Clinical trial: Safety and Tolerability Study of Oral LGD-6972 for Type 2 Diabetes Mellitus (NCT02250222)

Eligibility criteria:
INCLUSION CRITERIA:

        Part 1

          1. Healthy, adult man or woman, 21 to 65 years of age. If the subject is a woman, she
             must be surgically sterile or naturally post-menopausal to be considered for
             enrollment.

          2. Willing and able to provide written informed consent.

          3. Not diabetic and has a fasting plasma glucose (FPG) between 70 mg/dL and 105 mg/dL,
             inclusive.

          4. Good health with no significant concomitant pathology based on medical history,
             physical examination, electrocardiogram (ECG), routine laboratory tests (chemistry,
             hematology, lipid profile, international normalized ratio, and urinalysis), and vital
             signs.

        Part 2

          1. Healthy, adult man or woman, 21 to 65 years of age. If the subject is a woman, she
             must be surgically sterile or naturally post-menopausal to be considered for
             enrollment.

          2. Willing and able to provide written informed consent.

          3. Has T2DM according to American Diabetes Association criteria.

          4. Currently on stable metformin therapy (unchanged dose for greater than or equal to 12
             weeks prior to screening). At the discretion of the investigator, subjects who are
             drug naïve or whose metformin dose has not been stable for at least 12 weeks at
             screening, may be started on metformin or have their metformin dose stabilized.
             Following 12 weeks of stable metformin, they may undergo re screening including
             assessment of HbA1c and FPG (inclusion criteria 5 and 6).

          5. Has an HbA1c level between 6.5% and 10.5% at screening. One retest is permitted.

          6. Venous FPG is 125 mg/dL and 260 mg/dL at screening and either the Day -1 venous FPG or
             the Day 1 capillary blood glucose (CBG) is 115 mg/dL and 260 mg/dL. One retest is
             permitted.

          7. Has a body mass index between 20 and 45 kg/m2, inclusive.

        EXCLUSION CRITERIA:

        Part 1

          1. Has a recent history of drug and/or alcohol abuse.

          2. Unwilling to comply with tobacco, nicotine, alcohol, and caffeine restrictions as
             specified in the protocol.

          3. Unwilling to comply with restrictions on strenuous exercise as specified in the
             protocol.

          4. Has history of clinically significant cardiovascular, pulmonary, renal, endocrine,
             hepatic, neurologic, psychiatric, immunologic, hematologic, gastrointestinal
             (including pancreatitis), or metabolic disease requiring medical treatment or has any
             medical problems that pose an increased risk during the study or that may compromise
             the integrity of the study data.

          5. Has liver transaminase levels (aspartate transaminase [AST] or alanine transaminase
             [ALT]) >10% of the upper limit of normal (ULN), or has creatine kinase (CK) levels >2
             × ULN at screening or admission to clinic (Day -1).

          6. Has a plasma triglyceride level >400 mg/dL. If triglyceride level is between 400 mg/dL
             and 500 mg/dL.

          7. Has a recent history of uncontrolled high blood pressure or has systolic blood
             pressure <90 mmHg or >140 mmHg or diastolic blood pressure <60 mmHg or >90 mmHg at
             screening.

          8. Is taking prescription or non-prescription drugs, vitamins, herbal, and dietary
             supplements, within 14 days or 5 half-lives (whichever is longer) prior to the first
             dose of study drug, or is unwilling to refrain from taking any such medication until
             after the last protocol-specified blood sample. The use of acetaminophen, not to
             exceed a total daily dose of 1 g, is permitted up to 24 hours prior to admission to
             the investigational site and then prohibited until after the last protocol-specified
             blood sample. The use of stable hormone replacement medication by women, topical
             steroids, and stable thyroid medication is permitted.

        Part 2

          1. Has a history of hypoglycemic unawareness or recurrent hypoglycemia requiring
             assistance.

          2. Has liver transaminase levels (AST or ALT) >10% × ULN, or has CK levels >1.5 × ULN at
             screening or admission to clinic (Day -1).

          3. Has history of clinically significant cardiovascular, pulmonary, renal, endocrine
             (other than T2DM), hepatic, neurologic, psychiatric, immunologic, hematologic,
             gastrointestinal (including pancreatitis), or metabolic disease requiring medical
             treatment or has any medical problems that pose an increased risk during the study or
             that may compromise the integrity of the study data.

          4. Has a recent history of uncontrolled high blood pressure or has systolic blood
             pressure <90 mmHg or >140 mmHg or diastolic blood pressure <60 mmHg or >90 mmHg at
             screening. One retest of blood pressure within 24 hours is permissible at the
             discretion of the Investigator. Therapy for hypertension (beta blockers excluded) that
             has been stable for at least one month prior to screening is permitted. At the
             Investigator's discretion, one anti-hypertensive medication (angiotensin converting
             enzyme inhibitor, angiotensin receptor blocker, hydrochlorothiazide, or
             dihydropyridine calcium-channel blocker) may be initiated, or the dosage of a current
             antihypertensive medication up titrated, in a subject with blood pressure slightly
             above the eligibility criterion at screening. After at least 4 weeks of stable blood
             pressure treatment, if the subject's blood pressure has decreased to within the 140/90
             mmHg limit, the subject will be fully reassessed for eligibility.

          5. Has received insulin for more than 6 consecutive days within 6 months prior to
             screening or has received insulin within 3 months prior to screening.

          6. Has been treated with peroxisome proliferator-activated receptor gamma agonist,
             incretin therapy, amylin mimetics, or sodium-glucose linked transporter-2 inhibitor
             therapy within 12 weeks prior to screening; treatment with other diabetic medications
             (excluding metformin) within 3 weeks prior to screening.

          7. Is taking concomitant medications. At least 3 months of stable therapy for thyroid
             replacement and hypercholesterolemia (gemfibrozil, Welchol, and cholestyramine are not
             permitted) and at least 4 weeks of stable hypertension medications (as described
             above) and low dose aspirin are permitted.
No condition on gender to be admitted to the trial.
Accepts Healthy Volunteers
Subject must be at least 21 Years old.
Subject must be at most 65 Years

Patient description (medical language): A 50-year-old woman comes to the clinic with intermittent ear discharge and sense of hearing loss on her left ear.  Past medical history is significant for obesity, hyperlipidemia, and diabetes mellitus.  Her medications include Metformin, Atorvastatin and Vit D supplement. Vital signs are normal. BMI is 37. Otoscopy shows a small perforation in the left tympanic membrane and a pearly mass behind the membrane.  Conduction hearing loss is noted in the left ear.  The remainder of the ear, nose, and throat examination is normal.

Patient description (patient's own words): I went to the clinic the other day because I had some fluid in my ear and I felt like I could not hear as well as I used to in my left ear. I'm a 50-year-old woman, and I have been obese for a while now. I have diabetes and cholesterol. I take some medication. I take metformin, atorvastatin, and vitamin D supplements. When I was admitted, my vitals were normal. My BMI is 37. When they looked into my ears, they said that my left tympanic membrane was broken and there was some fluid behind the membrane. During the hearing test, they could assess that my left ear suffers from hearing loss. They also performed ear, nose, and throat examinations that turned out to be normal.

Does the patient match the trial criteria? 1