Efficacy of 500µg Roflumilast Once Daily Versus Placebo Over 12 Weeks in Patients With Diabetes Mellitus Type 2. A Double Blind, Parallel Group, Proof of Concept Clinical Study

Study Overview
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Brief Summary
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This study is a proof of concept study to confirm in a standardized manner the therapeutic efficacy of roflumilast in type 2 diabetes mellitus patients.

Official Title
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Efficacy of 500µg Roflumilast Once Daily Versus Placebo Over 12 Weeks in Patients With Diabetes Mellitus Type 2. A Double Blind, Parallel Group, Phase IIb, Proof of Concept Clinical Study

Conditions
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Diabetes Mellitus Type 2

Intervention / Treatment
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* Drug: Roflumilast


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: given written informed consent patients with diagnosis of type 2 diabetes according to American Diabetes Association (ADA) criteria and inadequately controlled on diet and exercise alone HbA1c at baseline: ≥7.5 percent to 8.5 percent (up to 9 percent in Mexico, Ukraine and Romania) BMI between ≥26 and ≤35 kg/m2 willingness of patient to check his/her blood glucose with equipment provided by the sponsor during the treatment phase in case of hypo-/hyperglycemia episodes willingness to adhere to the physician's advise to comply with diet and exercise Main Exclusion Criteria: patients diagnosed with type 1 diabetes or diabetes secondary to pancreatitis or resection of pancreas patients diagnosed with hemoglobinopathies, hemolytic anemia or other diseases which interfere with HbA1c measurement non-euthyroid patients or patients with a non-controlled hypo- or hyperthyroidism reported gain or loss of more than 5 percent of body weight within the last 2 months prior to V0 treatment with any diabetes medication prior to V0 treatment with any weight-loss medication within 3 months prior to V0 treatment with any not allowed medication or nutrition additives clinically relevant abnormal laboratory values suggesting an unknown disease and requiring further clinical evaluation (as assessed by the investigator) clinically significant cardiac abnormalities (diagnosed clinically, or by X-ray/ECG) that were not related to type 2 diabetes mellitus and that required further evaluation participation in a clinical study with study medication for weight loss or type 2 diabetes Patients were randomized after 2 weeks of the baseline period, if the following criteria were fulfilled: judged to be clinically stable tablet compliance ≥80 percent and ≤125 percent HbA1c in the range of 7.5 percent to 8.5 percent (up to 9 percent in Mexico, Ukraine and Romania) tested at V0 by the central laboratory

Ages Eligible for Study
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Minimum Age: 35 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Roflumilast<br>500µg, once daily | Drug: Roflumilast<br>* 500µg, once daily<br>|
| Placebo Comparator: Placebo<br> | Drug: Roflumilast<br>* 500µg, once daily<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean change in HbA1c [percent] from baseline to the last study visit (Vlast) |  | Baseline to last visit | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean change in HbA1c from baseline to each scheduled post-randomization visit |  |  | 
| Mean change from baseline to each scheduled post-randomization visit and Vlast in blood parameters | blood parameters: serum lipids (high-density-lipoprotein-cholesterol [HDL], low-density-lipoprotein-cholesterol [LDL], and triglycerides [TG]), fasting plasma glucose (FPG), fructosamine, glycerol, free fatty acids [FFA], plasma insulin, fasting pro-insulin, cholesterol, c-reactive protein (CRP), interleukin-6 (IL-6), TNF-α, intercellular adhesion molecule 1 (ICAM-1), E-selectin, plasminogen activator inhibitor 1 (PAI-1), adiponectin, and leptin |  | 
| Mean change from baseline to each scheduled post-randomization visit and Vlast based on a 5-hour period post meal area under the curve (AUC) for FFA, glycerol, glucose, glucagons, insulin, and C-peptide |  |  | 
| Mean change in body weight, waist and hip circumference, waist to hip ratio, and body mass index (BMI) from baseline to each scheduled post-randomization visit and Vlast |  |  | 
| Time to event (study withdrawal, time to study withdrawal due to an adverse event (AE) and time to lack of efficacy (LOE) |  |  | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Diabetes Mellitus Type 2, Roflumilast