Healthy Male Subjects
Conditions
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.
Interventions
DRUGTesomet 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.
DRUGTesomet 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.
DRUGComperator 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.
DRUGTesomet 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.
Sponsors
Saniona
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
OTHER
Masking
SINGLE (Subject)
Eligibility
Sex/Gender
MALE
Age
18 Years to 55 Years
Healthy volunteers
Yes
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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 |
Countries
Germany
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Tesomet High Dose in Fasted Condition Tesomet FDC tablet (20 mg immediate release \[IR\] metoprolol, 1 mg tesofensine, 80 mg extended release \[ER\] metoprolol) in fasted condition (High dose) | 15 |
| Tesomet Low Dose in Fasted Condition Tesomet FDC tablet (5 mg immediate IR metoprolol, 0.2 mg tesofensine, 20 mg ER metoprolol) in fasted condition. (Low dose) | 15 |
| Comparator 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 | 15 |
| Tesomet High Dose in Fed Condition Tesomet FDC tablet (20 mg immediate IR metoprolol, 1 mg tesofensine, 80 mg ER metoprolol in fed condition (High dose) | 15 |
| Total | 60 |
Baseline characteristics
| Characteristic | Tesomet High Dose in Fasted Condition | Tesomet Low Dose in Fasted Condition | Comparator | Tesomet High Dose in Fed Condition | Total |
|---|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 15 Participants | 15 Participants | 15 Participants | 15 Participants | 60 Participants |
| Age, Continuous | 40.3 years STANDARD_DEVIATION 11.55 | 41.1 years STANDARD_DEVIATION 8.81 | 39.5 years STANDARD_DEVIATION 10.19 | 41.9 years STANDARD_DEVIATION 9.91 | 40.7 years STANDARD_DEVIATION 9.93 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 14 Participants | 15 Participants | 15 Participants | 15 Participants | 59 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 15 Participants | 14 Participants | 15 Participants | 15 Participants | 59 Participants |
| Region of Enrollment Germany | 15 participants | 15 participants | 15 participants | 15 participants | 60 participants |
| Sex: Female, Male Female | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Male | 15 Participants | 15 Participants | 15 Participants | 15 Participants | 60 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 15 | 0 / 15 | 0 / 15 | 0 / 15 |
| other Total, other adverse events | 3 / 15 | 4 / 15 | 5 / 15 | 1 / 15 |
| serious Total, serious adverse events | 0 / 15 | 0 / 15 | 0 / 15 | 0 / 15 |
Outcome results
Primary
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
Time frame: Pre-dose and 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 20, 24, 30, 36 and 48 hours post-dose
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Tesomet High Dose in Fasted Condition | AUC0-48 | 32.06 ng*hr/mL | Geometric Coefficient of Variation 26.9 |
| Tesomet Low Dose in Fasted Condition | AUC0-48 | 6.491 ng*hr/mL | Geometric Coefficient of Variation 25.1 |
| Comparator | AUC0-48 | 45.89 ng*hr/mL | Geometric Coefficient of Variation 21.9 |
| Tesomet High Dose in Fed Condition | AUC0-48 | 30.14 ng*hr/mL | Geometric Coefficient of Variation 18.6 |
Secondary
Cmax
Maximum tesofensine and metoprolol concentrations determined directly from the concentration-time profile
Time frame: Pre-dose and 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 20, 24, 30, 36 and 48 hours post-dose
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Tesomet High Dose in Fasted Condition | Cmax | 0.9528 ng/mL | Geometric Coefficient of Variation 25.5 |
| Tesomet Low Dose in Fasted Condition | Cmax | 0.1934 ng/mL | Geometric Coefficient of Variation 23.6 |
| Comparator | Cmax | 1.357 ng/mL | Geometric Coefficient of Variation 23.8 |
| Tesomet High Dose in Fed Condition | Cmax | 0.8085 ng/mL | Geometric Coefficient of Variation 17.1 |
Secondary
Tmax
Time of maximum tesofensine and metoprolol concentrations determined directly from the concentration-time profile
Time frame: Pre-dose and 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 20, 24, 30, 36 and 48 hours post-dose
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Tesomet High Dose in Fasted Condition | Tmax | 6.12 hours | Geometric Coefficient of Variation 5.98 |
| Tesomet Low Dose in Fasted Condition | Tmax | 6.00 hours | Geometric Coefficient of Variation 5.98 |
| Comparator | Tmax | 6.00 hours | Geometric Coefficient of Variation 3.98 |
| Tesomet High Dose in Fed Condition | Tmax | 8.00 hours | Geometric Coefficient of Variation 4 |