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A Study of Dose Titration of LY2189265 in Overweight Participants With Type 2 Diabetes Mellitus (EGO)

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Eli Lilly and Company
ClinicalTrials.gov Identifier:
NCT00630825
First received: February 28, 2008
Last updated: December 8, 2014
Last verified: December 2014

February 28, 2008
December 8, 2014
April 2008
January 2009   (final data collection date for primary outcome measure)
Change From Baseline in Glycosylated Hemoglobin (HbA1c) in Overweight and Obese Participants With Type 2 Diabetes Mellitus [ Time Frame: Baseline, 16 weeks ] [ Designated as safety issue: No ]
Once weekly injections of LY2189265 (titrated and non-titrated doses) compared to placebo on blood glucose were evaluated. Least Squares (LS) means of change from baseline were calculated using analysis of covariance (ANCOVA) adjusting for treatment, combination of oral medications, and baseline glycosylated hemoglobin (HbA1c).
Evaluate once weekly injections of LY2189265 (adjusted and non-adjusted doses) compared to placebo on blood glucose as measured by HbA1C change from baseline in overweight patients with Type 2 Diabetes Mellitus [ Time Frame: at 16 weeks ] [ Designated as safety issue: Yes ]
Complete list of historical versions of study NCT00630825 on ClinicalTrials.gov Archive Site
  • Change From Baseline in Fasting Blood Glucose [ Time Frame: Baseline, 16 weeks ] [ Designated as safety issue: No ]
    Fasting blood glucose is a test to determine how much glucose (sugar) is in a blood sample after an overnight fast. Least Squares (LS) means of change were calculated using analysis of covariance (ANCOVA) adjusting for treatment, combination of oral medications, and baseline.
  • Meal Test Glucose Excursion (Change in Blood Glucose to Test Meal) [ Time Frame: Baseline and 16 weeks ] [ Designated as safety issue: No ]
    Glucose excursion in response to a standardized solid mixed meal test was evaluated at baseline (randomization) and at Week 16, or at early termination. Each of the 2 standardized meal tests required participants to fast starting at 2200 hours the night prior to the test. A standardized breakfast meal was provided to the participant (approximately 550 kilocalorie [Kcal], 103 grams [g] carbohydrates, 22 g protein, and 8.5 g fat) and was to be consumed within 15 minutes. Serial venous blood samples were taken at the start of the meal (fasting [0]) and 30, 60, 90, 120, and 180 minutes after the start of the meal. Least Squares (LS) means of change in mean glucose area under the curve excursion following a test meal were calculated adjusting for treatment, combination of oral medications, and baseline.
  • Change From Baseline in Daily Mean Blood Glucose Values From the 8-point Self Monitored Blood Glucose (SMBG) Profiles [ Time Frame: 2 separate days in the week preceding the Baseline, Week 4, Week 8, and Week 16 visits. ] [ Designated as safety issue: No ]
    Change from baseline in mean daily blood glucose values were measured using self-monitored blood glucose (SMBG) data collected at the following 8 time points: pre-morning meal; 2 hours post-morning meal; pre-midday meal; 2 hours post-midday meal; pre-evening meal; 2 hours post-evening meal; bedtime; and 2:00 am. The daily mean was calculated as the average of the 8 blood glucose values collected on a particular day. Least Squares (LS) means of change from baseline of the mean of the 8 time points (Daily Mean) were calculated using analysis of covariance (ANCOVA) adjusting for treatment, combination of oral medications, and baseline.
  • Change From Baseline in Beta (β)-Cell Function and Insulin Sensitivity as Estimated by the Updated Homeostasis Model Assessment Method (HOMA2) [ Time Frame: Baseline, 16 weeks ] [ Designated as safety issue: No ]
    Homeostasis Model Assessment tool (HOMA2) of β-cell function is a technique for estimating beta-cell function (HOMA2-%B) and insulin sensitivity (HOMA2-%S) using basal serum glucose, and c-peptide concentrations. A fasting blood glucose, c-peptide, and serum insulin level were drawn for purposes of this determination just prior to the mixed meal test.
  • Percentage of Participants Achieving a Glycosylated Hemoglobin (HbA1c) of <7% or ≤6.5% [ Time Frame: Baseline and 4 and 8 and 16 weeks ] [ Designated as safety issue: No ]
    Percentages of participants who achieved glycosylated hemoglobin (HbA1c) levels of <7% or ≤6.5% were analyzed with a logistic regression model with baseline, combination of oral medications, and treatment as factors included in the model.
  • Change From Baseline in Body Weight [ Time Frame: Baseline, 4, 8, and 16 weeks ] [ Designated as safety issue: Yes ]
    LS means of change from baseline were calculated using analysis of covariance (ANCOVA) adjusting for treatment, combination of oral medications, and baseline.
  • Change From Baseline in Waist Circumference [ Time Frame: Baseline, 16 weeks ] [ Designated as safety issue: Yes ]
    Mean change from baseline in waist circumference (a measure of central obesity).
  • Nausea and Dyspepsia Measured by Visual Analog Scale [ Time Frame: One week before and one week after each of the Baseline and Week 4 and Week 8 and Week 16 visits ] [ Designated as safety issue: Yes ]
    Participants were asked to score nausea and dyspepsia (abdominal pain and bloating) on a scale of 0 (none) to 100 after the largest meal of the day.
  • Change From Baseline in Gastroparesis Cardinal Symptom Index (GCSI) Scores [ Time Frame: Baseline and 4 and 8 and 16 weeks ] [ Designated as safety issue: Yes ]
    Gastroparesis Cardinal Symptom Index (GCSI) is a participant-completed questionnaire designed to assess the severity of symptoms consistent with delayed gastric emptying (nausea/vomiting, abdominal bloating, and stomach fullness) at each study visit. GCSI scores ranged from 0=none, 1=very mild, 2=mild, 3=moderate, 4=severe, to 5=very severe.
  • Number of Participants With a Hypoglycemic Event [ Time Frame: Baseline through 4, 8, and 16 weeks ] [ Designated as safety issue: Yes ]
    A documented hypoglycemic episode is defined as an event which is associated with a measured blood glucose of ≤70 milligrams per deciliter (mg/dL) (3.9 millimoles per liter [mmol/L]), even if it was not associated with symptoms, signs, or treatment. A severe hypoglycemic episode is defined as an event with a measured blood glucose of <50mg/dL. Participant reports of hypoglycemic events were collected at the beginning of each visit starting at Baseline. A summary of serious and other non-serious adverse events regardless of causality is located in the Reported Adverse Events module.
  • Rate of Hypoglycemia Per 30 Days [ Time Frame: Baseline through 16 weeks ] [ Designated as safety issue: Yes ]
    Hypoglycemic episodes are defined as an event which is associated with reported signs and/or symptoms of hypoglycemia (for example, sweating, shakiness, tachycardia, etc.) or a documented blood glucose (BG) concentration of ≤70 milligrams per deciliter (mg/dL) (3.9 millimoles per liter [mmol/L]), even if it was not associated with symptoms, signs, or treatment. The rate is the average number of days out of 30 that a participant reported hypoglycemia. A summary of serious and other non-serious adverse events regardless of causality is located in the Reported Adverse Events module.
  • Change From Baseline in Lipids [ Time Frame: Baseline, 16 weeks ] [ Designated as safety issue: Yes ]
    Lipids include total cholesterol, low-density lipoprotein (LDL)-cholesterol, high-density lipoprotein (HDL)-cholesterol, and triglycerides.
  • Participants Perception of Medication Effectiveness Using the Perceptions About Medications - Diabetes, Short Version (PAM-D-S) Questionnaire [ Time Frame: Baseline and 4 and 8 and 16 weeks ] [ Designated as safety issue: No ]
