Liver DiseasesPhase 1NCT01298063
Influence of Mild and Moderate Hepatic Impairment on the Pharmacokinetics, Safety and Tolerability of Various Doses of Afatinib
A Phase 1 study testing Afatinib in people with Liver Diseases and Healthy, run by Boehringer Ingelheim at 1 site in Germany.
Trial summary
Up to 38 subjects entered with the aim of entering 8 subjects with mild liver impairment (at highest dose of afatinib), 8 subjects with moderate liver impairment (at either highest dose or two lower doses) and 8 healthy matched controls to each of this two groups. Read more about this study
- Who is it for?
- Ages 18 to 75 yearsHealthy volunteers can take part
- Conditions the study is for
- Liver Diseases, Healthy
- What is being tested?
- Afatinib
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 35 participants
- Where
- 1 siteGermany
- Study dates
- Feb 2011to Jan 2012
- Phase
- Phase 1
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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 75 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- Healthy subjects:
- Healthy males and females according to a complete medical history, including a physical examination, vital signs (Blood Pressure, Pulse Rate), 12-lead Electrocardiogram, and clinical laboratory tests. The healthy subjects must meet the matching criteria based on the matching approach (cf. Section 3.3).
- Age =18 and =75 years
- Body Mass Index =18.5 and =34 kg/m2
- Creatinine clearance >70 mL/min according to Cockroft \& Gault (for healthy volunteers, cf. Section 10.2)
- Signed and dated written informed consent prior to admission to the study in accordance with Good Clinical Practice and the local legislation. Hepatically impaired subjects as determined by a hepatologist/ gastroenterologist:
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- Male and female liver impaired subjects determined by results of screening classified as Child-Pugh A; Child-Pugh score of 5-6 points or as Child-Pugh B; Child-Pugh score of 7-9 points, cf. Section 10.2. Child-Pugh criteria must be stable for at least 3 months prior to screening and during the trial.
- Age =18 and =75 years
- Body Mass Index =18.5 and =34 kg/m2
- Creatinine clearance >40 mL/min according to Cockroft \& Gault (for liver impaired subjects, cf. Section 10.2)
- Signed and dated written informed consent prior to admission to the study in accordance with Good Clinical Practice and the local legislation.
- For all females:
- Postmenopausal female subjects (postmenopausal defined as at least 1 year of spontaneous amenorrhea [in questionable cases or spontaneous amenorrhea below 1 year a blood sample with simultaneous follicle stimulating hormone (FSH) above 40 IU/l and estradiol below 30 ng/l is confirmatory]) or adequate contraception* for female subjects of childbearing potential during the study and until 2 months after study completion, e.g. any of the following: implants, injectables, combined oral contraceptives, IUD (intrauterine device), sexual abstinence for at least 1 month prior to first study drug administration, vasectomised partner (vasectomy performed at least 1 year prior to enrolment), or surgical sterilisation (including hysterectomy). Females, who do not have a vasectomised partner, are not sexually abstinent or surgically sterile have to use an additional barrier method (e.g. condom).
Who cannot join
- Any relevant deviation from healthy conditions (excluded conditions caused by liver impairment)
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Pharmacokinetics, Safety and Tolerability of Different Oral Doses of Afatinib, in Subjects With Mild to Moderate Hepatic Impairment Compared to Healthy Subjects - a Phase I, Single-dose, Open-label, Dose-escalation Study in a Matched Group Design
Up to 38 subjects entered with the aim of entering 8 subjects with mild liver impairment (at highest dose of afatinib), 8 subjects with moderate liver impairment (at either highest dose or two lower doses) and 8 healthy matched controls to each of this two groups.
