Co-administration of Tesofensine/Metoprolol in Subjects With Prader-Willi Syndrome (PWS) (2016-003694-18)

February 23, 2024 updated by: Saniona

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

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

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

Two-centre, double-blind, placebo-controlled, randomized, and multiple-dose clinical study. Study medication will be administered for 91 days. The study will be conducted in two steps:

  • Step 1 - 9 adult subjects with PWS was treated.
  • Sponsor review - following the completion of the treatment of the adult subjects, unblinded efficacy, safety, Pharmacokinetic (PK) data as well as all data from the study in subjects with type 2 diabetes (TM001) will be reviewed by sponsor and an interim analysis will be done. Following competent authority positive opinion regarding the interim analysis and unblinded data the study will proceed to:
  • Step 2 - 9 adolescent subjects with PWS was treated.
  • OLE (Open Label Extension) I - Participation in a 12-week OLE I was offered to subjects who completed Step 2. 8 subjects entered OLE I.
  • OLE (Open Label Extension) II - Participation in a 12-week OLE II was offered to subjects who completed OLE I. 6 subjects continued to OLE II.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
18

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Czechia
      • Prague, Czechia, 150 06
        • Motol University Hospital
  • Hungary
      • Budapest, Hungary, H-1094
        • Semmelweis University

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

14 years to 26 years (Child, Adult)

Accepts Healthy Volunteers

No

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: Tesofensine/Metoprolol
Tesofensine + metoprolol administered once a day, in the morning with a meal
Drug: Tesofensine/Metoprolol
Study medication will be administered for 91 days.
Other Names:
  • Tesofensine
  • Metoprolol
Placebo Comparator: Tesofensine/Metoprolol placebo
Placebo tablets matching tesofensine + metoprolol administered once a day, in the morning with meal
Drug: Placebos
Study medication will be administered for 91 days.
Other Names:
  • Placebo

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
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
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 Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
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 body weight [kg]. 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
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
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.
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
Steady state concentrations of tesofensine and metoprolol as measured by trough values. Observed 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)
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). Observed values.
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 BMD by dual X-ray absorptiometry (DEXA). Observed values.
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 BMC by dual X-ray absorptiometry (DEXA). Observed values.
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 HR (bpm). 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
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
Change from baseline to end of treatment in SBP (mmHg) and DBP (mmHg). 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
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
Total number of Adverse Events
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
Change from baseline to end of treatment in PR interval. Observed values.
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 ECG parameters - QRS duration, QT interval, QTcF and QTcB
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
Change from baseline to end of treatment in HbA1c (%). 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
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 insulin (mIU/L). 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
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 fasting pl. glucose (mmol/L), triglycerides (mmol/L), LDL and HDL cholesterol (mmol/L). 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
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
Number of subjects with Adverse Events and Serious Adverse Events
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

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Saniona

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Study Director: Kim Krogsgaard, MD, DMSc, Saniona

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
March 30, 2017

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
July 22, 2019

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
July 22, 2019

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
April 3, 2017

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
May 10, 2017

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
May 11, 2017

Study Record Updates

Last Update Posted (Estimated)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
February 26, 2024

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
February 23, 2024

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
February 1, 2024

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • TM002

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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Drug Interventions

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

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Locations

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