HealthyPhase 1NCT02224105
Safety, Tolerability, Pharmacodynamics and Pharmacokinetics of BI 653048 BS H3PO4 Capsule Assessing Endotoxin-induced Inflammatory Response in Healthy Male Subjects
A Phase 1 study testing BI 653048 BS, Prednisolone low and Prednisolone high in people with Healthy, run by Boehringer Ingelheim.
Trial summary
The general aim of the current study was to investigate the safety and tolerability, and pharmacodynamics (endotoxin-induced inflammatory response of a single intravenous bolus administration of 2 ng/kg body weight Escherichia coli lipopolysaccharide (LPS)) of BI 653048 BS H3PO4 capsules in healthy male subjects… Read more about this study
- Who is it for?
- Ages 18 to 50 years, men onlyHealthy volunteers can take part
- Conditions the study is for
- Healthy
- What is being tested?
- BI 653048 BS, Prednisolone low and Prednisolone high
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 56 participants
- Where
- No sites listed yet
- Study dates
- Mar 2010to May 2010
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 50 years
- Men only
- Healthy volunteers accepted
- Adult
Who may be able to join
- Healthy males according to the following criteria:
- Based upon a complete medical history, including the physical examination, vital signs (blood pressure, pulse rate and body temperature), 12-lead ECG, 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 Good Clinical Practice (GCP) and the local legislation
Who cannot join
- Any finding of the medical examination (including blood pressure, pulse rate, orthostatic test, body temperature 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
Show all 19Show fewer
- 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 based on the knowledge at the time of protocol preparation within 10 days prior to administration or during the trial
- Participation in another trial with an investigational drug within 30 days prior to administration or during the trial
- Smoker (>10 cigarettes or >3 cigars or >3 pipes/day)
- Inability to refrain from smoking for 1 day prior to first drug administration until discharge from the study site
- Alcohol abuse (more than 60 g/day)
- 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
- Inability to comply with dietary regimen of trial site
About this study
Official title: Safety, Tolerability, Pharmacodynamics and Pharmacokinetics of a BI 653048 BS H3PO4 Capsule Formulation Administered as Multiple Doses of 25 mg to 200 mg Once Daily (qd) for 3 Days Assessing Pharmacodynamics as Endotoxin-induced Inflammatory Response of a Single Intravenous Bolus Administration of 2 ng/kg Body Weight Lipopolysaccharide (LPS). A Randomised, Double-blind Within Dose Groups, Placebo-controlled, Multiple Rising Dose Phase I Trial With Open-label Active Comparator in Healthy Male Subjects
The general aim of the current study was to investigate the safety and tolerability, and pharmacodynamics (endotoxin-induced inflammatory response of a single intravenous bolus administration of 2 ng/kg body weight Escherichia coli lipopolysaccharide (LPS)) of BI 653048 BS H3PO4 capsules in healthy male subjects following oral administration of multiple rising doses of 25 mg to 200 mg over three days compared to the active comparator prednisolone and placebo.
Pharmacodynamics were assessed by investigating the influence of LPS administration on inflammatory parameters. More specifically, it was evaluated whether and to what extent the symptoms induced by LPS challenge can be attenuated by ascending BI 653048 BS H3PO4 doses using prednisolone as positive control and placebo as negative control. A secondary objective was the exploration of pharmacokinetics of BI 653048 BS, the investigation of other pharmacodynamic parameters (biomarker) and of the tolerability of LPS.
- Conditions
- Healthy
- Being tested
- BI 653048 BS, Prednisolone low, Prednisolone high, Placebo, sodium chloride infusion
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
BI 653048 BSDrug
Prednisolone lowDrug
Prednisolone highDrug
PlaceboDrug
sodium chloride infusionDrug
endotoxin escherichia coli (E. coli) lipopolysaccharide (LPS)Drug
| Study group | Role | What they receive |
|---|---|---|
| BI 653048 BS | Experimental | escalating doses Receives: Drug: BI 653048 BS; Drug: sodium chloride infusion; Drug: endotoxin escherichia coli (E. coli) lipopolysaccharide (LPS) |
| Prednisolone low | Active comparator | Not described Receives: Drug: Prednisolone low; Drug: sodium chloride infusion; Drug: endotoxin escherichia coli (E. coli) lipopolysaccharide (LPS) |
| Prednisolone high | Active comparator | Not described Receives: Drug: Prednisolone high; Drug: sodium chloride infusion; Drug: endotoxin escherichia coli (E. coli) lipopolysaccharide (LPS) |
| Placebo | Placebo comparator | Not described Receives: Drug: Placebo; Drug: sodium chloride infusion; Drug: endotoxin escherichia coli (E. coli) lipopolysaccharide (LPS) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of subjects with adverse events
Measured: up to 37 days
Number of subjects with clinically significant findings in vital signs
blood pressure, pulse rate and body temperature
Measured: up to day 15
