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

• ClinicalTrials.gov Identifier: NCT03488719
• Recruitment Status: Completed
• First Posted: April 5, 2018
• Last Update Posted: February 10, 2020
• Sponsor: Saniona
• Information provided by (Responsible Party): Saniona

Study Description

Brief Summary:

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

Condition or disease	Intervention/treatment	Phase
Phase 1	Drug: Metoprolol Succinate 25 MG; Drug: Metoprolol Succinate 50 MG; Drug: Metoprolol Succinate 100 MG	Phase 1

Detailed Description:

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.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 37 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Intervention 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 (Participant, Care Provider, Investigator)
• Masking Description: Tesofensine dosing will be performed open-label. Metoprolol dosing will be performed "single-blind".
• Primary Purpose: Treatment
• Official Title: A Phase 1 Study to Examine Pharmacodynamic Interaction Between Tesofensine and Metoprolol on 24-hours Mean Heart Rate
• Actual Study Start Date: July 10, 2018
• Actual Primary Completion Date: November 22, 2018
• Actual Study Completion Date: July 26, 2019

Arms and Interventions

Arm	Intervention/treatment
Experimental: Cohort 1; Tesofensine 0.25mg	Drug: Metoprolol Succinate 25 MG; Metoprolol 25mg; Other Name: Metoprolol 25mg; Drug: Metoprolol Succinate 50 MG; Metoprolol 50mg; Drug: Metoprolol Succinate 100 MG; Metoprolol 100mg
Experimental: Cohort 2; Tesofensine 0.50mg	Drug: Metoprolol Succinate 25 MG; Metoprolol 25mg; Other Name: Metoprolol 25mg; Drug: Metoprolol Succinate 50 MG; Metoprolol 50mg; Drug: Metoprolol Succinate 100 MG; Metoprolol 100mg
Experimental: Cohort 3; Tesofensine 0.75mg	Drug: Metoprolol Succinate 25 MG; Metoprolol 25mg; Other Name: Metoprolol 25mg; Drug: Metoprolol Succinate 50 MG; Metoprolol 50mg; Drug: Metoprolol Succinate 100 MG; Metoprolol 100mg

Outcome Measures

Primary Outcome Measures :

1. Dose-response relationship [ Time Frame: Day 1 to Day 24 ]
   The dose of metoprolol which will bring about no change in M24HR for each respective dose of tesofensine

Secondary Outcome Measures :

1. Mitigation effect [ Time Frame: Day 1 to Day 24 ]
   The dose of metoprolol which will mitigate the HR increasing effects of tesofensine

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 60 Years (Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Criteria

Inclusion Criteria:

1. 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.
2. Male and female subjects between 18 to 60 years of age, inclusive, at Screening.
3. 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.
4. Body mass index (BMI) between ≥ 27 and < 40 kg/m2 at Screening.

Exclusion Criteria:

1. 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.
2. Subject has any disorder that would interfere with the absorption, distribution, metabolism or excretion of drugs.

3. 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.

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Contacts and Locations

Locations

Germany

Parexel Early Phase Klinikum Westend

Berlin, Germany, 14050

Sponsors and Collaborators

Saniona

Investigators

• Study Director: Kim Krogsgaard, MD, DMSc; Saniona

More Information

• Responsible Party: Saniona
• ClinicalTrials.gov Identifier: NCT03488719
• Other Study ID Numbers: TM004
• First Posted: April 5, 2018
• Last Update Posted: February 10, 2020
• Last Verified: February 2020

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
• Product Manufactured in and Exported from the U.S.: No

Additional relevant MeSH terms:

Metoprolol; Anti-Arrhythmia Agents; Antihypertensive Agents; Sympatholytics; Autonomic Agents; Peripheral Nervous System Agents; Physiological Effects of Drugs; Adrenergic beta-1 Receptor Antagonists; Adrenergic beta-Antagonists; Adrenergic Antagonists; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action