Investigate the Effect of AZD1656 on the Pharmacokinetics of Digoxin in Type 2 Diabetes Mellitus Patients

Study Overview
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Brief Summary
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The purpose of this study is to determine whether AZD1656 will affect the pharmacokinetics (PK) of digoxin in type 2 diabetes mellitus (T2DM) patients.

Official Title
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An Open-label, Randomised, Placebo Controlled, Two-Way Crossover, Phase I Single Centre Study in Type 2 Diabetes Mellitus Patients Treated With Metformin to Evaluate the Pharmacokinetics of Digoxin During Co-administration With AZD1656

Conditions
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Type 2 Diabetes Mellitus

Intervention / Treatment
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* Drug: AZD1656
* Drug: Digoxin
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients with confirmed type 2 diabetes for at least 1 year and treated with metformin as a single treatment or in combination with one other oral anti diabetic for at least 2 months prior to screening. Body mass index between ≥19 and ≤42 kg/m2. Haemoglobin (Hb) A1c ≥6.5% and ≤9.5% at enrolment. Exclusion Criteria: History of cardiovascular disease, eg, left ventricular hypertrophy, uncontrolled hypertension, paroxysmal or persistent cardiac arrhythmia or ischemic heart disease. Systolic blood pressure >160 mmHg or diastolic blood pressure >95 mmHg at screening Use of amiodarone within 3 months prior to screening and the use of potent CYP450 inhibitors

Ages Eligible for Study
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Minimum Age: 18 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: Crossover Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1<br>twice daily Day 1 to Day 7; digoxin on day 4 | Drug: AZD1656<br>* Oral tablet bd, step-wise increased dosage<br>Drug: Digoxin<br>* Oral tablet od on Day 4<br>* Other names: Digacin;|
| Placebo Comparator: 2<br>twice daily Day 1 to Day 7; digoxin on day 4. | Drug: Digoxin<br>* Oral tablet od on Day 4<br>* Other names: Digacin;Drug: Placebo<br>* Oral tablet bd, step-wise increased dosage<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| evaluate the pharmacokinetics of digoxin after a single dose when administered alone and in combination with AZD1656 at steady state, by assessment of AUC and Cmax of digoxin |  | Serial PK blood samples will be taken on days 4-8 during the treatment periods | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| evaluate the safety of AZD1656 in combination with digoxin by assessment of electrocardiogram, weight, pulse, blood pressure, laboratory variables (including 7-point glucose), physical examination and adverse events. |  | Safety assessments will be monitored throughout the study, from screening visit until follow up visit. | 
| describe the pharmacokinetics of AZD1656 and its metabolite during concomitant digoxin administration by assessment of AUC(0-24), Cmax, Ctrough, tmax, t1/2 and CL/F (AZD1656 only). |  | Serial PK blood samples will be taken on days 4-8 during the treatment periods | 
| describe the pharmacokinetics of digoxin when administered alone or in combination with AZD1656 by assessment of tmax and t1/2. |  | Serial PK blood samples will be taken on days 4-8 during the treatment periods | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Diabetes, Type 2, Digoxin, drug-drug interaction