Study Assessing the PK of EFB0027 (Metformin Delayed-release) and Effect on Circulating Glucose and GI Hormone Concentrations in Subjects With T2DM

Type 2 Diabetes Mellitus Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01677299
• Other study ID #: LCPOC10
• Status: Completed
• Phase: Phase 1/Phase 2
• First received: August 23, 2012
• Last updated: May 15, 2014
• Start date: May 2012
• Est. completion date: September 2012

Study information

• Verified date: May 2014
• Source: Elcelyx Therapeutics, Inc.
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 24
• Est. completion date: September 2012
• Est. primary completion date: September 2012
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 19 Years to 70 Years

Eligibility

Inclusion Criteria:

1. Is 19 to 70 (inclusive) years old at Visit 1 (Screening).

2. 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.

3. 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].

4. Has a body mass index (BMI) of 25.0 to 40.0 kg/m2 (inclusive) at Screening.

5. 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

6. Has a physical examination with no clinically significant abnormalities as judged by the investigator.

7. Ability to understand and willingness to adhere to protocol requirements.

8. 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).

Exclusion Criteria:

1. 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

2. 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).

3. 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).

4. Has had major surgery of any kind within 6 months of Visit 1 (Screening).

5. Has received a blood transfusion within 6 months of Visit 1 (Screening).

6. Has a history of >5 kg weight change within 3 months of Visit 1 (Screening).

7. 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).

8. Has physical, psychological, or historical finding that, in the investigator's opinion, would make the subject unsuitable for the study.

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. Has donated blood within 2 months of Visit 1 (Screening) or is planning to donate blood during the study.

11. Has used insulin within 3 months of Visit 1 (Screening).

12. Has received GLP-1 receptor agonists and/or thiazolidinedione treatment within 6 months of Visit 1 (Screening).

13. Has known intolerance to metformin.

14. Has received any investigational drug within 1 month (or five half-lives of the investigational drug, whichever is greater) of Visit 1 (Screening).

15. Has known allergies or hypersensitivity to any component of study treatment.

16. Is employed by Elcelyx Therapeutics, Inc (that is an employee, temporary contract worker, or designee of the company).

17. Smokes more than 10 cigarettes per day, 2 cigars per day, or uses more than 1 can of smokeless tobacco per week.

Study Design

Allocation: Randomized, Endpoint Classification: Pharmacokinetics Study, Intervention Model: Crossover Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Basic Science

Related Conditions & MeSH terms

• Diabetes Mellitus
• Diabetes Mellitus, Type 2
• Type 2 Diabetes Mellitus

Intervention

Drug:
• EFB0027 (metformin delayed release)
Comparison of enteric-coating to assess effect on PK
• EFB0026 (metformin immediate-release)
Active comparator

Locations

Country	Name	City	State
United States	Celerion, Inc.	Lincoln	Nebraska
United States	Celerion, Inc.	Tempe	Arizona

Sponsors (1)

Lead Sponsor	Collaborator
Elcelyx Therapeutics, Inc.

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Area Under the Curve (0-t) of Plasma Metformin	Area Under the Curve (0-t) of Plasma Metformin	pre-dose to 11 hours post-dose	No
Primary	Change in Fasting Plasma Glucose	LS mean difference from Baseline (Day 1) to Day 5	Change from Baseline (Day 1) to Day 5	No
Primary	Within Treatment Comparison Based on Ratios of AUCs of GLP-1		Ratio of Day 5 to Baseline	No
Primary	Within Treatment Comparison Based on Ratios of AUCs of PYY		Ratio of Day 5 to Baseline	No