    The Perceptions about Medications - Diabetes, Short Version (PAM-D-S) questionnaire consisted of: 2 items in which respondents were asked about their satisfaction with their diabetes medication over the past week using a 6-point scale ranging from 1 "completely dissatisfied" to 6 "completely satisfied"; 10 items in which respondents were asked about the effectiveness of their diabetes medications in the past week using a 4-point scale ranging from 1 "all of the time" to 4 "none of the time"; and 15 items asking respondents to indicate the frequency of physical side effects in the past week using a 4-point scale ranging from 1 "all of the time" to 4 "none of the time." These items were exploratory items taken from a Diabetes Medicines Survey and had not been validated as a scale. The percentage of participants that rated their general health as good or better are summarized.
  • Validation of the Psychometric Properties of the Perceptions About Medications - Diabetes, Short Version (PAM-D-S) Questionnaire [ Time Frame: Baseline and 4 and 8 and 16 weeks ] [ Designated as safety issue: No ]
    This purpose of this outcome measure was to validate the PAM-D-S questionnaire for future use. Please refer to Outcome Measure #14 for a description of the PAM-D-S questionnaire and results collected. A preliminary analysis indicated modifications to the questionnaire were required and further study is necessary to complete the validation. Therefore, the PAM-D-S questionnaire was not validated as a part of Study H9X-MC-GBCJ.
  • Pharmacokinetics (PK) of LY2189265 - Area Under the Concentration Time Curve (AUC) [ Time Frame: Time zero to 168 hours after study drug administration at 4, 8, and 16 weeks ] [ Designated as safety issue: No ]
    The population mean estimates and standard deviations were calculated for pharmacokinetic parameters (area under the concentration time curve [AUC] at steady state from time zero to 168 hours after study drug administration).
  • Fasting blood glucose [ Time Frame: baseline and 16 weeks ] [ Designated as safety issue: Yes ]
  • Meal test glucose excursion (change in blood glucose to test meal) [ Time Frame: baseline and 16 weeks ] [ Designated as safety issue: Yes ]
  • Self-monitoring of blood glucose (SMBG) 8-point profile [ Time Frame: 2 separate days in weeks preceeding baseline visit, week 4, week 8, and at 16 weeks. ] [ Designated as safety issue: Yes ]
  • Body weight and waist circumference [ Time Frame: weight at every clinic visit and waist at baseline and week 16 ] [ Designated as safety issue: Yes ]
  • B-cell function and insulin sensitivity as estimated by the updated Homeostasis Model Assessment tool (HOMA2) [ Time Frame: baseline and at 16 weeks ] [ Designated as safety issue: Yes ]
  • Percentage of Patients achieving an HbA1C of < 7% and <, equal to 6.5% [ Time Frame: baseline, week 4,8, and 16 weeks ] [ Designated as safety issue: No ]
  • Evaluate safety/tolerability of LY2189265 compared to placebo; Evaluate symptoms of nausea,vomiting,diarrhea,dyspepsia measured by Visual Analog Scale and Gastroparesis Cardinal Symptom Index questionnaire; Evaluate hypoglycemia, hyperglycemia,lipids [ Time Frame: baseline, week 4,8, and 16 ] [ Designated as safety issue: Yes ]
  • To characterize the pharmacokinetics (PK) of LY2189265 and the relationship between LY2189265 exposure and safety measures. [ Time Frame: week 4,8,and 16 ] [ Designated as safety issue: Yes ]
  • To measure and evaluate patient perception of medication effectiveness using the Perceptions about Medications - Diabetes (PAM-D-S) questionnaire. [ Time Frame: baseline, week 4,8, and 16 ] [ Designated as safety issue: Yes ]
  • To test the psychometric properties of the PAM-D-S and to validate its use for future clinical trials. [ Time Frame: baseline, week 4,8 and 16 ] [ Designated as safety issue: Yes ]
Not Provided
Not Provided
 
A Study of Dose Titration of LY2189265 in Overweight Participants With Type 2 Diabetes Mellitus
The Effect of Dose Titration of LY2189265 in Overweight and Obese Patients With Type 2 Diabetes Mellitus

To study once weekly injections of LY2189265 compared to placebo on blood glucose by measuring glycosylated hemoglobin (HbA1c) change from baseline after 16 weeks in overweight Type 2 Diabetes Mellitus participants.

Not Provided
Interventional
Phase 2
Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator)
Primary Purpose: Treatment
Diabetes Mellitus Type 2
  • Drug: LY2189265
    Other Name: Dulaglutide
  • Drug: Placebo
  • Experimental: 1.0/2.0 milligram (mg) LY2189265
    LY2189265: 1.0 milligram (mg), subcutaneous (SC) injection, once weekly (QW) for 4 weeks; followed by 2.0 mg, SC injection, QW for 12 weeks
    Intervention: Drug: LY2189265
  • Experimental: 1.0/1.0 milligram (mg) LY2189265
    LY2189265: 1.0 mg, subcutaneous (SC) injection, once weekly (QW) for 16 weeks
    Intervention: Drug: LY2189265
  • Experimental: 0.5/1.0 milligram (mg) LY2189265
    LY2189265: 0.5 milligram (mg), subcutaneous (SC) injection, once weekly (QW) for 4 weeks; followed by 1.0 mg, SC injection, QW for 12 weeks
    Intervention: Drug: LY2189265
  • Placebo Comparator: Placebo
    Placebo: subcutaneous (SC) injection, once weekly (QW) for 16 weeks
    Intervention: Drug: Placebo
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
262
January 2009
January 2009   (final data collection date for primary outcome measure)

Inclusion Criteria:

  • Type 2 Diabetes Mellitus >3 months by history prior to entering the trial, based on disease diagnostic criteria from the American Diabetes Association (ADA 2007).
  • Men or women 18 years of age or older. Women must have a negative pregnancy test and be willing to use birth control during study duration and one month post.
  • Have glycosylated hemoglobin (HbA1c) of >7.0% to ≤10.5% as determined by central laboratory at screening.
  • Have a body mass index (BMI) between 27 and 40 kilograms/meter squared (kg/m^2), inclusive.
  • Have been on the same doses for 3 months of any approved combination of 2 oral antihyperglycemic medications in any combination of the following: sulfonylureas (e.g. Chlorpropamide or Diabinese, Glimepiride or Amaryl, Tolbutamide or Orinase, Tolazamide or Tolinase, Glipizide or Glucotrol, Glyburide also known as Micronase, Diabeta, or Glynase), biguanides (e.g. Glucophage or metformin), thiazolidinediones (e.g. Rosiglitazone or Avandia, or Pioglitazone or Actos), or dipeptidyl peptidase 4 (DPP-IV) inhibitors (e.g. Sitagliptin or Januvia). A combination pill of any 2 of these drugs is allowed (1 only), (e.g. Metformin and Glipizide or Metaglip), (e.g. Metformin and Glyburide or Glucovance), (e.g. Pioglitazone and Glimepiride or Duetact), or (e.g. Sitagliptin and Metformin or Janumet).

Exclusion Criteria:

  • Have known Type 1 Diabetes Mellitus
  • Have taken glucagon-like peptide-1 (GLP-1) or any GLP-1 analog drug (Byetta)
  • Have a history of unstable angina, heart attack (myocardial infarction), heart arrhythmia (ventricular), congestive heart failure, or other coronary intervention (percutaneous transluminal coronary angioplasty [PTCA], open heart surgery, or coronary artery bypass graft [CABG]), a transient ischemic attack (TIA) or stroke (cerebrovascular accident) in the last 6 months prior to screening.
  • Have acute or chronic hepatitis or elevated liver function tests (alanine transaminase), a history of chronic or recurrent pancreatitis. Have renal disease or a serum creatinine (blood test) >2 milligrams per deciliter (mg/dL). If taking biguanides (e.g. metformin or Glucophage), or DPP-IV inhibitors (e.g. Sitagliptin or Januvia or Janumet), creatinine must be ≤1.5 mg/dL.
  • Currently taking prescription or over the counter medications to prevent weight loss.
Both
18 Years and older
No
Contact information is only displayed when the study is recruiting subjects
United States,   Puerto Rico
 
NCT00630825
12068, H9X-MC-GBCJ
No
Eli Lilly and Company
Eli Lilly and Company
Not Provided
Study Director: Call 1-877-CTLILLY (1-877-285-4559) Mon-Fri 9AM-5PM Eastern time (UTC/GMT - 5 hours, EST) Eli Lilly and Company
Eli Lilly and Company
December 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP