Clinical trial NCT02182284: Bioavailability of Soft Gelatin Capsule Formulation of BI 201335 NA Compared to the Solution Formulation in Healthy Volunteers
Official title: An Open-label, Randomized, Crossover Relative Bioavailability Study of a New Soft Gelatin Capsule Formulation of BI 201335 NA Compared to the Current Solution Formulation (Powder in Bottle (PIB), After Single Dose Oral Administration in Healthy Volunteers
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy
Lead sponsor: Boehringer Ingelheim
Sponsor class: INDUSTRY
First posted: 2014-07-08
Enrollment: 34
Sex: ALL
Minimum age (years): 18
Maximum age (years): 50
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

Brief summary: The objective of this study was to establish the relative bioavailability of a new soft gelatin capsule (SGC) formulation of BI 201335 NA compared to the current solution formulation (powder in bottle, PIB) for two doses (40 mg, 240 mg) in a parallel, two-way cross-over study design.


Eligibility criteria: Inclusion Criteria:

* Healthy males and females according to the following criteria: Based upon a complete medical history, including the physical examination, vital signs (blood pressure (BP), pulse rate (PR)), 12-lead ECG (electrocardiogram), clinical laboratory tests
* Age ≥18 and Age ≤50 years
* Body Mass Index (BMI) ≥18.5 and BMI ≤29.9 kg/m2
* Signed and dated written informed consent prior to admission to the study in accordance with GCP (Good Clinical Practice) and the local legislation

Exclusion Criteria:

* Any finding from the medical examination (including BP, PR and ECG) deviating from normal and of clinical relevance, as assessed by the investigator
* Any evidence of a clinically relevant concomitant disease
* Gastrointestinal, hepatic, renal, respiratory, cardiovascular, metabolic, immunological or hormonal disorders
* Surgery of the gastrointestinal tract (except appendectomy)
* Chronic or relevant acute infections
* History of relevant allergy/hypersensitivity (including allergy to drug or its excipients)
* Concomitant drugs that in the opinion of the investigator (in consultation with the BI medical monitor or pharmacokinetics), would have interfered with the adsorption, distribution or metabolism of BI 201335
* Use of drugs which might reasonably influence the results of the trial or that prolong the QT/QTc (corrected QT interval) interval within 30 days prior to screening until trial completion
* Use of any investigational drug within 30 days prior to enrolment; or the planned usage of any investigational drug during the course of the current study
* Smoking (\>10 cigarettes or \>3 cigars or \>3 pipes/day)
* Inability to abstain from alcohol from Day -14 to day 22
* Drug abuse
* Blood donation (more than 100 mL within four weeks prior to administration or during the trial)
* Excessive physical activities (within one week prior to administration or during the trial)
* Any laboratory value outside the reference range that is of clinical relevance at screening, according to the judgement of the investigator
* A marked baseline prolongation of QT/QTc interval (e.g., repeated demonstration of a QTc interval \>450 ms)
* Infected with hepatitis A, hepatitis B or hepatitis C viruses (defined as either being hepatitis A antibody positive, hepatitis B surface antigen or HBV DNA positive, or hepatitis C antibody positive)
* Positive ELISA for HIV-1 (Human immunodeficiency virus) or HIV-2
* For female subjects:

  * Pregnancy or planning to become pregnant within 2 months of study completion
  * Positive pregnancy test
  * No adequate contraception, e.g. sterilisation, IUD (intrauterine device), have not been using a barrier method of contraception for at least 3 months prior to participation in the study
  * Are not willing or are unable to use a reliable method of barrier contraception (such as diaphragm with spermicidal cream/jelly or condoms with spermicidal foam), during and up to 2 months after completion/termination of the trial
  * Lactation period

Primary outcomes:
measure: AUC0-∞ (area under the concentration-time curve of the analyte in plasma over the time interval from 0 extrapolated to infinity)
timeFrame: Before and 1, 2, 3, 4, 5, 6, 7, 8, 10, 12, 16, 24, 36, 48, 72, 96, 120 hours after administration of study drug
measure: Cmax (measured maximum concentration of the analyte in plasma)
timeFrame: Before and 1, 2, 3, 4, 5, 6, 7, 8, 10, 12, 16, 24, 36, 48, 72, 96, 120 hours after administration of study drug
Secondary outcomes:
measure: tmax (time from dosing to the maximum concentration of the analyte in plasma)
timeFrame: Before and 1, 2, 3, 4, 5, 6, 7, 8, 10, 12, 16, 24, 36, 48, 72, 96, 120 hours after administration of study drug
measure: AUC0-tz (area under the concentration-time curve of the analyte in plasma over the time interval from 0 to the time of the last quantifiable data point)
timeFrame: Before and 1, 2, 3, 4, 5, 6, 7, 8, 10, 12, 16, 24, 36, 48, 72, 96, 120 hours after administration of study drug
measure: t1/2 (terminal half-life of the analyte in plasma)
timeFrame: Before and 1, 2, 3, 4, 5, 6, 7, 8, 10, 12, 16, 24, 36, 48, 72, 96, 120 hours after administration of study drug
measure: CL/F (apparent clearance of the analyte in the plasma after oral administration)
timeFrame: Before and 1, 2, 3, 4, 5, 6, 7, 8, 10, 12, 16, 24, 36, 48, 72, 96, 120 hours after administration of study drug
measure: λz (terminal elimination rate constant in plasma)
timeFrame: Before and 1, 2, 3, 4, 5, 6, 7, 8, 10, 12, 16, 24, 36, 48, 72, 96, 120 hours after administration of study drug
measure: MRTpo (mean residence time of the analyte in the body after oral administration)
timeFrame: Before and 1, 2, 3, 4, 5, 6, 7, 8, 10, 12, 16, 24, 36, 48, 72, 96, 120 hours after administration of study drug
measure: Vz/F (apparent volume of distribution during the terminal phase λz following an oral dose)
timeFrame: Before and 1, 2, 3, 4, 5, 6, 7, 8, 10, 12, 16, 24, 36, 48, 72, 96, 120 hours after administration of study drug
measure: C24 (measured concentration of the analyte in plasma 24 hours after oral administration)
timeFrame: Before and 1, 2, 3, 4, 5, 6, 7, 8, 10, 12, 16, 24, 36, 48, 72, 96, 120 hours after administration of study drug
measure: Number of patients with clinically significant changes in vital signs
timeFrame: Baseline, days 1-6 of each treatment period and day 22
measure: Number of patients with abnormal changes in laboratory parameters
timeFrame: Baseline, days 1 and 3-6 of each treatment period and day 22
measure: Number of patients with adverse events
timeFrame: up to 29 days
Other outcomes:
Locations:
Study officials:
References: