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Effect of Liraglutide for Weight Management in Pubertal Adolescent Subjects With Obesity

Primary Purpose

Metabolism and Nutrition Disorder, Obesity

Status

Completed

Phase

Phase 3

Locations

International

Study Type

Interventional

Intervention

Liraglutide

Placebo

About this trial

This is an interventional treatment trial for Metabolism and Nutrition Disorder

Eligibility Criteria

12 Years - 17 Years (Child)All SexesDoes not accept healthy volunteers

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
Male or female, age 12 to less than 18 years at the time of signing informed consent and less than 18 years at date of randomisation
BMI corresponding to equal to or above 30 kg/m^2 for adults by international cut-off points and equal or above the 95th percentile for age and sex (for diagnosis of obesity)
Stable body weight during the previous 90 days before screening V2 (below 5 kg self-reported weight change)
History of failing to lose sufficient weight with lifestyle modification as judged by the investigator and documented in subject's medical record

Exclusion Criteria:

Pre-pubertal subjects (Tanner stage 1) at screening V2
Type 1 diabetes mellitus (T1DM)
Family or personal history of multiple endocrine neoplasia type 2 (MEN2)
Medullary thyroid carcinoma (MTC)
History of pancreatitis (acute or chronic)
Subjects with secondary causes of obesity (i.e., hypothalamic, genetic or endocrine causes)
Treatment with medications within 90 days before screening V2 that, based on the investigator's judgement, may cause significant weight change. This should also include treatment with any of the following medications: pramlintide, orlistat, zonisamide, topiramate, lorcaserin, phenteremine, bupropion, naltrexone, glucagon-like peptide-1 (GLP-1) receptor agonists, or metformin (used as treatment for obesity)
Anti-diabetic treatment other than metformin
History of major depressive disorder within 2 years before screening V2

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

Liraglutide

Placebo

Arm Description

Outcomes

Primary Outcome Measures

Change in BMI SDS (Week 0, Week 56)

Change from baseline (week 0) in BMI SDS was evaluated at week 56. BMI SDS was calculated using the following formula: Z=[(value /M)^L - 1] / S*L; where L, M and S are median (M), skewness (L) and variation coefficient (S) of children/adolescents' BMI provided for each sex and age. For each subject, a standard deviation score Z (SDS) was calculated based on age and sex referring to the values L, M and S. The method is described in the world health organisation (WHO) Multicentre Growth Reference, which also contains the values for L, M and S by age and sex. For Z (SDS) scores below -3 and above 3, the score was adjusted as described in the WHO instruction. All available data were used for the analysis including data collected after treatment discontinuation. Results are based on both participants who completed the week 0-56 trial period and participants who prematurely discontinued the trial product but attended the follow-up visit at 56.

Secondary Outcome Measures

Percent of Subjects Achieving ≥5% Reduction in Baseline BMI

Participants achieving more than or equal to 5% reduction in their baseline (week 0) BMI was evaluated at weeks 30, 56 and 82. Results are based on both participants who completed the trial period, week 0-30, week 0-56 or week 0-82, and participants who could not complete the corresponding trial period, but attended the follow-up visit at week 30, 56 or 82, respectively.

Percent of Subjects Achieving ≥10% Reduction in Baseline BMI

Participants achieving more than or equal to 10% reduction in their baseline (week 0) BMI was evaluated at weeks 30, 56 and 82. Results are based on both participants who completed the trial period, week 0-30, week 0-56 or week 0-82, and participants who could not complete the corresponding trial period, but attended the follow-up visit at week 30, 56 or 82, respectively.

Change in BMI SDS ((Week 0, Week 30); (Week 0, Week 82); (Week 56, Week 82))

Change in BMI SDS was evaluated from baseline (week 0) to weeks 30 and 82, and from week 56 to week 82. BMI SDS was calculated using the following formula: Z=[(value /M)^L - 1] / S*L; where L, M and S are median (M), skewness (L) and variation coefficient (S) of children/adolescents' BMI provided for each sex and age. For each subject, a Z (SDS) score was calculated based on age and sex referring to the values L, M and S. The method is described in the WHO Multicentre Growth Reference, which also contains the values for L, M and S by age and sex. For Z (SDS) scores below -3 and above 3, the score was adjusted as described in the WHO instruction. All available data were used for the analysis including data collected after treatment discontinuation. Results are based on both participants who completed the trial period, week 0-30 or week 0-82, and participants who could not complete the corresponding trial period, but attended the follow-up visit at week 30 or 82, respectively.

Change in BMI

Change in BMI was evaluated from baseline (week 0) to weeks 30 and 56, and from week 56 to week 82. Results are based on both participants who completed the trial period, week 0-30, week 0-56 or week 0-82, and participants who could not complete the corresponding trial period, but attended the follow-up visit at week 30, 56 or 82, respectively.

Change in Body Weight (kg)

Change in body weight (kg) was evaluated from baseline (week 0) to weeks 30 and 56, and from week 56 to week 82. Results are based on both participants who completed the trial period, week 0-30, week 0-56 or week 0-82, and participants who could not complete the corresponding trial period, but attended the follow-up visit at week 30, 56 or 82, respectively.

Change in Body Weight (%)

Relative change in body weight (kg) was evaluated from baseline (week 0) to weeks 30 and 56, and from week 56 to week 82. Results are based on both participants who completed the trial period, week 0-30, week 0-56 or week 0-82, and participants who could not complete the corresponding trial period, but attended the follow-up visit at week 30, 56 or 82, respectively.

Change in Body Weight (lb)

Body weight was not analysed in pounds (lb). It was analysed for standard unit, 'kg' only.

