Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of BI 653048 BS H3PO4 Capsule Multiple Rising Doses in Healthy Male Volunteers

August 14, 2014 updated by: Boehringer Ingelheim

Safety, Tolerability, Pharmacokinetics and Pharmacodynamics (Biomarkers) of BI 653048 BS H3PO4 Capsule Formulation Administered as Multiple Doses of 25 mg to 200 mg qd for 10 Days. A Randomised, Double-blind Within Dose Groups, Placebo-controlled, Multiple Rising Dose Trial With Open-label Active Comparator

The objectives of the trial were to assess safety, tolerability, pharmacokinetics, and pharmacodynamics of multiple rising doses of BI 653048 BS H3PO4 compared with prednisolone.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
140

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 1

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years to 50 years (ADULT)

Accepts Healthy Volunteers

Yes

Genders Eligible for Study

Male

Description

Inclusion Criteria:

  • Healthy male subjects based on a complete medical history, physical examination, vital signs (blood pressure and pulse rate), 12-lead ECG, and clinical laboratory tests
  • Age of 18 to 50 years
  • Body mass index (BMI) of 18.5 to 29.9 kg/m2
  • Signed and dated written informed consent in accordance with Good Clinical Practice and the local legislation

Exclusion Criteria:

  • Any clinically relevant deviation from normal in the medical examination including blood pressure, pulse rate, and ECG
  • 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), 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 with a long half-life (>24 h) within at least 1 month or less than 10 half-lives of the respective drug before first treatment with study drug or during trial
  • Use of drugs which might reasonably influence the results of the trial or which prolong the QT/QTc interval within 10 days before first treatment with study drug or during trial
  • Participation in another trial with an investigational drug within 30 days before first treatment with study drug or during trial
  • Smoker (more than 10 cigarettes, 3 cigars, or 3 pipes per day)
  • Inability to refrain from smoking beginning from 1 day before first treatment with study drug until discharge from the clinical unit
  • Alcohol abuse (more than 60 grams per day)
  • Drug abuse
  • Blood donation of more than 100 mL within 4 weeks before first treatment with study drug or during trial
  • Excessive physical activities within 1 week before first treatment with study drug or during trial
  • Any laboratory value outside the reference range and of clinical relevance
  • Inability to comply with dietary regimen of trial site
  • A marked baseline prolongation of the QT/QTc interval (e.g. QTc intervals that are repeatedly longer than 450 ms)
  • A history of additional risk factors for torsades de points (e.g. heart failure, hypokalaemia, or family history of Long QT syndrome

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: TREATMENT
  • Allocation: RANDOMIZED
  • Interventional Model: PARALLEL
  • Masking: DOUBLE

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
PLACEBO_COMPARATOR: Placebo
Drug: Placebo
EXPERIMENTAL: BI 653048 BS H3PO4
dose escalation
Drug: BI 653048 BS H3PO4
ACTIVE_COMPARATOR: Prednisolone low dose
Drug: Prednisolone low dose
ACTIVE_COMPARATOR: Prednisolone high dose
Drug: Prednisolone high dose

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Number of patients with adverse events
Time Frame: up to day 14
up to day 14
Number of patients with clinically significant findings in vital signs
Time Frame: up to 10 days after last drug administration
blood pressure, pulse rate, body temperature, orthostatic test
up to 10 days after last drug administration
Number of patients with clinically significant findings in ECG
Time Frame: up to 10 days after last drug administration
up to 10 days after last drug administration
Number of patients with clinically significant findings in laboratory tests
Time Frame: up to 10 days after last drug administration
up to 10 days after last drug administration
Assessment of tolerability by the investigator on a four-point scale
Time Frame: up to 10 days after last drug administration
up to 10 days after last drug administration

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Time Frame
Maximum measured concentration of the analyte in plasma at different time points (Cmax)
Time Frame: up to day 13
up to day 13
time from dosing to maximum measured concentration of the analyte at different time points (tmax)
Time Frame: up to day 13
up to day 13
Area under the concentration-time curve of the analyte in the plasma over time interval from 0 to the last measurable time point of the dose at different time points (AUC0-tz)
Time Frame: up to day 13
up to day 13
Area under the concentration-time curve of the analyte in plasma over the time interval from 0 extrapolated to infinity at different time points (AUC0-∞)
Time Frame: up to day 13
up to day 13
Percentage of the AUC0-∞ that is obtained by extrapolation at different time points (%AUCtz-∞)
Time Frame: up to day 13
up to day 13
Terminal phase elimination rate constant at different time points (λz)
Time Frame: up to day 13
up to day 13
Mean residence time of the analyte in the body after oral administration at different time points (MRTpo)
Time Frame: up to day 13
up to day 13
Terminal phase elimination half life at different time points (t1/2)
Time Frame: up to day 13
up to day 13
Apparent clearance of the analyte in plasma following extravascular administration at steady state (CL/Fss)
Time Frame: up to day 13
up to day 13
Apparent volume of distribution during the terminal phase λz following an extravascular dose at steady state (Vz/Fss)
Time Frame: up to day 13
up to day 13
Minimum plasma concentration at steady state (Cmin,ss)
Time Frame: up to day 13
up to day 13
Dose-normalized Cmax at steady state (Cmax/Dss)
Time Frame: up to day 13
up to day 13
Dose-normalised AUC0-∞ at steady state (AUC0-∞/Dss)
Time Frame: up to day 13
up to day 13
Accumulation index of the analyte when comparing AUCτ (RA,AUCτ)
Time Frame: up to day 13
up to day 13
Accumulation index of the analyte when comparing Cmax (RA,Cmax)
Time Frame: up to day 13
up to day 13
Linearity index (LI)
Time Frame: up to day 13
up to day 13
Amount of analyte excreted in urine unchanged from t1 to t2 interval at different time points (Aet1-t2)
Time Frame: up to day 11
up to day 11
Renal clearance of the unchanged analyte at different time points (CLr)
Time Frame: up to day 11
up to day 11
Area under the serum biomarker concentration-time curve after the Nth dose (AUECN)
Time Frame: up to day 13
up to day 13
Area under the baseline (before dose level) but above serum biomarker concentration-time curve after the Nth dose (AUECbelow_base)
Time Frame: up to day 13
up to day 13
Minimum measured serum concentration of the biomarkers after the Nth dose (Emin,N)
Time Frame: up to day 13
up to day 13
Maximum measured serum concentration of the biomarkers after the Nth dose (Emax,N)
Time Frame: up to day 13
up to day 13
Serum biomarker concentration after the (N-1)th dose but before the Nth dose (Epre,N)
Time Frame: up to day 13
up to day 13
Measured value of the biomarkers in biological matrix at the set time point after Nth dose (EN)
Time Frame: up to day 13
up to day 13
Oral glucose insulin sensitivity (OGIS) index
Time Frame: up to day 13
up to day 13
Homeostasis model assessment (HOMA) value
Time Frame: up to day 13
up to day 13

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Boehringer Ingelheim

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
October 1, 2009

Primary Completion (ACTUAL)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
March 1, 2010

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
August 14, 2014

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
August 14, 2014

First Posted (ESTIMATE)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
August 15, 2014

Study Record Updates

Last Update Posted (ESTIMATE)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
August 15, 2014

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
August 14, 2014

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
August 1, 2014

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • 1262.2

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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