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

• Register: ClinicalTrials.gov
• Last refreshed on: 4 March 2024
• Main ID: NCT03149445
• Date of registration: 03/04/2017
• Prospective Registration: No
• Primary sponsor: Saniona
• Public title: Co-administration of Tesofensine/Metoprolol in Subjects With Prader-Willi Syndrome (PWS) 2016-003694-18
• Scientific title: A Double-Blind, Randomized, Placebo-Controlled, Multiple-Dose, Multi-Center Safety and Efficacy Study of Co-Administration of Tesofensine/Metoprolol for 12 Weeks in Adult and Adolescent Patients With Prader-Willi Syndrome (PWS), Followed by Two Open Label 12 Weeks Extension Periods for Adolescent Patients
• Date of first enrolment: March 30, 2017
• Target sample size: 18
• Recruitment status: Completed
• URL: https://clinicaltrials.gov/ct2/show/NCT03149445
• Study type: Interventional
• Study design: Allocation: Randomized. Intervention model: Parallel Assignment. Primary purpose: Treatment. Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor).
• Phase: Phase 2

Countries of recruitment

Czechia, Hungary

Contacts

• Name: Kim Krogsgaard, MD, DMSc
• Affiliation: Saniona

Key inclusion & exclusion criteria

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



Age minimum: 12 Years
Age maximum: 30 Years
Gender: All

Health Condition(s) or Problem(s) studied

Confirmed Genetic Diagnosis of Prader-Willi Syndrome

Intervention(s)

Drug: Tesofensine/Metoprolol

Drug: Placebos

Primary Outcome(s)

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]

Secondary Outcome(s)

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]

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]

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]

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]

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]

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]

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]

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]

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]

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]

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]

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]

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]

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]

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]

Secondary ID(s)

TM002

Source(s) of Monetary Support

Please refer to primary and secondary sponsors

Results

• Results available: Yes
• Date Posted: 26/02/2024
• URL: https://clinicaltrials.gov/ct2/show/results/NCT03149445