Relative Bioavailability Study With Enalapril in Healthy Volunteers

Heart Failure Clinical Trial

Official title:

Relative Bioavailability of Enalapril Administered as Orodispersible Minitablets in Healthy Adults

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT02252692
• Other study ID #: 2014-000956-28
• Status: Active, not recruiting
• Phase: Phase 1
• First received: September 6, 2014
• Last updated: September 26, 2014
• Start date: August 2014
• Est. completion date: October 2014

Study information

• Verified date: September 2014
• Source: Ethicare GmbH
• Contact: n/a
• Is FDA regulated: No
• Health authority: Belgium: Federal Agency for Medicines and Health Products, FAMHP
• Study type: Interventional

Clinical Trial Summary

Phase I study in healthy adult male and female volunteers to compare the bioavailability of enalapril administered in orodispersible Minitablets with or without water in comparison to the standard galenic tablet formulation of enalapril. The standard pharmacokinetic parameters will be calculated from the bioanalytical results for enalapril and enalaprilat and compared in a descriptive statistical analysis.

Description:

Trial design: Open label, randomized, 3-way cross-over, 3-treatments, 3-periods in 24 healthy male and female adult subjects.

Primary objectives:

1. To assess the relative bioavailability of 10 mg enalapril administered as orodispersible minitablets (ODMT) with water versus a standard enalapril tablet formulation (reference product: Renitec® 2 x 5 mg tablets) taken with water;

2. To assess the relative bioavailability of 10 mg enalapril administered as orodispersible minitablets (ODMT) dispersed in the oral cavity versus a standard enalapril tablet formulation (reference product: Renitec® 2 x 5 mg tablets) taken with water.

Secondary objectives:

1. To assess whether the PK of enalapril is affected when the orodispersible minitablet (ODMT) is entirely swallowed with water versus dispersion in the oral cavity.

2. To assess the general safety and tolerability including local tolerability and palatability of enalapril administered as orodispersible minitablet (ODMT).

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 24
• Est. completion date: October 2014
• Est. primary completion date: October 2014
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Both
• Age group: 18 Years to 55 Years

Eligibility

Inclusion Criteria:

1. Healthy male and female subjects aged between 18 and 55 years, inclusive.

2. Body mass index (BMI) between 18.5 and 30 kg/m2 inclusive (BMI = weight/height2).

3. Non-smoker (not smoked for at least 3 months prior to screening).

4. Physical examinations, clinical laboratory values, vital signs and ECGs are clinically acceptable to the investigator.

5. Subjects must have signed an informed consent document indicating that they understand the purpose of, and procedures required for the study and are willing to participate in the study and comply with the study procedures and restrictions.

Exclusion Criteria:

1. History or evidence of clinically significant disorder (including psychiatric), condition or disease that, in the opinion of the investigator would pose a risk to subject safety or interfere with the study evaluation, procedures, or completion.

2. Women who are lactating/breastfeeding.

3. Women planning to become pregnant during the duration of the study.

4. Men with pregnant partners or whose partners plan to become pregnant during the study.

5. Positive pregnancy test (women) on screening or predose.

6. A baseline systolic BP = 140 or < 90 mmHg and/or a baseline diastolic BP of = 90 or <50 mmHg. A baseline ECG QTcB > 440 ms (males) or >450 ms (females) or heart rate >100 bpm.

7. Positive for human immunodeficiency virus (HIV) antibodies, hepatitis B surface antigen, or hepatitis C antibodies at screening.

8. Known substance abuse (eg, alcohol, illicit or illegal drugs) within 1 year of dosing.

9. Positive test for drug or alcohol use at screening. If the retest during the screening period is negative, subject can be included.

10. Inability or unwillingness to refrain from alcohol consumption 24 hours prior to study visits and to limit consumption throughout the course of the study.

11. Has had major surgery, donated or lost 500 mL or more of blood within 2 months of the first study treatment or has a history of chronic anemia.

12. Receiving or has received any investigational drug (or is currently using an investigational drug or device) within 30 days or 5 half-lives (whichever is longer), prior to receiving the first study treatment.

13. Use of any over-the-counter or prescription medications within 7 days or 5 half-lives (whichever is longer), prior to receiving the first study treatment. However, if a subject has to use medication within 7 days of the first study drug administration, he/she can be included in the study the study if according to the investigator the medication is not relevant within the context of the trial. Paracetamol (up to 2 g per day) for analgesia, and hormonal birth control medication will be allowed.

14. Use of any herbal medicines (eg. St. John's wort), vitamins, and supplements consumed by the subject within 7 days prior to receiving the first study treatment. However, if a subject has used herbal medicines (eg, St. John's wort), vitamins, and supplements medication within 7 days of the first study drug administration, he/she can be included in the study if according to the investigator the medication is not relevant within the context of the trial.

