Study to Investigate the Pharmacokinetic Profile

Phase 1

Completed

• Conditions: Healthy Male Subjects
• Interventions: 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

• Registration Number: NCT03286829
• Lead Sponsor: Saniona

Brief Summary

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

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 Timeline

• Study First Submitted: 2017-09-05
• Study First Submitted QC: 2017-09-14
• Study First Posted: 2017-09-19
• Study Start: 2017-12-18
• Primary Completion: 2018-02-06
• Study Completion: 2018-02-06
• Results First Submitted: 2020-04-21
• Status Verified: 2020-05
• Results First Submitted QC: 2020-05-04
• Last Update Submitted: 2020-05-04
• Results First Posted: 2020-05-14
• Last Update Posted: 2020-05-14

Recruitment & Eligibility

• Status: COMPLETED
• Sex: Male
• Target Recruitment: 60

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Tesomet "Low dose" in fasted condition	Comperator 1 mg tesofensine, 25 mg commercial IR metoprolol, 75 mg commercial ER metoprolol, 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)
Comperator	Tesomet "High dose" in fasted condition	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
Tesomet "High dose" in fasted condition	Comperator 1 mg tesofensine, 25 mg commercial IR metoprolol, 75 mg commercial ER metoprolol, 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)
Comperator	Tesomet "Low dose" in fasted condition	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
Comperator	Tesomet "High dose" in fed condition	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
Tesomet "High dose" in fed condition	Tesomet "High dose" in fasted condition	A Tesomet FDC tablet (20 mg immediate IR metoprolol, 1 mg tesofensine, 80 mg ER metoprolol in fed condition ("High" dose)
Tesomet "High dose" in fed condition	Comperator 1 mg tesofensine, 25 mg commercial IR metoprolol, 75 mg commercial ER metoprolol, fasted condition.	A Tesomet FDC tablet (20 mg immediate IR metoprolol, 1 mg tesofensine, 80 mg ER metoprolol in fed condition ("High" dose)

Primary Outcome Measures

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

Secondary Outcome Measures

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

Trial Locations

Locations (1)

Early Phase Clinical Unit;Klinikum Westend, Haus 31; 🇩🇪 Berlin, Germany