Assessing the Behavior of Met DR in Subjects With Kidney Dysfunction

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Elcelyx Therapeutics, Inc.
ClinicalTrials.gov Identifier:
NCT01658514
First received: August 1, 2012
Last updated: November 25, 2015
Last verified: November 2015
  Purpose
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.

Condition Intervention Phase
Renal Insufficiency
Drug: Met DR
Drug: Met XR
Drug: Placebo
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Pharmacokinetics/Dynamics Study
Intervention Model: Crossover Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Basic Science
Official Title: A Randomized, Crossover Study Assessing the Single Dose Pharmacokinetics of Delayed-Release Metformin in Subjects With Renal Dysfunction

Resource links provided by NLM:


Further study details as provided by Elcelyx Therapeutics, Inc.:

Primary Outcome Measures:
  • AUC (0-t) of Plasma Metformin [ Time Frame: from the time of dosing (0 h) to 72 hours postdose ] [ Designated as safety issue: No ]
    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

  • Cmax of Plasma Metformin [ Time Frame: from the time of dosing (0 h) to 72 hours postdose ] [ Designated as safety issue: No ]
    Cmax = Maximum concentration from the time of dosing (0 h) to the time of the last quantifiable metformin concentration following dose administration

  • Correlation of Placebo-adjusted Change From Pre-dose Value in Lactate Versus Metformin Concentration [ Time Frame: from the time of dosing (0 h) to 24 hours postdose ] [ Designated as safety issue: Yes ]
    To determine the exposure-response relationship of metformin and plasma lactate concentrations


Enrollment: 39
Study Start Date: January 2014
Study Completion Date: June 2014
Primary Completion Date: June 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Met DR
One dose of 1000 mg metformin delayed-release
Drug: Met DR
metformin delayed-release tablets
Active Comparator: Met XR
One dose of 1000 mg metformin extended-release
Drug: Met XR
metformin extended-release tablets
Placebo Comparator: Placebo
One dose of Placebo
Drug: Placebo

  Eligibility

Ages Eligible for Study:   18 Years to 80 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  1. 18 to 80 (inclusive) years old at Visit 1 (Screening)
  2. 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
  3. Body mass index (BMI) of 18.0 to 40.0 kg/m² (inclusive) at Visit 1 (Screening)
  4. Had type 2 diabetes mellitus and an HbA1c ≤10.0%
  5. Had a physical examination with no clinically significant abnormalities as judged by the investigator
  6. Estimated glomerular filtration rate (eGFR) ≥15 mL/min/1.73 m² based on the Modification of Diet in Renal Disease (MDRD) equation
  7. Ability to understand and willingness to adhere to protocol requirements

Exclusion Criteria:

  1. Had End Stage Renal Disease requiring dialysis or severe renal dysfunction with eGFR <15 mL/min/1.73 m²
  2. Was on dialysis or had been on dialysis within 12 months of Visit 1 (Screening)
  3. Had received or planned to receive any iodinated contrast dye within 1 week prior to Visit 1 (Screening) or after study medication administration
  4. 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)
  5. 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
  6. Had any chronic disease requiring medication that had been adjusted in the past 14 days (subjects could take acute intermittent over-the-counter medications such as Tylenol, if needed)
  7. Had major surgery of any kind within 6 months of Visit 1 (Screening)
  8. Had a clinically significant finding of an electrocardiogram (ECG) as assessed by the investigator at Visit 1 (Screening)
  9. Had clinical laboratory test (clinical chemistry, hematology, or urinalysis) abnormalities, other than those related to diabetes or renal disease and other stable diseases, judged by the investigator to be clinically significant at Visit 1 (Screening)
  10. Had a hemoglobin result <8 g/dL or a level indicating severe anemia of renal origin
  11. Had a physical, psychological, or historical finding that, in the investigator's opinion, would make the subject unsuitable for the study
  12. Had received Byetta® or short-acting insulin within 3 days of Visit 1 (Screening)
  13. Had received metformin within 4 weeks of Visit 1 (Screening)
  14. Had any drug treatment that affects gastrointestinal motility or gastric pH (prescription or over-the-counter), including any antacids or medications such as Rolaids or Pepcid, within 2 days of Visit 2
  15. 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
  16. Smoked more than 10 cigarettes, 3 cigars, or 3 pipes per day
  17. Had donated blood within 2 months of Visit 1 (Screening) or was planning to donate blood during the study
  18. Had received any investigational drug within one month (or seven half-lives of the investigational drug, whichever was greater) of Visit 1 (Screening)
  19. Had known allergies or hypersensitivity to any component of study treatment
  20. Was employed by Elcelyx Therapeutics, Inc (that is an employee, temporary contract worker, or designee of the company)
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01658514

Sponsors and Collaborators
Elcelyx Therapeutics, Inc.
Investigators
Principal Investigator: 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
  More Information

Publications:
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.

Responsible Party: Elcelyx Therapeutics, Inc.
ClinicalTrials.gov Identifier: NCT01658514     History of Changes
Other Study ID Numbers: LCRM101 
Study First Received: August 1, 2012
Results First Received: October 12, 2015
Last Updated: November 25, 2015
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Renal Insufficiency
Kidney Diseases
Urologic Diseases
Metformin
Hypoglycemic Agents
Pharmacologic Actions
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on May 03, 2016