Clinical trial NCT02526524: Dose-Ranging Study to Evaluate the Glycemic Effects, Safety, and Tolerability of Metformin Delayed Release in Subjects With T2DM
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Type 2 Diabetes Mellitus
Lead sponsor: Elcelyx Therapeutics, Inc.
Sponsor class: INDUSTRY
First posted: 2015-08-18
Enrollment: 571
Sex: ALL
Minimum age (years): 25
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


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.

Primary outcomes:
measure: Change in HbA1c (%) at 16 Weeks
timeFrame: Baseline and 16 weeks after the first dose of study medication
Secondary outcomes:
Other outcomes:
Locations:
city: Anniston
country: United States
facility: Pinnacle Research Group, LLC
state: Alabama
city: Birmingham
country: United States
facility: Central Alabama Research
state: Alabama
city: Birmingham
country: United States
facility: Achieve Clinical Research, LLC
state: Alabama
city: Birmingham
country: United States
facility: University of Alabama at Birmingham
state: Alabama
city: Tuscumbia
country: United States
facility: Terence T. Hart, MD
state: Alabama
city: Chandler
country: United States
facility: Radiant Research - Phoenix
state: Arizona
city: Glendale
country: United States
facility: Arrowhead Health Centers
state: Arizona
city: Peoria
country: United States
facility: Holland Center for Family Health, LTD
state: Arizona
city: Phoenix
country: United States
facility: Elite Clinical Studies
state: Arizona
city: Phoenix
country: United States
facility: Thunderbird Internal Medicine - Indian School Rd.
state: Arizona
city: Surprise
country: United States
facility: Clinical Research Institute of Arizona, LLC
state: Arizona
city: Fayetteville
country: United States
facility: Summit Clinical Trials Center
state: Arkansas
city: Searcy
country: United States
facility: Searcy Medical Center
state: Arkansas
city: Escondido
country: United States
facility: Advanced Metabolic Care & Research Institute (AMCR)
state: California
city: Fountain Valley
country: United States
facility: MD Studies, Inc.
state: California
city: Huntington Park
country: United States
facility: National Research Institute
state: California
city: La Jolla
country: United States
facility: Scripps Whittier Diabetes Institute
state: California
city: Lincoln
country: United States
facility: Clinical Trials Research
state: California
city: Long Beach
country: United States
facility: Collaborative Neuroscience Network, LLC
state: California
city: Los Angeles
country: United States
facility: National Research Institute
state: California
city: Montclair
country: United States
facility: Catalina Research Institute
state: California
city: National City
country: United States
facility: SRSD, Inc. dba Synergy San Diego
state: California
city: North Hollywood
country: United States
facility: Providence Clinical Research
state: California
city: Oakland
country: United States
facility: Pacific Research Partners, LLC
state: California
city: Orange
country: United States
facility: SDS Clinical Trials, Inc.
state: California
city: Sacramento
country: United States
facility: Center for Clinical Trials of Sacramento
state: California
city: Sacramento
country: United States
facility: Center for Clinical Trials of Scaramento
state: California
city: Sacramento
country: United States
facility: Superior Research LLC
state: California
city: Santa Ana
country: United States
facility: Syrentis Clinical Research (formerly Research Across America)
state: California
city: Spring Valley
country: United States
facility: Encompass Clinical Research
state: California
city: Tustin
country: United States
facility: Clinical Trial Investigators
state: California
city: Van Nuys
country: United States
facility: Infosphere Clinical Research
state: California
city: Colorado Springs
country: United States
facility: Colorado Springs Health Partners
state: Colorado
city: Denver
country: United States
facility: Creekside Endocrine Associates
state: Colorado
city: Brooksville
country: United States
facility: Meridien Research - Brooksville
state: Florida
city: Cooper City
country: United States
facility: ALL Medical Research, LLC
state: Florida
city: Hialeah
country: United States
facility: Neostart Corporation dba AGA Clinical Trials
state: Florida
city: Jacksonville
country: United States
facility: Care Partners Clinical Research
state: Florida
city: Jupiter
country: United States
facility: Health Awareness, Inc.
state: Florida
city: Kissimmee
country: United States
facility: Family Health Care Clinical Studies
state: Florida
city: Lakeland
country: United States
facility: Clinical Research of Central Florida-Lakeland
state: Florida
city: Miami
country: United States
facility: Clinical Pharmacology of Miami, Inc.
state: Florida
city: Miami
country: United States
facility: Tellus Clinical Research, Inc.
