Safety and efficacy of tesofensine/metoprolol in subjects with Prader-Willi syndrome

• Register: EUCTR
• Last refreshed on: 1 February 2020
• Main ID: EUCTR2016-003694-18-HU
• Date of registration: 13/10/2016
• Prospective Registration: Yes
• Primary sponsor: Saniona A/S
• Public title: Safety and efficacy of tesofensine/metoprolol in subjects with Prader-Willi syndrome
• Scientific title: A double-blind, randomized, placebo-controlled, multiple-dose, multi-centre safety and efficacy study of co-administration of tesofensine/metoprolol in subjects with Prader-Willi syndrome (PWS) "A 12 weeks open label extension"
• Date of first enrolment: 22/12/2016
• Target sample size: 35
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2016-003694-18
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: no; Randomised: no; Open: yes; Single blind: no; Double blind: no; Parallel group: no; Cross over: no; Other: no; If controlled, specify comparator, Other Medicinial Product: no; Placebo: no; Other: no; Number of treatment arms in the trial: 1
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): yes Therapeutic confirmatory - (Phase III): no Therapeutic use (Phase IV): no

Countries of recruitment

Czech Republic, Hungary

Contacts

• Name: Clinical & Regulatory department
• Affiliation: Saniona A/S

• Name: Clinical & Regulatory department
• Affiliation: Saniona A/S

Key inclusion & exclusion criteria

Inclusion criteria:
Patient must meet all of the following inclusion criteria in order to be eligible for the study:
All male and female pediatric subjects with confirmed diagnosis of PWS who completed the double blind phase (12 weeks) will be invited to participate in the open label 12 weeksextension phase, if deemed eligible by the Investigators.
Are the trial subjects under 18? yes
Number of subjects for this age range: 15
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 20
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range

Exclusion criteria:
If subject/parents decide not to participate in the OLE, subject will finish the study based on the Protocol Amendment 1.4.


Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Prader Willi syndrome (PWS)
MedDRA version: 20.0 Level: PT Classification code 10036476 Term: Prader-Willi syndrome System Organ Class: 10010331 - Congenital, familial and genetic disorders

Therapeutic area: Diseases [C] - Congenital, Hereditary, and Neonatal Diseases and Abnormalities [C16]

Intervention(s)

Product Name: Tesofensine
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: Tesofensine
CAS Number: 195875-86-6
Current Sponsor code: NS2330
Other descriptive name: TESOFENSINE
Concentration unit: µg/ml microgram(s)/millilitre
Concentration type: equal
Concentration number: 500-
INN or Proposed INN: Tesofensine
CAS Number: 195875-86-6
Current Sponsor code: NS2330
Other descriptive name: TESOFENSINE
Concentration unit: µg/ml microgram(s)/millilitre
Concentration type: equal
Concentration number: 250-

Trade Name: Metoprololsuccinat "Orion" 25mg
Pharmaceutical Form: Prolonged-release tablet
INN or Proposed INN: metoprolol
Other descriptive name: METOPROLOL SUCCINATE
Concentration unit: µg microgram(s)
Concentration type: equal
Concentration number: 23750-

Primary Outcome(s)

Timepoint(s) of evaluation of this end point: Day 180

Main Objective: The purpose of this study is to investigate the safety and efficacy of co-administration of tesofensine/metoprolol treatment versus placebo in adult and pediatric subjects with Prader-Willi syndrome. The primary objective is to examine the effect of co-administration of tesofensine/metoprolol on body weight in subjects with PWS in an open labeled extension study.

Secondary Objective: The secondary objectives are:
1. To establish pharmacokinetic profile of tesofensine and metoprolol in subjects with PWS
2. To examine the change in hyperphagia-related behaviour in subjects with PWS by use of the Hyperphagia Questionnaire for Clinical Trials (HQ-CT)
3. To examine the effect of co-administration of tesofensine/metoprolol on glycaemic control and lipid profile in subjects with PWS
4. To examine the effect of co-administration of tesofensine/metoprolol on HR and BP in subjects with PWS
5. To examine the effects of co-administration of tesofensine/metoprolol on body composition in subjects with PWS
6. To evaluate overall safety and tolerability of co-administration of the tesofensine/metoprolol in subjects with PWS

Primary end point(s): The primary endpoint for this study is percent change from baseline to end of treatment in mean body weight.

Secondary Outcome(s)

Timepoint(s) of evaluation of this end point: From baseline to end of study treatment.

Secondary end point(s): Secondary endpoints include:
1. Steady state concentrations of tesofensine and metoprolol as measured by trough values
2. Uptake and initial plateau concentrations of metoprolol as measured by samples taken 2 and 4 hours after dose administration
3. Change from baseline to end of treatment in total HQCT score
4. Change from baseline to end of treatment in mean body weight (kg)
5. Change from baseline to end of treatment in fat- and fat-free mass (%) by dual X-ray absorptiometry (DXA)
6. Change from baseline to end of treatment in HR (bpm), SBP (mmHg), DBP (mmHg)
7. AEs, clinical labs, ECG
There are additional exploratory endpoints:
1. Change from baseline to end of treatment in FPG, insulin
2. Change from baseline to end of treatment in lipid profile
3. Change from baseline to end of treatment in waist circumference (cm)

Secondary ID(s)

2016-003694-18-CZ

n.a.

TM002

Source(s) of Monetary Support

Saniona A/S

Ethics review

Status: Approved
Approval date: 13/12/2016
Contact: