A study to assess the effect of 3 different doses of LIK066 in patients with type 2 diabetes and heart failure, compared to the effect of placebo or empagliflozin

• Register: EUCTR
• Last refreshed on: 20 August 2018
• Main ID: EUCTR2016-003084-19-CZ
• Date of registration: 13/04/2017
• Prospective Registration: Yes
• Primary sponsor: Novartis Pharma AG
• Public title: A study to assess the effect of 3 different doses of LIK066 in patients with type 2 diabetes and heart failure, compared to the effect of placebo or empagliflozin
• Scientific title: A multi-center, randomized, double-blind, parallel-group dose-finding study to assess the effect of 3 doses of LIK066 compared to placebo or empagliflozin in type 2 diabetes mellitus patients with heart failure - Dose finding study to assess effect of LIK066 in patients with type 2 diabetes and heart failure
• Date of first enrolment: 06/06/2017
• Target sample size: 1000
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2016-003084-19
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes; Randomised: yes; Open: no; Single blind: no; Double blind: yes; Parallel group: yes; Cross over: no; Other: no; If controlled, specify comparator, Other Medicinial Product: yes; Placebo: yes; Other: no; Number of treatment arms in the trial: 3
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): yes Therapeutic confirmatory - (Phase III): no Therapeutic use (Phase IV): no

Countries of recruitment

Argentina, Austria, Belgium, Bulgaria, Canada, Croatia, Czech Republic, Denmark, Germany, Guatemala, Hungary, Ireland, Italy, Korea, Republic of, Mexico, Netherlands, Norway, Poland, Singapore, South Africa, Spain, Taiwan, United Kingdom, United States

Contacts

• Name: Clinical Trial Information Desk
• Affiliation: Novartis Pharma AG

• Name: Clinical Trial Information Desk
• Affiliation: Novartis Pharma AG

Key inclusion & exclusion criteria

Inclusion criteria:
• BMI = 22kg/m^2
• Type 2 diabetes with HbA1c between 6.5% and 10.0%
• Documented symptomatic chronic heart failure (NYHA II-IV)
• Plasma NT-proBNP > 300pg/ml
• eGFR = 45ml/min/1.73m^2 (calculated by MDRD)
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 540
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 460

Exclusion criteria:
• Pregnant or nursing (lactating) women
• Type 1 diabetes, monogenic diabetes, diabetes resulting from pancreatic injury, or secondary forms of diabetes
• History of ketoacidosis, lactic acidosis, or hyperosmolar coma
• Symptomatic genital infection or UTI within 4 weeks of screening
• Myocardial infarction, stroke, surgery for heart disease, percutaneous coronary intervention within 3 months of screening
• Unstable angina within 3 months of screening
• Isolated right HF due to pulmonary disease
• Patients with a mean sitting systolic blood pressure = 100mmHg, at randomization


Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

patients with type 2 diabetes mellitus and heart failure
MedDRA version: 20.1 Level: LLT Classification code 10045242 Term: Type II diabetes mellitus System Organ Class: 100000004861
MedDRA version: 20.0 Level: LLT Classification code 10019279 Term: Heart failure System Organ Class: 100000004849

Therapeutic area: Diseases [C] - Cardiovascular Diseases [C14]

Intervention(s)

Product Name: LIK066 2.5 mg
Product Code: LIK066
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: not available
Other descriptive name: LIK066
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 2.5-
Pharmaceutical form of the placebo: Film-coated tablet
Route of administration of the placebo: Oral use

Product Name: LIK066 10 mg
Product Code: LIK066
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: not available
Other descriptive name: LIK066
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 10-
Pharmaceutical form of the placebo: Film-coated tablet
Route of administration of the placebo: Oral use

Product Name: LIK066 50 mg
Product Code: LIK066
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: not available
Other descriptive name: LIK066
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 50-
Pharmaceutical form of the placebo: Film-coated tablet
Route of administration of the placebo: Oral use

Trade Name: Jardiance
Product Name: Empagliflozin
Product Code: Empagliflozin
Pharmaceutical Form: Capsule
INN or Proposed INN: Empagliflozin
CAS Number: 864070-44-0
Other descriptive name: EMPAGLIFLOZIN
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 10-
Pharmaceutical form of the placebo: Capsule
Route of administration of the placebo: Oral use

Trade Name: Jardiance
Product Name: Empagliflozin
Product Code: Empagliflozin
Pharmaceutical Form: Capsule
INN or Proposed INN: Empagliflozin
CAS Number: 864070-44-0
Other descriptive name: EMPAGLIFLOZIN
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 25-
Pharmaceutical form of the placebo: Capsule
Route of administration of the placebo: Oral use

Primary Outcome(s)

Primary end point(s): Change from baseline in NTproBNP at week 12

Timepoint(s) of evaluation of this end point: baseline, week 12

Main Objective: To assess the dose-response relationship of three dose regimens of LIK066 as measured by the change from baseline in NT-proBNP relative to placebo after 12 weeks of treatment in T2DM patients with HF

Secondary Objective: 1. To evaluate the effect of all LIK066 doses vs placebo or empagliflozin at 12 weeks and 36 weeks on:
- Change from baseline (BL) in HbA1c
- Change from BL in fasting plasma glucose
- Change from BL in body weight
- Change from BL in body composition
- Change from BL in sitting SBP and DBP
- Change from BL in 24h urinary glucose and sodium excretion
- Change from BL in the fasting lipid profile and hsCRP
2. Change from BL in left atrial size and volume assessed by echocardiography relative to placebo after 12 and 36 weeks of treatment
3. Change from BL in NYHA class relative to placebo after 12 and 36 weeks of treatment
4. To evaluate the change from BL to 36 weeks in all LIK066 doses vs placebo on NT-proBNP.
5. To evaluate bone mineral density and 24h urinary calcium and phosphate excretion

Secondary Outcome(s)

Timepoint(s) of evaluation of this end point: baseline, week 12, week 36

Secondary end point(s): - Change from baseline (BL) in HbA1c
- Change from BL in fasting plasma glucose
- Change from BL in body weight
- Change from BL in body composition
- Change from BL in sitting SBP and DBP
- Change from BL in the fasting lipid profile and hsCRP
- Change from BL in 24h urinary glucose and sodium excretion
- Change from BL in left atrial size and volume assessed by echocardiography
- Change from BL in NYHA class
- Change from BL in NT-proBNP
- 24h urinary calcium and phosphate excretion
- bone mineral density

Secondary ID(s)

CLIK066B2204

2016-003084-19-AT

Source(s) of Monetary Support

Novartis Pharma AG