Metabolism and Nutrition Disorder, Obesity
Conditions
Brief summary
This trial is conducted in the United States of America (USA). The purpose of the trial is to investigate the effect and safety of liraglutide 3.0 mg as an adjunct to intensive behaviour therapy for obesity in a non-specialist setting (IBT-CMS: Intensive Behaviour Therapy for obesity in a primary care setting according to Centers for Medicare & Medicaid Services (CMS) visit schedule).
Interventions
DRUGliraglutide
Administered subcutaneously (s.c., under the skin) once daily for 56 weeks. Dose gradually increased to 3.0 mg
DRUGplacebo
Administered subcutaneously (s.c., under the skin) once daily for 56 weeks. Dose gradually increased to 3.0 mg
BEHAVIORALCMS Intensive Behavior Therapy
Intensive Behaviour Therapy for obesity
Sponsors
Novo Nordisk A/S
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Informed consent obtained before any trial-related activities. Trial-related activities are any procedures that are carried out as part of the trial, including activities to determine suitability for the trial * BMI above or equal to 30 kg/m\^2 * Male or female, age 18 years or older at the time of signing informed consent
Exclusion criteria
* HbA1c (glycosylated haemoglobin) above or equal to 6.5% (at screening visit), or diagnosis of type 1 or type 2 diabetes mellitus * Recent history of cardiovascular disease (myocardial infarction or stroke within the past 6 months), severe congestive heart failure (NYHA class III, IV), or second degree or greater heart block * Personal or family history of Medullary Thyroid Carcinoma (MTC), or Multiple Endocrine Neoplasia type 2 (MEN2) * Female who is pregnant, breast-feeding or intends to become pregnant or is of child-bearing potential and not using an adequate contraceptive method (adequate contraceptive measure as required by local regulation or practice) * Use in past 90 days of medications known to induce significant weight loss (e.g., prescription weight loss medications) or weight gain (e.g., chronic use of oral steroids, second generation antipsychotics) * History of pancreatitis (acute or chronic) * History of major depressive disorder within the past 2 years * Any lifetime history of a suicide attempt * Inadequately treated blood pressure defined as Grade 3 hypertension or higher (Systolic above or equal to 180 mmHg or diastolic above or equal to 110 mmHg) * History of malignancy (except for non-melanoma skin cancer) within the past 5 years
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Body Weight (%) | Week 0, week 56 | Observed mean change in body weight from baseline (week 0) to week 56 was evaluated for two different observation periods. In-trial observation period: the uninterrupted time interval from the date of randomisation until and including the date of the follow-up visit or date of last contact. On-drug observation period: includes all time intervals in which subjects are considered to be on treatment from the date of first trial product administration to 7 days (or 14 days for AEs) after the final trial product administration, excluding potential off-treatment time intervals triggered by at least 7 consecutive missed doses (or 14 consecutive missed doses for AEs). The test of superiority of liraglutide to placebo for the treatment policy estimand was tested in a hierarchical manner for the two primary and the consequent 7 confirmatory secondary endpoints presented. |
| Proportion of Subjects Losing at Least 5% of Baseline Body Weight at Week 56 | Week 56 | The estimated mean percentage of subjects losing at least 5% of baseline body weight at week 56 is presented. The endpoint was evaluated based on in-trial data and on-drug data. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Proportion of Subjects Losing 4% or More of Baseline Body Weight | Week 16 | The estimated mean percentage of subjects losing 4% or more of baseline body weight at week 16 is presented. The endpoint was evaluated for treatment policy estimand (in-trial data). |
| Change in Waist Circumference (cm) | Week 0, week 56 | Observed mean change from baseline in waist circumference. The endpoint was evaluated based on in-trial data and on-drug data. |
| Change in Laboratory Measurements: Haematology (Haemoglobin Blood) | Week 0, week 56 | Observed mean change from baseline in haematological parameter blood haemoglobin. |
| Change in Short Form-36 (SF-36) v2.0 Acute, Physical Functioning Score | Week 0, week 56 | SF-36 is a 36-item patient-reported survey of patient health that measures the subject's overall health-related quality of life (HRQoL). SF-36v2™ questionnaire measured the HRQoL on 8 domains on individual scale ranges. The scores 0-100 (where higher scores indicated a better HRQoL) from the SF-36 were converted to norm-based scores to enable a direct interpretation in relation to the distribution of the scores in the 2009 U.S. general population. A norm-based score of 50 corresponds to the mean score and 10 corresponds to the standard deviation of the 2009 U.S. general population. Change from baseline in SF-36 physical functioning score is presented. A positive change score indicates an improvement since baseline. The endpoint was evaluated based on in-trial data and on-drug data. |
| Change in IWQoL-Lite for CT, Physical Function Domain (5-items) Score | Week 0, week 56 | Observed mean change in Impact of Weight on Quality of Life-Lite for Clinical Trials Version (IWQoL-Lite for CT ) score. IWQoL-Lite for CT (Weight on Quality of Life-Lite for Clinical Trial Version) is a modified version of an instrument designed to assess weight-related quality of life. The scores ranged between 0-100 where higher scores indicated a better quality of life. The endpoint was evaluated based on in-trial data and on-drug data. |
| Change in Six Minutes Walking Distance Test (6MWT) | Week 0, week 56 | Observed mean change from baseline in 6 minutes walking distance test. The 6MWT is a common test of functional exercise capacity that assesses the distance a subject can walk in 6 minutes. The endpoint was evaluated based on in-trial data and on-drug data. |
| Change From Baseline in HbA1c (%) | Week 0, week 56 | Observed mean change from baseline to week 56 in glycosylated haemoglobin (HbA1c). Results based on FAS in-trial data is presented. |
| Change From Baseline in FPG (mg/dL) | Week 0, week 56 | Observed mean change from baseline (week 0) in fasting plasma glucose (FPG). Results based on FAS in-trial data is presented. |
| Change From Baseline sBP (mmHg) | Week 0, week 56 | Observed mean change in systolic blood pressure from baseline to week 56. |
| Change From Baseline dBP (mmHg) | Week 0, week 56 | Observed mean change from baseline (week 0) to week 56 in diastolic blood pressure (dBP). Results based on FAS in-trial data is presented. |
| Change From Baseline in Lipids -Total Cholesterol | Week 0, week 56 | Observed mean change from baseline (week 0) to week 56 in total cholesterol (TC). Results based on FAS in-trial data is presented. |
| Change From Baseline in Lipids - LDL Cholesterol | Week 0, week 56 | Observed mean change from baseline in low density cholesterol (LDL) from baseline (week 0) to week 56. Results based on FAS in-trial data is presented. |
| Change From Baseline in Lipids - HDL Cholesterol | Week 0, week 56 | Observed mean change from baseline in high density (HDL) cholesterol from baseline (week 0) to week 56. Results based on FAS in-trial data is presented. |
| Change From Baseline in Lipids - VLDL Cholesterol | Week 0, week 56 | Observed mean change from baseline in very low density cholesterol (VLDL) from baseline (week 0) to week 56. Results based on FAS in-trial data is presented. |
| Change From Baseline in Lipids - TG | Week 0, week 56 | Observed mean change from baseline in triglyceride (TG) from baseline (week 0) to week 56. Results based on FAS in-trial data is presented. |
| Change From Baseline in Lipids - FFA | Week 0, week 56 | Observed mean change from baseline in free fatty acids (FFA) from baseline (week 0) to week 56. Results based on FAS in-trial data is presented. |
| Change in Short Form-36 v2.0 Acute (SF-36) (Subdomains) | Week 0, week 56 | SF-36 is a 36-item patient-reported survey of patient health that measures the subject's overall health-related quality of life (HRQoL). SF-36v2™ questionnaire measured the HRQoL on 8 domains on individual scale ranges. The scores 0-100 (where higher scores indicated a better HRQoL) from the SF-36 were converted to norm-based scores to enable a direct interpretation in relation to the distribution of the scores in the 2009 U.S. general population. A norm-based score of 50 corresponds to the mean score and 10 corresponds to the standard deviation of the 2009 U.S. general population. Change from baseline in in the sub-domain scores is presented. A positive change score indicates an improvement since baseline. Results are evaluated based on in-trial data. |
| Change in Short Form-36 v2.0 Acute (SF-36) (Physical Component Summary (PCS)) | Week 0, week 56 | Observed mean change from baseline (week 0) to week 56 in short form 36 v2.0 acute domain physical component summary (PCS). SF-36v2™ questionnaire measured the HRQoL on 8 domains on individual scale ranges. The scores 0-100 (where higher scores indicated a better HRQoL) from the SF-36 were converted to norm-based scores to enable a direct interpretation in relation to the distribution of the scores in the 2009 U.S. general population. A norm-based score of 50 corresponds to the mean score and 10 corresponds to the standard deviation of the 2009 U.S. general population. Change from baseline in SF-36 physical component summary (PCS) score is presented. A positive change score indicates an improvement since baseline. The endpoint was evaluated based on in-trial data and on-drug data. |
| Change in Short Form-36 v2.0 Acute (SF-36) (Mental Component Summary (MCS) | Week 0, week 56 | Observed mean change from baseline (week 0) to week 56 in short form 36 v2.0 acute domain mental component summary (MCS). SF-36v2™ questionnaire measured the HRQoL on 8 domains on individual scale ranges. The scores 0-100 (where higher scores indicated a better HRQoL) from the SF-36 were converted to norm-based scores to enable a direct interpretation in relation to the distribution of the scores in the 2009 U.S. general population. A norm-based score of 50 corresponds to the mean score and 10 corresponds to the standard deviation of the 2009 U.S. general population. Change from baseline in SF-36 mental component summary is presented. A positive change score indicates an improvement since baseline. The endpoint was evaluated based on in-trial data and on-drug data. |
| Change in Impact of Weight on Quality of Life-Lite for Clinical Trial Version (IWQoL-Lite for CT): Pain/Discomfort Domain Score | Week 0, week 56 | Observed mean change in Impact of Weight on Quality of Life-Lite for Clinical Trial Version (IWQoL-Lite for CT) domain pain and discomfort. IWQoL-Lite for CT (Weight on Quality of Life-Lite for Clinical Trial Version) is a modified version of an instrument designed to assess weight-related quality of life. The scores ranged between 0-100 where higher scores indicated a better quality of life. A positive change score indicates an improvement since baseline. Results based on FAS in-trial data is presented. |
| Change in Impact of Weight on Quality of Life-Lite for Clinical Trial Version (IWQoL-Lite for CT): Psychosocial Domain Score | Week 0, week 56 | Observed mean change in Impact of Weight on Quality of Life-Lite for Clinical Trial Version (IWQoL-Lite for CT) psychosocial domain. IWQoL-Lite for CT (Weight on Quality of Life-Lite for Clinical Trial Version) is a modified version of an instrument designed to assess weight-related quality of life. The scores ranged between 0-100 where higher scores indicated a better quality of life. A positive change score indicates an improvement since baseline. Results based on FAS in-trial data is presented. |
