Trial Outcomes & Findings for A Research Study to Compare a New Medicine Oral Semaglutide to a Dummy Medicine in Children and Teenagers With Type 2 Diabetes (NCT NCT04596631)

Trial participants were randomized to treatment at 45 sites in 19 countries.

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).

A Research Study to Compare a New Medicine Oral Semaglutide to a Dummy Medicine in Children and Teenagers With Type 2 Diabetes

This outcome measure reports change from baseline to week 26 in HbA1c measured in terms of percentage point.

This outcome measure reports change from baseline to week 26 in HbA1c in terms of mmol/mol.

This outcome measure reports change from baseline in FPG to week 26 measured in terms of milligrams per deciliter (mg/dL).

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).

This outcome measure reports change from baseline to week 52 in HbA1c measured in terms of percentage point.

This outcome measure reports change from baseline to week 52 in HbA1c measured in terms of mmol/mol.

This outcome measure reports change from baseline to week 52 in FPG measured in terms of mg/dL.

This outcome measure reports change from baseline to week 26 and week 52 in body weight measured in terms of kg.

This outcome measure reports relative change from baseline to week 26 and week 52 in body weight measured in terms of percent change.

This outcome measure reports change from baseline to week 26 and week 52 in Waist circumference measured in terms of centimeters (cm).

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)

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.

This outcome measure reports change from baseline to week 52 in BMI measured in terms of Kilograms per meter square (kg/m\^2).

This outcome measure reports percent change from baseline to week 26 and week 52 in BMI measured in terms of percent change.

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.

This outcome measure reports change from baseline in systolic and diastolic blood pressure 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.

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.

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.

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.

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.

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)?

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).

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.

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)?

This outcome measure reports change in amylase from baseline (week 0) to week 26 and week 52.

This outcome measure reports change in lipase from baseline (week 0) to week 26 and week 52.

This outcome measure reports change in IGF-1 from baseline (week 0) to week 26 and week 52.

This outcome measure reports change in IGFBP 3 serum from baseline to week 26 and week 52.

This outcome measure reports change in calcitonin from baseline to week 26 and week 52.

This outcome measure reports change in estradiol from baseline to week 26 and week 52.

This outcome measure reports change in testosterone (for boys) from baseline to week 26 and week 52.

This outcome measure reports change in prolactin from baseline to week 26 and week 52.

This outcome measure reports change in TSH/thyrotropin from baseline to week 26 and week 52.

This outcome measure reports change in FSH from baseline to week 26 and week 52.

This outcome measure reports change in LH from baseline to week 26 and week 52.

This outcome measure reports change from baseline to week 26 and week 52 in DHEAS.

This outcome measure reports anti-semaglutide antibody status as positive, negative, and missing on week 0, week 26, week 52, and 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.

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.

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.

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.

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.

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).

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.

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.

This outcome measure reports change from pre-dose to post-dose (25 and 40 minutes) in Lactate at week 12 and week 26.

This outcome measure reports change from baseline (week 0) in pulse rate to week 26 and week 52.

This pharmacokinetic outcome reports CL/F at Week 26: Pre-dose (0 minute before glucose administration) and post dose at 25 and 40 minutes.

This pharmacokinetic outcome reports Cavg at Week 26.

This outcome measure reports SNAC plasma concentration at week 12 and week 26.