<clinical_study>
  <!-- This xml conforms to an XML Schema at:
    https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
  <required_header>
    <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
    <link_text>Link to the current ClinicalTrials.gov record.</link_text>
    <url>https://clinicaltrials.gov/ct2/show/NCT02250222</url>
  </required_header>
  <id_info>
    <org_study_id>L6972-02</org_study_id>
    <nct_id>NCT02250222</nct_id>
  </id_info>
  <brief_title>Safety and Tolerability Study of Oral LGD-6972 for Type 2 Diabetes Mellitus</brief_title>
  <acronym>L6972-02</acronym>
  <official_title>Randomized, Double-Blind, Placebo-Controlled, Multiple Ascending Oral Dose Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of LGD-6972 in Healthy Subjects and in Subjects With Type 2 Diabetes Mellitus</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Ligand Pharmaceuticals</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Ligand Pharmaceuticals</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      Ligand Pharmaceuticals Incorporated is developing LGD-6972, a novel, orally-bioavailable&#xD;
      addition to diet and exercise to improve glycemic control in adults with type 2 diabetes&#xD;
      mellitus. The mechanism of action of LGD-6972 is to reduce the excess liver glucose&#xD;
      production characteristic of type 2 diabetes mellitus that is a major contributor to&#xD;
      hyperglycemia. This clinical trial will evaluate the safety and tolerability of escalating&#xD;
      doses LGD-6972 administered daily over 2 weeks in both healthy subjects and subjects with&#xD;
      type 2 diabetes mellitus.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This is to be a randomized, double-blind, placebo-controlled, sequential, multiple oral dose&#xD;
      study conducted in normoglycemic healthy subjects (NHS) (Part 1) and subjects with type 2&#xD;
      diabetes mellitus (T2DM) who are treated with monotherapy metformin (a stable dose at&#xD;
      randomization) along with diet and exercise (Part 2). Subjects with T2DM who are not on a&#xD;
      stable dose of metformin but meet all other entry criteria may be enrolled in the study at&#xD;
      the discretion of the Investigator, but must undergo a stabilization period of at least 12&#xD;
      weeks before determining eligibility for the study. In Part 1, a single group of healthy&#xD;
      subjects will be dosed with repeated oral doses of 15 mg of LGD-6972 or placebo once daily&#xD;
      (QD) for 14 days. In Part 2, a maximum of 3 groups of subjects with T2DM will be dosed with 3&#xD;
      sequential, increasing doses of LGD-6972 (5 mg, 10 mg or 15 mg) or placebo QD for 14 days.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>October 2014</start_date>
  <completion_date type="Actual">June 2015</completion_date>
  <primary_completion_date type="Actual">May 2015</primary_completion_date>
  <phase>Phase 1</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Number of participants with one or more drug related adverse events or serious adverse events</measure>
    <time_frame>At least 14 days after last dose</time_frame>
    <description>Safety and tolerability of repeat (14 days for normoglycemic healthy subjects (NHS) and 14 days for type 2 diabetes mellitus (T2DM) subjects) and sequential increasing oral doses of LGD-6972 in NHS and subjects withT2DM will be compared to NHS and T2DM subjects receiving placebo.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Pharmacokinetic (PK) profile (area under the concentration curve (AUC) of LGD-6972 after repeat oral doses in NHS and in subjects with T2DM</measure>
    <time_frame>14 days</time_frame>
    <description>Steady state PK profile (AUC) of LGD-6972 in NHS and in subjects with T2DM will be characterized and compared.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change from baseline in fasting plasma glucose measured 24 hours after first dose and pre-dose Day 14 of treatment with LGD-6972 in NHS</measure>
    <time_frame>14 days</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change from baseline in fasting plasma glucagon measured 24 hours after first dose and pre-dose Day 14 of treatment with LGD-6972 in NHS</measure>
    <time_frame>14 days</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change from baseline in active and total glucagon-like-peptide (GLP-1) in fasting plasma measured 24 hours after first dose and pre-dose Day 14 of treatment with LGD-6972 in NHS</measure>
    <time_frame>14 days</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change from baseline in fasting plasma glucose measured 24 hours after first dose and at Day 14 of treatment with LGD-6972 in subjects with T2DM</measure>
    <time_frame>14 days</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change from baseline in fasting plasma glucagon measured 24 hours after first dose and at Day 14 of treatment with LGD-6972 in subjects with T2DM</measure>
    <time_frame>14 days</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change from baseline in fasting plasma insulin measured 24 hours after first dose and at Day 14 of treatment with LGD-6972 in subjects with T2DM</measure>
    <time_frame>14 days</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change from baseline in fasting plasma active and total GLP-1 measured 24 hours after first dose and at Day 14 of treatment with LGD-6972 in subjects with T2DM</measure>
    <time_frame>14 days</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change from baseline in 7-point weighted mean glucose during 14 days of treatment with different doses of LGD-6972 in subjects with T2DM</measure>
    <time_frame>14 days</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Hemoglobin A1c response during 14 days of treatment with different dosages of LGD-6972 in subjects with T2DM</measure>
    <time_frame>14 days</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>PK profile (maximum concentration (Cmax) of LGD-6972 after repeat oral doses in NHS and in subjects with T2DM</measure>
    <time_frame>14 days</time_frame>
    <description>Steady state PK profile (Cmax) of LGD-6972 in NHS and in subjects with T2DM will be characterized and compared.</description>
  </secondary_outcome>
  <other_outcome>
    <measure>Change from baseline in fasting plasma glucose measured during an oral glucose tolerance test (OGTT) on Day 14 of treatment with LGD-6972 at 0.5, 1, 1.5, 2, 3, and 4 hours post-glucose load in one dose group of subjects with T2DM</measure>
    <time_frame>14 days</time_frame>
  </other_outcome>
  <other_outcome>
    <measure>Change from baseline in fasting plasma glucagon measured during an OGTT on Day 14 of treatment with LGD-6972 at 0.5, 1, 1.5, 2, 3, and 4 hours post-glucose load in one dose group of subjects with T2DM</measure>
    <time_frame>14 days</time_frame>
  </other_outcome>
  <other_outcome>
    <measure>Change from baseline in fasting plasma insulin measured during an OGTT on Day 14 of treatment with LGD-6972 at 0.5, 1, 1.5, 2, 3, and 4 hours post-glucose load in one dose group of subjects with T2DM</measure>
    <time_frame>14 days</time_frame>
  </other_outcome>
  <other_outcome>
    <measure>Change from baseline in fasting plasma active and total GLP-1 measured during an OGTT on Day 14 of treatment with LGD-6972 at 0.5, 1, 1.5, 2, 3, and 4 hours post-glucose load in one dose group of subjects with T2DM</measure>
    <time_frame>14 days</time_frame>
  </other_outcome>
  <number_of_arms>6</number_of_arms>
  <enrollment type="Actual">48</enrollment>
  <condition>Type 2 Diabetes Mellitus</condition>
  <arm_group>
    <arm_group_label>Part 1: LGD-6972 15 mg</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>15 mg LGD-6972 administered once daily (QD) for 14 days.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Part 1: Placebo (Captisol ®)</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Placebo administered once daily (QD) for 14 days.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Part 2: LGD-6972 5 mg</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>5 mg LGD-6972 administered orally QD for 14 days.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Part 2: LGD-6972 10 mg</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>10 mg LGD-6972 administered orally QD for 14 days.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Part 2: LGD-6972 15 mg</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>15 mg LGD-6972 administered orally QD for 14 days.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Part 2: Placebo (Captisol ®)</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Placebo administered orally QD for 14 days.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>LGD-6972</intervention_name>
    <description>LGD-6972 sodium salt powder in Captisol ® (betadex [β-cyclodextrin] sulfobutylether sodium, NF)</description>
    <arm_group_label>Part 1: LGD-6972 15 mg</arm_group_label>
    <arm_group_label>Part 2: LGD-6972 10 mg</arm_group_label>
    <arm_group_label>Part 2: LGD-6972 15 mg</arm_group_label>
    <arm_group_label>Part 2: LGD-6972 5 mg</arm_group_label>
    <other_name>LGD-6972 sodium oral solution</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo (Captisol ®)</intervention_name>
    <description>betadex [β-cyclodextrin] sulfobutylether sodium, NF</description>
    <arm_group_label>Part 1: Placebo (Captisol ®)</arm_group_label>
    <arm_group_label>Part 2: Placebo (Captisol ®)</arm_group_label>
    <other_name>SBECD</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        INCLUSION CRITERIA:&#xD;
&#xD;
        Part 1&#xD;
&#xD;
          1. Healthy, adult man or woman, 21 to 65 years of age. If the subject is a woman, she&#xD;
             must be surgically sterile or naturally post-menopausal to be considered for&#xD;
             enrollment.&#xD;
&#xD;
          2. Willing and able to provide written informed consent.&#xD;
&#xD;
          3. Not diabetic and has a fasting plasma glucose (FPG) between 70 mg/dL and 105 mg/dL,&#xD;
             inclusive.&#xD;
&#xD;
          4. Good health with no significant concomitant pathology based on medical history,&#xD;
             physical examination, electrocardiogram (ECG), routine laboratory tests (chemistry,&#xD;
             hematology, lipid profile, international normalized ratio, and urinalysis), and vital&#xD;
             signs.&#xD;
&#xD;
        Part 2&#xD;
&#xD;
          1. Healthy, adult man or woman, 21 to 65 years of age. If the subject is a woman, she&#xD;
             must be surgically sterile or naturally post-menopausal to be considered for&#xD;
             enrollment.&#xD;
&#xD;
          2. Willing and able to provide written informed consent.&#xD;
&#xD;
          3. Has T2DM according to American Diabetes Association criteria.&#xD;
&#xD;
          4. Currently on stable metformin therapy (unchanged dose for greater than or equal to 12&#xD;
             weeks prior to screening). At the discretion of the investigator, subjects who are&#xD;
             drug naïve or whose metformin dose has not been stable for at least 12 weeks at&#xD;
             screening, may be started on metformin or have their metformin dose stabilized.&#xD;
             Following 12 weeks of stable metformin, they may undergo re screening including&#xD;
             assessment of HbA1c and FPG (inclusion criteria 5 and 6).&#xD;
&#xD;
          5. Has an HbA1c level between 6.5% and 10.5% at screening. One retest is permitted.&#xD;
&#xD;
          6. Venous FPG is 125 mg/dL and 260 mg/dL at screening and either the Day -1 venous FPG or&#xD;
             the Day 1 capillary blood glucose (CBG) is 115 mg/dL and 260 mg/dL. One retest is&#xD;
             permitted.&#xD;
&#xD;
          7. Has a body mass index between 20 and 45 kg/m2, inclusive.&#xD;
&#xD;
        EXCLUSION CRITERIA:&#xD;
&#xD;
        Part 1&#xD;
&#xD;
          1. Has a recent history of drug and/or alcohol abuse.&#xD;
&#xD;
          2. Unwilling to comply with tobacco, nicotine, alcohol, and caffeine restrictions as&#xD;
             specified in the protocol.&#xD;
&#xD;
          3. Unwilling to comply with restrictions on strenuous exercise as specified in the&#xD;
             protocol.&#xD;
&#xD;
          4. Has history of clinically significant cardiovascular, pulmonary, renal, endocrine,&#xD;
             hepatic, neurologic, psychiatric, immunologic, hematologic, gastrointestinal&#xD;
             (including pancreatitis), or metabolic disease requiring medical treatment or has any&#xD;
