Confirmed Genetic Diagnosis of Prader-Willi Syndrome
Conditions
Brief summary
Two-centre, double-blind, placebo-controlled, randomized, and multiple-dose clinical study followed by two open label extension periods.
Detailed description
Two-centre, double-blind, placebo-controlled, randomized, and multiple-dose clinical study. Study medication will be administered for 91 days. The study will be conducted in two steps: * Step 1 - 9 adult subjects with PWS was treated. * Sponsor review - following the completion of the treatment of the adult subjects, unblinded efficacy, safety, Pharmacokinetic (PK) data as well as all data from the study in subjects with type 2 diabetes (TM001) will be reviewed by sponsor and an interim analysis will be done. Following competent authority positive opinion regarding the interim analysis and unblinded data the study will proceed to: * Step 2 - 9 adolescent subjects with PWS was treated. * OLE (Open Label Extension) I - Participation in a 12-week OLE I was offered to subjects who completed Step 2. 8 subjects entered OLE I. * OLE (Open Label Extension) II - Participation in a 12-week OLE II was offered to subjects who completed OLE I. 6 subjects continued to OLE II.
Interventions
Study medication will be administered for 91 days.
DRUGPlacebos
Study medication will be administered for 91 days.
Sponsors
Saniona
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Masking description
double-blind
Intervention model description
Two-centre, double-blind, placebo-controlled, randomized, and multiple-dose clinical study.
Eligibility
Sex/Gender
ALL
Age
12 Years to 30 Years
Healthy volunteers
No
Inclusion criteria
1. Males and females with a confirmed genetic diagnosis of Prader-Willi syndrome 2. Age: 1. Step 1: Adults aged 18-30 2. Step 2: Adolescents aged 12-17 3. Body Mass Index (BMI): 1. Step 1: Adults with ≥25 kg/m2 2. Step 2: Children with a BMI \>85th percentile for the same age and sex 4. Normal Blood Pressure (BP) or well managed hypertension (only if dose of BP medication(s) has been stable for \>2 months) 5. Normal lipid profile or well managed dyslipidemia (only if dose of lipid-lowering medication(s) has been stable for \>2 months) 6. Growth hormone is allowed; but patient must be on stable dose of growth hormone \>2 months 7. Type 2 diabetes is allowed, but the following criteria must be met: 1. HbA1c \<10.0 % not being managed with insulin within the past 3 months 2. Patients taking GLP-1 analogues (e.g. exenatide, liraglutide) must have been on stable dose for \>3 months 3. Fasting plasma glucose \<11.0 mmol/l
Exclusion criteria
1. BP: 1. Step 1: Adults with \>140/90 2. Step 2: Adolescents with ≥95th percentile for gender, age, and height 2. Heart Rate (HR) ≥ 90, \<50 bpm 3. Hypersensitivity to tesofensine/metoprolol 4. Type 1 diabetes 5. Heart failure New York Heart Association (NYHA) level II or greater, decompensated heart failure 6. Previous myocardial infarction or stroke 7. Diagnosis of schizophrenia, bipolar disorder, personality disorder or other DSM-III disorders, or any other psychiatric condition, which in the investigator's opinion will interfere significantly with study compliance 8. History of major depressive disorder or suicidality 9. Any clinically significant cardiac arrhythmia 10. Treatment with calcium channel blockers and beta blockers 11. Concomitant use of monoaminooxidase inhibitors 12. Bulimia or anorexia nervosa 13. Any agent used for weight loss in the past 3 months 14. Untreated hypo- or hyperthyroidism 15. Clinically significant liver (\>3x ULN (Upper Limit of Normal range)) and/or kidney impairment 16. More than 5% weight loss within the last 3 months 17. Any other clinically meaningful condition, in the opinion of the investigator, which would make participation potentially unsafe 18. Contraindications to administration of metoprolol per current Summary of Product Characteristics
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percent Change From Baseline to End of Treatment in Mean Body Weight | DB Step 1: Day 1 to Day 91; DB Step 2: Day 1 to Day 91; OLE I: Day 91 to Day 181; OLE II: Day 181 to Day 271 | Percent change from baseline to end of treatment in mean body weight. LOCF. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline to End of Treatment in Hyperphagia Questionnaire for Clinical Trials (HQ-CT) Score | DB Step 1: Day 1 to Day 91; DB Step 2: Day 1 to Day 91; OLE I: Day 91 to Day 181; OLE II: Day 181 to Day 271 | Change from baseline to end of treatment in HQ-CT score. LOCF. HQ-CT score was based upon a questionnaire with 9 items, each of them yielding a score between 0 and 4 resulting in a maximum HQ-CT score of 36. Change in HQ-CT answers (by question and in total) calculated as score at visit 2, 5, 9 or 14 minus score at screening visit 1 was analysed and presented using standard descriptive statistics (mean, median, standard deviation, minimum and maximum value). A decrease in total score indicates an improvement in hyperphagia. If less than three questions were answered by a subject, the missing answers were imputed by the mean score of all other available answers. In case of more than three missing answers, the total score was not calculated. For further information please refer to protocol appendix section 17.1. |
| Steady State Concentrations of Tesofensine and Metoprolol as Measured by Trough Values | DB Step 1: Day 29; DB Step 2: Day 29; OLE I: Day 120; OLE II: Day 210 | Steady state concentrations of tesofensine and metoprolol as measured by trough values. Observed values. |
| Change From Baseline to End of Treatment in Fat- and Fat Free Mass (%) by Dual X-ray Absorptiometry (DEXA) | DB Step 1: Day 1 to Day 91; DB Step 2: Day 1 to Day 91; OLE I: Day 91 to Day 181; OLE II: Day 181 to Day 271 | Change from baseline to end of treatment in fat- and fat free mass (%) by dual X-ray absorptiometry (DEXA). Observed values. |
| Change From Baseline to End of Treatment in Bone Mineral Density (BMD) by Dual X-ray Absorptiometry (DEXA) | DB Step 1: Day 1 to Day 91; DB Step 2: Day 1 to Day 91; OLE I: Day 91 to Day 181; OLE II: Day 181 to Day 271 | Change from baseline to end of treatment in BMD by dual X-ray absorptiometry (DEXA). Observed values. |
| Change From Baseline to End of Treatment in Bone Mineral Content (BMC) by Dual X-ray Absorptiometry (DEXA) | DB Step 1: Day 1 to Day 91; DB Step 2: Day 1 to Day 91; OLE I: Day 91 to Day 181; OLE II: Day 181 to Day 271 | Change from baseline to end of treatment in BMC by dual X-ray absorptiometry (DEXA). Observed values. |
| Change From Baseline to End of Treatment in Heart Rate (HR) | DB Step 1: Day 1 to Day 91; DB Step 2: Day 1 to Day 91; OLE I: Day 91 to Day 181; OLE II: Day 181 to Day 271 | Change from baseline to end of treatment in HR (bpm). LOCF. |
| Change From Baseline to End of Treatment in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | DB Step 1: Day 1 to Day 91; DB Step 2: Day 1 to Day 91; OLE I: Day 91 to Day 181; OLE II: Day 181 to Day 271 | Change from baseline to end of treatment in SBP (mmHg) and DBP (mmHg). LOCF. |
| Change From Baseline to End of Treatment in Mean Body Weight | DB Step 1: Day 1 to Day 91; DB Step 2: Day 1 to Day 91; OLE I: Day 91 to Day 181; OLE II: Day 181 to Day 271 | Change from baseline to end of treatment in body weight \[kg\]. LOCF. |
| Change From Baseline to End of Treatment in PR Interval | DB Step 1: Day 1 to Day 91; DB Step 2: Day 1 to Day 91; OLE I: Day 91 to Day 181; OLE II: Day 181 to Day 271 | Change from baseline to end of treatment in PR interval. Observed values. |
| Change From Baseline to End of Treatment in Electrocardiogram (ECG) Parameters | DB Step 1: Day 1 to Day 91; DB Step 2: Day 1 to Day 91; OLE I: Day 91 to Day 181; OLE II: Day 181 to Day 271 | Change from baseline to end of treatment in ECG parameters - QRS duration, QT interval, QTcF and QTcB |
