Dose-finding Study of LIK066 Compared With Placebo or Sitagliptin to Evaluate Change in HbA1c in Patients With Diabetes

Type 2 Diabetes Mellitus Clinical Trial

Official title:

A Multi-center, Randomized, Double-blind, Parallel-group Dose-finding Study to Evaluate Change in HbA1c After 12 Weeks Monotherapy With 7 Doses of LIK066 Compared With Placebo or Sitagliptin in Patients With Type 2 Diabetes

Clinical Trial Details — Status: Withdrawn

Administrative data

• NCT number: NCT01824264
• Other study ID #: CLIK066A2202
• Secondary ID: 2012-005793-63
• Status: Withdrawn
• Phase: Phase 2
• First received: April 1, 2013
• Last updated: April 2, 2014
• Start date: November 2015
• Est. completion date: November 2016

Study information

• Verified date: April 2014
• Source: Novartis
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

The purpose of the study is to evaluate the efficacy, tolerability and short-term safety of LIK066 to support dose selection for phase 3.

Recruitment information / eligibility

• Status: Withdrawn
• Enrollment: 0
• Est. completion date: November 2016
• Est. primary completion date: November 2016
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 75 Years

Eligibility

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

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 inclusion/exclusion criteria may apply

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Diabetes Mellitus
• Diabetes Mellitus, Type 2
• Type 2 Diabetes Mellitus

Intervention

Drug:
• LIK066
Experimental treatment doses
• Sitagliptin
Active comparator treatment dose
• Placebo
Placebo comparator dose

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Novartis Pharmaceuticals

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change from baseline in glycated hemoglobin (HbA1c) after 12 weeks	Change from baseline in HbA1c after 12 weeks of treatment in each of the LIK066 doses and placebo	baseline, 12 weeks	No
Secondary	Change from baseline in Fasting Plasma Glucose	The effect of LIK066 on fasting plasma glucose after 12 weeks of treatment will be evaluated.	baseline, 12 weeks	No
Secondary	Change from baseline in urinary glucose to creatinine ratio	The effect of LIK066 on urinary glucose to creatinine ratio after 12 weeks of treatment will be evaluated	baseline, 12 weeks	No
Secondary	Change from baseline in Body weight	The effect of LIK066 on change in body weight after 12 weeks of treatment will be evaluated.	baseline, 12 weeks	No
Secondary	Change from baseline in Blood pressure	The effect of LIK066 on change in systolic and diastolic blood pressure after 12 weeks of treatment will be evaluated.	baseline, 12 weeks	No
Secondary	Change from baseline in postprandial glucose during a meal test	The effect of LIK066 on change in postprandial glucose during a meal test after 12 weeks of treatment will be evaluated.	baseline, 12 weeks	No
Secondary	Change from baseline in beta cell function during a meal test	The effect of LIK066 on change in beta cell function during a meal test after 12 weeks of treatment will be evaluated.	baseline, 12 weeks	No
Secondary	Change from baseline in insulin secretion relative to glucose during a meal test	The effect of LIK066on change in insulin secretion relative to glucose during a meal test after 12 weeks of treatment will be evaluated.	baseline, 12 weeks	No
Secondary	Change from baseline in oral glucose insulin sensitivity during a meal test	The effect of LIK066 on change in oral glucose insulin sensitivity during a meal test after 12 weeks of treatment will be evaluated.	baseline, 12 weeks	No
Secondary	Change from baseline in glucagon-like peptide response during a meal test	The effect of LIK066 on change in glucagon-like peptide during a meal test after 12 weeks of treatment will be evaluated.	baseline, 12 weeks	No
Secondary	Change from baseline in Peptide YY response during a meal test	The effect of LIK066 on change in peptide YY response during a meal test after 12 weeks of treatment will be evaluated.	baseline, 12 weeks	No
Secondary	Number of patients with adverse events to assess safety and tolerability of LIK066	The safety and tolerability of 7 doses of LIK066 after 12 weeks of treatment will be evaluated with number of patients reported for total adverse events, serious adverse events and death.	12 weeks	Yes
Secondary	Change from baseline in renal threshold for glucose excretion	The effect of LIK066 on renal threshold for glucose excretion will be calculated from glucose values in an overnight urine collection	baseline, 12 weeks	No