| Change in Impact of Weight on Quality of Life-Lite for Clinical Trial Version (IWQoL-Lite for CT): Total Score | Week 0, week 56 | Observed mean change from baseline (week 0) to week 56 in IWQoL-Lite for CT total score. IWQoL-Lite for CT (Weight on Quality of Life-Lite for Clinical Trial Version) is a modified version of an instrument designed to assess weight-related quality of life. The scores ranged between 0-100 where higher scores indicated a better quality of life. A positive change score indicates an improvement since baseline. Results based on FAS in-trial data is presented. |
| Change in Weight Related Sign and Symptom (WRSS) Measure, Total Score | Week 0, week 56 | Observed mean change from baseline (week 0) to week 56 in WRSS measure, total score. The WRSS measures the presence and bothersome associated with weight-related symptoms. The WRSS questionnaire was not validated until after database lock. Therefore the total score couldn't be calculated and the supportive secondary endpoint Weight related sign and symptom (WRSS) measure, total score couldn't be analysed. |
| Subjects Who After 56 Weeks Achieve (Yes/no): ≥ 4.3 T-score Points Increase From Baseline in SF-36 Physical Functioning Score | Week 56 | Percentage of subjects who achieved ≥ 4.3 T-score points increase from baseline in SF-36 physical functioning score at week 56 is presented. Results based on FAS in-trial data is presented. |
| Subjects Who After 56 Weeks Achieve (Yes/no): ≥ 3.8 T-score Points Increase From Baseline in SF-36 Physical Component Score | Week 56 | Percentage of subjects who achieved ≥ 3.8 T-score points increase from baseline in SF-36 physical component score at week 56 is presented. Results based on FAS in-trial data is presented. |
| Subjects Who After 56 Weeks Achieve (Yes/no): ≥ 4.6 T-score Points Increase From Baseline in SF-36 Mental Component Score | Week 56 | Percentage of subjects who achieved ≥ 4.6 T-score points increase from baseline in SF-36 mental component score at week 56 is presented. Results based on FAS in-trial data is presented. |
| Change in ECG | Week -1, week 56 | The ECGs were interpreted by the investigator at baseline (week -1) and week 56 and categorised as normal, abnormal NCS or abnormal CS. Number of subjects in each ECG category at baseline and week 56 are presented. |
| Responder Definition Value for IWQoL-Lite for CT Physical Function Domain (5-items) Score | Week 56 | Responder definition value for IWQoL-Lite for CT physical function domain (5-items) score' was defined as '≥ 20 responder definition value for IWQoL-Lite for CT physical function domain (5-items) score. Percentage of subjects considered IWQoL-Lite for CT physical function domain score responders (increase of ≥20 points) at week 56 is presented. Results based on FAS in-trial data is presented. |
| Number of Weeks (Completed Calendar Weeks) From Randomisation to Week 56 Adherent to Trial Product | Week 0, week 56 | Adherence to trial product is assessed regularly at CMS-IBT visits. The number of weeks from randomisation to week 56, adherent to trial product is presented. |
| Number of Weeks (Completed Calendar Weeks) From Randomisation to Week 56 Adherent to Caloric Diet | Week 0, week 56 | Adherence to caloric diet is assessed regularly at CMS-IBT visits. The number of weeks from randomisation to week 56, adherent to caloric diet is presented. |
| Number of Weeks (Completed Calendar Weeks) From Randomisation to Week 56 Adherent to Physical Activity | Week 0, week 56 | Adherence to physical activity is assessed regularly at CMS-IBT visits. The number of weeks from randomisation to week 56, adherent to physical activity is presented. |
| Number of Weeks (Completed Calendar Weeks) From Randomisation to Week 56 Adherent to Caloric Diet and Physical Activity | Week 0, week 56 | Adherence to caloric diet and physical activity is assessed regularly at CMS-IBT visits. The number of weeks from randomisation to week 56, adherent to caloric diet and physical activity is presented. |
| Number of Weeks (Completed Calendar Weeks) From Randomisation to Week 56 Adherent to Caloric Diet, Physical Activity and Trial Product | Week 0, week 56 | Adherence to caloric diet, physical activity and trial product is assessed regularly at CMS-IBT visits. The number of weeks from randomisation to week 56, adherent to caloric diet, physical activity and trial product is presented. |
| AEs From Randomisation Until and Including the Follow-up Period | Week 0 to week 56+30 days | Number of adverse events from randomisation to until the end of the post-treatment follow-up period (30 days). Results based on SAS on-drug data is presented. |
| Change in Physical Examination | Week 1, week 56 | Observed change from baseline to week 56 in physical examination are categorised under parameters namely abdomen, gastrointestinal system, cardiovascular system, central and peripheral nervous system, general appearence, head, ears, eyes, nose, throat and neck, lymph node palpation, musculoskeletal system, respiratory system, skin and thyroid gland. The percentage of subjects assessed as normal, abnormal not clinically significant and abnormal clinically significant at baseline and week 56 is presented. |
| Change in Resting Pulse | Week 0, week 56 | Observed mean change in pulse rate measured at resting position is presented. |
| Change in Laboratory Measurements: Haematology (Haematocrit Blood) | Week 0, week 56 | Observed mean change from baseline in haematological parameter blood haematocrit. Haematocrit is presented as the percentage of red blood cells in total blood. Results based on SAS on-drug data is presented. |
| Change in Laboratory Measurements: Haematology (Erythrocytes) | Week 0, week 56 | Observed mean change from baseline in haematological parameter - erythrocytes. |
| Change in Laboratory Measurements: Haematology (Thrombocytes and Leukocytes) | Week 0, week 56 | Observed mean change from baseline in haematological parameters - thrombocytss and leukocytes. |
| Change in Laboratory Measurements: Biochemistry (Albumin) | Week 0, week 56 | Observed mean change from baseline in biochemical parameter - albumin. Results based on SAS on-drug data is presented. |
| Change in Laboratory Measurements: Biochemistry (Alkaline Phosphatase, Alanine Aminotransferase, Amylase, Aspartate Aminotransferase and Lipase) | Week 0, week 56 | Observed mean change from baseline in biochemical parameters - alkaline phosphatase, alanine aminotransferase, amylase, aspartate aminotransferase and lipase. Results based on SAS on-drug data is presented. |
| Change in Laboratory Measurements: Biochemistry (Bilirubin and Creatinine) | Week 0, week 56 | Observed mean change from baseline in biochemical parameters - bilirubin and creatinine. Results based on SAS on-drug data is presented. |
| Proportion of Subjects Losing More Than 10% of Baseline Body Weight at Week 56 | Week 56 | The estimated mean percentage of subjects losing more than 10% of baseline body weight at week 56 is presented. The endpoint was evaluated based on in-trial data and on-drug data. |
| Change in Laboratory Measurements: Biochemistry (C-reactive Protein and Uric Acid) | Week 0, week 56 | Observed mean change from baseline in biochemical parameters - high sensitive c-reactive protein and uric acid. Results based on SAS on-drug data is presented. |
| Change in Laboratory Measurements: Biochemistry (Glomerular Filtration Rate, Serum) | Week 0, week 56 | Observed mean change from baseline in biochemical parameters - estimated glomerular filtration rate. Serum GFR is estimated using MDRD formula . Results based on SAS on-drug data is presented. |
| Change in Laboratory Measurements: Biochemistry (Calcitonin) | Week 0, week 56 | Observed mean change from baseline in biochemical parameter - calcitonin. Results based on SAS on-drug data is presented. |
| Change in Laboratory Measurements: Biochemistry (Thyroid Stimulating Hormone) | Week 0, week 56 | Observed mean change from baseline in biochemical parameters - thyroid stimulating hormone. Results based on SAS on-drug data is presented. |
| Change in Laboratory Measurements: Biochemistry (Total Calcium, Pottassium, Sodium and Urea) | Week 0, week 56 | Observed mean change from baseline in biochemical parameters - total calcium, pottassium, sodium and urea. Results based on SAS on-drug data is presented. |
| Proportion of Subjects Losing More Than 15% of Baseline Body Weight at Week 56 | Week 56 | The estimated mean percentage of subjects losing more than 15% of baseline body weight at week 56 is presented. The endpoint was evaluated based on in-trial data and on-drug data. |
Countries
United States
Participant flow
Recruitment details
The trial was conducted at 17 sites in the United States.
Pre-assignment details
All the subjects received Intensive Behaviour Therapy (IBT) for obesity in a primary care setting according to Centers for Medicare & Medicaid Services (CMS) visit schedule during the trial.
Participants by arm
| Arm | Count |
|---|---|
| Liraglutide 3.0 mg Subjects received liraglutide 3.0 mg once daily by subcutaneous injection (in the abdomen, thigh or upper arm) irrespective of the timing of meals. Subjects received 0.6 mg liraglutide during the first week. The dose was escalated in weekly increments of 0.6 mg until they reached a maintenance dose of 3.0 mg after 4 weeks. The treatment period was 56 weeks. Subjects were also on CMS-IBT during the trial. | 142 |
| Placebo Subjects received matching placebo once daily by subcutaneous injection (in the abdomen, thigh or upper arm) irrespective of the timing of meals. Dose escalation for placebo matched that of liraglutide. Subjects remained on a stable dose of placebo for 56 weeks. Subjects were also on CMS-IBT during the trial. | 140 |
| Total | 282 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 12 | 6 |
| Overall Study | Lack of Efficacy | 0 | 2 |
| Overall Study | Lost to Follow-up | 1 | 6 |
| Overall Study | Protocol Violation | 2 | 1 |
| Overall Study | Unclassified | 13 | 22 |
Baseline characteristics
| Characteristic | Liraglutide 3.0 mg | Placebo | Total |
|---|---|---|---|
| Age, Continuous | 45.4 Years STANDARD_DEVIATION 11.6 | 49 Years STANDARD_DEVIATION 11.2 | 47.2 Years STANDARD_DEVIATION 11.5 |
| Body weight | 108.5 kg STANDARD_DEVIATION 22.1 | 106.7 kg STANDARD_DEVIATION 22 | 107.6 kg STANDARD_DEVIATION 22 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 2 Participants | 3 Participants | 5 Participants |
| Race (NIH/OMB) Black or African American | 27 Participants | 22 Participants | 49 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 112 Participants | 115 Participants | 227 Participants |
| Sex: Female, Male Female | 119 Participants | 116 Participants | 235 Participants |
| Sex: Female, Male Male | 23 Participants | 24 Participants | 47 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 142 | 0 / 140 |
| other Total, other adverse events | 124 / 142 | 101 / 140 |
| serious Total, serious adverse events | 6 / 142 | 2 / 140 |
Outcome results
Primary
Change in Body Weight (%)
Observed mean change in body weight from baseline (week 0) to week 56 was evaluated for two different observation periods. In-trial observation period: the uninterrupted time interval from the date of randomisation until and including the date of the follow-up visit or date of last contact. On-drug observation period: includes all time intervals in which subjects are considered to be on treatment from the date of first trial product administration to 7 days (or 14 days for AEs) after the final trial product administration, excluding potential off-treatment time intervals triggered by at least 7 consecutive missed doses (or 14 consecutive missed doses for AEs). The test of superiority of liraglutide to placebo for the treatment policy estimand was tested in a hierarchical manner for the two primary and the consequent 7 confirmatory secondary endpoints presented.
