Collapse all under ranolazine pharmacokinetics (PK) [ Time Frame: Days 5 and 10 ]
  5. Trough plasma ranolazine concentrations (Ctrough) [ Time Frame: Days 5 and 10 ]
  6. Average plasma ranolazine concentration during a dosing interval at steady state (Css,ave) [ Time Frame: Days 5 and 10 ]
  7. Area under the plasma ranolazine concentration-time curve over dosing interval (AUCtau) [ Time Frame: Days 5 and 10 ]
  8. Apparent elimination half-life (t1/2) of ranolazine [ Time Frame: Days 5 and 10 ]
  9. Adverse events, physical examinations, clinical laboratory determinations, electrocardiograms (ECG), and vital sign assessments. [ Time Frame: From Screening to 7 days after the final dose ]

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 65 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT01843127

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

Responsible Party: Gilead Sciences Identifier: NCT01843127     History of Changes
Other Study ID Numbers: GS-US-259-0165
First Posted: April 30, 2013    Key Record Dates
Last Update Posted: March 31, 2014
Last Verified: March 2014

Additional relevant MeSH terms:
Diabetes Mellitus
Diabetes Mellitus, Type 2
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
Hypoglycemic Agents
Physiological Effects of Drugs
Hormones, Hormone Substitutes, and Hormone Antagonists
Gastrointestinal Agents
Sodium Channel Blockers
Membrane Transport Modulators
Molecular Mechanisms of Pharmacological Action