Study Assessing the Behavior of Delayed-Release Metformin in Subjects With Kidney Dysfunction

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Elcelyx Therapeutics, Inc.
ClinicalTrials.gov Identifier:
NCT01658514
First received: August 1, 2012
Last updated: June 2, 2014
Last verified: June 2014
  Purpose

This study will evaluate how a single dose delayed-release metformin behaves in subjects with normal kidney function, mild kidney dysfunction, moderate kidney dysfunction, and severe kidney dysfunction. The safety and tolerability of delayed-release metformin will also be examined.

In addition, this study will compare the behavior of a single dose of delayed-release metformin with that of extended-release metformin and placebo in subjects with the varying levels of kidney function described above.


Condition Intervention Phase
Renal Insufficiency
Drug: Delayed-release metformin
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Pharmacokinetics 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:
  • Pharmacokinetics of delayed-release metformin [ Time Frame: PK will be assessed over 3 days following a single dose; washout of 2 to 5 days until next administration ] [ Designated as safety issue: No ]
    Single dose AUC of delayed-release metformin in subjects with renal impairment Single dose Cmax of delayed-release metformin in subjects with renal impairment

  • Characterize single dose exposure-response relationship of metformin and plasma lactate concentrations [ Time Frame: Plasma lactate measures over 3 days following single dose administration; 2-5 days washout until next dose ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 32
Study Start Date: August 2013
Estimated Study Completion Date: September 2014
Estimated Primary Completion Date: June 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Delayed-release metformin Drug: Delayed-release metformin
Comparison of enteric-coating to assess effect on PK
Active Comparator: Extended-release metformin Drug: Delayed-release metformin
Active comparator
Placebo Comparator: Placebo

  Eligibility

Ages Eligible for Study:   18 Years to 80 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Is 18 to 80 (inclusive) years old at Visit 1 (Screening).
  2. Is male, or is female and meets 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, must practice and be willing to continue to practice appropriate birth control during the entire duration of the study
    • Has body weight of ≥ 45 kg
  3. Has a BMI of 18.0 to 40.0 kg/m2 (inclusive) at Visit 1 (Screening).
  4. Has type 2 diabetes mellitus and an HbA1c ≤10.0%.
  5. Has a physical examination with no clinically significant abnormalities as judged by the investigator.
  6. Has eGFR ≥15 mL/min/1.73 m2 based on the MDRD equation.
  7. Ability to understand and willingness to adhere to protocol requirements

Exclusion Criteria:

  1. Has End Stage Renal Disease requiring dialysis or severe renal dysfunction with eGFR <15 mL/min/1.73 m2.
  2. Is currently on dialysis or has been on dialysis within 12 months of Visit 1 (Screening).
  3. Has received or plans to receive any iodinated contrast dye within 1 week prior to Visit 1 (Screening) or after study medication administration.
  4. Is currently taking or has 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. Has 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 is 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. Has any chronic disease requiring medication that has been adjusted in the past 14 days(subjects may take acute intermittent over-the-counter medications such as Tylenol, if needed).
  7. Has had major surgery of any kind within 6 months of Visit 1 (Screening).
  8. Has a clinically significant finding of an electrocardiogram (ECG) as assessed by the investigator at Visit 1 (Screening).
  9. Has 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. Has a hemoglobin result <8 g/dL or a level indicating severe anemia of renal origin.
  11. Has physical, psychological, or historical finding that, in the investigator's opinion, would make the subject unsuitable for the study.
  12. Has received Byetta® or short-acting insulin within 3 days of Visit 1 (Screening).
  13. Has received metformin within 4 weeks of Visit 1 (Screening).
  14. Has 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 2.
  15. Currently abuses drugs or alcohol or has a history of abuse that in the investigator's opinion would cause the individual to be noncompliant with study procedures.
  16. Smokes more than 10 cigarettes, 3 cigars, or 3 pipes per day.
  17. Has donated blood within 2 months of Visit 1 (Screening) or is planning to donate blood during the study.
  18. Has received any investigational drug within one month (or seven half-lives of the investigational drug, whichever is greater) of Visit 1 (Screening).
  19. Has known allergies or hypersensitivity to any component of study treatment.
  20. Is 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

Locations
United States, Florida
Clinical Pharmacology of Miami
Miami, Florida, United States, 33014
Compass Research
Orlando, Florida, United States, 32806
Prgressive Medical Research
Port Orange, Florida, United States, 32127
United States, Kentucky
Louisville Metabolic and Atherosclerosis Research Center
Louisville, Kentucky, United States, 40213
United States, Minnesota
Prism Research
St Paul, Minnesota, United States, 55114
Sponsors and Collaborators
Elcelyx Therapeutics, Inc.
Investigators
Principal Investigator: George Canas, MD Prism Research
Principal Investigator: Kenneth Lasseter, MD Clinical Pharmacology of Miami
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
  More Information

No publications provided

Responsible Party: Elcelyx Therapeutics, Inc.
ClinicalTrials.gov Identifier: NCT01658514     History of Changes
Other Study ID Numbers: LCRM101
Study First Received: August 1, 2012
Last Updated: June 2, 2014
Health Authority: United States: Food and Drug Administration

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

ClinicalTrials.gov processed this record on September 16, 2014