Time frame: Week 0, week 56
Population: Full analysis set included all randomised subjects. Number analysed=subjects with available data.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Liraglutide 3.0 mg | Change in Body Weight (%) | In-trial observation period | -7.4 percent change | Standard Deviation 7.9 |
| Liraglutide 3.0 mg | Change in Body Weight (%) | On-drug observation period | -9.1 percent change | Standard Deviation 7.4 |
| Placebo | Change in Body Weight (%) | In-trial observation period | -4.0 percent change | Standard Deviation 7.4 |
| Placebo | Change in Body Weight (%) | On-drug observation period | -4.8 percent change | Standard Deviation 7.6 |
Comparison: Treatrment policy estimand. The hypothesis and the alternative are: H: μliraglutide ≥ μplacebo against the alternative HA: μliraglutide \< μplacebo. μliraglutide and μplacebo denote the true mean of % weight change for liraglutide 3.0 mg and placebo group, respectively. Week 56 responses were analysed using an analysis of covariance model with treatment, BMI groups, and sex as factors and baseline body weight as covariate.p-value: 0.000395% CI: [-5.31, -1.59]ANCOVA
Comparison: Hypothetical estimand. Analysis of on-drug data before first drug discontinuation date using a mixed model for repeated measurements with treatment, BMI groups, and sex as factors and baseline body weight as covariate, all nested within visit.p-value: 095% CI: [-6.54, -2.64]Mixed models repeated measurement (MMRM)
Primary
Proportion of Subjects Losing at Least 5% of Baseline Body Weight at Week 56
The estimated mean percentage of subjects losing at least 5% of baseline body weight at week 56 is presented. The endpoint was evaluated based on in-trial data and on-drug data.
Time frame: Week 56
Population: Full analysis set included all randomised subjects. Number analysed=subjects with available data.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Liraglutide 3.0 mg | Proportion of Subjects Losing at Least 5% of Baseline Body Weight at Week 56 | In-trial observation period | 61.47 percentage of participants |
| Liraglutide 3.0 mg | Proportion of Subjects Losing at Least 5% of Baseline Body Weight at Week 56 | On-drug observation period | 64.08 percentage of participants |
| Placebo | Proportion of Subjects Losing at Least 5% of Baseline Body Weight at Week 56 | In-trial observation period | 38.82 percentage of participants |
| Placebo | Proportion of Subjects Losing at Least 5% of Baseline Body Weight at Week 56 | On-drug observation period | 38.57 percentage of participants |
Comparison: Treatment policy estimand. Week 56 responses were analysed using a logistic regression model with treatment, BMI groups, and sex as factors and baseline body weight as covariate. Analysis of in-trial data with missing observations imputed from the placebo arm based on a jump to reference multiple (x100) imputation approach.p-value: 0.000395% CI: [1.53, 4.14]Regression, Logistic
Comparison: Hypothetical estimand. Analysis of on-drug before first drug discontinuation date using a mixed model for repeated measurements with treatment, BMI groups, and sex as factors and baseline body weight as covariate, all nested within visit. The MMRM was used to classify responders and analysed with a logistic regression with treatment as the only factor.p-value: 095% CI: [1.75, 4.61]Mixed models repeated measurement (MMRM)
Secondary
AEs From Randomisation Until and Including the Follow-up Period
Number of adverse events from randomisation to until the end of the post-treatment follow-up period (30 days). Results based on SAS on-drug data is presented.
Time frame: Week 0 to week 56+30 days
Population: Safety analysis set included all randomised subjects exposed to at least one dose of trial drug. Number analysed=subjects with available data.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Liraglutide 3.0 mg | AEs From Randomisation Until and Including the Follow-up Period | 867 events |
| Placebo | AEs From Randomisation Until and Including the Follow-up Period | 601 events |
Secondary
Change From Baseline dBP (mmHg)
Observed mean change from baseline (week 0) to week 56 in diastolic blood pressure (dBP). Results based on FAS in-trial data is presented.
Time frame: Week 0, week 56
Population: Full analysis set included all randomised subjects. Number analysed=subjects with available data.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Liraglutide 3.0 mg | Change From Baseline dBP (mmHg) | -1 mmHg | Standard Deviation 11 |
| Placebo | Change From Baseline dBP (mmHg) | -1 mmHg | Standard Deviation 10 |
Secondary
Change From Baseline in FPG (mg/dL)
Observed mean change from baseline (week 0) in fasting plasma glucose (FPG). Results based on FAS in-trial data is presented.
Time frame: Week 0, week 56
Population: Full analysis set included all randomised subjects. Number analysed=subjects with available data.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Liraglutide 3.0 mg | Change From Baseline in FPG (mg/dL) | -4.04 mg/dL | Standard Deviation 9.59 |
| Placebo | Change From Baseline in FPG (mg/dL) | -0.28 mg/dL | Standard Deviation 11.46 |
Secondary
Change From Baseline in HbA1c (%)
Observed mean change from baseline to week 56 in glycosylated haemoglobin (HbA1c). Results based on FAS in-trial data is presented.
Time frame: Week 0, week 56
Population: Full analysis set included all randomised subjects. Number analysed=subjects with available data.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Liraglutide 3.0 mg | Change From Baseline in HbA1c (%) | -0.2 percentage | Standard Deviation 0.3 |
| Placebo | Change From Baseline in HbA1c (%) | -0.1 percentage | Standard Deviation 0.2 |
Secondary
Change From Baseline in Lipids - FFA
Observed mean change from baseline in free fatty acids (FFA) from baseline (week 0) to week 56. Results based on FAS in-trial data is presented.
Time frame: Week 0, week 56
Population: Full analysis set included all randomised subjects. Number analysed=subjects with available data.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Liraglutide 3.0 mg | Change From Baseline in Lipids - FFA | -0.07 mmol/L | Standard Deviation 0.28 |
| Placebo | Change From Baseline in Lipids - FFA | -0.06 mmol/L | Standard Deviation 0.31 |
Secondary
Change From Baseline in Lipids - HDL Cholesterol
Observed mean change from baseline in high density (HDL) cholesterol from baseline (week 0) to week 56. Results based on FAS in-trial data is presented.
Time frame: Week 0, week 56
Population: Full analysis set included all randomised subjects. Number analysed=subjects with available data.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Liraglutide 3.0 mg | Change From Baseline in Lipids - HDL Cholesterol | 0.06 mmol/L | Standard Deviation 0.19 |
| Placebo | Change From Baseline in Lipids - HDL Cholesterol | 0.02 mmol/L | Standard Deviation 0.22 |
Secondary
Change From Baseline in Lipids - LDL Cholesterol
Observed mean change from baseline in low density cholesterol (LDL) from baseline (week 0) to week 56. Results based on FAS in-trial data is presented.
Time frame: Week 0, week 56
Population: Full analysis set included all randomised subjects. Number analysed=subjects with available data.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Liraglutide 3.0 mg | Change From Baseline in Lipids - LDL Cholesterol | -0.01 mmol/L | Standard Deviation 0.52 |
| Placebo | Change From Baseline in Lipids - LDL Cholesterol | -0.01 mmol/L | Standard Deviation 0.64 |
Secondary
Change From Baseline in Lipids - TG
Observed mean change from baseline in triglyceride (TG) from baseline (week 0) to week 56. Results based on FAS in-trial data is presented.
Time frame: Week 0, week 56
Population: Full analysis set included all randomised subjects. Number analysed=subjects with available data.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Liraglutide 3.0 mg | Change From Baseline in Lipids - TG | -0.19 mmol/L | Standard Deviation 1.04 |
| Placebo | Change From Baseline in Lipids - TG | -0.01 mmol/L | Standard Deviation 0.58 |
Secondary
Change From Baseline in Lipids -Total Cholesterol
Observed mean change from baseline (week 0) to week 56 in total cholesterol (TC). Results based on FAS in-trial data is presented.
Time frame: Week 0, week 56
Population: Full analysis set included all randomised subjects. Number analysed=subjects with available data.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Liraglutide 3.0 mg | Change From Baseline in Lipids -Total Cholesterol | -0.01 mmol/L | Standard Deviation 0.59 |
| Placebo | Change From Baseline in Lipids -Total Cholesterol | 0.00 mmol/L | Standard Deviation 0.77 |
Secondary
Change From Baseline in Lipids - VLDL Cholesterol
Observed mean change from baseline in very low density cholesterol (VLDL) from baseline (week 0) to week 56. Results based on FAS in-trial data is presented.
Time frame: Week 0, week 56
Population: Full analysis set included all randomised subjects. Number analysed=subjects with available data.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Liraglutide 3.0 mg | Change From Baseline in Lipids - VLDL Cholesterol | -0.06 mmol/L | Standard Deviation 0.31 |
| Placebo | Change From Baseline in Lipids - VLDL Cholesterol | -0.01 mmol/L | Standard Deviation 0.26 |
Secondary
Change From Baseline sBP (mmHg)
Observed mean change in systolic blood pressure from baseline to week 56.
Time frame: Week 0, week 56
Population: Full analysis set included all randomised subjects. Number analysed=subjects with available data.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Liraglutide 3.0 mg | Change From Baseline sBP (mmHg) | -2 mmHg | Standard Deviation 14 |
| Placebo | Change From Baseline sBP (mmHg) | -1 mmHg | Standard Deviation 13 |
Secondary
Change in ECG
The ECGs were interpreted by the investigator at baseline (week -1) and week 56 and categorised as normal, abnormal NCS or abnormal CS. Number of subjects in each ECG category at baseline and week 56 are presented.
Time frame: Week -1, week 56
Population: Safety analysis set included all randomised subjects exposed to at least one dose of trial drug. Number analysed=subjects with available data.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Liraglutide 3.0 mg | Change in ECG | Normal (week -1) | 100 participants |
| Liraglutide 3.0 mg | Change in ECG | Abnormal NCS (week -1) | 41 participants |
| Liraglutide 3.0 mg | Change in ECG | Abnormal CS (week -1) | 1 participants |
| Liraglutide 3.0 mg | Change in ECG | Normal (week 56) | 102 participants |
| Liraglutide 3.0 mg | Change in ECG | Abnormal NCS (week 56) | 36 participants |
| Liraglutide 3.0 mg | Change in ECG | Abnormal CS (week 56) | 0 participants |
| Placebo | Change in ECG | Abnormal NCS (week 56) | 42 participants |
| Placebo | Change in ECG | Normal (week -1) | 91 participants |
| Placebo | Change in ECG | Normal (week 56) | 81 participants |
| Placebo | Change in ECG | Abnormal NCS (week -1) | 49 participants |
| Placebo | Change in ECG | Abnormal CS (week 56) | 1 participants |
| Placebo | Change in ECG | Abnormal CS (week -1) | 0 participants |
Secondary
Change in Impact of Weight on Quality of Life-Lite for Clinical Trial Version (IWQoL-Lite for CT): Pain/Discomfort Domain Score
Observed mean change in Impact of Weight on Quality of Life-Lite for Clinical Trial Version (IWQoL-Lite for CT) domain pain and discomfort. IWQoL-Lite for CT (Weight on Quality of Life-Lite for Clinical Trial Version) is a modified version of an instrument designed to assess weight-related quality of life. The scores ranged between 0-100 where higher scores indicated a better quality of life. A positive change score indicates an improvement since baseline. Results based on FAS in-trial data is presented.
Time frame: Week 0, week 56
Population: Full analysis set included all randomised subjects. Number analysed=subjects with available data.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Liraglutide 3.0 mg | Change in Impact of Weight on Quality of Life-Lite for Clinical Trial Version (IWQoL-Lite for CT): Pain/Discomfort Domain Score | 10.1 scores on a scale | Standard Deviation 21.2 |
| Placebo | Change in Impact of Weight on Quality of Life-Lite for Clinical Trial Version (IWQoL-Lite for CT): Pain/Discomfort Domain Score | 8.6 scores on a scale | Standard Deviation 23.1 |
Secondary
Change in Impact of Weight on Quality of Life-Lite for Clinical Trial Version (IWQoL-Lite for CT): Psychosocial Domain Score
Observed mean change in Impact of Weight on Quality of Life-Lite for Clinical Trial Version (IWQoL-Lite for CT) psychosocial domain. IWQoL-Lite for CT (Weight on Quality of Life-Lite for Clinical Trial Version) is a modified version of an instrument designed to assess weight-related quality of life. The scores ranged between 0-100 where higher scores indicated a better quality of life. A positive change score indicates an improvement since baseline. Results based on FAS in-trial data is presented.
Time frame: Week 0, week 56
Population: Full analysis set included all randomised subjects. Number analysed=subjects with available data.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Liraglutide 3.0 mg | Change in Impact of Weight on Quality of Life-Lite for Clinical Trial Version (IWQoL-Lite for CT): Psychosocial Domain Score | 13.5 score | Standard Deviation 20.3 |
| Placebo | Change in Impact of Weight on Quality of Life-Lite for Clinical Trial Version (IWQoL-Lite for CT): Psychosocial Domain Score | 12.4 score | Standard Deviation 21.8 |
Secondary
Change in Impact of Weight on Quality of Life-Lite for Clinical Trial Version (IWQoL-Lite for CT): Total Score
Observed mean change from baseline (week 0) to week 56 in IWQoL-Lite for CT total score. IWQoL-Lite for CT (Weight on Quality of Life-Lite for Clinical Trial Version) is a modified version of an instrument designed to assess weight-related quality of life. The scores ranged between 0-100 where higher scores indicated a better quality of life. A positive change score indicates an improvement since baseline. Results based on FAS in-trial data is presented.
Time frame: Week 0, week 56
Population: Full analysis set included all randomised subjects. Number analysed=subjects with available data.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Liraglutide 3.0 mg | Change in Impact of Weight on Quality of Life-Lite for Clinical Trial Version (IWQoL-Lite for CT): Total Score | 13.2 scores on a scale | Standard Deviation 18.5 |
| Placebo | Change in Impact of Weight on Quality of Life-Lite for Clinical Trial Version (IWQoL-Lite for CT): Total Score | 12.8 scores on a scale | Standard Deviation 20.7 |
Secondary
Change in IWQoL-Lite for CT, Physical Function Domain (5-items) Score
Observed mean change in Impact of Weight on Quality of Life-Lite for Clinical Trials Version (IWQoL-Lite for CT ) score. IWQoL-Lite for CT (Weight on Quality of Life-Lite for Clinical Trial Version) is a modified version of an instrument designed to assess weight-related quality of life. The scores ranged between 0-100 where higher scores indicated a better quality of life. The endpoint was evaluated based on in-trial data and on-drug data.
Time frame: Week 0, week 56
Population: Full analysis set included all randomised subjects. Number analysed=subjects with available data.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Liraglutide 3.0 mg | Change in IWQoL-Lite for CT, Physical Function Domain (5-items) Score | In-trial observation period | 13.5 Scores on a scale | Standard Deviation 21.4 |
| Liraglutide 3.0 mg | Change in IWQoL-Lite for CT, Physical Function Domain (5-items) Score | On-drug observation period | 15.2 Scores on a scale | Standard Deviation 21.4 |
| Placebo | Change in IWQoL-Lite for CT, Physical Function Domain (5-items) Score | In-trial observation period | 15.5 Scores on a scale | Standard Deviation 23 |
| Placebo | Change in IWQoL-Lite for CT, Physical Function Domain (5-items) Score | On-drug observation period | 17.5 Scores on a scale | Standard Deviation 21.4 |
Comparison: Treatment policy estimand. Analysis of in-trial data with missing observations imputed from the placebo arm based on a jump to reference multiple (x100) imputation approach. Week 56 responses were analysed using an analysis of covariance model with treatment, BMI groups, and sex as factors and baseline measurement of endpoint as covariate.p-value: 0.691695% CI: [-3.41, 5.14]ANCOVA
Comparison: Hypothetical estimand. Analysis of on-drug before first drug discontinuation date using a mixed model for repeated measurements with treatment, BMI groups, and sex as factors and baseline measurement of endpoint as covariate, all nested within visit.p-value: 0.557295% CI: [-2.95, 5.45]Mixed models repeated measurements (MMRM
Secondary
Change in Laboratory Measurements: Biochemistry (Albumin)
Observed mean change from baseline in biochemical parameter - albumin. Results based on SAS on-drug data is presented.
Time frame: Week 0, week 56
Population: Safety analysis set included all randomised subjects exposed to at least one dose of trial drug. Number analysed=subjects with available data.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Liraglutide 3.0 mg | Change in Laboratory Measurements: Biochemistry (Albumin) | -0.1 g/L | Standard Deviation 0.2 |
| Placebo | Change in Laboratory Measurements: Biochemistry (Albumin) | -0.1 g/L | Standard Deviation 0.2 |
Secondary
Change in Laboratory Measurements: Biochemistry (Alkaline Phosphatase, Alanine Aminotransferase, Amylase, Aspartate Aminotransferase and Lipase)
Observed mean change from baseline in biochemical parameters - alkaline phosphatase, alanine aminotransferase, amylase, aspartate aminotransferase and lipase. Results based on SAS on-drug data is presented.
Time frame: Week 0, week 56
Population: Safety analysis set included all randomised subjects exposed to at least one dose of trial drug. Number analysed=subjects with available data.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Liraglutide 3.0 mg | Change in Laboratory Measurements: Biochemistry (Alkaline Phosphatase, Alanine Aminotransferase, Amylase, Aspartate Aminotransferase and Lipase) | Alanine Aminotransferase | -5 U/L | Standard Deviation 14 |
| Liraglutide 3.0 mg | Change in Laboratory Measurements: Biochemistry (Alkaline Phosphatase, Alanine Aminotransferase, Amylase, Aspartate Aminotransferase and Lipase) | Aspartate aminotransferase | -3 U/L | Standard Deviation 10 |
| Liraglutide 3.0 mg | Change in Laboratory Measurements: Biochemistry (Alkaline Phosphatase, Alanine Aminotransferase, Amylase, Aspartate Aminotransferase and Lipase) | Amylase | 4 U/L | Standard Deviation 10 |
| Liraglutide 3.0 mg | Change in Laboratory Measurements: Biochemistry (Alkaline Phosphatase, Alanine Aminotransferase, Amylase, Aspartate Aminotransferase and Lipase) | Lipase | 7 U/L | Standard Deviation 18 |
| Liraglutide 3.0 mg | Change in Laboratory Measurements: Biochemistry (Alkaline Phosphatase, Alanine Aminotransferase, Amylase, Aspartate Aminotransferase and Lipase) | Alkaline Phosphatase | -2 U/L | Standard Deviation 12 |
| Placebo | Change in Laboratory Measurements: Biochemistry (Alkaline Phosphatase, Alanine Aminotransferase, Amylase, Aspartate Aminotransferase and Lipase) | Lipase | 2 U/L | Standard Deviation 22 |
| Placebo | Change in Laboratory Measurements: Biochemistry (Alkaline Phosphatase, Alanine Aminotransferase, Amylase, Aspartate Aminotransferase and Lipase) | Alkaline Phosphatase | -1 U/L | Standard Deviation 13 |
| Placebo | Change in Laboratory Measurements: Biochemistry (Alkaline Phosphatase, Alanine Aminotransferase, Amylase, Aspartate Aminotransferase and Lipase) | Alanine Aminotransferase | -4 U/L | Standard Deviation 16 |
| Placebo | Change in Laboratory Measurements: Biochemistry (Alkaline Phosphatase, Alanine Aminotransferase, Amylase, Aspartate Aminotransferase and Lipase) | Amylase | 1 U/L | Standard Deviation 13 |
| Placebo | Change in Laboratory Measurements: Biochemistry (Alkaline Phosphatase, Alanine Aminotransferase, Amylase, Aspartate Aminotransferase and Lipase) | Aspartate aminotransferase | -2 U/L | Standard Deviation 12 |
Secondary
Change in Laboratory Measurements: Biochemistry (Bilirubin and Creatinine)
Observed mean change from baseline in biochemical parameters - bilirubin and creatinine. Results based on SAS on-drug data is presented.
Time frame: Week 0, week 56
Population: Safety analysis set included all randomised subjects exposed to at least one dose of trial drug. Number analysed=subjects with available data.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Liraglutide 3.0 mg | Change in Laboratory Measurements: Biochemistry (Bilirubin and Creatinine) | Bilirubin | 1.1 umol/L | Standard Deviation 3.2 |
| Liraglutide 3.0 mg | Change in Laboratory Measurements: Biochemistry (Bilirubin and Creatinine) | Creatinine | -1.8 umol/L | Standard Deviation 7.9 |
| Placebo | Change in Laboratory Measurements: Biochemistry (Bilirubin and Creatinine) | Bilirubin | 1.0 umol/L | Standard Deviation 3.2 |
| Placebo | Change in Laboratory Measurements: Biochemistry (Bilirubin and Creatinine) | Creatinine | -1.4 umol/L | Standard Deviation 6.1 |
Secondary
Change in Laboratory Measurements: Biochemistry (Calcitonin)
Observed mean change from baseline in biochemical parameter - calcitonin. Results based on SAS on-drug data is presented.
Time frame: Week 0, week 56
Population: Safety analysis set included all randomised subjects exposed to at least one dose of trial drug. Number analysed=subjects with available data.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Liraglutide 3.0 mg | Change in Laboratory Measurements: Biochemistry (Calcitonin) | 0.2 ng/L | Standard Deviation 0.8 |
| Placebo | Change in Laboratory Measurements: Biochemistry (Calcitonin) | 0.1 ng/L | Standard Deviation 0.8 |
Secondary
Change in Laboratory Measurements: Biochemistry (C-reactive Protein and Uric Acid)
Observed mean change from baseline in biochemical parameters - high sensitive c-reactive protein and uric acid. Results based on SAS on-drug data is presented.
Time frame: Week 0, week 56
Population: Safety analysis set included all randomised subjects exposed to at least one dose of trial drug. Number analysed=subjects with available data.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Liraglutide 3.0 mg | Change in Laboratory Measurements: Biochemistry (C-reactive Protein and Uric Acid) | High sensitive c-reactive protein | -2.51 mg/dL | Standard Deviation 4.67 |
| Liraglutide 3.0 mg | Change in Laboratory Measurements: Biochemistry (C-reactive Protein and Uric Acid) | Uric acid | -0.6 mg/dL | Standard Deviation 0.9 |
| Placebo | Change in Laboratory Measurements: Biochemistry (C-reactive Protein and Uric Acid) | High sensitive c-reactive protein | -0.85 mg/dL | Standard Deviation 8.96 |
| Placebo | Change in Laboratory Measurements: Biochemistry (C-reactive Protein and Uric Acid) | Uric acid | -0.3 mg/dL | Standard Deviation 0.9 |
Secondary
Change in Laboratory Measurements: Biochemistry (Glomerular Filtration Rate, Serum)
Observed mean change from baseline in biochemical parameters - estimated glomerular filtration rate. Serum GFR is estimated using MDRD formula . Results based on SAS on-drug data is presented.
Time frame: Week 0, week 56
Population: Safety analysis set included all randomised subjects exposed to at least one dose of trial drug. Number analysed=subjects with available data.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Liraglutide 3.0 mg | Change in Laboratory Measurements: Biochemistry (Glomerular Filtration Rate, Serum) | 2 mL/min/1.73m^2 | Standard Deviation 11 |
| Placebo | Change in Laboratory Measurements: Biochemistry (Glomerular Filtration Rate, Serum) | 2 mL/min/1.73m^2 | Standard Deviation 9 |
Secondary
Change in Laboratory Measurements: Biochemistry (Thyroid Stimulating Hormone)
Observed mean change from baseline in biochemical parameters - thyroid stimulating hormone. Results based on SAS on-drug data is presented.
Time frame: Week 0, week 56
Population: Safety analysis set included all randomised subjects exposed to at least one dose of trial drug. Number analysed=subjects with available data.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Liraglutide 3.0 mg | Change in Laboratory Measurements: Biochemistry (Thyroid Stimulating Hormone) | -0.2313 mIU/L | Standard Deviation 1.0366 |
| Placebo | Change in Laboratory Measurements: Biochemistry (Thyroid Stimulating Hormone) | 0.2685 mIU/L | Standard Deviation 3.6814 |
Secondary
Change in Laboratory Measurements: Biochemistry (Total Calcium, Pottassium, Sodium and Urea)
Observed mean change from baseline in biochemical parameters - total calcium, pottassium, sodium and urea. Results based on SAS on-drug data is presented.
Time frame: Week 0, week 56
Population: Safety analysis set included all randomised subjects exposed to at least one dose of trial drug. Number analysed=subjects with available data.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Liraglutide 3.0 mg | Change in Laboratory Measurements: Biochemistry (Total Calcium, Pottassium, Sodium and Urea) | Total Calcium | 0.01 mmol/L | Standard Deviation 0.1 |
| Liraglutide 3.0 mg | Change in Laboratory Measurements: Biochemistry (Total Calcium, Pottassium, Sodium and Urea) | Potassium | -0.0 mmol/L | Standard Deviation 0.5 |
| Liraglutide 3.0 mg | Change in Laboratory Measurements: Biochemistry (Total Calcium, Pottassium, Sodium and Urea) | Sodium | -0.0 mmol/L | Standard Deviation 2 |
| Liraglutide 3.0 mg | Change in Laboratory Measurements: Biochemistry (Total Calcium, Pottassium, Sodium and Urea) | Urea | 0.0 mmol/L | Standard Deviation 1.2 |
| Placebo | Change in Laboratory Measurements: Biochemistry (Total Calcium, Pottassium, Sodium and Urea) | Urea | 0.2 mmol/L | Standard Deviation 1.2 |
| Placebo | Change in Laboratory Measurements: Biochemistry (Total Calcium, Pottassium, Sodium and Urea) | Total Calcium | 0.01 mmol/L | Standard Deviation 0.09 |
| Placebo | Change in Laboratory Measurements: Biochemistry (Total Calcium, Pottassium, Sodium and Urea) | Sodium | -0 mmol/L | Standard Deviation 2 |
| Placebo | Change in Laboratory Measurements: Biochemistry (Total Calcium, Pottassium, Sodium and Urea) | Potassium | -0.0 mmol/L | Standard Deviation 0.4 |
Secondary
Change in Laboratory Measurements: Haematology (Erythrocytes)
Observed mean change from baseline in haematological parameter - erythrocytes.
Time frame: Week 0, week 56
Population: Safety analysis set included all randomised subjects exposed to at least one dose of trial drug. Number analysed=subjects with available data.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Liraglutide 3.0 mg | Change in Laboratory Measurements: Haematology (Erythrocytes) | -0.11 10^12 cells/L | Standard Deviation 0.25 |
| Placebo | Change in Laboratory Measurements: Haematology (Erythrocytes) | -0.08 10^12 cells/L | Standard Deviation 0.25 |
Secondary
Change in Laboratory Measurements: Haematology (Haematocrit Blood)
Observed mean change from baseline in haematological parameter blood haematocrit. Haematocrit is presented as the percentage of red blood cells in total blood. Results based on SAS on-drug data is presented.
Time frame: Week 0, week 56
Population: Safety analysis set included all randomised subjects exposed to at least one dose of trial drug. Number analysed=subjects with available data.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Liraglutide 3.0 mg | Change in Laboratory Measurements: Haematology (Haematocrit Blood) | -1.5 percentage of red blood cells | Standard Deviation 2.3 |
| Placebo | Change in Laboratory Measurements: Haematology (Haematocrit Blood) | -0.9 percentage of red blood cells | Standard Deviation 2.6 |
Secondary
Change in Laboratory Measurements: Haematology (Haemoglobin Blood)
Observed mean change from baseline in haematological parameter blood haemoglobin.
Time frame: Week 0, week 56
Population: Safety analysis set included all randomised subjects exposed to at least one dose of trial drug. Number analysed=subjects with available data.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Liraglutide 3.0 mg | Change in Laboratory Measurements: Haematology (Haemoglobin Blood) | -0.2 mmol/L | Standard Deviation 0.5 |
| Placebo | Change in Laboratory Measurements: Haematology (Haemoglobin Blood) | -0.1 mmol/L | Standard Deviation 0.6 |
Secondary
Change in Laboratory Measurements: Haematology (Thrombocytes and Leukocytes)
Observed mean change from baseline in haematological parameters - thrombocytss and leukocytes.
Time frame: Week 0, week 56
Population: Safety analysis set included all randomised subjects exposed to at least one dose of trial drug. Number analysed=subjects with available data.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Liraglutide 3.0 mg | Change in Laboratory Measurements: Haematology (Thrombocytes and Leukocytes) | Thrombocytes | 4 10^9 cells/L | Standard Deviation 30 |
| Liraglutide 3.0 mg | Change in Laboratory Measurements: Haematology (Thrombocytes and Leukocytes) | Leukocytes | -0.14 10^9 cells/L | Standard Deviation 1.53 |
| Placebo | Change in Laboratory Measurements: Haematology (Thrombocytes and Leukocytes) | Thrombocytes | 0 10^9 cells/L | Standard Deviation 36 |
| Placebo | Change in Laboratory Measurements: Haematology (Thrombocytes and Leukocytes) | Leukocytes | -0.11 10^9 cells/L | Standard Deviation 1.2 |
Secondary
Change in Physical Examination
Observed change from baseline to week 56 in physical examination are categorised under parameters namely abdomen, gastrointestinal system, cardiovascular system, central and peripheral nervous system, general appearence, head, ears, eyes, nose, throat and neck, lymph node palpation, musculoskeletal system, respiratory system, skin and thyroid gland. The percentage of subjects assessed as normal, abnormal not clinically significant and abnormal clinically significant at baseline and week 56 is presented.
Time frame: Week 1, week 56
Population: Safety analysis set included all randomised subjects exposed to at least one dose of trial drug. Number analysed=subjects with available data.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Liraglutide 3.0 mg | Change in Physical Examination | Cardiovascular System (week 56) Abnormal NCS | 1 participants |
| Liraglutide 3.0 mg | Change in Physical Examination | Abdomen (week -1) Abnormal, NCS | 34 participants |
| Liraglutide 3.0 mg | Change in Physical Examination | Abdomen (week -1) Abnormal CS | 0 participants |
| Liraglutide 3.0 mg | Change in Physical Examination | Abdomen (week 56) Normal | 114 participants |
| Liraglutide 3.0 mg | Change in Physical Examination | Abdomen (week 56) Abnormal, NCS | 25 participants |
| Liraglutide 3.0 mg | Change in Physical Examination | Abdomen (week 56) Abnormal, CS | 0 participants |
| Liraglutide 3.0 mg | Change in Physical Examination | Gastrointestinal System (week -1) Normal | 130 participants |
| Liraglutide 3.0 mg | Change in Physical Examination | Gastrointestinal System (week -1) Abnormal NCS | 12 participants |
| Liraglutide 3.0 mg | Change in Physical Examination | Gastrointestinal System (week -1) Abnormal CS | 0 participants |
| Liraglutide 3.0 mg | Change in Physical Examination | Gastrointestinal System (week 56) Normal | 132 participants |
| Liraglutide 3.0 mg | Change in Physical Examination | Gastrointestinal System (week 56) Abnormal NCS | 7 participants |
| Liraglutide 3.0 mg | Change in Physical Examination | Gastrointestinal System (week 56) Abnormal CS | 0 participants |
| Liraglutide 3.0 mg | Change in Physical Examination | Cardiovascular System (week-1) Normal | 136 participants |
| Liraglutide 3.0 mg | Change in Physical Examination | Cardiovascular System (week-1) Abnormal NCS | 6 participants |
| Liraglutide 3.0 mg | Change in Physical Examination | Cardiovascular System (week-1) Abnormal CS | 0 participants |
| Liraglutide 3.0 mg | Change in Physical Examination | Cardiovascular System (week 56) Normal | 138 participants |
| Liraglutide 3.0 mg | Change in Physical Examination | Abdomen (week -1) Normal | 108 participants |
| Liraglutide 3.0 mg | Change in Physical Examination | Cardiovascular System (week 56) Abnormal CS | 0 participants |
| Liraglutide 3.0 mg | Change in Physical Examination | Nervous System (week -1) Normal | 135 participants |
| Liraglutide 3.0 mg | Change in Physical Examination | Nervous System (week -1) Abnormal NCS | 5 participants |
| Liraglutide 3.0 mg | Change in Physical Examination | Nervous System (week -1) Abnormal CS | 2 participants |
| Liraglutide 3.0 mg | Change in Physical Examination | Nervous System (week 56) Normal | 132 participants |
| Liraglutide 3.0 mg | Change in Physical Examination | Nervous System (week 56) Abnormal NCS | 6 participants |
| Liraglutide 3.0 mg | Change in Physical Examination | Nervous System (week 56) Abnormal CS | 1 participants |
| Liraglutide 3.0 mg | Change in Physical Examination | General Appearance (week -1) Normal | 118 participants |
| Liraglutide 3.0 mg | Change in Physical Examination | General Appearance (week -1) Abnormal NCS | 24 participants |
| Liraglutide 3.0 mg | Change in Physical Examination | General Appearance (week -1) Abnormal CS | 0 participants |
| Liraglutide 3.0 mg | Change in Physical Examination | General Appearance (week 56) Normal | 122 participants |
| Liraglutide 3.0 mg | Change in Physical Examination | General Appearance (week 56) Abnormal NCS | 17 participants |
| Liraglutide 3.0 mg | Change in Physical Examination | General Appearance (week 56) Abnormal CS | 0 participants |
| Liraglutide 3.0 mg | Change in Physical Examination | Head, ENTand Neck (week -1) Normal | 129 participants |
| Liraglutide 3.0 mg | Change in Physical Examination | Head, ENTand Neck (week -1) Abnormal NCS | 13 participants |
| Liraglutide 3.0 mg | Change in Physical Examination | Head, ENTand Neck (week -1) Abnormal CS | 0 participants |
| Liraglutide 3.0 mg | Change in Physical Examination | Head, ENTand Neck (week 56) Normal | 126 participants |
| Liraglutide 3.0 mg | Change in Physical Examination | Head, ENTand Neck (week 56) Abnormal NCS | 13 participants |
| Liraglutide 3.0 mg | Change in Physical Examination | Head, ENTand Neck (week 56) Abnormal CS | 0 participants |
| Liraglutide 3.0 mg | Change in Physical Examination | Lymph Node Palpation (week -1) Normal | 142 participants |
| Liraglutide 3.0 mg | Change in Physical Examination | Lymph Node Palpation (week -1) Abnormal NCS | 0 participants |
| Liraglutide 3.0 mg | Change in Physical Examination | Lymph Node Palpation (week -1) Abnormal CS | 0 participants |
| Liraglutide 3.0 mg | Change in Physical Examination | Lymph Node Palpation (week 56) Normal | 139 participants |
| Liraglutide 3.0 mg | Change in Physical Examination | Lymph Node Palpation (week 56) Abnormal NCS | 0 participants |
| Liraglutide 3.0 mg | Change in Physical Examination | Lymph Node Palpation (week 56) Abnormal CS | 0 participants |
| Liraglutide 3.0 mg | Change in Physical Examination | Musculoskeletal System (week -1) Normal | 131 participants |
| Liraglutide 3.0 mg | Change in Physical Examination | Musculoskeletal System (week -1) Abnormal NCS | 11 participants |
| Liraglutide 3.0 mg | Change in Physical Examination | Musculoskeletal System (week -1) Abnormal CS | 0 participants |
| Liraglutide 3.0 mg | Change in Physical Examination | Musculoskeletal System (week 56) Normal | 130 participants |
| Liraglutide 3.0 mg | Change in Physical Examination | Musculoskeletal System (week 56) Abnormal NCS | 9 participants |
| Liraglutide 3.0 mg | Change in Physical Examination | Musculoskeletal System (week 56) Abnormal CS | 0 participants |
| Liraglutide 3.0 mg | Change in Physical Examination | Respiratory System (week -1) Normal | 140 participants |
| Liraglutide 3.0 mg | Change in Physical Examination | Respiratory System (week -1) Abnormal NCS | 2 participants |
| Liraglutide 3.0 mg | Change in Physical Examination | Respiratory System (week -1) Abnormal CS | 0 participants |
| Liraglutide 3.0 mg | Change in Physical Examination | Respiratory System (week 56) Normal | 138 participants |
| Liraglutide 3.0 mg | Change in Physical Examination | Respiratory System (week 56) Abnormal NCS | 1 participants |
| Liraglutide 3.0 mg | Change in Physical Examination | Respiratory System (week 56) Abnormal CS | 0 participants |
| Liraglutide 3.0 mg | Change in Physical Examination | Skin (week -1) Normal | 116 participants |
| Liraglutide 3.0 mg | Change in Physical Examination | Skin (week -1) Abnormal NCS | 26 participants |
| Liraglutide 3.0 mg | Change in Physical Examination | Skin (week -1) Abnormal CS | 1 participants |
| Liraglutide 3.0 mg | Change in Physical Examination | Skin (week 56) Normal | 117 participants |
| Liraglutide 3.0 mg | Change in Physical Examination | Skin (week 56) Abnormal NCS | 21 participants |
| Liraglutide 3.0 mg | Change in Physical Examination | Skin (week 56) Abnormal CS | 1 participants |
| Liraglutide 3.0 mg | Change in Physical Examination | Thyroid Gland (week -1) Normal | 138 participants |
| Liraglutide 3.0 mg | Change in Physical Examination | Thyroid Gland (week -1) Abnormal NCS | 4 participants |
| Liraglutide 3.0 mg | Change in Physical Examination | Thyroid Gland (week -1) Abnormal CS | 0 participants |
| Liraglutide 3.0 mg | Change in Physical Examination | Thyroid Gland (week 56) Normal | 136 participants |
| Liraglutide 3.0 mg | Change in Physical Examination | Thyroid Gland (week 56) Abnormal NCS | 3 participants |
| Liraglutide 3.0 mg | Change in Physical Examination | Thyroid Gland (week 56) Abnormal CS | 0 participants |
| Placebo | Change in Physical Examination | Respiratory System (week -1) Abnormal NCS | 2 participants |
| Placebo | Change in Physical Examination | Abdomen (week -1) Normal | 121 participants |
| Placebo | Change in Physical Examination | Head, ENTand Neck (week 56) Normal | 115 participants |
| Placebo | Change in Physical Examination | Abdomen (week -1) Abnormal, NCS | 19 participants |
| Placebo | Change in Physical Examination | Thyroid Gland (week 56) Abnormal CS | 0 participants |
| Placebo | Change in Physical Examination | Abdomen (week -1) Abnormal CS | 0 participants |
| Placebo | Change in Physical Examination | Head, ENTand Neck (week 56) Abnormal NCS | 7 participants |
| Placebo | Change in Physical Examination | Abdomen (week 56) Normal | 108 participants |
| Placebo | Change in Physical Examination | Respiratory System (week -1) Abnormal CS | 0 participants |
| Placebo | Change in Physical Examination | Abdomen (week 56) Abnormal, NCS | 12 participants |
| Placebo | Change in Physical Examination | Head, ENTand Neck (week 56) Abnormal CS | 0 participants |
| Placebo | Change in Physical Examination | Abdomen (week 56) Abnormal, CS | 2 participants |
| Placebo | Change in Physical Examination | Skin (week 56) Abnormal NCS | 24 participants |
| Placebo | Change in Physical Examination | Gastrointestinal System (week -1) Normal | 129 participants |
| Placebo | Change in Physical Examination | Lymph Node Palpation (week -1) Normal | 140 participants |
| Placebo | Change in Physical Examination | Gastrointestinal System (week -1) Abnormal NCS | 11 participants |
| Placebo | Change in Physical Examination | Respiratory System (week 56) Normal | 120 participants |
| Placebo | Change in Physical Examination | Gastrointestinal System (week -1) Abnormal CS | 0 participants |
| Placebo | Change in Physical Examination | Lymph Node Palpation (week -1) Abnormal NCS | 0 participants |
| Placebo | Change in Physical Examination | Gastrointestinal System (week 56) Normal | 116 participants |
| Placebo | Change in Physical Examination | Thyroid Gland (week -1) Abnormal CS | 0 participants |
| Placebo | Change in Physical Examination | Gastrointestinal System (week 56) Abnormal NCS | 6 participants |
| Placebo | Change in Physical Examination | Lymph Node Palpation (week -1) Abnormal CS | 0 participants |
| Placebo | Change in Physical Examination | Gastrointestinal System (week 56) Abnormal CS | 0 participants |
| Placebo | Change in Physical Examination | Respiratory System (week 56) Abnormal NCS | 2 participants |
| Placebo | Change in Physical Examination | Cardiovascular System (week-1) Normal | 127 participants |
| Placebo | Change in Physical Examination | Lymph Node Palpation (week 56) Normal | 121 participants |
| Placebo | Change in Physical Examination | Cardiovascular System (week-1) Abnormal NCS | 13 participants |
| Placebo | Change in Physical Examination | Skin (week 56) Abnormal CS | 0 participants |
| Placebo | Change in Physical Examination | Cardiovascular System (week-1) Abnormal CS | 0 participants |
| Placebo | Change in Physical Examination | Lymph Node Palpation (week 56) Abnormal NCS | 0 participants |
| Placebo | Change in Physical Examination | Cardiovascular System (week 56) Normal | 116 participants |
| Placebo | Change in Physical Examination | Respiratory System (week 56) Abnormal CS | 0 participants |
| Placebo | Change in Physical Examination | Cardiovascular System (week 56) Abnormal NCS | 5 participants |
| Placebo | Change in Physical Examination | Lymph Node Palpation (week 56) Abnormal CS | 1 participants |
| Placebo | Change in Physical Examination | Cardiovascular System (week 56) Abnormal CS | 1 participants |
| Placebo | Change in Physical Examination | Thyroid Gland (week 56) Abnormal NCS | 2 participants |
| Placebo | Change in Physical Examination | Nervous System (week -1) Normal | 127 participants |
| Placebo | Change in Physical Examination | Musculoskeletal System (week -1) Normal | 128 participants |
| Placebo | Change in Physical Examination | Nervous System (week -1) Abnormal NCS | 6 participants |
| Placebo | Change in Physical Examination | Skin (week -1) Normal | 114 participants |
| Placebo | Change in Physical Examination | Nervous System (week -1) Abnormal CS | 7 participants |
| Placebo | Change in Physical Examination | Musculoskeletal System (week -1) Abnormal NCS | 12 participants |
| Placebo | Change in Physical Examination | Nervous System (week 56) Normal | 112 participants |
| Placebo | Change in Physical Examination | Thyroid Gland (week -1) Normal | 138 participants |
| Placebo | Change in Physical Examination | Nervous System (week 56) Abnormal NCS | 9 participants |
| Placebo | Change in Physical Examination | Musculoskeletal System (week -1) Abnormal CS | 0 participants |
| Placebo | Change in Physical Examination | Nervous System (week 56) Abnormal CS | 1 participants |
| Placebo | Change in Physical Examination | Skin (week -1) Abnormal NCS | 24 participants |
| Placebo | Change in Physical Examination | General Appearance (week -1) Normal | 123 participants |
| Placebo | Change in Physical Examination | Musculoskeletal System (week 56) Normal | 112 participants |
| Placebo | Change in Physical Examination | General Appearance (week -1) Abnormal NCS | 17 participants |
| Placebo | Change in Physical Examination | Thyroid Gland (week 56) Normal | 120 participants |
| Placebo | Change in Physical Examination | General Appearance (week -1) Abnormal CS | 0 participants |
| Placebo | Change in Physical Examination | Musculoskeletal System (week 56) Abnormal NCS | 9 participants |
| Placebo | Change in Physical Examination | General Appearance (week 56) Normal | 112 participants |
| Placebo | Change in Physical Examination | Skin (week -1) Abnormal CS | 0 participants |
| Placebo | Change in Physical Examination | General Appearance (week 56) Abnormal NCS | 10 participants |
| Placebo | Change in Physical Examination | Musculoskeletal System (week 56) Abnormal CS | 1 participants |
| Placebo | Change in Physical Examination | General Appearance (week 56) Abnormal CS | 0 participants |
| Placebo | Change in Physical Examination | Thyroid Gland (week -1) Abnormal NCS | 2 participants |
| Placebo | Change in Physical Examination | Head, ENTand Neck (week -1) Normal | 128 participants |
| Placebo | Change in Physical Examination | Respiratory System (week -1) Normal | 138 participants |
| Placebo | Change in Physical Examination | Head, ENTand Neck (week -1) Abnormal NCS | 12 participants |
| Placebo | Change in Physical Examination | Skin (week 56) Normal | 98 participants |
| Placebo | Change in Physical Examination | Head, ENTand Neck (week -1) Abnormal CS | 0 participants |
Secondary
Change in Resting Pulse
Observed mean change in pulse rate measured at resting position is presented.
Time frame: Week 0, week 56
Population: Safety analysis set included all randomised subjects exposed to at least one dose of trial drug. Number analysed=subjects with available data.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Liraglutide 3.0 mg | Change in Resting Pulse | 2 beats/min | Standard Deviation 10 |
| Placebo | Change in Resting Pulse | 1 beats/min | Standard Deviation 10 |
Secondary
Change in Short Form-36 (SF-36) v2.0 Acute, Physical Functioning Score
SF-36 is a 36-item patient-reported survey of patient health that measures the subject's overall health-related quality of life (HRQoL). SF-36v2™ questionnaire measured the HRQoL on 8 domains on individual scale ranges. The scores 0-100 (where higher scores indicated a better HRQoL) from the SF-36 were converted to norm-based scores to enable a direct interpretation in relation to the distribution of the scores in the 2009 U.S. general population. A norm-based score of 50 corresponds to the mean score and 10 corresponds to the standard deviation of the 2009 U.S. general population. Change from baseline in SF-36 physical functioning score is presented. A positive change score indicates an improvement since baseline. The endpoint was evaluated based on in-trial data and on-drug data.
Time frame: Week 0, week 56
Population: Full analysis set included all randomised subjects. Number analysed=subjects with available data.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Liraglutide 3.0 mg | Change in Short Form-36 (SF-36) v2.0 Acute, Physical Functioning Score | In-trial observation period | 3.55 Scores on a scale | Standard Deviation 6.98 |
| Liraglutide 3.0 mg | Change in Short Form-36 (SF-36) v2.0 Acute, Physical Functioning Score | On-drug observation period | 4.03 Scores on a scale | Standard Deviation 6.49 |
| Placebo | Change in Short Form-36 (SF-36) v2.0 Acute, Physical Functioning Score | In-trial observation period | 4.21 Scores on a scale | Standard Deviation 6.85 |
| Placebo | Change in Short Form-36 (SF-36) v2.0 Acute, Physical Functioning Score | On-drug observation period | 4.77 Scores on a scale | Standard Deviation 6.03 |
Comparison: Treatment policy estimand. Analysis of in-trial data with missing observations imputed from the placebo arm based on a jump to reference multiple (x100) imputation approach. Week 56 responses were analysed using an analysis of covariance model with treatment, BMI groups, and sex as factors and baseline measurement of endpoint as covariate.p-value: 0.813795% CI: [-1.19, 1.52]ANCOVA
Comparison: Hypothetical estimand. Analysis of on-drug before first drug discontinuation date using a mixed model for repeated measurements with treatment, BMI groups, and sex as factors and baseline measurement of endpoint as covariate, all nested within visit.p-value: 0.805395% CI: [-1.12, 1.43]Mixed model repeated measurements (MMRM)
Secondary
Change in Short Form-36 v2.0 Acute (SF-36) (Mental Component Summary (MCS)
Observed mean change from baseline (week 0) to week 56 in short form 36 v2.0 acute domain mental component summary (MCS). SF-36v2™ questionnaire measured the HRQoL on 8 domains on individual scale ranges. The scores 0-100 (where higher scores indicated a better HRQoL) from the SF-36 were converted to norm-based scores to enable a direct interpretation in relation to the distribution of the scores in the 2009 U.S. general population. A norm-based score of 50 corresponds to the mean score and 10 corresponds to the standard deviation of the 2009 U.S. general population. Change from baseline in SF-36 mental component summary is presented. A positive change score indicates an improvement since baseline. The endpoint was evaluated based on in-trial data and on-drug data.
Time frame: Week 0, week 56
Population: Full analysis set included all randomised subjects. Number analysed=subjects with available data.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Liraglutide 3.0 mg | Change in Short Form-36 v2.0 Acute (SF-36) (Mental Component Summary (MCS) | -1.22 scores on a scale | Standard Deviation 8.74 |
| Placebo | Change in Short Form-36 v2.0 Acute (SF-36) (Mental Component Summary (MCS) | -2.20 scores on a scale | Standard Deviation 8.11 |
Secondary
Change in Short Form-36 v2.0 Acute (SF-36) (Physical Component Summary (PCS))
Observed mean change from baseline (week 0) to week 56 in short form 36 v2.0 acute domain physical component summary (PCS). SF-36v2™ questionnaire measured the HRQoL on 8 domains on individual scale ranges. The scores 0-100 (where higher scores indicated a better HRQoL) from the SF-36 were converted to norm-based scores to enable a direct interpretation in relation to the distribution of the scores in the 2009 U.S. general population. A norm-based score of 50 corresponds to the mean score and 10 corresponds to the standard deviation of the 2009 U.S. general population. Change from baseline in SF-36 physical component summary (PCS) score is presented. A positive change score indicates an improvement since baseline. The endpoint was evaluated based on in-trial data and on-drug data.
Time frame: Week 0, week 56
Population: Full analysis set included all randomised subjects. Number analysed=subjects with available data.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Liraglutide 3.0 mg | Change in Short Form-36 v2.0 Acute (SF-36) (Physical Component Summary (PCS)) | 3.41 scores on a scale | Standard Deviation 6.65 |
| Placebo | Change in Short Form-36 v2.0 Acute (SF-36) (Physical Component Summary (PCS)) | 3.83 scores on a scale | Standard Deviation 7.22 |
Secondary
Change in Short Form-36 v2.0 Acute (SF-36) (Subdomains)
SF-36 is a 36-item patient-reported survey of patient health that measures the subject's overall health-related quality of life (HRQoL). SF-36v2™ questionnaire measured the HRQoL on 8 domains on individual scale ranges. The scores 0-100 (where higher scores indicated a better HRQoL) from the SF-36 were converted to norm-based scores to enable a direct interpretation in relation to the distribution of the scores in the 2009 U.S. general population. A norm-based score of 50 corresponds to the mean score and 10 corresponds to the standard deviation of the 2009 U.S. general population. Change from baseline in in the sub-domain scores is presented. A positive change score indicates an improvement since baseline. Results are evaluated based on in-trial data.
Time frame: Week 0, week 56
Population: Full analysis set included all randomised subjects. Number analysed=subjects with available data.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Liraglutide 3.0 mg | Change in Short Form-36 v2.0 Acute (SF-36) (Subdomains) | Mental Health | -0.93 scores on a scale | Standard Deviation 7.8 |
| Liraglutide 3.0 mg | Change in Short Form-36 v2.0 Acute (SF-36) (Subdomains) | Role Lim. Phy Health | 2.01 scores on a scale | Standard Deviation 6.55 |
| Liraglutide 3.0 mg | Change in Short Form-36 v2.0 Acute (SF-36) (Subdomains) | General Health Perception | 1.89 scores on a scale | Standard Deviation 6.31 |
| Liraglutide 3.0 mg | Change in Short Form-36 v2.0 Acute (SF-36) (Subdomains) | Social Functioning | 1.22 scores on a scale | Standard Deviation 8.69 |
| Liraglutide 3.0 mg | Change in Short Form-36 v2.0 Acute (SF-36) (Subdomains) | Role Lim Emotion Prob | -1.27 scores on a scale | Standard Deviation 7.72 |
| Liraglutide 3.0 mg | Change in Short Form-36 v2.0 Acute (SF-36) (Subdomains) | Vitality | 2.64 scores on a scale | Standard Deviation 8.99 |
| Liraglutide 3.0 mg | Change in Short Form-36 v2.0 Acute (SF-36) (Subdomains) | Bodily Pain | 0.67 scores on a scale | Standard Deviation 7.61 |
| Placebo | Change in Short Form-36 v2.0 Acute (SF-36) (Subdomains) | Vitality | 2.43 scores on a scale | Standard Deviation 7.78 |
| Placebo | Change in Short Form-36 v2.0 Acute (SF-36) (Subdomains) | Bodily Pain | 1.21 scores on a scale | Standard Deviation 8.88 |
| Placebo | Change in Short Form-36 v2.0 Acute (SF-36) (Subdomains) | General Health Perception | 1.08 scores on a scale | Standard Deviation 6.62 |
| Placebo | Change in Short Form-36 v2.0 Acute (SF-36) (Subdomains) | Mental Health | -0.68 scores on a scale | Standard Deviation 6.89 |
| Placebo | Change in Short Form-36 v2.0 Acute (SF-36) (Subdomains) | Role Lim Emotion Prob | -2.21 scores on a scale | Standard Deviation 8.59 |
| Placebo | Change in Short Form-36 v2.0 Acute (SF-36) (Subdomains) | Role Lim. Phy Health | 2.11 scores on a scale | Standard Deviation 7.68 |
| Placebo | Change in Short Form-36 v2.0 Acute (SF-36) (Subdomains) | Social Functioning | -0.45 scores on a scale | Standard Deviation 9.61 |
Secondary
Change in Six Minutes Walking Distance Test (6MWT)
Observed mean change from baseline in 6 minutes walking distance test. The 6MWT is a common test of functional exercise capacity that assesses the distance a subject can walk in 6 minutes. The endpoint was evaluated based on in-trial data and on-drug data.
Time frame: Week 0, week 56
Population: Full analysis set included all randomised subjects. Number analysed=subjects with available data.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Liraglutide 3.0 mg | Change in Six Minutes Walking Distance Test (6MWT) | In-trial observation period | 47 meter | Standard Deviation 59 |
| Liraglutide 3.0 mg | Change in Six Minutes Walking Distance Test (6MWT) | On-drug observation period | 53 meter | Standard Deviation 61 |
| Placebo | Change in Six Minutes Walking Distance Test (6MWT) | In-trial observation period | 49 meter | Standard Deviation 69 |
| Placebo | Change in Six Minutes Walking Distance Test (6MWT) | On-drug observation period | 51 meter | Standard Deviation 69 |
Comparison: Treatment policy estimand. Analysis of in-trial data with missing observations imputed from the placebo arm based on a jump to reference multiple (x100) imputation approach. Week 56 responses were analysed using an analysis of covariance model with treatment, BMI groups, and sex as factors and baseline measurement of endpoint as covariate.p-value: 0.698695% CI: [-12.68, 18.92]ANCOVA
Comparison: Hypothetical estimand. Analysis of on-drug before first drug discontinuation date using a mixed model for repeated measurements with treatment, BMI groups, and sex as factors and baseline measurement of endpoint as covariate, all nested within visit.p-value: 0.3795% CI: [-9.15, 24.48]Mixed model repeated measurements (MMRM)
Secondary
Change in Waist Circumference (cm)
Observed mean change from baseline in waist circumference. The endpoint was evaluated based on in-trial data and on-drug data.
Time frame: Week 0, week 56
Population: Full analysis set included all randomised subjects. Number analysed=subjects with available data.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Liraglutide 3.0 mg | Change in Waist Circumference (cm) | In-trial observation period | -9.27 cm | Standard Deviation 9.22 |
| Liraglutide 3.0 mg | Change in Waist Circumference (cm) | On-drug observation period | -10.46 cm | Standard Deviation 9.22 |
| Placebo | Change in Waist Circumference (cm) | In-trial observation period | -6.91 cm | Standard Deviation 8.22 |
| Placebo | Change in Waist Circumference (cm) | On-drug observation period | -7.24 cm | Standard Deviation 8.67 |
Comparison: Analysis of in-trial data with missing observations imputed from the placebo arm based on a jump to reference multiple (x100) imputation approach. Week 56 responses were analysed using an analysis of covariance model with treatment, BMI groups, and sex as factors and baseline measurement of endpoint as covariate.p-value: 0.006395% CI: [-4.68, -0.77]ANCOVA
Comparison: Analysis of on-drug before first drug discontinuation date using a mixed model for repeated measurements with treatment, BMI groups, and sex as factors and baseline measurement of endpoint as covariate, all nested within visit.p-value: 0.00295% CI: [-5.62, -1.28]Mixed model repeated measurements (MMRM)
Secondary
Change in Weight Related Sign and Symptom (WRSS) Measure, Total Score
Observed mean change from baseline (week 0) to week 56 in WRSS measure, total score. The WRSS measures the presence and bothersome associated with weight-related symptoms. The WRSS questionnaire was not validated until after database lock. Therefore the total score couldn't be calculated and the supportive secondary endpoint Weight related sign and symptom (WRSS) measure, total score couldn't be analysed.
Time frame: Week 0, week 56
Population: Full analysis set included all randomised subjects. Number analysed=subjects with available data.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Liraglutide 3.0 mg | Change in Weight Related Sign and Symptom (WRSS) Measure, Total Score | NA Score on a scale |
| Placebo | Change in Weight Related Sign and Symptom (WRSS) Measure, Total Score | NA Score on a scale |
Secondary
Number of Weeks (Completed Calendar Weeks) From Randomisation to Week 56 Adherent to Caloric Diet
Adherence to caloric diet is assessed regularly at CMS-IBT visits. The number of weeks from randomisation to week 56, adherent to caloric diet is presented.
Time frame: Week 0, week 56
Population: Full analysis set included all randomised subjects. Number analysed=subjects with available data.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Liraglutide 3.0 mg | Number of Weeks (Completed Calendar Weeks) From Randomisation to Week 56 Adherent to Caloric Diet | 38.4 weeks | Standard Deviation 16 |
| Placebo | Number of Weeks (Completed Calendar Weeks) From Randomisation to Week 56 Adherent to Caloric Diet | 36.1 weeks | Standard Deviation 17.3 |
Secondary
Number of Weeks (Completed Calendar Weeks) From Randomisation to Week 56 Adherent to Caloric Diet and Physical Activity
Adherence to caloric diet and physical activity is assessed regularly at CMS-IBT visits. The number of weeks from randomisation to week 56, adherent to caloric diet and physical activity is presented.
Time frame: Week 0, week 56
Population: Full analysis set included all randomised subjects. Number analysed=subjects with available data.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Liraglutide 3.0 mg | Number of Weeks (Completed Calendar Weeks) From Randomisation to Week 56 Adherent to Caloric Diet and Physical Activity | 24.0 weeks | Standard Deviation 16 |
| Placebo | Number of Weeks (Completed Calendar Weeks) From Randomisation to Week 56 Adherent to Caloric Diet and Physical Activity | 24.5 weeks | Standard Deviation 15.7 |
Secondary
Number of Weeks (Completed Calendar Weeks) From Randomisation to Week 56 Adherent to Caloric Diet, Physical Activity and Trial Product
Adherence to caloric diet, physical activity and trial product is assessed regularly at CMS-IBT visits. The number of weeks from randomisation to week 56, adherent to caloric diet, physical activity and trial product is presented.
Time frame: Week 0, week 56
Population: Full analysis set included all randomised subjects. Number analysed=subjects with available data.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Liraglutide 3.0 mg | Number of Weeks (Completed Calendar Weeks) From Randomisation to Week 56 Adherent to Caloric Diet, Physical Activity and Trial Product | 22.9 weeks | Standard Deviation 16.1 |
| Placebo | Number of Weeks (Completed Calendar Weeks) From Randomisation to Week 56 Adherent to Caloric Diet, Physical Activity and Trial Product | 24.0 weeks | Standard Deviation 15.9 |
Secondary
Number of Weeks (Completed Calendar Weeks) From Randomisation to Week 56 Adherent to Physical Activity
Adherence to physical activity is assessed regularly at CMS-IBT visits. The number of weeks from randomisation to week 56, adherent to physical activity is presented.
Time frame: Week 0, week 56
Population: Full analysis set included all randomised subjects. Number analysed=subjects with available data.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Liraglutide 3.0 mg | Number of Weeks (Completed Calendar Weeks) From Randomisation to Week 56 Adherent to Physical Activity | 29.0 weeks | Standard Deviation 17.1 |
| Placebo | Number of Weeks (Completed Calendar Weeks) From Randomisation to Week 56 Adherent to Physical Activity | 30.0 weeks | Standard Deviation 17.2 |
Secondary
Number of Weeks (Completed Calendar Weeks) From Randomisation to Week 56 Adherent to Trial Product
Adherence to trial product is assessed regularly at CMS-IBT visits. The number of weeks from randomisation to week 56, adherent to trial product is presented.
Time frame: Week 0, week 56
Population: Full analysis set included all randomised subjects. Number analysed=subjects with available data.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Liraglutide 3.0 mg | Number of Weeks (Completed Calendar Weeks) From Randomisation to Week 56 Adherent to Trial Product | 49.5 weeks | Standard Deviation 14 |
| Placebo | Number of Weeks (Completed Calendar Weeks) From Randomisation to Week 56 Adherent to Trial Product | 46.8 weeks | Standard Deviation 16.1 |
Secondary
Proportion of Subjects Losing 4% or More of Baseline Body Weight
The estimated mean percentage of subjects losing 4% or more of baseline body weight at week 16 is presented. The endpoint was evaluated for treatment policy estimand (in-trial data).
Time frame: Week 16
Population: Full analysis set included all randomised subjects. Number analysed=subjects with available data.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Liraglutide 3.0 mg | Proportion of Subjects Losing 4% or More of Baseline Body Weight | 78.73 percentage of participants |
| Placebo | Proportion of Subjects Losing 4% or More of Baseline Body Weight | 52.70 percentage of participants |
Comparison: Treatment policy estimand. Week 16 responders were analysed using a logistic regression model with treatment, BMI groups, and sex as factors and baseline body weight as covariate.~Missing values are considered as non-responders.p-value: <0.000195% CI: [1.93, 5.72]Regression, Logistic
Secondary
Proportion of Subjects Losing More Than 10% of Baseline Body Weight at Week 56
The estimated mean percentage of subjects losing more than 10% of baseline body weight at week 56 is presented. The endpoint was evaluated based on in-trial data and on-drug data.
Time frame: Week 56
Population: Full analysis set included all randomised subjects. Number analysed=subjects with available data.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Liraglutide 3.0 mg | Proportion of Subjects Losing More Than 10% of Baseline Body Weight at Week 56 | In-trial observation period | 30.45 percentage of participants |
| Liraglutide 3.0 mg | Proportion of Subjects Losing More Than 10% of Baseline Body Weight at Week 56 | On-drug observation period | 33.80 percentage of participants |
| Placebo | Proportion of Subjects Losing More Than 10% of Baseline Body Weight at Week 56 | In-trial observation period | 19.75 percentage of participants |
| Placebo | Proportion of Subjects Losing More Than 10% of Baseline Body Weight at Week 56 | On-drug observation period | 19.29 percentage of participants |
Comparison: Treatment policy estimand. Week 56 responses were analysed using a logistic regression model with treatment, BMI groups, and sex as factors and baseline body weight as covariate. Analysis of in-trial data with missing observations imputed from the placebo arm based on a jump to reference multiple (x10000) imputation approach.p-value: 0.046995% CI: [1.01, 3.14]Regression, Logistic
Comparison: Hypothetical estimand. Analysis of on-drug before first drug discontinuation date using a mixed model for repeated measurements with treatment, BMI groups, and sex as factors and baseline body weight as covariate, all nested within visit. The MMRM was used to classify responders and analysed with a logistic regression with treatment as the only factor.p-value: 0.006395% CI: [1.24, 3.69]Mixed models repeated measurement (MMRM)
Secondary
Proportion of Subjects Losing More Than 15% of Baseline Body Weight at Week 56
The estimated mean percentage of subjects losing more than 15% of baseline body weight at week 56 is presented. The endpoint was evaluated based on in-trial data and on-drug data.
Time frame: Week 56
Population: Full analysis set included all randomised subjects. Number analysed=subjects with available data.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Liraglutide 3.0 mg | Proportion of Subjects Losing More Than 15% of Baseline Body Weight at Week 56 | In-trial observation period | 18.11 percentage of participants |
| Liraglutide 3.0 mg | Proportion of Subjects Losing More Than 15% of Baseline Body Weight at Week 56 | On-drug observation period | 20.42 percentage of participants |
| Placebo | Proportion of Subjects Losing More Than 15% of Baseline Body Weight at Week 56 | In-trial observation period | 8.92 percentage of participants |
| Placebo | Proportion of Subjects Losing More Than 15% of Baseline Body Weight at Week 56 | On-drug observation period | 8.57 percentage of participants |
Comparison: Treatment policy estimand. Week 56 responses were analysed using a logistic regression model with treatment, BMI groups, and sex as factors and baseline body weight as covariate. Analysis of in-trial data with missing observations imputed from the placebo arm based on a jump to reference multiple (x100) imputation approach.p-value: 0.031195% CI: [1.08, 4.74]Regression, Logistic
Comparison: Hypothetical estimand. Analysis of on-drug before first drug discontinuation date using a mixed model for repeated measurements with treatment, BMI groups, and sex as factors and baseline body weight as covariate, all nested within visit. The MMRM was used to classify responders and analysed with a logistic regression with treatment as the only factor.p-value: 0.00695% CI: [1.33, 5.62]Mixed models repeated measurement (MMRM)
Secondary
Responder Definition Value for IWQoL-Lite for CT Physical Function Domain (5-items) Score
Responder definition value for IWQoL-Lite for CT physical function domain (5-items) score' was defined as '≥ 20 responder definition value for IWQoL-Lite for CT physical function domain (5-items) score. Percentage of subjects considered IWQoL-Lite for CT physical function domain score responders (increase of ≥20 points) at week 56 is presented. Results based on FAS in-trial data is presented.
Time frame: Week 56
Population: Full analysis set included all randomised subjects. Number analysed=subjects with available data.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Liraglutide 3.0 mg | Responder Definition Value for IWQoL-Lite for CT Physical Function Domain (5-items) Score | 37.3 Percentage of participants |
| Placebo | Responder Definition Value for IWQoL-Lite for CT Physical Function Domain (5-items) Score | 34.3 Percentage of participants |
Secondary
Subjects Who After 56 Weeks Achieve (Yes/no): ≥ 3.8 T-score Points Increase From Baseline in SF-36 Physical Component Score
Percentage of subjects who achieved ≥ 3.8 T-score points increase from baseline in SF-36 physical component score at week 56 is presented. Results based on FAS in-trial data is presented.
Time frame: Week 56
Population: Full analysis set included all randomised subjects. Number analysed=subjects with available data.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Liraglutide 3.0 mg | Subjects Who After 56 Weeks Achieve (Yes/no): ≥ 3.8 T-score Points Increase From Baseline in SF-36 Physical Component Score | 43.7 Percentage of participants |
| Placebo | Subjects Who After 56 Weeks Achieve (Yes/no): ≥ 3.8 T-score Points Increase From Baseline in SF-36 Physical Component Score | 41.4 Percentage of participants |
Secondary
Subjects Who After 56 Weeks Achieve (Yes/no): ≥ 4.3 T-score Points Increase From Baseline in SF-36 Physical Functioning Score
Percentage of subjects who achieved ≥ 4.3 T-score points increase from baseline in SF-36 physical functioning score at week 56 is presented. Results based on FAS in-trial data is presented.
Time frame: Week 56
Population: Full analysis set included all randomised subjects. Number analysed=subjects with available data.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Liraglutide 3.0 mg | Subjects Who After 56 Weeks Achieve (Yes/no): ≥ 4.3 T-score Points Increase From Baseline in SF-36 Physical Functioning Score | 38.7 percentage of participants |
| Placebo | Subjects Who After 56 Weeks Achieve (Yes/no): ≥ 4.3 T-score Points Increase From Baseline in SF-36 Physical Functioning Score | 37.9 percentage of participants |
Secondary
Subjects Who After 56 Weeks Achieve (Yes/no): ≥ 4.6 T-score Points Increase From Baseline in SF-36 Mental Component Score
Percentage of subjects who achieved ≥ 4.6 T-score points increase from baseline in SF-36 mental component score at week 56 is presented. Results based on FAS in-trial data is presented.
Time frame: Week 56
Population: Full analysis set included all randomised subjects. Number analysed=subjects with available data.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Liraglutide 3.0 mg | Subjects Who After 56 Weeks Achieve (Yes/no): ≥ 4.6 T-score Points Increase From Baseline in SF-36 Mental Component Score | 20.4 Percentage of participants |
| Placebo | Subjects Who After 56 Weeks Achieve (Yes/no): ≥ 4.6 T-score Points Increase From Baseline in SF-36 Mental Component Score | 9.3 Percentage of participants |