- Conditions
- Liver Diseases, Healthy
- Being tested
- Afatinib
- Medical subject headings
- Liver Diseases
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AfatinibDrug
1 tablet, once qd in the morning
AfatinibDrug
1 tablet, once qd in the morning
AfatinibDrug
1 tablet, once qd in the morning
| Study group | Role | What they receive |
|---|---|---|
| Afatinib Group A, B (2), D | Experimental | healthy subjects, mild and moderate liver impaired subjects to receive one single dose treatment containing the highest dose afatinib Receives: Drug: Afatinib |
| Afatinib Group B (3), D | Experimental | healthy subjects, moderate liver impaired subjects to receive one single dose treatment containing the medium dose of afatinib Receives: Drug: Afatinib |
| Afatinib Group B (1), D | Experimental | healthy subjects, moderate liver impaired subjects to receive one single dose treatment containing the low dose of afatinib Receives: Drug: Afatinib |
What is being measured
The primary outcome is the main question the study is designed to answer.
Area Under Curve From 0 to Infinity (AUC0-infinity)
AUC0-infinity represents the area under the concentration-time curve of the analyte in plasma over the time interval from 0 extrapolated to infinity
Measured: 30 minutes (min) prior to first dosing and 30 min, 1 hour (h), 2 h, 3 h, 4 h, 5 h, 6 h, 7 h, 8 h, 9 h, 12 h, 24 h, 36 h, 48 h, 72 h, 96 h, 120 h, 144 h, 168 h, 240 h after first dosing
Maximum Concentration (Cmax)
Cmax represents the maximum measured concentration of the analyte in plasma
Measured: 30 minutes (min) prior to first dosing and 30 min, 1 hour (h), 2 h, 3 h, 4 h, 5 h, 6 h, 7 h, 8 h, 9 h, 12 h, 24 h, 36 h, 48 h, 72 h, 96 h, 120 h, 144 h, 168 h, 240 h after first dosing
Secondary outcomes (2)
Area Under Curve From 0 to tz (AUC0-tz)
AUC0-tz represents the 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
Measured: 30 minutes (min) prior to first dosing and 30 min, 1 hour (h), 2 h, 3 h, 4 h, 5 h, 6 h, 7 h, 8 h, 9 h, 12 h, 24 h, 36 h, 48 h, 72 h, 96 h, 120 h, 144 h, 168 h, 240 h after first dosing
Clinical Relevant Abnormalitites for Physical Examination, Vital Signs, 12-lead ECG, Clinical Laboratory Tests, Adverse Event, Investigator's Global Tolerability
Clinical relevant abnormalitites for physical examination, vital signs, 12-lead electrocardiogramm (ECG), clinical laboratory test (including hematology, clinical chemistry, coagulation, urinalysis), adverse event, investigator's global tolerability. New abnormal findings or worsening of baseline conditions were reported as Adverse Events.
Measured: First administration of trial medication until 28 days after last administration of trial medication
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 Feb 2011 (estimated)
- Study startFeb 2011
- Primary completionJan 2012
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Liver DiseasesStudies 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
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 35 participants (actual)
Sponsor and investigators
- Lead sponsor
- Boehringer Ingelheim
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Boehringer Ingelheim, Study chair, Boehringer Ingelheim
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01298063
- Sponsor's protocol ID
- 1200.86
- Other IDs
- 2010-021140-18
- Status last verified
- Aug 2013
- First submitted
- 15 Feb 2011
- Last updated
- 31 Dec 2013
- Results posted
- Yes, on ClinicalTrials.gov
Study at a glance
From the registry record, last updated by the sponsor on 31 Dec 2013. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Pharmacokinetics, Safety and Tolerability of Different Oral Doses of Afatinib, in Subjects With Mild to Moderate Hepatic Impairment Compared to Healthy Subjects - a Phase I, Single-dose, Open-label, Dose-escalation Study in a Matched Group Design
- ClinicalTrials.gov ID
- NCT01298063
- Acronym / sponsor ID
- 1200.86
- Conditions
- Liver Diseases, Healthy
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 35 participants (actual)
- Lead sponsor
- Boehringer IngelheimIndustry (pharma, biotech, devices)
- Study start
- Feb 2011
- Primary completion
- Jan 2012 (actual)
- First posted
- 17 Feb 2011 (estimated)
- Results
- Posted 17 Oct 2013
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Up to 38 subjects entered with the aim of entering 8 subjects with mild liver impairment (at highest dose of afatinib), 8 subjects with moderate liver impairment (at either highest dose or two lower doses) and 8 healthy matched controls to each of this two groups.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Afatinib Group A, B (2), D | Experimental | Drug: Afatinibhealthy subjects, mild and moderate liver impaired subjects to receive one single dose treatment containing the highest dose afatinib |
| Afatinib Group B (3), D | Experimental | Drug: Afatinibhealthy subjects, moderate liver impaired subjects to receive one single dose treatment containing the medium dose of afatinib |
| Afatinib Group B (1), D | Experimental | Drug: Afatinibhealthy subjects, moderate liver impaired subjects to receive one single dose treatment containing the low dose of afatinib |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (13 listed)
- Healthy males and females according to a complete medical history, including a physical examination, vital signs (Blood Pressure, Pulse Rate), 12-lead Electrocardiogram, and clinical laboratory tests. The healthy subjects must meet the matching criteria based on the matching approach (cf. Section 3.3).
- Age =18 and =75 years
- Body Mass Index =18.5 and =34 kg/m2
- Creatinine clearance >70 mL/min according to Cockroft \& Gault (for healthy volunteers, cf. Section 10.2)
- Signed and dated written informed consent prior to admission to the study in accordance with Good Clinical Practice and the local legislation. Hepatically impaired subjects as determined by a hepatologist/ gastroenterologist:
Key exclusion criteria (1 listed)
- Any relevant deviation from healthy conditions (excluded conditions caused by liver impairment)
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 |
|---|---|---|
| Afatinib1 tablet, once qd in the morning | Drug | Afatinib Group A, B (2), D |
| Afatinib1 tablet, once qd in the morning | Drug | Afatinib Group B (3), D |
| Afatinib1 tablet, once qd in the morning | Drug | Afatinib Group B (1), D |
Primary outcome
Area Under Curve From 0 to Infinity (AUC0-infinity)
Time frame: 30 minutes (min) prior to first dosing and 30 min, 1 hour (h), 2 h, 3 h, 4 h, 5 h, 6 h, 7 h, 8 h, 9 h, 12 h, 24 h, 36 h, 48 h, 72 h, 96 h, 120 h, 144 h, 168 h, 240 h after first dosing
AUC0-infinity represents the area under the concentration-time curve of the analyte in plasma over the time interval from 0 extrapolated to infinity
Maximum Concentration (Cmax)
Time frame: 30 minutes (min) prior to first dosing and 30 min, 1 hour (h), 2 h, 3 h, 4 h, 5 h, 6 h, 7 h, 8 h, 9 h, 12 h, 24 h, 36 h, 48 h, 72 h, 96 h, 120 h, 144 h, 168 h, 240 h after first dosing
Cmax represents the maximum measured concentration of the analyte in plasma
2 secondary outcomes
Area Under Curve From 0 to tz (AUC0-tz)
Time frame: 30 minutes (min) prior to first dosing and 30 min, 1 hour (h), 2 h, 3 h, 4 h, 5 h, 6 h, 7 h, 8 h, 9 h, 12 h, 24 h, 36 h, 48 h, 72 h, 96 h, 120 h, 144 h, 168 h, 240 h after first dosing
Clinical Relevant Abnormalitites for Physical Examination, Vital Signs, 12-lead ECG, Clinical Laboratory Tests, Adverse Event, Investigator's Global Tolerability
Time frame: First administration of trial medication until 28 days after last administration of trial medication
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 31 Dec 2013.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Related InfoLink provided by the sponsor.
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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.
Boehringer Ingelheim study chair
Boehringer Ingelheim
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Afatinib in people with Liver Diseases and Healthy, run by Boehringer Ingelheim at 1 site in Germany.
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 13 inclusion and 1 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 31 Dec 2013. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Germany. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. 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?
Yes. Results are posted in the registry (first posted 17 Oct 2013). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
Area Under Curve From 0 to Infinity (AUC0-infinity) (time frame: 30 minutes (min) prior to first dosing and 30 min, 1 hour (h), 2 h, 3 h, 4 h, 5 h, 6 h, 7 h, 8 h, 9 h, 12 h, 24 h, 36 h, 48 h, 72 h, 96 h, 120 h, 144 h, 168 h, 240 h after first dosing). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 31 Dec 2013.