             medical problems that pose an increased risk during the study or that may compromise&#xD;
             the integrity of the study data.&#xD;
&#xD;
          5. Has liver transaminase levels (aspartate transaminase [AST] or alanine transaminase&#xD;
             [ALT]) &gt;10% of the upper limit of normal (ULN), or has creatine kinase (CK) levels &gt;2&#xD;
             × ULN at screening or admission to clinic (Day -1).&#xD;
&#xD;
          6. Has a plasma triglyceride level &gt;400 mg/dL. If triglyceride level is between 400 mg/dL&#xD;
             and 500 mg/dL.&#xD;
&#xD;
          7. Has a recent history of uncontrolled high blood pressure or has systolic blood&#xD;
             pressure &lt;90 mmHg or &gt;140 mmHg or diastolic blood pressure &lt;60 mmHg or &gt;90 mmHg at&#xD;
             screening.&#xD;
&#xD;
          8. Is taking prescription or non-prescription drugs, vitamins, herbal, and dietary&#xD;
             supplements, within 14 days or 5 half-lives (whichever is longer) prior to the first&#xD;
             dose of study drug, or is unwilling to refrain from taking any such medication until&#xD;
             after the last protocol-specified blood sample. The use of acetaminophen, not to&#xD;
             exceed a total daily dose of 1 g, is permitted up to 24 hours prior to admission to&#xD;
             the investigational site and then prohibited until after the last protocol-specified&#xD;
             blood sample. The use of stable hormone replacement medication by women, topical&#xD;
             steroids, and stable thyroid medication is permitted.&#xD;
&#xD;
        Part 2&#xD;
&#xD;
          1. Has a history of hypoglycemic unawareness or recurrent hypoglycemia requiring&#xD;
             assistance.&#xD;
&#xD;
          2. Has liver transaminase levels (AST or ALT) &gt;10% × ULN, or has CK levels &gt;1.5 × ULN at&#xD;
             screening or admission to clinic (Day -1).&#xD;
&#xD;
          3. Has history of clinically significant cardiovascular, pulmonary, renal, endocrine&#xD;
             (other than T2DM), hepatic, neurologic, psychiatric, immunologic, hematologic,&#xD;
             gastrointestinal (including pancreatitis), or metabolic disease requiring medical&#xD;
             treatment or has any medical problems that pose an increased risk during the study or&#xD;
             that may compromise the integrity of the study data.&#xD;
&#xD;
          4. Has a recent history of uncontrolled high blood pressure or has systolic blood&#xD;
             pressure &lt;90 mmHg or &gt;140 mmHg or diastolic blood pressure &lt;60 mmHg or &gt;90 mmHg at&#xD;
             screening. One retest of blood pressure within 24 hours is permissible at the&#xD;
             discretion of the Investigator. Therapy for hypertension (beta blockers excluded) that&#xD;
             has been stable for at least one month prior to screening is permitted. At the&#xD;
             Investigator's discretion, one anti-hypertensive medication (angiotensin converting&#xD;
             enzyme inhibitor, angiotensin receptor blocker, hydrochlorothiazide, or&#xD;
             dihydropyridine calcium-channel blocker) may be initiated, or the dosage of a current&#xD;
             antihypertensive medication up titrated, in a subject with blood pressure slightly&#xD;
             above the eligibility criterion at screening. After at least 4 weeks of stable blood&#xD;
             pressure treatment, if the subject's blood pressure has decreased to within the 140/90&#xD;
             mmHg limit, the subject will be fully reassessed for eligibility.&#xD;
&#xD;
          5. Has received insulin for more than 6 consecutive days within 6 months prior to&#xD;
             screening or has received insulin within 3 months prior to screening.&#xD;
&#xD;
          6. Has been treated with peroxisome proliferator-activated receptor gamma agonist,&#xD;
             incretin therapy, amylin mimetics, or sodium-glucose linked transporter-2 inhibitor&#xD;
             therapy within 12 weeks prior to screening; treatment with other diabetic medications&#xD;
             (excluding metformin) within 3 weeks prior to screening.&#xD;
&#xD;
