Study to Investigate the Pharmacokinetic Profile

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.

• Tesomet "High dose" in fasted condition (Drug), also known as Tesofensine, Metoprolol: 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.
• Tesomet "Low dose" in fasted condition (Drug), also known as Tesofensine, Metoprolol: 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.
• Comperator 1 mg tesofensine, 25 mg commercial IR metoprolol, 75 mg commercial ER metoprolol, fasted condition. (Drug), also known as Tesofensine, Metoprolol: 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.
• Tesomet "High dose" in fed condition (Drug), also known as Tesofensine, Metoprolol: 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.

Primary outcomes

• 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 outcomes

• 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

Sex: Male, ages: 18 Years to 55 Years, accepts healthy volunteers

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.

Participant flow

Outcome results

• AUC0-48 (Primary), Geometric mean, ng*hr/mL: Tesomet "High Dose" in Fasted Condition 32.06 +/- 26.9; Tesomet "Low Dose" in Fasted Condition 6.491 +/- 25.1; Comparator 45.89 +/- 21.9; Tesomet "High Dose" in Fed Condition 30.14 +/- 18.6
• Cmax (Secondary), Geometric mean, ng/mL: Tesomet "High Dose" in Fasted Condition 0.9528 +/- 25.5; Tesomet "Low Dose" in Fasted Condition 0.1934 +/- 23.6; Comparator 1.357 +/- 23.8; Tesomet "High Dose" in Fed Condition 0.8085 +/- 17.1
• Tmax (Secondary), Geometric mean, hours: Tesomet "High Dose" in Fasted Condition 6.12 +/- 5.98; Tesomet "Low Dose" in Fasted Condition 6.00 +/- 5.98; Comparator 6.00 +/- 3.98; Tesomet "High Dose" in Fed Condition 8.00 +/- 4.00

Adverse events

Time frame: 38days

Other adverse events by term

• Study Protocol (PDF, 2017-09-15)
• Informed Consent Form (PDF, 2017-09-18)
• Statistical Analysis Plan (PDF, 2018-01-19)

• Jorgen Drejer, PhD, Study director, Saniona