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

NCT01843127 | Completed Phase 1

• 1 other identifier: GS-US-259-0165
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 3

Brief Summary

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

Conditions

Type 2 Diabetes Mellitus

Outcome Measures

Primary Outcomes (1)

• Area under the concentration-time curve (AUC) of plasma glucagon during the standard meal test (SMT)

  Days 5, 10, and 14

Secondary Outcomes (9)

• Plasma glucose, serum insulin, and serum C-peptide AUCs during the SMT

  Days 5, 10, and 14

• Collapse under Acetaminophen PK

  Days 5 and 10

• Area under the plasma acetaminophen concentration-time curve from time 0 to 240 min (AUC0-240 min)

  Days 5 and 10

• Collapse all under ranolazine pharmacokinetics (PK)

  Days 5 and 10

• Trough plasma ranolazine concentrations (Ctrough)

  Days 5 and 10

Study Arms (2)

Placebo, Ranolazine, Exenatide

ACTIVE COMPARATOR

Drug: Ranolazine; Drug: Placebo; Drug: Exenatide

Ranolazine, Placebo, Exenatide

ACTIVE COMPARATOR

Drug: Ranolazine; Drug: Placebo; Drug: Exenatide

Interventions

Ranolazine DRUG

Placebo, Ranolazine, Exenatide; Ranolazine, Placebo, Exenatide

Placebo DRUG

Placebo, Ranolazine, Exenatide; Ranolazine, Placebo, Exenatide

Exenatide DRUG

Placebo, Ranolazine, Exenatide; Ranolazine, Placebo, Exenatide

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• Gilead Sciences: lead

Study Sites (3)

Profil Institute for Clinical Research, Inc.

Chula Vista, California, 91911, United States

Location

SeaView Research, Inc

Miami, Florida, 33126, United States

Location

Translational Research Institute-Florida Hospital

Orlando, Florida, 32804, United States

Location

MeSH Terms

Conditions

Diabetes Mellitus, Type 2

Interventions

Ranolazine; Exenatide

Condition Hierarchy (Ancestors)

Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases

Intervention Hierarchy (Ancestors)

Acetanilides; Anilides; Amides; Organic Chemicals; Aniline Compounds; Amines; Piperazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Peptides; Amino Acids, Peptides, and Proteins; Venoms; Complex Mixtures; Toxins, Biological; Biological Factors

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 17, 2013
• First Posted: April 30, 2013
• Study Start: April 1, 2013
• Primary Completion: September 1, 2013
• Study Completion: September 1, 2013
• Last Updated: March 31, 2014

Record last verified: 2014-03

Locations

US (3)