Relative Bioavailability of Different Formulations of BI 671800 in Healthy Male and Female Volunteers

Boehringer Ingelheim

Status and phase: Completed; Phase 1

Conditions: Healthy

Treatments: Drug: BI 671800 HEA, 200 mg tablets; Drug: BI 671800 HEA EC, 200 mg tablets; Drug: BI 671800 ED, 100 mg capsules; Drug: BI 671800 HEA, 50 mg tablets; Other: Standard meal

Study type: Interventional

Funder types: Industry

Identifiers

NCT02221388

1268.56

Details and patient eligibility

About

To compare the oral bioavailability and rate of absorption of two different formulations of BI 671800 HEA (choline salt) tablets 200 mg, one with enteric coating (EC) and one without EC, versus 2 x 100 mg BI 671800 ED (ethylenediamine salt) capsules. Both BI 671800 HEA formulations were further investigated concerning food effect and one of the two BI 671800 HEA formulations identified by interim pharmacokinetic analysis was further investigated concerning dose proportionality with 50 mg.

Enrollment: 24 patients

Sex: All

Ages: 21 to 50 years old

Volunteers: Accepts Healthy Volunteers

Inclusion criteria

• Healthy males and females according to the following criteria: Based upon a complete medical history, including physical examination, vital signs (BP, PR), 12-lead ECG, clinical laboratory tests
• Age 21 to 50 years (incl.)
• BMI 18.5 to 29.9 kg/m2 (incl.)
• Signed and dated written informed consent prior to admission to the study in accordance with GCP and the local legislation

Exclusion criteria

• Any finding of the medical examination (including BP, PR and ECG) deviating from normal and of clinical relevance
• 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)
• Diseases of the central nervous system (such as epilepsy) or psychiatric disorders or neurological disorders
• History of relevant orthostatic hypotension, fainting spells or blackouts
• Chronic or relevant acute infections
• History of relevant allergy or hypersensitivity (including allergy to drug or its excipients)
• Intake of drugs within one month or less than 10 half-lives of the respective drug prior to first study drug administration
• Participation in another trial with an investigational drug within 2 months prior to administration or during the trial
• Smoker (more than 10 cigarettes or 3 cigars or 3 pipes daily)
• Alcohol abuse (average consumption of more than 20 g/day in females and 30 g/day in males)
• Drug abuse
• Blood donation (more than 100 mL within four weeks prior to day 1 of visit 2)
• Any laboratory value outside the reference range that is of clinical relevance, especially repeated alanine aminotransferase (ALT), aspartate aminotransferase (AST), gamma-glutamyltransferase (GGT), alkaline phosphatase (ALP) or total bilirubin above upper limit of normal (ULN) at screening and not resolved before dosing.
• Inability to comply with dietary regimen of trial site
• Unwilling to avoid excessive sunlight exposure
• Use of drugs which might reasonably influence the results of the trial or that prolong the QT/QTc interval within 10 days prior to administration or during the trial, and CYP2C8 substrates such as amiodarone, amodiaquine, paclitaxel, rosiglitazone, pioglitazone and repaglinide or CYP2C9 such as warfarin, tolbutamide, phenytoin, losartan, acenocoumarol within 1 month or six half lives (whichever is greater).
• A marked baseline prolongation of the QTc interval (e.g., repeated demonstration of a QTc interval >450 ms)
• A history of additional risk factors for torsade de pointes (e.g., heart failure, hypokalaemia, family history of Long QT Syndrome)

For female subjects of childbearing potential only:

• Positive pregnancy test, pregnancy or planning to become pregnant during the study or within 2 months after study completion
• No adequate contraception during the study including three months before first dosing until 2 month after study completion, e.g. not any of the following: implants, injectables, combined hormonal contraceptives, intrauterine device, or surgical sterilisation (including hysterectomy). In addition to this, also a barrier method (e.g. condom) will be required, if the female is not surgically sterilised.
• Lactation

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Crossover Assignment

Masking: None (Open label)

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24 participants in 6 patient groups

BI 671800 ED capsules

Active Comparator group

Treatment:

Drug: BI 671800 ED, 100 mg capsules

BI 671800 HEA tablet in fasted state

Experimental group

Treatment:

Drug: BI 671800 HEA, 200 mg tablets

BI 671800 HEA EC tablet in fasted state

Experimental group

Treatment:

Drug: BI 671800 HEA EC, 200 mg tablets

BI 671800 HEA tablet in fed state

Experimental group

Treatment:

Drug: BI 671800 HEA, 200 mg tablets

Other: Standard meal

BI 671800 HEA EC tablet in fed state

Experimental group

Treatment:

Other: Standard meal

Drug: BI 671800 HEA EC, 200 mg tablets

BI 671800 HEA, 50 mg tablet in fasted state

Experimental group

Treatment:

Drug: BI 671800 HEA, 50 mg tablets