Assessing the Behavior of Met DR in Subjects With Kidney Dysfunction
Condition: Renal Insufficiency
MeSH terms: Renal Insufficiency
Intervention: Met DR; Met XR; Placebo
Intervention description: metformin delayed-release tablets; metformin extended-release tablets
Phase: Phase 2
Study type: Interventional
Primary purpose: Basic Science
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: Double (Participant, Investigator)
Enrollment: 39.0
Sex: All
Minimum age: 18 Years
Maximum age: 80 Years
Healthy volunteers: Accepts Healthy Volunteers

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.
    

Eligibility 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)