state: Florida
city: Miami
country: United States
facility: Internal Research Associates LLC - Breton
state: Florida
city: Orlando
country: United States
facility: Clinical Neuroscience Solutions, Inc. Healthcare Orlando
state: Florida
city: Ormond Beach
country: United States
facility: Ormond Medical Arts Pharmaceutical Research Center
state: Florida
city: Pembroke Pines
country: United States
facility: Private Practice - Andres Patron, DO
state: Florida
city: Port Orange
country: United States
facility: Progressive Medical Research
state: Florida
city: Saint Petersburg
country: United States
facility: Meridien Reserach - St. Petersburg
state: Florida
city: Tampa
country: United States
facility: Clinical Reserch Trials of Florida
state: Florida
city: Tampa
country: United States
facility: Meridien Research - Tampa
state: Florida
city: West Palm Beach
country: United States
facility: Metabolic Research Institute, Inc.
state: Florida
city: Addison
country: United States
facility: Biofortis, Inc.
state: Illinois
city: Aurora
country: United States
facility: AMR Sakeena Research
state: Illinois
city: Chicago
country: United States
facility: Cedar-Crosse Research Center
state: Illinois
city: Evanston
country: United States
facility: Evanston Premier Healthcare Research LLC
state: Illinois
city: Valparaiso
country: United States
facility: Buynak Clinical Research, PC
state: Indiana
city: West Des Moines
country: United States
facility: The Iowa Clinic; Cardiovascular Services
state: Iowa
city: Augusta
country: United States
facility: Heartland Research Associates, LLC - Augusta
state: Kansas
city: Topeka
country: United States
facility: Cotton-O'Neil Clinical Research Center
state: Kansas
city: Edgewood
country: United States
facility: Otrimed
state: Kentucky
city: Lexington
country: United States
facility: Kentucky Diabetes Endocrinology Center
state: Kentucky
city: Louisville
country: United States
facility: Louisville Metabolic and Atherosclerosis Research Center (L-MARC)
state: Kentucky
city: Paducah
country: United States
facility: Four Rivers Clinical Research
state: Kentucky
city: Crowley
country: United States
facility: Avant Research Associates
state: Louisiana
city: Lake Charles
country: United States
facility: Centex Studies, Inc. - lake Charles
state: Louisiana
city: Columbia
country: United States
facility: Columbia Medical Practice
state: Maryland
city: Hyattsville
country: United States
facility: Medstar Health Research Institute
state: Maryland
city: Oxon Hill
country: United States
facility: MD Medical Research
state: Maryland
city: Quincy
country: United States
facility: Beacon Clinical Research
state: Massachusetts
city: Edina
country: United States
facility: Radiant Research - Edina
state: Minnesota
city: Port Gibson
country: United States
facility: Planters Clinic
state: Mississippi
city: Butte
country: United States
facility: Mercury Street Medical Group, PLLC
state: Montana
city: Omaha
country: United States
facility: Quality Clinical Research, Inc.
state: Nebraska
city: Omaha
country: United States
facility: Heartland Clinical Research
state: Nebraska
city: Las Vegas
country: United States
facility: Alliance Against Diabetes
state: Nevada
city: Las Vegas
country: United States
facility: AB Clinical Trials
state: Nevada
city: Las Vegas
country: United States
facility: Palm Medical Research
state: Nevada
city: Las Vegas
country: United States
facility: Ingham Neuroscience Group, LLC
state: Nevada
city: Berlin
country: United States
facility: Comprehensive Clinical Research
state: New Jersey
city: Albuquerque
country: United States
facility: Albuquerque Clinical Trials
state: New Mexico
city: Albuquerque
country: United States
facility: Albuquerque Neuroscience, Inc.