| Change From Baseline to End of Treatment in HbA1c | DB Step 1: Day 1 to Day 91; DB Step 2: Day 1 to Day 91; OLE I: Day 91 to Day 181; OLE II: Day 181 to Day 271 | Change from baseline to end of treatment in HbA1c (%). LOCF. |
| Change From Baseline to End of Treatment in Insulin | DB Step 1: Day 1 to Day 91; DB Step 2: Day 1 to Day 91; OLE I: Day 91 to Day 181; OLE II: Day 181 to Day 271 | Change from baseline to end of treatment in insulin (mIU/L). LOCF. |
| Change From Baseline to End of Treatment in Fasting pl. Glucose, Triglycerides, Low-density Lipoprotein (LDL) and High-density Lipoprotein (HDL) Cholesterol | DB Step 1: Day 1 to Day 91; DB Step 2: Day 1 to Day 91; OLE I: Day 91 to Day 181; OLE II: Day 181 to Day 271 | Change from baseline to end of treatment in fasting pl. glucose (mmol/L), triglycerides (mmol/L), LDL and HDL cholesterol (mmol/L). LOCF. |
| Number of Subjects With Adverse Events (AE) and Serious Adverse Events (SAE) | DB Step 1: Day 1 to Day 91; DB Step 2: Day 1 to Day 91; OLE I: Day 91 to Day 181; OLE II: Day 181 to Day 271 | Number of subjects with Adverse Events and Serious Adverse Events |
| Total Number of Adverse Events | DB Step 1: Day 1 to Day 91; DB Step 2: Day 1 to Day 91; OLE I: Day 91 to Day 181; OLE II: Day 181 to Day 271 | Total number of Adverse Events |
Countries
Czechia, Hungary
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Tesomet 0.50/50 mg Subjects (adults) were randomized to receive co-administration of 0.5 mg tesofensine/50 mg metoprolol (active medication Tesomet) once daily for 91 days (+2 days after the final assessments with halfdose of metoprolol) during Step 1. | 6 |
| Placebo (Adult) Subjects (adults) were randomized to receive placebo once daily for 91 days during Step 1. | 3 |
| Tesomet 0.125/25 mg (DB) Subjects (adolescents) were randomized to receive co-administration of 0.125 mg tesofensine/25 mg metoprolol (active medication Tesomet) once daily for 91 days: +2days after the final assessments with halfdose. | 5 |
| Placebo (Adolescent) Subjects (adolescents) were randomized to receive placebo once daily for 91 days. | 4 |
| Total | 18 |
Baseline characteristics
| Characteristic | Tesomet 0.50/50 mg | Placebo (Adult) | Tesomet 0.125/25 mg (DB) | Placebo (Adolescent) | Total |
|---|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 5 Participants | 4 Participants | 9 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 6 Participants | 3 Participants | 0 Participants | 0 Participants | 9 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 6 Participants | 3 Participants | 5 Participants | 4 Participants | 18 Participants |
| Region of Enrollment Czechia | 3 participants | 1 participants | 2 participants | 2 participants | 8 participants |
| Region of Enrollment Hungary | 3 participants | 2 participants | 3 participants | 2 participants | 10 participants |
| Sex: Female, Male Female | 4 Participants | 2 Participants | 2 Participants | 2 Participants | 10 Participants |
| Sex: Female, Male Male | 2 Participants | 1 Participants | 3 Participants | 2 Participants | 8 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk | EG006 affected / at risk | EG007 affected / at risk |
|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 6 | 0 / 3 | 0 / 5 | 0 / 4 | 0 / 4 | 0 / 4 | 0 / 5 | 0 / 1 |
| other Total, other adverse events | 6 / 6 | 3 / 3 | 5 / 5 | 3 / 4 | 4 / 4 | 4 / 4 | 5 / 5 | 1 / 1 |
| serious Total, serious adverse events | 3 / 6 | 0 / 3 | 0 / 5 | 0 / 4 | 0 / 4 | 0 / 4 | 2 / 5 | 0 / 1 |
Outcome results
Primary
Percent Change From Baseline to End of Treatment in Mean Body Weight
Percent change from baseline to end of treatment in mean body weight. LOCF.
Time frame: DB Step 1: Day 1 to Day 91; DB Step 2: Day 1 to Day 91; OLE I: Day 91 to Day 181; OLE II: Day 181 to Day 271
Population: 5 patients started on Tesomet 0.25/25mg in OLE II however 1 subject discontinued early without any further observations and data are therefore only available from 4 subjects.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Tesomet 0.50/50 mg | Percent Change From Baseline to End of Treatment in Mean Body Weight | -4.09 Percent (%) change in mean body weight | Standard Deviation 3.73 |
| Placebo (Adult) | Percent Change From Baseline to End of Treatment in Mean Body Weight | -0.38 Percent (%) change in mean body weight | Standard Deviation 2.05 |
| Tesomet 0.125/25 mg (DB) | Percent Change From Baseline to End of Treatment in Mean Body Weight | 3.56 Percent (%) change in mean body weight | Standard Deviation 2.73 |
| Placebo (Adolescent) | Percent Change From Baseline to End of Treatment in Mean Body Weight | 3.00 Percent (%) change in mean body weight | Standard Deviation 2.35 |
| Tesomet 0.125/25 mg -> Tesomet 0.125/25 mg | Percent Change From Baseline to End of Treatment in Mean Body Weight | 5.79 Percent (%) change in mean body weight | Standard Deviation 2.08 |
| Placebo -> Tesomet 0.125/25 mg | Percent Change From Baseline to End of Treatment in Mean Body Weight | 0.33 Percent (%) change in mean body weight | Standard Deviation 3.26 |
| Tesomet 0.25/25 mg | Percent Change From Baseline to End of Treatment in Mean Body Weight | -1.20 Percent (%) change in mean body weight | Standard Deviation 3.8 |
| Tesomet 0.125/25 mg (OLE II) | Percent Change From Baseline to End of Treatment in Mean Body Weight | -5.51 Percent (%) change in mean body weight | — |
p-value: 0.104595% CI: [-12.3, 1.5]ANCOVA
p-value: 0.742295% CI: [-4, 5.3]ANCOVA
p-value: 0.04695% CI: [0.1, 11]ANCOVA
p-value: 0.384795% CI: [-9.2, 17.8]ANCOVA
Secondary
Change From Baseline to End of Treatment in Bone Mineral Content (BMC) by Dual X-ray Absorptiometry (DEXA)
Change from baseline to end of treatment in BMC by dual X-ray absorptiometry (DEXA). Observed values.
Time frame: DB Step 1: Day 1 to Day 91; DB Step 2: Day 1 to Day 91; OLE I: Day 91 to Day 181; OLE II: Day 181 to Day 271
Population: Data only available for 3 patients in Step I (Tesomet 0.50/50 mg). Data not available for the Placebo (adult) arm. Data only available for 3 patients in Step 2 (Tesomet 0.125/25 mg (DB)). Data only available for 2 patients in Step 2 (Placebo (adolescent)). Data only available for 3 patients in OLE I (Tesomet 0.125/25 mg -\> Tesomet 0.125/25 mg).~Data only available for 2 patients in OLE I (Placebo -\> Tesomet 0.125/25 mg). Data only available for 2 patients in OLE II (Tesomet 0.25/25 mg).
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Tesomet 0.50/50 mg | Change From Baseline to End of Treatment in Bone Mineral Content (BMC) by Dual X-ray Absorptiometry (DEXA) | 9.5 gram | Standard Deviation 63.8 |
| Tesomet 0.125/25 mg (DB) | Change From Baseline to End of Treatment in Bone Mineral Content (BMC) by Dual X-ray Absorptiometry (DEXA) | 74.77 gram | Standard Deviation 22.46 |
| Placebo (Adolescent) | Change From Baseline to End of Treatment in Bone Mineral Content (BMC) by Dual X-ray Absorptiometry (DEXA) | 35.53 gram | Standard Deviation 55.37 |
| Tesomet 0.125/25 mg -> Tesomet 0.125/25 mg | Change From Baseline to End of Treatment in Bone Mineral Content (BMC) by Dual X-ray Absorptiometry (DEXA) | -1.12 gram | Standard Deviation 17.86 |
| Placebo -> Tesomet 0.125/25 mg | Change From Baseline to End of Treatment in Bone Mineral Content (BMC) by Dual X-ray Absorptiometry (DEXA) | 5.69 gram | Standard Deviation 66.33 |
| Tesomet 0.25/25 mg | Change From Baseline to End of Treatment in Bone Mineral Content (BMC) by Dual X-ray Absorptiometry (DEXA) | 22.51 gram | Standard Deviation 46.6 |
| Tesomet 0.125/25 mg (OLE II) | Change From Baseline to End of Treatment in Bone Mineral Content (BMC) by Dual X-ray Absorptiometry (DEXA) | -21.90 gram | — |
Secondary
Change From Baseline to End of Treatment in Bone Mineral Density (BMD) by Dual X-ray Absorptiometry (DEXA)
Change from baseline to end of treatment in BMD by dual X-ray absorptiometry (DEXA). Observed values.
