Dose-Ranging Study to Evaluate the Glycemic Effects, Safety, and Tolerability of Metformin Delayed Release in Subjects With T2DM

NCT ID: NCT02526524

Last Updated: 2018-04-27

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 571 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2015-09-30
• Study Completion Date: 2016-09-30

Brief Summary

The purpose of the study is to compare the glycemic effects of delayed-release metformin (Met DR) to placebo in subjects with type 2 diabetes mellitus (T2DM) over 16 weeks. The study is designed to evaluate several doses of Met DR (600 to 1500 mg once daily in the morning [qAM]) compared to placebo. A single-blind reference treatment of 2000 mg metformin immediate-release (Met IR) per day administered as equal divided doses (1000 mg Met IR BID) will also be included.

Conditions

Type 2 Diabetes Mellitus

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

600 mg Met DR qAM

600 mg metformin delayed-release once daily in the morning

Group Type: EXPERIMENTAL

Met DR

Intervention Type: DRUG

metformin delayed-release tablets

900 mg Met DR qAM

900 mg metformin delayed-release once daily in the morning

Group Type: EXPERIMENTAL

Met DR

Intervention Type: DRUG

metformin delayed-release tablets

1200 mg Met DR qAM

1200 mg metformin delayed-release once daily in the morning

Group Type: EXPERIMENTAL

Met DR

Intervention Type: DRUG

metformin delayed-release tablets

1500 mg Met DR qAM

1500 mg metformin delayed-release once daily in the morning

Group Type: EXPERIMENTAL

Met DR

Intervention Type: DRUG

metformin delayed-release tablets

Placebo-1

placebo match for 600 and 1200 mg Met DR qAM treatment groups

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Placebo-2

placebo match for 900 and 1500 mg Met DR qAM treatment groups

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

2000 mg Met IR

1000 mg metformin immediate-release twice daily

Group Type: ACTIVE_COMPARATOR

Met IR

Intervention Type: DRUG

metformin immediate-release tablets

Interventions

Met DR

metformin delayed-release tablets

Intervention Type: DRUG

Met IR

metformin immediate-release tablets

Intervention Type: DRUG

Placebo

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

1. Is at least 25 years old at Visit 1 (Screening).

2. Is male, or is female and meets all of the following criteria:

1. Not breastfeeding

2. Negative pregnancy test result at Visit 1 (not applicable to post-menopausal or surgically sterile females)

3. Surgically sterile, postmenopausal, or if of childbearing potential, must practice and be willing to continue to practice appropriate birth control during the entire duration of the study.

3. Body mass index (BMI) 20.0 to 45.0 kg/m² (inclusive) at Visit 1 (Screening).

4. Has a physical examination with no clinically significant abnormalities as judged by the investigator.

5. Has T2DM and an HbA1c of 7.5% to 10.5%, inclusive, at Visit 1.

6. Has an estimated glomerular filtration rate (eGFR) value of ≥60 mL/min/1.73 m² based on the Modification of Diet in Renal Disease (MDRD) equation.

7. Either is not treated with or has been on a stable treatment regimen with any of the following medications for a minimum of 3 months prior to Visit 1:

1. Thiazolidinedione, sulfonylurea, dipeptidyl peptidase-4 inhibitors, and alpha-glucosidase inhibitors

2. Hormone replacement therapy (female subjects) and testosterone (male subjects)

3. Oral contraceptives (female subjects)

4. Antihypertensive agents

5. Lipid-lowering agents

6. Thyroid replacement therapy

7. Antidepressant agents

8. Ability to understand and willingness to adhere to protocol requirements.

Exclusion Criteria

1. Has a clinically significant medical condition as judged by the investigator that could potentially affect study participation and/or personal well-being, including but not limited to the following conditions:

1. Hepatic disease

2. Gastrointestinal disease

3. Endocrine disorder (T2DM is allowed)

4. Cardiovascular disease

5. Central nervous system diseases

6. Psychiatric or neurological disorders

7. Organ transplantation

8. Chronic or acute infection

9. Orthostatic hypotension, fainting spells or blackouts

10. Allergy or hypersensitivity.

2. A history of diabetic ketoacidosis or hyperosmolar non-ketotic hyperglycemia within the past year.

3. Prior major surgery of any kind within 6 months of Visit 1.

4. A history of >3% weight change within 3 months of Visit 1.

5. A clinical laboratory test (clinical chemistry, hematology, or urinalysis) abnormality, other than that related to T2DM, judged by the investigator to be clinically significant at Visit 1.

