Assessing the Effect of Met DR on Plasma Glucose and PK in Subjects With T2DM

Type 2 Diabetes Mellitus Clinical Trial

Official title:

A Randomized, Crossover Study Assessing the Effect of EFB0027 on Plasma Glucose and Pharmacokinetics in Subjects With Type 2 Diabetes Mellitus

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01804842
• Other study ID #: LCRM104
• Status: Completed
• Phase: Phase 1/Phase 2
• First received: March 4, 2013
• Last updated: October 19, 2016
• Start date: December 2012
• Est. completion date: April 2013

Study information

• Verified date: October 2016
• Source: Elcelyx Therapeutics, Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This study compared the effects of delayed-release metformin (Met DR, EFB0027) administered once daily in the morning (qAM), administered once daily in the evening (qPM), and administered twice daily (BID) on circulating glucose concentrations and metformin pharmacokinetics (PK) in subjects with type 2 diabetes mellitus (T2DM).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 26
• Est. completion date: April 2013
• Est. primary completion date: April 2013
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 70 Years

Eligibility

Inclusion Criteria:

1. 18 to 70 (inclusive) years old at Visit 1 (Screening)

2. Was 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. Had normal renal function with an estimated glomerular filtration rate (eGFR) =90 mL/min/1.73 m^2 based on the Modification of Diet in Renal Disease (MDRD) equation

4. Body mass index (BMI) of 25.0 to 40.0 kg/m^2 (inclusive) at Screening

5. Male, or if female and met 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, practiced and was willing to continue to practice appropriate birth control during the entire duration of the study

6. Had 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 have been 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. 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 diabetes

• Cardiovascular disease

• Central nervous system diseases

• Psychiatric or neurological disorders

• Organ transplantation

• Chronic or acute infection

• Orthostatic hypotension, fainting spells or blackouts

• Allergy or hypersensitivity

2. Had any chronic disease requiring medication that was adjusted in the past 90 days (subjects could take acute intermittent over-the-counter medications such as Tylenol, if needed)

3. Had 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. Had major surgery of any kind within 6 months of Visit 1 (Screening)

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

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

7. Had clinical laboratory test (clinical chemistry, hematology, or urinalysis) abnormalities other than those expected in subjects with type 2 diabetes and judged by the investigator to be clinically significant at Visit 1 (Screening)

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

9. Abused drugs or alcohol or had a history of abuse that in the investigator's opinion would cause the individual to be noncompliant with study procedures

10. Had donated blood within 3 months of the date of the first dose of randomized study medication, or was planning to donate blood during the study

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

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

13. Had known intolerance to metformin

14. Had received any investigational drug within 2 months (or five half-lives of the investigational drug, whichever was greater) of Visit 1 (Screening)

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

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

17. Smoked more than 10 cigarettes per day, 3 cigars per day, 3 pipes per day, used more than 1 can of smokeless tobacco per week, or used a combination of tobacco products that approximate nicotine doses equivalent to 10 cigarettes per day

Related Conditions & MeSH terms

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

Intervention

Drug:
• Met DR
metformin delayed-release tablets

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Elcelyx Therapeutics, Inc.

References & Publications (2)

Buse JB, DeFronzo RA, Rosenstock J, Kim T, Burns C, Skare S, Baron A, Fineman M. The Primary Glucose-Lowering Effect of Metformin Resides in the Gut, Not the Circulation: Results From Short-term Pharmacokinetic and 12-Week Dose-Ranging Studies. Diabetes Care. 2016 Feb;39(2):198-205. doi: 10.2337/dc15-0488. Epub 2015 Aug 18. — View Citation

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	AUC (0-24) of Plasma Metformin	AUC (0-24) = Area under the curve from the start time of the standardized dinner (0 h) to 24 hours after the standardized dinner. Study medication was administered at t = 0 hours for Treatments B and C and at t = 12 hours for Treatments A and C.	Times points to create the AUC (0-24) were: t = -0.08, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, 10, 11, 11.92, 12.5, 13, 13.5, 14, 14.5, 15, 16, 17, 18, 19, 20, 21, 22, 23, and 24 hours relative to the start time of the standardized dinner.
Primary	Cmax of Plasma Metformin	Cmax = maximum response from the start time of the standardized dinner (0 h) to 24 hours after the standardized dinner. Study medication was administered at t = 0 hours for Treatments B and C and at t = 12 hours for Treatments A and C.	Times points to determine Cmax were: t = -0.08, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, 10, 11, 11.92, 12.5, 13, 13.5, 14, 14.5, 15, 16, 17, 18, 19, 20, 21, 22, 23, and 24 hours relative to the start time of the standardized dinner.
Primary	AUC (0-24) of Plasma Glucose	AUC (0-24) = Area under the curve from the start time of the standardized dinner (0 h) to 24 hours after the standardized dinner. Study medication was administered at t = 0 hours for Treatments B and C and at t = 12 hours for Treatments A and C.	Times points to create the AUC (0-24) were: t = -0.08, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, 10, 11, 11.75, 11.92, 12.5, 13, 13.5, 14, 14.5, 15, 16, 17, 18, 18.5, 19, 19.5, 20, 21, 22, 23, and 24 hours relative to the time of the standardized dinner.
Primary	Rmax (0-24) of Plasma Glucose	Rmax (0-24) = maximum response from the start time of the standardized dinner (0 h) to 24 hours after the standardized dinner. Study medication was administered at t = 0 hours for Treatments B and C and at t = 12 hours for Treatments A and C.	Times points to determine Rmax were: t = -0.08, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, 10, 11, 11.75, 11.92, 12.5, 13, 13.5, 14, 14.5, 15, 16, 17, 18, 18.5, 19, 19.5, 20, 21, 22, 23, and 24 hours relative to the start time of the standardized dinner.