Diabetes Mellitus, Type 2
Conditions
Brief summary
This study compares 2 medicines for type 2 diabetes: semaglutide (new medicine) and a dummy medicine (placebo). Semaglutide will be tested to see how well it works compared to the dummy medicine. The study will also test if semaglutide is safe in children and teenagers. Participants will either get semaglutide or the dummy medicine - which one is decided by chance. Participants will take 1 tablet of the study medicine every morning on an empty stomach. They have to wait 30 minutes before they eat, drink or take any other medication by mouth. The study will last for about 1 year and 3 months (66 weeks). Participants will have 12 clinic visits and 8 phone calls with the study doctor. At all 12 clinic visits, participants will have blood samples taken. Participants will also be asked some questions.
Interventions
DRUGOral semaglutide
Oral semaglutide treatment for 52 weeks. All participants will be dose-escalated to an individual maximum tolerated dose.
DRUGPlacebo (semaglutide)
Placebo treatment for 52 weeks.
Sponsors
Novo Nordisk A/S
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
10 Years to 18 Years
Healthy volunteers
No
Inclusion criteria
* Informed consent from parent(s) or legally acceptable representative (LAR) and child assent from the subject 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, aged 10 to below 18 years at the day of randomisation * HbA1c 6.5%-11.0% (47-97 mmol/mol) (both inclusive) * Diagnosed with type 2 diabetes mellitus according to the American Diabetes Association criteria and treated with: * stable metformin dose (stable metformin dose is defined as at least 1000 mg daily or the maximum tolerated dose for 56 days or longer prior to screening) or * stable metformin dose and a stable dose of basal insulin (stable dose of basal insulin is defined as basal insulin treatment equal to or more than 30 days prior to screening, compared to the dose at screening, dose adjustments of ± 25% are allowed) or * stable dose of basal insulin
Exclusion criteria
* Diagnosis of type 1 diabetes * Maturity onset diabetes of the young (MODY) * Positive insulinoma associated-protein 2 (IA-2) antibodies or anti-glutamic acid decarboxylase (anti-GAD) antibodies.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline (Week 0) to Week 26 in Glycosylated Haemoglobin (HbA1c)- Percentage Point | Baseline (Week 0), Week 26 | This outcome measure reports change from baseline to week 26 in HbA1c measured in terms of percentage point. |
| Change From Baseline (Week 0) in HbA1c to Week 26- Millimoles Per Mole (mmol/Mol) | Baseline (Week 0), Week 26 | This outcome measure reports change from baseline to week 26 in HbA1c in terms of mmol/mol. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline (Week 0) in Fasting Plasma Glucose (FPG) to Week 26 | Baseline (Week 0), Week 26 | This outcome measure reports change from baseline in FPG to week 26 measured in terms of milligrams per deciliter (mg/dL). |
| Change From Baseline (Week 0) in Body Mass Index (BMI) Standard Deviation Score (SDS) to Week 26 | Baseline (Week 0), Week 26 | This outcome measure reports change from baseline to week 26 in BMI measured in terms of the SDS. BMI SDS was calculated based on the WHO 2007 growth reference for children and adolescents. The BMI SDS formula comes from the LMS method as: Z = (\[BMI/M)\]\^L-1)/ L×S where: L=Skewness (Box-Cox power); M=Median; S= (Coefficient of Variation). |
| Change From Baseline in HbA1c at Week 52 (Percentage Point) | Baseline (Week 0), Week 52 | This outcome measure reports change from baseline to week 52 in HbA1c measured in terms of percentage point. |
| Change From Baseline in HbA1c at Week 52 (mmol/Mol) | Baseline (Week 0), Week 52 | This outcome measure reports change from baseline to week 52 in HbA1c measured in terms of mmol/mol. |
| Change From Baseline in Fasting Plasma Glucose at Week 52 (mg/dL) | Baseline (Week 0), Week 52 | This outcome measure reports change from baseline to week 52 in FPG measured in terms of mg/dL. |
| Change From Baseline in Body Weight to Week 26 and Week 52 (Kilograms [kg]) | Baseline (Week 0), Week 26, Week 52 | This outcome measure reports change from baseline to week 26 and week 52 in body weight measured in terms of kg. |
| Relative Change From Baseline in Body Weight to Week 26 and Week 52 | Baseline (Week 0), Week 26, Week 52 | This outcome measure reports relative change from baseline to week 26 and week 52 in body weight measured in terms of percent change. |
| Change From Baseline in Waist Circumference to Week 26 and Week 52 | Baseline (Week 0), Week 26, Week 52 | This outcome measure reports change from baseline to week 26 and week 52 in Waist circumference measured in terms of centimeters (cm). |
| Change From Baseline in Body Mass Index Standard Deviation Score at Week 52 | Baseline (Week 0), Week 52 | This outcome measure reports change from baseline to week 52 in BMI measured in terms of SDS. BMI SDS was calculated based on the WHO 2007 growth reference for children and adolescents. The BMI SDS formula comes from the LMS method: Z = (\[BMI/M)\]\^L-1)/ L×S where: L=Skewness (Box-Cox power), M=Median, S= (Coefficient of Variation) |
| Change From Baseline (Week 0) in BMI Percentile (Age and Gender Adjusted) to Week 26 and Week 52 | Baseline (Week 0), Week 26, Week 52 | This outcome measure reports change from baseline (Week 0) in BMI percentile on gender and age-specific growth charts change in terms of percentile of BMI to week 26 and week 52. BMI Percentile was calculated using the CDC 2000 Reference Growth Charts and was derived using the standard LMS method. The CDC reference-specific parameters - L (Lambda), M (Median) and S (Coefficient of Variation) were extracted from the CDC reference tables based on each subject's age (in months) and sex. These parameters were used to compute BMI Z-scores, which were subsequently converted to percentiles using the standard normal distribution function. |
| Change From Baseline in Body Mass Index at Week 26 and Week 52 | Baseline (Week 0), Week 26, Week 52 | This outcome measure reports change from baseline to week 52 in BMI measured in terms of Kilograms per meter square (kg/m\^2). |
| Percent Change From Baseline in Body Mass Index at Week 26 and Week 52 | Baseline (Week 0), Week 26, Week 52 | This outcome measure reports percent change from baseline to week 26 and week 52 in BMI measured in terms of percent change. |
| Change From Baseline (Week 0) in Body Mass Index Percentage of the 95th Percentile to Week 26 and to Week 52 | Baseline (Week 0), Week 26, Week 52 | This outcome measure reports change from baseline (week 0) in BMI percentage of the 95th percentile in terms of percentage point to week 26 and week 52. BMI Percentage of the 95th Percentile was calculated using the CDC 2000 Reference Growth Charts and was calculated as the ratio of the subject's observed BMI to the CDC age-and-sex-specific 95th percentile BMI reference value, expressed as a percentage. |
| Change From Baseline in Systolic Blood Pressure and Diastolic Blood Pressure at Week 26 and Week 52 | Baseline (Week 0), Week 26, Week 52 | This outcome measure reports change from baseline in systolic and diastolic blood pressure at week 26 and week 52. |
| Percentage of Participants With HbA1c Less Than (<) 7.0% (53 mmol/Mol) at Week 26 and Week 52 (Yes/No/Missing) | At Week 26 and Week 52 | This outcome measure reports percentage of participants with HbA1c \<7.0% at week 26 and week 52 in terms of Yes, No, and Missing. |
| Percentage of Participants With HbA1c Less Than or Equals (≤) 6.5% (48 mmol/Mol) at Week 26 and Week 52 (Yes/No/Missing) | At Week 26 and Week 52 | This outcome measure reports percentage of participants with HbA1c \<6.5% (48 mmol/mol) at week 26 and week 52 in terms of Yes, No, and Missing. |
| Number of Events With Initiation of Additional Anti-diabetic Medication | At Week 52 | This outcome measure reports number of events with initiation of additional anti-diabetic medication . Anti-diabetic medication was defined as new anti-diabetic medication and/or intensification of anti-diabetic medication initiated at or after randomization and before (planned) end-of-treatment. |
| Number of Events With Initiation of Rescue Medication | At Week 52 | This outcome measure reports number of events with initiation of rescue medication. Rescue medication is defined as new anti-diabetic medication and/or intensification of antidiabetic medication initiated at or after randomization and before last date on trial product. This is a subset of the additional anti-diabetic medication. |
| Number of Treatment-emergent Adverse Events (TEAEs) During Exposure to Trial Product for All Participants | From Baseline (Week 0) to Week 57 | This outcome measure reports number of TEAEs during exposure to trial product for all participants in each arm were assessed up to approximately 57 weeks. Adverse event (AE) is an unfavorable change in the health of a participant, including abnormal laboratory findings, that happens during a clinical study or within a certain amount of time after the study has ended. TEAE is defined as an AE with onset in the on-treatment observation period. |
| Anti-semaglutide Antibodies With in Vitro Neutralising Effect to Semaglutide | From Week 0 to Week 57 | This outcome measure as to report anti-semaglutide antibodies with in vitro neutralising effect to semaglutide from week 0 to week 57. The positive anti-semaglutide antibody samples was planned to be further characterised for titer and cross reactivity to native GLP-1 and for in vitro neutralising effect towards semaglutide. The samples which were positive for cross-reactivity against native GLP-1 was planned to be further analysed for in vitro neutralising effect towards native GLP-1. However, the positive titer at any time was zero. Hence, anti-semaglutide antibodies assessment could not be performed in this study. |
| Number of Treatment-emergent Severe or Blood Glucose Confirmed Symptomatic Hypoglycaemic Episodes From Randomization to Week 26 for All Participants | From Baseline (Week 0) to Week 26 | This outcome measure reports number of treatment-emergent severe or blood glucose confirmed symptomatic hypoglycaemic episodes from randomization to week 26. Data reflects the total number of episodes across all participants in each arm. Treatment-emergent hypoglycaemic episodes is defined as treatment-emergent, if the onset of the episode occurs in the on-treatment period. Severe hypoglycaemia according to the International Society for Paediatric and Adolescent Diabetes (ISPAD) classification included response to the following question as yes or no; Question- was the hypoglycaemic episode associated with severe neuroglycopenia, usually resulting in coma or seizure and requiring parenteral therapy (glucagon or intravenous glucose)? |
| Number of Treatment-emergent Severe or Blood Glucose Confirmed Symptomatic Hypoglycaemic Episodes, Assessed for 57 Weeks | From Baseline (Week 0) to Week 57 | This outcome measure represented number of treatment-emergent severe or blood glucose confirmed symptomatic hypoglycaemic episodes during exposure to trial product, assessed up to approximately 57 weeks. Data reflects the total number of episodes across all participants in each Arm. Treatment-emergent hypoglycaemic episodes is defined as treatment-emergent, if the onset of the episode occurs in the on-treatment period. Severe hypoglycaemia according to ISPAD classification included response to the following question as yes or no; Question- was the hypoglycaemic episode associated with severe neuroglycopenia, usually resulting in coma or seizure and requiring parenteral therapy (glucagon or intravenous glucose). |
| Number of Participants With Treatment-emergent Severe or Blood Glucose Confirmed Symptomatic Hypoglycaemia Episode From Randomization to Week 26 (Yes/No) | From Baseline (Week 0) to Week 26 | This outcome measures report number of participants with treatment-emergent severe or blood glucose confirmed symptomatic hypoglycaemia episode from randomization to week 26. AE is an unfavorable change in the health of a participant, including abnormal laboratory findings, that happens during a clinical study or within a certain amount of time after the study has ended. TEAE is defined as an AE with onset in the on-treatment observation period. Hypoglycaemic episodes was defined as treatment-emergent, if the onset of the episode occurred in the on-treatment period. |
| Number of Participants With Treatment-emergent Severe or Blood Glucose Confirmed Symptomatic Hypoglycaemia Episode During Exposure to Trial Product, Assessed up to Approximately 57 Weeks (Yes/No) | From Baseline (Week 0) to Week 57 | This outcome measure reports number of participants with treatment-emergent severe or blood glucose confirmed symptomatic hypoglycaemia episode during exposure to trial product, assessed up to approximately 57 weeks. Hypoglycaemic episodes was defined as treatment-emergent, if the onset of the episode occurred in the on-treatment period. Treatment-emergent hypoglycaemic episodes is defined as treatment-emergent, if the onset of the episode occurs in the on-treatment period. Severe hypoglycaemia according to the ISPAD classification included response to the following question as yes or no; Question- was the hypoglycaemic episode associated with severe neuroglycopenia, usually resulting in coma or seizure and requiring parenteral therapy (glucagon or intravenous glucose)? |
| Change From Baseline (Week 0) in Amylase to Week 26 and Week 52 | Baseline (Week 0), Week 26, Week 52 | This outcome measure reports change in amylase from baseline (week 0) to week 26 and week 52. |
| Change From Baseline (Week 0) in Lipase to Week 26 and Week 52, Ratio to Baseline | Baseline (Week 0), Week 26, Week 52 | This outcome measure reports change in lipase from baseline (week 0) to week 26 and week 52. |
| Change From Baseline (Week 0) in Insulin-like Growth Factor 1 (IGF-1) to Week 26 and Week 52 | Baseline (Week 0), Week 26, Week 52 | This outcome measure reports change in IGF-1 from baseline (week 0) to week 26 and week 52. |
