Hypothalamic Injury-induced Obesity (HIO)Phase 2NCT03845075
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 Phase 2 study testing Tesofensine/Metoprolol in people with Hypothalamic Injury-induced Obesity (HIO), run by Saniona at 1 site in Denmark.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Hypothalamic Injury-induced Obesity (HIO)
- What is being tested?
- Tesofensine/Metoprolol
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 21 participants
- Where
- 1 siteDenmark
- Study dates
- 25 Feb 2019to 16 Oct 2020
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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)
Who cannot join
- 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
Trial locations and contacts
1 site in 1 country.
About this study
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
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
Read the 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.
- Being tested
- Tesofensine/Metoprolol, Placebo
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Tesofensine/MetoprololDrug
During Part 1 subjects will be randomized to treatment with co-administration of 0.5 mg tesofensine/50mg metoprolol (active medication)
PlaceboDrug
During Part 1 subjects will be randomized to matching placebo tesofensine and placebo metoprolol
| Study group | Role | What they receive |
|---|---|---|
| active arm | Experimental | The active medication arm will be given co-administration of 0.5 mg tesofensine/50 mg metoprolol daily for 24 weeks. Receives: Drug: Tesofensine/Metoprolol |
| placebo arm | Placebo comparator | The placebo arm will receive matching placebo tesofensine and placebo metoprolol. Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Participants With Treatment Emergent Adverse Events
Number and percentage of participants with adverse events in each of the two treatment arms
Measured: 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.
Measured: 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
Measured: 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
Measured: 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
Measured: 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
Measured: 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
Measured: 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
Measured: 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
Measured: from Baseline to week 24
Secondary outcomes (17)
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)
Measured: 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
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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
Measured: 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.
Measured: 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
Measured: 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.
Measured: 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.
Measured: 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.
Measured: from baseline to week 24, from baseline to week 48 and from week 24 to week 48
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Feb 2019
- Study start25 Feb 2019
- Primary completion16 Oct 2020
- Study completion16 Oct 2020
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Hypothalamic Injury-induced Obesity (HIO)Studies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 21 participants (actual)
Sponsor and investigators
- Lead sponsor
- Saniona
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Ulla Feldt-Rasmussen, MD, DMSc, Principal investigator, Department of Medical Endocrinology and metabolism Rigshospitalet,Copenhagen, DK
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03845075
- Sponsor's protocol ID
- TM005
- Status last verified
- Feb 2024
- First submitted
- 30 Jan 2019
- Last updated
- 13 Feb 2024
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 13 Feb 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT03845075
- Acronym / sponsor ID
- TM005
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 21 participants (actual)
- Lead sponsor
- SanionaIndustry (pharma, biotech, devices)
- Study start
- 25 Feb 2019 (actual)
- Primary completion
- 16 Oct 2020 (actual)
- Study completion
- 16 Oct 2020 (actual)
- First posted
- 19 Feb 2019 (actual)
- Results
- Posted 13 Feb 2024
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| active arm | Experimental | Drug: Tesofensine/MetoprololThe active medication arm will be given co-administration of 0.5 mg tesofensine/50 mg metoprolol daily for 24 weeks. |
| placebo arm | Placebo comparator | Drug: PlaceboThe placebo arm will receive matching placebo tesofensine and placebo metoprolol. |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- 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)
Key exclusion criteria (5 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Tesofensine/MetoprololDuring Part 1 subjects will be randomized to treatment with co-administration of 0.5 mg tesofensine/50mg metoprolol (active medication) | Drug | active arm |
| PlaceboDuring Part 1 subjects will be randomized to matching placebo tesofensine and placebo metoprolol | Drug | placebo arm |
Primary outcome
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
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.
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
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
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
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
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
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
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
17 secondary outcomes
Composite Satiety Score (CSS)
Time frame: from baseline to week 24, from baseline to week 48 and from week 24 to week 48
Body Weight
Time frame: from baseline to week 24, from baseline to week 48 and from week 24 to week 48
Body Composition - Fat Mass
Time frame: from baseline to week 24, from baseline to week 48 and from week 24 to week 48
Body Composition - Lean Body Mass
Time frame: from baseline to week 24, from baseline to week 48 and from week 24 to week 48
Glycemic Control - HbA1c
Time frame: from baseline to week 24, from baseline to week 48 and from week 24 to week 48
Glycemic Control - Fasting Plasma Glucose
Time frame: 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
Time frame: from baseline to week 24, from baseline to week 48 and from week 24 to week 48
Thirst
Time frame: from baseline to week 24, from baseline to week 48 and from week 24 to week 48
Waist Circumference
Time frame: from baseline to week 24, from baseline to week 48 and from week 24 to week 48
Lipid Profile
Time frame: from baseline to week 24, from baseline to week 48 and from week 24 to week 48
Quality of Life - SF-36
Time frame: 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
Time frame: from week 24 to week 48
Blood Pressure (Change)
Time frame: from baseline to week 24, from baseline to week 48 and from week 24 to week 48
24 Hours Blood Pressure
Time frame: from baseline to week 12 and baseline to week 24
Plasma Trough Concentrations
Time frame: baseline to week 48
48 Hours Heart Rate and QT Interval at Baseline, Week 12 and Week 24
Time frame: baseline, week 12 and week 24
Heart Rate (Change)
Time frame: from baseline to week 24, from baseline to week 48 and from week 24 to week 48
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 13 Feb 2024.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: No
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Ulla Feldt-Rasmussen, MD, DMSc principal investigator
Department of Medical Endocrinology and metabolism Rigshospitalet,Copenhagen, DK
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Tesofensine/Metoprolol in people with Hypothalamic Injury-induced Obesity (HIO), run by Saniona at 1 site in Denmark.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 13 Feb 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Denmark. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 13 Feb 2024). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of Participants With Treatment Emergent Adverse Events (time frame: from Baseline to week 24). The study lists 9 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 13 Feb 2024.