Number of subjects with clinically significant findings in 12-lead electrocardiogram (ECG)
Measured: up to day 15
Number of subjects with clinically significant findings in laboratory tests
Measured: up to day 15
Assessment of tolerability by investigator on a 4-point scale
Measured: up to day 15
Maximum measured concentration of the biomarker level in plasma (Emax)
Measured: up to 96 hours after first drug administration
Area under the concentration-time curve of the biomarker in plasma over the time interval from 0 to the last measurable time point of the dose (AUEC)
Measured: up to 96 hours after first drug administration
Secondary outcomes (13)
Maximum measured concentration of the analyte in plasma at steady state (Cmax,ss)
Measured: up to 96 hours after first drug administration
Time from dosing to maximum measured concentration of the analyte at steady state (tmax,ss)
Measured: up to 96 hours after first drug administration
Area under the concentration-time curve of the analyte in the plasma over the time interval from 0 to the last measurable time point of the dose at steady state (AUC0-tz,ss)
Measured: up to 96 hours after first drug administration
Area under the concentration-time curve of the analyte in plasma over the time interval from 0 extrapolated to infinity at steady state (AUC0-∞,ss)
Measured: up to 96 hours after first drug administration
Percentage of the AUC0-∞ that is obtained by extrapolation at steady state (%AUCtz-∞,ss)
Measured: up to 96 hours after first drug administration
Terminal phase elimination rate constant at steady state (λz,ss)
Measured: up to 96 hours after first drug administration
Terminal phase elimination half life at steady state (t1/2,ss)
Measured: up to 96 hours after first drug administration
Mean residence time of the analyte in the body after oral administration at steady state (MRTpo,ss)
Measured: up to 96 hours after first drug administration
Apparent clearance of the analyte in plasma following extravascular administration at steady state (CL/Fss)
Measured: up to 96 hours after first drug administration
Apparent volume of distribution during the terminal phase λz following an extravascular dose at steady state (Vz/Fss)
Measured: up to 96 hours after first drug administration
Minimum measured concentration of the biomarker during the treatment interval (Emin)
Measured: up to 96 hours after first drug administration
Area under the concentration-time curve of the biomarker in serum over the time interval from 0 to the last measurable time point of the dose (AUEC)
Measured: up to 96 hours after first drug administration
Measured concentration of the biomarker at time t after the beginning of the treatment interval (Et)
Measured: up to 96 hours after first drug administration
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 Aug 2014 (estimated)
- Study startMar 2010
- Primary completionMay 2010
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for HealthyStudies of the same condition, open and under way.
- More trials run by Boehringer IngelheimThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Enrolment
- 56 participants (actual)
Sponsor and investigators
- Lead sponsor
- Boehringer Ingelheim
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02224105
- Sponsor's protocol ID
- 1262.9
- Status last verified
- Aug 2014
- First submitted
- 21 Aug 2014
- Last updated
- 25 Aug 2014
- Results posted
- No
Publications
Harcken C, Scholl P, Nabozny G, Thomson D, Bianchi D. Clinical profile of the functionally selective glucocorticoid receptor agonist BI 653048 in healthy male subjects. Expert Opin Investig Drugs. 2019 May;28(5):489-496. doi: 10.1080/13543784.2019.1599859. Epub 2019 Apr 9.
PubMed 30908082
Study at a glance
From the registry record, last updated by the sponsor on 25 Aug 2014. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Safety, Tolerability, Pharmacodynamics and Pharmacokinetics of a BI 653048 BS H3PO4 Capsule Formulation Administered as Multiple Doses of 25 mg to 200 mg Once Daily (qd) for 3 Days Assessing Pharmacodynamics as Endotoxin-induced Inflammatory Response of a Single Intravenous Bolus Administration of 2 ng/kg Body Weight Lipopolysaccharide (LPS). A Randomised, Double-blind Within Dose Groups, Placebo-controlled, Multiple Rising Dose Phase I Trial With Open-label Active Comparator in Healthy Male Subjects
- ClinicalTrials.gov ID
- NCT02224105
- Acronym / sponsor ID
- 1262.9
- Conditions
- Healthy
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 56 participants (actual)
- Lead sponsor
- Boehringer IngelheimIndustry (pharma, biotech, devices)
- Study start
- Mar 2010
- Primary completion
- May 2010 (actual)
- First posted
- 25 Aug 2014 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The general aim of the current study was to investigate the safety and tolerability, and pharmacodynamics (endotoxin-induced inflammatory response of a single intravenous bolus administration of 2 ng/kg body weight Escherichia coli lipopolysaccharide (LPS)) of BI 653048 BS H3PO4 capsules in healthy male subjects following oral administration of multiple rising doses of 25 mg to 200 mg over three days compared to the active comparator prednisolone and placebo.