Time frame: DB Step 1: Day 1 to Day 91; DB Step 2: Day 1 to Day 91; OLE I: Day 91 to Day 181; OLE II: Day 181 to Day 271
Population: Data only available for 3 patients in Step I (Tesomet 0.50/50 mg). Data not available for the Placebo (adult) arm. Data only available for 3 patients in Step 2 (Tesomet 0.125/25 mg (DB)). Data only available for 2 patients in Step 2 (Placebo (adolescent)). Data only available for 3 patients in OLE I (Tesomet 0.125/25 mg -\> Tesomet 0.125/25 mg).~Data only available for 2 patients in OLE I (Placebo -\> Tesomet 0.125/25 mg). Data only available for 2 patients in OLE II (Tesomet 0.25/25 mg).
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Tesomet 0.50/50 mg | Change From Baseline to End of Treatment in Bone Mineral Density (BMD) by Dual X-ray Absorptiometry (DEXA) | 0.002 g/cm^2 | Standard Deviation 0.0017 |
| Tesomet 0.125/25 mg (DB) | Change From Baseline to End of Treatment in Bone Mineral Density (BMD) by Dual X-ray Absorptiometry (DEXA) | 0.019 g/cm^2 | Standard Deviation 0.009 |
| Placebo (Adolescent) | Change From Baseline to End of Treatment in Bone Mineral Density (BMD) by Dual X-ray Absorptiometry (DEXA) | 0.035 g/cm^2 | Standard Deviation 0.008 |
| Tesomet 0.125/25 mg -> Tesomet 0.125/25 mg | Change From Baseline to End of Treatment in Bone Mineral Density (BMD) by Dual X-ray Absorptiometry (DEXA) | -0.006 g/cm^2 | Standard Deviation 0.008 |
| Placebo -> Tesomet 0.125/25 mg | Change From Baseline to End of Treatment in Bone Mineral Density (BMD) by Dual X-ray Absorptiometry (DEXA) | -0.007 g/cm^2 | Standard Deviation 0.009 |
| Tesomet 0.25/25 mg | Change From Baseline to End of Treatment in Bone Mineral Density (BMD) by Dual X-ray Absorptiometry (DEXA) | 0.023 g/cm^2 | Standard Deviation 0 |
| Tesomet 0.125/25 mg (OLE II) | Change From Baseline to End of Treatment in Bone Mineral Density (BMD) by Dual X-ray Absorptiometry (DEXA) | 0.009 g/cm^2 | — |
Secondary
Change From Baseline to End of Treatment in Electrocardiogram (ECG) Parameters
Change from baseline to end of treatment in ECG parameters - QRS duration, QT interval, QTcF and QTcB
Time frame: DB Step 1: Day 1 to Day 91; DB Step 2: Day 1 to Day 91; OLE I: Day 91 to Day 181; OLE II: Day 181 to Day 271
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Tesomet 0.50/50 mg | Change From Baseline to End of Treatment in Electrocardiogram (ECG) Parameters | QRS duration | -4.0 ms | Standard Deviation 8.5 |
| Tesomet 0.50/50 mg | Change From Baseline to End of Treatment in Electrocardiogram (ECG) Parameters | QTcB | -16.0 ms | Standard Deviation 2.8 |
| Tesomet 0.50/50 mg | Change From Baseline to End of Treatment in Electrocardiogram (ECG) Parameters | QTcF | -12.9 ms | Standard Deviation 4.4 |
| Tesomet 0.50/50 mg | Change From Baseline to End of Treatment in Electrocardiogram (ECG) Parameters | QT interval | -7.0 ms | Standard Deviation 18.4 |
| Placebo (Adult) | Change From Baseline to End of Treatment in Electrocardiogram (ECG) Parameters | QT interval | 19.0 ms | Standard Deviation 9.9 |
| Placebo (Adult) | Change From Baseline to End of Treatment in Electrocardiogram (ECG) Parameters | QRS duration | 4.0 ms | Standard Deviation 0 |
| Placebo (Adult) | Change From Baseline to End of Treatment in Electrocardiogram (ECG) Parameters | QTcF | 12.8 ms | Standard Deviation 19.8 |
| Placebo (Adult) | Change From Baseline to End of Treatment in Electrocardiogram (ECG) Parameters | QTcB | 9.0 ms | Standard Deviation 25.5 |
| Tesomet 0.125/25 mg (DB) | Change From Baseline to End of Treatment in Electrocardiogram (ECG) Parameters | QTcF | 0.1 ms | Standard Deviation 24.4 |
| Tesomet 0.125/25 mg (DB) | Change From Baseline to End of Treatment in Electrocardiogram (ECG) Parameters | QRS duration | 2.0 ms | Standard Deviation 2.3 |
| Tesomet 0.125/25 mg (DB) | Change From Baseline to End of Treatment in Electrocardiogram (ECG) Parameters | QTcB | 3.5 ms | Standard Deviation 31.8 |
| Tesomet 0.125/25 mg (DB) | Change From Baseline to End of Treatment in Electrocardiogram (ECG) Parameters | QT interval | -5.5 ms | Standard Deviation 27.2 |
| Placebo (Adolescent) | Change From Baseline to End of Treatment in Electrocardiogram (ECG) Parameters | QT interval | 5.5 ms | Standard Deviation 27.2 |
| Placebo (Adolescent) | Change From Baseline to End of Treatment in Electrocardiogram (ECG) Parameters | QTcF | 11.0 ms | Standard Deviation 20.4 |
| Placebo (Adolescent) | Change From Baseline to End of Treatment in Electrocardiogram (ECG) Parameters | QTcB | 13.9 ms | Standard Deviation 21.4 |
| Placebo (Adolescent) | Change From Baseline to End of Treatment in Electrocardiogram (ECG) Parameters | QRS duration | 2.0 ms | Standard Deviation 8.5 |
| Tesomet 0.125/25 mg -> Tesomet 0.125/25 mg | Change From Baseline to End of Treatment in Electrocardiogram (ECG) Parameters | QT interval | -5.0 ms | Standard Deviation 19.2 |
| Tesomet 0.125/25 mg -> Tesomet 0.125/25 mg | Change From Baseline to End of Treatment in Electrocardiogram (ECG) Parameters | QTcB | -2.6 ms | Standard Deviation 22.8 |
| Tesomet 0.125/25 mg -> Tesomet 0.125/25 mg | Change From Baseline to End of Treatment in Electrocardiogram (ECG) Parameters | QRS duration | -1.5 ms | Standard Deviation 3 |
| Tesomet 0.125/25 mg -> Tesomet 0.125/25 mg | Change From Baseline to End of Treatment in Electrocardiogram (ECG) Parameters | QTcF | -3.7 ms | Standard Deviation 14.5 |
| Placebo -> Tesomet 0.125/25 mg | Change From Baseline to End of Treatment in Electrocardiogram (ECG) Parameters | QT interval | -13.3 ms | Standard Deviation 16.2 |
| Placebo -> Tesomet 0.125/25 mg | Change From Baseline to End of Treatment in Electrocardiogram (ECG) Parameters | QRS duration | 0.7 ms | Standard Deviation 5 |
| Placebo -> Tesomet 0.125/25 mg | Change From Baseline to End of Treatment in Electrocardiogram (ECG) Parameters | QTcF | -10.3 ms | Standard Deviation 29.3 |
| Placebo -> Tesomet 0.125/25 mg | Change From Baseline to End of Treatment in Electrocardiogram (ECG) Parameters | QTcB | -8.2 ms | Standard Deviation 37.3 |
| Tesomet 0.25/25 mg | Change From Baseline to End of Treatment in Electrocardiogram (ECG) Parameters | QTcB | 23.0 ms | Standard Deviation 2.9 |
| Tesomet 0.25/25 mg | Change From Baseline to End of Treatment in Electrocardiogram (ECG) Parameters | QRS duration | -4.0 ms | Standard Deviation 5.7 |
| Tesomet 0.25/25 mg | Change From Baseline to End of Treatment in Electrocardiogram (ECG) Parameters | QT interval | 7.0 ms | Standard Deviation 7.1 |
| Tesomet 0.25/25 mg | Change From Baseline to End of Treatment in Electrocardiogram (ECG) Parameters | QTcF | 17.1 ms | Standard Deviation 4.5 |
| Tesomet 0.125/25 mg (OLE II) | Change From Baseline to End of Treatment in Electrocardiogram (ECG) Parameters | QT interval | -20.0 ms | — |
| Tesomet 0.125/25 mg (OLE II) | Change From Baseline to End of Treatment in Electrocardiogram (ECG) Parameters | QTcF | -2.9 ms | — |
| Tesomet 0.125/25 mg (OLE II) | Change From Baseline to End of Treatment in Electrocardiogram (ECG) Parameters | QRS duration | 0.0 ms | — |
| Tesomet 0.125/25 mg (OLE II) | Change From Baseline to End of Treatment in Electrocardiogram (ECG) Parameters | QTcB | 8.2 ms | — |
Secondary
Change From Baseline to End of Treatment in Fasting pl. Glucose, Triglycerides, Low-density Lipoprotein (LDL) and High-density Lipoprotein (HDL) Cholesterol
Change from baseline to end of treatment in fasting pl. glucose (mmol/L), triglycerides (mmol/L), LDL and HDL cholesterol (mmol/L). LOCF.
