Hepatic ImpairmentPhase 1NCT01727128
Pharmacokinetic Study of BKM120 in Subjects With Hepatic Impairment
A Phase 1 study testing BKM120 in people with Hepatic Impairment, run by Novartis Pharmaceuticals at 3 sites in 3 countries.
Trial summary
To assess pharamcokinetics, safety and tolerability of a single oral dose of BKM120 in subjects with mild, moderate and severe hepatic impairment Read more about this study
- Who is it for?
- Ages 18 to 75 yearsHealthy volunteers can take part
- Conditions the study is for
- Hepatic Impairment
- What is being tested?
- BKM120
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 31 participants
- Where
- 3 sitesin 3 countries
- Study dates
- Oct 2011to Aug 2013
- 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 75 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- Subjects should be in good health (except for additional/ specific inclusion criteria related to hepatic impaired subjects) as determined by past medical history, physical examination, vital signs, electrocardiogram, and laboratory tests of no significance at screening
- Subjects must weigh at least 45 kg to participate in this study, and must have a body mass index (BMI) from (18.5-35.0 kg/m2)
- Subjects must be able to communicate well with the investigator, to understand the requirements of the study and agree to use strict contraception for 16 weeks after the last BKM120 dose
- ---Additional inclusion criteria Group 1 - control healthy subjects
- Subjects should be matched to the hepatic impaired subjects of group 2 in gender, age (± 10 years), weight (± 20%), and BMI (±5%)
- ---Additional inclusion criteria Group 2 - hepatic impaired subjects
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- Subjects with physical signs consistent with stable hepatic impairment
- Child-Pugh Clinical Assessment Score consistent with degree of hepatic impairment (mild , moderate or severe)
- Subjects must be free of significant medical disorders unrelated to the subject's hepatic disorder as judged by the investigator.
- Absolute neutrophil count (ANC) ≥ 1.5 x 109 /L
- Platelet count ≥ 50 x 109 /L
- serum creatinine ≤ 1.5 x ULN
Who cannot join
- Significant illness, including infections, or hospitalization within the 2 weeks prior to dosing, except for the hepatic impaired subjects who due to their liver disease may be affected by significant medical problems which require frequent hospitalizations. Invasive systemic fungal infections need to be fully resolved prior to study entry
- Use of tobacco products within 2 weeks prior to dosing or during the study.
- Consumption of alcohol within 2 days prior to dosing or during the study
- Subjects with known ongoing alcohol and or/drug abuse within 1 month prior to dosing, or evidence of such abuse as indicated by the laboratory assays conducted during screening and/or at baseline
- Subjects not willing to avoid certain study prohibited food, drink, over the counter medicines and supplements
- Any surgical or medical condition which might significantly alter the absorption, distribution, metabolism, or excretion of drugs, or which may jeopardize the subject in case of participation in the study.
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- Medical history of cardiac disease and/or clinically significant ECG abnormalities.
- History of clinically significant hematologic, renal, endocrinologic, pulmonary cardiovascular, hepatic, or allergic disease medically documented
- Medical history of relevant psychiatric disorders
- Subjects with Diabetes Mellitus or subjects with glucose levels out of normal range as judge by the investigator
- History of immunodeficiency diseases, including Human Immunodeficiency Virus (HIV), as confirmed by (HIV-1, HIV-2) test
- Additional exclusion criteria Group 1 (matched healthy control subjects) History or presence of liver disease or liver injury as indicated by an abnormal liver function profile A positive Hepatitis C test or a positive Hepatitis B surface antigen (HBsAg)
- Additional exclusion criteria Group 2- hepatic impaired subjects
- Subjects with clinically significant abnormal findings, not consistent with clinical disease, upon physical examination, ECG or laboratory evaluation
- Any evidence of progressive liver disease (within the last 4 weeks prior to the screening visit) as indicated by liver transaminases, alkaline phosphatase and GGT or a ≥ 50% worsening of serum bilirubin or prothrombin time
- Total bilirubin > 6mg/dl
- Subject has ascites requiring intervention
Trial locations and contacts
3 sites in 3 countries.