Pharmacodynamics were assessed by investigating the influence of LPS administration on inflammatory parameters. More specifically, it was evaluated whether and to what extent the symptoms induced by LPS challenge can be attenuated by ascending BI 653048 BS H3PO4 doses using prednisolone as positive control and placebo as negative control. A secondary objective was the exploration of pharmacokinetics of BI 653048 BS, the investigation of other pharmacodynamic parameters (biomarker) and of the tolerability of LPS.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| BI 653048 BS | Experimental | Drug: BI 653048 BS, Drug: sodium chloride infusion, Drug: endotoxin escherichia coli (E. coli) lipopolysaccharide (LPS)escalating doses |
| Prednisolone low | Active comparator | Drug: Prednisolone low, Drug: sodium chloride infusion, Drug: endotoxin escherichia coli (E. coli) lipopolysaccharide (LPS) |
| Prednisolone high | Active comparator | Drug: Prednisolone high, Drug: sodium chloride infusion, Drug: endotoxin escherichia coli (E. coli) lipopolysaccharide (LPS) |
| Placebo | Placebo comparator | Drug: Placebo, Drug: sodium chloride infusion, Drug: endotoxin escherichia coli (E. coli) lipopolysaccharide (LPS) |
Who may qualify
- Ages
- 18 to 50 years
- Sex
- Male only
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (5 listed)
- Healthy males according to the following criteria:
- Based upon a complete medical history, including the physical examination, vital signs (blood pressure, pulse rate and body temperature), 12-lead ECG, 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 Good Clinical Practice (GCP) and the local legislation
Key exclusion criteria (19 listed)
- Any finding of the medical examination (including blood pressure, pulse rate, orthostatic test, body temperature 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| BI 653048 BS | Drug | BI 653048 BS |
| Prednisolone low | Drug | Prednisolone low |
| Prednisolone high | Drug | Prednisolone high |
| Placebo | Drug | Placebo |
| sodium chloride infusion | Drug | BI 653048 BS, Placebo, Prednisolone high, Prednisolone low |
| endotoxin escherichia coli (E. coli) lipopolysaccharide (LPS) | Drug | BI 653048 BS, Placebo, Prednisolone high, Prednisolone low |
Primary outcome
Number of subjects with adverse events
Time frame: up to 37 days
Number of subjects with clinically significant findings in vital signs
Time frame: up to day 15
blood pressure, pulse rate and body temperature
Number of subjects with clinically significant findings in 12-lead electrocardiogram (ECG)
Time frame: up to day 15
Number of subjects with clinically significant findings in laboratory tests
Time frame: up to day 15
Assessment of tolerability by investigator on a 4-point scale
Time frame: up to day 15
Maximum measured concentration of the biomarker level in plasma (Emax)
Time frame: up to 96 hours after first drug administration
Area under the concentration-time curve of the biomarker in plasma over the time interval from 0 to the last measurable time point of the dose (AUEC)
Time frame: up to 96 hours after first drug administration
13 secondary outcomes
Maximum measured concentration of the analyte in plasma at steady state (Cmax,ss)
Time frame: up to 96 hours after first drug administration
Time from dosing to maximum measured concentration of the analyte at steady state (tmax,ss)
Time frame: up to 96 hours after first drug administration
Area under the concentration-time curve of the analyte in the plasma over the time interval from 0 to the last measurable time point of the dose at steady state (AUC0-tz,ss)
Time frame: up to 96 hours after first drug administration
Area under the concentration-time curve of the analyte in plasma over the time interval from 0 extrapolated to infinity at steady state (AUC0-∞,ss)
Time frame: up to 96 hours after first drug administration
Percentage of the AUC0-∞ that is obtained by extrapolation at steady state (%AUCtz-∞,ss)
Time frame: up to 96 hours after first drug administration
Terminal phase elimination rate constant at steady state (λz,ss)
Time frame: up to 96 hours after first drug administration
Terminal phase elimination half life at steady state (t1/2,ss)
Time frame: up to 96 hours after first drug administration
Mean residence time of the analyte in the body after oral administration at steady state (MRTpo,ss)
Time frame: up to 96 hours after first drug administration
Apparent clearance of the analyte in plasma following extravascular administration at steady state (CL/Fss)
Time frame: up to 96 hours after first drug administration
Apparent volume of distribution during the terminal phase λz following an extravascular dose at steady state (Vz/Fss)
Time frame: up to 96 hours after first drug administration
Minimum measured concentration of the biomarker during the treatment interval (Emin)
Time frame: up to 96 hours after first drug administration
Area under the concentration-time curve of the biomarker in serum over the time interval from 0 to the last measurable time point of the dose (AUEC)
Time frame: up to 96 hours after first drug administration
Measured concentration of the biomarker at time t after the beginning of the treatment interval (Et)
Time frame: up to 96 hours after first drug administration
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 25 Aug 2014.
- Derived from this study: PubMed 30908082Harcken C, Scholl P, Nabozny G, Thomson D, Bianchi D. Clinical profile of the functionally selective glucocorticoid receptor agonist BI 653048 in healthy male subjects. Expert Opin Investig Drugs. 2019 May;28(5):489-496. doi: 10.1080/13543784.2019.1599859. Epub 2019 Apr 9.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing BI 653048 BS, Prednisolone low and Prednisolone high in people with Healthy, run by Boehringer Ingelheim.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 19 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 25 Aug 2014. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of subjects with adverse events (time frame: up to 37 days). The study lists 7 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02224105, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 25 Aug 2014.