Time frame: DB Step 1: Day 1 to Day 91; DB Step 2: Day 1 to Day 91; OLE I: Day 91 to Day 181; OLE II: Day 181 to Day 271
Population: Data only available for 2 patients in the Placebo (adult) arm. Data only available for 3 patients in OLE I (Placebo -\> Tesomet 0.125/25 mg). 5 patients started on Tesomet 0.25/25mg in OLE II however 1 subject discontinued early without any further observations and data are therefore only available from 4 subjects.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Tesomet 0.50/50 mg | Change From Baseline to End of Treatment in Fasting pl. Glucose, Triglycerides, Low-density Lipoprotein (LDL) and High-density Lipoprotein (HDL) Cholesterol | Triglycerides | -0.07 mmol/L | Standard Deviation 0.29 |
| Tesomet 0.50/50 mg | Change From Baseline to End of Treatment in Fasting pl. Glucose, Triglycerides, Low-density Lipoprotein (LDL) and High-density Lipoprotein (HDL) Cholesterol | LDL cholesterol | -0.16 mmol/L | Standard Deviation 0.44 |
| Tesomet 0.50/50 mg | Change From Baseline to End of Treatment in Fasting pl. Glucose, Triglycerides, Low-density Lipoprotein (LDL) and High-density Lipoprotein (HDL) Cholesterol | Fasting pl. glucose | 0.27 mmol/L | Standard Deviation 0.59 |
| Tesomet 0.50/50 mg | Change From Baseline to End of Treatment in Fasting pl. Glucose, Triglycerides, Low-density Lipoprotein (LDL) and High-density Lipoprotein (HDL) Cholesterol | HDL cholesterol | -0.10 mmol/L | Standard Deviation 0.2 |
| Placebo (Adult) | Change From Baseline to End of Treatment in Fasting pl. Glucose, Triglycerides, Low-density Lipoprotein (LDL) and High-density Lipoprotein (HDL) Cholesterol | HDL cholesterol | -0.17 mmol/L | Standard Deviation 0.01 |
| Placebo (Adult) | Change From Baseline to End of Treatment in Fasting pl. Glucose, Triglycerides, Low-density Lipoprotein (LDL) and High-density Lipoprotein (HDL) Cholesterol | Fasting pl. glucose | 0.30 mmol/L | Standard Deviation 0.14 |
| Placebo (Adult) | Change From Baseline to End of Treatment in Fasting pl. Glucose, Triglycerides, Low-density Lipoprotein (LDL) and High-density Lipoprotein (HDL) Cholesterol | LDL cholesterol | -0.12 mmol/L | Standard Deviation 0.32 |
| Placebo (Adult) | Change From Baseline to End of Treatment in Fasting pl. Glucose, Triglycerides, Low-density Lipoprotein (LDL) and High-density Lipoprotein (HDL) Cholesterol | Triglycerides | -0.02 mmol/L | Standard Deviation 0.06 |
| Tesomet 0.125/25 mg (DB) | Change From Baseline to End of Treatment in Fasting pl. Glucose, Triglycerides, Low-density Lipoprotein (LDL) and High-density Lipoprotein (HDL) Cholesterol | Triglycerides | 0.56 mmol/L | Standard Deviation 1.32 |
| Tesomet 0.125/25 mg (DB) | Change From Baseline to End of Treatment in Fasting pl. Glucose, Triglycerides, Low-density Lipoprotein (LDL) and High-density Lipoprotein (HDL) Cholesterol | HDL cholesterol | -0.03 mmol/L | Standard Deviation 0.18 |
| Tesomet 0.125/25 mg (DB) | Change From Baseline to End of Treatment in Fasting pl. Glucose, Triglycerides, Low-density Lipoprotein (LDL) and High-density Lipoprotein (HDL) Cholesterol | Fasting pl. glucose | -0.20 mmol/L | Standard Deviation 0.58 |
| Tesomet 0.125/25 mg (DB) | Change From Baseline to End of Treatment in Fasting pl. Glucose, Triglycerides, Low-density Lipoprotein (LDL) and High-density Lipoprotein (HDL) Cholesterol | LDL cholesterol | 0.16 mmol/L | Standard Deviation 0.21 |
| Placebo (Adolescent) | Change From Baseline to End of Treatment in Fasting pl. Glucose, Triglycerides, Low-density Lipoprotein (LDL) and High-density Lipoprotein (HDL) Cholesterol | Triglycerides | -1.33 mmol/L | Standard Deviation 1.54 |
| Placebo (Adolescent) | Change From Baseline to End of Treatment in Fasting pl. Glucose, Triglycerides, Low-density Lipoprotein (LDL) and High-density Lipoprotein (HDL) Cholesterol | Fasting pl. glucose | -0.30 mmol/L | Standard Deviation 0.29 |
| Placebo (Adolescent) | Change From Baseline to End of Treatment in Fasting pl. Glucose, Triglycerides, Low-density Lipoprotein (LDL) and High-density Lipoprotein (HDL) Cholesterol | HDL cholesterol | -0.03 mmol/L | Standard Deviation 0.17 |
| Placebo (Adolescent) | Change From Baseline to End of Treatment in Fasting pl. Glucose, Triglycerides, Low-density Lipoprotein (LDL) and High-density Lipoprotein (HDL) Cholesterol | LDL cholesterol | -0.32 mmol/L | Standard Deviation 0.99 |
| Tesomet 0.125/25 mg -> Tesomet 0.125/25 mg | Change From Baseline to End of Treatment in Fasting pl. Glucose, Triglycerides, Low-density Lipoprotein (LDL) and High-density Lipoprotein (HDL) Cholesterol | Triglycerides | -0.54 mmol/L | Standard Deviation 1.23 |
| Tesomet 0.125/25 mg -> Tesomet 0.125/25 mg | Change From Baseline to End of Treatment in Fasting pl. Glucose, Triglycerides, Low-density Lipoprotein (LDL) and High-density Lipoprotein (HDL) Cholesterol | LDL cholesterol | -0.02 mmol/L | Standard Deviation 0.43 |
| Tesomet 0.125/25 mg -> Tesomet 0.125/25 mg | Change From Baseline to End of Treatment in Fasting pl. Glucose, Triglycerides, Low-density Lipoprotein (LDL) and High-density Lipoprotein (HDL) Cholesterol | HDL cholesterol | 0.16 mmol/L | Standard Deviation 0.22 |
| Tesomet 0.125/25 mg -> Tesomet 0.125/25 mg | Change From Baseline to End of Treatment in Fasting pl. Glucose, Triglycerides, Low-density Lipoprotein (LDL) and High-density Lipoprotein (HDL) Cholesterol | Fasting pl. glucose | 1.07 mmol/L | Standard Deviation 1.19 |
| Placebo -> Tesomet 0.125/25 mg | Change From Baseline to End of Treatment in Fasting pl. Glucose, Triglycerides, Low-density Lipoprotein (LDL) and High-density Lipoprotein (HDL) Cholesterol | HDL cholesterol | 0.22 mmol/L | Standard Deviation 0.11 |
| Placebo -> Tesomet 0.125/25 mg | Change From Baseline to End of Treatment in Fasting pl. Glucose, Triglycerides, Low-density Lipoprotein (LDL) and High-density Lipoprotein (HDL) Cholesterol | LDL cholesterol | -0.01 mmol/L | Standard Deviation 0.43 |
