Hepatic ImpairmentPhase 1NCT02873650
Pharmacokinetics of Dabrafenib in Subjects With Hepatic Impairment
A Phase 1 study testing dabrafenib in people with Hepatic Impairment, run by Novartis Pharmaceuticals at 4 sites in United States.
Trial summary
To characterize the pharmacokinetics and safety of dabrafenib following a single 100 mg oral dose in subjects with 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?
- dabrafenib
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 5 participants
- Where
- 4 sitesUnited States
- Study dates
- 20 Dec 2016to 8 Apr 2019
- 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
- Male and/or female subjects 18-75 years of age
- Females must be of non-childbearing potential . All non-postmenopausal females must have a confirmed negative serum pregnancy
- Subjects in good health condition as determined by no clinically significant findings from medical history and physical examination.
- Body mass index (BMI) between ≥18.0 and ≤38.0 kg/m2, with body weight ≥ 50 kg and no more than 140 kg
- Laboratory values must be within normal limits (correction allowed) or considered clinically insignificant
- Do not participate in any other clinical trials with a BRAF or other RAF inhibitors
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- Additional inclusion criteria for patients with normal hepatic function (Control group):
- Absence of clinically significant deviation from normal in medical history, physical examination, vital signs, electrocardiograms and clinical laboratory determinations.
- Must match to at least one hepatic impairment subject by age, gender and bodyweight
- Additional inclusion criteria for hepatic impaired subjects:
- Confirmed hepatic disease
- Stable Child-Pugh status within 28 days prior to dosing.
Who cannot join
- Participation in any clinical investigation within 4 weeks prior to dosing
- Significant acute illness within the two weeks prior to dosing
- History of immunodeficiency diseases, including a positive HIV
- History of malignancy of any organ system, treated or untreated, within 5 years
- Any prior history of keratoacanthoma and/or cutaneous squamous cell carcinoma
- A known diagnosis of any of the RASopathies, such as NF-1, Noonan syndrome, or related conditions.
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- History of drug or alcohol abuse within the 6 months prior to dosing
- Smoking: urine cotinine levels below 500 ng/mL on Day -1.
- Use of drugs known to affect CYP3A4 and/or CYP2C8 including both (strong or moderate) inhibitors and inducers, within 7 days prior to dosing
- Administration of medications that prolong the QT interval within 4 weeks prior to dosing and until EOT.
- History or current diagnosis of cardiac disease indicating significant risk of safety
- Any surgical or medical condition which might significantly alter the absorption, distribution, metabolism or excretion of drugs.
- Additional exclusion criteria for healthy subjects (control group):
- Clinical evidence of liver disease or liver injury
- History or presence of renal impairment as indicated by abnormal creatinine or BUN values
- A positive Hepatitis B surface antigen (HBsAg) or Hepatitis C antibody
- Additional exclusion criteria for subjects with hepatic impairment:
- Alcohol or drug abuse within one month prior to dosing or evidence of such
- History of liver transplantation at any time in the past and is on immunosuppressant therapy.
- Encephalopathy Grade 3 or worse within 28 days of dosing.
- History of surgical portosystemic shunt.
- Life expectancy ≤3 months
- Other protocol-defined inclusion/exclusion may apply.
Trial locations and contacts
4 sites in 1 country.
United States4 sites
Hassman Research Institute
Berlin, New Jersey, 08009
Omega Research Consultants LLC
DeBary, Florida, 32713
American Institute of Research
Los Angeles, California, 900017
Wake Research Associates Oncology
Raleigh, North Carolina, 27612
About this study
Official title: A Phase I, Open Label, Multicenter, Single Dose Study to Evaluate the Pharmacokinetics of Dabrafenib in Healthy Subjects With Normal Hepatic Function and Subjects With Impaired Hepatic Function
To characterize the pharmacokinetics and safety of dabrafenib following a single 100 mg oral dose in subjects with moderate and severe hepatic impairment.
- Conditions
- Hepatic Impairment
- Being tested
- dabrafenib
- Keywords
- Hepatic impairment, Healthy volunteers, Clinical pharmacology study, DRB436, dabrafenib, normal hepatic function, impaired hepatic function
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
dabrafenibDrug
Also called DRB436
Single dose of 100 mg dabrafenib on Day 1
| Study group | Role | What they receive |
|---|---|---|
| Group 1 - Control group | Experimental | Not described Receives: Drug: dabrafenib |
| Group 2-Moderate hepatic impairment | Experimental | Not described Receives: Drug: dabrafenib |
| Group 3-Severe hepatic impairment | Experimental | Not described Receives: Drug: dabrafenib |
What is being measured
The primary outcome is the main question the study is designed to answer.
Maximum plasma concentration (Cmax)
Measured: Predose through 96 hours postdose
Area under the curve (AUClast)
Measured: Predose through 96 hours postdose
Area under the curve (AUFinf)
Measured: Predose through 96 hours postdose
Systemic drug clearance (CL/F)
Measured: Predose through 96 hours postdose
Time to reach maximum concentration (Tmax)
Measured: Predose through 96 hours postdose
Terminal elimination rate (Lambda_z)
Measured: Predose through 96 hours postdose
Elimination half-life (T1/2)
Measured: Predose through 96 hours postdose
Volume of distribution (Vz/F)
Measured: Predose through 96 hours postdose
Secondary outcomes (7)
Number of subjects with adverse events
Measured: Time of study drug administration through 30 days postdose
Number of subjects with abnormal lab values related to study drug
Measured: Time of study drug administration through 30 days postdose
Number of subjects with abnormal blood pressure related to study drug
Measured: Time of study drug administration through 30 days postdose
Number of subjects with abnormal pulse rate related to study drug
Measured: Time of study drug administration through 30 days postdose
Number of subjects with abnormal respiratory rate related to study drug
Measured: Time of study drug administration through 30 days postdose
Number of subjects with abnormal body temperature related to study drug
Measured: Time of study drug administration through 30 days postdose
Changes in electrocardiogram (ECG)
Measured: Time of study drug administration through 30 days postdose
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Aug 2016 (estimated)
- Study start20 Dec 2016
- Primary completion12 Oct 2018
- Study completion8 Apr 2019
Why it stopped: Study was terminated due to continued enrolment difficulties.
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
- Parallel groups
- Model description
- open-label, parallel group
- Masking
- None (open label)
- Enrolment
- 5 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
- NCT02873650
- Sponsor's protocol ID
- CDRB436A2107
- Status last verified
- Apr 2020
- First submitted
- 16 Aug 2016
- Last updated
- 8 Dec 2020
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 8 Dec 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase I, Open Label, Multicenter, Single Dose Study to Evaluate the Pharmacokinetics of Dabrafenib in Healthy Subjects With Normal Hepatic Function and Subjects With Impaired Hepatic Function
- ClinicalTrials.gov ID
- NCT02873650
- Acronym / sponsor ID
- CDRB436A2107
- Conditions
- Hepatic Impairment
- Keywords
- Hepatic impairment, Healthy volunteers, Clinical pharmacology study, DRB436, dabrafenib, normal hepatic function, impaired hepatic function
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Study was terminated due to continued enrolment difficulties.
- Enrolment
- 5 participants (actual)
- Lead sponsor
- Novartis PharmaceuticalsIndustry (pharma, biotech, devices)
- Study start
- 20 Dec 2016 (actual)
- Primary completion
- 12 Oct 2018 (actual)
- Study completion
- 8 Apr 2019 (actual)
- First posted
- 19 Aug 2016 (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 characterize the pharmacokinetics and safety of dabrafenib following a single 100 mg oral dose in subjects with moderate and severe hepatic impairment.
Study design
- Primary purpose
- Basic science
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 3
- Model description
- open-label, parallel group
| Arm | Type | Receives |
|---|---|---|
| Group 1 - Control group | Experimental | Drug: dabrafenib |
| Group 2-Moderate hepatic impairment | Experimental | Drug: dabrafenib |
| Group 3-Severe hepatic impairment | Experimental | Drug: dabrafenib |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (12 listed)
- Male and/or female subjects 18-75 years of age
- Females must be of non-childbearing potential . All non-postmenopausal females must have a confirmed negative serum pregnancy
- Subjects in good health condition as determined by no clinically significant findings from medical history and physical examination.
- Body mass index (BMI) between ≥18.0 and ≤38.0 kg/m2, with body weight ≥ 50 kg and no more than 140 kg
- Laboratory values must be within normal limits (correction allowed) or considered clinically insignificant
Key exclusion criteria (23 listed)
- Participation in any clinical investigation within 4 weeks prior to dosing
- Significant acute illness within the two weeks prior to dosing
- History of immunodeficiency diseases, including a positive HIV
- History of malignancy of any organ system, treated or untreated, within 5 years
- Any prior history of keratoacanthoma and/or cutaneous squamous cell carcinoma
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 |
|---|---|---|
| dabrafenibAlso: DRB436Single dose of 100 mg dabrafenib on Day 1 | Drug | Group 1 - Control group, Group 2-Moderate hepatic impairment, Group 3-Severe hepatic impairment |
Primary outcome
Maximum plasma concentration (Cmax)
Time frame: Predose through 96 hours postdose
Area under the curve (AUClast)
Time frame: Predose through 96 hours postdose
Area under the curve (AUFinf)
Time frame: Predose through 96 hours postdose
Systemic drug clearance (CL/F)
Time frame: Predose through 96 hours postdose
Time to reach maximum concentration (Tmax)
Time frame: Predose through 96 hours postdose
Terminal elimination rate (Lambda_z)
Time frame: Predose through 96 hours postdose
Elimination half-life (T1/2)
Time frame: Predose through 96 hours postdose
Volume of distribution (Vz/F)
Time frame: Predose through 96 hours postdose
7 secondary outcomes
Number of subjects with adverse events
Time frame: Time of study drug administration through 30 days postdose
Number of subjects with abnormal lab values related to study drug
Time frame: Time of study drug administration through 30 days postdose
Number of subjects with abnormal blood pressure related to study drug
Time frame: Time of study drug administration through 30 days postdose
Number of subjects with abnormal pulse rate related to study drug
Time frame: Time of study drug administration through 30 days postdose
Number of subjects with abnormal respiratory rate related to study drug
Time frame: Time of study drug administration through 30 days postdose
Number of subjects with abnormal body temperature related to study drug
Time frame: Time of study drug administration through 30 days postdose
Changes in electrocardiogram (ECG)
Time frame: Time of study drug administration through 30 days postdose
Results and safety
The study was stopped early (reason given: Study was terminated due to continued enrolment difficulties.). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 8 Dec 2020.
- Related InfoLink provided by the sponsor.
- Individual participant dataSharing planned: No
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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
4 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing dabrafenib in people with Hepatic Impairment, run by Novartis Pharmaceuticals at 4 sites in United States.
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 23 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: stopped early, as of the sponsor's last update on 8 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 4 sites in United States. 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 was stopped early (reason given: Study was terminated due to continued enrolment difficulties.). Results are not available in the source record.
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?
Maximum plasma concentration (Cmax) (time frame: Predose through 96 hours postdose). 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 8 Dec 2020.