Pharmacokinetics of Dabrafenib in Subjects With Renal Impairment

NCT02852239 | Completed Phase 1 FDA Drug

• 1 other identifier: CDRB436A2106
• Study Type: interventional
• Target: 22
• Locations: 1 country
• Sites: 3

Brief 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.

Conditions

Renal Impairment

Keywords

Renal impairment; Healthy volunteers; Clinical pharmacology study; DRB436; dabrafenib; normal renal function; impaired renal function

Outcome Measures

Primary Outcomes (10)

• Maximum plasma concentration (Cmax)

  The maximum (peak) observed plasma drug concentration after a single dose of dabrafenib

  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

  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

  Predose through 96 hours postdose

• Systemic drug clearance (CL/F)

  Systemic clearance from plasma of dabrafenib after a single dose

  Predose through 96 hours postdose

• Time to reach maximum concentration (Tmax)

  The time to reach maximum (peak) concentration of dabrafenib after a single dose

  Predose through 96 hours postdose

• Terminal elimination rate (Lambda_z)

  Terminal elimination rate of dabrafenib after a single dose

  Predose through 96 hours postdose

• Elimination half-life (T1/2)

  Elimination half-life of dabrafenib after a single dose

  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

  Predose through 96 hours postdose

• Unchanged drug excreted in urine (Aet)

  The amount of unchanged dabrafenib excreted in urine after a single dose

  Predose through 96 hours postdose

• Renal clearance (CLr)

  Renal clearance of dabrafenib calculated using plasma AUC after a single dose

  Predose through 96 hours postdose

Secondary Outcomes (6)

• Number of subjects with adverse events

  Time of drug administration through 30 days postdose

• Number of subjects with abnormal lab values related to study drug

  Time of study drug administration through 30 days postdose

• Number of subjects with abnormal blood pressure related to study drug

  Time of study drug administration through 30 days postdose

• Changes in electrocardiogram (ECG)

  Time of study drug administration through 30 days postdose

• Number of subjects with abnormal pulse rate related to study drug

  Time of study drug administration through 30 days postdose

Study Arms (3)

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.

Drug: dabrafenib

Group 2 - Severe renal function

EXPERIMENTAL

Subjects with severe renal impairment defined as GFR of 15-29 mL/min at baseline.

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.

Drug: dabrafenib

Interventions

dabrafenib DRUG

Single dose dabrafenib 100 mg

Also known as: DRB436

Group 1 - Normal renal function; Group 2 - Severe renal function; Group 3 - End stage renal disease (ESRD)

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Novartis Pharmaceuticals: lead

Study Sites (3)

Omega Research Consultants LLC

DeBary, Florida, 32713, United States

Location

Hassman Research Institute

Berlin, New Jersey, 08009, United States

Location

Wake Research Associates Oncology

Raleigh, North Carolina, 27612, United States

Location

Related Links

• CDRB436A2106 sudy results on the Novartis results database

MeSH Terms

Conditions

Renal Insufficiency

Interventions

dabrafenib

Condition Hierarchy (Ancestors)

Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases

Study Officials

• Novartis Pharmaceuticals

  Novartis Pharmaceuticals

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 26, 2016
• First Posted: August 2, 2016
• Study Start: December 19, 2016
• Primary Completion: September 27, 2019
• Study Completion: September 27, 2019
• Last Updated: December 9, 2020

Record last verified: 2020-07

Data Sharing

• IPD Sharing: Will not share

Locations

US (3)