6. An alanine aminotransferase or aspartate aminotransferase result >2.5 × upper limit of normal (ULN) or a bilirubin result >1.5 × ULN.

7. A physical, psychological, or historical finding that, in the investigator's opinion, would make the subject unsuitable for the study.

8. Has been treated, is currently being treated, or is expected to require or undergo treatment with any of the following excluded medications:

1. Metformin within 2 months of Visit 1 (Screening)

2. Insulin within 2 weeks of Visit 1 (Screening) or for more than 1 week within 3 months of Visit 1 (Screening)

3. Glucagon-like peptide-1 receptor agonists or sodium-glucose co-transporter 2 inhibitors within 3 months of Visit 1

4. Drugs known to affect body weight, including prescription medications and over-the-counter anti obesity agents within 3 months of Visit 1.

5. Systemic corticosteroids by oral, intravenous, or intramuscular route; or potent, inhaled, or intrapulmonary steroids known to have a high rate of systemic absorption within 3 months of Visit 1

6. Planned use of any drug treatment that affects gastric pH (prescription or over-the-counter), such as H2-receptor antagonists and proton pump inhibitors, after Visit 2 (Week -2), or planned chronic use of any antacids (i.e., more than twice per week) after Visit 2 (Week -2)

7. Cationic drugs that are eliminated by renal tubular secretion within 1 week of Visit 1.

8. Iodinated contrast dye within 1 week prior to Visit 1.

9. Investigational drug within 2 months (or five half-lives of the investigational drug, whichever is greater) of the date of the first dose of randomized study medication.

10. Met DR or double-blind matching placebo for Met DR at any time prior to Visit 1 (Screening)

9. Currently abuses drugs or alcohol or has a history of abuse that in the investigator's opinion would cause the individual to be noncompliant with study procedures.

10. Had a blood transfusion or experienced significant blood loss (i.e., >500 mL), including loss due to blood donation, within 2 months prior to Visit 1 (Screening), or is planning to donate blood during the study.

11. Has known immune system based allergies or hypersensitivity to any component of study treatment. A history of gastrointestinal intolerance to metformin is not exclusionary.

12. Is employed by Elcelyx Therapeutics, Inc. (that is an employee, contract worker, or designee of the company).

13. Has a fasting plasma glucose value >270 mg/dL at Visit 1 (Screening), Visit 2 (Week -2), and an unscheduled visit to be completed within 1 week following Visit 2. The unscheduled visit is to be completed only for subjects with a fasting plasma glucose value >270 mg/dL at Visit 1 and Visit 2.

• Minimum Eligible Age: 25 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Elcelyx Therapeutics, Inc.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Juan P Frias, MD

Role: PRINCIPAL_INVESTIGATOR

National Research Institute - Wilshire

Locations

Pinnacle Research Group, LLC

Anniston, Alabama, United States

Central Alabama Research

Birmingham, Alabama, United States

Achieve Clinical Research, LLC

Birmingham, Alabama, United States

University of Alabama at Birmingham

Birmingham, Alabama, United States

Terence T. Hart, MD

Tuscumbia, Alabama, United States

Radiant Research - Phoenix

Chandler, Arizona, United States

Arrowhead Health Centers

Glendale, Arizona, United States

Holland Center for Family Health, LTD

Peoria, Arizona, United States

Elite Clinical Studies

Phoenix, Arizona, United States

Thunderbird Internal Medicine - Indian School Rd.

Phoenix, Arizona, United States

Clinical Research Institute of Arizona, LLC

Surprise, Arizona, United States

Summit Clinical Trials Center

Fayetteville, Arkansas, United States

Searcy Medical Center

Searcy, Arkansas, United States

Advanced Metabolic Care & Research Institute (AMCR)

Escondido, California, United States

MD Studies, Inc.

Fountain Valley, California, United States

National Research Institute

Huntington Park, California, United States

Scripps Whittier Diabetes Institute

La Jolla, California, United States

Clinical Trials Research

Lincoln, California, United States

Collaborative Neuroscience Network, LLC

Long Beach, California, United States

National Research Institute

Los Angeles, California, United States

Catalina Research Institute

Montclair, California, United States

SRSD, Inc. dba Synergy San Diego

National City, California, United States

Providence Clinical Research

North Hollywood, California, United States

Pacific Research Partners, LLC

Oakland, California, United States

SDS Clinical Trials, Inc.

