Effect of Liraglutide on Gastrointestinal Absorption of Several Drugs and Potential Influence of Liraglutide on Intragastric pH

Study Overview
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Brief Summary
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The trial is conducted in Europe. The aim of the trial is to investigate if there is any drug to drug interaction between liraglutide and atorvastatin (Lipitor®), lisinopril (Zestril®), griseofulvin and digoxin (Lanoxin®).

Official Title
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A Two-way Cross-over, Placebo-controlled Interaction Trial in Two Parts (in Healthy Subjects), Studying Liraglutide's Potential Influence on the Absorption Pharmacokinetics of Lisinopril, Atorvastatin, Griseofulvin and Digoxin, and Liraglutide's Potential Influence on Intragastric pH

Conditions
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Diabetes, Healthy

Intervention / Treatment
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* Drug: liraglutide
* Drug: placebo
* Drug: atorvastatin
* Drug: lisinopril
* Drug: griseofulvin
* Drug: digoxin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Female subjects if using adequate anti-contraception or is sterile Body Mass Index (BMI) of 18-30 kg/m^2 (both inclusive) Good general health as judged by the investigator, based on medical history, physical examination including 12-lead ECG (electrocardiogram), vital signs and blood and urinary laboratory assessments Willing and capable to self-administer a subcutaneous injection Exclusion Criteria: History of any clinically significant renal, hepatic, cardiovascular, pulmonary, gastrointestinal, metabolic, endocrine, haematological, neurological, psychiatric disease or other major disorders that may interfere with the objectives of the trial, as judged by the investigator Impaired renal function Blood pressure and heart rate in supine position outside the ranges 90-140 mmHg systolic, 50-90 mmHg diastolic and heart rate 40-100 beats/min Any clinically significant abnormal ECG Active hepatitis B and/or active hepatitis C Positive HIV (human immunodeficiency virus) antibodies Known or suspected allergy to trial product(s) or related products Use of any prescription or non-prescription medication except for paracetamol, nasal spray or drops for nasal congestion, and vitamins within 2 weeks prior to first dosing and during the entire trial period History of alcoholism or drug abuse during the last 12 months Smoking of more than 10 cigarettes per day, or the equivalent for other tobacco products Habitual excessive consumption of methylxanthine-containing beverages and foods (coffee, tea, soft drinks such as cola, chocolate) as judged by the Investigator

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 55 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

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: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Trial period A<br> | Drug: liraglutide<br>* Administered as a subcutaneous injection. Initial dose 0.6 mg daily, adjusted to 1.2 mg daily in week 2 and escalated to 1.8 mg daily in week 3<br>Drug: placebo<br>* Administered as a subcutaneous injection. Given as daily volume of 100 mcl, 200 mcl and 300 mcl respectively<br>Drug: atorvastatin<br>* One single dose of 40 mg. Tablet<br>Drug: lisinopril<br>* One single dose of 20 mg. Tablet<br>|
| Experimental: Trial period B<br> | Drug: liraglutide<br>* Administered as a subcutaneous injection. Initial dose 0.6 mg daily, adjusted to 1.2 mg daily in week 2 and escalated to 1.8 mg daily in week 3<br>Drug: placebo<br>* Administered as a subcutaneous injection. Given as daily volume of 100 mcl, 200 mcl and 300 mcl respectively<br>Drug: griseofulvin<br>* One single dose of 500 mg. Tablet<br>Drug: digoxin<br>* One single dose of 1 mg. Tablet<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Area under the curve of atorvastatin |  |  | 
| Area under the curve of lisinopril |  |  | 
| Area under the curve of griseofulvin |  |  | 
| Area under the curve of digoxin |  |  | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Area under the curve of liraglutide |  |  | 
| Cmax, maximum concentration |  |  | 
| tmax, time to reach Cmax |  |  | 
| Terminal elimination rate constant |  |  | 
| Intragastric pH |  |  | 
| Adverse events |  |  |