| Change From Baseline (Week 0) in Insulin-Like Growth Factor Binding Protein 3 (IGFBP 3) Serum to Week 26 and Week 52 | Baseline (Week 0), Week 26, Week 52 | This outcome measure reports change in IGFBP 3 serum from baseline to week 26 and week 52. |
| Change From Baseline (Week 0) in Calcitonin to Week 26 and Week 52 | Baseline (Week 0), Week 26, Week 52 | This outcome measure reports change in calcitonin from baseline to week 26 and week 52. |
| Change From Baseline (Week 0) in Estradiol (for Girls) to Week 26 and Week 52 | Baseline (Week 0), Week 26, Week 52 | This outcome measure reports change in estradiol from baseline to week 26 and week 52. |
| Change From Baseline (Week 0) in Testosterone (for Boys) to Week 26 and Week 52 | Baseline (Week 0), Week 26, Week 52 | This outcome measure reports change in testosterone (for boys) from baseline to week 26 and week 52. |
| Change From Baseline (Week 0) in Prolactin to Week 26 and Week 52 | Baseline (Week 0), Week 26, Week 52 | This outcome measure reports change in prolactin from baseline to week 26 and week 52. |
| Change From Baseline (Week 0) in Thyroid Stimulating Hormone (TSH/Thyrotropin) to Week 26 and Week 52 | Baseline (Week 0), Week 26, Week 52 | This outcome measure reports change in TSH/thyrotropin from baseline to week 26 and week 52. |
| Change From Baseline (Week 0) in Follicle Stimulating Hormone (FSH) to Week 26 and Week 52 | Baseline (Week 0), Week 26, Week 52 | This outcome measure reports change in FSH from baseline to week 26 and week 52. |
| Change From Baseline (Week 0) in Luteinizing Hormone (LH) to Week 26 and Week 52 | Baseline (Week 0), Week 26, Week 52 | This outcome measure reports change in LH from baseline to week 26 and week 52. |
| Change From Baseline (Week 0) in Dehydroepiandrosterone Sulfate (DHEAS) to Week 26 and Week 52 | Baseline (Week 0), Week 26, Week 52 | This outcome measure reports change from baseline to week 26 and week 52 in DHEAS. |
| Anti-semaglutide Antibody Status (Positive/Negative/Missing) | Week 0, week 26, week 52, and week 57 | This outcome measure reports anti-semaglutide antibody status as positive, negative, and missing on week 0, week 26, week 52, and week 57. |
| Anti-semaglutide Antibody Titer | From Week 0 to Week 57 | This outcome measure was to report anti-semaglutide antibody titer. The positive anti-semaglutide antibody samples was planned to be further characterised for titer and cross reactivity to native GLP-1 and for in vitro neutralising effect towards semaglutide. The samples which were positive for cross-reactivity against native GLP-1 was planned to be further analysed for in vitro neutralising effect towards native GLP-1. However, the positive titers at any time was zero. Hence, anti-semaglutide antibodies assessment could not be performed in this study. |
| Anti-semaglutide Antibodies Cross Reacting With Endogenous GLP-1 (Positive/Negative) | From Week 0 to Week 57 | This outcome measure reports anti-semaglutide antibodies cross reacting with endogenous GLP-1 status as positive and negative. The positive anti-semaglutide antibody samples was planned to be further characterised for titer and cross reactivity to native GLP-1 and for in vitro neutralising effect towards semaglutide. The samples which were positive for cross-reactivity against native GLP-1 was planned to be further analysed for in vitro neutralising effect towards native GLP-1. However, the positive titer at any time was zero. Hence, anti-semaglutide antibodies assessment could not be performed in this study. |
| Cross Reacting Antibodies With in Vitro Neutralising Effect to Endogenous GLP-1 | From Week 0 to Week 57 | This outcome measure reports number of participants with cross reacting antibodies with in vitro neutralising effect to endogenous GLP-1 from week 0 to week 57. The positive anti-semaglutide antibody samples was planned to be further characterised for titer and cross reactivity to native GLP-1 and for in vitro neutralising effect towards semaglutide. The samples which were positive for cross-reactivity against native GLP-1 was planned to be further analysed for in vitro neutralising effect towards native GLP-1. However, the positive titer at any time was zero. Hence, anti-semaglutide antibodies assessment could not be performed in this study. Hence, anti-semaglutide antibodies assessment could not be performed in this study. |
| Height Velocity at Week 26 and Week 52 | At week 26 and week 52 | This outcome measure reports height velocity at week 26 and week 52. The height velocity was calculated at week 26 and week 52. Height velocity at week 26 is the difference in height at week 26 and baseline, divided by the actual time elapsed in that period. Height velocity at week 52 is the difference in height at week 26, divided by the actual time elapsed in that period. |