Orange, California, United States

Center for Clinical Trials of Sacramento

Sacramento, California, United States

Center for Clinical Trials of Scaramento

Sacramento, California, United States

Superior Research LLC

Sacramento, California, United States

Syrentis Clinical Research (formerly Research Across America)

Santa Ana, California, United States

Encompass Clinical Research

Spring Valley, California, United States

Clinical Trial Investigators

Tustin, California, United States

Infosphere Clinical Research

Van Nuys, California, United States

Colorado Springs Health Partners

Colorado Springs, Colorado, United States

Creekside Endocrine Associates

Denver, Colorado, United States

Meridien Research - Brooksville

Brooksville, Florida, United States

ALL Medical Research, LLC

Cooper City, Florida, United States

Neostart Corporation dba AGA Clinical Trials

Hialeah, Florida, United States

Care Partners Clinical Research

Jacksonville, Florida, United States

Health Awareness, Inc.

Jupiter, Florida, United States

Family Health Care Clinical Studies

Kissimmee, Florida, United States

Clinical Research of Central Florida-Lakeland

Lakeland, Florida, United States

Clinical Pharmacology of Miami, Inc.

Miami, Florida, United States

Tellus Clinical Research, Inc.

Miami, Florida, United States

Internal Research Associates LLC - Breton

Miami, Florida, United States

Clinical Neuroscience Solutions, Inc. Healthcare Orlando

Orlando, Florida, United States

Ormond Medical Arts Pharmaceutical Research Center

Ormond Beach, Florida, United States

Private Practice - Andres Patron, DO

Pembroke Pines, Florida, United States

Progressive Medical Research

Port Orange, Florida, United States

Meridien Reserach - St. Petersburg

St. Petersburg, Florida, United States

Clinical Reserch Trials of Florida

Tampa, Florida, United States

Meridien Research - Tampa

Tampa, Florida, United States

Metabolic Research Institute, Inc.

West Palm Beach, Florida, United States

Biofortis, Inc.

Addison, Illinois, United States

AMR Sakeena Research

Aurora, Illinois, United States

Cedar-Crosse Research Center

Chicago, Illinois, United States

Evanston Premier Healthcare Research LLC

Evanston, Illinois, United States

Buynak Clinical Research, PC

Valparaiso, Indiana, United States

The Iowa Clinic; Cardiovascular Services

West Des Moines, Iowa, United States

Heartland Research Associates, LLC - Augusta

Augusta, Kansas, United States

Cotton-O'Neil Clinical Research Center

Topeka, Kansas, United States

Otrimed

Edgewood, Kentucky, United States

Kentucky Diabetes Endocrinology Center

Lexington, Kentucky, United States

Louisville Metabolic and Atherosclerosis Research Center (L-MARC)

Louisville, Kentucky, United States

Four Rivers Clinical Research

Paducah, Kentucky, United States

Avant Research Associates

Crowley, Louisiana, United States

Centex Studies, Inc. - lake Charles

Lake Charles, Louisiana, United States

Columbia Medical Practice

Columbia, Maryland, United States

Medstar Health Research Institute

Hyattsville, Maryland, United States

MD Medical Research

Oxon Hill, Maryland, United States

Beacon Clinical Research

Quincy, Massachusetts, United States

Radiant Research - Edina

Edina, Minnesota, United States

Planters Clinic

Port Gibson, Mississippi, United States

Mercury Street Medical Group, PLLC

Butte, Montana, United States

Quality Clinical Research, Inc.

Omaha, Nebraska, United States

Heartland Clinical Research

Omaha, Nebraska, United States

Alliance Against Diabetes

Las Vegas, Nevada, United States

AB Clinical Trials

Las Vegas, Nevada, United States

Palm Medical Research

Las Vegas, Nevada, United States

Ingham Neuroscience Group, LLC

Las Vegas, Nevada, United States

Comprehensive Clinical Research

Berlin, New Jersey, United States

Albuquerque Clinical Trials

Albuquerque, New Mexico, United States

Albuquerque Neuroscience, Inc.

