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

Sponsor

Novo Nordisk A/S (Industry)

Overall Status

Completed

CT.gov ID

NCT01518166

Collaborator

(none)

Enrollment

Location

Arms

Duration (Months)

6.4

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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®).

Condition or Disease	Intervention/Treatment	Phase
Diabetes Healthy	Drug: liraglutide Drug: placebo Drug: atorvastatin Drug: lisinopril Drug: griseofulvin Drug: digoxin	Phase 1

Study Design

Study Type:

Interventional

Actual Enrollment :

70 participants

Allocation:

Randomized

Intervention Model:

Crossover Assignment

Masking:

Double (Participant, Investigator)

Primary Purpose:

Treatment

Official Title:

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

Study Start Date :

May 1, 2006

Actual Primary Completion Date :

Apr 1, 2007

Actual Study Completion Date :

Apr 1, 2007

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Trial period A	Drug: liraglutide 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 Drug: placebo Administered as a subcutaneous injection. Given as daily volume of 100 mcl, 200 mcl and 300 mcl respectively Drug: atorvastatin One single dose of 40 mg. Tablet Drug: lisinopril One single dose of 20 mg. Tablet
Experimental: Trial period B	Drug: liraglutide 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 Drug: placebo Administered as a subcutaneous injection. Given as daily volume of 100 mcl, 200 mcl and 300 mcl respectively Drug: griseofulvin One single dose of 500 mg. Tablet Drug: digoxin One single dose of 1 mg. Tablet

Arm

Intervention/Treatment

Experimental: Trial period A

Drug: liraglutide

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

Drug: placebo

Administered as a subcutaneous injection. Given as daily volume of 100 mcl, 200 mcl and 300 mcl respectively

Drug: atorvastatin

One single dose of 40 mg. Tablet

Drug: lisinopril

One single dose of 20 mg. Tablet

Experimental: Trial period B

Drug: liraglutide

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

Drug: placebo

Administered as a subcutaneous injection. Given as daily volume of 100 mcl, 200 mcl and 300 mcl respectively

Drug: griseofulvin

One single dose of 500 mg. Tablet

Drug: digoxin

One single dose of 1 mg. Tablet

Outcome Measures

Primary Outcome Measures

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

Area under the curve of liraglutide []
Cmax, maximum concentration []
tmax, time to reach Cmax []
Terminal elimination rate constant []
Intragastric pH []
Adverse events []

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 55 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Yes

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