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

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

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

Study Overview

• Status: Withdrawn
• Conditions: Type 2 Diabetes Mellitus
• Intervention / Treatment: Drug: Placebo; Drug: LIK066; Drug: Sitagliptin

• Study Type: Interventional
• Phase: Phase 2

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

9

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: LIK066 2.5 mg; Patients receive 2.5 mg of LIK066 once daily for 12 weeks	Drug: LIK066; Experimental treatment doses
Experimental: LIK066 5 mg; Patients receive 5 mg of LIK066 once daily for 12 weeks	Drug: LIK066; Experimental treatment doses
Experimental: LIK066 10 mg; Patients receive 10 mg of LIK066 once daily for 12 weeks	Drug: LIK066; Experimental treatment doses
Experimental: LIK066 25 mg; Patients receive 25 mg of LIK066 once daily for 12 weeks	Drug: LIK066; Experimental treatment doses
Experimental: LIK066 50 mg; Patients receive 50 mg of LIK066 once daily for 12 weeks	Drug: LIK066; Experimental treatment doses
Experimental: LIK066 100 mg; Patients receive 100 mg of LIK066 once daily for 12 weeks	Drug: LIK066; Experimental treatment doses
Experimental: LIK066 150 mg; Patients receive 150 mg of LIK066 once daily for 12 weeks	Drug: LIK066; Experimental treatment doses
Active Comparator: Sitagliptin 100 mg; Patients receive 100 mg sitagliptin once daily for 12 weeks	Drug: Sitagliptin; Active comparator treatment dose
Placebo Comparator: Placebo; Patients receive placebo for 12 weeks	Drug: Placebo; Placebo comparator dose

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
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
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
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
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
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
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
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
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
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
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
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

Collaborators and Investigators

• Sponsor: Novartis Pharmaceuticals

Study record dates

Study Major Dates

• Study Start: November 1, 2015
• Primary Completion (Anticipated): November 1, 2016
• Study Completion (Anticipated): November 1, 2016

Study Registration Dates

• First Submitted: April 1, 2013
• First Submitted That Met QC Criteria: April 1, 2013
• First Posted (Estimate): April 4, 2013

Study Record Updates

• Last Update Posted (Estimate): April 3, 2014
• Last Update Submitted That Met QC Criteria: April 2, 2014
• Last Verified: April 1, 2014

More Information

Terms related to this study

• Keywords: Type 2 Diabetes mellitus, SGLT inhibitors, dose-response
• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases; Diabetes Mellitus; Diabetes Mellitus, Type 2; Hypoglycemic Agents; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Protease Inhibitors; Incretins; Sodium-Glucose Transporter 2 Inhibitors; Dipeptidyl-Peptidase IV Inhibitors; Sitagliptin Phosphate; Licogliflozin
• Other Study ID Numbers: CLIK066A2202; 2012-005793-63 (EudraCT Number)