Gastrointestinal Behavior of Posaconazol in Healthy Volunteers

NCT ID: NCT02048345

Last Updated: 2014-01-29

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: NA
• Total Enrollment: 10 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2014-01-31

Brief Summary

The aim of this study is to understand the behavior of posaconazol gives as a suspension and solution in the gastrointestinal tract in human volunteers. The investigators know that supersaturation for this compound can be achieved by the influence of the gastrointestinal tract: The acid environment of the stomach creates a optimized environment for the basic compound to reach a high solubility, while the neutral environment of the small intestine creates a low solubility environment for the compound. The transit from stomach to small intestine gives the opportunity for the drug to create a supersaturated solution. Giving the drug as a solution to the healthy volunteer makes sure that precipitation is not occurring in the stomach and that precipitation has to happen in the small intestine. After all, supersaturation is a state that is not thermodynamic stable and always will want to precipitate. Giving the drug as a suspension to the healthy volunteers, can make it possible that still some particles of the drug are not in dissolution and that those particles will flow to the small intestine where other particles easily can bind to. This will make that almost the whole supersaturated solution is immediately precipitated.

The investigators want to give the suspension by the authorized drug called Noxafil. On the other hand an aqueous solution will be made by adjusting the pH to 1.2 (which is conform with the pH of the stomach) and given to the volunteers by the stomach catheter. This 2 formulations will be tested in a fasted state and a fed state (by giving 2 Ensure plus shakes to the volunteers before the experiment starts). After intake of the formulation, gastric and duodenal fluids will be aspirated by the catheters and analyzed at their laboratory. So the four conditions the investigators want to study are:

1. 10 mL Suspension of posaconazol (Noxafil 40mg/mL) together with a glass of 240 mL water in a fasted state

2. 250 mL solution of posaconazol, by dissolving 2.6 mL autohorized suspension (Noxafil) in 247 mL water, adjusted to pH 1.2 by hydrochloric acid given to the volunteer in a fasted state.

3. 10 mL Suspension of posaconazol (Noxafil 40mg/mL) together with a glass of 240 mL water in a fed state (by giving 20 minute before intake of the formulation, 2 ensure plus shakes)

4. 250 mL solution of posaconazol, by dissolving 2.6 mL autohorized suspension (Noxafil) in 247 mL water, adjusted to pH 1.2 by hydrochloric acid given to the volunteer in a fed state (by giving 20 minute before intake of the formulation, 2 ensure plus shakes).

By getting more knowledge about the behavior of posaconazol (interplay supersaturation / precipitation) more insights can be achieved for the development of supersaturating drug delivery systems.

Conditions

Healthy

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: BASIC_SCIENCE
• Blinding Strategy: NONE

Study Groups

Suspension, fasted state

Suspension Noxafil will be administered in the fasted state to the volunteers.

Group Type: EXPERIMENTAL

Suspension Fasted State

Intervention Type: DRUG

Suspension, with sugar (delay gastric emptying)

Suspension will be co-administered with glucose to delay the gastric emptying time

Group Type: EXPERIMENTAL

Suspension Fed State

Intervention Type: DRUG

Solution, fasted state

A solution (by acidifying the suspension in water to pH 1.2) will be administered to healthy volunteers in a fasted state.

Group Type: EXPERIMENTAL

Solution Fasted State

Intervention Type: DRUG

Solution, with sugar (delaying gastric emptying)

A solution of posaconazol (by acidifying the suspension in water to pH 1.2) will be administered together with sugar to delay the gastric emptying.

Group Type: EXPERIMENTAL

Solution Fed State

Intervention Type: DRUG

Interventions

Suspension Fasted State

Intervention Type: DRUG

Suspension Fed State

Intervention Type: DRUG

Solution Fasted State

Intervention Type: DRUG

Solution Fed State

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• 18-40 years Healthy volunteers

Exclusion Criteria

• disease Hiv, Hepatitis B, Hepatitis C Pregnant Drug abuse

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 40 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

KU Leuven

OTHER

Sponsor Role: lead

Responsible Party

Bart Hens

Pharmacist

Responsibility Role: PRINCIPAL_INVESTIGATOR

Locations

UZ Leuven Gasthuisberg

Leuven, , Belgium

Site Status: RECRUITING

Countries

Belgium

Central Contacts

Bart Hens, Pharmacist

Role: CONTACT

bart.hens@pharm.kuleuven.be

+3216330302

Facility Contacts

Bart Hens, Pharmacist

Role: primary

bart.hens@pharm.kuleuven.be

+3216330302

Other Identifiers

DDD13POSA

Identifier Type: -

Identifier Source: org_study_id