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Trial · Interventional

CompletedPhase 2Results postedRegistry data

Co-administration of Tesofensine/Metoprolol in Subjects With Prader-Willi Syndrome (PWS)

Short name 2016-003694-18

NCTNCT03149445 (opens ClinicalTrials.gov in a new tab)Other idTM002
Open at ClinicalTrials.govAsk about this trial

Overview

Status
Completed
Phase
Phase 2
Enrollment
18 participants (actual)
Sponsor
Saniona · Industry
Design
Randomized · Quadruple masking
Countries
2 countries

Czechia, Hungary

Start
30 Mar 2017
Primary completion
22 Jul 2019
Completion
22 Jul 2019
First posted
11 May 2017
Last update posted
26 Feb 2024
Conditions
Confirmed Genetic Diagnosis of Prader-Willi Syndrome

Timeline

1 trial · 1 completed · 1 with posted results

  • Completed
  • Ongoing
  • Not yet recruiting
  • Stopped
  • Estimated dates (est.)
  • Results posted
2017201820192020
  1. Ph 2

    2016-003694-18

    NCT03149445

    30 Mar 2017 to 22 Jul 2019

Registry summary

Text and fields below are the sponsor's entries at ClinicalTrials.gov, shown as posted.

Two-centre, double-blind, placebo-controlled, randomized, and multiple-dose clinical study followed by two open label extension periods.

Interventions

  • Tesofensine/MetoprololDrug
  • PlacebosDrug

Arms2

  • Experimental

    Tesofensine/Metoprolol

    Tesofensine + metoprolol administered once a day, in the morning with a meal

  • Placebo comparator

    Tesofensine/Metoprolol placebo

    Placebo tablets matching tesofensine + metoprolol administered once a day, in the morning with meal

Primary outcomes1

Outcomes the sponsor listed as primary.

  1. Percent Change From Baseline to End of Treatment in Mean Body Weight

    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

    Registry description

    Percent change from baseline to end of treatment in mean body weight. LOCF.

Secondary outcomes(15)

  1. Change From Baseline to End of Treatment in Mean Body Weight

    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

    Registry description

    Change from baseline to end of treatment in body weight \[kg\]. LOCF.

  2. Change From Baseline to End of Treatment in Hyperphagia Questionnaire for Clinical Trials (HQ-CT) Score

    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

    Registry description

    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.

  3. Steady State Concentrations of Tesofensine and Metoprolol as Measured by Trough Values

    Time frame · DB Step 1: Day 29; DB Step 2: Day 29; OLE I: Day 120; OLE II: Day 210

    Registry description

    Steady state concentrations of tesofensine and metoprolol as measured by trough values. Observed values.

  4. Change From Baseline to End of Treatment in Fat- and Fat Free Mass (%) by Dual X-ray Absorptiometry (DEXA)

    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

    Registry description

    Change from baseline to end of treatment in fat- and fat free mass (%) by dual X-ray absorptiometry (DEXA). Observed values.

  5. Change From Baseline to End of Treatment in Bone Mineral Density (BMD) by Dual X-ray Absorptiometry (DEXA)

    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

    Registry description

    Change from baseline to end of treatment in BMD by dual X-ray absorptiometry (DEXA). Observed values.

  6. Change From Baseline to End of Treatment in Bone Mineral Content (BMC) by Dual X-ray Absorptiometry (DEXA)

    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

    Registry description

    Change from baseline to end of treatment in BMC by dual X-ray absorptiometry (DEXA). Observed values.

  7. Change From Baseline to End of Treatment in Heart Rate (HR)

    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

    Registry description

    Change from baseline to end of treatment in HR (bpm). LOCF.

  8. Change From Baseline to End of Treatment in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP)

    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

    Registry description

    Change from baseline to end of treatment in SBP (mmHg) and DBP (mmHg). LOCF.

  9. 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

    Registry description

    Total number of Adverse Events

  10. Change From Baseline to End of Treatment in PR Interval

    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

    Registry description

    Change from baseline to end of treatment in PR interval. Observed values.