state: New Mexico
city: Brooklyn
country: United States
facility: NY Scientific
state: New York
city: Great Neck
country: United States
facility: Long Island Gastrointestinal Research Group
state: New York
city: Hopewell Junction
country: United States
facility: Mid-Hudson Medical Research, PLLC
state: New York
city: Westfield
country: United States
facility: Great Lakes Medical Research
state: New York
city: Greensboro
country: United States
facility: PharmQuest
state: North Carolina
city: Greensboro
country: United States
facility: Triad Clinical Trials LLC
state: North Carolina
city: Rocky Mount
country: United States
facility: PMG Research of Rocky Mount
state: North Carolina
city: Salisbury
country: United States
facility: PMG Research of Salisbury, LLC
state: North Carolina
city: Wilmington
country: United States
facility: PMG Research of Wilmington, LLC
state: North Carolina
city: Cincinnati
country: United States
facility: Sterling Research Group, Ltd
state: Ohio
city: Cincinnati
country: United States
facility: Metabolic Atherosclerosis Research Center
state: Ohio
city: Cincinnati
country: United States
facility: New Horizons Clinical Research
state: Ohio
city: Columbus
country: United States
facility: Urgent Care Specialists, LLC DBA Hometown Urgent Care and Occupational Health
state: Ohio
city: Franklin
country: United States
facility: Prestige Clinical Research
state: Ohio
city: Huber Heights
country: United States
facility: Hometown Urgent Care and Research - Huber Heights
state: Ohio
city: Marion
country: United States
facility: RAS Health LTD
state: Ohio
city: Stow
country: United States
facility: Summit Reserach Group, LLC
state: Ohio
city: Oklahoma City
country: United States
facility: COR Clinical Research, LLC
state: Oklahoma
city: Eugene
country: United States
facility: Willamette Valley Clinical Studies
state: Oregon
city: Downingtown
country: United States
facility: Brandywine Clinical Research
state: Pennsylvania
city: Charleston
country: United States
facility: Medical Research South, LLC
state: South Carolina
city: Greer
country: United States
facility: Mountain View Clinical Research - Greer
state: South Carolina
city: Mount Pleasant
country: United States
facility: PMG of Charleston, LLC
state: South Carolina
city: Myrtle Beach
country: United States
facility: Family Medicine of SayeBrook, LLC
state: South Carolina
city: Simpsonville
country: United States
facility: Hillcrest Clinical Research, LLC
state: South Carolina
city: Spartanburg
country: United States
facility: Palmetto Proactive Healthcare, LLC
state: South Carolina
city: Spartanburg
country: United States
facility: Spartanburg Medical Research
state: South Carolina
city: Summerville
country: United States
facility: Palmetto Clinical Research
state: South Carolina
city: Bristol
country: United States
facility: PMG Research of Bristol, LC - State
state: Tennessee
city: Knoxville
country: United States
facility: PMG Research of Knoxville
state: Tennessee
city: Memphis
country: United States
facility: Clinical Neuroscience Solutions, Inc. - Memphis
state: Tennessee
city: Tullahoma
country: United States
facility: Trinity Clinical Research
state: Tennessee
city: Austin
country: United States
facility: Central Texas Clinical Research
state: Texas
city: Carrollton
country: United States
facility: Trinity Universal Research Associates, Inc.
state: Texas
city: Dallas
country: United States
facility: Dallas Diabetes and Endocrine Center
state: Texas
city: Dallas
country: United States
facility: Research Institute of Dallas
state: Texas
city: Dallas
country: United States
facility: Galenos Research
state: Texas
city: Houston
country: United States
facility: Pioneer Research Solutions, Inc.
state: Texas
city: Houston
country: United States
facility: Centex Studies, Inc.
state: Texas
city: Houston
country: United States
facility: Clinical Trial Network - Houston
state: Texas
city: Houston
country: United States
facility: Juno Research, LLC-Houston
state: Texas
city: Katy
country: United States
facility: Juno Research, LLC-Katy
state: Texas
city: San Antonio
country: United States
facility: Texas Diabetes Institute Research Center
state: Texas
city: San Antonio
country: United States
facility: Sun Research Institute
state: Texas
city: San Antonio
country: United States
facility: Victorium Clinical Research
state: Texas
city: Shavano Park
country: United States
facility: Consano Clinical Research
state: Texas
city: Sugar Land
country: United States
facility: Southwest Health Associates, P.A.
state: Texas
city: Saint George
country: United States
facility: Chrysalis Clinical Research
state: Utah
city: Burke
country: United States
facility: Burke Internal Medicine & Research
state: Virginia
city: Manassas
country: United States
facility: Manassas Clinical Research Center
state: Virginia
city: Richmond
country: United States
facility: Clinical Research Partners, LLC
state: Virginia
city: Tacoma
country: United States
facility: Universal Research Group, LLC
state: Washington
city: Carolina
country: Puerto Rico
facility: Puerto Rico Renal and Health Research, Inc.
city: Cidra
country: Puerto Rico
facility: Advanced Medical Concepts
city: Manati
country: Puerto Rico
facility: Manati Center for Clinical Reserach Doctor's Center Hospital
Study officials:
affiliation: National Research Institute - Wilshire
name: Juan P Frias, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.