Tesofensine and metoprolol for treatment of hypertension
a technology of metoprolol and tesofensine, which is applied in the field of hypertension treatment, can solve problems such as blood pressure drop, and achieve the effect of increasing the bioavailability of metoprolol
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example 1
Tesofensine on Metoprolol Pharmacokinetics
[0156]The ability of tesofensine to inhibit CYP2D6 in the clinical setting was investigated in a Phase 1 drug-drug interaction (DDI) study with metoprolol, which is a known substrate for CYP2D6.
Subjects
[0157]Healthy human male volunteers, 18-50 years of age. A total of 14 subjects were included in the study.
Methodology
[0158]Two consecutive study periods separated by a washout period of at least three days. The sequence of events was the same for all subjects. In period 1, a single dose of metoprolol was administered. In period 2, the same dose of metoprolol was administered at a steady state concentration of tesofensine.
Metoprolol: 50 mg single dose
Tesofensine: 2 mg loading dose at days 1-3, 0.5 mg maintenance dose at days 4-14
Results
[0159]The single dose metoprolol pharmacokinetics (PK) obtained at day 0 was compared to the PK obtained after 14 days of tesofensine once daily administration.
[0160]The results are depicted in FIG. 1. The resul...
example 2
Tesofensine and Metoprolol on Heart Rate and Blood Pressure in Humans
[0161]In a retrospective analysis of the data obtained in the above-mentioned Phase 1 DDI study the effect of a single dose of metoprolol in subjects treated with tesofensine was investigated. Particularly, the effect of tesofensine-metoprolol on heart rate and blood pressure at rest, was investigated.
[0162]Metoprolol was found to normalize the tesofensine-induced increase in heart rate after 7 hours (FIG. 2, 3rd column) as previously shown pre-clinically. In accordance with the pharmacokinetics of metoprolol (plasma T1 / 2 3-4 hours)—the effect on the heart rate disappeared after ˜24 hours (FIG. 2, 4th column). The data indicates that co-administration of tesofensine and metoprolol is capable of inhibiting the tesofensine-induced increase in heart rate in human subjects to levels approximating pre-treatment levels.
[0163]In the present study, 14 days of tesofensine treatment was found to increase systolic BP slightly...
example 3 phase 2a
Trial Entitled “A Double-Blind, Randomized, Placebo-Controlled, Multiple-Dose, Two-Center Safety, and Efficacy Study of Co-Administration of Tesofensin / Metoprolol (Tesomet) in Subjects with Type 2 Diabetes Mellitus (NCT02737891)
[0166]The trial comprised a total of 60 patients with a mean BMI of 32.59 randomized into two groups of each 30 patients: Arm 1 were administered tesofensine 0.5 mg (tablets)+metoprolol 100 mg (MetoHEXAL® 100 mg retard tablets) once a day (Tesomet); Arm 2 were administered Placebo matching tablets once a day. Patients were treated for 90 days. The patients at enrolment had an average BMI of 32.59.
Inclusion Criteria:
[0167]1. Males and females
2. Confirmed diagnosis of T2DM
3. 18-70 years of age
4. HbA1c≥7.0%
Exclusion Criteria:
[0168]1. Hypersensitivity to tesofensine / metoprolol
2. Heart failure class II or greater according to the New York Heart Association (NYHA) or decompensated heart failure
3. History of myocardial infarction or stroke within 12 months prior to ...
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