Assessing the Behavior of Met DR in Subjects With Kidney Dysfunction

NCT01658514 | Completed Phase 2 Results

• 1 other identifier: LCRM101
• Study Type: interventional
• Target: 39
• Locations: 0 countries
• Sites: N/A

Brief Summary

This study evaluated how a single dose of delayed-release metformin (Met DR) behaves in subjects with normal kidney function, mild kidney dysfunction, moderate kidney dysfunction, or severe kidney dysfunction. The safety and tolerability of Met DR was also examined. In addition, this study compared the behavior of a single dose of Met DR with that of extended-release metformin (Met XR) and placebo in subjects with the varying levels of kidney function described above.

Conditions

Renal Insufficiency

Outcome Measures

Primary Outcomes (3)

• 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 following dose administration

  from the time of dosing (0 h) to 72 hours postdose

• Cmax of Plasma Metformin

  Cmax = Maximum concentration from the time of dosing (0 h) to the time of the last quantifiable metformin concentration following dose administration

  from the time of dosing (0 h) to 72 hours postdose

• Correlation of Placebo-adjusted Change From Pre-dose Value in Lactate Versus Metformin Concentration

  To determine the exposure-response relationship of metformin and plasma lactate concentrations

  from the time of dosing (0 h) to 24 hours postdose

Study Arms (3)

Met DR

EXPERIMENTAL

One dose of 1000 mg metformin delayed-release

Drug: Met DR

Met XR

ACTIVE COMPARATOR

One dose of 1000 mg metformin extended-release

Drug: Met XR

Placebo

PLACEBO COMPARATOR

One dose of Placebo

Drug: Placebo

Interventions

Met DR DRUG

metformin delayed-release tablets

Met DR

Met XR DRUG

metformin extended-release tablets

Met XR

Placebo DRUG

Placebo

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• to 80 (inclusive) years old at Visit 1 (Screening)
• Male, or female and met all of the following criteria:
• Not breastfeeding
• Negative pregnancy test result at Visit 1 (Screening) (not applicable to postmenopausal or surgically sterile 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 weight of ≥45 kg
• Body mass index (BMI) of 18.0 to 40.0 kg/m² (inclusive) at Visit 1 (Screening)
• Had type 2 diabetes mellitus and an HbA1c ≤10.0%
• Had a physical examination with no clinically significant abnormalities as judged by the investigator
• Estimated glomerular filtration rate (eGFR) ≥15 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 End Stage Renal Disease requiring dialysis or severe renal dysfunction with eGFR \<15 mL/min/1.73 m²
• Was on dialysis or had been on dialysis within 12 months of Visit 1 (Screening)
• Had received or planned to receive any iodinated contrast dye within 1 week prior to Visit 1 (Screening) or after study medication administration
• Was taking or had taken within 1 week of Visit 1 cationic drugs that are eliminated by renal tubular secretion (e.g., amiloride, digoxin, morphine, procainamide, quinidine, quinine, ranitidine, triamterene, trimethoprim, and vancomycin)
• 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
• Gastrointestinal disease
• Endocrine disorder (type 2 diabetes mellitus was allowed)
• 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

Sponsors & Collaborators

• Elcelyx Therapeutics, Inc.: lead

Related Publications (2)

• Bakris GL, Mudaliar, S, Kim T, Burns C, Skare S, Baron A, Fineman M. Effects of New Metformin Formulation in Stage 3 and 4 CKD: A Pilot Study. J Am Soc Nephrol. 2014; 25:549A.

  RESULT

• DeFronzo R, Fleming GA, Chen K, Bicsak TA. Metformin-associated lactic acidosis: Current perspectives on causes and risk. Metabolism. 2016 Feb;65(2):20-9. doi: 10.1016/j.metabol.2015.10.014. Epub 2015 Oct 9.

  PMID: 26773926 RESULT

MeSH Terms

Conditions

Renal Insufficiency

Condition Hierarchy (Ancestors)

Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases

Results Point of Contact

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

info@elcelyx.com

858-876-1814

Study Officials

• George Canas, MD

  Prism Research

  PRINCIPAL INVESTIGATOR

• Kenneth Lasseter, MD

  Clinical Pharmacology of Miami, Inc

  PRINCIPAL INVESTIGATOR

• Alexander White, MD

  Progressive Medical Research

  PRINCIPAL INVESTIGATOR

• Harold Bays, MD

  Louisville Metabolic and Atherosclerosis Research Center

  PRINCIPAL INVESTIGATOR

• Craig Curtis, MD

  Compass Research

  PRINCIPAL INVESTIGATOR

• Prabir Roy-Chaudhury

  Cincinnati Veterans Affairs Medical Center Department of Internal Medicine

  PRINCIPAL INVESTIGATOR

• Sunder Mudaliar

  San Diego Veterans Healthcare System

  PRINCIPAL INVESTIGATOR

• Nelson Kopyt

  Northeast Clinical Research Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

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

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: BASIC SCIENCE
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 1, 2012
• First Posted: August 7, 2012
• Study Start: January 1, 2014
• Primary Completion: June 1, 2014
• Study Completion: June 1, 2014
• Last Updated: December 30, 2015
• Results First Posted: December 30, 2015

Record last verified: 2015-11