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Completed

NCT Number: NCT03845075

48 Weeks, Study to Evaluate Overall Safety and Tolerability of Co-administration of Tesofensine and Metoprolol in Subjects With Hypothalamic Injury-induced Obesity (HIO)

Double-blind, randomized, placebo-controlled, single- center study followed by an open-label extension period.

• The study will have two parts:

* Part 1: 24 weeks double-blind treatment (DB), followed by * Part 2: 24 weeks open-label extension (OLE) - all subjects still participating at the end of Part 1 will be given an option to continue for additional 24 weeks on the active drug if evaluated eligible by the Investigator

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Key information

Conditions

Hypothalamic Injury-induced Obesity (HIO)

Age range

18 year–75 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 2

Primary location

Rigshospitalet

Copenhagen, 210, Denmark

About this study

Part 1 - the double-blind (DB) part: The active medication arm will be given co-administration of 0.5 mg tesofensine/50 mg metoprolol daily for 24 weeks. The placebo arm will receive matching placebo tablets.

Part 2 - the open-label extension (OLE) part: All active participants at the end of the double-blind part will be given the active medication 0.5 mg tesofensine/50 mg metoprolol daily for 24 weeks.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • Informed consent obtained before any trial-related activities
  • Males and females, aged 18-75
  • Confirmed diagnosis of HIO
  • BMI ≥27 kg/m2 (where overweight is related to the HIO)

Exclusion criteria

  • Blood Pressure (BP) ≥160/90 mmHg
  • Heart rate (HR) ≥ 90, <50 bpm
  • Type 1 diabetes, Cushings disease, acromegaly, hypophysitis, infiltrative diseases or Prader-Willi syndrome
  • Heart failure New York Heart Association (NYHA) level II or greater, decompensated heart failure
  • Previous myocardial infarction or stroke within the last 5 years

Treatment and study plan

Tesofensine/Metoprolol

Drug

During Part 1 subjects will be randomized to treatment with co-administration of 0.5 mg tesofensine/50mg metoprolol (active medication)

Placebo

Drug

During Part 1 subjects will be randomized to matching placebo tesofensine and placebo metoprolol

Primary outcomes

  1. Number of Participants With Treatment Emergent Adverse Events

    Time frame: from Baseline to week 24

    Number and percentage of participants with adverse events in each of the two treatment arms

  2. Number of Participants With at Least One Mild, Moderate or Severe Adverse Event

    Time frame: from Baseline to week 24

    Number and percentage of participants with mild, moderate or severe adverse events in each of the two treatment arms.

  3. Participants (Number and Percentage) With and Type of Serious Adverse Events

    Time frame: from Baseline to week 24

    Number and percentage of participants with at least one serious adverse event, indicating type, in each of the two treatment arms

  4. Safety as Assessed by Systolic Blood Pressure [mmHg]

    Time frame: from Baseline to week 24

    Systolic blood pressure in mmHg measured at each visit in each of the two treatment arms

  5. Safety as Assessed by Diastolic Blood Pressure [mmHg]

    Time frame: from Baseline to week 24

    Diastolic blood pressure in mmHg measured at each visit in each of the two treatment arms

  6. Safety as Assessed by Heart Rate [Bpm]

    Time frame: from Baseline to week 24

    Heart rate measured in beats per minute (bpm) at each visit in each of the two treatment arms

  7. Safety as Assessed by Hematology Parameters

    Time frame: from Baseline to week 24

    Number and percentage of deviations from normal range (as defined by the investigational site's laboratory) for hemoglobin, platelet counts, white cells count, differential counts at baseline, week 12 and week 24 in each of the two treatment arms

  8. Safety as Assessed by Electrolytes and Creatinine

    Time frame: from Baseline to week 24

    Number and percentage of deviations from normal range (as defined by the investigational site's laboratory) for sodium, potassium, creatinine at each visit in each of the two treatment arms

  9. Safety as Assessed by Liver and Kidney Function Tests

    Time frame: from Baseline to week 24

    Number and percentage of deviations from normal range (as defined by the investigational site's laboratory) for gamma glutamyl transferase (GGT), aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), glomerular filtration rate (GFR), and urea at baseline, week 12, and week 24 in each of the two treatment arms

Secondary outcomes

  1. Composite Satiety Score (CSS)

    Time frame: from baseline to week 24, from baseline to week 48 and from week 24 to week 48

    Change in satiety and appetite using the CSS from Baseline to week 24, from Baseline to week 48 and from week 24 to week 48 measured at each visit for each of the two treatment arms

    Full name of the scale: composite satiety score (CSS), sometimes referred to as "appetite suppression score". Range of values is 0-100; lower the value, hungrier a person is. CSS = (satiety + fullness + [100 - hunger] + [100 - prospective food consumption]) / 4. The four variables included are measured by visual analog scales (0-100 mm)

  2. Body Weight

    Time frame: from baseline to week 24, from baseline to week 48 and from week 24 to week 48

    Change in body weight from baseline to week 24, from baseline to 48 and from week 24 to week 48 measured at each visit for each of the two treatment arms

  3. Body Composition - Fat Mass

    Time frame: from baseline to week 24, from baseline to week 48 and from week 24 to week 48

    Change in body fat mass as measured in kg by DXA scan measured at baseline, week 24 and week 48 for each of the two treatment arms. mITT observed values.

