Roflumilast Plus Alogliptin Proof-of-Mechanism Study in Type2 Diabetes

Inclusion Criteria

• Male or female, aged 18 to 80 years, inclusive, at the time of dosing on Day 1.
• Has an historical diagnosis of type 2 diabetes mellitus (T2DM) disease.
• Has a documented history of a diet and exercise plan and is receiving metformin as monotherapy at a stable dose for at least 8 weeks prior to Screening; has no chronic use (>7 days) of any other antidiabetic therapy within the 8 weeks prior to Screening.
• Has inadequate glycemic control at Screening, as evidenced by HbA1c (glycosylated hemoglobin) level between 7.0% and 10.0%, inclusive.
• Has a body mass index (BMI) of ≥23.0 kg/m^2 and ≤45.0 kg/m^2, at Screening.
• A female of childbearing potential who is sexually active with a nonsterilized male partner agrees to use routinely adequate contraception from signing of informed consent throughout the duration of the study and for 30 days after the last dose of study drug.
• A male who is nonsterilized and sexually active with a female partner of childbearing potential agrees to use adequate contraception from signing of informed consent throughout the duration of the study and for 30 days after last dose of study drug
• In the opinion of the investigator, the participant is capable of understanding and complying with protocol requirements.
• The participant or, when applicable, the participant's legally acceptable representative signs and dates a written, informed consent form and any required privacy authorization prior to the initiation of any study procedures.

Exclusion Criteria

• Has a history of type 1 diabetes.
• Has a history of acute metabolic diabetic complications.
• Has has abnormal Screening or Check-in (Day -2) laboratory values that suggest a clinically significant underlying disease (eg, active liver disease or jaundice) or participant with the following laboratory abnormalities: alanine aminotransferase (ALT) and/or aspartate aminotransferase (AST) >3 × upper limit of normal (ULN).
• Has a history of diabetic gastroparesis or history of gastric bypass surgery.
• Has a history of coronary angioplasty, coronary stent placement, coronary bypass surgery, or myocardial infarction within 6 months prior to Screening.
• Has New York Heart Association heart failure of Class (III-IV) regardless of therapy.
• Has a supine blood pressure >150 mm Hg for systolic or >90 mm Hg for diastolic, confirmed on repeat testing within a maximum of 5 minutes, at Screening and Check-in (Day -2).
• Has presence or history of neuropsychiatric disorder (eg, psychosis, psychotic disorders, depression associated with suicidal thinking, suicidal ideation or behavior).
• Has a history of drug abuse (defined as illicit drug use) or a history of alcohol abuse (defined as regular or daily consumption of more than 4 alcoholic drinks per day) within the past 2 years or is unwilling to agree to abstain from alcohol and drugs throughout the study.
• Has a hemoglobin ≤120 g/L for men and ≤100 g/L for women.
• Has a history of clinically significant allergies or idiosyncrasies to roflumilast, alogliptin and exenatide or any inactive ingredient(s) of these products, eg, rare hereditary problems of galactose intolerance, the Lapp lactase deficiency, glucose-galactose malabsorption or phenylketonuria.
• Has received alogliptin or roflumilast in a previous clinical study or as a therapeutic agent within 2 months prior to Screening, or is taking prescription roflumilast for chronic obstructive pulmonary disease (COPD), or has received any other investigational compound within 30 days prior to the first dose of study medication, or is participating or plans to participate in any other clinical trial during this study.
• If female, is pregnant or lactating or intending to become pregnant before, during, or within 30 days after last dose; or intending to donate ova during such time period.
• If male, intends to donate sperm during the course of the study or for 30 days after last dose of study medication