Study to Investigate the Pharmacokinetic Profile

A Randomized, Open-label, Single-dose, Parallel-arm, Phase 1 Study to Investigate the Pharmacokinetic Profile of a Fixed-Dose Combination Tablet of Tesofensine and Metoprolol (Tesomet) and Co-Administration of Tesofensine Plus Commercial Metoprolol in Adult Healthy Subjects

A randomized, open-label, single-dose, parallel-arm, Phase 1 study to investigate the pharmacokinetic profile of a fixed-dose combination tablet of tesofensine and metoprolol (Tesomet) and co-administration of tesofensine plus commercial metoprolol in adult healthy subjects

Study Overview

• Status: Completed
• Conditions: Healthy Male Subjects
• Intervention / Treatment: Drug: Comperator 1 mg tesofensine, 25 mg commercial IR metoprolol, 75 mg commercial ER metoprolol, fasted condition.; Drug: Tesomet "High dose" in fasted condition; Drug: Tesomet "Low dose" in fasted condition; Drug: Tesomet "High dose" in fed condition

Detailed Description

This is a randomized, open-label, parallel-arm study in 60 healthy male subjects who meet the inclusion and none of the exclusion criteria for the study. Each subject will participate in a screening period, a baseline period (the day preceding drug administration), and a single-dose treatment period with an on-site observation period of at least 48 hours after the dose.

• Study Type: Interventional
• Enrollment (Actual): 60
• Phase: Phase 1

Contacts and Locations

Study Locations

• Germany
  • Berlin, Germany, 14050
    • Early Phase Clinical Unit;Klinikum Westend, Haus 31

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 53 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

Description

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 Visit procedures.
2. Males between 18 to 55 years of age, inclusive, at the Screening Visit.
3. Nonsmokers (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 the Screening Visit and admission.
4. BMI between 18.5 and 30.0 kg/m2, inclusive, at the Screening Visit.
5. Healthy, determined by pre-study medical evaluation (medical history, physical examination, vital signs, 12-lead ECG and clinical laboratory evaluations).

Exclusion Criteria:

1. Subject has history or evidence of any clinically significant cardiovascular, gastrointestinal, endocrinologic, hematologic, hepatic, immunologic, metabolic, urologic, pulmonary, 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 history of alcohol and/or illicit drug abuse within 2 years of entry.
4. Subject is unwilling to avoid consumption of coffee and caffeine-containing beverages within 48 hours prior to admission until discharge from the clinical site.
5. Subject is unwilling to avoid use of alcohol or alcohol-containing foods, medications or beverages, within 48 hours prior to admission until discharge from the clinical site.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Tesomet "High dose" in fasted condition; A Tesomet FDC tablet (20 mg immediate release [IR] metoprolol, 1 mg tesofensine, 80 mg extended release [ER] metoprolol) in fasted condition ("High" dose)	Drug: Comperator 1 mg tesofensine, 25 mg commercial IR metoprolol, 75 mg commercial ER metoprolol, fasted condition.; To evaluate the PK profile and relative bioavailability of a single dose of the Tesomet fixed-dose combination (FDC) tablet and co-administration of tesofensine plus commercial metoprolol.; Other Names: Tesofensine; Metoprolol
Experimental: Tesomet "Low dose" in fasted condition; Treatment B (Test 2): A Tesomet FDC tablet (5 mg immediate IR metoprolol, 0.2 mg tesofensine, 20 mg ER metoprolol) in fasted condition. ("Low" dose)	Drug: Comperator 1 mg tesofensine, 25 mg commercial IR metoprolol, 75 mg commercial ER metoprolol, fasted condition.; To evaluate the PK profile and relative bioavailability of a single dose of the Tesomet fixed-dose combination (FDC) tablet and co-administration of tesofensine plus commercial metoprolol.; Other Names: Tesofensine; Metoprolol
Active Comparator: Comperator; 1 mg tesofensine (2 tablets of 0.5 mg), 25 mg commercial IR metoprolol (1 tablet of 25 mg), 75 mg commercial ER metoprolol (1 tablet of 25 mg ER metoprolol and 1 tablet of 50 mg ER metoprolol), fasted condition	Drug: Tesomet "High dose" in fasted condition; To evaluate the PK profile and relative bioavailability of a single dose of the Tesomet fixed-dose combination (FDC) tablet and co-administration of tesofensine plus commercial metoprolol.; Other Names: Tesofensine; Metoprolol; Drug: Tesomet "Low dose" in fasted condition; To evaluate the PK profile and relative bioavailability of a single dose of the Tesomet fixed-dose combination (FDC) tablet and co-administration of tesofensine plus commercial metoprolol.; Other Names: Tesofensine; Metoprolol; Drug: Tesomet "High dose" in fed condition; To evaluate the PK profile and relative bioavailability of a single dose of the Tesomet fixed-dose combination (FDC) tablet and co-administration of tesofensine plus commercial metoprolol.; Other Names: Tesofensine; Metoprolol
Experimental: Tesomet "High dose" in fed condition; A Tesomet FDC tablet (20 mg immediate IR metoprolol, 1 mg tesofensine, 80 mg ER metoprolol in fed condition ("High" dose)	Drug: Comperator 1 mg tesofensine, 25 mg commercial IR metoprolol, 75 mg commercial ER metoprolol, fasted condition.; To evaluate the PK profile and relative bioavailability of a single dose of the Tesomet fixed-dose combination (FDC) tablet and co-administration of tesofensine plus commercial metoprolol.; Other Names: Tesofensine; Metoprolol; Drug: Tesomet "High dose" in fasted condition; To evaluate the PK profile and relative bioavailability of a single dose of the Tesomet fixed-dose combination (FDC) tablet and co-administration of tesofensine plus commercial metoprolol.; Other Names: Tesofensine; Metoprolol

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
AUC0-48	Area under the concentration-time curve from pre-dose (time 0) to 48 hours post-dose calculated using the linear-log trapezoidal rule	Pre-dose and 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 20, 24, 30, 36 and 48 hours post-dose

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cmax	Maximum tesofensine and metoprolol concentrations determined directly from the concentration-time profile	Pre-dose and 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 20, 24, 30, 36 and 48 hours post-dose
Tmax	Time of maximum tesofensine and metoprolol concentrations determined directly from the concentration-time profile	Pre-dose and 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 20, 24, 30, 36 and 48 hours post-dose

Collaborators and Investigators

• Sponsor: Saniona
• Investigators: Study Director: Jorgen Drejer, PhD, Saniona

Study record dates

Study Major Dates

• Study Start (Actual): December 18, 2017
• Primary Completion (Actual): February 6, 2018
• Study Completion (Actual): February 6, 2018

Study Registration Dates

• First Submitted: September 5, 2017
• First Submitted That Met QC Criteria: September 14, 2017
• First Posted (Actual): September 19, 2017

Study Record Updates

• Last Update Posted (Actual): May 14, 2020
• Last Update Submitted That Met QC Criteria: May 4, 2020
• Last Verified: May 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Adrenergic beta-Antagonists; Adrenergic Antagonists; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Anti-Arrhythmia Agents; Antihypertensive Agents; Autonomic Agents; Peripheral Nervous System Agents; Sympatholytics; Adrenergic beta-1 Receptor Antagonists; Metoprolol
• Other Study ID Numbers: TM003

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No