Phase 2
N=9
Co-administration of Tesofensine/Metoprolol in Subjects With Prader-Willi Syndrome (PWS)
Confirmed Genetic Diagnosis of Prader-Willi Syndrome
Bottom Line
View on ClinicalTrials.gov: NCT03149445 ↗Enrolled (actual)
9
Serious AEs
15.6%
Results posted
Feb 2024
Primary outcome: Primary: Percent Change From Baseline to End of Treatment in Mean Body Weight — -4.09; -0.38; 3.56; 3.00 Percent (%) change in mean body weight — p=0.1045
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 2
- Interventions
- Tesofensine/Metoprolol (Drug); Placebos (Drug)
- Age
- Pediatric, Adult · 12+ yrs
- Sex
- All
- Sponsor
- Saniona
- Primary completion
- Jul 2019
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Percent Change From Baseline to End of Treatment in Mean Body Weight |
-4.09; -0.38; 3.56; 3.00; 5.79; 0.33 | 0.1045 |
| SECONDARY Change From Baseline to End of Treatment in Mean Body Weight |
-4.15; -0.77; 3.10; 2.25; 4.75; 0.45 | 0.1326 |
| SECONDARY Change From Baseline to End of Treatment in Hyperphagia Questionnaire for Clinical Trials (HQ-CT) Score |
-8.50; -4.00; -3.30; -6.75; 1.25; -1.75 | 0.0058 sig |
| SECONDARY Steady State Concentrations of Tesofensine and Metoprolol as Measured by Trough Values |
16.29; 3.34; 4.14; 5.06; 4.13; 6.43 | — |
| SECONDARY Change From Baseline to End of Treatment in Fat- and Fat Free Mass (%) by Dual X-ray Absorptiometry (DEXA) |
-1.27; -0.13; -0.50; 1.20; -0.05; -1.70 | — |
| SECONDARY Change From Baseline to End of Treatment in Bone Mineral Density (BMD) by Dual X-ray Absorptiometry (DEXA) |
0.002; 0.019; 0.035; -0.006; -0.007; 0.023 | — |
| SECONDARY Change From Baseline to End of Treatment in Bone Mineral Content (BMC) by Dual X-ray Absorptiometry (DEXA) |
9.5; 74.77; 35.53; -1.12; 5.69; 22.51 | — |
| SECONDARY Change From Baseline to End of Treatment in Heart Rate (HR) |
8.22; 7.89; 5.87; 2.75; 2.42; 0.33 | — |
| SECONDARY Change From Baseline to End of Treatment in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) |
-2.72; 0.11; -0.13; -5.00; 5.67; 8.08 | — |
| SECONDARY Total Number of Adverse Events |
23; 10; 19; 9; 11; 12 | — |
| SECONDARY Change From Baseline to End of Treatment in PR Interval |
-20.0; 0.0; 20.0; 0.0; -20.0; 10.0 | — |
| SECONDARY Change From Baseline to End of Treatment in Electrocardiogram (ECG) Parameters |
-4.0; 4.0; 2.0; 2.0; -1.5; 0.7 | — |
| SECONDARY Change From Baseline to End of Treatment in HbA1c |
0.11; 0.15; 0.06; 0.15; 0.12; 0.10 | — |
| SECONDARY Change From Baseline to End of Treatment in Insulin |
2.67; 1.50; 1.95; -10.32; 13.14; 4.93 | — |
| SECONDARY Change From Baseline to End of Treatment in Fasting pl. Glucose, Triglycerides, Low-density Lipoprotein (LDL) and High-density Lipoprotein (HDL) Cholesterol |
0.27; 0.30; -0.20; -0.30; 1.07; 0.37 | — |
| SECONDARY Number of Subjects With Adverse Events (AE) and Serious Adverse Events (SAE) |
6; 3; 5; 3; 4; 4 | — |
Summary
Two-centre, double-blind, placebo-controlled, randomized, and multiple-dose clinical study followed by two open label extension periods.
Eligibility Criteria
Inclusion Criteria
- Males and females with a confirmed genetic diagnosis of Prader-Willi syndrome
- Age:
- Step 1: Adults aged 18-30
- Step 2: Adolescents aged 12-17
- Body Mass Index (BMI):
- Step 1: Adults with ≥25 kg/m2
- Step 2: Children with a BMI >85th percentile for the same age and sex
- Normal Blood Pressure (BP) or well managed hypertension (only if dose of BP medication(s) has been stable for >2 months)
- Normal lipid profile or well managed dyslipidemia (only if dose of lipid-lowering medication(s) has been stable for >2 months)
- Growth hormone is allowed; but patient must be on stable dose of growth hormone >2 months
- Type 2 diabetes is allowed, but the following criteria must be met:
- HbA1c 3 months
- Fasting plasma glucose 140/90
- Step 2: Adolescents with ≥95th percentile for gender, age, and height
- Heart Rate (HR) ≥ 90, 3x ULN (Upper Limit of Normal range)) and/or kidney impairment
- More than 5% weight loss within the last 3 months
- Any other clinically meaningful condition, in the opinion of the investigator, which would make participation potentially unsafe
- Contraindications to administration of metoprolol per current Summary of Product Characteristics
Data sourced from ClinicalTrials.gov (NCT03149445). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.