| Placebo -> Tesomet 0.125/25 mg | Change From Baseline to End of Treatment in Fasting pl. Glucose, Triglycerides, Low-density Lipoprotein (LDL) and High-density Lipoprotein (HDL) Cholesterol | Triglycerides | 0.38 mmol/L | Standard Deviation 0.14 |
| Placebo -> Tesomet 0.125/25 mg | Change From Baseline to End of Treatment in Fasting pl. Glucose, Triglycerides, Low-density Lipoprotein (LDL) and High-density Lipoprotein (HDL) Cholesterol | Fasting pl. glucose | 0.37 mmol/L | Standard Deviation 0.31 |
| Tesomet 0.25/25 mg | Change From Baseline to End of Treatment in Fasting pl. Glucose, Triglycerides, Low-density Lipoprotein (LDL) and High-density Lipoprotein (HDL) Cholesterol | Fasting pl. glucose | 0.60 mmol/L | Standard Deviation 0.35 |
| Tesomet 0.25/25 mg | Change From Baseline to End of Treatment in Fasting pl. Glucose, Triglycerides, Low-density Lipoprotein (LDL) and High-density Lipoprotein (HDL) Cholesterol | HDL cholesterol | -0.05 mmol/L | Standard Deviation 0.05 |
| Tesomet 0.25/25 mg | Change From Baseline to End of Treatment in Fasting pl. Glucose, Triglycerides, Low-density Lipoprotein (LDL) and High-density Lipoprotein (HDL) Cholesterol | LDL cholesterol | 0.10 mmol/L | Standard Deviation 0.32 |
| Tesomet 0.25/25 mg | Change From Baseline to End of Treatment in Fasting pl. Glucose, Triglycerides, Low-density Lipoprotein (LDL) and High-density Lipoprotein (HDL) Cholesterol | Triglycerides | -0.13 mmol/L | Standard Deviation 0.26 |
| Tesomet 0.125/25 mg (OLE II) | Change From Baseline to End of Treatment in Fasting pl. Glucose, Triglycerides, Low-density Lipoprotein (LDL) and High-density Lipoprotein (HDL) Cholesterol | HDL cholesterol | -0.14 mmol/L | — |
| Tesomet 0.125/25 mg (OLE II) | Change From Baseline to End of Treatment in Fasting pl. Glucose, Triglycerides, Low-density Lipoprotein (LDL) and High-density Lipoprotein (HDL) Cholesterol | LDL cholesterol | -0.25 mmol/L | — |
| Tesomet 0.125/25 mg (OLE II) | Change From Baseline to End of Treatment in Fasting pl. Glucose, Triglycerides, Low-density Lipoprotein (LDL) and High-density Lipoprotein (HDL) Cholesterol | Fasting pl. glucose | -0.40 mmol/L | — |
| Tesomet 0.125/25 mg (OLE II) | Change From Baseline to End of Treatment in Fasting pl. Glucose, Triglycerides, Low-density Lipoprotein (LDL) and High-density Lipoprotein (HDL) Cholesterol | Triglycerides | 0.13 mmol/L | — |
Secondary
Change From Baseline to End of Treatment in Fat- and Fat Free Mass (%) by Dual X-ray Absorptiometry (DEXA)
Change from baseline to end of treatment in fat- and fat free mass (%) by dual X-ray absorptiometry (DEXA). Observed values.
Time frame: DB Step 1: Day 1 to Day 91; DB Step 2: Day 1 to Day 91; OLE I: Day 91 to Day 181; OLE II: Day 181 to Day 271
Population: Data only available for 3 patients in Step I (Tesomet 0.50/50 mg). Data not available for the Placebo (adult) arm. Data only available for 3 patients in Step 2 (Tesomet 0.125/25 mg (DB)). Data only available for 2 patients in Step 2 (Placebo (adolescent)). Data only available for 3 patients in OLE I (Tesomet 0.125/25 mg -\> Tesomet 0.125/25 mg).~Data only available for 2 patients in OLE I (Placebo -\> Tesomet 0.125/25 mg). Data only available for 2 patients in OLE II (Tesomet 0.25/25 mg).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Tesomet 0.50/50 mg | Change From Baseline to End of Treatment in Fat- and Fat Free Mass (%) by Dual X-ray Absorptiometry (DEXA) | Fat mass | -1.27 Percent (%) | Standard Deviation 1.07 |
| Tesomet 0.50/50 mg | Change From Baseline to End of Treatment in Fat- and Fat Free Mass (%) by Dual X-ray Absorptiometry (DEXA) | Fat free mass | 1.19 Percent (%) | Standard Deviation 1.11 |
| Tesomet 0.125/25 mg (DB) | Change From Baseline to End of Treatment in Fat- and Fat Free Mass (%) by Dual X-ray Absorptiometry (DEXA) | Fat mass | -0.13 Percent (%) | Standard Deviation 0.25 |
| Tesomet 0.125/25 mg (DB) | Change From Baseline to End of Treatment in Fat- and Fat Free Mass (%) by Dual X-ray Absorptiometry (DEXA) | Fat free mass | 0.137 Percent (%) | Standard Deviation 0.217 |
| Placebo (Adolescent) | Change From Baseline to End of Treatment in Fat- and Fat Free Mass (%) by Dual X-ray Absorptiometry (DEXA) | Fat mass | -0.50 Percent (%) | Standard Deviation 0.85 |
| Placebo (Adolescent) | Change From Baseline to End of Treatment in Fat- and Fat Free Mass (%) by Dual X-ray Absorptiometry (DEXA) | Fat free mass | -2.080 Percent (%) | Standard Deviation 4.511 |
| Tesomet 0.125/25 mg -> Tesomet 0.125/25 mg | Change From Baseline to End of Treatment in Fat- and Fat Free Mass (%) by Dual X-ray Absorptiometry (DEXA) | Fat mass | 1.20 Percent (%) | Standard Deviation 1.74 |
| Tesomet 0.125/25 mg -> Tesomet 0.125/25 mg | Change From Baseline to End of Treatment in Fat- and Fat Free Mass (%) by Dual X-ray Absorptiometry (DEXA) | Fat free mass | 0.053 Percent (%) | Standard Deviation 2.559 |
| Placebo -> Tesomet 0.125/25 mg | Change From Baseline to End of Treatment in Fat- and Fat Free Mass (%) by Dual X-ray Absorptiometry (DEXA) | Fat mass | -0.05 Percent (%) | Standard Deviation 0.21 |
| Placebo -> Tesomet 0.125/25 mg | Change From Baseline to End of Treatment in Fat- and Fat Free Mass (%) by Dual X-ray Absorptiometry (DEXA) | Fat free mass | 4.290 Percent (%) | Standard Deviation 3.974 |
| Tesomet 0.25/25 mg | Change From Baseline to End of Treatment in Fat- and Fat Free Mass (%) by Dual X-ray Absorptiometry (DEXA) | Fat mass | -1.70 Percent (%) | Standard Deviation 0.1 |
| Tesomet 0.25/25 mg | Change From Baseline to End of Treatment in Fat- and Fat Free Mass (%) by Dual X-ray Absorptiometry (DEXA) | Fat free mass | 0.000 Percent (%) | Standard Deviation 0.1 |
| Tesomet 0.125/25 mg (OLE II) | Change From Baseline to End of Treatment in Fat- and Fat Free Mass (%) by Dual X-ray Absorptiometry (DEXA) | Fat mass | -1.50 Percent (%) | — |
| Tesomet 0.125/25 mg (OLE II) | Change From Baseline to End of Treatment in Fat- and Fat Free Mass (%) by Dual X-ray Absorptiometry (DEXA) | Fat free mass | 1.470 Percent (%) | — |
Secondary
Change From Baseline to End of Treatment in HbA1c
Change from baseline to end of treatment in HbA1c (%). LOCF.
Time frame: DB Step 1: Day 1 to Day 91; DB Step 2: Day 1 to Day 91; OLE I: Day 91 to Day 181; OLE II: Day 181 to Day 271
Population: Data only available for 2 patients in the Placebo (adult) arm. Data only available for 3 patients in OLE I (Placebo -\> Tesomet 0.125/25 mg). 5 patients started on Tesomet 0.25/25mg in OLE II however 1 subject discontinued early without any further observations and data are therefore only available from 4 subjects.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Tesomet 0.50/50 mg | Change From Baseline to End of Treatment in HbA1c | 0.11 Percentage of HbA1c | Standard Deviation 0.13 |
| Placebo (Adult) | Change From Baseline to End of Treatment in HbA1c | 0.15 Percentage of HbA1c | Standard Deviation 0.21 |
| Tesomet 0.125/25 mg (DB) | Change From Baseline to End of Treatment in HbA1c | 0.06 Percentage of HbA1c | Standard Deviation 0.05 |
| Placebo (Adolescent) | Change From Baseline to End of Treatment in HbA1c | 0.15 Percentage of HbA1c | Standard Deviation 0.24 |
| Tesomet 0.125/25 mg -> Tesomet 0.125/25 mg | Change From Baseline to End of Treatment in HbA1c | 0.12 Percentage of HbA1c | Standard Deviation 0.26 |
| Placebo -> Tesomet 0.125/25 mg | Change From Baseline to End of Treatment in HbA1c | 0.10 Percentage of HbA1c | Standard Deviation 0.17 |
| Tesomet 0.25/25 mg | Change From Baseline to End of Treatment in HbA1c | 0.00 Percentage of HbA1c | Standard Deviation 0.12 |
| Tesomet 0.125/25 mg (OLE II) | Change From Baseline to End of Treatment in HbA1c | 0.00 Percentage of HbA1c | — |
Secondary
Change From Baseline to End of Treatment in Heart Rate (HR)
Change from baseline to end of treatment in HR (bpm). LOCF.
Time frame: DB Step 1: Day 1 to Day 91; DB Step 2: Day 1 to Day 91; OLE I: Day 91 to Day 181; OLE II: Day 181 to Day 271
Population: 5 patients started on Tesomet 0.25/25mg in OLE II however 1 subject discontinued early without any further observations and data are therefore only available from 4 subjects.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Tesomet 0.50/50 mg | Change From Baseline to End of Treatment in Heart Rate (HR) | 8.22 bpm | Standard Deviation 4.26 |
| Placebo (Adult) | Change From Baseline to End of Treatment in Heart Rate (HR) | 7.89 bpm | Standard Deviation 7.88 |
| Tesomet 0.125/25 mg (DB) | Change From Baseline to End of Treatment in Heart Rate (HR) | 5.87 bpm | Standard Deviation 11.01 |
| Placebo (Adolescent) | Change From Baseline to End of Treatment in Heart Rate (HR) | 2.75 bpm | Standard Deviation 8.96 |
| Tesomet 0.125/25 mg -> Tesomet 0.125/25 mg | Change From Baseline to End of Treatment in Heart Rate (HR) | 2.42 bpm | Standard Deviation 15.14 |
| Placebo -> Tesomet 0.125/25 mg | Change From Baseline to End of Treatment in Heart Rate (HR) | 0.33 bpm | Standard Deviation 8.65 |
| Tesomet 0.25/25 mg | Change From Baseline to End of Treatment in Heart Rate (HR) | -9.50 bpm | Standard Deviation 10.86 |
| Tesomet 0.125/25 mg (OLE II) | Change From Baseline to End of Treatment in Heart Rate (HR) | -5.67 bpm | — |
Secondary
Change From Baseline to End of Treatment in Hyperphagia Questionnaire for Clinical Trials (HQ-CT) Score
Change from baseline to end of treatment in HQ-CT score. LOCF. HQ-CT score was based upon a questionnaire with 9 items, each of them yielding a score between 0 and 4 resulting in a maximum HQ-CT score of 36. Change in HQ-CT answers (by question and in total) calculated as score at visit 2, 5, 9 or 14 minus score at screening visit 1 was analysed and presented using standard descriptive statistics (mean, median, standard deviation, minimum and maximum value). A decrease in total score indicates an improvement in hyperphagia. If less than three questions were answered by a subject, the missing answers were imputed by the mean score of all other available answers. In case of more than three missing answers, the total score was not calculated. For further information please refer to protocol appendix section 17.1.
Time frame: DB Step 1: Day 1 to Day 91; DB Step 2: Day 1 to Day 91; OLE I: Day 91 to Day 181; OLE II: Day 181 to Day 271
Population: Data only available for 2 patients in Step I placebo arm. 5 patients started on Tesomet 0.25/25mg in OLE II however 1 subject discontinued early without any further observations and data are therefore only available from 4 subjects.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Tesomet 0.50/50 mg | Change From Baseline to End of Treatment in Hyperphagia Questionnaire for Clinical Trials (HQ-CT) Score | -8.50 score on a scale | Standard Deviation 9.25 |
| Placebo (Adult) | Change From Baseline to End of Treatment in Hyperphagia Questionnaire for Clinical Trials (HQ-CT) Score | -4.00 score on a scale | Standard Deviation 7.07 |
| Tesomet 0.125/25 mg (DB) | Change From Baseline to End of Treatment in Hyperphagia Questionnaire for Clinical Trials (HQ-CT) Score | -3.30 score on a scale | Standard Deviation 6.82 |
| Placebo (Adolescent) | Change From Baseline to End of Treatment in Hyperphagia Questionnaire for Clinical Trials (HQ-CT) Score | -6.75 score on a scale | Standard Deviation 3.69 |
| Tesomet 0.125/25 mg -> Tesomet 0.125/25 mg | Change From Baseline to End of Treatment in Hyperphagia Questionnaire for Clinical Trials (HQ-CT) Score | 1.25 score on a scale | Standard Deviation 5.68 |
| Placebo -> Tesomet 0.125/25 mg | Change From Baseline to End of Treatment in Hyperphagia Questionnaire for Clinical Trials (HQ-CT) Score | -1.75 score on a scale | Standard Deviation 1.5 |
| Tesomet 0.25/25 mg | Change From Baseline to End of Treatment in Hyperphagia Questionnaire for Clinical Trials (HQ-CT) Score | -1.00 score on a scale | Standard Deviation 2 |
| Tesomet 0.125/25 mg (OLE II) | Change From Baseline to End of Treatment in Hyperphagia Questionnaire for Clinical Trials (HQ-CT) Score | -2.00 score on a scale | — |
p-value: 0.005895% CI: [-12.5, -3.6]ANCOVA
p-value: 0.514295% CI: [-5.3, 9.5]ANCOVA
p-value: 0.379495% CI: [-5.1, 11.3]ANCOVA
p-value: 0.68595% CI: [-6.1, 8.1]ANCOVA
Secondary
Change From Baseline to End of Treatment in Insulin
Change from baseline to end of treatment in insulin (mIU/L). LOCF.
