<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/NCT02229240</url>
  </required_header>
  <id_info>
    <org_study_id>111892</org_study_id>
    <nct_id>NCT02229240</nct_id>
  </id_info>
  <brief_title>Albiglutide Versus Placebo Added-on to Basal-Bolus Insulin Therapy in Subjects With Type 2 Diabetes Mellitus</brief_title>
  <official_title>Study GLP111892: Albiglutide Versus Placebo as Add-on to Intensified Basal-Bolus Insulin Therapy in Subjects With Type 2 Diabetes Mellitus</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>GlaxoSmithKline</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>PPD</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>GlaxoSmithKline</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      This Phase IIIb, randomized, double-blind, parallel-group, placebo-controlled, multicenter,&#xD;
      treat-to-target study of 26 weeks treatment duration will evaluate the efficacy and safety of&#xD;
      once-weekly albiglutide versus placebo as add-on to intensified basal-bolus insulin therapy&#xD;
      (with or without metformin) in subjects with Type 2 Diabetes Mellitus (T2DM). Approximately&#xD;
      450 subjects will be randomly assigned in a 1:1 ratio to 1 of 2 treatment groups: albiglutide&#xD;
      + intensified basal-bolus insulin therapy (with or without metformin) or placebo +&#xD;
      intensified basal-bolus insulin therapy (with or without metformin. The total duration of a&#xD;
      subject's participation will be approximately 32 weeks.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Withdrawn</overall_status>
  <why_stopped>
    Study was cancelled prior to enrolling any patients&#xD;
  </why_stopped>
  <start_date>August 2015</start_date>
  <completion_date type="Anticipated">December 2015</completion_date>
  <primary_completion_date type="Anticipated">December 2015</primary_completion_date>
  <phase>Phase 3</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>Double (Participant, Investigator)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Percentage of subjects with severe or documented symptomatic hypoglycemia through Week 26</measure>
    <time_frame>Up to Week 26</time_frame>
    <description>Severe hypoglycemia is defined as requiring third-party intervention. Documented symptomatic hypoglycaemia is defined as typical symptoms of hypoglycemia with an accompanying plasma glucose concentration &lt;=70 milligram (mg) per decilitre (dL) (&lt;=3.9 millimole per liter [mmol/L]).</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Change from baseline in glycosylated hemoglobin (HbA1c) at Week 26</measure>
    <time_frame>Week 26</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>Change from baseline in body weight at Week 26 and over time</measure>
    <time_frame>Up to Week 26</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Total daily insulin dose, basal insulin dose and bolus insulin dose at Week 26 and over time</measure>
    <time_frame>Up to Week 26</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>HbA1c change from baseline in over time</measure>
    <time_frame>Up to Week 26</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Fasting plasma glucose (FPG) change from Baseline at Week 26 and over time</measure>
    <time_frame>Up to Week 26</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Proportion of subjects achieving a HbA1c &lt;7.0% and &lt; 6.5% at Week 26 and over time</measure>
    <time_frame>Up to Week 26</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percentage of subjects achieving HbA1c &lt;7.0% without weight gain after 26 weeks of treatment</measure>
    <time_frame>Up to Week 26</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percentage of subjects achieving HbA1c &lt;7.0% without severe or documented symptomatic hypoglycemia after 26 weeks of treatment</measure>
    <time_frame>Up to Week 26</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percentage of subjects achieving HbA1c &lt;7.0% without weight gain and without severe or documented hypoglycemia after 26 weeks of treatment</measure>
    <time_frame>Up to Week 26</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of subjects with non-serious adverse events (AE), serious adverse events (SAE), and AEs and SAEs leading to discontinuation</measure>
    <time_frame>Up to Week 30</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Incidence of hypoglycemic events</measure>
    <time_frame>Up to Week 30</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Assessment of clinical laboratory tests, lipids, vital signs, ECGs and physical examinations</measure>
    <time_frame>Up to Week 30</time_frame>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">0</enrollment>
  <condition>Diabetes Mellitus, Type 2</condition>
  <arm_group>
