A Study to Assess the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of GLWL-01
Condition: Diabetes Mellitus, Type 2
MeSH terms: Diabetes Mellitus, Type 2
Intervention: GLWL-01, Part A; Placebo, Part A; GLWL-01, Part B; Placebo, Part B; GLWL-01, Part C; Placebo, Part C
Intervention description: Capsules administered orally, in 2 out of 3 periods; Capsules administered orally in 1 out of 3 periods; Capsules administered orally either once or twice daily for 27 days, with a single dose on Day 28; Capsules administered orally either once or twice daily for 27 days with a single dose on Day 28; Capsules administered orally either once or twice daily for 27 days with a single dose on Day 28; Capsules administered orally either once or twice daily for 27 days with a single dose on Day 28
Phase: Phase 1
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Enrollment: 74.0
Sex: All
Minimum age: 18 Years
Maximum age: 70 Years
Healthy volunteers: Accepts Healthy Volunteers

Summary:

      This 3-part study will explore the safety and tolerability of GLWL-01 in overweight/obese
      healthy participants after single doses (in Part A), and in participants with type 2 diabetes
      mellitus after multiple doses during a 28-day period (Parts B and C).
    

Eligibility criteria:

        Inclusion Criteria:

        PARTS A-C:

          -  Non-vasectomized males (or those vasectomized less than 4 months prior to study start)
             must agree to use a condom with spermicide or abstain from sexual intercourse during
             the study until 90 days beyond the last dose of study drug

          -  Males agree to not donate sperm from dosing until 90 days after dosing

          -  Laboratory test results within normal range or acceptable deviation, and Aspartate
             Aminotransferase (AST) / Alanine Aminotransferase (ALT) / Gamma Glutamyl Transferase
             (GGT) / Alkaline Phosphatase (ALP) to be less than or equal to (≤)1.5 x upper limit of
             normal (ULN), and total bilirubin has to be within normal limit

          -  Estimated glomerular filtration rate (eGFR) greater than or equal to (≥) 60 milliliter
             (mL)/minute/1.73m2

          -  No evidence of weight excursion beyond 5% of baseline weight within 3 months of
             screening

        PART A Only:

          -  Overtly healthy males or females, as determined by medical history and physical
             examination

          -  Males must be 18 to 65 years old; females must be 40 to 65 years old

          -  Female participants must be:

               1. Women with prior history of hysterectomy who are at least 45 years of age and
                  with follicle-stimulating hormone (FSH) greater than (>) 40 milli-international
                  units per milliliter (mIU/mL), or

               2. Menopausal women with either: spontaneous amenorrhea for at least 12 months (not
                  induced by a medical condition or medications); or spontaneous amenorrhea for 6
                  to 12 months and a FSH > 40 mIU/mL

          -  Body mass index (BMI) of 28 to 35 kilograms divided by height in meters squared
             (kg/m2)

          -  Normotensive (supine systolic blood pressure (BP) less than (<) 140 millimeter of
             mercury (mmHg) and diastolic BP <90 mmHg

          -  No evidence of weight excursion beyond 5% of baseline weight within 3 months of
             screening

        PARTS B and C:

          -  Must have Type 2 Diabetes Mellitus

          -  Be 18 to 70 years old

          -  Have BMI of 28 to 42 kg/m2

          -  Female participants must be of non-childbearing potential, and must have undergone one
             of the following sterilization procedures at least 6 months prior to first dose:
             hysteroscopic sterilization, bilateral tubal ligation or bilateral salpingectomy,
             hysterectomy, or bilateral oophorectomy; or be postmenopausal with amenorrhea for at
             least 1 year prior to the first dose and with FSH serum levels consistent with
             postmenopausal status

          -  Normotensive (supine systolic BP) < 150 mmHg and diastolic BP <95 mmHg or
             well-controlled hypertension while on a stable hypertensive

        Exclusion Criteria:

        PARTS A-C:

          -  Currently enrolled in a clinical trial or any other medical research judged to be not
             compatible with the study, or have participated in the last 30 days prior to dosing in
             a clinical trial involving an investigational product or non-approved use of a drug
             with short half-life, or within 5 half-lives of an investigational product with a
             half-life longer than 6 days

          -  Abnormality in the 12-lead electrocardiogram (ECG) including corrected QT (QTc)
             interval with Bazett's correction >450 milliseconds (msec) for men and >470 msec for
             women, or an abnormality that, in the opinion of the Investigator, increases the risks
             associated with participating in the study

          -  Significant cardiovascular disease or other disorders

          -  Evidence of human immunodeficiency virus (HIV) infection, hepatitis B, hepatitis C, or
             other chronic liver or biliary disease

          -  Average weekly alcohol intake that exceeds 21 units per week (males) and 14 units per
             week (females), or is unwilling to stop use of Cytochrome P450 (CYP3A)
             inhibitors/inducers (St. John's Wort) or alcohol consumption for the study, or regular
             use of known drugs of abuse or positive finding on urinary drug screen, use of
             cigarettes or nicotine products within last 3 months, or blood donation or loss within
             56 days prior to the study

          -  Neuropsychiatric disease or pharmacological therapy for such conditions within 1 year
             of dosing, or antidepressants or antipsychotics within 3 months of dosing, or surgery
             within last 60 days

          -  Eating disorder or weight loss medications within 4 months of dosing, or bariatric
             surgery

          -  Unsuitable for inclusion in the study in the opinion of the investigator or sponsor

        PART A Only:

          -  History of hypertension (or on treatment with any antihypertensives)

          -  Endocrine illness such as diabetes, growth hormone insufficiency / acromegaly, adrenal
             gland or thyroid illness

        PARTS B and C:

          -  Currently taking simvastatin > 10 mg per day, or atorvastatin > 20 mg per day, or
             lovastatin >20 mg per day, or history of statin-induced myopathy / rhabdomyolysis.
             Participants taking any dose of simvastatin will be excluded from some cohorts

          -  Allergic to the components of the Mixed Meal Tolerance Test