Clinical trial 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)
Official 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Hypothalamic Injury-induced Obesity (HIO)
Lead sponsor: Saniona
Sponsor class: INDUSTRY
First posted: 2019-02-19
Enrollment: 21
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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

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.

Eligibility criteria: 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

Primary outcomes:
measure: Number of Participants With Treatment Emergent Adverse Events
timeFrame: from Baseline to week 24
measure: Number of Participants With at Least One Mild, Moderate or Severe Adverse Event
timeFrame: from Baseline to week 24
measure: Participants (Number and Percentage) With and Type of Serious Adverse Events
timeFrame: from Baseline to week 24
measure: Safety as Assessed by Systolic Blood Pressure [mmHg]
timeFrame: from Baseline to week 24
measure: Safety as Assessed by Diastolic Blood Pressure [mmHg]
timeFrame: from Baseline to week 24
measure: Safety as Assessed by Heart Rate [Bpm]
timeFrame: from Baseline to week 24
measure: Safety as Assessed by Hematology Parameters
timeFrame: from Baseline to week 24
measure: Safety as Assessed by Electrolytes and Creatinine
timeFrame: from Baseline to week 24
measure: Safety as Assessed by Liver and Kidney Function Tests
timeFrame: from Baseline to week 24
Secondary outcomes:
measure: Composite Satiety Score (CSS)
timeFrame: from baseline to week 24, from baseline to week 48 and from week 24 to week 48
measure: Body Weight
timeFrame: from baseline to week 24, from baseline to week 48 and from week 24 to week 48
measure: Body Composition - Fat Mass
timeFrame: from baseline to week 24, from baseline to week 48 and from week 24 to week 48
measure: Body Composition - Lean Body Mass
timeFrame: from baseline to week 24, from baseline to week 48 and from week 24 to week 48
measure: Glycemic Control - HbA1c
timeFrame: from baseline to week 24, from baseline to week 48 and from week 24 to week 48
measure: Glycemic Control - Fasting Plasma Glucose
timeFrame: from baseline to week 24, from baseline to week 48 and from week 24 to week 48
measure: Craving for Something Sweet, Salty, Meat/Fish, or Fatty
timeFrame: from baseline to week 24, from baseline to week 48 and from week 24 to week 48
measure: Thirst
timeFrame: from baseline to week 24, from baseline to week 48 and from week 24 to week 48
measure: Waist Circumference
timeFrame: from baseline to week 24, from baseline to week 48 and from week 24 to week 48
measure: Lipid Profile
timeFrame: from baseline to week 24, from baseline to week 48 and from week 24 to week 48
measure: Quality of Life - SF-36
timeFrame: from baseline to week 24, from baseline to week 48 and from week 24 to week 48
measure: Number of Participants With Adverse Event(s) and/or Serious Adverse Event(s) - Open-label Extension
timeFrame: from week 24 to week 48
measure: Blood Pressure (Change)
timeFrame: from baseline to week 24, from baseline to week 48 and from week 24 to week 48
measure: 24 Hours Blood Pressure
timeFrame: from baseline to week 12 and baseline to week 24
measure: Plasma Trough Concentrations
timeFrame: baseline to week 48
measure: 48 Hours Heart Rate and QT Interval at Baseline, Week 12 and Week 24
timeFrame: baseline, week 12 and week 24
measure: Heart Rate (Change)
timeFrame: from baseline to week 24, from baseline to week 48 and from week 24 to week 48
Other outcomes:
Locations:
city: Copenhagen
country: Denmark
facility: Rigshospitalet
Study officials:
affiliation: Department of Medical Endocrinology and metabolism Rigshospitalet,Copenhagen, DK
name: Ulla Feldt-Rasmussen, MD, DMSc
role: PRINCIPAL_INVESTIGATOR
References: