Assessing the PK and Effect on Glucose and GI Hormone Concentrations of Metformin Delayed-Release in Subjects With T2DM
A Randomized, Crossover Study Assessing the Effects of pH 6.5 Enteric Coating of Metformin HCl Tablets on Pharmacokinetics and Changes in Circulating Glucose and Gastrointestinal Hormone Concentrations in Subjects With Type 2 Diabetes Mellitus
1 other identifier
interventional
24
1 country
2
Brief Summary
This study will evaluate how EFB0027 and EFB0026 behave in subjects with type 2 diabetes mellitus. In addition, this study will compare the effects of EFB0027 and EFB0026 on circulating concentrations of glucose and gastrointestinal hormones in subjects with type 2 diabetes mellitus.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P25-P50 for phase_1 type-2-diabetes-mellitus
Started May 2012
2 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
Study Start
First participant enrolled
May 1, 2012
CompletedFirst Submitted
Initial submission to the registry
August 23, 2012
CompletedPrimary Completion
Last participant's last visit for primary outcome
September 1, 2012
CompletedStudy Completion
Last participant's last visit for all outcomes
September 1, 2012
CompletedFirst Posted
Study publicly available on registry
September 3, 2012
CompletedResults Posted
Study results publicly available
June 16, 2014
CompletedSeptember 20, 2016
August 1, 2016
4 months
August 23, 2012
February 12, 2014
August 12, 2016
Conditions
Outcome Measures
Primary Outcomes (4)
Area Under the Curve (0-t) of Plasma Metformin
Measures from the time of dosing (0 h) to the time of the last quantifiable concentration following dose administration. The dose of study medication was administered at t = -1 min relative to the start time of the standardized breakfast.
Time points at which data were collected to create the area under the curve (0-t) for plasma metformin were: t = -0.08, 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, and 11 h relative to the start time of the standardized breakfast.
Change in Fasting Plasma Glucose
LS mean difference from Baseline (Day 1) to Day 5
Change from Baseline (Day 1) to Day 5
Within Treatment Comparison Based on Ratios of AUCs of GLP-1
Ratio of Day 5 to Baseline
Within Treatment Comparison Based on Ratios of AUCs of PYY
Ratio of Day 5 to Baseline
Study Arms (4)
1000 mg EFB0026 (metformin immediate-release)
ACTIVE COMPARATORBID
1000 mg EFB0027 (metformin delayed-release)
EXPERIMENTALBID
500 mg EFB0027 (metformin delayed-release)
EXPERIMENTALBID
500 mg EFB0026 + 1000 mg EFB0027
EXPERIMENTALBID
Interventions
Comparison of enteric-coating to assess effect on PK
Active comparator
Eligibility Criteria
You may qualify if:
- Is 19 to 70 (inclusive) years old at Visit 1 (Screening).
- Is diagnosed with Type 2 Diabetes Mellitus with
- HbA1c between 6.0 to 9.5% (inclusive) for subjects managing their diabetes with:
- i. Diet and exercise alone, or ii. A stable regimen (minimum of 2 months at Visit 1) of metformin alone, or iii. A stable regimen (minimum of 2 months at Visit 1) of DPP-4 inhibitor alone, OR
- HbA1c between 6.0 to 8.5% (inclusive) for subjects managing their diabetes with a stable (minimum of 2 months at Visit 1) combination regimen of metformin and DPP-4 inhibitors.
- Has serum creatinine below the upper limit of normal at Visit 1 and an estimated creatinine clearance above 80 using the Crockroft and Gault equation (CrCl = \[(140 - age) x body weight in kg\] / (serum creatinine x 72) x (0.85 for females) \[ref. 3\].
- Has a body mass index (BMI) of 25.0 to 40.0 kg/m\^2 (inclusive) at Screening.
- Is male, or is female and meets all of the following criteria:
- Not breastfeeding
- Negative pregnancy test result (human chorionic gonadotropin, beta subunit) at Visit 1 (Screening) (not applicable to hysterectomized females)
- 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
- Has a physical examination with no clinically significant abnormalities as judged by the investigator.
- Ability to understand and willingness to adhere to protocol requirements.
- If on chronic thyroid pharmacologic therapy, the dose must be stable for at least 3 months prior to Visit 1 (Screening), and must have thyroid-stimulating hormone (TSH) test result in normal range at Visit 1 (Screening).
You may not qualify if:
- Has 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 diabetes
- Cardiovascular disease
- Seizure disorder
- Organ transplantation
- Chronic infection
- Has any chronic disease requiring medication that has been adjusted in the past 90 days (subjects may take acute intermittent over-the-counter medications such as Tylenol, if needed).
- Has any drug treatment that affects gastric pH (prescription or over-the-counter), including any antacids or medications such as Rolaids or Pepcid within 2 days of Visit 1 (Screening).
- Has had major surgery of any kind within 6 months of Visit 1 (Screening).
- Has received a blood transfusion within 6 months of Visit 1 (Screening).
- Has a history of \>5 kg weight change within 3 months of Visit 1 (Screening).
- Has clinical laboratory test (clinical chemistry, hematology, or urinalysis) abnormalities other than those expected in subjects with diabetes and judged by the investigator to be clinically significant at Visit 1 (Screening).
- +10 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (2)
Celerion, Inc.
Tempe, Arizona, 85283, United States
Celerion, Inc.
Lincoln, Nebraska, 68502, United States
Related Publications (1)
DeFronzo RA, Buse JB, Kim T, Burns C, Skare S, Baron A, Fineman M. Once-daily delayed-release metformin lowers plasma glucose and enhances fasting and postprandial GLP-1 and PYY: results from two randomised trials. Diabetologia. 2016 Aug;59(8):1645-54. doi: 10.1007/s00125-016-3992-6. Epub 2016 May 23.
PMID: 27216492BACKGROUND
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Results Point of Contact
- Title
- Senior Director, Development
- Organization
- Elcelyx Therapeutics, Inc
Publication Agreements
- PI is Sponsor Employee
- No
- Restriction Type
- OTHER
- Restrictive Agreement
- Yes
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- RANDOMIZED
- Masking
- DOUBLE
- Who Masked
- PARTICIPANT, INVESTIGATOR
- Purpose
- BASIC SCIENCE
- Intervention Model
- CROSSOVER
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
August 23, 2012
First Posted
September 3, 2012
Study Start
May 1, 2012
Primary Completion
September 1, 2012
Study Completion
September 1, 2012
Last Updated
September 20, 2016
Results First Posted
June 16, 2014
Record last verified: 2016-08