Study Design

Allocation: Randomized, Endpoint Classification: Bio-availability Study, Intervention Model: Crossover Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Heart Failure

Intervention

Drug:
• Enalapril
oral administration

Locations

Country	Name	City	State
Belgium	Center for Clinical Pharmacology, UZ Leuven	Leuven

Sponsors (2)

Lead Sponsor	Collaborator
Ethicare GmbH	European Commission

Country where clinical trial is conducted

Belgium, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	AUC 0-8	Area under the serum concentration-time curve from time of administration to infinite time for enalaprilat	predose, 10 min, 20 min, 30 min, 45 min, 1 hour, 1.25 hours,1.5 hours, 2 hours, 2.5 hours, 3 hours, 3.5 hours, 4 hours, 4.5 hours, 5 hours, 6 hours, 8 hours, 10 hours, 12 hours, 24 hours, 36 hours, 48 hours post-dose	No
Secondary	Safety parameters	adverse events	0-48 hours post dose, at follow-up visit	Yes
Secondary	Tolerability Outcome Parameter	orodispersible minitablet palatability questionnaire	Immediately and 10 minutes after orodispersible minitablet administration	Yes
Secondary	AUC 0-8	Area under the serum-concentration time curve from time of administration extrapolated to infinite time for enalapil	predose, 10 min, 20 min, 30 min, 45 min, 1 hour, 1.25 hours,1.5 hours, 2 hours, 2.5 hours, 3 hours, 3.5 hours, 4 hours, 4.5 hours, 5 hours, 6 hours, 8 hours, 10 hours, 12 hours, 24 hours, 36 hours, 48 hours post-dose	No
Secondary	AUC 0-t	Area under the serum concentration-time curve from from administration to the last measurable concentration or last sampling time point (48h) for enalapril	predose, 10 min, 20 min, 30 min, 45 min, 1 hour, 1.25 hours,1.5 hours, 2 hours, 2.5 hours, 3 hours, 3.5 hours, 4 hours, 4.5 hours, 5 hours, 6 hours, 8 hours, 10 hours, 12 hours, 24 hours, 36 hours, 48 hours post-dose	No
Secondary	AUC 0-t	Area under the serum concentration-time curve from from administration to the last measurable concentration or last sampling time point (48h) for enalaprilat	predose, 10 min, 20 min, 30 min, 45 min, 1 hour, 1.25 hours,1.5 hours, 2 hours, 2.5 hours, 3 hours, 3.5 hours, 4 hours, 4.5 hours, 5 hours, 6 hours, 8 hours, 10 hours, 12 hours, 24 hours, 36 hours, 48 hours post-dose	No
Secondary	Cmax	Maximum serum concentration for enalapril	predose, 10 min, 20 min, 30 min, 45 min, 1 hour, 1.25 hours,1.5 hours, 2 hours, 2.5 hours, 3 hours, 3.5 hours, 4 hours, 4.5 hours, 5 hours, 6 hours, 8 hours, 10 hours, 12 hours, 24 hours, 36 hours, 48 hours post-dose	No
Secondary	Cmax	Maximum serum concentration of enalaprilat	predose, 10 min, 20 min, 30 min, 45 min, 1 hour, 1.25 hours,1.5 hours, 2 hours, 2.5 hours, 3 hours, 3.5 hours, 4 hours, 4.5 hours, 5 hours, 6 hours, 8 hours, 10 hours, 12 hours, 24 hours, 36 hours, 48 hours post-dose	No
Secondary	tmax	Time of maximum serum concentration of enalapril	predose, 10 min, 20 min, 30 min, 45 min, 1 hour, 1.25 hours,1.5 hours, 2 hours, 2.5 hours, 3 hours, 3.5 hours, 4 hours, 4.5 hours, 5 hours, 6 hours, 8 hours, 10 hours, 12 hours, 24 hours, 36 hours, 48 hours post-dose	No
Secondary	tmax	Time of maximum serum concentration for enalaprilat	predose, 10 min, 20 min, 30 min, 45 min, 1 hour, 1.25 hours,1.5 hours, 2 hours, 2.5 hours, 3 hours, 3.5 hours, 4 hours, 4.5 hours, 5 hours, 6 hours, 8 hours, 10 hours, 12 hours, 24 hours, 36 hours, 48 hours post-dose	No
Secondary	Ae	Amount of enalaprilat or the sum of enalapril and enalaprilat excreted in urine over the time interval 0-t	0-2, 2-4, 4-8, 8-12, 12-24, 24-36, 36-48 hours post-dose	No