  11. Change From Baseline to End of Treatment in Electrocardiogram (ECG) Parameters

    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

    Registry description

    Change from baseline to end of treatment in ECG parameters - QRS duration, QT interval, QTcF and QTcB

  12. Change From Baseline to End of Treatment in HbA1c

    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

    Registry description

    Change from baseline to end of treatment in HbA1c (%). LOCF.

  13. Change From Baseline to End of Treatment in Insulin

    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

    Registry description

    Change from baseline to end of treatment in insulin (mIU/L). LOCF.

  14. Change From Baseline to End of Treatment in Fasting pl. Glucose, Triglycerides, Low-density Lipoprotein (LDL) and High-density Lipoprotein (HDL) Cholesterol

    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

    Registry description

    Change from baseline to end of treatment in fasting pl. glucose (mmol/L), triglycerides (mmol/L), LDL and HDL cholesterol (mmol/L). LOCF.

  15. Number of Subjects With Adverse Events (AE) and Serious Adverse Events (SAE)

    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

    Registry description

    Number of subjects with Adverse Events and Serious Adverse Events

Posted results

Values are shown as posted at ClinicalTrials.gov, with their units. PepBank has not converted, pooled or compared them.

Primary outcome results

Primary outcomeMean· 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

GroupValue (Percent (%) change in mean body weight)Spread
Tesomet 0.50/50 mg-4.093.73
Placebo (Adult)-0.382.05
Tesomet 0.125/25 mg (DB)3.562.73
Placebo (Adolescent)3.002.35
Tesomet 0.125/25 mg -> Tesomet 0.125/25 mg5.792.08
Placebo -> Tesomet 0.125/25 mg0.333.26
Tesomet 0.25/25 mg-1.203.80
Tesomet 0.125/25 mg (OLE II)-5.51NA
Secondary and other outcome results(7)
Secondary outcomeMean· 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 Mean Body Weight

GroupValue (kg)Spread
Tesomet 0.50/50 mg-4.154.82
Placebo (Adult)-0.773.23
Tesomet 0.125/25 mg (DB)3.102.85
Placebo (Adolescent)2.251.71
Tesomet 0.125/25 mg -> Tesomet 0.125/25 mg4.752.41
Placebo -> Tesomet 0.125/25 mg0.452.82
Tesomet 0.25/25 mg-0.903.20
Tesomet 0.125/25 mg (OLE II)-3.50NA
Secondary outcomeMean· 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 Hyperphagia Questionnaire for Clinical Trials (HQ-CT) Score

GroupValue (score on a scale)Spread
Tesomet 0.50/50 mg-8.509.25
Placebo (Adult)-4.007.07
Tesomet 0.125/25 mg (DB)-3.306.82
Placebo (Adolescent)-6.753.69
Tesomet 0.125/25 mg -> Tesomet 0.125/25 mg1.255.68
Placebo -> Tesomet 0.125/25 mg-1.751.50
Tesomet 0.25/25 mg-1.002.00
Tesomet 0.125/25 mg (OLE II)-2.00NA
Secondary outcomeGeometric mean· 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

GroupValue (μg/L)Spread
Tesomet 0.50/50 mg16.2949.8
Placebo (Adult)not posted–
Tesomet 0.125/25 mg (DB)3.3432.2
Placebo (Adolescent)not posted–
Tesomet 0.125/25 mg -> Tesomet 0.125/25 mg4.1417.3
Placebo -> Tesomet 0.125/25 mg5.0618.0
Tesomet 0.25/25 mg4.13137.5
Tesomet 0.125/25 mg (OLE II)6.43NA
Secondary outcomeMean· 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)

GroupValue (Percent (%))Spread
Tesomet 0.50/50 mg-1.271.07
Placebo (Adult)not posted–
Tesomet 0.125/25 mg (DB)-0.130.25
Placebo (Adolescent)-0.500.85
Tesomet 0.125/25 mg -> Tesomet 0.125/25 mg1.201.74
Placebo -> Tesomet 0.125/25 mg-0.050.21
Tesomet 0.25/25 mg-1.700.1
Tesomet 0.125/25 mg (OLE II)-1.50NA
Secondary outcomeMean· 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 Bone Mineral Density (BMD) by Dual X-ray Absorptiometry (DEXA)

GroupValue (g/cm^2)Spread
Tesomet 0.50/50 mg0.0020.0017
Placebo (Adult)not posted–
Tesomet 0.125/25 mg (DB)0.0190.009
Placebo (Adolescent)0.0350.008
Tesomet 0.125/25 mg -> Tesomet 0.125/25 mg-0.0060.008
Placebo -> Tesomet 0.125/25 mg-0.0070.009
Tesomet 0.25/25 mg0.0230.0
Tesomet 0.125/25 mg (OLE II)0.009NA
Secondary outcomeMean· 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 Bone Mineral Content (BMC) by Dual X-ray Absorptiometry (DEXA)

GroupValue (gram)Spread
Tesomet 0.50/50 mg9.563.8
Placebo (Adult)not posted–
Tesomet 0.125/25 mg (DB)74.7722.46
Placebo (Adolescent)35.5355.37
Tesomet 0.125/25 mg -> Tesomet 0.125/25 mg-1.1217.86
Placebo -> Tesomet 0.125/25 mg5.6966.33
Tesomet 0.25/25 mg22.5146.6
Tesomet 0.125/25 mg (OLE II)-21.90NA
Secondary outcomeMean· 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 Heart Rate (HR)

GroupValue (bpm)Spread
Tesomet 0.50/50 mg8.224.26
Placebo (Adult)7.897.88
Tesomet 0.125/25 mg (DB)5.8711.01
Placebo (Adolescent)2.758.96
Tesomet 0.125/25 mg -> Tesomet 0.125/25 mg2.4215.14
Placebo -> Tesomet 0.125/25 mg0.338.65
Tesomet 0.25/25 mg-9.5010.86
Tesomet 0.125/25 mg (OLE II)-5.67NA

Adverse events, as posted

Adverse events as posted: participants affected out of participants at risk, by group
GroupDeathsSerious eventsOther events
Tesomet 0.50/50 mgSubjects (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 1.0 / 63 / 66 / 6
Placebo (Adult)Subjects (adults) were randomized to receive placebo once daily for 91 days during Step 1.0 / 30 / 33 / 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.0 / 50 / 55 / 5
Placebo (Adolescent)Subjects (adolescents) were randomized to receive placebo once daily for 91 days.0 / 40 / 43 / 4
Tesomet 0.125/25 mg -> Tesomet 0.125/25 mgParticipation in a 12-week OLE I was offered to patients who completed Step 2. Patients were receiving co-administration of 0.125 mg tesofensine/25 mg metoprolol (active medication Tesomet) once daily for 12 weeks during OLE I.0 / 40 / 44 / 4
Placebo -> Tesomet 0.125/25 mgParticipation in a 12-week OLE I was offered to patients who completed Step 2. Patients were receiving co-administration of 0.125 mg tesofensine/25 mg metoprolol (active medication Tesomet) once daily for 12 weeks during OLE I.0 / 40 / 44 / 4
Tesomet 0.25/25 mgParticipation in a 12 week OLE II was offered to all eligible patients of OLE I. Patients were receiving coadministration of 0.25 mg tesofensine/25 mg metoprolol (active medication Tesomet) once daily for 12 weeks during OLE II.0 / 52 / 55 / 5
Tesomet 0.125/25 mg (OLE II)Participation in a 12 week OLE II was offered to all eligible patients of OLE I. Patients were receiving coadministration of 0.125 mg tesofensine/25 mg metoprolol (active medication) once daily for 12 weeks.0 / 10 / 11 / 1

Each cell reads participants affected / participants at risk, as the registry posted them.

Registry data comes from ClinicalTrials.gov. Study results come from studies, not from the registry. How PepBank works

Studies0

Studies that cite this trial.

No study cites this trial.

Eligibility

Who could join, as posted.

Sex
All
Age
from 12 Years up to 30 Years
Healthy volunteers
Not accepted
Inclusion and exclusion criteria, as posted
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

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