Methodology Study To Examine 6-Week Food Intake With Liraglutide In Obese Subjects

Study Overview
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Brief Summary
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This will be a randomized, double blind, placebo controlled, 2 arm, parallel group, methodology study to assess the effect of 6 weeks of liraglutide administration on food intake in obese subjects.

Official Title
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A 6-WEEK, RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED, TWO-ARM, PARALLEL METHODOLOGY STUDY TO ASSESS THE EFFECT OF LIRAGLUTIDE ON FOOD INTAKE IN OBESE SUBJECTS

Conditions
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Obesity

Intervention / Treatment
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* Drug: Liraglutide
* Other: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Males and female subjects; Body Mass Index 30-40 kg/m2; Exclusion Criteria: Evidence of history of clinically significant hematological, renal, endocrine, pulmonary, gastrointestinal, cardiovascular, hepatic, psychiatric, neurologic, or allergic disease (including drug allergises, but excluding untreated, asymptomatic, seasonal allergies at time of dosing)

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Active<br>Liraglutide | Drug: Liraglutide<br>* Liraglutide<br>|
| Placebo Comparator: Placebo<br>Placebo comparator | Other: Placebo<br>* Placebo<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline (Visit 3) in Mean Energy Intake During Ad Libitum Lunches at Visits 4 and 5 | The mean energy intake was collected to assess the effect of liraglutide on food intake in non-diabetic, obese participants. Observed food intake was measured as the total number of calories consumed during the specified time period, calculated as the difference of the total number of calories provided minus the total number of calories remaining after meals. Mean energy intakes at Visit 4 was defined as the mean values of the measurements at Study Day 20 and 21. Same definition applies to Visit 5 (Study Day 41 and 42). Baseline was defined as the mean of Visit 3 (Study Day -1 and 0). | Visit 3, Visit 4 and Visit 5 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Vital Signs Data Meeting Categorical Criteria | Absolute values and changes from baseline in systolic blood pressure (SBP) and diastolic blood pressure (DBP), pulse rate (PR) were recorded in supine position. Vital signs categorical summarization criteria were 1), blood pressure: SBP greater than or equal to (>=) 30 millimeters of mercury (mm Hg) change from baseline, SBP less than (<) 90 mm Hg; DBP >=20 mm Hg change from baseline, DBP <50 mm Hg; 2), PR <40 or greater than (>) 120 beats per minute (bpm). Baseline was defined as pre-treatment measurement on Day 1. | Baseline (Visit 3) up to Visit 6 (Study Day 53) | 
| Number of Participants With Treatment-Emergent Adverse Events (All-Causality) | Adverse event (AE) was defined as any untoward medical occurrence in a study participant administered a product or medical device, regardless of its causal relationship with study treatment. An AE is considered treatment-emergent relative to a given treatment if: the event occurs for the first time during the effective duration of treatment and was not seen prior to the start of treatment (for example, during the baseline or run-in period); or the event was seen prior to the start of treatment but increased in severity during treatment. | Baseline (Visit 3) up to 31 days post last dose (75 days) | 
| Number of Participants With Abnormal 12-lead Electrocardiogram (ECG) | ECG categorical summarization criteria: 1) PR interval (the interval between the start of the P wave and the start of the QRS complex, corresponding to the time between the onset of the atrial depolarization and onset of ventricular depolarization): absolute value greater than or equal to (>=) 300 msec, percent change >=25% if baseline was greater than (>) 200 msec, and >=50% if baseline was less than or equal to (<=) 200 msec; 2) QRS interval (time from ECG Q wave to the end of the S wave corresponding to ventricle depolarization): absolute value >=200 msec, percent change >=25% if baseline was 100 msec, and >=50% if baseline was <=100 msec; 3) QTcF interval (QT corrected for heart rate using Fridericia's formula): absolute value >450 to <=480 msec, >480 to <=500 msec, >500 msec, an increase from baseline >30 to <=60 msec or >60 msec. Baseline was defined as pre-treatment measurement on Day -2. | Baseline (Visit 3) up to Visit 6 (Study Day 53) | 
