- 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.
- 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).