Time frame: DB Step 1: Day 1 to Day 91; DB Step 2: Day 1 to Day 91; OLE I: Day 91 to Day 181; OLE II: Day 181 to Day 271
Population: Data only available for 2 patients in the Placebo (adult) arm. Data only available for 3 patients in OLE I (Placebo -\> Tesomet 0.125/25 mg). 5 patients started on Tesomet 0.25/25mg in OLE II however 1 subject discontinued early without any further observations and data are therefore only available from 4 subjects.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Tesomet 0.50/50 mg | Change From Baseline to End of Treatment in Insulin | 2.67 mIU/L | Standard Deviation 10.93 |
| Placebo (Adult) | Change From Baseline to End of Treatment in Insulin | 1.50 mIU/L | Standard Deviation 10.61 |
| Tesomet 0.125/25 mg (DB) | Change From Baseline to End of Treatment in Insulin | 1.95 mIU/L | Standard Deviation 13.85 |
| Placebo (Adolescent) | Change From Baseline to End of Treatment in Insulin | -10.32 mIU/L | Standard Deviation 17.2 |
| Tesomet 0.125/25 mg -> Tesomet 0.125/25 mg | Change From Baseline to End of Treatment in Insulin | 13.14 mIU/L | Standard Deviation 22.15 |
| Placebo -> Tesomet 0.125/25 mg | Change From Baseline to End of Treatment in Insulin | 4.93 mIU/L | Standard Deviation 5.25 |
| Tesomet 0.25/25 mg | Change From Baseline to End of Treatment in Insulin | -1.35 mIU/L | Standard Deviation 24.56 |
| Tesomet 0.125/25 mg (OLE II) | Change From Baseline to End of Treatment in Insulin | -5.90 mIU/L | — |
Secondary
Change From Baseline to End of Treatment in Mean Body Weight
Change from baseline to end of treatment in body weight \[kg\]. LOCF.
Time frame: DB Step 1: Day 1 to Day 91; DB Step 2: Day 1 to Day 91; OLE I: Day 91 to Day 181; OLE II: Day 181 to Day 271
Population: 5 patients started on Tesomet 0.25/25mg in OLE II however 1 subject discontinued early without any further observations and data are therefore only available from 4 subjects.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Tesomet 0.50/50 mg | Change From Baseline to End of Treatment in Mean Body Weight | -4.15 kg | Standard Deviation 4.82 |
| Placebo (Adult) | Change From Baseline to End of Treatment in Mean Body Weight | -0.77 kg | Standard Deviation 3.23 |
| Tesomet 0.125/25 mg (DB) | Change From Baseline to End of Treatment in Mean Body Weight | 3.10 kg | Standard Deviation 2.85 |
| Placebo (Adolescent) | Change From Baseline to End of Treatment in Mean Body Weight | 2.25 kg | Standard Deviation 1.71 |
| Tesomet 0.125/25 mg -> Tesomet 0.125/25 mg | Change From Baseline to End of Treatment in Mean Body Weight | 4.75 kg | Standard Deviation 2.41 |
| Placebo -> Tesomet 0.125/25 mg | Change From Baseline to End of Treatment in Mean Body Weight | 0.45 kg | Standard Deviation 2.82 |
| Tesomet 0.25/25 mg | Change From Baseline to End of Treatment in Mean Body Weight | -0.90 kg | Standard Deviation 3.2 |
| Tesomet 0.125/25 mg (OLE II) | Change From Baseline to End of Treatment in Mean Body Weight | -3.50 kg | — |
p-value: 0.132695% CI: [-14.9, 2.5]ANCOVA
p-value: 0.514895% CI: [-2.9, 5.3]ANCOVA
p-value: 0.060595% CI: [-0.3, 9.4]ANCOVA
p-value: 0.519895% CI: [-8.8, 14]ANCOVA
Secondary
Change From Baseline to End of Treatment in PR Interval
Change from baseline to end of treatment in PR interval. Observed values.
Time frame: DB Step 1: Day 1 to Day 91; DB Step 2: Day 1 to Day 91; OLE I: Day 91 to Day 181; OLE II: Day 181 to Day 271
Population: Data only available for 1 patient in Step I (Tesomet 0.50/50 mg). Data not available for the Placebo (adult) arm. Data only available for 1 patient in Step 2 (Tesomet 0.125/25 mg (DB)). Data only available for 2 patients in Step 2 (Placebo (adolescent)). Data only available for 1 patient in OLE I (Tesomet 0.125/25 mg -\> Tesomet 0.125/25 mg).~Data only available for 1 patient in OLE I (Placebo -\> Tesomet 0.125/25 mg). Data not available for OLE II (Tesomet 0.25/25 mg).
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Tesomet 0.50/50 mg | Change From Baseline to End of Treatment in PR Interval | -20.0 ms | — |
| Tesomet 0.125/25 mg (DB) | Change From Baseline to End of Treatment in PR Interval | 0.0 ms | — |
| Placebo (Adolescent) | Change From Baseline to End of Treatment in PR Interval | 20.0 ms | Standard Deviation 0 |
| Tesomet 0.125/25 mg -> Tesomet 0.125/25 mg | Change From Baseline to End of Treatment in PR Interval | 0.0 ms | — |
| Placebo -> Tesomet 0.125/25 mg | Change From Baseline to End of Treatment in PR Interval | -20.0 ms | — |
| Tesomet 0.125/25 mg (OLE II) | Change From Baseline to End of Treatment in PR Interval | 10.0 ms | — |
Secondary
Change From Baseline to End of Treatment in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP)
Change from baseline to end of treatment in SBP (mmHg) and DBP (mmHg). LOCF.
Time frame: DB Step 1: Day 1 to Day 91; DB Step 2: Day 1 to Day 91; OLE I: Day 91 to Day 181; OLE II: Day 181 to Day 271
Population: 5 patients started on Tesomet 0.25/25mg in OLE II however 1 subject discontinued early without any further observations and data are therefore only available from 4 subjects.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Tesomet 0.50/50 mg | Change From Baseline to End of Treatment in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | Change in SBP | -2.72 mmHg | Standard Deviation 9.96 |
| Tesomet 0.50/50 mg | Change From Baseline to End of Treatment in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | Change in DBP | 0.94 mmHg | Standard Deviation 10.72 |
| Placebo (Adult) | Change From Baseline to End of Treatment in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | Change in SBP | 0.11 mmHg | Standard Deviation 15.22 |
| Placebo (Adult) | Change From Baseline to End of Treatment in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | Change in DBP | -8.89 mmHg | Standard Deviation 8 |
| Tesomet 0.125/25 mg (DB) | Change From Baseline to End of Treatment in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | Change in SBP | -0.13 mmHg | Standard Deviation 15.79 |
| Tesomet 0.125/25 mg (DB) | Change From Baseline to End of Treatment in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | Change in DBP | -1.07 mmHg | Standard Deviation 7.06 |
| Placebo (Adolescent) | Change From Baseline to End of Treatment in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | Change in SBP | -5.00 mmHg | Standard Deviation 9.26 |
| Placebo (Adolescent) | Change From Baseline to End of Treatment in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | Change in DBP | 0.33 mmHg | Standard Deviation 2.54 |
| Tesomet 0.125/25 mg -> Tesomet 0.125/25 mg | Change From Baseline to End of Treatment in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | Change in SBP | 5.67 mmHg | Standard Deviation 11.3 |
| Tesomet 0.125/25 mg -> Tesomet 0.125/25 mg | Change From Baseline to End of Treatment in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | Change in DBP | 2.92 mmHg | Standard Deviation 10.22 |
| Placebo -> Tesomet 0.125/25 mg | Change From Baseline to End of Treatment in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | Change in SBP | 8.08 mmHg | Standard Deviation 6.45 |
| Placebo -> Tesomet 0.125/25 mg | Change From Baseline to End of Treatment in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | Change in DBP | 4.00 mmHg | Standard Deviation 5.4 |
| Tesomet 0.25/25 mg | Change From Baseline to End of Treatment in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | Change in DBP | -6.42 mmHg | Standard Deviation 3.95 |
| Tesomet 0.25/25 mg | Change From Baseline to End of Treatment in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | Change in SBP | -5.33 mmHg | Standard Deviation 2.6 |
| Tesomet 0.125/25 mg (OLE II) | Change From Baseline to End of Treatment in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | Change in SBP | -9.67 mmHg | — |
