Relative Bioavailability Study With Enalapril in Healthy Volunteers

NCT02252692 | Unknown Phase 1

• 1 other identifier: 2014-000956-28
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Heart Failure

Keywords

Bioavailability; pharmacokinetics; enalapril; enalaprilat

Outcome Measures

Primary Outcomes (1)

• AUC 0-∞

  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

Secondary Outcomes (10)

• Safety parameters

  0-48 hours post dose, at follow-up visit

• Tolerability Outcome Parameter

  Immediately and 10 minutes after orodispersible minitablet administration

• AUC 0-∞

  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

• AUC 0-t

  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

• AUC 0-t

  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

Study Arms (3)

Enalapril

ACTIVE COMPARATOR

Renitec® 2 x 5 mg tablets administered at once, to be entirely swallowed with 240 ml water

Drug: Enalapril

Enalapril ODMT

EXPERIMENTAL

10 x 1mg of Enalapril ODMT, swallowed entirely with 240ml of water

Drug: Enalapril

Enalapril ODMT dispersed

EXPERIMENTAL

10 x 1mg of Enalapril ODMT, dispersed on tongue

Drug: Enalapril

Interventions

Enalapril DRUG

oral administration

Also known as: Renitec

Enalapril; Enalapril ODMT; Enalapril ODMT dispersed

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Healthy male and female subjects aged between 18 and 55 years, inclusive.
• Body mass index (BMI) between 18.5 and 30 kg/m2 inclusive (BMI = weight/height2).
• Non-smoker (not smoked for at least 3 months prior to screening).
• Physical examinations, clinical laboratory values, vital signs and ECGs are clinically acceptable to the investigator.
• 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.

You may not qualify if:

• 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.
• Women who are lactating/breastfeeding.
• Women planning to become pregnant during the duration of the study.
• Men with pregnant partners or whose partners plan to become pregnant during the study.
• Positive pregnancy test (women) on screening or predose.
• 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.
• Positive for human immunodeficiency virus (HIV) antibodies, hepatitis B surface antigen, or hepatitis C antibodies at screening.
• Known substance abuse (eg, alcohol, illicit or illegal drugs) within 1 year of dosing.
• Positive test for drug or alcohol use at screening. If the retest during the screening period is negative, subject can be included.
• Inability or unwillingness to refrain from alcohol consumption 24 hours prior to study visits and to limit consumption throughout the course of the study.
• 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.
• 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.
• 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.
• 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.

Sponsors & Collaborators

• Ethicare GmbH: lead
• European Commission: collaborator

Study Sites (1)

Center for Clinical Pharmacology, UZ Leuven

Leuven, 3000, Belgium

Location

MeSH Terms

Conditions

Heart Failure

Interventions

Enalapril

Condition Hierarchy (Ancestors)

Heart Diseases; Cardiovascular Diseases

Intervention Hierarchy (Ancestors)

Dipeptides; Oligopeptides; Peptides; Amino Acids, Peptides, and Proteins

Study Officials

• Jan De Hoon, Professor

  Center of Clinical Pharmacology, University Hospital Leuven, Leuven, Belgium

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 6, 2014
• First Posted: September 30, 2014
• Study Start: August 1, 2014
• Primary Completion: October 1, 2014
• Study Completion: October 1, 2014
• Last Updated: September 30, 2014

Record last verified: 2014-09

Locations

BE (1)