| Change From Baseline (Week 0) in Height SDS to Week 26 and Week 52 | Baseline (Week 0), Week 26, Week 52 | This outcome measure reports change from baseline in height SDS to week 26 and week 52. Height SDS described individual's height compares to the average height of a reference population of the same age and sex, where a score of 0 represents the population mean, negative values indicate shorter-than-average height, and positive values indicate taller-than-average height. Height SDS was calculated based on the WHO 2007 growth reference for children and adolescents. The Height SDS formula comes from the LMS method: Z = (\[Height SDS/M)\]\^L-1)/ L×S where: L=Skewness (Box-Cox power), M=Median, S= (Coefficient of Variation). |
| Change From Baseline (Week 0) in Bone Age Assessment Through X-ray at Week 52 | Baseline (Week 0), Week 52 | This outcome measure reports change from baseline (week 0) in bone age at week 52 where the assessment was done using X-ray. An X-ray of the left hand and wrist were performed at randomization and at the end of treatment visit for all participants for evaluation of bone age. The X-rays was analyzed by a central reader for determination of bone age. |
| Change From Baseline (Week 0) in Number of Participants With Pubertal Assessment (Tanner Staging) (Stage 1-5 Where 5 is Full Sexual Maturity) to Week 52 | Baseline (Week 0), Week 52 | This outcome measure reports change from baseline (week 0) in number of participants with pubertal assessment which was assessed by the Tanner staging in accordance with the stages I-V (stage 1-5 where 5 is full sexual maturity) to week 52. Tanner stage is an overall stage which is the highest stage for girls: Breast development and Pubic hair development; and for boys: genital development and pubic hair development. |
| Change From Pre-dose to Post-dose (25 and 40 Minutes) in Lactate at Week 12 and Week 26 | Pre-dose: Baseline (Week 0), Post-dose (25 mins and 40 mins): Week 12 and Week 26 | This outcome measure reports change from pre-dose to post-dose (25 and 40 minutes) in Lactate at week 12 and week 26. |
| Change From Baseline (Week 0) in Pulse Rate to Week 26 and Week 52 | Baseline (Week 0), Week 26, and Week 52 | This outcome measure reports change from baseline (week 0) in pulse rate to week 26 and week 52. |
| Pharmacokinetic (PK): Apparent Clearance (CL/F) | Week 26: Pre-dose (0 minute before glucose administration), Post dose- 25 and 40 minutes | This pharmacokinetic outcome reports CL/F at Week 26: Pre-dose (0 minute before glucose administration) and post dose at 25 and 40 minutes. |
| PK: Average Concentration (Cavg) | Week 26: Pre-dose (0 minute before glucose administration), Post dose- 25 and 40 minutes | This pharmacokinetic outcome reports Cavg at Week 26. |
| PK: Sodium N-[8-(2-hydroxybenzoyl) Amino] Caprylate (SNAC) Plasma Concentrations | Week 12 and Week 26: Pre-dose (0 minute before glucose administration), Post dose- 25 and 40 minutes | This outcome measure reports SNAC plasma concentration at week 12 and week 26. |
Countries
Australia, Austria, Belgium, Czechia, Greece, India, Israel, Lebanon, Malaysia, Mexico, Morocco, Netherlands, New Zealand, North Macedonia, Portugal, Puerto Rico, Romania, Russia, Taiwan, Ukraine, United Kingdom, United States
Contacts
STUDY_DIRECTORClinical Reporting Anchor and Disclosure (1452)
Novo Nordisk A/S
Participant flow
Recruitment details
Trial participants were randomized to treatment at 45 sites in 19 countries.
Pre-assignment details
A total of 132 eligible participants were randomized (1:1) to treatment with oral semaglutide or placebo. The study included a treatment period (up to 52 weeks) and a follow-up period (12 weeks).
Baseline characteristics
| Characteristic | — |
|---|---|
| Age, Continuous | 14.4 Years STANDARD_DEVIATION 2 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 12 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 54 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race/Ethnicity, Customized RACE Asian | 23 Participants |
| Race/Ethnicity, Customized RACE Black or African American | 18 Participants |
| Race/Ethnicity, Customized RACE Native Hawaiian or Other Pacific Islander | 1 Participants |
| Race/Ethnicity, Customized RACE Other- Unspecified | 22 Participants |
| Race/Ethnicity, Customized RACE White | 50 Participants |
| Sex: Female, Male Female | 82 Participants |
| Sex: Female, Male Male | 25 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 66 | 0 / 66 |
| other Total, other adverse events | 45 / 66 | 40 / 66 |
| serious Total, serious adverse events | 5 / 66 | 2 / 66 |
Outcome results
None listed