| Tesomet 0.125/25 mg (OLE II) | Change From Baseline to End of Treatment in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | Change in DBP | 1.33 mmHg | — |
Secondary
Number of Subjects With Adverse Events (AE) and Serious Adverse Events (SAE)
Number of subjects with Adverse Events and Serious Adverse Events
Time frame: DB Step 1: Day 1 to Day 91; DB Step 2: Day 1 to Day 91; OLE I: Day 91 to Day 181; OLE II: Day 181 to Day 271
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Tesomet 0.50/50 mg | Number of Subjects With Adverse Events (AE) and Serious Adverse Events (SAE) | Subjects with at least one SAE | 3 Participants |
| Tesomet 0.50/50 mg | Number of Subjects With Adverse Events (AE) and Serious Adverse Events (SAE) | Subjects with at least one AE | 6 Participants |
| Placebo (Adult) | Number of Subjects With Adverse Events (AE) and Serious Adverse Events (SAE) | Subjects with at least one AE | 3 Participants |
| Placebo (Adult) | Number of Subjects With Adverse Events (AE) and Serious Adverse Events (SAE) | Subjects with at least one SAE | 0 Participants |
| Tesomet 0.125/25 mg (DB) | Number of Subjects With Adverse Events (AE) and Serious Adverse Events (SAE) | Subjects with at least one AE | 5 Participants |
| Tesomet 0.125/25 mg (DB) | Number of Subjects With Adverse Events (AE) and Serious Adverse Events (SAE) | Subjects with at least one SAE | 0 Participants |
| Placebo (Adolescent) | Number of Subjects With Adverse Events (AE) and Serious Adverse Events (SAE) | Subjects with at least one SAE | 0 Participants |
| Placebo (Adolescent) | Number of Subjects With Adverse Events (AE) and Serious Adverse Events (SAE) | Subjects with at least one AE | 3 Participants |
| Tesomet 0.125/25 mg -> Tesomet 0.125/25 mg | Number of Subjects With Adverse Events (AE) and Serious Adverse Events (SAE) | Subjects with at least one AE | 4 Participants |
| Tesomet 0.125/25 mg -> Tesomet 0.125/25 mg | Number of Subjects With Adverse Events (AE) and Serious Adverse Events (SAE) | Subjects with at least one SAE | 0 Participants |
| Placebo -> Tesomet 0.125/25 mg | Number of Subjects With Adverse Events (AE) and Serious Adverse Events (SAE) | Subjects with at least one SAE | 0 Participants |
| Placebo -> Tesomet 0.125/25 mg | Number of Subjects With Adverse Events (AE) and Serious Adverse Events (SAE) | Subjects with at least one AE | 4 Participants |
| Tesomet 0.25/25 mg | Number of Subjects With Adverse Events (AE) and Serious Adverse Events (SAE) | Subjects with at least one AE | 5 Participants |
| Tesomet 0.25/25 mg | Number of Subjects With Adverse Events (AE) and Serious Adverse Events (SAE) | Subjects with at least one SAE | 2 Participants |
| Tesomet 0.125/25 mg (OLE II) | Number of Subjects With Adverse Events (AE) and Serious Adverse Events (SAE) | Subjects with at least one SAE | 0 Participants |
| Tesomet 0.125/25 mg (OLE II) | Number of Subjects With Adverse Events (AE) and Serious Adverse Events (SAE) | Subjects with at least one AE | 1 Participants |
Secondary
Steady State Concentrations of Tesofensine and Metoprolol as Measured by Trough Values
Steady state concentrations of tesofensine and metoprolol as measured by trough values. Observed values.
Time frame: DB Step 1: Day 29; DB Step 2: Day 29; OLE I: Day 120; OLE II: Day 210
Population: No data available for placebo arm in Step I and Step 2. Data only available for 3 patients in OLE I (Placebo -\> Tesomet 0.125/25 mg). 5 patients started on Tesomet 0.25/25mg in OLE II however 1 subject discontinued early without any further observations and data are therefore only available from 4 subjects.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Tesomet 0.50/50 mg | Steady State Concentrations of Tesofensine and Metoprolol as Measured by Trough Values | Teso. metab. | 2.97 μg/L | Geometric Coefficient of Variation 52.6 |
| Tesomet 0.50/50 mg | Steady State Concentrations of Tesofensine and Metoprolol as Measured by Trough Values | Tesofensine | 16.29 μg/L | Geometric Coefficient of Variation 49.8 |
| Tesomet 0.50/50 mg | Steady State Concentrations of Tesofensine and Metoprolol as Measured by Trough Values | Metoprolol | 1.61 μg/L | Geometric Coefficient of Variation 903.7 |
| Tesomet 0.125/25 mg (DB) | Steady State Concentrations of Tesofensine and Metoprolol as Measured by Trough Values | Teso. metab. | 0.79 μg/L | Geometric Coefficient of Variation 17.1 |
| Tesomet 0.125/25 mg (DB) | Steady State Concentrations of Tesofensine and Metoprolol as Measured by Trough Values | Tesofensine | 3.34 μg/L | Geometric Coefficient of Variation 32.2 |
| Tesomet 0.125/25 mg (DB) | Steady State Concentrations of Tesofensine and Metoprolol as Measured by Trough Values | Metoprolol | 1.97 μg/L | Geometric Coefficient of Variation 285.5 |
| Tesomet 0.125/25 mg -> Tesomet 0.125/25 mg | Steady State Concentrations of Tesofensine and Metoprolol as Measured by Trough Values | Teso. metab. | 1.45 μg/L | Geometric Coefficient of Variation 23.3 |
| Tesomet 0.125/25 mg -> Tesomet 0.125/25 mg | Steady State Concentrations of Tesofensine and Metoprolol as Measured by Trough Values | Tesofensine | 4.14 μg/L | Geometric Coefficient of Variation 17.3 |
| Tesomet 0.125/25 mg -> Tesomet 0.125/25 mg | Steady State Concentrations of Tesofensine and Metoprolol as Measured by Trough Values | Metoprolol | 2.81 μg/L | Geometric Coefficient of Variation 119 |
| Placebo -> Tesomet 0.125/25 mg | Steady State Concentrations of Tesofensine and Metoprolol as Measured by Trough Values | Teso. metab. | 1.00 μg/L | Geometric Coefficient of Variation 41.9 |
| Placebo -> Tesomet 0.125/25 mg | Steady State Concentrations of Tesofensine and Metoprolol as Measured by Trough Values | Tesofensine | 5.06 μg/L | Geometric Coefficient of Variation 18 |
| Placebo -> Tesomet 0.125/25 mg | Steady State Concentrations of Tesofensine and Metoprolol as Measured by Trough Values | Metoprolol | 3.32 μg/L | Geometric Coefficient of Variation 32 |
| Tesomet 0.25/25 mg | Steady State Concentrations of Tesofensine and Metoprolol as Measured by Trough Values | Teso. metab. | 1.56 μg/L | Geometric Coefficient of Variation 49.1 |
| Tesomet 0.25/25 mg | Steady State Concentrations of Tesofensine and Metoprolol as Measured by Trough Values | Tesofensine | 4.13 μg/L | Geometric Coefficient of Variation 137.5 |
| Tesomet 0.25/25 mg | Steady State Concentrations of Tesofensine and Metoprolol as Measured by Trough Values | Metoprolol | 1.76 μg/L | Geometric Coefficient of Variation 242.5 |
| Tesomet 0.125/25 mg (OLE II) | Steady State Concentrations of Tesofensine and Metoprolol as Measured by Trough Values | Tesofensine | 6.43 μg/L | — |
| Tesomet 0.125/25 mg (OLE II) | Steady State Concentrations of Tesofensine and Metoprolol as Measured by Trough Values | Metoprolol | 14.50 μg/L | — |
| Tesomet 0.125/25 mg (OLE II) | Steady State Concentrations of Tesofensine and Metoprolol as Measured by Trough Values | Teso. metab. | 1.98 μg/L | — |
Secondary
Total Number of Adverse Events
Total number of Adverse Events
Time frame: DB Step 1: Day 1 to Day 91; DB Step 2: Day 1 to Day 91; OLE I: Day 91 to Day 181; OLE II: Day 181 to Day 271
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Tesomet 0.50/50 mg | Total Number of Adverse Events | 23 Total number of adverse events |
| Placebo (Adult) | Total Number of Adverse Events | 10 Total number of adverse events |
| Tesomet 0.125/25 mg (DB) | Total Number of Adverse Events | 19 Total number of adverse events |
| Placebo (Adolescent) | Total Number of Adverse Events | 9 Total number of adverse events |
| Tesomet 0.125/25 mg -> Tesomet 0.125/25 mg | Total Number of Adverse Events | 11 Total number of adverse events |
| Placebo -> Tesomet 0.125/25 mg | Total Number of Adverse Events | 12 Total number of adverse events |
| Tesomet 0.25/25 mg | Total Number of Adverse Events | 14 Total number of adverse events |
| Tesomet 0.125/25 mg (OLE II) | Total Number of Adverse Events | 5 Total number of adverse events |