  4. Body Composition - Lean Body Mass

    Time frame: from baseline to week 24, from baseline to week 48 and from week 24 to week 48

    Change in lean body mass as measured in kg by DXA scan measured at baseline, week 24 and week 48 for each of the two treatment arms. mITT observed values.

  5. Glycemic Control - HbA1c

    Time frame: from baseline to week 24, from baseline to week 48 and from week 24 to week 48

    Change in HbA1c from baseline to week 24, baseline to week 48 and week 24 to week 48 for each of the two treatment arms. mITT observed values.

  6. Glycemic Control - Fasting Plasma Glucose

    Time frame: from baseline to week 24, from baseline to week 48 and from week 24 to week 48

    Change in fasting plasma glucose from baseline to week 24, baseline to week 48 and week 24 to week 48 measured at each visit for each of the two treatments arms. mITT observed values.

  7. Craving for Something Sweet, Salty, Meat/Fish, or Fatty

    Time frame: from baseline to week 24, from baseline to week 48 and from week 24 to week 48

    Change in craving for something sweet, salty, meat/fish, or fatty by the use of visual analogue scales (VAS) from baseline to week 24, from baseline to week 48, and from week 24 to week 48

    The VAS consisted of a 100-mm horizontal line; subjects placed a vertical line on the VAS to indicate the level of intensity of their food craving. The VAS value is the distance in mm (0-100 mm) from the left end of the line to the subject's vertical line (higher value represents less craving).

    mITT observed values.

  8. Thirst

    Time frame: from baseline to week 24, from baseline to week 48 and from week 24 to week 48

    Change in thirst by the use of a visual analog scale (VAS) from baseline to week 24, from baseline to week 48, and from week 24 to week 48

    The VAS consisted of a 100-mm horizontal line; subjects placed a vertical line on the VAS to indicate the level of intensity of their thirst. The VAS value is the distance in mm (0-100 mm) from the left end of the line to the subject's vertical line (higher value represents an increase in perception of thirst).

    mITT observed values.

  9. Waist Circumference

    Time frame: from baseline to week 24, from baseline to week 48 and from week 24 to week 48

    Change in waist circumference from baseline to week 24, from baseline to week 48, and from week 24 to week 48. mITT observed values.

  10. Lipid Profile

    Time frame: from baseline to week 24, from baseline to week 48 and from week 24 to week 48

    Change in lipid profile from baseline to week 24, from baseline to week 48, and from week 24 to week 48. mITT observed values.

  11. Quality of Life - SF-36

    Time frame: from baseline to week 24, from baseline to week 48 and from week 24 to week 48

    Change in quality of life by use of the Short Form 36 Health Survey (SF-36) scores from baseline to week 24, from baseline to week 48, and from week 24 to week 48

    The physical component summary score includes the aggregated scores for scales of physical functioning, role-physical, bodily pain, and general health. The mental health component summary score includes the aggregated scores for scales of vitality, social functioning, role-emotional, and mental health. Scores range from 0 to 100; higher score indicates better health.

    mITT observed values.

  12. Number of Participants With Adverse Event(s) and/or Serious Adverse Event(s) - Open-label Extension

    Time frame: from week 24 to week 48

    Number of participants with adverse event(s) and/or serious adverse event(s) reported from week 24 to week 48

  13. Blood Pressure (Change)

    Time frame: from baseline to week 24, from baseline to week 48 and from week 24 to week 48

    Change in blood pressure from baseline to week 24, from baseline to week 48, and from week 24 to week 48. mITT observed values.

  14. 24 Hours Blood Pressure

    Time frame: from baseline to week 12 and baseline to week 24

    Changes in 24 hours blood pressure from baseline to week 12 and baseline to week 24

  15. Plasma Trough Concentrations

    Time frame: baseline to week 48

    Plasma trough concentrations of tesofensine, metabolite NS2360 and metoprolol for the active arm (the first 24 weeks and then continuously up to week 48) and placebo arm (start of treatment at week 25 and then continuously up to week 48). mITT observed values.

  16. 48 Hours Heart Rate and QT Interval at Baseline, Week 12 and Week 24

    Time frame: baseline, week 12 and week 24

    For Part 1, 48 hours HR and QT interval from week 12 to week 24 were not recorded in the database and analysis of changes not evaluated. Instead, abnormal findings over visits were summarized.

    Abnormal ECG findings detected in the three Tesomet treated subjects are:

    • QTc prolongation (466 ms)
    • Bradycardia (56 bpm)
    • QTc prolongation (460 ms) All were considered not clinically significant.

  17. Heart Rate (Change)

    Time frame: from baseline to week 24, from baseline to week 48 and from week 24 to week 48

    Change in heart rate from baseline to week 24, from baseline to week 48, and from week 24 to week 48. mITT observed values.

Sponsors and collaborators

Lead sponsor

Saniona

Industry

Registry information

Official study title

A 24-week Phase 2, Double-blind, Randomized, Placebo- Controlled, Single-center Safety and Efficacy Study to Evaluate Overall Safety and Tolerability of Co-administration of Tesofensine and Metoprolol in Subjects With Hypothalamic Injury-induced Obesity (HIO), and With a 24-week Open-label Extension, in Total 48 Weeks

Important dates

Study start
2019
Primary completion
2020
Study completion
2020
First posted
Feb 19, 2019
Registry last updated
Feb 13, 2024

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.