Albuquerque, New Mexico, United States

NY Scientific

Brooklyn, New York, United States

Long Island Gastrointestinal Research Group

Great Neck, New York, United States

Mid-Hudson Medical Research, PLLC

Hopewell Junction, New York, United States

Great Lakes Medical Research

Westfield, New York, United States

PharmQuest

Greensboro, North Carolina, United States

Triad Clinical Trials LLC

Greensboro, North Carolina, United States

PMG Research of Rocky Mount

Rocky Mount, North Carolina, United States

PMG Research of Salisbury, LLC

Salisbury, North Carolina, United States

PMG Research of Wilmington, LLC

Wilmington, North Carolina, United States

Sterling Research Group, Ltd

Cincinnati, Ohio, United States

Metabolic Atherosclerosis Research Center

Cincinnati, Ohio, United States

New Horizons Clinical Research

Cincinnati, Ohio, United States

Urgent Care Specialists, LLC DBA Hometown Urgent Care and Occupational Health

Columbus, Ohio, United States

Prestige Clinical Research

Franklin, Ohio, United States

Hometown Urgent Care and Research - Huber Heights

Huber Heights, Ohio, United States

RAS Health LTD

Marion, Ohio, United States

Summit Reserach Group, LLC

Stow, Ohio, United States

COR Clinical Research, LLC

Oklahoma City, Oklahoma, United States

Willamette Valley Clinical Studies

Eugene, Oregon, United States

Brandywine Clinical Research

Downingtown, Pennsylvania, United States

Medical Research South, LLC

Charleston, South Carolina, United States

Mountain View Clinical Research - Greer

Greer, South Carolina, United States

PMG of Charleston, LLC

Mt. Pleasant, South Carolina, United States

Family Medicine of SayeBrook, LLC

Myrtle Beach, South Carolina, United States

Hillcrest Clinical Research, LLC

Simpsonville, South Carolina, United States

Palmetto Proactive Healthcare, LLC

Spartanburg, South Carolina, United States

Spartanburg Medical Research

Spartanburg, South Carolina, United States

Palmetto Clinical Research

Summerville, South Carolina, United States

PMG Research of Bristol, LC - State

Bristol, Tennessee, United States

PMG Research of Knoxville

Knoxville, Tennessee, United States

Clinical Neuroscience Solutions, Inc. - Memphis

Memphis, Tennessee, United States

Trinity Clinical Research

Tullahoma, Tennessee, United States

Central Texas Clinical Research

Austin, Texas, United States

Trinity Universal Research Associates, Inc.

Carrollton, Texas, United States

Dallas Diabetes and Endocrine Center

Dallas, Texas, United States

Research Institute of Dallas

Dallas, Texas, United States

Galenos Research

Dallas, Texas, United States

Pioneer Research Solutions, Inc.

Houston, Texas, United States

Centex Studies, Inc.

Houston, Texas, United States

Clinical Trial Network - Houston

Houston, Texas, United States

Juno Research, LLC-Houston

Houston, Texas, United States

Juno Research, LLC-Katy

Katy, Texas, United States

Texas Diabetes Institute Research Center

San Antonio, Texas, United States

Sun Research Institute

San Antonio, Texas, United States

Victorium Clinical Research

San Antonio, Texas, United States

Consano Clinical Research

Shavano Park, Texas, United States

Southwest Health Associates, P.A.

Sugar Land, Texas, United States

Chrysalis Clinical Research

St. George, Utah, United States

Burke Internal Medicine & Research

Burke, Virginia, United States

Manassas Clinical Research Center

Manassas, Virginia, United States

Clinical Research Partners, LLC

Richmond, Virginia, United States

Universal Research Group, LLC

Tacoma, Washington, United States

Puerto Rico Renal and Health Research, Inc.

Carolina, , Puerto Rico

Advanced Medical Concepts

Cidra, , Puerto Rico

Manati Center for Clinical Reserach Doctor's Center Hospital

Manatí, , Puerto Rico

Countries

United States; Puerto Rico

References

Henry RR, Frias JP, Walsh B, Skare S, Hemming J, Burns C, Bicsak TA, Baron A, Fineman M. Improved glycemic control with minimal systemic metformin exposure: Effects of Metformin Delayed-Release (Metformin DR) targeting the lower bowel over 16 weeks in a randomized trial in subjects with type 2 diabetes. PLoS One. 2018 Sep 25;13(9):e0203946. doi: 10.1371/journal.pone.0203946. eCollection 2018.

Reference Type: DERIVED

PMID: 30252913 (View on PubMed)

Other Identifiers

LCRM112

Identifier Type: -

Identifier Source: org_study_id