E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Patients with type-2-diabetes mellitus |
|
E.1.1.1 | Medical condition in easily understood language |
|
E.1.1.2 | Therapeutic area | Body processes [G] - Metabolic Phenomena [G03] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 13.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10045242 |
E.1.2 | Term | Type II diabetes mellitus |
E.1.2 | System Organ Class | 10027433 - Metabolism and nutrition disorders |
|
E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
The objective of the current study is to investigate the efficacy and safety of BI 10773 (10 and 25 mg) compared to placebo on glucose control and BP over 12 weeks in hypertensive patients with T2DM. |
|
E.2.2 | Secondary objectives of the trial |
The primary endpoint in this study is change from baseline in HbA1c after 12 weeks of treatment
Co-primary endpoint is change from baseline in mean 24 hour SBP after 12 weeks of treatment
Key secondary endpoint is change from baseline in mean 24 hour DBP after 12 weeks of treatment
Other secondary endpoints are defined in protocol section 5.1.1.
|
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1.Diagnosis of T2DM prior to informed consent
2.Male and female patients on diet and exercise regimen who are:
drug-naïve, (defined as absence of any oral antidiabetic therapy or insulin for 12 weeks, 16 weeks for pioglitazone prior to randomisation)
or
pre-treated with any oral antidiabetic therapy, GLP-1 analog or insulin for 12 weeks prior to randomisation.
3.HbA1c of ≥ 7.0% (53 mmol/mol) and ≤ 10% (86 mmol/mol) at Visit 1 (screening)
4.Mean seated SBP 130-159 mmHg and DBP 80-99 mmHg at Visit 1 (screening)
5.Treatment with stable doses of antihypertensive medication ≥ 4 weeks at Visit 1 (screening) and throughout the screening/run-in phase
6.Number of previous antihypertensive medication ≤ 2 at Visit 1 (screening) and throughout the screening/run-in phase
7.Age ≥ 18 years at Visit 1 (screening)
8.BMI ≤ 45 kg/m2 (Body Mass Index) at Visit 1 (screening)
9.Signed and dated written informed consent by date of Visit 1 in accordance with GCP and local legislation
|
|
E.4 | Principal exclusion criteria |
1.Uncontrolled hyperglycaemia with a glucose level >240 mg/dl (>13.3 mmol/L) after an overnight fast during placebo run-in and confirmed by a second measurement (not on the same day)
2.Mean seated SBP ≥160 mmHg and/or mean seated DBP≥100 mmHg during placebo run-in visit and confirmed by a second measurement (not on the same day) preferably within one day
3.Upper arm circumference that exceeds the upper circumference level of the cuff size of either ABPM and/or BP measurement device used in the study
4.Night shift workers who routinely sleep during the daytime and whose work hours include midnight to 4:00 a.m.
5.Current treatment and/or treatment within the last 16 weeks with Rosiglitazone
6.Known or suspected secondary hypertension (e.g. renal artery stenosis, phaeochromocytoma)
7.History or evidence of hypertensive retinopathy (Keith-Wagener grade III or IV) and/or hypertensive encephalopathy
8.Clinically significant valvular heart disease or severe aortic stenosis
9.Acute coronary syndrome (non-STEMI, STEMI and unstable angina pectoris), stroke or TIA within 3 months prior to informed consent
10.Indication of liver disease, defined by serum levels of either ALT (SGPT), AST (SGOT), or alkaline phosphatase above 3 x upper limit of normal (ULN) as determined during screening and/or run-in phase
11.Impaired renal function, defined as eGFR< 60 ml/min (moderate renal impairment, MDRD formula) as determined during screening and/or run-in phase
12.Bariatric surgery within the past two years and other gastrointestinal surgeries that induce chronic malabsorption
13.Medical history of cancer (except for basal cell carcinoma) and/or treatment for cancer within the last 5 years
14.Blood dyscrasias or any disorders causing hemolysis or unstable Red Blood Cell (e.g. malaria, babesiosis, haemolytic anemia)
15.Any contraindications to background antidiabetic medications according to the local label
16.Any contraindications to background antihypertensive medications according to the local label
17.Treatment with anti-obesity drugs 3 months prior to informed consent or any other treatment at the time of screening (i.e. surgery, aggressive diet regimen, etc.) leading to unstable body weight
18.Current treatment with systemic steroids at time of informed consent or change in dosage of thyroid hormones within 6 weeks prior to informed consent or any other uncontrolled endocrine disorder except T2D
19.Pre-menopausal women (last menstruation 1 year prior to informed consent) who:
- are nursing or pregnant or
- are of child-bearing potential and are not practicing an acceptable method of birth control, or do not plan to continue using this method throughout the study and do not agree to submit to periodic pregnancy testing during participation in the trial. Acceptable methods of birth control include tubal ligation, transdermal patch, intra uterine devices/systems (IUDs/IUSs), oral, implantable or injectable contraceptives, complete sexual abstinence (if acceptable by local authorities), double barrier method and vasectomised partner
20.Alcohol, drug or confectionary liquorice abuse within the 3 months prior to informed consent that would interfere with trial participation or any ongoing condition leading to a decreased compliance to study procedures or study drug intake in the investigator’s opinion
21.Participation in another trial with application of any investigational drug within 30 days prior to informed consent
22.Any other clinical condition that would jeopardize patients safety while participating in this clinical trial
|
|
E.5 End points |
E.5.1 | Primary end point(s) |
The primary endpoint is change from baseline in HbA1c after 12 weeks of treatment. Co-primary endpoint is change from baseline in mean 24-hour SBP after 12 weeks of treatment.
|
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
Primary endpoint and co-primary endpoint are evaluated after 12 weeks of treatment.
Throughout the study protocol, the term ‘’baseline’’ refers to the last observation prior to randomization of the patient. |
|
E.5.2 | Secondary end point(s) |
Key secondary endpoint is change from baseline in mean 24-hour DBP after 12 weeks of treatment
Other secondary endpoints are:
Proportion of patients with HbA1c < 7% after 12 weeks of treatment
Change from baseline in fasting plasma glucose (FPG) after 12 weeks of treatment
Change from baseline in body weight after 12 weeks of treatment
Change from baseline in daytime mean SBP after 12 weeks of treatment
Change from baseline in daytime mean DBP after 12 weeks of treatment
Change from baseline in nighttime mean SBP after 12 weeks of treatment
Change from baseline in nighttime mean DBP after 12 weeks of treatment
Change from baseline in trough mean sitting SBP after 12 weeks
Change from baseline in trough mean sitting DBP after 12 weeks
Change from baseline in orthostatic blood pressure after 12 weeks of treatment
Proportion of patients reaching BP<130/80 mmHg after 12 weeks of treatment
Composite endpoint of the following conditions at week 12 (all three fulfilled)
- Change from baseline HbA1c of more than -0.5%;
- Change from baseline in SBP of > -3 mmHg;
- Change from baseline in weight of > -2%
|
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
Secondary endpoints are evaluated after 12 weeks of treatment.
Throughout the study protocol, the term ‘’baseline’’ refers to the last observation prior to randomization of the patient. |
|
E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | Yes |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 3 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 65 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
Canada |
Czech Republic |
Denmark |
Estonia |
Finland |
France |
Germany |
India |
Lebanon |
Netherlands |
Norway |
Sweden |
United States |
|
E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
|
|
E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | |
E.8.9.1 | In the Member State concerned months | |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 1 |
E.8.9.2 | In all countries concerned by the trial months | 0 |
E.8.9.2 | In all countries concerned by the trial days | 0 |