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

Type 2 Diabetes Mellitus Clinical Trial

Official title:

Randomized, Double-Blind, Parallel-Group, Multicenter, Placebo-Controlled, Dose-Ranging Study to Evaluate the Glycemic Effects, Safety, and Tolerability of Metformin Delayed Release In Subjects With Type 2 Diabetes Mellitus

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02526524
• Other study ID #: LCRM112
• Status: Completed
• Phase: Phase 2
• First received: August 16, 2015
• Last updated: March 27, 2018
• Start date: September 2015
• Est. completion date: September 2016

Study information

• Verified date: March 2018
• Source: Elcelyx Therapeutics, Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 571
• Est. completion date: September 2016
• Est. primary completion date: September 2016
• Accepts healthy volunteers: No
• Gender: All
• Age group: 25 Years and older

Eligibility

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.

Related Conditions & MeSH terms

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

Intervention

Drug:
• Met DR
metformin delayed-release tablets
• Met IR
metformin immediate-release tablets
• Placebo

Locations

Country	Name	City	State
Puerto Rico	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	Manati
United States	Biofortis, Inc.	Addison	Illinois
United States	Albuquerque Clinical Trials	Albuquerque	New Mexico
United States	Albuquerque Neuroscience, Inc.	Albuquerque	New Mexico
United States	Pinnacle Research Group, LLC	Anniston	Alabama
United States	Heartland Research Associates, LLC - Augusta	Augusta	Kansas
United States	AMR Sakeena Research	Aurora	Illinois
United States	Central Texas Clinical Research	Austin	Texas
United States	Comprehensive Clinical Research	Berlin	New Jersey
United States	Achieve Clinical Research, LLC	Birmingham	Alabama
United States	Central Alabama Research	Birmingham	Alabama
United States	University of Alabama at Birmingham	Birmingham	Alabama
United States	PMG Research of Bristol, LC - State	Bristol	Tennessee
United States	NY Scientific	Brooklyn	New York
United States	Meridien Research - Brooksville	Brooksville	Florida
United States	Burke Internal Medicine & Research	Burke	Virginia
United States	Mercury Street Medical Group, PLLC	Butte	Montana
United States	Trinity Universal Research Associates, Inc.	Carrollton	Texas
United States	Radiant Research - Phoenix	Chandler	Arizona
United States	Medical Research South, LLC	Charleston	South Carolina
United States	Cedar-Crosse Research Center	Chicago	Illinois
United States	Metabolic Atherosclerosis Research Center	Cincinnati	Ohio
United States	New Horizons Clinical Research	Cincinnati	Ohio
United States	Sterling Research Group, Ltd	Cincinnati	Ohio
United States	Colorado Springs Health Partners	Colorado Springs	Colorado
United States	Columbia Medical Practice	Columbia	Maryland
United States	Urgent Care Specialists, LLC DBA Hometown Urgent Care and Occupational Health	Columbus	Ohio
United States	ALL Medical Research, LLC	Cooper City	Florida
United States	Avant Research Associates	Crowley	Louisiana
United States	Dallas Diabetes and Endocrine Center	Dallas	Texas
United States	Galenos Research	Dallas	Texas
United States	Research Institute of Dallas	Dallas	Texas
United States	Creekside Endocrine Associates	Denver	Colorado
United States	Brandywine Clinical Research	Downingtown	Pennsylvania
United States	Otrimed	Edgewood	Kentucky
United States	Radiant Research - Edina	Edina	Minnesota
United States	Advanced Metabolic Care & Research Institute (AMCR)	Escondido	California
United States	Willamette Valley Clinical Studies	Eugene	Oregon
United States	Evanston Premier Healthcare Research LLC	Evanston	Illinois
United States	Summit Clinical Trials Center	Fayetteville	Arkansas
United States	MD Studies, Inc.	Fountain Valley	California
United States	Prestige Clinical Research	Franklin	Ohio
United States	Arrowhead Health Centers	Glendale	Arizona
United States	Long Island Gastrointestinal Research Group	Great Neck	New York
United States	PharmQuest	Greensboro	North Carolina
United States	Triad Clinical Trials LLC	Greensboro	North Carolina
United States	Mountain View Clinical Research - Greer	Greer	South Carolina
United States	Neostart Corporation dba AGA Clinical Trials	Hialeah	Florida
United States	Mid-Hudson Medical Research, PLLC	Hopewell Junction	New York
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	Pioneer Research Solutions, Inc.	Houston	Texas
United States	Hometown Urgent Care and Research - Huber Heights	Huber Heights	Ohio
United States	National Research Institute	Huntington Park	California
United States	Medstar Health Research Institute	Hyattsville	Maryland
United States	Care Partners Clinical Research	Jacksonville	Florida
United States	Health Awareness, Inc.	Jupiter	Florida
United States	Juno Research, LLC-Katy	Katy	Texas
United States	Family Health Care Clinical Studies	Kissimmee	Florida
United States	PMG Research of Knoxville	Knoxville	Tennessee
United States	Scripps Whittier Diabetes Institute	La Jolla	California
United States	Centex Studies, Inc. - lake Charles	Lake Charles	Louisiana
United States	Clinical Research of Central Florida-Lakeland	Lakeland	Florida
United States	AB Clinical Trials	Las Vegas	Nevada
United States	Alliance Against Diabetes	Las Vegas	Nevada
United States	Ingham Neuroscience Group, LLC	Las Vegas	Nevada
United States	Palm Medical Research	Las Vegas	Nevada
United States	Kentucky Diabetes Endocrinology Center	Lexington	Kentucky
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	Louisville Metabolic and Atherosclerosis Research Center (L-MARC)	Louisville	Kentucky
United States	Manassas Clinical Research Center	Manassas	Virginia
United States	RAS Health LTD	Marion	Ohio
United States	Clinical Neuroscience Solutions, Inc. - Memphis	Memphis	Tennessee
United States	Clinical Pharmacology of Miami, Inc.	Miami	Florida
United States	Internal Research Associates LLC - Breton	Miami	Florida
United States	Tellus Clinical Research, Inc.	Miami	Florida
United States	Catalina Research Institute	Montclair	California
United States	PMG of Charleston, LLC	Mount Pleasant	South Carolina
United States	Family Medicine of SayeBrook, LLC	Myrtle Beach	South Carolina
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	COR Clinical Research, LLC	Oklahoma City	Oklahoma
United States	Heartland Clinical Research	Omaha	Nebraska
United States	Quality Clinical Research, Inc.	Omaha	Nebraska
United States	SDS Clinical Trials, Inc.	Orange	California
United States	Clinical Neuroscience Solutions, Inc. Healthcare Orlando	Orlando	Florida
United States	Ormond Medical Arts Pharmaceutical Research Center	Ormond Beach	Florida
United States	MD Medical Research	Oxon Hill	Maryland
United States	Four Rivers Clinical Research	Paducah	Kentucky
United States	Private Practice - Andres Patron, DO	Pembroke Pines	Florida
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	Planters Clinic	Port Gibson	Mississippi
United States	Progressive Medical Research	Port Orange	Florida
United States	Beacon Clinical Research	Quincy	Massachusetts
United States	Clinical Research Partners, LLC	Richmond	Virginia
United States	PMG Research of Rocky Mount	Rocky Mount	North Carolina
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	Chrysalis Clinical Research	Saint George	Utah
United States	Meridien Reserach - St. Petersburg	Saint Petersburg	Florida
United States	PMG Research of Salisbury, LLC	Salisbury	North Carolina
United States	Sun Research Institute	San Antonio	Texas
United States	Texas Diabetes Institute Research Center	San Antonio	Texas
United States	Victorium Clinical Research	San Antonio	Texas
United States	Syrentis Clinical Research (formerly Research Across America)	Santa Ana	California
United States	Searcy Medical Center	Searcy	Arkansas
United States	Consano Clinical Research	Shavano Park	Texas
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	Encompass Clinical Research	Spring Valley	California
United States	Summit Reserach Group, LLC	Stow	Ohio
United States	Southwest Health Associates, P.A.	Sugar Land	Texas
United States	Palmetto Clinical Research	Summerville	South Carolina
United States	Clinical Research Institute of Arizona, LLC	Surprise	Arizona
United States	Universal Research Group, LLC	Tacoma	Washington
United States	Clinical Reserch Trials of Florida	Tampa	Florida
United States	Meridien Research - Tampa	Tampa	Florida
United States	Cotton-O'Neil Clinical Research Center	Topeka	Kansas
United States	Trinity Clinical Research	Tullahoma	Tennessee
United States	Terence T. Hart, MD	Tuscumbia	Alabama
United States	Clinical Trial Investigators	Tustin	California
United States	Buynak Clinical Research, PC	Valparaiso	Indiana
United States	Infosphere Clinical Research	Van Nuys	California
United States	The Iowa Clinic; Cardiovascular Services	West Des Moines	Iowa
United States	Metabolic Research Institute, Inc.	West Palm Beach	Florida
United States	Great Lakes Medical Research	Westfield	New York
United States	PMG Research of Wilmington, LLC	Wilmington	North Carolina

Sponsors (1)

Lead Sponsor	Collaborator
Elcelyx Therapeutics, Inc.

Countries where clinical trial is conducted

United States,  Puerto Rico, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change in HbA1c (%) at 16 Weeks		Baseline and 16 weeks after the first dose of study medication