3 sites in 3 countries
About this study
Official title: A Phase I, Multicenter, Open-label, Single-dose, Parallel Group Study to Assess the Pharmacokinetics of BKM120 in Subjects With Mild, Moderate and Severe Hepatic Impairmen
To assess pharamcokinetics, safety and tolerability of a single oral dose of BKM120 in subjects with mild, moderate and severe hepatic impairment
- Conditions
- Hepatic Impairment
- Being tested
- BKM120
- Keywords
- Hepatic impairment, Clinical pharmacology study, Volunteer study
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
BKM120Drug
| Study group | Role | What they receive |
|---|---|---|
| Mild Hepatic Impaired Group | Experimental | Subjects can only be enroled into this group if they fit the Child -Pugh score criteria of severity category - mildly hepatically impaired Receives: Drug: BKM120 |
| Moderate Hepatic Impaired group | Experimental | Subjects can only be enroled into this group if they fit the Child -Pugh score criteria of severity category - moderately hepatically impaired Receives: Drug: BKM120 |
| Severe Hepatic Impaired Group | Experimental | Subjects can only be enroled into this group if they fit the Child -Pugh score criteria of severity category - Severely hepatically impaired Receives: Drug: BKM120 |
| Control Group | Experimental | Matching healthy control subjects who do not have hepatic impairment and are matched to the hepatic impaired subjects by sex, age, gender and BMI Receives: Drug: BKM120 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Plasma concentration of pharmacokinctis (PK) parameter Tmax
Measurment of effect of liver impairment on PK of BKM120 by assessment of the PK parameter TMax (time to maximum concentration)
Measured: predose,0.5,1,1.5,2,3,4,6,8,12,24,48,72,96,144,192,240,288,336 hours post dose
Plasma concentration of PK parameter Cmax
Measurment of effect of liver impairment on PK of BKM120 by assessment of the PK parameter CMax (maximum concentration)
Measured: predose,0.5,1,1.5,2,3,4,6,8,12,24,48,72,96,144,192,240,288,336 hours post dose
Plasma concentration of PK parameter AUC-t
Measurment of effect of liver impairment on PK of BKM120 by assessment of the PK parameter AUC-t (Area under the curve at specified timepoint) The specific key measure(s) or observation(s) that will be used to determine the effect of the intervention(s). Example: Change in left ventricular end systolic volume (LVESD) as measured by echocardiography Time to tumor progression Overall tumor response
Measured: predose,0.5,1,1.5,2,3,4,6,8,12,24,48,72,96,144,192,240,288,336 hours post dose
Plasma concentration of PK parameter AUC-last
Measurment of effect of liver impairment on PK of BKM120 by assessment of the PK parameter AUC-last (Area under the curve at last timepoint) The specific key measure(s) or observation(s) that will be used to determine the effect of the intervention(s). Example: Change in left ventricular end systolic volume (LVESD) as measured by echocardiography Time to tumor progression Overall tumor response
Measured: predose,0.5,1,1.5,2,3,4,6,8,12,24,48,72,96,144,192,240,288,336 hours post dose
Plasma concentration of PK parameter AUC-inf
Measurment of effect of liver impairment on PK of BKM120 by assessment of the PK parameter AUC-inf (Area under the curve to time infinity)
Measured: predose,0.5,1,1.5,2,3,4,6,8,12,24,48,72,96,144,192,240,288,336 hours post dose
Plasma concentration of PK parameter CL/F
infMeasurment of effect of liver impairment on PK of BKM120 by assessment of the PK parameter CL/F (clearance)
Measured: predose,0.5,1,1.5,2,3,4,6,8,12,24,48,72,96,144,192,240,288,336 hours post dose
Plasma concentration of PK parameter Vz/F
FMeasurment of effect of liver impairment on PK of BKM120 by assessment of the PK parameter Vz/F (Volume distribution)
Measured: predose,0.5,1,1.5,2,3,4,6,8,12,24,48,72,96,144,192,240,288,336 hours post dose
Plasma concentration of PK parameter terminal T 1/2
Measurment of effect of liver impairment on PK of BKM120 by assessment of the PK parameter terminal T 1/2 (terminal half-life)
Measured: predose,0.5,1,1.5,2,3,4,6,8,12,24,48,72,96,144,192,240,288,336 hours post dose
Secondary outcomes (6)
Adverse events severity
Severtiy of adverse events severity based on the CTCAE criteria to assess safety and tolerability of a single dose of BKM120
Measured: From baseline day-1 to 30 days post dose
Change from baseline in laboratory parameters
Change from baseline in hematological and biochemical laboratory parameters
Measured: From baseline day-1 to 30 days post dose
Change from baseline in ECG parameters
Change from baseline in ECG parameters
Measured: From baseline day-1 to 30 days post dose
Change from baseline between PK parameters and total bilirubin, prothrombin time or INR and serum albumin
Relationship between PK parameters and baseline hepatic function parameters
Measured: From baseline day-1 to 15 days post dose
measurement of plasma binding
Determination of the free fraction of BKM120 in plasmaexpressed weher relevant in terms of unbound drug concentration
Measured: From baseline day-1 to 15 days post dose
Adverse events frequency
Frequency of adverse events severity based on the CTCAE criteria to assess safety and tolerability of a single dose of BKM120
Measured: From baseline day-1 to 30 days post dose
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 Nov 2012 (estimated)
- Study startOct 2011
- Primary completionAug 2013
- Study completionAug 2013
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Hepatic ImpairmentStudies of the same condition, open and under way.