    <arm_group_label>Albiglutide</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Subjects will receive once-weekly subcutaneous injections of albiglutide 30 mg (with forced uptitration to albiglutide 50 mg at Week 4) in addition to intensification of background basal-bolus insulin therapy (with or without metformin) according to predefined titration algorithms.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Matching albiglutide placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Subjects will receive once-weekly subcutaneous injections of matching albiglutide placebo in addition to intensification of background basal-bolus insulin therapy (with or without metformin) according to predefined titration algorithms</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Albiglutide</intervention_name>
    <description>Albiglutide is intended for self-administration as a SC injection. It is provided as a fixed dose of 30 mg of albiglutide or 50 mg of albiglutide in a 0.5 mL injection volume, fully disposable pen injector</description>
    <arm_group_label>Albiglutide</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Matching albiglutide placebo</intervention_name>
    <description>Matching albiglutide placebo will be provided as 0.5-mL injection, fully disposable pen injector system</description>
    <arm_group_label>Matching albiglutide placebo</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Male or female, 18 years of age or older (inclusive at the time of Screening) with&#xD;
             T2DM&#xD;
&#xD;
          -  HbA1c &gt;=7.5% and &lt;=10.0% at Screening.&#xD;
&#xD;
          -  Currently treated with a basal-bolus insulin regimen (with or without metformin) for&#xD;
             at least 3 months before Screening. The subject must be taking the following: Basal&#xD;
             insulin (1 or 2 daily injections of neutral protamine Hagedorn insulin, insulin&#xD;
             glargine, insulin detemir, or insulin degludec) AND Bolus insulin (at least 2&#xD;
             injections of regular insulin, insulin glulisine, insulin aspart, or insulin lispro);&#xD;
             In addition, the total daily dose of insulin must be &lt;=150 units; If taking metformin,&#xD;
             a stable dose for at least 8 weeks before Screening. Note: Subject should not have&#xD;
             received any other antidiabetic medication within 30 days before Screening (e.g.,&#xD;
             glucagon-like peptide-1 receptor [GLP-1R] agonist, dipeptidyl peptidase-IV inhibitor,&#xD;
             sulfonylurea, or thiazolidinedione). Subjects receiving commercially available&#xD;
             premixed basal and prandial insulin are not eligible for this study.&#xD;
&#xD;
          -  Body mass index &lt;=40 kilogram (kg) per squaremeter (m^2)&#xD;
&#xD;
          -  Thyroid-stimulating hormone (TSH) level is normal or clinically euthyroid as&#xD;
             demonstrated by further thyroid tests (e.g., free T4 )&#xD;
&#xD;
          -  Female subjects of childbearing potential (i.e., not surgically sterile and/or not&#xD;
             postmenopausal) must be practicing adequate contraception (as defined in the protocol)&#xD;
             for the duration of participation in the study including the 4-week Posttreatment&#xD;
             Follow-up Period.&#xD;
&#xD;
          -  Willing and able to comply with all study procedures including intensive insulin&#xD;
             administration and performance of frequent SMBG profiles according to the protocol&#xD;
&#xD;
          -  Able and willing to provide written informed consent&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Type 1 diabetes mellitus&#xD;
&#xD;
          -  History of cancer that has not been in full remission for at least 3 years before&#xD;
             Screening. (A history of squamous cell or basal cell carcinoma of the skin or treated&#xD;
             cervical intra-epithelial neoplasia I or II is allowed)&#xD;
&#xD;
          -  Personal or family history of medullary thyroid carcinoma or multiple endocrine&#xD;
             neoplasia type 2&#xD;
&#xD;
          -  Current symptomatic biliary disease or history of acute or chronic pancreatitis&#xD;
&#xD;
          -  Severe gastroparesis, i.e., requiring regular therapy within 6 months before Screening&#xD;
&#xD;
          -  History of significant GI surgery that in the opinion of the investigator is likely to&#xD;
             significantly affect upper GI or pancreatic function (e.g., gastric bypass and&#xD;
             banding, antrectomy, Roux en Y bypass, gastric vagotomy, small bowel resection, or&#xD;
             surgeries thought to significantly affect upper GI function)&#xD;
&#xD;
          -  History of severe hypoglycemia unawareness&#xD;
&#xD;
