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 (FORTUNA)

• Mean change in HbA1c from baseline to each scheduled post-randomization visit [ Designated as safety issue: No ]
• Mean change from baseline to each scheduled post-randomization visit and Vlast in blood parameters [ Designated as safety issue: No ]
  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 [ Designated as safety issue: No ]
• 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 [ Designated as safety issue: No ]
• Time to event (study withdrawal, time to study withdrawal due to an adverse event (AE) and time to lack of efficacy (LOE) [ Designated as safety issue: No ]

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.

• Active Comparator: Roflumilast
  500µg, once daily
  Intervention: Drug: Roflumilast
• Placebo Comparator: Placebo
  Intervention: Drug: Roflumilast

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