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

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

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

Study Overview

• Status: Completed
• Conditions: Hypothalamic Injury-induced Obesity (HIO)
• Intervention / Treatment: Drug: Tesofensine/Metoprolol; Drug: Placebo

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 21
• Phase: Phase 2

Contacts and Locations

Study Locations

• Denmark
  • Copenhagen, Denmark, 210
    • Rigshospitalet

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years to 71 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: active arm; The active medication arm will be given co-administration of 0.5 mg tesofensine/50 mg metoprolol daily for 24 weeks.	Drug: Tesofensine/Metoprolol; During Part 1 subjects will be randomized to treatment with co-administration of 0.5 mg tesofensine/50mg metoprolol (active medication)
Placebo Comparator: placebo arm; The placebo arm will receive matching placebo tesofensine and placebo metoprolol.	Drug: Placebo; During Part 1 subjects will be randomized to matching placebo tesofensine and placebo metoprolol

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Treatment Emergent Adverse Events	Number and percentage of participants with adverse events in each of the two treatment arms	from Baseline to week 24
Number of Participants With at Least One Mild, Moderate or Severe Adverse Event	Number and percentage of participants with mild, moderate or severe adverse events in each of the two treatment arms.	from Baseline to week 24
Participants (Number and Percentage) With and Type of Serious Adverse Events	Number and percentage of participants with at least one serious adverse event, indicating type, in each of the two treatment arms	from Baseline to week 24
Safety as Assessed by Systolic Blood Pressure [mmHg]	Systolic blood pressure in mmHg measured at each visit in each of the two treatment arms	from Baseline to week 24
Safety as Assessed by Diastolic Blood Pressure [mmHg]	Diastolic blood pressure in mmHg measured at each visit in each of the two treatment arms	from Baseline to week 24
Safety as Assessed by Heart Rate [Bpm]	Heart rate measured in beats per minute (bpm) at each visit in each of the two treatment arms	from Baseline to week 24
Safety as Assessed by Hematology Parameters	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	from Baseline to week 24
Safety as Assessed by Electrolytes and Creatinine	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	from Baseline to week 24
Safety as Assessed by Liver and Kidney Function Tests	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	from Baseline to week 24

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Composite Satiety Score (CSS)	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)	from baseline to week 24, from baseline to week 48 and from week 24 to week 48
Body Weight	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	from baseline to week 24, from baseline to week 48 and from week 24 to week 48
Body Composition - Fat Mass	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.	from baseline to week 24, from baseline to week 48 and from week 24 to week 48
Body Composition - Lean Body Mass	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.	from baseline to week 24, from baseline to week 48 and from week 24 to week 48
Glycemic Control - HbA1c	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.	from baseline to week 24, from baseline to week 48 and from week 24 to week 48
Glycemic Control - Fasting Plasma Glucose	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.	from baseline to week 24, from baseline to week 48 and from week 24 to week 48
Craving for Something Sweet, Salty, Meat/Fish, or Fatty	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.	from baseline to week 24, from baseline to week 48 and from week 24 to week 48
Thirst	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.	from baseline to week 24, from baseline to week 48 and from week 24 to week 48
Waist Circumference	Change in waist circumference from baseline to week 24, from baseline to week 48, and from week 24 to week 48. mITT observed values.	from baseline to week 24, from baseline to week 48 and from week 24 to week 48
Lipid Profile	Change in lipid profile from baseline to week 24, from baseline to week 48, and from week 24 to week 48. mITT observed values.	from baseline to week 24, from baseline to week 48 and from week 24 to week 48
Quality of Life - SF-36	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.	from baseline to week 24, from baseline to week 48 and from week 24 to week 48
Number of Participants With Adverse Event(s) and/or Serious Adverse Event(s) - Open-label Extension	Number of participants with adverse event(s) and/or serious adverse event(s) reported from week 24 to week 48	from week 24 to week 48
Blood Pressure (Change)	Change in blood pressure from baseline to week 24, from baseline to week 48, and from week 24 to week 48. mITT observed values.	from baseline to week 24, from baseline to week 48 and from week 24 to week 48
24 Hours Blood Pressure	Changes in 24 hours blood pressure from baseline to week 12 and baseline to week 24	from baseline to week 12 and baseline to week 24
Plasma Trough Concentrations	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.	baseline to week 48
48 Hours Heart Rate and QT Interval at 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.	baseline, week 12 and week 24
Heart Rate (Change)	Change in heart rate from baseline to week 24, from baseline to week 48, and from week 24 to week 48. mITT observed values.	from baseline to week 24, from baseline to week 48 and from week 24 to week 48

Collaborators and Investigators

• Sponsor: Saniona
• Investigators: Principal Investigator: Ulla Feldt-Rasmussen, MD, DMSc, Department of Medical Endocrinology and metabolism Rigshospitalet,Copenhagen, DK

Study record dates

Study Major Dates

• Study Start (Actual): February 25, 2019
• Primary Completion (Actual): October 16, 2020
• Study Completion (Actual): October 16, 2020

Study Registration Dates

• First Submitted: January 30, 2019
• First Submitted That Met QC Criteria: February 18, 2019
• First Posted (Actual): February 19, 2019

Study Record Updates

• Last Update Posted (Estimated): February 13, 2024
• Last Update Submitted That Met QC Criteria: February 9, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Overnutrition; Nutrition Disorders; Overweight; Body Weight; Obesity; Wounds and Injuries; Physiological Effects of Drugs; Adrenergic beta-Antagonists; Adrenergic Antagonists; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Anti-Arrhythmia Agents; Antihypertensive Agents; Autonomic Agents; Peripheral Nervous System Agents; Sympatholytics; Adrenergic beta-1 Receptor Antagonists; Metoprolol
• Other Study ID Numbers: TM005

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