- More trials run by Novartis PharmaceuticalsThe 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
- Basic science
- Allocation
- Non-randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Enrolment
- 31 participants (actual)
Sponsor and investigators
- Lead sponsor
- Novartis Pharmaceuticals
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Novartis Pharmaceuticals, Study director, Novartis Pharmaceuticals
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01727128
- Sponsor's protocol ID
- CBKM120C2104
- Other IDs
- 2011-002311-28
- Status last verified
- Apr 2014
- First submitted
- 12 Nov 2012
- Last updated
- 9 Dec 2020
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 9 Dec 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase I, Multicenter, Open-label, Single-dose, Parallel Group Study to Assess the Pharmacokinetics of BKM120 in Subjects With Mild, Moderate and Severe Hepatic Impairmen
- ClinicalTrials.gov ID
- NCT01727128
- Acronym / sponsor ID
- CBKM120C2104
- Conditions
- Hepatic Impairment
- Keywords
- Hepatic impairment, Clinical pharmacology study, Volunteer study
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 31 participants (actual)
- Lead sponsor
- Novartis PharmaceuticalsIndustry (pharma, biotech, devices)
- Study start
- Oct 2011
- Primary completion
- Aug 2013 (actual)
- Study completion
- Aug 2013 (actual)
- First posted
- 15 Nov 2012 (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.
To assess pharamcokinetics, safety and tolerability of a single oral dose of BKM120 in subjects with mild, moderate and severe hepatic impairment
Study design
- Primary purpose
- Basic science
- Allocation
- Non-randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| Mild Hepatic Impaired Group | Experimental | Drug: BKM120Subjects can only be enroled into this group if they fit the Child -Pugh score criteria of severity category - mildly hepatically impaired |
| Moderate Hepatic Impaired group | Experimental | Drug: BKM120Subjects can only be enroled into this group if they fit the Child -Pugh score criteria of severity category - moderately hepatically impaired |
| Severe Hepatic Impaired Group | Experimental | Drug: BKM120Subjects can only be enroled into this group if they fit the Child -Pugh score criteria of severity category - Severely hepatically impaired |
| Control Group | Experimental | Drug: BKM120Matching healthy control subjects who do not have hepatic impairment and are matched to the hepatic impaired subjects by sex, age, gender and BMI |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (12 listed)
- Subjects should be in good health (except for additional/ specific inclusion criteria related to hepatic impaired subjects) as determined by past medical history, physical examination, vital signs, electrocardiogram, and laboratory tests of no significance at screening
- Subjects must weigh at least 45 kg to participate in this study, and must have a body mass index (BMI) from (18.5-35.0 kg/m2)
- Subjects must be able to communicate well with the investigator, to understand the requirements of the study and agree to use strict contraception for 16 weeks after the last BKM120 dose
- ---Additional inclusion criteria Group 1 - control healthy subjects
- Subjects should be matched to the hepatic impaired subjects of group 2 in gender, age (± 10 years), weight (± 20%), and BMI (±5%)
Key exclusion criteria (17 listed)
- Significant illness, including infections, or hospitalization within the 2 weeks prior to dosing, except for the hepatic impaired subjects who due to their liver disease may be affected by significant medical problems which require frequent hospitalizations. Invasive systemic fungal infections need to be fully resolved prior to study entry
- Use of tobacco products within 2 weeks prior to dosing or during the study.