| Number of Participants With Laboratory Abnormalities (Without Regard to Baseline Abnormality) | Below parameters were evaluated:1), Hematology: hemoglobin (HGB), hematocrit, erythrocytes (absolute value/mean corpuscular volume/mean corpuscular HGB/mean corpuscular HGB concentration), platelets, leukocytes, lymphocytes, neutrophils, basophils, monocytes; 2), clinical chemistry: bilirubin, aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, protein, albumin, blood urea nitrogen, creatinine, cholesterol, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, triglycerides, sodium, potassium, chloride, calcium, bicarbonate, amylase, triacylglycerol lipase; 3), urinalysis: pH, urine glucose, ketones, urine protein, urine hemoglobin, urobilinogen, urine bilirubin, nitrite, leukocyte esterase, urine erythrocytes, urine leukocytes, hyaline casts, bacteria. | Baseline (Visit 3) up to Visit 6 (Study Day 53) | 
| Change From Baseline in Mean 48-hour Energy Intake at Visits 4 and 5 | Energy intake was measured over a period of 48 hours to assess day to day variability in food intake. Observed food intake was measured as the total number of calories consumed during the specified time period, calculated as the difference of the total number of calories provided minus the total number of calories remaining after meals. Baseline was defined as the 48 hour period at Visit 3 (Study Day -1 and 0). | Visit 3, Visit 4 (Study Day 20 and 21) and Visit 5 (Study Day 41 and 42) | 
| Change From Baseline in Appetite Score (Mean Rating Area Under Curve From Time 30 to 120 Minutes [AUC30-120min]) for Mean Lunch at Visits 4 and 5 | Appetite, satiety, fullness, hunger, and prospective consumption were measured using a validated Visual Analog scale (VAS) questionnaire. VAS was an assessment in which participants place a vertical line across a validated 100 millimeter (mm) line with the example of Not At All Full and Totally Full at either end, scoring from 0 to 100. The overall appetite score was calculated as the average of the four individual scores [satiety + fullness + (100 - prospective food consumption)+(100 - hunger)] divided by 4. The VAS questionnaire was completed by the participant immediately prior to meal administration, and at 30, 60 and 120 minutes after start of the specified meals. Baseline of Mean Rating AUC30-120min was defined as the rating for mean lunch at Visit 3 (Study Day -1 and 0). | Visit 3, Visit 4 (Study Day 20 and 21) and Visit 5 (Study Day 41 and 42) | 
| Change From Baseline in Satiety, Fullness, Prospective Food Consumption and Hunger Scores (Mean Rating AUC30-120min) for Mean Lunch at Visits 4 and 5 | Satiety, fullness, hunger, and prospective consumption were measured at the study site using a validated VAS questionnaire. The VAS measurement of the subcomponent scores were the same as that of the appetite score. Baseline of Mean Rating AUC30-120min was defined as the rating for mean lunch at Visit 3 (Study Day -1 and 0).The VAS was an assessment in which subjects place a vertical line across a validated 100 millimeter (mm) line to rank their response to various questions. The line was anchored by responses such as Not At All Full and Totally Full at either end. Scoring consisted of measuring the distance in mm of the vertical line from the response at the left end. The scores (total and subscale) ranged from 0 to 100. The lower values represent the better outcomes.The overall appetite score was calculated as the average of the 4 individual scores [satiety+fullness+(100-prospective food consumption)+(100-hunger)] divided by 4. | Visit 3, Visit 4 (Study Day 20 and 21) and Visit 5 (Study Day 41 and 42) | 
| Change From Baseline in Area Under the Plasma Concentration-Time Profile of Acetaminophen for 0-60 Minutes and 0-300 Minutes (AUC0-60min and AUC0-300min) After Acetaminophen Dose at Visits 4 and 5 | A non investigational medicinal product (acetaminophen 1.5 gram [g]) was administered as a challenge agent for the assessment of gastric emptying. The blood sampling for determining acetaminophen concentrations was performed at 7 time points: prior to breakfast and at 30, 60, 90, 120, 180 and 300 minutes after intake of the acetaminophen with breakfast. Baseline was calculated at Visit 3 (Study Day -1). | Prior to breakfast and at 30,60,90,120,180 and 300 minutes after intake of the acetaminophen with breakfast on Visit 3,Visit 4 (Study Day 20) and Visit 5 (Study Day 41) |