Change in Waist Circumference

Change in waist circumference was evaluated from baseline (week 0) to weeks 30 and 56, and from week 56 to week 82. Results are based on the participants who completed the corresponding trial period, week 0-30, week 0-56 or week 0-82.

Change in Waist-to-hip Circumference Ratio

Change in waist-to-hip circumference ratio was evaluated from baseline (week 0) to weeks 30 and 56, and from week 56 to week 82. Results are based on the participants who completed the corresponding trial period, week 0-30, week 0-56 or week 0-82.

Change in hsCRP

Change in high sensitivity C reactive protein (hsCRP) was evaluated from baseline (week 0) to weeks 30 and 56, and from week 56 to week 82. Results are based on the participants who completed the corresponding trial period, week 0-30, week 0-56 or week 0-82.

Change in Fasting Lipid: Total Cholesterol (Ratio to Baseline)

Change in total cholesterol from baseline (week 0) to weeks 30 and 56, and from week 56 to week 82 are presented as ratio to baseline. Results are based on the participants who completed the corresponding trial period, week 0-30, week 0-56 or week 0-82.

Change in Fasting Lipid: LDL-cholesterol (Ratio to Baseline)

Change in low density lipoprotein (LDL) cholesterol from baseline (week 0) to weeks 30 and 56, and from week 56 to week 82 are presented as ratio to baseline. Results are based on the participants who completed the corresponding trial period, week 0-30, week 0-56 or week 0-82.

Change in Fasting Lipid: HDL-cholesterol (Ratio to Baseline)

Change in high density lipoprotein (HDL) cholesterol from baseline (week 0) to weeks 30 and 56, and from week 56 to week 82 are presented as ratio to baseline. Results are based on the participants who completed the corresponding trial period, week 0-30, week 0-56 or week 0-82.

Change in Fasting Lipid: Non-HDL Cholesterol (Ratio to Baseline)

Change in non-HDL cholesterol from baseline (week 0) to weeks 30 and 56, and from week 56 to week 82 are presented as ratio to baseline. Results are based on the participants who completed the corresponding trial period, week 0-30, week 0-56 or week 0-82.

Change in Fasting Lipid: VLDL Cholesterol (Ratio to Baseline)

Change in very low density lipoprotein (VLDL) cholesterol from baseline (week 0) to weeks 30 and 56, and from week 56 to week 82 are presented as ratio to baseline. Results are based on the participants who completed the corresponding trial period, week 0-30, week 0-56 or week 0-82.

Change in Fasting Lipid: Triglycerides (Ratio to Baseline)

Change in triglycerides from baseline (week 0) to weeks 30 and 56, and from week 56 to week 82 are presented as ratio to baseline. Results are based on the participants who completed the corresponding trial period, week 0-30, week 0-56 or week 0-82.

Change in Fasting Lipid: FFA (Ratio to Baseline)

Change in free fatty acids (FFA) from baseline (week 0) to weeks 30 and 56, and from week 56 to week 82 are presented as ratio to baseline. Results are based on the participants who completed the corresponding trial period, week 0-30, week 0-56 or week 0-82.

Change in Systolic and Diastolic Blood Pressure

Change in systolic blood pressure (SBP) and diastolic blood pressure (DBP) was evaluated from baseline (week 0) to weeks 30 and 56, and from week 56 to week 82. Results are based on the participants who completed the corresponding trial period, week 0-30, week 0-56 or week 0-82.

Change in HbA1c

Change in glycosylated haemoglobin (HbA1c) was evaluated from baseline (week 0) to weeks 30 and 56, and from week 56 to week 82. Results are based on the participants who completed the corresponding trial period, week 0-30, week 0-56 or week 0-82.

Change in FPG

Change in fasting plasma glucose (FPG) was evaluated from baseline (week 0) to weeks 30 and 56, and from week 56 to week 82. Results are based on the participants who completed treatment for the corresponding treatment period (week 0-30, week 0-56 or week 0-82).

Change in Fasting Insulin (Ratio to Baseline)

Change in fasting insulin from baseline (week 0) to weeks 30 and 56, and from week 56 to week 82 are presented as ratio to baseline. Results are based on the participants who completed the corresponding trial period, week 0-30, week 0-56 or week 0-82.

Change in Fasting C-peptide (Ratio to Baseline)

Change in fasting C-peptide from baseline (week 0) to weeks 30 and 56, and from week 56 to week 82 are presented as ratio to baseline. Results are based on the participants who completed the corresponding trial period, week 0-30, week 0-56 or week 0-82.

Change in Glycaemic Category

Number of participants in glycaemic categories, "normoglycaemia, pre-diabetes and type 2 diabetes (T2DM)" at baseline (weeks -2), and weeks 30, 56 and 82 are presented. These categories were set as per the following criteria: 1) Normoglycaemia: FPG <5.6 mmol/L (<100 mg/dL) and/or HbA1c <5.7%. 2) Pre-diabetes: FPG 5.6-6.9 mmol/L (both inclusive), FPG 100-125 mg/dL (both inclusive) or HbA1c 5.7-6.4% (both inclusive). 3) Type 2 diabetes (T2DM): FPG ≥7.0 mmol/L (≥126 mg/dL) and/or HbA1c ≥6.5%. Week 30, 56 and 82 results are based on the participants who completed the corresponding trial period, week 0-30, week 0-56 or week 0-82.

Change in HOMA-B (Ratio to Baseline)

Change in homeostasis model assessment of beta-cell function (HOMA-B) from baseline (week 0) to weeks 30 and 56, and from week 56 to week 82 are presented as ratio to baseline. HOMA-B was calculated as: Beta-cell function (%) = 20·fasting insulin[mU/L]/(FPG[mmol/L]-3.5). Results are based on the participants who completed the corresponding trial period, week 0-30, week 0-56 or week 0-82.

Change in HOMA-IR (Ratio to Baseline)

Change in homeostasis model assessment of insulin resistance (HOMA-IR) from baseline (week 0) to weeks 30 and 56, and from week 56 to week 82 are presented as ratio to baseline. HOMA-IR was calculated as: Insulin resistance (%) = fasting insulin [mU/L] x FPG [mmol/L]/ 22.5. Results are based on the participants who completed the corresponding trial period, week 0-30, week 0-56 or week 0-82.

Change in IWQOL-Kids

Change in Impact of Weight on Quality of Life-Kids (IWQOL-Kids) was evaluated from baseline (week 0) to weeks 30 and 56, and from week 56 to week 82. The IWQOL-Kids is a 27-item measure of weight-related quality of life. There are four domain scores (Physical Comfort, Body Esteem, Social Life and Family Life) and a total score. Scores for all domains and total score range from 0-100, with higher scores representing better health-related quality of life. IWQOL-kids data at week 82 was not collected, thus could not be evaluated. Results are based on the participants who completed the corresponding trial period, week 0-30, week 0-56 or week 0-82.

Change in BMI SDS (%)

Relative change in BMI SDS was evaluated from baseline (week 0) to weeks 30 and 56. Results are based on the participants who completed the corresponding trial period, week 0-30 or week 0-56.

Change in Nutritional Compliance

This outcome measure presents "nutritional compliance results" recorded at baseline (week 0), week 30 and week 56. Nutritional compliance was recorded on a 0 to 10 numeric rating scale, with higher scores representing better compliance. Week 30 and 56 results are based on the participants who completed the corresponding trial period, week 0-30 or week 0-56.

Number of Treatment Emergent Adverse Events

A treatment emergent adverse event (TEAE) was defined as an event that occurred in the "on-treatment" period. 'On-treatment' period: Events with onset date between the first day of trial product administration and any of the following date, whichever came first: 1) 14 days after the last day on trial product, or 2) follow-up visit (week 58) for participants who discontinued trial product, or 3) last study visit (participants withdrawn without follow-up visit).

Number of Treatment Emergent Hypoglycaemic Episodes (ADA/ISPAD Classification)

A hypoglycaemic episode was defined as treatment emergent if the onset of the episode was on or after the first day of exposure to randomised treatment and no later than 14 days after the last day on randomised treatment. Severe hypoglycaemia episodes were recorded as per international society for pediatric and adolescent diabetes (ISPAD) definition. And the following presented hypoglycaemia episodes were recorded as per American Diabetes Association (ADA) definition: asymptomatic hypoglycaemia, documented symptomatic hypoglycaemia, pseudo-hypoglycaemia and probable symptomatic hypoglycaemia.

Number of Treatment Emergent Hypoglycaemic Episodes (Novo Nordisk/ISPAD Classification)

Severe hypoglycaemia episodes were recorded as per the ISPAD definition. And the following presented hypoglycaemia episodes were recorded as per Novo Nordisk definition: Symptomatic BG-confirmed: An episode that is blood glucose (BG) confirmed by plasma glucose (PG) value <3.1 mmol/L with symptoms consistent with hypoglycaemia. Asymptomatic BG-confirmed: An episode that is BG-confirmed by PG value <3.1 mmol/L without symptoms consistent with hypoglycaemia. 4) Severe or BG-confirmed symptomatic: An episode that is severe according to the ISPAD classification or BG-confirmed by a PG value <3.1 mmol/L with symptoms consistent with hypoglycaemia. 5) BG-confirmed: An episode that is BG-confirmed by a PG value <3.1 mmol/L with or without symptoms consistent with hypoglycaemia. 6) Severe or BG-confirmed: An episode that is severe according to the ISPAD classification or BG-confirmed by a PG value <3.1 mmol/L with or without symptoms consistent with hypoglycaemia.

Occurrence of Anti-liraglutide Antibodies

This outcome measure is only applicable for the liraglutide 3.0 mg treatment arm. Number of participants who measured with anti-liraglutide binding antibodies at weeks 0, 30, 56, 58, 70 and 82 are presented.

Change in Pulse

Change in pulse was evaluated from baseline (week 0) to weeks 30 and 56, and from week 56 to week 82. Results are based on the participants who completed the corresponding trial period, week 0-30, week 0-56 or week 0-82.

Change in ECG

This outcome measure presents number of subjects with electrocardiogram findings, "normal; abnormal, not clinically significant (NCS) or abnormal, clinically significant (CS)" recorded at baseline (week -14), week 30 and week 56. These findings were categorised by the investigator. Electrocardiogram (ECG) data at week 82 was not collected, thus could not be evaluated. Week 30 and 56 results are based on the participants who completed the corresponding trial period, week 0-30 or week 0-56.

Change in Haematology: Haemoglobin

Change in haemoglobin was evaluated from baseline (week 0) to weeks 30 and 56, and from week 56 to week 82. Results are based on the participants who completed the corresponding trial period, week 0-30, week 0-56 or week 0-82.

Change in Haematology: Haematocrit

Change in haematocrit was evaluated from baseline (week 0) to weeks 30 and 56, and from week 56 to week 82. Results are based on the participants who completed the corresponding trial period, week 0-30, week 0-56 or week 0-82.

Change in Haematology: Thrombocytes, Leucocytes, Eosinophils, Neutrophils, Basophils, Lymphocytes and Monocytes

Change in haematological parameters, "thrombocytes, leucocytes, eosinophils, neutrophils, basophils, lymphocytes and monocytes" was evaluated from baseline (week 0) to weeks 30 and 56, and from week 56 to week 82. Results are based on the participants who completed the corresponding trial period, week 0-30, week 0-56 or week 0-82.

Change in Haematology: Erythrocytes

Change in erythrocytes was evaluated from baseline (week 0) to weeks 30 and 56, and from week 56 to week 82. Results are based on the participants who completed the corresponding trial period, week 0-30, week 0-56 or week 0-82.

Change in Biochemistry: Creatinine and Bilirubin (Total)

Change in creatinine and bilirubin (total) was evaluated from baseline (week 0) to weeks 30 and 56, and from week 56 to week 82. Results are based on the participants who completed the corresponding trial period, week 0-30, week 0-56 or week 0-82.

Change in Biochemistry: Creatinine Kinase, Amylase, Lipase, ALT, AST and ALP

Change in biochemistry parameters, "creatinine kinase, amylase, lipase, alanine aminotransferase (ALT), aspartate aminotransferase (AST) and alkaline phosphatase (ALP)" was evaluated from baseline (week 0) to weeks 30 and 56, and from week 56 to week 82. Results are based on the participants who completed the corresponding trial period, week 0-30, week 0-56 or week 0-82.

Change in Biochemistry: Urea (BUN), Sodium, Potassium, Calcium Total and Calcium Albumin-corrected

Change in biochemistry parameters, "urea (blood urea nitrogen [BUN]), sodium, potassium, calcium total and calcium (Ca) albumin-corrected" was evaluated from baseline (week [Wk] 0) to weeks 30 and 56, and from week 56 to week 82. Results are based on the participants who completed the corresponding trial period, week 0-30, week 0-56 or week 0-82.

Change in Biochemistry: Albumin

Change in albumin was evaluated from baseline (week 0) to weeks 30 and 56, and from week 56 to week 82. Results are based on the participants who completed the corresponding trial period, week 0-30, week 0-56 or week 0-82.

Change in Biochemistry: CEA

Change in carcinoembryonic antigen (CEA) was evaluated from baseline (week 0) to weeks 30 and 56, and from week 56 to week 82. Results are based on the participants who completed the corresponding trial period, week 0-30, week 0-56 or week 0-82.

Change in Hormone Level: Calcitonin

Change in calcitonin was evaluated from baseline (week 0) to weeks 30 and 56, and from week 56 to week 82. Results are based on the participants who completed the corresponding trial period, week 0-30, week 0-56 or week 0-82.

Change in Hormone Level: TSH and Prolactin

Change in hormone levels, "thyroid stimulating hormone (TSH) and prolactin" was evaluated from baseline (week 0) to weeks 30 and 56, and from week 56 to week 82. Results are based on the participants who completed the corresponding trial period, week 0-30, week 0-56 or week 0-82.

Change in Hormone Level: Free T4 and ACTH

Change in hormone levels, "thyroxine (T4) and adrenocorticotropic hormone (ACTH)" was evaluated from baseline (week 0) to weeks 30 and 56, and from week 56 to week 82. Results are based on the participants who completed the corresponding trial period, week 0-30, week 0-56 or week 0-82.

Change in Hormone Level: IGF-1 and Cortisol

Change in hormone levels, "insulin-like growth factor-1 (IGF-1) and cortisol" was evaluated from baseline (week 0) to weeks 30 and 56, and from week 56 to week 82. Results are based on the participants who completed the corresponding trial period, week 0-30, week 0-56 or week 0-82.

Change in Hormone Level: DHEAS

Change in dehydroepiandrosterone sulfate (DHEAS) was evaluated from baseline (week 0) to weeks 30 and 56, and from week 56 to week 82. Results are based on the participants who completed the corresponding trial period, week 0-30, week 0-56 or week 0-82.

Change in Hormone Level: LH and FSH

Change in hormone levels, "luteinising hormone (LH) and follicle stimulating hormone (FSH)" was evaluated from baseline (week 0) to weeks 30 and 56, and from week 56 to week 82. Results are based on the participants who completed the corresponding trial period, week 0-30, week 0-56 or week 0-82.

Change in Hormone Level: Estradiol (Females)

Change in estradiol (only for female) was evaluated from baseline (week 0) to weeks 30 and 56, and from week 56 to week 82. Results are based on the participants who completed the corresponding trial period, week 0-30, week 0-56 or week 0-82.

Change in Hormone Level: Testosterone (Males)

This outcome measure presents "testosterone (only for males) results" for baseline (week 0), week 30, week 56 and week 82. ADVIA Centaur Testosterone (TSTO) assay was used for the evaluation of testosterone hormone. Week 30, 56 and 82 results are based on the participants who completed the corresponding trial period, week 0-30, week 0-56 or week 0-82.

Change in NTX1

Change in type I collagen N-telopeptide (NTX1) was evaluated from baseline (week 0) to weeks 30 and 56, and from week 56 to week 82. Results are presented in "nmol bone collagen equivalents (BCE)/L". Results are based on the participants who completed the corresponding trial period, week 0-30, week 0-56 or week 0-82.

Change in CTX1

Change in type I collagen C-telopeptide (CTX1) was evaluated from baseline (week 0) to weeks 30 and 56, and from week 56 to week 82. Results are based on the participants who completed the corresponding trial period, week 0-30, week 0-56 or week 0-82.

Change in P1NP

Change in procollagen 1 N-terminal propeptide (P1NP) was evaluated from baseline (week 0) to weeks 30 and 56, and from week 56 to week 82. Results are based on the participants who completed the corresponding trial period, week 0-30, week 0-56 or week 0-82.

Change in Alkaline Phosphatase (Bone)

Change in alkaline phosphatase (bone specific) was evaluated from baseline (week 0) to weeks 30 and 56, and from week 56 to week 82. Results are based on the participants who completed the corresponding trial period, week 0-30, week 0-56 or week 0-82.

Change in Pubertal Status

This outcome measure presents "pubertal status results" which is based on Tanner staging (Tanner stage 2-5), recorded at baseline (week 0), week 30, week 56 and week 82. Results are presented for the following categories: 1) For female: breast development and pubic hair development (by Tanner staging). 2) For male: penis development and pubic hair development (by Tanner staging). Each category shows number of participants in stages 2 to 5, where stage 2 represents "early pubertal development" and stage 5 represents "pubertal development equivalent to that of an adult". Week 30, 56 and 82 results are based on the participants who completed the corresponding trial period, week 0-30, week 0-56 or week 0-82.

Change in Physical Examination

This outcome measure presents number of subjects with physical examination findings, "normal; abnormal, not clinically significant (NCS) or abnormal, clinically significant (CS)" at baseline (week 0), week 30, week 56 and week 82. These findings were categorised by the investigator. Results include examination of: "general appearance"; "head, ears, eyes, nose, throat, neck"; "respiratory system"; "cardiovascular system (CVS)"; "gastrointestinal (GI) system including mouth"; "musculoskeletal system"; "central nervous system (CNS) and peripheral nervous system (PNS)"; "skin"; "thyroid gland" and "lymph node palpation". Week 30, 56 and 82 results are based on the participants who completed the corresponding trial period, week 0-30, week 0-56 or week 0-82.

Change in Height SDS

Change in height standard deviation score (SDS) was evaluated from baseline (week 0) to weeks 30 and 56, and from week 56 to week 82. Height SDS was calculated using the following formula: Z=[(value /M)^L - 1] / S*L; where L, M and S are median (M), skewness (L) and variation coefficient (S) of children/adolescents' height provided for each sex and age. For each subject, a standard deviation score Z (SDS) was calculated based on age and sex referring to the values L, M and S. The method is described in the WHO Multicentre Growth Reference, which also contains the values for L, M and S by age and sex. For Z (SDS) scores below -3 and above 3, the score was adjusted as described in the WHO instruction. Results are based on both participants who completed the trial period, week 0-30, week 0-56 or week 0-82, and participants who could not complete the corresponding trial period, but attended the follow-up visit at week 30, 56 or 82, respectively.

Change in C-SSRS

This outcome measure presents number of subjects with "suicidal ideation or suicidal behaviour on the Columbia Suicidality Severity Rating Scale (C-SSRS)" assessed at baseline (week 0), week 30, week 56 and week 82. Week 30, 56 and 82 results are based on the participants who completed the corresponding trial period, week 0-30, week 0-56 or week 0-82.

Change in PHQ-9

Change in Patient Health Questionnaire 9 (PHQ-9) was evaluated from baseline (week 0) to weeks 30 and 56, and from week 56 to week 82. The PHQ-9 questionnaire is a 9-item depression module included in the patient health questionnaire, a self-administered diagnostic tool used for assessment of mental disorders. The PHQ-9 total score ranges from 0-27; total scores of 1-4 represent no depression, total scores of 5-9 represent mild depression, total scores of 10-14 represent moderate depression, total scores of 15-19 represent moderately severe depression and total scores of 20-27 represent severe depression. Results are based on the participants who completed the corresponding trial period, week 0-30, week 0-56 or week 0-82.

Full Information

NCT ID

NCT02918279

First Posted

September 27, 2016

Last Updated

April 15, 2020

Sponsor

Novo Nordisk A/S

1. Study Identification

Unique Protocol Identification Number

NCT02918279

Brief Title

Effect of Liraglutide for Weight Management in Pubertal Adolescent Subjects With Obesity

Official Title

Effect of Liraglutide for Weight Management in Pubertal Adolescent Subjects With Obesity. 56-week, Double-blind, Randomised, Parallel-group, Placebo-controlled Multi-national Trial Followed by a 26-week Period Off Study-drug

Study Type

Interventional

2. Study Status

Record Verification Date

April 2020

Overall Recruitment Status

Completed

Study Start Date

September 29, 2016 (Actual)

Primary Completion Date

February 14, 2019 (Actual)

Study Completion Date

August 8, 2019 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Novo Nordisk A/S

4. Oversight

Data Monitoring Committee

Yes

5. Study Description

Brief Summary

This trial is conducted globally. The aim of this trial is to investigate the effect of liraglutide for weight management in pubertal adolescent subjects with obesity.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Metabolism and Nutrition Disorder, Obesity

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 3

Interventional Study Model

Parallel Assignment

Masking

ParticipantInvestigator

Allocation

Randomized

Enrollment

251 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Liraglutide

Arm Type

Experimental

Arm Title

Placebo

Arm Type

Placebo Comparator

Intervention Type

Drug

Intervention Name(s)

Liraglutide

Intervention Description

Administered once daily subcutaneously (s.c., under the skin)

Intervention Type

Drug

Intervention Name(s)

Placebo

Intervention Description

Administered once daily subcutaneously (s.c., under the skin)

Primary Outcome Measure Information:

Title

Change in BMI SDS (Week 0, Week 56)

Description

Time Frame

Week 0, week 56

Secondary Outcome Measure Information:

Title

Percent of Subjects Achieving ≥5% Reduction in Baseline BMI

Description

Time Frame

Weeks 30, 56 and 82

Title

Percent of Subjects Achieving ≥10% Reduction in Baseline BMI

Description

Time Frame

Weeks 30, 56 and 82

Title

Change in BMI SDS ((Week 0, Week 30); (Week 0, Week 82); (Week 56, Week 82))

Description

Time Frame

(Week 0, week 30); (Week 0, week 82); (Week 56, week 82)

Title

Change in BMI

Description

Time Frame

(Week 0, week 30); (Week 0, week 56); (Week 56, week 82)

Title

Change in Body Weight (kg)

Description

Time Frame

(Week 0, week 30); (Week 0, week 56); (Week 56, week 82)

Title

Change in Body Weight (%)

Description

Time Frame

(Week 0, week 30); (Week 0, week 56); (Week 56, week 82)

Title

Change in Body Weight (lb)

Description

Body weight was not analysed in pounds (lb). It was analysed for standard unit, 'kg' only.

Time Frame

(Week 0, week 30); (Week 0, week 56); (Week 56, week 82)

Title

Change in Waist Circumference

Description

Time Frame

(Week 0, week 30); (Week 0, week 56); (Week 56, week 82)

Title

Change in Waist-to-hip Circumference Ratio

Description

Time Frame

(Week 0, week 30); (Week 0, week 56); (Week 56, week 82)

Title

Change in hsCRP

Description

Time Frame

(Week 0, week 30); (Week 0, week 56); (Week 56, week 82)

Title

Change in Fasting Lipid: Total Cholesterol (Ratio to Baseline)

Description

Time Frame

(Week 0, week 30); (Week 0, week 56); (Week 56, week 82)

Title

Change in Fasting Lipid: LDL-cholesterol (Ratio to Baseline)

Description

Time Frame

(Week 0, week 30); (Week 0, week 56); (Week 56, week 82)

Title

Change in Fasting Lipid: HDL-cholesterol (Ratio to Baseline)

Description

Time Frame

(Week 0, week 30); (Week 0, week 56); (Week 56, week 82)

Title

Change in Fasting Lipid: Non-HDL Cholesterol (Ratio to Baseline)

Description

Time Frame

(Week 0, week 30); (Week 0, week 56); (Week 56, week 82)

Title

Change in Fasting Lipid: VLDL Cholesterol (Ratio to Baseline)

Description

Time Frame

(Week 0, week 30); (Week 0, week 56); (Week 56, week 82)

Title

Change in Fasting Lipid: Triglycerides (Ratio to Baseline)

Description

Time Frame

(Week 0, week 30); (Week 0, week 56); (Week 56, week 82)

Title

Change in Fasting Lipid: FFA (Ratio to Baseline)

Description

Time Frame

(Week 0, week 30); (Week 0, week 56); (Week 56, week 82)

Title

Change in Systolic and Diastolic Blood Pressure

Description

Time Frame

(Week 0, week 30); (Week 0, week 56); (Week 56, week 82)

Title

Change in HbA1c

Description

Time Frame

(Week 0, week 30); (Week 0, week 56); (Week 56, week 82)

Title

Change in FPG

Description

Time Frame

(Week 0, week 30); (Week 0, week 56); (Week 56, week 82)

Title

Change in Fasting Insulin (Ratio to Baseline)

Description

Time Frame

(Week 0, week 30); (Week 0, week 56); (Week 56, week 82)

Title

Change in Fasting C-peptide (Ratio to Baseline)

Description

Time Frame

(Week 0, week 30); (Week 0, week 56); (Week 56, week 82)

Title

Change in Glycaemic Category

Description

Time Frame

Week -2, week 30, week 56 and week 82

Title

Change in HOMA-B (Ratio to Baseline)

Description

Time Frame

(Week 0, week 30); (Week 0, week 56); (Week 56, week 82)

Title

Change in HOMA-IR (Ratio to Baseline)

Description

Time Frame

(Week 0, week 30); (Week 0, week 56); (Week 56, week 82)

Title

Change in IWQOL-Kids

Description

Time Frame

(Week 0, week 30); (Week 0, week 56); (Week 56, week 82)

Title

Change in BMI SDS (%)

Description

Relative change in BMI SDS was evaluated from baseline (week 0) to weeks 30 and 56. Results are based on the participants who completed the corresponding trial period, week 0-30 or week 0-56.

Time Frame

(Week 0, week 30); (Week 0, week 56)

Title

Change in Nutritional Compliance

Description

Time Frame

Week 0, week 30 and week 56

Title

Number of Treatment Emergent Adverse Events

Description

Time Frame

Week 0-56 + 14 days

Title

Number of Treatment Emergent Hypoglycaemic Episodes (ADA/ISPAD Classification)

Description

Time Frame

Week 0-56 + 14 days

Title

Number of Treatment Emergent Hypoglycaemic Episodes (Novo Nordisk/ISPAD Classification)

Description

Time Frame

Week 0-56 + 14 days

Title

Occurrence of Anti-liraglutide Antibodies

Description

Time Frame

Weeks 0, 30, 56, 58, 70 and 82

Title

Change in Pulse

Description

Time Frame

(Week 0, week 30); (Week 0, week 56); (Week 56, week 82)

Title

Change in ECG

Description

Time Frame

Week -14, week 30, week 56 and week 82

Title

Change in Haematology: Haemoglobin

Description

Time Frame

(Week 0, week 30); (Week 0, week 56); (Week 56, week 82)

Title

Change in Haematology: Haematocrit

Description

Time Frame

(Week 0, week 30); (Week 0, week 56); (Week 56, week 82)

Title

Change in Haematology: Thrombocytes, Leucocytes, Eosinophils, Neutrophils, Basophils, Lymphocytes and Monocytes

Description

Time Frame

(Week 0, week 30); (Week 0, week 56); (Week 56, week 82)

Title

Change in Haematology: Erythrocytes

Description

Time Frame

(Week 0, week 30); (Week 0, week 56); (Week 56, week 82)

Title

Change in Biochemistry: Creatinine and Bilirubin (Total)

Description

Time Frame

(Week 0, week 30); (Week 0, week 56); (Week 56, week 82)

Title

Change in Biochemistry: Creatinine Kinase, Amylase, Lipase, ALT, AST and ALP

Description

Time Frame

(Week 0, week 30); (Week 0, week 56); (Week 56, week 82)

Title

Change in Biochemistry: Urea (BUN), Sodium, Potassium, Calcium Total and Calcium Albumin-corrected

Description

Time Frame

(Week 0, week 30); (Week 0, week 56); (Week 56, week 82)

Title

Change in Biochemistry: Albumin

Description

Time Frame

(Week 0, week 30); (Week 0, week 56); (Week 56, week 82)

Title

Change in Biochemistry: CEA

Description

Time Frame

(Week 0, week 30); (Week 0, week 56); (Week 56, week 82)

Title

Change in Hormone Level: Calcitonin

Description

Time Frame

(Week 0, week 30); (Week 0, week 56); (Week 56, week 82)

Title

Change in Hormone Level: TSH and Prolactin

Description

Time Frame

(Week 0, week 30); (Week 0, week 56); (Week 56, week 82)

Title

Change in Hormone Level: Free T4 and ACTH

Description

Time Frame

(Week 0, week 30); (Week 0, week 56); (Week 56, week 82)

Title

Change in Hormone Level: IGF-1 and Cortisol

Description

Time Frame

(Week 0, week 30); (Week 0, week 56); (Week 56, week 82)

Title

Change in Hormone Level: DHEAS

Description

Time Frame

(Week 0, week 30); (Week 0, week 56); (Week 56, week 82)

Title

Change in Hormone Level: LH and FSH

Description

Time Frame

(Week 0, week 30); (Week 0, week 56); (Week 56, week 82)

Title

Change in Hormone Level: Estradiol (Females)

Description

Time Frame

(Week 0, week 30); (Week 0, week 56); (Week 56, week 82)

Title

Change in Hormone Level: Testosterone (Males)

Description

Time Frame

Week 0, week 30, week 56 and week 82

Title

Change in NTX1

Description

Time Frame

(Week 0, week 30); (Week 0, week 56); (Week 56, week 82)

Title

Change in CTX1

Description

Time Frame

(Week 0, week 30); (Week 0, week 56); (Week 56, week 82)

Title

Change in P1NP

Description

Time Frame

(Week 0, week 30); (Week 0, week 56); (Week 56, week 82)

Title

Change in Alkaline Phosphatase (Bone)

Description

Time Frame

(Week 0, week 30); (Week 0, week 56); (Week 56, week 82)

Title

Change in Pubertal Status

Description

Time Frame

(Week 0, week 30); (Week 0, week 56); (Week 56, week 82)

Title

Change in Physical Examination

Description

Time Frame

Week 0, week 30, week 56 and week 82

Title

Change in Height SDS

Description

Time Frame

(Week 0, week 30); (Week 0, week 56); (Week 56, week 82)

Title

Change in C-SSRS

Description

Time Frame

(Week 0, week 30); (Week 0, week 56); (Week 56, week 82)

Title

Change in PHQ-9

Description

Time Frame

(Week 0, week 30); (Week 0, week 56); (Week 56, week 82)

10. Eligibility

Sex

All

Minimum Age & Unit of Time

12 Years

Maximum Age & Unit of Time

17 Years

Accepts Healthy Volunteers

Eligibility Criteria

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 Male or female, age 12 to less than 18 years at the time of signing informed consent and less than 18 years at date of randomisation BMI corresponding to equal to or above 30 kg/m^2 for adults by international cut-off points and equal or above the 95th percentile for age and sex (for diagnosis of obesity) Stable body weight during the previous 90 days before screening V2 (below 5 kg self-reported weight change) History of failing to lose sufficient weight with lifestyle modification as judged by the investigator and documented in subject's medical record Exclusion Criteria: Pre-pubertal subjects (Tanner stage 1) at screening V2 Type 1 diabetes mellitus (T1DM) Family or personal history of multiple endocrine neoplasia type 2 (MEN2) Medullary thyroid carcinoma (MTC) History of pancreatitis (acute or chronic) Subjects with secondary causes of obesity (i.e., hypothalamic, genetic or endocrine causes) Treatment with medications within 90 days before screening V2 that, based on the investigator's judgement, may cause significant weight change. This should also include treatment with any of the following medications: pramlintide, orlistat, zonisamide, topiramate, lorcaserin, phenteremine, bupropion, naltrexone, glucagon-like peptide-1 (GLP-1) receptor agonists, or metformin (used as treatment for obesity) Anti-diabetic treatment other than metformin History of major depressive disorder within 2 years before screening V2

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Global Clinical Registry (GCR)

Organizational Affiliation

Novo Nordisk A/S

Official's Role

Study Director

Facility Information:

Facility Name

Novo Nordisk Investigational Site

City

Meridian

State/Province

Idaho

ZIP/Postal Code

83646

Country

United States

Facility Name

Novo Nordisk Investigational Site

City

Baton Rouge

State/Province

Louisiana

ZIP/Postal Code

70808-4124

Country

United States

Facility Name

Novo Nordisk Investigational Site

City

Baltimore

State/Province

Maryland

ZIP/Postal Code

21229

Country

United States

Facility Name

Novo Nordisk Investigational Site

City

Minneapolis

State/Province

Minnesota

ZIP/Postal Code

55455

Country

United States

Facility Name

Novo Nordisk Investigational Site

City

Buffalo

State/Province

New York

ZIP/Postal Code

14222

Country

United States

Facility Name

Novo Nordisk Investigational Site

City

Columbus

State/Province

Ohio

ZIP/Postal Code

43213

Country

United States

Facility Name

Novo Nordisk Investigational Site

City

Dayton

State/Province

Ohio

ZIP/Postal Code

45406

Country

United States

Facility Name

Novo Nordisk Investigational Site

City

Dayton

State/Province

Ohio

ZIP/Postal Code

45419

Country

United States

Facility Name

Novo Nordisk Investigational Site

City

Pittsburgh

State/Province

Pennsylvania

ZIP/Postal Code

15224

Country

United States

Facility Name

Novo Nordisk Investigational Site

City

Charleston

State/Province

South Carolina

ZIP/Postal Code

29425

Country

United States

Facility Name

Novo Nordisk Investigational Site

City

Goose Creek

State/Province

South Carolina

ZIP/Postal Code

29445

Country

United States

Facility Name

Novo Nordisk Investigational Site

City

Greenville

State/Province

South Carolina

ZIP/Postal Code

29615

Country

United States

Facility Name

Novo Nordisk Investigational Site

City

Memphis

State/Province

Tennessee

ZIP/Postal Code

38119

Country

United States

Facility Name

Novo Nordisk Investigational Site

City

Brussels

ZIP/Postal Code

1090

Country

Belgium

Facility Name

Novo Nordisk Investigational Site

City

Brussels

ZIP/Postal Code

1200

Country

Belgium

Facility Name

Novo Nordisk Investigational Site

City

Edegem

ZIP/Postal Code

2650

Country

Belgium

Facility Name

Novo Nordisk Investigational Site

City

Hasselt

ZIP/Postal Code

3500

Country

Belgium

Facility Name

Novo Nordisk Investigational Site

City

Leuven

ZIP/Postal Code

3000

Country

Belgium

Facility Name

Novo Nordisk Investigational Site

City

Namur

ZIP/Postal Code

5000

Country

Belgium

Facility Name

Novo Nordisk Investigational Site

City

Ciudad Madero

State/Province

Tamaulipas

ZIP/Postal Code

89440

Country

Mexico

Facility Name

Novo Nordisk Investigational Site

City

Puebla

ZIP/Postal Code

72190

Country

Mexico

Facility Name

Novo Nordisk Investigational Site

City

Moscow

ZIP/Postal Code

125373

Country

Russian Federation

Facility Name

Novo Nordisk Investigational Site

City

Novosibirsk

ZIP/Postal Code

630048

Country

Russian Federation

Facility Name

Novo Nordisk Investigational Site

City

Rostov-on-Don

ZIP/Postal Code

344013

Country

Russian Federation

Facility Name

Novo Nordisk Investigational Site

City

Saint-Petersburg

ZIP/Postal Code

191144

Country

Russian Federation

Facility Name

Novo Nordisk Investigational Site

City

Samara

ZIP/Postal Code

443079

Country

Russian Federation

Facility Name

Novo Nordisk Investigational Site

City

Stavropol

ZIP/Postal Code

355035

Country

Russian Federation

Facility Name

Novo Nordisk Investigational Site

City

Tomsk

ZIP/Postal Code

634050

Country

Russian Federation

Facility Name

Novo Nordisk Investigational Site

City

Ufa

ZIP/Postal Code

450106

Country

Russian Federation

Facility Name

Novo Nordisk Investigational Site

City

Göteborg

ZIP/Postal Code

416 85

Country

Sweden

Facility Name

Novo Nordisk Investigational Site

City

Huddinge

ZIP/Postal Code

141 57

Country

Sweden

Facility Name

Novo Nordisk Investigational Site

City

Malmö

ZIP/Postal Code

205 02

Country

Sweden

Facility Name

Novo Nordisk Investigational Site

City

Uppsala

ZIP/Postal Code

751 85

Country

Sweden

12. IPD Sharing Statement

Citations:

PubMed Identifier

32233338

Citation

Kelly AS, Auerbach P, Barrientos-Perez M, Gies I, Hale PM, Marcus C, Mastrandrea LD, Prabhu N, Arslanian S; NN8022-4180 Trial Investigators. A Randomized, Controlled Trial of Liraglutide for Adolescents with Obesity. N Engl J Med. 2020 May 28;382(22):2117-2128. doi: 10.1056/NEJMoa1916038. Epub 2020 Mar 31.

Results Reference

result

Learn more about this trial

Effect of Liraglutide for Weight Management in Pubertal Adolescent Subjects With Obesity

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Effect of Liraglutide for Weight Management in Pubertal Adolescent Subjects With Obesity

Metabolism and Nutrition Disorder, Obesity

About this trial

Eligibility Criteria

Sites / Locations

Arms of the Study

Arm 1

Arm 2

Outcomes

Primary Outcome Measures

Secondary Outcome Measures

Full Information

1. Study Identification

2. Study Status

3. Sponsor/Collaborators

4. Oversight

5. Study Description

6. Conditions and Keywords

7. Study Design

8. Arms, Groups, and Interventions

10. Eligibility

12. IPD Sharing Statement

Learn more about this trial