A multi-center, randomized, double-blind, double-dummy, parallel-group dose-finding study to evaluate the change in HbA1c after 12 weeks monotherapy with seven doses of LIK066 compared with placebo or sitagliptin in patients with type 2 diabetes

• Register: EUCTR
• Last refreshed on: 4 November 2013
• Main ID: EUCTR2012-005793-63-HU
• Date of registration: 25/04/2013
• Prospective Registration: Yes
• Primary sponsor: Novartis Pharma Services AG
• Public title: A multi-center, randomized, double-blind, double-dummy, parallel-group dose-finding study to evaluate the change in HbA1c after 12 weeks monotherapy with seven doses of LIK066 compared with placebo or sitagliptin in patients with type 2 diabetes
• Scientific title: A multi-center, randomized, double-blind, double-dummy, parallel-group dose-finding study to evaluate the change in HbA1c after 12 weeks monotherapy with seven doses of LIK066 compared with placebo or sitagliptin in patients with type 2 diabetes - Dose-finding study of LIK066 compared with placebo or sitagliptin to evaluate change in HbA1c
• Date of first enrolment: 30/10/2013
• Target sample size: 491
• Recruitment status: Authorised-recruitment may be ongoing or finished
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2012-005793-63
• 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: yes Other trial design description: double-dummy If controlled, specify comparator, Other Medicinial Product: yes Placebo: yes Other: no Number of treatment arms in the trial: 9

Countries of recruitment

Argentina, Canada, Germany, Guatemala, Hungary, India, Italy, Mexico, Poland, Portugal, Russian Federation, Slovakia, South Africa, Taiwan, 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:
1.Confirmed diagnosis of T2DM by standard criteria
2.Drug-naïve patients, defined as patients not having received any anti-diabetic medication previously,
3.Currently untreated patients , who, after the diagnosis of T2DM, have received anti-diabetic medication for not more than 12 consecutive weeks, and have not received any anti-diabetic treatment within 12 weeks prior to Visit 1
4.Patients being treated with mono-therapy for at least 8 consecutive weeks prior to Visit 1 with the following OADs: metformin, dipeptidyl peptidase-4 inhibitors (DPP-4i), SU, glinide, alpha-glucosidase inhibitor (AGI)
5.HbA1c = 7 to = 10.5% at Visit 1 for drug-naïve/currently untreated patients
6.HbA1c = 7 to = 9.5% at Visit 1 for patients treated with OAD monotherapy
7.HbA1c = 7 to = 10.5% at Visit 199 for ALL patients
8.Age: =18 and = 75 years old at Visit 1
9.BMI =22 to =45 kg/m2 at Visit 1

Other protocol-defined inclusion criteria may apply

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 368
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 123

Exclusion criteria:
1.FPG =270 mg/dl (15 mmol/L) for drug-naïve/currently untreated patients or =240 mg/dl (13.3 mmol/L) for patients on OAD monotherapy at Visit 1
2.Insulin treatment >4 consecutive weeks in the last 6 months, corticosteroid use >7 days in the last 8 weeks, use of growth hormones in the last 6 months, or use of weight control products > 4 weeks in the last 6 months
3.History of acute metabolic complications, CV disease, type 1 diabetes mellitus, hepatic disorders, pancreatitis, chronic diarrhea
4.Significant lab abnormalities such as TSH outside of normal range, UACR>300 mg/g creatinine, eGFR <60 ml/min/1.73m2, hemoglobin <12 g/L in men and <11 g/L in women, hematuria
5.ECG abnormalities including AV block, long QT syndrome or QTc>450 msec for men and >470 msec for women
6.History of malignancy
7.Women of child-bearing potential not using effective methods of contraception

Other protocol-defined exclusion criteria may apply



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

Health Condition(s) or Problem(s) studied

Therapeutic area: Diseases [C] - Nutritional and Metabolic Diseases [C18]

Type II Diabetes mellitus

Intervention(s)

Product Name: LIK066
Product Code: LIK066
Pharmaceutical Form: Tablet
Pharmaceutical form of the placebo: Tablet
Route of administration of the placebo: Oral use

Trade Name: JANUVIA
Product Name: sitagliptin
Pharmaceutical Form: Capsule
Pharmaceutical form of the placebo: Capsule
Route of administration of the placebo: Oral use

Primary Outcome(s)

Main Objective: To evaluate the dose-response relationship for LIK066 in terms of changes from baseline in HbA1c after 12 weeks of treatment across 7 oral doses (2.5 mg, 5 mg, 10 mg, 25 mg, 50 mg, 100 mg, or 150 mg q.d.) of LIK066 or placebo.

Secondary Objective: 1. To evaluate the effect of LIK066 on:
• fasting plasma glucose (FPG)
• urinary glucose-to-creatinine ratio (UGCR)
• renal threshold for glucose excretion (RTg)
• body weight
• systolic and diastolic blood pressure
• postprandial glucose, beta cell function, insulin secretion relative to glucose (ISR/G), oral glucose insulin sensitivity (OGIS), GLP-1 and PYY response during a meal test

2. To evaluate the safety and tolerability of LIK066

Primary end point(s): change from baseline in HbA1c after 12 weeks of treatment in each of the LIK066 doses and placebo

Timepoint(s) of evaluation of this end point: 12 weeks

Secondary Outcome(s)

Timepoint(s) of evaluation of this end point: 12 weeks

Secondary end point(s): Change from baseline after 12 weeks of treatment
- Fasting plasma glucose (FPG)
- Urinary glucose-to-creatinine ratio (UGCR)
- Renal threshold for glucose excretion (RTg)
- body weight
- systolic and diastolic blood pressure
- postprandial glucose, beta cell function, insulin secretion relative to glucose (ISR/G), oral glucose insulin sensitivity (OGIS), GLP-1 and PYY response during a meal test
-the safety and tolerability of 7 doses of LIK066 after 12 weeks of treatment will be evluated with number of patients reported for total adverse events, serious adverse events and death

Secondary ID(s)

CLIK066A2202

Source(s) of Monetary Support

Novartis Pharma Services AG