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

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

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.

Study Overview

• Status: Completed
• Conditions: Type 2 Diabetes Mellitus
• Intervention / Treatment: Drug: Placebo; Drug: Met DR; Drug: Met IR

• Study Type: Interventional
• Enrollment (Actual): 571
• Phase: Phase 2

Contacts and Locations

Study Locations

• Puerto Rico
  • Carolina, Puerto Rico, 00987
    • Puerto Rico Renal and Health Research, Inc.
  • Cidra, Puerto Rico, 00736
    • Advanced Medical Concepts
  • Manati, Puerto Rico, 00674
    • Manati Center for Clinical Reserach Doctor's Center Hospital
• United States
  • Alabama
    • Anniston, Alabama, United States, 36207
      • Pinnacle Research Group, LLC
    • Birmingham, Alabama, United States, 35294
      • University of Alabama at Birmingham
    • Birmingham, Alabama, United States, 35216
      • Achieve Clinical Research, LLC
    • Birmingham, Alabama, United States, 35209
      • Central Alabama Research
    • Tuscumbia, Alabama, United States, 35674
      • Terence T. Hart, MD
  • Arizona
    • Chandler, Arizona, United States, 85224
      • Radiant Research - Phoenix
    • Glendale, Arizona, United States, 85306
      • Arrowhead Health Centers
    • Peoria, Arizona, United States, 85381
      • Holland Center for Family Health, LTD
    • Phoenix, Arizona, United States, 85018
      • Elite Clinical Studies
    • Phoenix, Arizona, United States, 85037
      • Thunderbird Internal Medicine - Indian School Rd.
    • Surprise, Arizona, United States, 85374
      • Clinical Research Institute of Arizona, LLC
  • Arkansas
    • Fayetteville, Arkansas, United States, 72703
      • Summit Clinical Trials Center
    • Searcy, Arkansas, United States, 72143
      • Searcy Medical Center
  • California
    • Escondido, California, United States, 92025
      • Advanced Metabolic Care & Research Institute (AMCR)
    • Fountain Valley, California, United States, 92708
      • MD Studies, Inc.
    • Huntington Park, California, United States, 90255
      • National Research Institute
    • La Jolla, California, United States, 92037
      • Scripps Whittier Diabetes Institute
    • Lincoln, California, United States, 95648
      • Clinical Trials Research
    • Long Beach, California, United States, 90806
      • Collaborative Neuroscience Network, LLC
    • Los Angeles, California, United States, 90057
      • National Research Institute
    • Montclair, California, United States, 91763
      • Catalina Research Institute
    • National City, California, United States, 91950
      • SRSD, Inc. dba Synergy San Diego
    • North Hollywood, California, United States, 91606
      • Providence Clinical Research
    • Oakland, California, United States, 94607
      • Pacific Research Partners, LLC
    • Orange, California, United States, 92868
      • SDS Clinical Trials, Inc.
    • Sacramento, California, United States, 95825
      • Superior Research LLC
    • Sacramento, California, United States, 95823
      • Center for Clinical Trials of Sacramento
    • Sacramento, California, United States, 95823
      • Center for Clinical Trials of Scaramento
    • Santa Ana, California, United States, 92705
      • Syrentis Clinical Research (formerly Research Across America)
    • Spring Valley, California, United States, 91978
      • Encompass Clinical Research
    • Tustin, California, United States, 92780
      • Clinical Trial Investigators
    • Van Nuys, California, United States, 91405
      • Infosphere Clinical Research
  • Colorado
    • Colorado Springs, Colorado, United States, 80906
      • Colorado Springs Health Partners
    • Denver, Colorado, United States, 80209
      • Creekside Endocrine Associates
  • Florida
    • Brooksville, Florida, United States, 34601
      • Meridien Research - Brooksville
    • Cooper City, Florida, United States, 33024
      • ALL Medical Research, LLC
    • Hialeah, Florida, United States, 33012
      • Neostart Corporation dba AGA Clinical Trials
    • Jacksonville, Florida, United States, 32277
      • Care Partners Clinical Research
    • Jupiter, Florida, United States, 33458
      • Health Awareness, Inc.
    • Kissimmee, Florida, United States, 34741
      • Family Health Care Clinical Studies
    • Lakeland, Florida, United States, 33810
      • Clinical Research of Central Florida-Lakeland
    • Miami, Florida, United States, 33014
      • Clinical Pharmacology of Miami, Inc.
    • Miami, Florida, United States, 33173
      • Tellus Clinical Research, Inc.
    • Miami, Florida, United States, 33183
      • Internal Research Associates LLC - Breton
    • Orlando, Florida, United States, 32801
      • Clinical Neuroscience Solutions, Inc. Healthcare Orlando
    • Ormond Beach, Florida, United States, 32174
      • Ormond Medical Arts Pharmaceutical Research Center
    • Pembroke Pines, Florida, United States, 33026
      • Private Practice - Andres Patron, DO
    • Port Orange, Florida, United States, 32127
      • Progressive Medical Research
    • Saint Petersburg, Florida, United States, 33709
      • Meridien Reserach - St. Petersburg
    • Tampa, Florida, United States, 33634
      • Meridien Research - Tampa
    • Tampa, Florida, United States, 33607
      • Clinical Reserch Trials of Florida
    • West Palm Beach, Florida, United States, 33401
      • Metabolic Research Institute, Inc.
  • Illinois
    • Addison, Illinois, United States, 60101
      • Biofortis, Inc.
    • Aurora, Illinois, United States, 60506
      • AMR Sakeena Research
    • Chicago, Illinois, United States, 60607
      • Cedar-Crosse Research Center
    • Evanston, Illinois, United States, 60201
      • Evanston Premier Healthcare Research LLC
  • Indiana
    • Valparaiso, Indiana, United States, 46383
      • Buynak Clinical Research, PC
  • Iowa
    • West Des Moines, Iowa, United States, 50266
      • The Iowa Clinic; Cardiovascular Services
  • Kansas
    • Augusta, Kansas, United States, 67010
      • Heartland Research Associates, LLC - Augusta
    • Topeka, Kansas, United States, 66606
      • Cotton-O'Neil Clinical Research Center
  • Kentucky
    • Edgewood, Kentucky, United States, 41017
      • Otrimed
    • Lexington, Kentucky, United States, 40503
      • Kentucky Diabetes Endocrinology Center
    • Louisville, Kentucky, United States, 40213
      • Louisville Metabolic and Atherosclerosis Research Center (L-MARC)
