Study To Assess the Pharmacokinetics of AZD1656 During Coadministration With Simvastatin

Study Overview
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Brief Summary
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To assess the pharmacokinetics of AZD1656 during coadministration with Simvastatin.

Official Title
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A Randomized, Open-label, 3-way Crossover Phase I Study in Type 2 Diabetes Mellitus Patients Treated With Metformin to Evaluate the Pharmacokinetics and Pharmacodynamics of Simvastatin During Coadministration With AZD1656 and to Evaluate the Pharmacokinetics of AZD1656 During Coadministration With Simvastatin

Conditions
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Type 2 Diabetes Mellitus

Intervention / Treatment
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* Drug: AZD1656
* Drug: simvastatin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients with a clinical diagnosis of T2DM for at least 1 year, treated with any metformin or metformin with one other oral anti-diabetic drug (OAD) Body mass index between greater than or equal to 19 and less than or equal to 42 kg/m2 HbA1c greater than 6.5% at enrollment Exclusion Criteria: Clinically significant illness or clinically relevant trauma, as judged by the Investigator, within 2 weeks before the first administration of the IP Significant cardiovascular event within the last 6 months prior to enrollment (eg, myocardial infarction/acute coronary syndrome, revascularisation procedure, stroke or transient ischaemic attack) or heart failure New York Heart Association (NYHA) class III-IV

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

Allocation: Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1<br>AZD1656 | Drug: AZD1656<br>* Oral tablet, BID dose<br>|
| Experimental: 2<br>Simvastatin | Drug: simvastatin<br>* Oral tablet, single dose<br>|
| Experimental: 3<br>AZD1656 + simvastatin | Drug: AZD1656<br>* Oral tablet, BID dose<br>Drug: simvastatin<br>* Oral tablet, single dose<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To evaluate the effect of AZD1656 on the steady state pharmacokinetics of simvastatin (including simvastatin acid) and vice versa by assessment of AUC(0-24) and Cmax. |  | Frequent blood samples for PK analysis will be drawn during 24 hours post morning dose on day 4 in each treatment period (1-3) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To evaluate the effect of AZD1656 on the steady state pharmacokinetics of simvastatin and simvastatin acid and vice versa by assessment of tmax, t1/2 and CL/F (only for AZD1656) |  | Frequent serial blood samples will be drawn during 24 hours post morning dose on Day 4 in each treatment period (1-3) | 
| To evaluate the steady state pharmacokinetics of the AZD1656 metabolite when AZD1656 is administered with and without simvastatin, by assessment of AUC(0-24), Cmax and tmax. |  | Frequent serial blood samples will be drawn during 24 hours post morning dose on Day 4 in each treatment period (1-3) | 
| To evaluate the effect of AZD1656 on the pharmacodynamics of simvastatin by assessment of AUC(0-t) and Cmax of active 3-hydroxy-3-methyl-glutaryl-CoA reductase inhibitors. |  | Frequent serial blood samples will be drawn during 24 hours post morning dose on Day 4 in each treatment period (1-3) | 
| To evaluate the safety and tolerability of AZD1656 alone and in combination with simvastatin by assessments of adverse events, laboratory variables, electrocardiogram, blood pressure, pulse, results of physical examination, and weight. |  | At pre entry, during the study days, | 

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