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

Phase 1

Completed

• Conditions: Type 2 Diabetes Mellitus
• Interventions: Drug: Met DR

• Registration Number: NCT01804842
• Lead Sponsor: Elcelyx Therapeutics, Inc.

Brief 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).

Detailed Description

Not available

Study Timeline

• Study Start: 2012-12
• Study First Submitted: 2013-03-04
• Study First Submitted QC: 2013-03-04
• Study First Posted: 2013-03-05
• Primary Completion: 2013-04
• Study Completion: 2013-04
• Disposition First Submitted: 2014-08-20
• Disposition First Submitted QC: 2014-08-20
• Disposition First Posted: 2014-08-22
• Results First Submitted: 2016-03-08
• Results First Submitted QC: 2016-03-08
• Results First Posted: 2016-04-07
• Status Verified: 2016-10
• Last Update Submitted: 2016-10-19
• Last Update Posted: 2016-10-21

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 26

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)

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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

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
500 mg Met DR BID	Met DR	Two doses of 500 mg metformin delayed-release
1000 mg Met DR qAM	Met DR	One dose of 1000 mg metformin delayed-release in the morning
1000 mg Met DR qPM	Met DR	One dose of 1000 mg metformin delayed-release in the evening

Primary Outcome Measures

Name	Time	Method
AUC (0-24) of Plasma Metformin	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.	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.
AUC (0-24) of Plasma Glucose	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.	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.
Cmax of Plasma Metformin	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.	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.
Rmax (0-24) of Plasma Glucose	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.	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.