    • Paducah, Kentucky, United States, 42003
      • Four Rivers Clinical Research
  • Louisiana
    • Crowley, Louisiana, United States, 70526
      • Avant Research Associates
    • Lake Charles, Louisiana, United States, 70601
      • Centex Studies, Inc. - Lake Charles
  • Maryland
    • Columbia, Maryland, United States, 21045
      • Columbia Medical Practice
    • Hyattsville, Maryland, United States, 20782
      • Medstar Health Research Institute
    • Oxon Hill, Maryland, United States, 20745
      • MD Medical Research
  • Massachusetts
    • Quincy, Massachusetts, United States, 02169
      • Beacon Clinical Research
  • Minnesota
    • Edina, Minnesota, United States, 55435
      • Radiant Research - Edina
  • Mississippi
    • Port Gibson, Mississippi, United States, 39150
      • Planters Clinic
  • Montana
    • Butte, Montana, United States, 59701
      • Mercury Street Medical Group, PLLC
  • Nebraska
    • Omaha, Nebraska, United States, 68114
      • Quality Clinical Research, Inc.
    • Omaha, Nebraska, United States, 68134
      • Heartland Clinical Research
  • Nevada
    • Las Vegas, Nevada, United States, 89119
      • AB Clinical Trials
    • Las Vegas, Nevada, United States, 89101
      • Alliance Against Diabetes
    • Las Vegas, Nevada, United States, 89128
      • Palm Medical Research
    • Las Vegas, Nevada, United States, 89146
      • Ingham Neuroscience Group, LLC
  • New Jersey
    • Berlin, New Jersey, United States, 08009
      • Comprehensive Clinical Research
  • New Mexico
    • Albuquerque, New Mexico, United States, 87109
      • Albuquerque Neuroscience, Inc.
    • Albuquerque, New Mexico, United States, 87102
      • Albuquerque Clinical Trials
  • New York
    • Brooklyn, New York, United States, 11235
      • NY Scientific
    • Great Neck, New York, United States, 11023
      • Long Island Gastrointestinal Research Group
    • Hopewell Junction, New York, United States, 12533
      • Mid-Hudson Medical Research, PLLC
    • Westfield, New York, United States, 14787
      • Great Lakes Medical Research
  • North Carolina
    • Greensboro, North Carolina, United States, 27408
      • PharmQuest
    • Greensboro, North Carolina, United States, 27410
      • Triad Clinical Trials LLC
    • Rocky Mount, North Carolina, United States, 27804
      • PMG Research of Rocky Mount
    • Salisbury, North Carolina, United States, 28144
      • PMG Research of Salisbury, LLC
    • Wilmington, North Carolina, United States, 28401
      • PMG Research of Wilmington, LLC
  • Ohio
    • Cincinnati, Ohio, United States, 45242
      • New Horizons Clinical Research
    • Cincinnati, Ohio, United States, 45219
      • Sterling Research Group, Ltd
    • Cincinnati, Ohio, United States, 45227
      • Metabolic Atherosclerosis Research Center
    • Columbus, Ohio, United States, 43214
      • Urgent Care Specialists, LLC DBA Hometown Urgent Care and Occupational Health
    • Franklin, Ohio, United States, 45005
      • Prestige Clinical Research
    • Huber Heights, Ohio, United States, 45424
      • Hometown Urgent Care and Research - Huber Heights
    • Marion, Ohio, United States, 43302
      • RAS Health LTD
    • Stow, Ohio, United States, 44224
      • Summit Reserach Group, LLC
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73103
      • COR Clinical Research, LLC
  • Oregon
    • Eugene, Oregon, United States, 97404
      • Willamette Valley Clinical Studies
  • Pennsylvania
    • Downingtown, Pennsylvania, United States, 19335
      • Brandywine Clinical Research
  • South Carolina
    • Charleston, South Carolina, United States, 29407
      • Medical Research South, LLC
    • Greer, South Carolina, United States, 29651
      • Mountain View CLinical Research - Greer
    • Mount Pleasant, South Carolina, United States, 29464
      • PMG of Charleston, LLC
    • Myrtle Beach, South Carolina, United States, 29588
      • Family Medicine of SayeBrook, LLC
    • Simpsonville, South Carolina, United States, 29681
      • Hillcrest Clinical Research, LLC
    • Spartanburg, South Carolina, United States, 29303
      • Spartanburg Medical Research
    • Spartanburg, South Carolina, United States, 29301
      • Palmetto Proactive Healthcare, LLC
    • Summerville, South Carolina, United States, 29485
      • Palmetto Clinical Research
  • Tennessee
    • Bristol, Tennessee, United States, 37620
      • PMG Research of Bristol, LC - State
    • Knoxville, Tennessee, United States, 37912
      • PMG Research of Knoxville
    • Memphis, Tennessee, United States, 38119
      • Clinical Neuroscience Solutions, Inc. - Memphis
    • Tullahoma, Tennessee, United States, 37388
      • Trinity Clinical Research
  • Texas
    • Austin, Texas, United States, 78705
      • Central Texas Clinical Research
    • Carrollton, Texas, United States, 75007
      • Trinity Universal Research Associates, Inc.
    • Dallas, Texas, United States, 75230
      • Dallas Diabetes and Endocrine Center
    • Dallas, Texas, United States, 75231
      • Research Institute of Dallas
    • Dallas, Texas, United States, 75251
      • Galenos Research
    • Houston, Texas, United States, 77058
      • Centex Studies, Inc.
    • Houston, Texas, United States, 77036
      • Pioneer Research Solutions, Inc.
    • Houston, Texas, United States, 77074
      • Clinical Trial Network - Houston
    • Houston, Texas, United States, 77074
      • Juno Research, LLC-Houston
    • Katy, Texas, United States, 77450
      • Juno Research, LLC-Katy
    • San Antonio, Texas, United States, 78215
      • Sun Research Institute
    • San Antonio, Texas, United States, 78231
      • Victorium Clinical Research
    • San Antonio, Texas, United States, 78207
      • Texas Diabetes Institute Research Center
    • Shavano Park, Texas, United States, 78231
      • Consano Clinical Research
    • Sugar Land, Texas, United States, 77478
      • Southwest Health Associates, P.A.
  • Utah
    • Saint George, Utah, United States, 84790
      • Chrysalis Clinical Research
  • Virginia
    • Burke, Virginia, United States, 22015
      • Burke Internal Medicine & Research
    • Manassas, Virginia, United States, 20110
      • Manassas Clinical Research Center
    • Richmond, Virginia, United States, 23235
      • Clinical Research Partners, LLC
  • Washington
    • Tacoma, Washington, United States, 98405
      • Universal Research Group, LLC

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 25 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

7

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 600 mg Met DR qAM; 600 mg metformin delayed-release once daily in the morning	Drug: Met DR; metformin delayed-release tablets
Experimental: 900 mg Met DR qAM; 900 mg metformin delayed-release once daily in the morning	Drug: Met DR; metformin delayed-release tablets
Experimental: 1200 mg Met DR qAM; 1200 mg metformin delayed-release once daily in the morning	Drug: Met DR; metformin delayed-release tablets
Experimental: 1500 mg Met DR qAM; 1500 mg metformin delayed-release once daily in the morning	Drug: Met DR; metformin delayed-release tablets
Placebo Comparator: Placebo-1; placebo match for 600 and 1200 mg Met DR qAM treatment groups	Drug: Placebo
Placebo Comparator: Placebo-2; placebo match for 900 and 1500 mg Met DR qAM treatment groups	Drug: Placebo
Active Comparator: 2000 mg Met IR; 1000 mg metformin immediate-release twice daily	Drug: Met IR; metformin immediate-release tablets

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Change in HbA1c (%) at 16 Weeks	Baseline and 16 weeks after the first dose of study medication

Collaborators and Investigators

• Sponsor: Elcelyx Therapeutics, Inc.
• Investigators: Principal Investigator: Juan P Frias, MD, National Research Institute - Wilshire

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start: September 1, 2015
• Primary Completion (Actual): September 1, 2016
• Study Completion (Actual): September 1, 2016

Study Registration Dates

• First Submitted: August 16, 2015
• First Submitted That Met QC Criteria: August 17, 2015
• First Posted (Estimate): August 18, 2015

Study Record Updates

• Last Update Posted (Actual): April 27, 2018
• Last Update Submitted That Met QC Criteria: March 27, 2018
• Last Verified: March 1, 2018

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases; Diabetes Mellitus; Diabetes Mellitus, Type 2
• Other Study ID Numbers: LCRM112