Assessing the Efficacy, Safety, and Tolerability of Met DR in Subjects With T2DM Over 12 Weeks
Condition: Type 2 Diabetes Mellitus
MeSH terms: Diabetes Mellitus; Diabetes Mellitus, Type 2
Intervention: Met DR; Met XR; Placebo
Intervention description: metformin delayed-release tablets; metformin extended-release tablets; placebo delayed-release tablets
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 240.0
Sex: All
Minimum age: 18 Years
Maximum age: 65 Years
Healthy volunteers: No

Summary:

      This study compared the effect of delayed-release metformin (Met DR) to placebo and extended
      release metformin (Met XR) on glycemic control (fasting plasma glucose and HbA1c) and body
      weight, and assessed the safety and tolerability of a range of doses of Met DR when
      administered in subjects with type 2 diabetes mellitus (T2DM).
    

Eligibility criteria:

        Inclusion Criteria:

          1. Male or female with T2DM who was ≥18 and ≤65 years of age at Visit 1

          2. Had a body mass index (BMI) of 25.0 kg/m² to 45.0 kg/m², inclusive, at Visit 1

          3. Screening HbA1c 7.0 to 9.5% (inclusive) at Visit 1 if treated with diet and exercise
             alone, or 6.0 to 9.5% (inclusive) if on a stable dose of either metformin or DPP-4
             inhibitor monotherapy for a minimum of 2 months at Visit 1, or a combination of these
             2 agents only on a stable regimen for a minimum of 2 months at Visit 1

          4. Had serum creatinine concentration of <1.5 mg/dL (male) or <1.4 mg/dL (female) and an
             estimated glomerular filtration rate (eGFR) of ≥60 mL/min/1.73 m² based on the
             Modification of Diet in Renal Disease (MDRD) equation

          5. Had a fasting glucose concentration of <280 mg/dL at Visit 1

          6. Had a stable body weight, i.e., not varying by >5% for at least 6 months prior to
             Visit 1 as documented by the investigator

          7. Was male, or if female and met all of the following criteria:

               1. Not breastfeeding

               2. Negative pregnancy test result (human chorionic gonadotropin, beta subunit
                  [βhCG]) at Visit 1 (not applicable to hysterectomized females)

               3. If of child bearing potential (including perimenopausal women who have had a
                  menstrual period within 1 year), must have practiced and be willing to continue
                  to practice appropriate birth control during the entire duration of the study

          8. Had a physical examination and ECG with no clinically significant abnormalities as
             judged by the investigator at Visit 1

          9. Had no clinically significant laboratory test values (clinical chemistry, hematology,
             urinalysis) other than those expected in subjects with diabetes as judged by the
             investigator at Visit 1

         10. Either was not treated with or had been on a stable treatment regimen with any of the
             following medications for a minimum of 2 months prior to Visit 1:

               1. Hormone replacement therapy (female subjects)

               2. Oral contraceptives (female subjects)

               3. Antihypertensive agents

               4. Lipid-lowering agents

               5. Thyroid replacement therapy

               6. Antidepressant agents

               7. Testosterone therapy (male subjects)

         11. If on chronic thyroid pharmacologic therapy, had a serum thyroid-stimulating hormone
             test result within the normal range at Visit 1

         12. Was willing and able to follow study procedures

         13. Was able to read, understand, and sign the Informed Consent Form and an Authorization
             to Use and Disclose Protected Health Information form, answer the study questions,
             communicate with the investigator, and understand and comply with protocol
             requirements

        Exclusion Criteria:

          1. Had a clinically significant medical condition that could potentially affect study
             participation and/or personal well-being, as judged by the investigator, including but
             not limited to the following conditions:

               1. Hepatic disease

               2. Renal disease

               3. Gastrointestinal disease

               4. Endocrine disorder except T2DM

               5. Cardiovascular disease

               6. Central nervous system diseases

               7. Psychiatric or neurological disorders

               8. Organ transplantation

               9. Chronic or acute infection (e.g., tuberculosis, human immunodeficiency virus,
                  hepatitis B virus, or hepatitis C virus)

              10. Orthostatic hypotension, fainting spells or blackouts

              11. Allergy or hypersensitivity

          2. Clinically significant malignant disease (with the exception of basal and squamous
             cell carcinoma of the skin) within 5 years of Visit 1

          3. Had known hypersensitivity, intolerability, or allergies to metformin HCl or any
             component of study treatment

          4. Had a physical, psychological, or historical finding that, in the investigator's
             opinion, would make the subject unsuitable for the study

          5. Current drugs or alcohol abuse or had a history of abuse that in the investigator's
             opinion would cause the individual to be noncompliant with study procedures

          6. Had major surgery or a blood transfusion within 2 months of Visit 1 or was planning to
             donate blood during the study, or had a significant blood loss within 2 months prior
             to Visit 1

          7. Had been treated, was being treated, or was expected to require or undergo treatment
             with any of the following excluded medications:

               1. Insulin or sulphonylurea treatment within 3 months of Visit 1

               2. GLP-1 receptor agonists and/or thiazolidinedione treatment within 6 months of
                  Visit 1

               3. Nifedipine within 3 months of Visit 1

               4. Systemic corticosteroids by oral, intravenous, intra-articular, or intra-muscular
                  route within 30 days of screening or for more than 1 week within 3 months of
                  Visit 1

               5. Prescription weight loss medications within 3 months of Visit 1

               6. Chronic or frequent use, in the judgment of the investigator, of any drug
                  treatment that affects gastric pH (prescription or over-the-counter), including
                  proton pump inhibitors or any antacids or medications such as Rolaids or Pepcid
                  within 1 month of Visit 1

               7. Had received or planned to receive any iodinated contrast dye within 1 week prior
                  to Visit 1 (Screening)

          8. Had a surgical gastrointestinal procedure that may impact the gut hormonal response to
             study medication

          9. History or presence of inflammatory bowel disease or other severe gastrointestinal
             disease, particularly those which may impact gastric emptying, such as gastroparesis,
             pyloric stenosis, gastric bypass surgery or gastric banding surgery

         10. Had received any investigational drug within 30 days (or five half-lives of the
             investigational drug, whichever was greater) of Visit 1

         11. Was an immediate family member (spouse, parent, child, or sibling; biological or
             legally adopted) of personnel directly affiliated with the study at the clinical study
             site, or was directly affiliated with the study at the clinical study site

         12. Was employed by Elcelyx Therapeutics, Inc. (that is an employee, temporary contract
             worker, or designee responsible for the conduct of the study)