- Consumption of alcohol within 2 days prior to dosing or during the study
- Subjects with known ongoing alcohol and or/drug abuse within 1 month prior to dosing, or evidence of such abuse as indicated by the laboratory assays conducted during screening and/or at baseline
- Subjects not willing to avoid certain study prohibited food, drink, over the counter medicines and supplements
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 |
|---|---|---|
| BKM120 | Drug | Control Group, Mild Hepatic Impaired Group, Moderate Hepatic Impaired group, Severe Hepatic Impaired Group |
Primary outcome
Plasma concentration of pharmacokinctis (PK) parameter Tmax
Time frame: predose,0.5,1,1.5,2,3,4,6,8,12,24,48,72,96,144,192,240,288,336 hours post dose
Measurment of effect of liver impairment on PK of BKM120 by assessment of the PK parameter TMax (time to maximum concentration)
Plasma concentration of PK parameter Cmax
Time frame: predose,0.5,1,1.5,2,3,4,6,8,12,24,48,72,96,144,192,240,288,336 hours post dose
Measurment of effect of liver impairment on PK of BKM120 by assessment of the PK parameter CMax (maximum concentration)
Plasma concentration of PK parameter AUC-t
Time frame: predose,0.5,1,1.5,2,3,4,6,8,12,24,48,72,96,144,192,240,288,336 hours post dose
Measurment of effect of liver impairment on PK of BKM120 by assessment of the PK parameter AUC-t (Area under the curve at specified timepoint) The specific key measure(s) or observation(s) that will be used to determine the effect of the intervention(s). Example: Change in left ventricular end systolic volume (LVESD) as measured by echocardiography Time to tumor progression Overall tumor response
Plasma concentration of PK parameter AUC-last
Time frame: predose,0.5,1,1.5,2,3,4,6,8,12,24,48,72,96,144,192,240,288,336 hours post dose
Measurment of effect of liver impairment on PK of BKM120 by assessment of the PK parameter AUC-last (Area under the curve at last timepoint) The specific key measure(s) or observation(s) that will be used to determine the effect of the intervention(s). Example: Change in left ventricular end systolic volume (LVESD) as measured by echocardiography Time to tumor progression Overall tumor response
Plasma concentration of PK parameter AUC-inf
Time frame: predose,0.5,1,1.5,2,3,4,6,8,12,24,48,72,96,144,192,240,288,336 hours post dose
Measurment of effect of liver impairment on PK of BKM120 by assessment of the PK parameter AUC-inf (Area under the curve to time infinity)
Plasma concentration of PK parameter CL/F
Time frame: predose,0.5,1,1.5,2,3,4,6,8,12,24,48,72,96,144,192,240,288,336 hours post dose
infMeasurment of effect of liver impairment on PK of BKM120 by assessment of the PK parameter CL/F (clearance)
Plasma concentration of PK parameter Vz/F
Time frame: predose,0.5,1,1.5,2,3,4,6,8,12,24,48,72,96,144,192,240,288,336 hours post dose
FMeasurment of effect of liver impairment on PK of BKM120 by assessment of the PK parameter Vz/F (Volume distribution)
Plasma concentration of PK parameter terminal T 1/2
Time frame: predose,0.5,1,1.5,2,3,4,6,8,12,24,48,72,96,144,192,240,288,336 hours post dose
Measurment of effect of liver impairment on PK of BKM120 by assessment of the PK parameter terminal T 1/2 (terminal half-life)
6 secondary outcomes
Adverse events severity
Time frame: From baseline day-1 to 30 days post dose
Change from baseline in laboratory parameters
Time frame: From baseline day-1 to 30 days post dose
Change from baseline in ECG parameters
Time frame: From baseline day-1 to 30 days post dose
Change from baseline between PK parameters and total bilirubin, prothrombin time or INR and serum albumin
Time frame: From baseline day-1 to 15 days post dose
measurement of plasma binding
Time frame: From baseline day-1 to 15 days post dose
Adverse events frequency
Time frame: From baseline day-1 to 30 days post dose
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 9 Dec 2020.
- Results for CBKM120C2104 can be found on the Novartis Clinical Trial Results WebsiteLink 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.
Novartis Pharmaceuticals study director
Novartis Pharmaceuticals
3 sites in 3 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing BKM120 in people with Hepatic Impairment, run by Novartis Pharmaceuticals at 3 sites in 3 countries.
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 12 inclusion and 17 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 9 Dec 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 sites in Bulgaria, Germany, Russia. 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?
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?
Plasma concentration of pharmacokinctis (PK) parameter Tmax (time frame: predose,0.5,1,1.5,2,3,4,6,8,12,24,48,72,96,144,192,240,288,336 hours post dose). The study lists 8 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 9 Dec 2020.