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

• ClinicalTrials.gov Identifier: NCT03845075
• Recruitment Status: Completed
• First Posted: February 19, 2019
• Last Update Posted: January 8, 2021
• Sponsor: Saniona
• Information provided by (Responsible Party): Saniona

Study Description

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, followed by
• Part 2: 24 weeks open-label extension - 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

Condition or disease	Intervention/treatment	Phase
Hypothalamic Injury-induced Obesity (HIO)	Drug: Tesofensine; Drug: Placebo	Phase 2

Detailed Description:

Part 1 - the double-blind 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 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 Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 21 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• 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
• Actual Study Start Date: February 20, 2019
• Actual Primary Completion Date: October 16, 2020
• Actual Study Completion Date: October 16, 2020

Arms and Interventions

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; 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 tablets.	Drug: Placebo; During Part 1 subjects will be randomized to matching placebo treatment with co-administration of 0.5 mg tesofensine/50mg metoprolol

Outcome Measures

Primary Outcome Measures :

1. Frequency of treatment emergent adverse events [ Time Frame: from Baseline to week 24 ]
   Number and percentage of adverse events in each of the two treatment arms
2. Severity of treatment emergent adverse events [ Time Frame: from Baseline to week 24 ]
   Number and percentage of mild, moderate and severe adverse events in each of the two treatment arms
3. Frequency and type of serious adverse events [ Time Frame: from Baseline to week 24 ]
   Number, percentage and type of serious adverse events 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 [b/min] [ Time Frame: from Baseline to week 24 ]
   Heart rate measured in 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 for hemoglobin, platelet counts, white cells count, differential counts at baseline, week 14 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 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 for gamma glutamyl transferase, aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, glomerular filtration rate and urea at baseline, week 14 and week 24 in each of the two treatment arms

Secondary Outcome Measures :

1. Composite satiety score (CSS) [ Time Frame: from baseline 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 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 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
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
5. Glycemic control - HbA1c [ Time Frame: from baseline to week 48 ]
   Change in HbA1c from baseline to week 24, baseline to week 48 and week 24 to week 48 measured at baseline, week 14, week 24, week 36 and week 48 for each of the two treatment arms
6. Glycemic control - Fasting Plasma Glucose [ Time Frame: from baseline to week 48 ]
   Change in fasting plasma glucose from baseline to week 24, baseline to week 48 and week 24 to wee 48 measured at each visit for each of the two treatments arms

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 75 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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:

• BP ≥160/90 mmHg
• 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

Contacts and Locations

Locations

Denmark

Rigshospitalet

Copenhagen, Denmark, 210

Sponsors and Collaborators

Saniona

Investigators

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

  Study Documents (Full-Text)

Documents provided by Saniona:

Study Protocol  [PDF] December 10, 2019

Statistical Analysis Plan  [PDF] May 17, 2019

More Information

• Responsible Party: Saniona
• ClinicalTrials.gov Identifier: NCT03845075
• Other Study ID Numbers: TM005
• First Posted: February 19, 2019
• Last Update Posted: January 8, 2021
• Last Verified: January 2021

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:

Obesity; Wounds and Injuries; Overnutrition; Nutrition Disorders; Overweight; Body Weight