Study of the Safety and Tolerability of Switching to ITCA 650 in Patients With Type 2 Diabetes Receiving Liraglutide

Study Overview
=================
Brief Summary
-----------------
A Phase 3b, open-label, randomized, multicenter, safety and tolerability study of ITCA 650 in subjects with Type 2 diabetes taking liraglutide and metformin.

Official Title
-----------------
An Open-Label, Multi-Center, Randomized, Phase 3b Study to Evaluate the Safety and Tolerability of Switching to One of Two Dosing Strategies of ITCA 650 in Patients With Type 2 Diabetes Receiving Stable Doses of Liraglutide

Conditions
-----------------
Diabetes Mellitus, Type 2

Intervention / Treatment
-----------------
* Drug: ITCA 650 Osmotic Mini Pump 20/60 mcg/day
* Drug: ITCA 650 Osmotic Mini Pump 60 mcg/day
* Drug: Metformin
* Drug: Liraglutide


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Diagnosis of type 2 diabetes ≥ 3 months. Stable regimen of diet and exercise in combination with a stable treatment of liraglutide ≥1.2 mg/day and metformin ≥1000 mg/day. HbA1c ≤9.5%. Stable body weight ≥ 3 months. Body mass index (BMI) ≥25 to ≤45 kg per meter squared. Calcitonin <50 ng/L (50 pg/mL) at the Screening Visit. Exclusion Criteria: History of type 1 diabetes. Recent use or of anti-diabetic medications other than liraglutide or metformin. History of significant/severe nausea and/or vomiting due to liraglutide. Significant symptomatic hyperglycemia. History or evidence, within the last 6 months prior to the Screening Visit, of myocardial infarction, coronary revascularization (coronary artery bypass grafting or percutaneous coronary intervention), unstable angina, or cerebrovascular accident or stroke. History or evidence of acute or chronic pancreatitis. History of liver disease. History of medullary thyroid cancer or a family or personal history of multiple endocrine neoplasia type 2. Poor thyroid, liver, or renal function. Serum creatinine levels >1.5mg/dL (132 μmol/L) for male patients, or >1.4 mg/dL (123 μmol/L) for female patients. Weight loss surgery or requires weight loss medications. History of malignancy (not including basal or squamous cell carcinoma of the skin with past 5 years). History of active alcohol or substance abuse. Treatment with medications that affect GI motility. History of hypersensitivity to exenatide or liraglutide. Women that are pregnant, lactating, or planning to become pregnant.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Group 1<br>ITCA 650 20/60 mcg/day | Drug: ITCA 650 Osmotic Mini Pump 20/60 mcg/day<br>* ITCA 650 osmotic mini pump delivering exenatide 20/60 mcg/day<br>Drug: Metformin<br>* Stable dose for at least 3 months (at least 1000 mg/day)<br>Drug: Liraglutide<br>* Stable dose for at least 3 months (at least 1.2 mg/day)<br>|
| Experimental: Group 2<br>ITCA 650 60 mcg/day | Drug: ITCA 650 Osmotic Mini Pump 60 mcg/day<br>* ITCA 650 osmotic mini pump delivering exenatide 60 mcg/day<br>Drug: Metformin<br>* Stable dose for at least 3 months (at least 1000 mg/day)<br>Drug: Liraglutide<br>* Stable dose for at least 3 months (at least 1.2 mg/day)<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number (percentage) and severity of treatment-emergent adverse events (TEAEs) of nausea and/or vomiting | Number (percentage) and severity of treatment-emergent AEs (TEAEs) of nausea and/or vomiting over the 26-week treatment period; treatment discontinuation for nausea and/or vomiting; and pattern of nausea and/or vomiting over time. | From Randomization to 34 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number (percentage) and severity of all treatment-emergent adverse events | All TEAEs 2 dose regimens of ITCA 650 over 26 weeks in patients with T2D after switching from stable therapy with liraglutide | From Randomization to 34 weeks | 
| Incidence of hypoglycemia |  | From Randomization to 34 weeks | 
| Change in percentage of glycosylated hemoglobin (HbA1c) in the blood |  | From baseline to Week 26 | 
| Change in body weight | Change from baseline in body weight at Week 26 | from baseline to Week 26 |