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

NCT03149445 | Completed Phase 2 Results

• 1 other identifier: TM002
• Study Type: interventional
• Target: 18
• Locations: 2 countries
• Sites: 2

Brief Summary

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

Conditions

Confirmed Genetic Diagnosis of Prader-Willi Syndrome

Outcome Measures

Primary Outcomes (1)

• 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.

  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 Outcomes (15)

• 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 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

• 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

• 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 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

Study Arms (2)

Tesofensine/Metoprolol

EXPERIMENTAL

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

Drug: Tesofensine/Metoprolol

Tesofensine/Metoprolol placebo

PLACEBO COMPARATOR

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

Drug: Placebos

Interventions

Tesofensine/Metoprolol DRUG

Study medication will be administered for 91 days.

Also known as: Tesofensine, Metoprolol

Tesofensine/Metoprolol

Placebos DRUG

Study medication will be administered for 91 days.

Also known as: Placebo

Tesofensine/Metoprolol placebo

Eligibility Criteria

• Age: 12 Years - 30 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• 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 \<10.0 % not being managed with insulin within the past 3 months
• Patients taking GLP-1 analogues (e.g. exenatide, liraglutide) must have been on stable dose for \>3 months
• Fasting plasma glucose \<11.0 mmol/l

You may not qualify if:

• BP:
• Step 1: Adults with \>140/90
• Step 2: Adolescents with ≥95th percentile for gender, age, and height
• Heart Rate (HR) ≥ 90, \<50 bpm
• Hypersensitivity to tesofensine/metoprolol
• Type 1 diabetes
• Heart failure New York Heart Association (NYHA) level II or greater, decompensated heart failure
• Previous myocardial infarction or stroke
• 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
• History of major depressive disorder or suicidality
• Any clinically significant cardiac arrhythmia
• Treatment with calcium channel blockers and beta blockers
• Concomitant use of monoaminooxidase inhibitors
• Bulimia or anorexia nervosa
• Any agent used for weight loss in the past 3 months

Sponsors & Collaborators

• Saniona: lead

Study Sites (2)

Motol University Hospital

Prague, 150 06, Czechia

Location

Semmelweis University

Budapest, H-1094, Hungary

Location

MeSH Terms

Interventions

Tesofensine; Metoprolol

Intervention Hierarchy (Ancestors)

Phenoxypropanolamines; Propanolamines; Amino Alcohols; Alcohols; Organic Chemicals; Propanols; Amines

Results Point of Contact

• Title: Janus Schreiber Larsen
• Organization: Saniona A/S

janus.larsen@saniona.com

+457070 5225

Study Officials

• Kim Krogsgaard, MD, DMSc

  Saniona

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: double-blind
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Two-centre, double-blind, placebo-controlled, randomized, and multiple-dose clinical study.

Study Record Dates

• First Submitted: April 3, 2017
• First Posted: May 11, 2017
• Study Start: March 30, 2017
• Primary Completion: July 22, 2019
• Study Completion: July 22, 2019
• Last Updated: February 26, 2024
• Results First Posted: February 26, 2024

Record last verified: 2024-02

Data Sharing

• IPD Sharing: Will not share

Locations

CZ (1); HU (1)