Safety, Tolerability and Pharmacokinetics of Multiple Rising Doses of BI 201335 NA in Healthy Male Subjects

NCT02182362 | Completed Phase 1

• 1 other identifier: 1220.6
• Study Type: interventional
• Target: 39
• Locations: 0 countries
• Sites: N/A

Brief Summary

The main objective was to investigate the safety, tolerability and the pharmacokinetics (PK) of BI 201335 NA in healthy male subjects without Gilbert's syndrome or polymorphism (GS) following oral administration of a single dose (Day 1) and repeated doses (Days 4-24) of 20 mg, 48 mg, 120 mg, and 240 mg. Additionally, the safety, tolerability, and the PK of the highest tolerated dose of BI 201335 NA (determined during the multiple-rising-dose phase) were assessed in healthy male subjects with GS over a 28-day continuous drug administration period.

Conditions

Healthy

Outcome Measures

Primary Outcomes (6)

• Number of patients with abnormal findings in physical examination

  Baseline and up to 46 days

• Number of patients with clinically relevant changes in vital signs (blood pressure (BP), pulse rate (PR))

  Baseline and up to 32 days

• Number of patients with clinically relevant changes in 12-lead ECG (electrocardiogram)

  Baseline and up to 32 days

• Number of patients with clinically relevant changes in clinical laboratory tests (haematology, clinical chemistry, urinalysis)

  Baseline and up to 32 days

• Incidence of adverse events

  up to day 46

• Assessment of tolerability by investigator

  Day 28 or 32

Secondary Outcomes (18)

• Cmax (maximum measured concentration of the analyte in plasma)

  Pre-dose and 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 24, 30, 36, 48, 60 hours after first treatment

• tmax (time from dosing to maximum measured concentration of the analyte in plasma)

  Pre-dose and 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 24, 30, 36, 48, 60 hours after first treatment

• AUCτ,1 (area under the concentration-time curve of the analyte in plasma over a uniform dosing interval τ after administration of the first dose)

  Pre-dose and 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 24, 30, 36, 48, 60 hours after first treatment

• AUC0-∞ (area under the concentration-time curve of the analyte in plasma over the time interval from 0 extrapolated to infinity)

  Pre-dose and 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 24, 30, 36, 48, 60 hours after first treatment

• λz (terminal rate constant in plasma)

  Pre-dose and 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 24, 30, 36, 48, 60 hours after first treatment

Study Arms (3)

BI 201335 NA in rising doses

EXPERIMENTAL

single dose of BI 201335 NA on day 1, multiple dosing days 4-24

Drug: BI 201335 NA

Placebo

PLACEBO COMPARATOR

Drug: Placebo

BI 201335 NA

EXPERIMENTAL

highest tolerated dose of BI 201335 on day 1-28 in patients with Gilbert's syndrome

Drug: BI 201335 NA

Interventions

BI 201335 NA DRUG

BI 201335 NA; BI 201335 NA in rising doses

Placebo DRUG

Placebo

Eligibility Criteria

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

You may qualify if:

• Healthy males according to the following criteria:
• Complete medical history, physical examination, vital signs (Blood Pressure, Pulse Rate), 12-lead ECG (electrocardiogram), and clinical laboratory tests
• Age ≥18 and Age ≤55 years
• BMI ≥18.5 and BMI ≤30 kg/m2 (Body Mass Index)
• Signed and dated written informed consent prior to admission to the study in accordance with GCP (Good Clinical Practice) and the local legislation

You may not qualify if:

• 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
• Subjects with polymorphisms associated with Gilbert's syndrome will be excluded from the initial 4 groups of the multiple rising dose phase of the study. However, only subjects with Gilbert's polymorphism will be allowed to participate in the last group which will be treated with the highest tolerated dose determined in the multiple rising dose phase of the trial
• Prior history of jaundice for subjects without Gilbert's polymorphism
• 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/hypersensitivity (including allergy to drug or its excipients)
• Intake of drugs with a long half-life (\> 24 hours) within at least one month or less than 10 half-lives of the respective drug prior to administration or during the trial
• Use of drugs which might reasonably influence the results of the trial or that prolong the QT/QTc interval within 30 days prior to screening until trial completion
• Participation in another trial with an investigational drug within two months prior to administration or during the trial
• Smoking (\> 10 cigarettes or \> 3 cigars or \> 3 pipes/day)
• Inability to refrain from smoking during the trial

Sponsors & Collaborators

• Boehringer Ingelheim: lead

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 2, 2014
• First Posted: July 8, 2014
• Study Start: May 1, 2007
• Primary Completion: February 1, 2008
• Last Updated: July 18, 2014

Record last verified: 2014-07