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

NCT01804842 | Completed Phase 1 Results

• 1 other identifier: LCRM104
• Study Type: interventional
• Target: 26
• Locations: 0 countries
• Sites: N/A

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).

Conditions

Type 2 Diabetes Mellitus

Outcome Measures

Primary Outcomes (4)

• 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.

• 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.

• 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.

• 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.

Study Arms (3)

500 mg Met DR BID

ACTIVE COMPARATOR

Two doses of 500 mg metformin delayed-release

Drug: Met DR

1000 mg Met DR qAM

EXPERIMENTAL

One dose of 1000 mg metformin delayed-release in the morning

Drug: Met DR

1000 mg Met DR qPM

EXPERIMENTAL

One dose of 1000 mg metformin delayed-release in the evening

Drug: Met DR

Interventions

Met DR DRUG

metformin delayed-release tablets

Also known as: EFB0027

1000 mg Met DR qAM; 1000 mg Met DR qPM; 500 mg Met DR BID

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• to 70 (inclusive) years old at Visit 1 (Screening)
• 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
• 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
• Body mass index (BMI) of 25.0 to 40.0 kg/m\^2 (inclusive) at Screening
• 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
• Had 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 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)

You may not qualify if:

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

Sponsors & Collaborators

• Elcelyx Therapeutics, Inc.: lead

Related 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.

  PMID: 26285584 BACKGROUND

• 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: 27216492 BACKGROUND

MeSH Terms

Conditions

Diabetes Mellitus, Type 2

Condition Hierarchy (Ancestors)

Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases

Results Point of Contact

• Title: Senior Director, Development
• Organization: Elcelyx Therapeutics, Inc

info@elcelyx.com

858-876-1814

Study Officials

• Danielle Armas, MD

  Celerion

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 4, 2013
• First Posted: March 5, 2013
• Study Start: December 1, 2012
• Primary Completion: April 1, 2013
• Study Completion: April 1, 2013
• Last Updated: October 21, 2016
• Results First Posted: April 7, 2016

Record last verified: 2016-10