          -  Diabetic complications (e.g., active proliferative retinopathy or severe diabetic&#xD;
             neuropathy) or any other clinically significant abnormality (including a psychiatric&#xD;
             disorder) that, in the opinion of the investigator, may pose additional risk in&#xD;
             administering the investigational product&#xD;
&#xD;
          -  Clinically significant cardiovascular and/or cerebrovascular disease within 3 months&#xD;
             before Screening including, but not limited to, the following: Stroke or transient&#xD;
             ischemic attack; Acute coronary syndrome (myocardial infarction [MI] or unstable&#xD;
             angina not responsive to nitroglycerin); Cardiac surgery or percutaneous coronary&#xD;
             procedure; Current or history of heart failure (New York Heart Association class III&#xD;
             or IV)&#xD;
&#xD;
          -  Alanine aminotransferase (ALT) &gt;2.5 × upper limit of normal (ULN) or bilirubin &gt;1.5 ×&#xD;
             ULN (isolated bilirubin &gt;1.5 × ULN is acceptable if bilirubin is fractionated and&#xD;
             direct bilirubin &lt;35%)&#xD;
&#xD;
          -  Unstable liver disease (as defined by the presence of ascites, encephalopathy,&#xD;
             coagulopathy, hypoalbuminemia, esophageal or gastric varices, or persistent jaundice),&#xD;
             cirrhosis, known biliary abnormalities (with the exception of Gilbert's syndrome or&#xD;
             asymptomatic gallstones). (Chronic stable hepatitis B and C are acceptable if subject&#xD;
             otherwise meets entry criteria and is not on active antiviral treatment [e.g.,&#xD;
             presence of hepatitis B surface antigen or positive hepatitis C test result within 3&#xD;
             months of Screening])&#xD;
&#xD;
          -  Hemoglobin &lt;11 g/dL (&lt;110 gram per liter [g/L]) for male subjects and &lt;10 g/dL (&lt;100&#xD;
             g/L) for female subjects at Screening&#xD;
&#xD;
          -  Estimated glomerular filtration rate (eGFR) &lt;=30 mL/minute/1.73 m^2 (calculated using&#xD;
             the Modification of Diet in Renal Disease [MDRD] formula) at Screening. Note: As the&#xD;
             use of metformin in subjects with varying degrees of renal function may differ from&#xD;
             country to country, use of metformin should be in accordance with the metformin&#xD;
             product label within the participating country.&#xD;
&#xD;
          -  Fasting triglyceride level &gt;750 mg/dL at Screening&#xD;
&#xD;
          -  Hemoglobinopathy that may affect proper interpretation of HbA1c&#xD;
&#xD;
          -  Known allergy to albiglutide or any product components (including yeast and human&#xD;
             albumin), any other GLP-1 analogue, insulin, or other study medication's excipients OR&#xD;
             other contraindications (per the prescribing information) for the use of potential&#xD;
             study medications (e.g., basal-bolus insulin)&#xD;
&#xD;
          -  Use of oral or systemically injected glucocorticoids within the 3 months before&#xD;
             randomization or high likelihood of a requirement for prolonged treatment (&gt;1 week) in&#xD;
             the 6 months following randomization. However, short courses of oral steroids (single&#xD;
             dose or multiple doses for up to 7 days) may be permitted provided these cases are&#xD;
             discussed with the medical monitor. Inhaled, intra-articular, epidural, and topical&#xD;
             corticosteroids are allowed&#xD;
&#xD;
          -  Female subject is pregnant (confirmed by laboratory testing) or lactating&#xD;
&#xD;
          -  Receipt of any investigational drug within the 30 days or 5 half-lives, whichever is&#xD;
             longer, before Screening, a history of receipt of an investigational antidiabetic drug&#xD;
             within the 3 months before randomization, or receipt of albiglutide in previous&#xD;
             studies&#xD;
&#xD;
          -  Subject that, in the opinion of the investigator, will not benefit from participating&#xD;
             in a treat to target study aimed at achieving HbA1c of 7.0%&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>GSK Clinical Trials</last_name>
    <role>Study Director</role>
    <affiliation>GlaxoSmithKline</affiliation>
  </overall_official>
  <verification_date>January 2016</verification_date>
  <study_first_submitted>August 28, 2014</study_first_submitted>
  <study_first_submitted_qc>August 28, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">September 1, 2014</study_first_posted>
  <last_update_submitted>January 7, 2016</last_update_submitted>
  <last_update_submitted_qc>January 7, 2016</last_update_submitted_qc>
