Bioavailability of Soft Gelatin Capsule Formulation of BI 201335 NA Compared to the Solution Formulation in Healthy Volunteers

• Sponsor: Boehringer Ingelheim
• Information provided by (Responsible Party): Boehringer Ingelheim

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Healthy	Drug: low dose BI 201335 NA soft gelatine capsule (SGC); Drug: high dose BI 201335 NA soft gelatine capsule (SGC); Drug: low dose BI 201335 NA powder in bottle (PIB); Drug: high dose BI 201335 NA powder in bottle (PIB)	Phase 1

Study Design

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Study Type :	Interventional (Clinical Trial)
Actual Enrollment :	34 participants
Allocation:	Randomized
Intervention Model:	Crossover Assignment
Masking:	None (Open Label)
Primary Purpose:	Treatment
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 Start Date :	January 2008
Actual Primary Completion Date :	February 2008

Arms and Interventions

Arm	Intervention/treatment
Experimental: BI 201335 NA - low dose	Drug: low dose BI 201335 NA soft gelatine capsule (SGC); Drug: low dose BI 201335 NA powder in bottle (PIB)
Experimental: BI 201335 NA - high dose	Drug: high dose BI 201335 NA soft gelatine capsule (SGC); Drug: high dose BI 201335 NA powder in bottle (PIB)

Outcome Measures

Primary Outcome Measures :

1. AUC0-∞ (area under the concentration-time curve of the analyte in plasma over the time interval from 0 extrapolated to infinity) [ Time Frame: 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 ]
2. Cmax (measured maximum concentration of the analyte in plasma) [ Time Frame: 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 Outcome Measures :

1. tmax (time from dosing to the maximum concentration of the analyte in plasma) [ Time Frame: 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 ]
2. 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) [ Time Frame: 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 ]
3. t1/2 (terminal half-life of the analyte in plasma) [ Time Frame: 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 ]
4. CL/F (apparent clearance of the analyte in the plasma after oral administration) [ Time Frame: 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 ]
5. λz (terminal elimination rate constant in plasma) [ Time Frame: 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 ]
6. MRTpo (mean residence time of the analyte in the body after oral administration) [ Time Frame: 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 ]
7. Vz/F (apparent volume of distribution during the terminal phase λz following an oral dose) [ Time Frame: 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 ]
8. C24 (measured concentration of the analyte in plasma 24 hours after oral administration) [ Time Frame: 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 ]
9. Number of patients with clinically significant changes in vital signs [ Time Frame: Baseline, days 1-6 of each treatment period and day 22 ]
10. Number of patients with abnormal changes in laboratory parameters [ Time Frame: Baseline, days 1 and 3-6 of each treatment period and day 22 ]
11. Number of patients with adverse events [ Time Frame: up to 29 days ]

Eligibility Criteria

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Ages Eligible for Study:	18 Years to 50 Years (Adult)
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	Yes

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

Contacts and Locations

No Contacts or Locations Provided

More Information

Additional Information:

Related Info 

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Responsible Party:	Boehringer Ingelheim
ClinicalTrials.gov Identifier:	NCT02182284 History of Changes
Other Study ID Numbers:	1220.10
First Posted:	July 8, 2014
Last Update Posted:	July 18, 2014
Last Verified:	July 2014