          7. Is taking concomitant medications. At least 3 months of stable therapy for thyroid&#xD;
             replacement and hypercholesterolemia (gemfibrozil, Welchol, and cholestyramine are not&#xD;
             permitted) and at least 4 weeks of stable hypertension medications (as described&#xD;
             above) and low dose aspirin are permitted.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>21 Years</minimum_age>
    <maximum_age>65 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Keith Marschke, Ph.D.</last_name>
    <role>Study Director</role>
    <affiliation>Ligand Pharmaceuticals</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Celerion, Inc</name>
      <address>
        <city>Tempe</city>
        <state>Arizona</state>
        <zip>85283</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Clinical Pharmacology of Miami, Inc</name>
      <address>
        <city>Miami</city>
        <state>Florida</state>
        <zip>33014</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Medpace Clinical Pharmacology</name>
      <address>
        <city>Cincinnati</city>
        <state>Ohio</state>
        <zip>45227</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>June 2015</verification_date>
  <study_first_submitted>September 19, 2014</study_first_submitted>
  <study_first_submitted_qc>September 25, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">September 26, 2014</study_first_posted>
  <last_update_submitted>June 10, 2015</last_update_submitted>
  <last_update_submitted_qc>June 10, 2015</last_update_submitted_qc>
  <last_update_posted type="Estimate">June 11, 2015</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Diabetes Mellitus</mesh_term>
    <mesh_term>Diabetes Mellitus, Type 2</mesh_term>
  </condition_browse>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT02250222
org study id: L6972-02
nct id: NCT02250222
lead sponsor: 
has dmc: Yes
Ligand Pharmaceuticals Incorporated is developing LGD-6972, a novel, orally-bioavailable
      addition to diet and exercise to improve glycemic control in adults with type 2 diabetes
      mellitus. The mechanism of action of LGD-6972 is to reduce the excess liver glucose
      production characteristic of type 2 diabetes mellitus that is a major contributor to
      hyperglycemia. This clinical trial will evaluate the safety and tolerability of escalating
      doses LGD-6972 administered daily over 2 weeks in both healthy subjects and subjects with
      type 2 diabetes mellitus.
This is to be a randomized, double-blind, placebo-controlled, sequential, multiple oral dose
      study conducted in normoglycemic healthy subjects (NHS) (Part 1) and subjects with type 2
      diabetes mellitus (T2DM) who are treated with monotherapy metformin (a stable dose at
      randomization) along with diet and exercise (Part 2). Subjects with T2DM who are not on a
      stable dose of metformin but meet all other entry criteria may be enrolled in the study at
      the discretion of the Investigator, but must undergo a stabilization period of at least 12
      weeks before determining eligibility for the study. In Part 1, a single group of healthy
      subjects will be dosed with repeated oral doses of 15 mg of LGD-6972 or placebo once daily
      (QD) for 14 days. In Part 2, a maximum of 3 groups of subjects with T2DM will be dosed with 3
      sequential, increasing doses of LGD-6972 (5 mg, 10 mg or 15 mg) or placebo QD for 14 days.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
measure: Number of participants with one or more drug related adverse events or serious adverse events
time frame: At least 14 days after last dose
description: Safety and tolerability of repeat (14 days for normoglycemic healthy subjects (NHS) and 14 days for type 2 diabetes mellitus (T2DM) subjects) and sequential increasing oral doses of LGD-6972 in NHS and subjects withT2DM will be compared to NHS and T2DM subjects receiving placebo.
measure: Pharmacokinetic (PK) profile (area under the concentration curve (AUC) of LGD-6972 after repeat oral doses in NHS and in subjects with T2DM
time frame: 14 days
description: Steady state PK profile (AUC) of LGD-6972 in NHS and in subjects with T2DM will be characterized and compared.
measure: Change from baseline in fasting plasma glucose measured 24 hours after first dose and pre-dose Day 14 of treatment with LGD-6972 in NHS
time frame: 14 days
measure: Change from baseline in fasting plasma glucagon measured 24 hours after first dose and pre-dose Day 14 of treatment with LGD-6972 in NHS
time frame: 14 days
measure: Change from baseline in active and total glucagon-like-peptide (GLP-1) in fasting plasma measured 24 hours after first dose and pre-dose Day 14 of treatment with LGD-6972 in NHS
time frame: 14 days
measure: Change from baseline in fasting plasma glucose measured 24 hours after first dose and at Day 14 of treatment with LGD-6972 in subjects with T2DM
time frame: 14 days
measure: Change from baseline in fasting plasma glucagon measured 24 hours after first dose and at Day 14 of treatment with LGD-6972 in subjects with T2DM
time frame: 14 days
measure: Change from baseline in fasting plasma insulin measured 24 hours after first dose and at Day 14 of treatment with LGD-6972 in subjects with T2DM
time frame: 14 days
measure: Change from baseline in fasting plasma active and total GLP-1 measured 24 hours after first dose and at Day 14 of treatment with LGD-6972 in subjects with T2DM
time frame: 14 days
measure: Change from baseline in 7-point weighted mean glucose during 14 days of treatment with different doses of LGD-6972 in subjects with T2DM
time frame: 14 days
measure: Hemoglobin A1c response during 14 days of treatment with different dosages of LGD-6972 in subjects with T2DM
time frame: 14 days
measure: PK profile (maximum concentration (Cmax) of LGD-6972 after repeat oral doses in NHS and in subjects with T2DM
time frame: 14 days
description: Steady state PK profile (Cmax) of LGD-6972 in NHS and in subjects with T2DM will be characterized and compared.
measure: Change from baseline in fasting plasma glucose measured during an oral glucose tolerance test (OGTT) on Day 14 of treatment with LGD-6972 at 0.5, 1, 1.5, 2, 3, and 4 hours post-glucose load in one dose group of subjects with T2DM
time frame: 14 days
measure: Change from baseline in fasting plasma glucagon measured during an OGTT on Day 14 of treatment with LGD-6972 at 0.5, 1, 1.5, 2, 3, and 4 hours post-glucose load in one dose group of subjects with T2DM
time frame: 14 days
measure: Change from baseline in fasting plasma insulin measured during an OGTT on Day 14 of treatment with LGD-6972 at 0.5, 1, 1.5, 2, 3, and 4 hours post-glucose load in one dose group of subjects with T2DM
time frame: 14 days
measure: Change from baseline in fasting plasma active and total GLP-1 measured during an OGTT on Day 14 of treatment with LGD-6972 at 0.5, 1, 1.5, 2, 3, and 4 hours post-glucose load in one dose group of subjects with T2DM
time frame: 14 days
arm group label: Part 1: LGD-6972 15 mg
arm group type: Experimental
description: 15 mg LGD-6972 administered once daily (QD) for 14 days.
arm group label: Part 1: Placebo (Captisol ®)
arm group type: Placebo Comparator
description: Placebo administered once daily (QD) for 14 days.
arm group label: Part 2: LGD-6972 5 mg
arm group type: Experimental
description: 5 mg LGD-6972 administered orally QD for 14 days.
arm group label: Part 2: LGD-6972 10 mg
arm group type: Experimental
description: 10 mg LGD-6972 administered orally QD for 14 days.
arm group label: Part 2: LGD-6972 15 mg
arm group type: Experimental
description: 15 mg LGD-6972 administered orally QD for 14 days.
arm group label: Part 2: Placebo (Captisol ®)
arm group type: Placebo Comparator
description: Placebo administered orally QD for 14 days.
intervention type: Drug
intervention name: LGD-6972
description: LGD-6972 sodium salt powder in Captisol ® (betadex [β-cyclodextrin] sulfobutylether sodium, NF)
arm group label: Part 1: LGD-6972 15 mg
arm group label: Part 2: LGD-6972 10 mg
arm group label: Part 2: LGD-6972 15 mg
arm group label: Part 2: LGD-6972 5 mg
other name: LGD-6972 sodium oral solution
intervention type: Drug
intervention name: Placebo (Captisol ®)
description: betadex [β-cyclodextrin] sulfobutylether sodium, NF
arm group label: Part 1: Placebo (Captisol ®)
arm group label: Part 2: Placebo (Captisol ®)
other name: SBECD
criteria: 
gender: All
minimum age: 21 Years
maximum age: 65 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Keith Marschke, Ph.D.
role: Study Director
affiliation: Ligand Pharmaceuticals
facility: 
facility: 
facility: 
country: United States
responsible party type: Sponsor
mesh term: Diabetes Mellitus
mesh term: Diabetes Mellitus, Type 2