Renal ImpairmentPhase 1NCT02852239
Pharmacokinetics of Dabrafenib in Subjects With Renal Impairment
A Phase 1 study testing dabrafenib in people with Renal Impairment, run by Novartis Pharmaceuticals at 3 sites in United States.
Trial summary
To characterize the pharmacokinetics and safety of dabrafenib following a single 100 mg oral dose in subjects with severe renal impairment and end stage renal disease not on dialysis. Read more about this study
- Who is it for?
- Ages 18 to 75 yearsHealthy volunteers can take part
- Conditions the study is for
- Renal Impairment
- What is being tested?
- dabrafenib
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 22 participants
- Where
- 3 sitesUnited States
- Study dates
- 19 Dec 2016to 27 Sep 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
- All subjects:
- Females must be of non-childbearing potential or must have negative pregnancy results at screening
- Good health as determined by lack of clinically significant findings
- Subjects must have a BMI between 18.0 kg/m2 and 38.0 kg/m2, with a body weight of at least 50 kg and no more than 140 kg
- Vitals signs within normal range
- Laboratory values at screening within local normal ranges or considered non-clinically significant
Show all 11Show fewer
- Additional criteria for renal impairment subjects:
- -Stable renal disease without evidence of renal progression in the past 28 days prior to dosing
- Additional criteria for healthy matched subjects:
- Matched to at least 1 renal impairment subject by race, age (+/-10 years), gender and weight (+/-10%)
- An absolute GFR of at least 90 ml/min
Who cannot join
- Significant acute illness within the two weeks prior to dosing
- History or current diagnosis of cardiac disease indicating significant risk such as uncontrolled or significant cardiac disease or clinically significant ECG abnormalities
- Subjects will be screened for drugs of abuse
- History of drug or alcohol abuse within 6 months prior to dosing or evidence of such abuse as indicated by laboratory values at screening or baseline.
- Any surgical or medical condition which might significantly alter the absorption, distribution, metabolism or excretion of drugs.
- History of malignancy of any organ system, treated or untreated, within 5 years, regardless of where there is recurrence or metastases.
- Use of drugs known to prolong the QT interval within 4 weeks prior to dosing and for the duration of the study.
- Use of drugs know to affect CYP3A4 and/or CYP2C8 including both (strong or moderate) inhibitors and inducers, within 7 days prior to dosing or during the current study are prohibited
Trial locations and contacts
3 sites in 1 country.
United States3 sites
Hassman Research Institute
Berlin, New Jersey, 08009
Omega Research Consultants LLC
DeBary, Florida, 32713
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 Renal Function and Subjects With Impaired Renal Function
To characterize the pharmacokinetics and safety of dabrafenib following a single 100 mg oral dose in subjects with severe renal impairment and end stage renal disease not on dialysis.
Read the detailed description
The main objective of this trial is to evaluate the pharmacokinetics of dabrafenib and metabolites after a single oral dose of dabrafenib in subjects with renal impairment as compared to healthy subjects with normal renal function.
This was a single-dose, open-label, parallel group single dose study to evaluate the pharmacokinetics (PK) and safety of a single oral dose of dabrafenib 100 mg in subjects with severe RI or ESRD compared to matched healthy subjects with normal renal function (control group).
The study consisted of a screening period, a treatment period and a follow-up period.
The Screening period started up to 28 days prior to dosing. Subjects who satisfied the inclusion/exclusion criteria at screening were admitted for baseline evaluations, which was done locally by the investigator. In the treatment period, subjects received a single 100 mg oral dose of dabrafenib administered as two 50 mg capsules with a whole glass of non-carbonated water (approximately 240 mL) in the morning of Day 1 following an overnight fast (minimum 10 hours). Subjects were confined to the study facility from Day -1 to Day 5, for collection of serial blood and urine samples. Subjects were discharged on Day 5.
In the follow-up period a telephone call was made to subjects 30 days post-dose to evaluate subject safety during the weeks after discharge from the facility. Adverse events occurring prior to Day 30 were followed until resolution or until judged to be permanent. Subjects returned to the clinic on Days 90 and 180 for the post-dose dermatological examination follow up.
For this study, the terms "investigational drug", "study drug" or "study treatment" refer to dabrafenib, administered as a single dose.
- Conditions
- Renal Impairment
- Being tested
- dabrafenib
- Keywords
- Renal impairment, Healthy volunteers, Clinical pharmacology study, DRB436, dabrafenib, normal renal function, impaired renal function
- Medical subject headings
- Renal Insufficiency
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 dabrafenib 100 mg
| Study group | Role | What they receive |
|---|---|---|
| Group 1 - Normal renal function | Experimental | Subjects with normal renal function defined as GFR ≥ 90 mL/min at baseline and matching to the renal impaired subject based on gender, race, age, and weight. Receives: Drug: dabrafenib |
| Group 2 - Severe renal function | Experimental | Subjects with severe renal impairment defined as GFR of 15-29 mL/min at baseline. Receives: Drug: dabrafenib |
| Group 3 - End stage renal disease (ESRD) | Experimental | Subjects with end stage renal disease (ESRD), defined as GFR of <15 mL/min at baseline. Receives: Drug: dabrafenib |
What is being measured
The primary outcome is the main question the study is designed to answer.
