Assessing the PK of Met DR, Met IR, and Met XR in Healthy Subjects

NCT02291510 | Completed Phase 1 Results

• 1 other identifier: LCRM103
• Study Type: interventional
• Target: 20
• Locations: 0 countries
• Sites: N/A

Brief Summary

This study compared the pharmacokinetics (PK) and assessed the safety of delayed-release metformin (Met DR, EFB0027) at two dosage levels, immediate-release metformin (Met IR, ETB0015), and extended-release metformin (Met XR, ETB0014) in healthy subjects.

Conditions

Healthy Subjects

Outcome Measures

Primary Outcomes (2)

• AUC (0-t) of Plasma Metformin

  AUC (0-t) = Area under the curve from the time of dosing (0 h) to the time of the last quantifiable concentration after the standardized dinner. Doses were administered 1 min prior to 0 h (standardized dinner) for once daily in the evening (qPM) and twice daily (BID) dosing and 1 min prior to 12 h (standardized breakfast) for once daily in the morning (qAM) and BID dosing.

  Time points to create AUC (0-t) 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 concentration from the first dose of study medication administration (0 h) to the time of the last quantifiable concentration following dose administration. Doses were administered 1 min prior to 0 h (standardized dinner) for qPM and BID dosing and 1 min prior to 12 h (standardized breakfast) for qAM and BID dosing.

  Time points to create 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.

Study Arms (4)

500 mg Met DR BID

EXPERIMENTAL

Two doses of 500 mg metformin delayed-release

Drug: Met DR

1000 mg Met DR BID

EXPERIMENTAL

Two doses of 1000 mg metformin delayed-release

Drug: Met DR

1000 mg Met IR BID

ACTIVE COMPARATOR

Two doses of 1000 mg metformin immediate-release

Drug: Met IR

2000 mg Met XR QD

ACTIVE COMPARATOR

Single dose of 2000 mg metformin extended-release

Drug: Met XR

Interventions

Met DR DRUG

metformin delayed-release tablets

1000 mg Met DR BID; 500 mg Met DR BID

Met XR DRUG

metformin extended-release tablets

2000 mg Met XR QD

Met IR DRUG

metformin immediate-release tablets

1000 mg Met IR BID

Eligibility Criteria

• Age: 19 Years - 65 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• to 65 (inclusive) years old at Visit 1 (Screening)
• Male, or if female and met all of the following criteria:
• Not breastfeeding
• Negative pregnancy test result 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
• Body mass index (BMI) of 25.0 to 35.0 kg/m² (inclusive) at Visit 1 (Screening)
• Had a physical examination with no clinically significant abnormalities as judged by the investigator
• Had normal renal function with an estimated glomerular filtration rate (eGFR) ≥90 mL/min/1.73 m² based on the Modification of Diet in Renal Disease (MDRD) equation
• Ability to understand and willingness to adhere to protocol requirements

You may not qualify if:

• Had a clinically significant medical condition as judged by the investigator that could potentially affect study participation and/or personal well-being, including but not limited to the following conditions:
• Hepatic disease
• Gastrointestinal disease
• Endocrine disorder (including diabetes and impaired glucose tolerance)
• 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 major surgery of any kind within 6 months of Visit 1 (Screening)
• Had a history of \>6 kg weight change within 3 months of Visit 1 (Screening)
• Had clinical laboratory test (clinical chemistry, hematology, or urinalysis) abnormalities judged by the investigator to be clinically significant at Visit 1 (Screening)

Sponsors & Collaborators

• Elcelyx Therapeutics, Inc.: lead

Related Publications (2)

• DeFronzo RA, Buse JB, Kim T, Skare S, Baron A, Fineman M, editors. Dissociation between Metformin Plasma Exposure and its Glucose-Lowering Effect: A Novel Gut-Mediated Mechanism of Action. 73rd Annual Scientific Meeting of The American Diabetes Association; 2013 June 21-25th; Chicago, Il.

  BACKGROUND

• 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

Results Point of Contact

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

info@elcelyx.com

858-876-1814

Study Officials

• Scott Rasmussen, 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: SINGLE
• Who Masked: PARTICIPANT
• Purpose: BASIC SCIENCE
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 11, 2014
• First Posted: November 14, 2014
• Study Start: October 1, 2012
• Primary Completion: December 1, 2012
• Study Completion: December 1, 2012
• Last Updated: December 2, 2016
• Results First Posted: September 21, 2015

Record last verified: 2016-10