Title

Assessing the Efficacy, Safety, and Tolerability of Met DR in Subjects With T2DM Over 12 Weeks
A 12-Week, Randomized, Double-Blind, Placebo-Controlled, Parallel-Group, Multicenter Study to Assess the Efficacy, Safety, and Tolerability of Delayed-Release Metformin in Subjects With Type 2 Diabetes Mellitus
  • Phase

    Phase 2
  • Study Type

    Interventional
  • Intervention/Treatment

    sitagliptin ...
  • Study Participants

    240
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).
Study Started
Apr 30
2013
Primary Completion
Sep 30
2013
Study Completion
Sep 30
2013
Results Posted
Sep 21
2015
Estimate
Last Update
Mar 15
2017

Drug Met DR

metformin delayed-release tablets

Drug Met XR

metformin extended-release tablets

Drug Placebo

placebo delayed-release tablets

1000 mg XR Active Comparator

1000 mg extended-release metformin once daily in the evening

2000 mg XR Active Comparator

2000 mg extended-release metformin once daily in the evening

Placebo Placebo Comparator

Placebo once daily in the morning

1000 mg DR Experimental

1000 mg delayed-release metformin once daily in the morning

600 mg DR Experimental

600 mg delayed-release metformin once daily in the morning

800 mg DR Experimental

800 mg delayed-release metformin once daily in the morning

Criteria

Inclusion Criteria:

Male or female with T2DM who was ≥18 and ≤65 years of age at Visit 1
Had a body mass index (BMI) of 25.0 kg/m² to 45.0 kg/m², inclusive, at Visit 1
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
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
Had a fasting glucose concentration of <280 mg/dL at Visit 1
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

Was male, or if female and met all of the following criteria:

Not breastfeeding
Negative pregnancy test result (human chorionic gonadotropin, beta subunit [βhCG]) at Visit 1 (not applicable to hysterectomized females)
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
Had a physical examination and ECG with no clinically significant abnormalities as judged by the investigator at Visit 1
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

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:

Hormone replacement therapy (female subjects)
Oral contraceptives (female subjects)
Antihypertensive agents
Lipid-lowering agents
Thyroid replacement therapy
Antidepressant agents
Testosterone therapy (male subjects)
If on chronic thyroid pharmacologic therapy, had a serum thyroid-stimulating hormone test result within the normal range at Visit 1
Was willing and able to follow study procedures
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:

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:

Hepatic disease
Renal disease
Gastrointestinal disease
Endocrine disorder except T2DM
Cardiovascular disease
Central nervous system diseases
Psychiatric or neurological disorders
Organ transplantation
Chronic or acute infection (e.g., tuberculosis, human immunodeficiency virus, hepatitis B virus, or hepatitis C virus)
Orthostatic hypotension, fainting spells or blackouts
Allergy or hypersensitivity
Clinically significant malignant disease (with the exception of basal and squamous cell carcinoma of the skin) within 5 years of Visit 1
Had known hypersensitivity, intolerability, or allergies to metformin HCl or any component of study treatment
Had a physical, psychological, or historical finding that, in the investigator's opinion, would make the subject unsuitable for the study
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
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

Had been treated, was being treated, or was expected to require or undergo treatment with any of the following excluded medications:

Insulin or sulphonylurea treatment within 3 months of Visit 1
GLP-1 receptor agonists and/or thiazolidinedione treatment within 6 months of Visit 1
Nifedipine within 3 months of Visit 1
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
Prescription weight loss medications within 3 months of Visit 1
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
Had received or planned to receive any iodinated contrast dye within 1 week prior to Visit 1 (Screening)
Had a surgical gastrointestinal procedure that may impact the gut hormonal response to study medication
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
Had received any investigational drug within 30 days (or five half-lives of the investigational drug, whichever was greater) of Visit 1
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
Was employed by Elcelyx Therapeutics, Inc. (that is an employee, temporary contract worker, or designee responsible for the conduct of the study)

Summary

Placebo

600 mg DR

800 mg DR

1000 mg DR

1000 mg XR

2000 mg XR

All Events

Event Type Organ System Event Term Placebo 600 mg DR 800 mg DR 1000 mg DR 1000 mg XR 2000 mg XR

Change in Fasting Plasma Glucose (mg/dL) at 4 Weeks

Placebo

-4.0
mg/dL (Median)
Full Range: -69.0 to 48.0

600 mg DR

-11.0
mg/dL (Median)
Full Range: -124.0 to 150.0

800 mg DR

-13.0
mg/dL (Median)
Full Range: -62.0 to 145.0

1000 mg DR

-18.0
mg/dL (Median)
Full Range: -90.0 to 113.0

1000 mg XR

-12.0
mg/dL (Median)
Full Range: -111.0 to 58.0

2000 mg XR

-25.0
mg/dL (Median)
Full Range: -110.0 to 20.0

AUC4-12wk of Change in Fasting Plasma Glucose (mg/dL*Week) Concentrations From Baseline to 12 Weeks

Placebo

4.0
mg/dL*week (Median)
Full Range: -784.0 to 698.0

600 mg DR

-96.0
mg/dL*week (Median)
Full Range: -894.0 to 414.0

800 mg DR

-108.0
mg/dL*week (Median)
Full Range: -556.0 to 612.0

1000 mg DR

-156.0
mg/dL*week (Median)
Full Range: -782.0 to 522.0

1000 mg XR

-98.0
mg/dL*week (Median)
Full Range: -880.0 to 314.0

2000 mg XR

-215.0
mg/dL*week (Median)
Full Range: -856.0 to 186.0

Change in HbA1c (%) at 12 Weeks

Placebo

0.45
HbA1c (%) (Least Squares Mean)
Standard Error: 0.137

600 mg DR

-0.03
HbA1c (%) (Least Squares Mean)
Standard Error: 0.125

800 mg DR

1000 mg DR

0.1
HbA1c (%) (Least Squares Mean)
Standard Error: 0.124

1000 mg XR

2000 mg XR

-0.21
HbA1c (%) (Least Squares Mean)
Standard Error: 0.133

Total

240
Participants

Age, Continuous

52.0
years (Mean)
Standard Deviation: 9.37

Baseline Fasting Plasma Glucose

173.0
mg/dL (Mean)
Standard Deviation: 49.72

Baseline HbA1c

7.38
% (Mean)
Standard Deviation: 0.928

BMI

33.3
kg/m² (Mean)
Standard Deviation: 5.44

Screening Fasting Plasma Glucose

144.3
mg/dL (Mean)
Standard Deviation: 36.57

Screening HbA1c

7.17
% (Mean)
Standard Deviation: 0.846

Ethnicity (NIH/OMB)

Previous T2DM Regimen

Race (NIH/OMB)

Sex: Female, Male

Overall Study

Placebo

600 mg DR

800 mg DR

1000 mg DR

1000 mg XR

2000 mg XR

Drop/Withdrawal Reasons

Placebo

600 mg DR

800 mg DR

1000 mg DR

1000 mg XR

2000 mg XR