Maximum plasma concentration (Cmax)
The maximum (peak) observed plasma drug concentration after a single dose of dabrafenib
Measured: Predose through 96 hours postdose
Area under the curve (AUClast)
AUClast is the area under the curve calculated to the last quantifiable concentration point after a single dose of dabrafenib
Measured: Predose through 96 hours postdose
Area under the curve (AUFinf)
AUCinf is the area under the plasma concentration time curve extrapolated to infinity after a single dose of dabrafenib
Measured: Predose through 96 hours postdose
Systemic drug clearance (CL/F)
Systemic clearance from plasma of dabrafenib after a single dose
Measured: Predose through 96 hours postdose
Time to reach maximum concentration (Tmax)
The time to reach maximum (peak) concentration of dabrafenib after a single dose
Measured: Predose through 96 hours postdose
Terminal elimination rate (Lambda_z)
Terminal elimination rate of dabrafenib after a single dose
Measured: Predose through 96 hours postdose
Elimination half-life (T1/2)
Elimination half-life of dabrafenib after a single dose
Measured: Predose through 96 hours postdose
Volume of distribution (Vz/F)
The apparent volume of distribution during the terminal elimination phase of dabrafenib after a single dose
Measured: Predose through 96 hours postdose
Unchanged drug excreted in urine (Aet)
The amount of unchanged dabrafenib excreted in urine after a single dose
Measured: Predose through 96 hours postdose
Renal clearance (CLr)
Renal clearance of dabrafenib calculated using plasma AUC after a single dose
Measured: Predose through 96 hours postdose
Secondary outcomes (6)
Number of subjects with adverse events
Assess the safety of a single dose of dabrafenib through AE reports of subjects from drug administration through 30 days postdose
Measured: Time of drug administration through 30 days postdose
Number of subjects with abnormal lab values related to study drug
Assess the safety of a single dose of dabrafenib through hematology and chemistry blood tests
Measured: Time of study drug administration through 30 days postdose
Number of subjects with abnormal blood pressure related to study drug
Assess the safety of a single dose of dabrafenib by monitoring changes in blood pressure
Measured: Time of study drug administration through 30 days postdose
Changes in electrocardiogram (ECG)
Assess the safety of a single dose of dabrafenib by monitoring changes in ECG
Measured: Time of study drug administration through 30 days postdose
Number of subjects with abnormal pulse rate related to study drug
Assess the safety of a single dose of dabrafenib by monitoring changes in heart rate
Measured: Time of study drug administration through 30 days postdose
Number of subjects with abnormal respiratory rate related to study drug
Assess the safety of a single dose of dabrafenib by monitoring changes in respiratory rate
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 posted2 Aug 2016 (estimated)
- Study start19 Dec 2016
- Primary completion27 Sep 2019
- Study completion27 Sep 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Renal 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
- Masking
- None (open label)
- Enrolment
- 22 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
- NCT02852239
- Sponsor's protocol ID
- CDRB436A2106
- Status last verified
- Jul 2020
- First submitted
- 26 Jul 2016
- Last updated
- 9 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 9 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 Renal Function and Subjects With Impaired Renal Function
- ClinicalTrials.gov ID
- NCT02852239
- Acronym / sponsor ID
- CDRB436A2106
- Conditions
- Renal Impairment
- Keywords
- Renal impairment, Healthy volunteers, Clinical pharmacology study, DRB436, dabrafenib, normal renal function, impaired renal function
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 22 participants (actual)
- Lead sponsor
- Novartis PharmaceuticalsIndustry (pharma, biotech, devices)
- Study start
- 19 Dec 2016 (actual)
- Primary completion
- 27 Sep 2019 (actual)
- Study completion
- 27 Sep 2019 (actual)
- First posted
- 2 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 severe renal impairment and end stage renal disease not on dialysis.
Detailed description
The main objective of this trial is to evaluate the pharmacokinetics of dabrafenib and metabolites after a single oral dose of dabrafenib in subjects with renal impairment as compared to healthy subjects with normal renal function.
This was a single-dose, open-label, parallel group single dose study to evaluate the pharmacokinetics (PK) and safety of a single oral dose of dabrafenib 100 mg in subjects with severe RI or ESRD compared to matched healthy subjects with normal renal function (control group).