  <last_update_posted type="Estimate">January 11, 2016</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Albiglutide</keyword>
  <keyword>Add-on to basal-bolus insulin therapy</keyword>
  <keyword>Glucagon-like peptide-1 receptor agonist</keyword>
  <keyword>Type 2 diabetes mellitus</keyword>
  <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>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>rGLP-1 protein</mesh_term>
    <mesh_term>Glucagon-Like Peptide 1</mesh_term>
  </intervention_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/NCT02229240
org study id: 111892
nct id: NCT02229240
lead sponsor: 
collaborator: 
has dmc: No
This Phase IIIb, randomized, double-blind, parallel-group, placebo-controlled, multicenter,
      treat-to-target study of 26 weeks treatment duration will evaluate the efficacy and safety of
      once-weekly albiglutide versus placebo as add-on to intensified basal-bolus insulin therapy
      (with or without metformin) in subjects with Type 2 Diabetes Mellitus (T2DM). Approximately
      450 subjects will be randomly assigned in a 1:1 ratio to 1 of 2 treatment groups: albiglutide
      + intensified basal-bolus insulin therapy (with or without metformin) or placebo +
      intensified basal-bolus insulin therapy (with or without metformin. The total duration of a
      subject's participation will be approximately 32 weeks.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Double (Participant, Investigator)
measure: Percentage of subjects with severe or documented symptomatic hypoglycemia through Week 26
time frame: Up to Week 26
description: Severe hypoglycemia is defined as requiring third-party intervention. Documented symptomatic hypoglycaemia is defined as typical symptoms of hypoglycemia with an accompanying plasma glucose concentration <=70 milligram (mg) per decilitre (dL) (<=3.9 millimole per liter [mmol/L]).
measure: Change from baseline in glycosylated hemoglobin (HbA1c) at Week 26
time frame: Week 26
measure: Change from baseline in body weight at Week 26 and over time
time frame: Up to Week 26
measure: Total daily insulin dose, basal insulin dose and bolus insulin dose at Week 26 and over time
time frame: Up to Week 26
measure: HbA1c change from baseline in over time
time frame: Up to Week 26
measure: Fasting plasma glucose (FPG) change from Baseline at Week 26 and over time
time frame: Up to Week 26
measure: Proportion of subjects achieving a HbA1c <7.0% and < 6.5% at Week 26 and over time
time frame: Up to Week 26
measure: Percentage of subjects achieving HbA1c <7.0% without weight gain after 26 weeks of treatment
time frame: Up to Week 26
measure: Percentage of subjects achieving HbA1c <7.0% without severe or documented symptomatic hypoglycemia after 26 weeks of treatment
time frame: Up to Week 26
measure: Percentage of subjects achieving HbA1c <7.0% without weight gain and without severe or documented hypoglycemia after 26 weeks of treatment
time frame: Up to Week 26
measure: Number of subjects with non-serious adverse events (AE), serious adverse events (SAE), and AEs and SAEs leading to discontinuation
time frame: Up to Week 30
measure: Incidence of hypoglycemic events
time frame: Up to Week 30
measure: Assessment of clinical laboratory tests, lipids, vital signs, ECGs and physical examinations
time frame: Up to Week 30
arm group label: Albiglutide
arm group type: Experimental
description: Subjects will receive once-weekly subcutaneous injections of albiglutide 30 mg (with forced uptitration to albiglutide 50 mg at Week 4) in addition to intensification of background basal-bolus insulin therapy (with or without metformin) according to predefined titration algorithms.
arm group label: Matching albiglutide placebo
arm group type: Placebo Comparator
description: Subjects will receive once-weekly subcutaneous injections of matching albiglutide placebo in addition to intensification of background basal-bolus insulin therapy (with or without metformin) according to predefined titration algorithms
intervention type: Drug
intervention name: Albiglutide
description: Albiglutide is intended for self-administration as a SC injection. It is provided as a fixed dose of 30 mg of albiglutide or 50 mg of albiglutide in a 0.5 mL injection volume, fully disposable pen injector
arm group label: Albiglutide
intervention type: Drug
intervention name: Matching albiglutide placebo
description: Matching albiglutide placebo will be provided as 0.5-mL injection, fully disposable pen injector system
arm group label: Matching albiglutide placebo
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: GSK Clinical Trials
role: Study Director
affiliation: GlaxoSmithKline
responsible party type: Sponsor
mesh term: Diabetes Mellitus
mesh term: Diabetes Mellitus, Type 2
mesh term: rGLP-1 protein
mesh term: Glucagon-Like Peptide 1