Hypothalamic Injury-induced Obesity (HIO) Clinical Trial
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
| Verified date | February 2024 |
| Source | Saniona |
| Contact | n/a |
| Is FDA regulated | No |
| Health authority | |
| Study type | Interventional |
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
| Status | Completed |
| Enrollment | 21 |
| Est. completion date | October 16, 2020 |
| Est. primary completion date | October 16, 2020 |
| Accepts healthy volunteers | No |
| Gender | All |
| Age group | 18 Years to 75 Years |
| Eligibility | 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 |
| Country | Name | City | State |
|---|---|---|---|
| Denmark | Rigshospitalet | Copenhagen |
| Lead Sponsor | Collaborator |
|---|---|
| Saniona |
Denmark,
| Type | Measure | Description | Time frame | Safety issue |
|---|---|---|---|---|
| Primary | 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 | |
| Primary | 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 | |
| Primary | 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 | |
| Primary | 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 | |
| Primary | 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 | |
| Primary | 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 | |
| Primary | 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 | |
| Primary | 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 | |
| Primary | 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 | 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 | |
| Secondary | 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 | |
| Secondary | 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 | |
| Secondary | 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 | |
| Secondary | 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 | |
| Secondary | 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 | |
| Secondary | 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 | |
| Secondary | 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 | |
| Secondary | 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 | |
| Secondary | 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 | |
| Secondary | 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 | |
| Secondary | 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 | |
| Secondary | 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 | |
| Secondary | 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 | |
| Secondary | 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 | |
| Secondary | 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 | |
| Secondary | 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 |