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

Inclusion Criteria

• Subject voluntarily agreed to participate in this study and signed 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.
• Overweight and obese subjects with a body mass index (BMI) between ≥ 27 and 1.2 x upper limit of normal (ULN)
• Alanine aminotransferase (ALT) > 1.1 x upper limit of normal (ULN)
• Subject had a pulse 90 beats per minute (bpm); systolic blood pressure (SBP) 140 mmHg; diastolic blood pressure (DBP) 90 mmHg (using the mean of triplicate measurements) at Screening or admission. One re-test was allowed, if (a) test result(s) was outside these limits.
• History of any clinically significant cardiac arrhythmia. Subject had a corrected QT interval using Fridericia's formula (QTcF) interval > 450 msec or 2nd or 3rd degree atrioventricular (AV) block, high-grade sinoatrial block or PQ interval > 0.24 seconds at Screening (using the mean of triplicate measurements). If a mean ECG parameter of a triplicate ECG exceeded the limits above, an additional triplicate ECG could have been taken. If this also gave an abnormal result, the subject was excluded. Also, the following cardiac conditions led to exclusion of the subjects: Untreated heart failure (pulmonary oedema, impaired blood flow or hypotension) and continuous or intermittent treatment leading to an increased contractility of the heart muscle (beta-receptor agonism); sick sinus syndrome; cardiogenic shock; severe peripheral arterial circulatory disturbances.
• Had a creatinine value exceeding the ULN.
• Subject had a positive test for hepatitis B surface antigen (HBsAg), or hepatitis B core antibody (indicative of active hepatitis B), hepatitis A virus antibodies (immunoglobulin M), hepatitis C virus (HCV) antibodies or human immunodeficiency virus (HIV) type 1 and/or type 2 antibodies.
• Use of any prescribed or non-prescribed drugs (including vitamins, natural and herbal remedies, e.g., St. John's Wort) in the 2 weeks prior to admission or 5 half-lives of the drug, whichever was longer, except for the occasional use of paracetamol (up to 2 g/day) or other non-steroidal anti-inflammatory drugs (NSAIDs) and hormonal contraception for female subjects.
• Subject had history of alcohol and/or illicit drug abuse within 2 years of entry.
• Subject had positive urine drug test (e.g., cocaine, amphetamines, barbiturates, opiates, benzodiazepines, cannabinoids) or alcohol test at Screening or at admission.
• History of drinking > 168 g (males) and > 84 g (females) pure alcohol per week (10 g pure alcohol = 259 mL of beer [5%] or 35 mL of spirits [35%] or 100 mL of wine [12%] within 3 months prior to admission to the clinical unit.
• Subject consumed more than 600 mg caffeine per day (e.g., more than 3 cups of coffee containing 200 mg caffeine per cup) within the 4 weeks before admission or the subject was unwilling to avoid consumption of coffee and caffeine-containing beverages within 48 hours prior to admission until discharge from the clinical unit.
• Subject was unwilling to avoid use of alcohol or alcohol-containing foods, medications or beverages, within 48 hours prior to Screening and from admission until discharge from the clinical unit.
• Any significant blood loss, donated 1 unit (450 mL) of blood or more, or received a transfusion of any blood or blood products within 60 days, or donated plasma within 7 days prior to the admission to the clinical unit.
• Participation in any clinical study within 3 months or 5 half-lives of the drug, whichever was longer, prior to the expected date of IMP administration, or participation in more than 3 clinical studies within 12 months.
• Subject with a relevant history or with a present psychiatric disorder, including depression, suicidal ideation, or eating disorders (e.g., bulimia or anorexia nervosa). Subjects with a medical history