PF-06291874 Multiple Ascending Dose Study In Type 2 Diabetes Mellitus Patients
Condition: Diabetes Mellitus, Type 2
MeSH terms: Diabetes Mellitus; Diabetes Mellitus, Type 2
Intervention: PF-06291874; Placebo
Intervention description: The dosing schedule is 5, 15, 50, 100 and 150 mg QD for 14 days for the first 5 cohorts in Part A. The dosing schedule for the first cohort in Part B is 15 mg QD for 14 days and 30 mg QD for 28 days; Placebo tablets will be administered QD in each of the cohorts for 14 days (Part A cohorts 1- 5 and Part B cohort 1) or 28 days (Part B cohort 2).
Phase: Phase 1
Study type: Interventional
Primary purpose: Basic Science
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Enrollment: 117.0
Sex: All
Minimum age: 18 Years
Maximum age: 70 Years
Healthy volunteers: No

Summary:

      The purpose of this study is to assess the safety, tolerability, pharmacokinetics and
      pharmacodynamics of multiple ascending doses of PF-06291874 in Type 2 Diabetes patients.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Males and female subjects of non-childbearing potential between the ages of 18 and 70
             years, inclusive of age at the time of the screening visit.

        Female subjects of non-childbearing potential must meet at least one of the following
        criteria:

          1. Achieved postmenopausal status, defined as: cessation of regular menses for at least
             12 consecutive months with no alternative pathological or physiological cause; and
             have a serum FSH level within the laboratory's reference range for postmenopausal
             females;

          2. Have undergone a documented hysterectomy and/or bilateral oophorectomy;

          3. Have medically confirmed ovarian failure.

          4. All other female subjects (including females with tubal ligations and females that do
             NOT have a documented hysterectomy, bilateral oophorectomy and/or ovarian failure)
             will be considered to be of childbearing potential.

               -  Body Mass Index (BMI) of 18.0 to 45.0 kg/m2; and a total body weight >50 kg (110
                  lbs).

               -  An informed consent document signed and dated by the subject.

               -  Subjects who are willing and able to comply with scheduled visits, treatment
                  plan, laboratory tests, and other study procedures.

        PART A ONLY: Subjects treated with metformin monotherapy for at least 3 months at the time
        of the screening visit; and have been on a stable dose of metformin for at least 6 weeks
        prior to the first dose of study drug on Day 1. Subjects must be taking a minimum total
        metformin daily dose of least 1000 mg. Subjects treated with a dipeptidyl peptidase-4
        inhibitor (DPP-4i), a sulfonylurea or a sodium-glucose cotransporter-2 inhibitor (SGLT-2i)
        in combination with metformin may be eligible if washed off the DPP-4i, sulfonylurea or
        SGLT-2i for a minimum of 4 weeks prior to dosing. Subjects being washed off a DPP-4i,
        sulfonylurea or SGLT-2i will still need to meet the fasting glucose requirements as defined
        in the Inclusion Criteria.

        PART B ONLY: Subjects treated with metformin plus a sulfonylurea for at least 3 months at
        the time of the screening visit; and have been on a stable dose of metformin and a
        sulfonylurea for at least 6 weeks prior to first dose of study drug on Day 1. Subjects must
        be taking a minimum total metformin daily dose of least 1000 mg and a total daily dose of
        sulfonylurea that is at least the minimum recommended starting dose found in the product
        label. Subjects treated with a DPP-4i or SGLT-2i in combination with metformin and a
        sulfonylurea may be eligible if washed off the DPP-4i or SGLT-2i for a minimum of 4 weeks
        before dosing.

        Exclusion Criteria:

          -  History of Type 1 diabetes mellitus or secondary forms of diabetes.

          -  One or more self-reported hypoglycemic episodes of severe intensity within 3 months of
             screening; or two or more self-reported hypoglycemic episodes of severe intensity
             within the last 6 months.

          -  Recent [ie, within six (6) months prior to screening] evidence or medical history of
             unstable concurrent disease such as: clinically significant hematological,
             endocrine,pulmonary, gastrointestinal (including severe gastroparesis),
             cardiovascular, hepatic, psychiatric, neurologic, or clinically significant allergic
             disease (excluding treated and untreated seasonal allergies at time of dosing).
             Subjects who have chronic conditions other than T2DM (for example,
             hypercholesterolemia or hypertension) but are controlled by either diet or stable (for
             the last 4 weeks prior to screening) doses of medications may be included as well (for
             example, a subject with hypercholesterolemia on appropriate treatment is eligible).