Type 2 Diabetes Mellitus
Conditions
Brief summary
Safety and Efficacy Study of Tesofensine/Metoprolol Treatment in Subjects With Type 2 Diabetes Mellitus
Detailed description
This is a double-blind, randomized, placebo-controlled, multiple-dose, two-center, safety and efficacy study of co-administration of tesofensine/metoprolol treatment in subjects with T2DM. Study medication will be administered for ninety (90) days (+2 days after the final assessments with half-dose of metoprolol). Following all baseline assessments, eligible subjects will be randomly assigned to one of the two arms (1:1).
Interventions
Tesofensine 0.5 mg + Metoprolol 100 mg
DRUGPlacebo
Sponsors
Profil Institut für Stoffwechselforschung GmbH
Saniona
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
No
Inclusion criteria
1. Males and females 2. Confirmed diagnosis of T2DM 3. 18-70 years of age 4. HbA1c ≥7.0%
Exclusion criteria
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 enrolment 4. History of coronary revascularisation or angioplasty in the last 12 months prior to enrolment 5. Patients reporting angina in the last 6 months prior to enrolment 6. Treatment with insulin and/or other injectable anti-diabetic medications, or TZDs 7. Any clinically significant cardiac arrhythmia
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Effects of Co-administration of Tesofensine/Metoprolol Treatment vs. Placebo on 24-hour Mean Heart Rate | Baseline to Day 90 | 24-hour heart rate monitoring was based on telemetry measurements at baseline (Day -1 to 1, V2) and at the end of treatment (Day 90 to 91, V10). The heart rate was measured every minute and the mean was recorded for every hour. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline to End of Treatment in HbA1c | Baseline to Day 90 | HbA1c was measured from blood samples collected at baseline (Day 1, V2) and at the end of treatment (Day 90, V10). Additional HbA1c measurements were done during various visits (V6, V8 and V12). |
| Change From Baseline to End of Treatment in Body Weight | Baseline to Day 90 | Change in kg body weight measured from baseline to day 90 |
Countries
Germany
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Tesofensine/Metoprolol Oral tablets Tesofensine/Metoprolol
Tesofensine/Metoprolol: Tesofensine 0.5 mg + Metoprolol 100 mg | 30 |
| Placebo Placebo tablets matching oral Tesofensine/Metoprolol
Placebo | 30 |
| Total | 60 |
Baseline characteristics
| Characteristic | Tesofensine/Metoprolol | Placebo | Total |
|---|---|---|---|
| Age, Continuous | 62 years STANDARD_DEVIATION 7 | 64 years STANDARD_DEVIATION 5 | 64 years STANDARD_DEVIATION 6 |
| Sex: Female, Male Female | 15 Participants | 6 Participants | 21 Participants |
| Sex: Female, Male Male | 15 Participants | 24 Participants | 39 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 30 | 0 / 30 |
| other Total, other adverse events | 20 / 30 | 12 / 30 |
| serious Total, serious adverse events | 0 / 30 | 1 / 30 |
Outcome results
Primary
Effects of Co-administration of Tesofensine/Metoprolol Treatment vs. Placebo on 24-hour Mean Heart Rate
24-hour heart rate monitoring was based on telemetry measurements at baseline (Day -1 to 1, V2) and at the end of treatment (Day 90 to 91, V10). The heart rate was measured every minute and the mean was recorded for every hour.
Time frame: Baseline to Day 90
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Tesofensine/Metoprolol | Effects of Co-administration of Tesofensine/Metoprolol Treatment vs. Placebo on 24-hour Mean Heart Rate | 67 beats per minutes (BPM) | Standard Deviation 7 |
| Placebo | Effects of Co-administration of Tesofensine/Metoprolol Treatment vs. Placebo on 24-hour Mean Heart Rate | 70 beats per minutes (BPM) | Standard Deviation 9 |
Comparison: The analysis was based on a parametric model, i.e. compared between treatment arms by means of an analysis of covariance (ANCOVA) model (proc MIXED) using change from baseline to the end of treatment as dependent variable, treatment and study site as fixed effects and the value from baseline as covariate. The residual errors were assumed independent and identically distributed (i.i.d.) and normally distributed.p-value: 0.00495% CI: [-6.36, -1.29]ANCOVA
Secondary
Change From Baseline to End of Treatment in Body Weight
Change in kg body weight measured from baseline to day 90
Time frame: Baseline to Day 90
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Tesofensine/Metoprolol | Change From Baseline to End of Treatment in Body Weight | -3.5 kg | Standard Deviation 19.9 |
| Placebo | Change From Baseline to End of Treatment in Body Weight | -0.3 kg | Standard Deviation 12.9 |
Comparison: The analysis was based on a parametric model, i.e. compared between treatment arms by means of an analysis of covariance (ANCOVA) model (proc MIXED) using change from baseline to the end of treatment as dependent variable, treatment and study site as fixed effects and the value from baseline as covariate. The residual errors were assumed independent and identically distributed (i.i.d.) and normally distributed.p-value: <0.000195% CI: [-4.65, -2.3]ANCOVA
Secondary
Change From Baseline to End of Treatment in HbA1c
HbA1c was measured from blood samples collected at baseline (Day 1, V2) and at the end of treatment (Day 90, V10). Additional HbA1c measurements were done during various visits (V6, V8 and V12).
Time frame: Baseline to Day 90
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Tesofensine/Metoprolol | Change From Baseline to End of Treatment in HbA1c | 7.3 percentage of HbA1c | Standard Deviation 0.6 |
| Placebo | Change From Baseline to End of Treatment in HbA1c | 7.4 percentage of HbA1c | Standard Deviation 0.7 |
Comparison: The analysis was based on a parametric model, i.e. compared between treatment arms by means of an analysis of covariance (ANCOVA) model (proc MIXED) using change from baseline to the end of treatment as dependent variable, treatment and study site as fixed effects and the value from baseline as covariate. The residual errors were assumed independent and identically distributed (i.i.d.) and normally distributed.p-value: 0.72495% CI: [-0.23, 0.33]ANCOVA