The study consisted of a screening period, a treatment period and a follow-up period.
The Screening period started up to 28 days prior to dosing. Subjects who satisfied the inclusion/exclusion criteria at screening were admitted for baseline evaluations, which was done locally by the investigator. In the treatment period, subjects received a single 100 mg oral dose of dabrafenib administered as two 50 mg capsules with a whole glass of non-carbonated water (approximately 240 mL) in the morning of Day 1 following an overnight fast (minimum 10 hours). Subjects were confined to the study facility from Day -1 to Day 5, for collection of serial blood and urine samples. Subjects were discharged on Day 5.
In the follow-up period a telephone call was made to subjects 30 days post-dose to evaluate subject safety during the weeks after discharge from the facility. Adverse events occurring prior to Day 30 were followed until resolution or until judged to be permanent. Subjects returned to the clinic on Days 90 and 180 for the post-dose dermatological examination follow up.
For this study, the terms "investigational drug", "study drug" or "study treatment" refer to dabrafenib, administered as a single dose.
Study design
- Primary purpose
- Basic science
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Group 1 - Normal renal function | Experimental | Drug: dabrafenibSubjects with normal renal function defined as GFR ≥ 90 mL/min at baseline and matching to the renal impaired subject based on gender, race, age, and weight. |
| Group 2 - Severe renal function | Experimental | Drug: dabrafenibSubjects with severe renal impairment defined as GFR of 15-29 mL/min at baseline. |
| Group 3 - End stage renal disease (ESRD) | Experimental | Drug: dabrafenibSubjects with end stage renal disease (ESRD), defined as GFR of <15 mL/min at baseline. |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (11 listed)
- Females must be of non-childbearing potential or must have negative pregnancy results at screening
- Good health as determined by lack of clinically significant findings
- Subjects must have a BMI between 18.0 kg/m2 and 38.0 kg/m2, with a body weight of at least 50 kg and no more than 140 kg
- Vitals signs within normal range
- Laboratory values at screening within local normal ranges or considered non-clinically significant
Key exclusion criteria (8 listed)
- Significant acute illness within the two weeks prior to dosing
- History or current diagnosis of cardiac disease indicating significant risk such as uncontrolled or significant cardiac disease or clinically significant ECG abnormalities
- Subjects will be screened for drugs of abuse
- History of drug or alcohol abuse within 6 months prior to dosing or evidence of such abuse as indicated by laboratory values at screening or baseline.
- Any surgical or medical condition which might significantly alter the absorption, distribution, metabolism or excretion of drugs.
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 dabrafenib 100 mg | Drug | Group 1 - Normal renal function, Group 2 - Severe renal function, Group 3 - End stage renal disease (ESRD) |
Primary outcome
Maximum plasma concentration (Cmax)
Time frame: Predose through 96 hours postdose
The maximum (peak) observed plasma drug concentration after a single dose of dabrafenib
Area under the curve (AUClast)
Time frame: Predose through 96 hours postdose
AUClast is the area under the curve calculated to the last quantifiable concentration point after a single dose of dabrafenib
Area under the curve (AUFinf)
Time frame: Predose through 96 hours postdose
AUCinf is the area under the plasma concentration time curve extrapolated to infinity after a single dose of dabrafenib
Systemic drug clearance (CL/F)
Time frame: Predose through 96 hours postdose
Systemic clearance from plasma of dabrafenib after a single dose
Time to reach maximum concentration (Tmax)
Time frame: Predose through 96 hours postdose
The time to reach maximum (peak) concentration of dabrafenib after a single dose
Terminal elimination rate (Lambda_z)
Time frame: Predose through 96 hours postdose
Terminal elimination rate of dabrafenib after a single dose
Elimination half-life (T1/2)
Time frame: Predose through 96 hours postdose
Elimination half-life of dabrafenib after a single dose
Volume of distribution (Vz/F)
Time frame: Predose through 96 hours postdose
The apparent volume of distribution during the terminal elimination phase of dabrafenib after a single dose
Unchanged drug excreted in urine (Aet)
Time frame: Predose through 96 hours postdose
The amount of unchanged dabrafenib excreted in urine after a single dose
Renal clearance (CLr)
Time frame: Predose through 96 hours postdose
Renal clearance of dabrafenib calculated using plasma AUC after a single dose
6 secondary outcomes
Number of subjects with adverse events
Time frame: Time of 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
Changes in electrocardiogram (ECG)
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
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.
- CDRB436A2106 sudy results on the Novartis results databaseLink 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
3 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 Renal Impairment, run by Novartis Pharmaceuticals at 3 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 11 inclusion and 8 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 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 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?
Maximum plasma concentration (Cmax) (time frame: Predose through 96 hours postdose). The study lists 10 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; AzTrials last refreshed its copy on 8 Nov 2026.