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

Type 2 Diabetes Mellitus Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01843127
• Other study ID #: GS-US-259-0165
• Status: Completed
• Phase: Phase 1
• First received: April 17, 2013
• Last updated: March 28, 2014
• Start date: April 2013
• Est. completion date: September 2013

Study information

• Verified date: March 2014
• Source: Gilead Sciences
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 24
• Est. completion date: September 2013
• Est. primary completion date: September 2013
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 65 Years

Eligibility

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.

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Crossover Assignment, Masking: Single Blind (Subject), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Diabetes Mellitus
• Diabetes Mellitus, Type 2
• Type 2 Diabetes Mellitus

Intervention

Drug:
• Ranolazine

• Placebo

• Exenatide

Locations

Country	Name	City	State
United States	Profil Institute for Clinical Research, Inc.	Chula Vista	California
United States	SeaView Research, Inc	Miami	Florida
United States	Translational Research Institute-Florida Hospital	Orlando	Florida

Sponsors (1)

Lead Sponsor	Collaborator
Gilead Sciences

Country where clinical trial is conducted

United States, 

Outcome

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