A Study to Examine the Effect of Tesofensine and Metoprolol on the 24-hour Mean Heart Rate

Study Overview
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Brief Summary
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A Phase 1 Study to Examine Pharmacodynamic Interaction Between Tesofensine and Metoprolol on 24-hours Mean Heart Rate

Detailed Description
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In this study, the dose-response relationship between tesofensine and metoprolol will be examined and thus the optimal dose of metoprolol to mitigate the effects of tesofensine on HR will be determined. HR is the primary endpoint because in the previous studies it has been shown to be the most affected safety endpoint by the effects of tesofensine.

Official Title
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A Phase 1 Study to Examine Pharmacodynamic Interaction Between Tesofensine and Metoprolol on 24-hours Mean Heart Rate

Conditions
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Phase 1

Intervention / Treatment
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* Drug: Metoprolol Succinate 25 MG
* Drug: Metoprolol Succinate 50 MG
* Drug: Metoprolol Succinate 100 MG


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subject voluntarily agrees to participate in this study and signs an Independent Ethics Committee (IEC)-approved informed consent prior to performing any of the Screening procedures. Male and female subjects between 18 to 60 years of age, inclusive, at Screening. Non-smokers (or other nicotine use) as determined by history (no nicotine use over the past 6 months) and by urine cotinine concentration (< 500 ng/mL) at Screening and admissions. Body mass index (BMI) between ≥ 27 and < 40 kg/m2 at Screening. Exclusion Criteria: Subject has history or evidence of any clinically significant cardiovascular, gastrointestinal, endocrinologic, hematologic, hepatic, immunologic, metabolic (e.g., diabetes), urologic, pulmonary (e.g., asthma or chronic obstructive pulmonary disease), neurologic, dermatologic, psychiatric, renal, and/or other major disease or malignancy as judged by the Investigator. Subject has any disorder that would interfere with the absorption, distribution, metabolism or excretion of drugs. Subject has a clinically significant abnormality following the Investigator's review of the physical examination, ECG and clinical study protocol-defined clinical laboratory tests at Screening or admission to the clinical unit or has any concurrent disease or condition that, in the opinion of the Investigator, would make the subject unsuitable for participation in the clinical study. One re-test is allowed, if (a) test result(s) is outside the limits. -

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 60 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Interventional Model Description: Each subject will participate in a Screening Period (Day 28 to Day 3), a Baseline Period (Day -2 to Day -1) and a Treatment Period (Day 1 to Day 24) and will have two Follow-up phone calls (Day 30 and Day 50).
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cohort 1<br>Tesofensine 0.25mg | Drug: Metoprolol Succinate 25 MG<br>* Metoprolol 25mg<br>* Other names: Metoprolol 25mg;Drug: Metoprolol Succinate 50 MG<br>* Metoprolol 50mg<br>Drug: Metoprolol Succinate 100 MG<br>* Metoprolol 100mg<br>|
| Experimental: Cohort 2<br>Tesofensine 0.50mg | Drug: Metoprolol Succinate 25 MG<br>* Metoprolol 25mg<br>* Other names: Metoprolol 25mg;Drug: Metoprolol Succinate 50 MG<br>* Metoprolol 50mg<br>Drug: Metoprolol Succinate 100 MG<br>* Metoprolol 100mg<br>|
| Experimental: Cohort 3<br>Tesofensine 0.75mg | Drug: Metoprolol Succinate 25 MG<br>* Metoprolol 25mg<br>* Other names: Metoprolol 25mg;Drug: Metoprolol Succinate 50 MG<br>* Metoprolol 50mg<br>Drug: Metoprolol Succinate 100 MG<br>* Metoprolol 100mg<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Dose-response relationship | The dose of metoprolol which will bring about no change in M24HR for each respective dose of tesofensine | Day 1 to Day 24 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mitigation effect | The dose of metoprolol which will mitigate the HR increasing effects of tesofensine | Day 1 to Day 24 |